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Syntheses of strapped, capped and bent porphyrins Wijesekera, Tilak Panini 1980

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c/  SYNTHESES OF STRAPPED, CAPPED AND BENT PORPHYRINS  by TILAK PANINI WIJESEKERA B.Sc.  (Honours), U n i v e r s i t y M.Sc,  Simon F r a s e r  o f S r i L a n k a , 1973  University,  1977  A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE  REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in ;  THE  FACULTY OF GRADUATE STUDIES (Department o f C h e m i s t r y )  We a c c e p t t h i s t h e s i s a s c o n f o r m i n g t o the r e q u i r e d s t a n d a r d  THE  UNIVERSITY OF BRITISH COLUMBIA AUGUST 1980 (g)  Tilak Panini  Wijesekera  In  presenting  this  an a d v a n c e d  degree  the  shall  I  Library  further  for  agree  scholarly  by  his  of  this  written  in  at  University  the  make that  purposes  thesis  for  partial  freely  permission may  fulfilment of  It  is  for  by  ' £T£  University  of  British  S  '  ^  the  understood  gain  Columbia  for  extensive  shall  permission.  of  British  available  be g r a n t e d  financial  2075 Wesbrook P l a c e V a n c o u v e r , Canada V6T 1W5  Date  it  representatives.  Department  The  thesis  y  the  reference  Head o f  be  requirements  Columbia,  copying  that  not  of  of  I  agree  and this  for  that  study. thesis  my D e p a r t m e n t  or  publication  copying  or  allowed  without  my  ABSTRACT The  doming o f  the  porphyrin  a c c o m p a n i e d movement o f  the  c e n t r a l i r o n atom i n and  have p r e v i o u s l y  macrocycle,.and  the  plane,  the  mechanism o f r e v e r s i b l e o x y g e n b i n d i n g  o f heme p r o t e i n s . a synthetic  route  would  as  serve  thesis 109  objective  f o r the  the  a diagonally  t i o n was its  synthesis,  the  configuration. the  the  to  of  short  as  i s extremely i n the  first  i t s terminal  diborane reduction  stituted quently  90_,  the  pyrrole  9_2.  protected  derivative of the  9_4  9_4.  (using  by  Two  of  the  3-unsubstituted  ketonic  formylpyrrole  b i s carboxypyrrole two  formyl  converting  this  was  the  The  93_ v i a t h e 9_1 and  groups of  sulfuryl  of  followed chain to  bis  the  bis  93_ were  by  linked the  pyrrole a-unsubsubse-  a-methyl groups  chloride)  pyrrole  the  by  followed  b i s a-chloromethyl d e r i v a t i v e with  a-unsubstituted  in  dicyanovinyl  m o n o c h l o r i n a t i o n s a t the of  stable  converted  t o the  cycliza-  p y r r o l e £6  groups.  89_ so o b t a i n e d  2 equivalents  condensation of  equivalents  the  The  enough  dicarboxylic acid,  the  ester  type  step  simultaneous F r i e d e l - C r a f t s a c y l a t i o n reactions  benzyl  the  strap p r i o r to  two  useful bis  the  This  short  l i n k e d t o two  synthetically  that  systems.  was  bis pyrrole ethyl ester  develop  of bent porphyrins  carbon chain,  porphyrin  strap obtained  of  in  cooperativity  porphyrins  Therefore,  moles of  of  porphyrin.  i n t r o d u c t i o n of  mandatory s i n c e  planar  attached  the  and  biological  the  out  important  t h i s work was  construction  syntheses of  to cause d i s t o r t i o n of The  of  simple models f o r the  describes  containing  The  b e e n s u g g e s t e d t o be  the  79  produced  the  by two  dipyrromethane dimer  9_6.  The s a p o n i f i c a t i o n o f t h e two  g r o u p s and t h e d e p r o t e c t i o n in  of the formyl  a s i n g l e s t e p by t h e u s e o f s t r o n g  a-formyl-a'-carboxydipyrromethane subjected  t o thermal  decarboxylation  formamide) and t h e r e s u l t i n g methane d i m e r using  108 was  g r o u p s were e f f e c t e d  aqueous a l k a l i .  dimer  toluene-p-sulfonic acid  (in refluxing  shorter  carbon chains  synthesize 109c  accomplished,  were a t t e m p t e d .  t h e 10 and 9 - c a r b o n  I t was  strapped  93^.  used  similar  o f 108d  T h i s was  t o t h a t used 8_0) .  precursor  converted  to prepare  Compound  117 was  as p r e v i o u s l y  The  durene-bis-pentanoic  bis-pentanoic  acid  compound converted  143.  115  117 i n a manner  96_ ( t h e a - f r e e p y r r o l e to the prophyrin to acid-catalyzed  acid  carried  the construc-  The key s y n t h e t i c 130 w h i c h was  d u r e n e v i a two m a l o n a t e was  the b i s formyl-  to the b i s cyanoacrylate  n e x t p h a s e o f t h i s work d e a l t w i t h  bis(chloromethyl)  porphyrins  described.  o f t h e capped p o r p h y r i n  a t e was  (n=8) d i d n o t  The b r a n c h o f f p o i n t was  108 v i a 118 and 119 and s u b j e c t e d  cyclization  tion  with  (109b and  to strapped  t o produce t h e dipyrromethane dimer  u s e d was  was  porphyrin.  109 i s a l s o d e s c r i b e d .  and  (n=ll)  possible to  porphyrins  An a l t e r n a t i v e s y n t h e t i c r o u t e  pyrrole  109.  the syntheses of the porphyrins  r e s p e c t i v e l y ) but the c y c l i z a t i o n  produce a  dipyrro-  dilution  t o produce the p o r p h y r i n 109a  was  dimethyl-  under e x t r e m e l y h i g h  Once t h e s y n t h e s i s o f t h e p o r p h y r i n successfully  The  107 so o b t a i n e d  ct-f o r m y l - a ' - u n s u b s t i t u t e d  cyclized  ester  intermedi-  prepared  syntheses.  from  The d u r e n e -  t h r o u g h t h e same r e a c t i o n  sequence  as  previously described  for  the  simple  (the d i c y a n o v i n y l - e t h y l e s t e r  dicarboxylic acids  to give  the  capped  route) porphyrin  143. The on  presence of a short  the e l e c t r o n i c a b s o r p t i o n  definite 143 109b  t r e n d was  t o the  porphyrins  ->• 109c) .  macrocycle. the  This "*"H NMR  current  i n going  change was spectra  r e s o n a n c e due of the  spectra of  the  a rhodofying  effect  porphyrins.  A  from the  capped  of p r o g r e s s i v e l y shorter  chain methylene proton  methyl proton ring  observed  s t r a p had  porphyrin  chains  (109a  a t t r i b u t e d to d i s t o r t i o n  exhibited  large upfield  r e s o n a n c e s and to the  porphyrin.  iv  also of  i n f l u e n c e of  shifts  the  the  of  -> the of  durene  diamagnetic  V  TABLE OF CONTENTS Page Abstract Table  i i  of Contents  vi  List  of Tables  ix  List  of Figures  List  of Abbreviations  x xiii  Acknowledgements 1.  xiv  INTRODUCTION AND  LITERATURE  REVIEW  1  - A General  Survey  2  1.1  Porphyrins  1.2  Synthetic Aspects  of Porphyrins  1.3  Metalloporphyrins Carriers  as B i o l o g i c a l  1.4  5 Oxygen 15  S y n t h e t i c Models f o r B i o l o g i c a l  Oxygen  Carriers 2.  RESULTS AND  20  DISCUSSION  35  2.1  Synthetic Objective  2.2  Synthetic Plan  2.3 2.4  Synthesis of Undecanedioic A c i d M o n o p y r r o l i c S t a r t i n g M a t e r i a l s and Intermediates 2.4.1 2.4.2  2.5 2.6  . . . . . .  36  .  39  Syntheses o f P y r r o l e s from Precursors  46 50  Acylic 51  Preparation of Synthetically Useful Pyrroles v i a Transformations of a-Substituents  C h a i n L i n k e d B i s P y r r o l e s and t h e i r Modifications D i p y r r o m e t h a n e s and P o r p h y r i n s  vi  55  Chemical  Therefrom  63 . .  79  Page 2.7  Durene-Bis-Pentanoic Acid ation into a Porphyrin 2.7.1 2.7.2  124  Synthesis of Durene-Bis-Pentanoic Acid  125  Incorporation of Durene-Bis-Pentanoic Acid  3.  and i t s I n c o r p o r -  into  the Porphyrin  140  EXPERIMENTAL  150  3.1 3.2  151  G e n e r a l Methods N o m e n c l a t u r e o f P o r p h y r i n s and t h e i r mediates . . . ;  Inter153  3.3  Syntheses  of Acyclic  3.4  Syntheses  o f Monopyrroles  3.5  S y n t h e s i s o f t h e M o d e l P o r p h y r i n and i t s Dipyrromethane P r e c u r s o r s  17 8  Syntheses  202  3.6  3.7  Precursors  155 161  of Chain Linked B i s Pyrroles  . . . .  3.6.1  Bis Pyrrole  Diketones  202  3.6.2  Bis Pyrrole  Ethyl  210  3.6.3  Bis Pyrrole  Benzyl Esters  3.6.4  B i s Formylpyrroles  221  3.6.5  Bis Cyanovinylpyrroles  2 31  Syntheses  of Chain Linked  Esters  216  Dipyrromethane  Dimers 3.8  Syntheses 3.8.1 3.8.2 3.8.3  3.9  241 of Strapped Porphyrins  .  265  1,17-Diethyl-2,8,12,18-tetramethyl3,13-undecamethyleneporphyrin 109a . . 7,17-Diethyl-2,8,12,18-tetramethyl3,13-decamethyleneporphyrin 109b . .  265  7,17-Diethyl-2,8,12,18-tetramethyl3,13-nonamethyleneporphyrin 109c . .  S y n t h e s e s o f D u r e n e - B i s - P e n t a n o i c A c i d and i t s Precursors  3.10 S y n t h e s e s o f D u r e n e - B i s - P e n t a n e B r i d g e d D i m e r s and t h e P o r p h y r i n 143 . vii  271 273  275  289  Page 4.  SPECTRAL ASSIGNMENTS AND COMPARISON 4.1  TABLES  307  "'"H NMR S p e c t r a and C o m p a r i s o n T a b l e s o f Strapped Porphyrin Intermediates  308  13 4.2 4.3  C NMR S p e c t r a and C o m p a r i s o n T a b l e s o f Strapped Porphyrin Intermediates 1  H NMR  Data o f Strapped  337  Porphyrins  358  13 4.4 4.5  C NMR  Data o f Strapped  Electronic Absorption  Porphyrins  Spectra of Porphyrins  REFERENCES  383 . .  392 40 3  viii  L I S T OF Table I II III  IV V VI VII VIII  TABLES  Title 1  H  1  H NMR D a t a o f C h a i n a-Ethyl Esters  Linked Bis Pyrrole  H NMR D a t a o f C h a i n a-Benzyl E s t e r s  Linked Bis Pyrrole  H NMR D a t a o f C h a i n pyrroles  Linked  H NMR D a t a o f C h a i n vinylpyrrole  Linked  1  1  1  1  1  NMR  Data o f Chain  Page  L i n k e d B i s P y r r o l e Diketones.  .  314  316 319 Bis-Formyl321 Bis-a-Dicyano32 3  H NMR D a t a o f C h a i n L i n k e d a - D i c y a n o v i n y l a ' - E t h o x y c a r b o n y l Dipyrromethane Dimers  325  H NMR D a t a o f C h a i n L i n k e d ct-Formyl-ct - C a r b o x y Dipyrromethane Dimers . . . . .  328  C NMR D a t a o f C h a i n Diketones  341  1  1 3  Linked Bis-Pyrrole  13 IX  C NMR D a t a o f C h a i n a-Ethyl Esters  Linked Bis Pyrrole 344  13 X XI  XII XIII  C NMR D a t a o f a-Benzyl E s t e r s 13 C NMR D a t a o f pyrroles 13 C NMR D a t a o f vinylpyrroles 13 C NMR D a t a o f a -Ethoxycarbonyl 1  XIV  Chain  Linked Bis Pyrrole 347  Chain  Linked Bis  a-Formyl350  Chain  Linked Bis  a-Dicyano352  Chain Linked a-DicyanovinylDipyrromethane Dimers  Comparison o f Chemical S h i f t s Resonances o f P o r p h y r i n s  355  for Selected 366  13 XV XVI XVII  Comparison o f  C Chemical  Shifts  of Porphyrins  . .  390  Comparison of E l e c t r o n i c A b s o r p t i o n S p e c t r a l Data o f P o r p h y r i n s  399  Comparison of E l e c t r o n i c A b s o r p t i o n Data o f P o r p h y r i n s  401  ix  Spectral  L I S T OF Figure 1.  2. 3. 4.  5. 6.  FIGURES  Title  F i s c h e r and IUPAC Numbering Porphyrin Nucleus . Linear Tetrapyrrolic Syntheses  Systems f o r  2+2  Coupling  of 12  S y n t h e s i s o f the Cyclophane P o r p h y r i n Traylor et. a l . S y n t h e s i s of the Baldwin e t . a l .  "Capped" P o r p h y r i n  S y n t h e s i s of the  "Strapped"  of 23  of 25  Porphyrin  of  et. a l .  27  A R e t r o s y n t h e t i c A n a l y s i s of the  8.  Synthesis of Undecanedioic  12.  i n Porphyrin 8  7.  11.  the 2  Intermediates  P o r p h y r i n Syntheses v i a the Dipyrromethane s  Baldwin  9. 10.  Page  Target Molecule.  Acid  Synthesis of Knorr's P y r r o l e S y n t h e s e s o f M o n o p y r r o l e s 6_6 and V a r i a t i o n s of Knorr Reaction  .  41 47 52  6_7 by  the 54  Preparation of S y n t h e t i c a l l y Useful Monopyrroles v i a Transformations of a-Substituents  56  Syntheses of Chain mediates  64  Linked Bis P y r r o l i c  Inter-  13.  S y n t h e s i s of the  14.  S y n t h e s i s o f the Model P o r p h y r i n - E t i o p o r p h y r i n I I (106)  89  A c i d - C a t a l y z e d Rearrangements o f methane s  92  15. 16. 17.  18.  D i p y r r o m e t h a n e Dimer 9j[  80  Dipyrro-  C o n v e r s i o n o f t h e D i p y r r o m e t h a n e Dimer 9_6 t h e S t r a p p e d P o r p h y r i n 109  to 98  An A l t e r n a t i v e S y n t h e t i c Route t o E t i o p o r p h y r i n I I (106)  106  An A l t e r n a t i v e S y n t h e t i c Route t o t h e P o r p h y r i n s 109  122;  x  Strapped  Figure  Title  Page  19.  Synthesis o f Durene-Bis-Pentanoic Acid  20.  Syntheses o f Durene-Bis-Pentane Linked B i s P y r r o l i c Intermediates  21.  (130) . . . .  Syntheses o f Durene-Bis-Pentane Linked D i p y r r o m e t h a n e D i m e r s and o f t h e P o r p h y r i n  22.  1  23.  1  24.  1  25.  1  26.  1  27.  1  28.  1  29.  126  141 143 . . .  H NMR  Spectrum  (100 MHz) o f 88a i n 10% TFA-CDC1 -  H NMR  Spectrum  (100 MHz) o f 89a i n C D C 1  3  315  H NMR  Spectrum  (100 MHz) o f 90a i n C D C 1  3  317  H NMR  Spectrum  (100 MHz) o f 134 i n C D C 1  3  318  H NMR  S p e c t r u m o f 93a i n C D C 1  H NMR  Spectrum  (100 MHz) o f 94a i n C D C 1  3  322  H NMR  Spectrum  (100 MHz) o f 96a i n C D C 1  3  324  1  H NMR  Spectrum  (100 MHz) o f 107a i n DMSO-dg  30.  1  H NMR  Spectrum  (100 MHz) o f 115 i n C D C 1  3  332  31.  1  H NMR  Spectrum  (100 MHz) o f 117 i n C D C 1  3  333  32.  1  H NMR  Spectrum  (100 MHz) o f 118 i n DMSO-dg  33.  X  H NMR  Spectrum  (100 MHz) o f 119 i n C D C 1  34.  1  H NMR  Spectrum  (100 MHz) o f 108a i n C D C 1  35.  1 3  36.  1 3  37.  1 3  38.  1 3  39.  1 3  40.  1 3  41.  1  42.  1  43.  1  44.  1  3  .  148 313  320  3  . . . .  . . . .  327  334 335  3  336  3  C  NMR  S p e c t r u m o f 88a i n 10% T F A - C D C 1  C  NMR  S p e c t r u m o f 89a i n C D C 1  3  343  C NMR  S p e c t r u m o f 90a i n C D C 1  3  346  C  NMR  S p e c t r u m o f 93a i n C D C 1  3  349  C  NMR S p e c t r u m o f 94a i n C D C 1  3  351  C  NMR  3  354  S p e c t r u m o f 96a i n C D C 1  340  3  H NMR  S p e c t r u m o f (270 MHz) o f 143 i n C D C 1  H NMR  Spectrum  (400 MHz) o f 109c i n C D C 1  3  360  H NMR  Spectrum  (400 MHz) o f 109b i n C D C 1  3  361  H NMR  Spectrum  (400 MHz) o f 109a i n C D C 1  3  362  xi  3  . . . .  359  Figure 45.  46. 47. 48.  49.  Title  Page  Partial H N M R S p e c t r a o f 109b (400 M H z ) w i t h S i m u l t a n e o u s I r r a d i a t i o n s a t 6 3.67 and 6 3.46  . . .  372  Partial H N M R S p e c t r a o f 109b (400 M H z ) w i t h S i m u l t a n e o u s I r r a d i a t i o n s a t <5 1.51 and S 0.46  . . .  373  Partial H N M R S p e c t r a o f 109b (400 M H z ) w i t h S i m u l t a n e o u s I r r a d i a t i o n s a t 6 0.03 and 6 - 1 . 1 7  . .  375  Partial H N M R S p e c t r a o f 109b (400 M H z ) w i t h S i m u l t a n e o u s I r r a d i a t i o n s a t 6 -1.79 and 6 -2.23  . .  376  Partial H N M R S p e c t r a o f 109b (400 M H z ) w i t h S i m u l t a n e o u s I r r a d i a t i o n s a t 6 -5.13 and 6 -5.87  . .  377  1  1  1  1  1  50.  1 3  C  N M R S p e c t r u m o f 143  384  51.  1 3  C  N M R S p e c t r u m o f 109a  385  52.  1 3  C  N M R S p e c t r u m o f 109b  386  53.  1 3  C  N M R S p e c t r u m o f 109c  387  54.  Electronic  Absorption  S p e c t r a o f 106  394  55.  Electronic Absorption  S p e c t r a o f 143  395  56.  Electronic Absorption  S p e c t r a o f 109a  396  57.  Electronic  Absorption  S p e c t r a o f 109b  397  58.  Electronic Absorption  S p e c t r a o f 109c  39 8  x i i  ABBREVIATIONS 13 C NMR  =  carbon-13  n u c l e a r magnetic  Et  =  ethyl  ''"H NMR  =  IR  =  Ph  =  phenyl  TFA  =  trifluoroacetic  THF  =  tetrahydrofuran  TLC  =  thin  proton n u c l e a r magnetic  resonance  resonance  infrared  layer  Abbreviations  acid  chromatography  i n NMR  Assignments  s  =  singlet  m  d  =  doublet  bs =  broad  singlet  t  =  triplet  br =  broad  rise  q  =  quartet  xiii  =  multiplets  ACKNOWLEDGEMENTS It the  has b e e n a r e w a r d i n g  experience  s u p e r v i s i o n o f P r o f e s s o r David  e n c o u r a g e m e n t have p r o v i d e d course  I extend  during the  my s i n c e r e t h a n k s  I a l s o w i s h t o t h a n k P r o f e s s o r B r i a n R. James f o r t h e  v a l u a b l e d i s c u s s i o n s we have h a d d u r i n g I am i n d e b t e d .useful  H i s g u i d a n c e and  i n v a l u a b l e support  o f t h i s work a n d f o r t h i s ,  t o him.  Dolphin.  t o work u n d e r  suggestions  t o D r . J o h n B. P a i n e  made d u r i n g  for p r o v i d i n g access  the past  years.  I I I f o r t h e many  t h e s y n t h e t i c work and a l s o  t o unpublished  t h a n k D r . J.K.M. S a n d e r s  three  data.  I a l s o wish to  (Cambridge U n i v e r s i t y ) f o r h e l p f u l  d i s c u s s i o n s on t h e a n a l y s e s  of  NMR  spectra o f strapped  porphyrins. I like  t o take  this  members o f P r o f e s s o r D o l p h i n ' s present, Special  opportunity research  t o thank a l l t h e  g r o u p , p a s t and  f o r m a k i n g my s t a y a t U.B.C. a v e r y  p l e a s a n t one.  t h a n k s a r e due t o Mr. J o h n Hiom and D r . Q u i n t u s  for proofreading  parts o f the manuscript  Hiom and M r s . J o y c i e M i u r a  Perera  and t o M r s . A n n e t t e  f o r so c o m p e t e n t l y  typing  this  thesis. Financial Columbia,  support  from t h e U n i v e r s i t y o f B r i t i s h  i n t h e form o f a U n i v e r s i t y Graduate  (1979-80) and a t e a c h i n g  Fellowship  a s s i s t a n t s h i p (1977-80) i s g r a t e f u l l y  acknowledged. Finally, directed and  a deep s e n s e o f g r a t i t u d e and l o v e i s  t o w a r d s my w i f e ,  constant  K a n t h i , whose p a t i e n c e ,  e n c o u r a g e m e n t made t h i s xiv  tolerance  thesis possible.  To my  parents  for  their  u n d e r s t a n d i n g and  xv  encouragement  1  CHAPTER 1  INTRODUCTION AND  LITERATURE  REVIEW  2 1.1  PORPHYRINS  - A GENERAL  "Tetrapyrrole" member of  of a class  the pyrrole  bridges four  type,  rings  f o r which  as  i n the b i l e porphin  (Figure  1  : Fischer  used  whose  linked  widely  molecules together  T h e common  t h i s name  i s used  and r e l a t e d  pigments.  the peripheral  FIGURE  usually  at their appositions.  i n the porphyrins  of  i s a term  o f compounds  as  from  SURVEY  have  by s i n g l e  a r e , (a) and  to a  four  arrangements  compounds  Porphyrins  to refer  rings  atom of the  macrocyclic, (b) l i n e a r ,  are formally  derived  1) b y t h e s u b s t i t u t i o n o f some o r a l l  hydrogens  a n d IUPAC  with  various  Numbering  groups.  Systems  Nucleus  B  f o r the  Porphyrin  The n o m e n c l a t u r e most g e n e r a l l y of F i s c h e r , which Figure  IA.  i s b a s e d on a n u m e r a t i o n  ct ,  "meso" a r e d e s i g n a t e d involves  a very  l a r g e number  on t h e t y p e o f s u b s t i t u e n t s  s y s t e m b a s e d on t h e i r  porphyrin  w i t h one m e t h y l  periphery  h a s b e e n named  isomers"  / M  Me  \ .  e  Et  \  M  Me  Me  Me  \  I  TYPE  compounds  porphyrins  derived  \  Et  /  Me  Me  Me  Me  ' /  .  \  Et  II  Et  TYPE  E.g., the  with four  Me  \  f o r m a complex  pyrrole  "type-  Me  Me  Et  /  III  and do n o t f o r m an a d e q u a t e  basis  \ Me Et  /  Me  TYPE  Me  IV  occurring and i n o r d e r  f a r t o o many t r i v i a l  t h e names do n o t c o n v e y  Et  \  Et  series of structures  Et  /  Et  f r o m t h e common n a t u r a l l y  t o name them, F i s c h e r u s e d Moreover  and an i s o m e r  below:  Et  Et  nomenclature  names d e p e n d i n g  arrangements.  "Etioporphyrin",  Et  /  Et  e  TYPE  The  /  Et  of t r i v i a l  termed  and one e t h y l g r o u p on e a c h  I t o IV as shown  Et  The F i s c h e r  a t the p e r i p h e r y  numbering  from 1 t o  positions, usually  3 , y and <5 .  that  scheme shown i n  The p e r i p h e r a l p o s i t i o n s a r e numbered  8 and t h e " i n t e r p y r r o l i c " m e t h i n e  also  u s e d has been  names.  clear structural f o r naming new  information compounds.  l  In a r e c e n t  review  Bonnett  has o u t l i n e d t h e . n o m e n c l a t u r e o f  4 biologically is  i m p o r t a n t p o r p h y r i n s and r e l a t e d compounds.  interesting  c l a t u r e i s now still  prefer  It  t o n o t e t h a t a l t h o u g h a more s y s t e m a t i c nomenavailable  (vide i n f r a ) , most p o r p h y r i n c h e m i s t s  t o use F i s c h e r ' s , t r i v i a l  nomenclature.  A complete numbering system f o r the p o r p h y r i n nucleus to  this,  ( F i g u r e IB) was  first  p u t f o r w a r d i n 1960.  According  t h e c a r b o n atoms a r e numbered f r o m 1 t o 20 w i t h  f o u r n i t r o g e n atoms b e i n g 21 t o 24. scheme a j o i n t c o m m i s s i o n  B a s e d on t h i s  and t h e i r d e r i v a t i v e s .  The  (IUPAC-IUB)  for a l l porphyrins  a p p l i c a t i o n o f t h e s e recommend-  a t i o n s p e r m i t s t h e s e s u b s t a n c e s t o be named more u s i n g fewer t r i v i a l  numbering  on b i o c h e m i c a l - n o m e n c l a t u r e  has p r o p o s e d , a s y s t e m a t i c n o m e n c l a t u r e  the  systematically-  names t h a n . a r e c u r r e n t l y u s e d i n t h e  literature. The p o r p h y r i n m a c r o c y c l e i s h i g h l y c o n j u g a t e d a n d a number o f r e s o n a n c e f o r m s c a n be w r i t t e n .  There are  22  n - e l e c t r o n s on t h e c a r b o n s k e l e t o n b u t o n l y 18 o f t h e s e a r e included  i n any one d e l o c a l i z a t i o n p a t h w a y  c o n f o r m s w i t h H u c k e l ' s 4n+2 r u l e e x p l a i n s why  (Figure 1).  f o r a r o m a t i c i t y and  t h e s e compounds a r e e x t r e m e l y s t a b l e .  This  also The  a r o m a t i c c h a r a c t e r i n p o r p h y r i n compounds h a s b e e n c o n f i r m e d by m e a s u r e m e n t s o f t h e i r h e a t s o f c o m b u s t i o n .  Further,  i n v e s t i g a t i o n s o f b o t h m e t a l - f r e e p o r p h y r i n s and  X-ray  metallo-  p o r p h y r i n s h a v e shown t h e p l a n a r i t y o f t h e n u c l e u s , w h i c h is  a basic requirement f o r aromatic character. Porphyrins are h i g h l y c o l o r e d w i t h a v e r y i n t e n s e  5  a b s o r p t i o n b a n d i n t h e r e g i o n o f 400nm. c h a r a c t e r i s t i c of the macrocyclic of the macrocycle r e s u l t s  This  " S o r e t " band i s  conjugation  and t h e r u p t u r e  i n the disappearance of t h i s  band.  I n a d d i t i o n , t h e r e a r e f o u r bands i n t h e v i s i b l e r e g i o n , t h e relative  i n t e n s i t i e s o f w h i c h v a r y d e p e n d i n g on t h e p e r i p h e r a l  substituents of the nucleus. The  i o n i z a t i o n o f t h e two i m i n e  N-H p r o t o n s  p o r p h y r i n y i e l d s a dianion, which f u n c t i o n s as a very  stable  t e t r a d e n t a t e l i g a n d towards a v a r i e t y o f metal i o n s . porphinato  l i g a n d has turned  coordination chemistry  porphyrins  are c l a s s i f i e d  or geometry o r both.  The  o u t t o be v e r y v e r s a t i l e i n  but nature  F e , Mg, C o , Cu a n d Zn b e i n g  of the  utilizes  o n l y a few m e t a l s ,  t h e m o s t common o n e s .  according  to their  Four coordinate,  Metallo-  stoichiometry  square-planar  geometry  i s r a t h e r r a r e and m o s t c e n t r a l m e t a l i o n s t a k e up a d d i t i o n a l l i g a n d s t o complete t h e i r c o o r d i n a t i o n  1.2  sphere.  SYNTHETIC ASPECTS OF PORPHYRINS  In t h e l a b o r a t o r y , as w e l l as i n n a t u r e ,  porphyrins  are s y n t h e s i z e d from p y r r o l e s which i n t u r n a r e r e a d i l y from a c y c l i c p r e c u r s o r s .  obtained  The meso c a r b o n atoms b r i d g e t h e  a - p o s i t i o n s o f t h e s t a r t i n g p y r r o l e s , t h e 3-carbons becoming the  8 p e r i p h e r a l carbons i n the porphyrin macrocycle.  Thus t h e  6  substitution marily is  on  p a t t e r n a t the p o r p h y r i n  the  3 - s u b s t i t u t i o n of the  a l s o p o s s i b l e to introduce  ones, a f t e r  the p o r p h y r i n  The three  fundamentally The  single  (b)  The  stepwise  nucleus  to a l i n e a r  to-tail  cyclization.  coupling of  two  The Siedel by  and  Winkler  heating,  general  first 4  a  obtained or  of  It  existing  constructed  in  are:  monopyrroles  individual  dipyrrolic  method has  e i t h e r dry  of  They  t e t r a p y r r o l e and  commonly r e f e r r e d t o as  pri-  i s constructed.  step condensation condensation  pyrroles.  groups or modify  d i f f e r e n t ways.  leading  The  starting  p o r p h y r i n m a c r o c y c l e c o u l d be  (a)  (c)  new  p e r i p h e r y depends  pyrroles  a final  head-  intermediates,  "2+2  synthesis";; ' ,  very  limited  synthetic value.  several 3-substituted  in solution,  compounds  porphyrins  .having  the  s t r u c t u r e shown b e l o w :  HOOC  When R = CH porphyrin  3  , heating  (OMP).  condensation  was  a t 160 -170 C gave 46.5% O)  o:i  of  octamethyl-  This reaction involving decarboxylation u n s u c c e s s f u l when one  or both  3-positions  and  7  were u n s u b s t i t u t e d . from the r e a c t i o n in acetic extended  acid  Haberle  o b t a i n e d 77%  5  of 3,4-dimethylpyrrole  and  pyridine.  to prepare  most common one  T r e i b s and  of  OMP  w i t h formaldehyde  This l a t t e r  r e a c t i o n has  several meso-substituted  ,  been  p o r p h y r i n s , the  being meso-tetraphenylporphyrin  1  (TPP)  6  1  Porphyrins substituted  i n b o t h meso and  prepared  Haberle  by  T r e i b s and  The ularly  5  and  search f o r a l t e r n a t i v e  Dolphin . 7  synthetic  methods,[partic-  f o r those porphyrins with unsymmetrically  B-substituents  Such methods u t i l i z e d  stable  types of l i n e a r 2.  involving  i n an unambiguous manner.  intermediates l e a d i n g to  t e t r a p y r r o l e s which are c y c l i z e d  in Figure  arranged  l e d to the development of syntheses  the c o u p l i n g of i n d i v i d u a l p y r r o l e s  basic  3 - p o s i t i o n s have been  i n the  tetrapyrrolic  last  step.  linear  The  intermediates are  four  shown  8  H  H  H  H  1,19-Dideoxybilane  H  °  H  b  c  H  1,19-Dideoxybilene-b  H  b  a  H  1,19-Dideoxybiladiene-ac  1,19-Dideoxybilatriene-abc  FIGURE 2 : L i n e a r T e t r a p y r r o l i c Syntheses  Intermediates i n Porphyrin  9 The p r e p a r a t i o n o f s u c h i n t e r m e d i a t e s porphyrin  syntheses  are discussed  Syntheses of porphyrins two d i p y r r o l i c widely  used  porphyrin  intermediates  i n porphyrin  syntheses  8  b a s e d on t h e c o u p l i n g o f syntheses)  chemistry.  intermediates  are:  (a)  Dipyrromethanes  (b)  Dipyrromethenes  (c)  Dipyrroketones  use i n  Johnson .  Many  have been a c c o m p l i s h e d  The t h r e e d i p y r r o l i c syntheses  (2+2  by  and t h e i r  have been  outstanding using  encountered  this  i n such  method.  10  Dipyrromethanes The u n s y m m e t r i c a l the  reaction  stituted  of  dipyrromethanes  a pyrrylcarbinyl  pyrrole  4 as  shown  cation  5 are  3_ w i t h  prepared  by  ct- nsub-  an  U  below.  etc.  The p y r r y l c a r b i n y l s u c h as  2 and a r e  cations  c a n be  stabilized  by  formed  the  readily  from  derealization  of  precursors the  11  p o s i t i v e The of  charge  s t a b i l i t y e l e c t r o n  e t c .  (at  has  been  w i t h  an  used  are  proceeds  of  the  i n  one  the  the  e l e c t r o n  per  s u b s t i t u e n t s r i n g ) .  The  c a t a l y s e d The  two  shown  i n  3.  In  v i a  b i l e n e - b  a u t o x i d a t i o n n  to  p y r r o l e  depends  on  such  e s t e r s ,  o n l y  c o u p l i n g  p y r r o l e .  a  r i c h  as  F i g u r e  the  to  a  of  types  an of  e i t h e r  n u c l e u s .  the  r e a c t i o n  2+2 ' p o r p h y r i n ^ s y n t h e s e s ^ v i a  a c i d  a - f r e e  the  dipyrromethanes  w i t h d r a w i n g  l e a s t  e x p l o i t e d  throughout  presence aldehydes  e f f e c t i v e l y  d i p y r r o m e t h a n e s ,  a - f o r m y l  group  r e a c t a n t s  c a s e ,  porphodimethene  the  commonly  r e a c t i o n  which  undergoes  p o r p h y r i n .  Dipyrromethenes Dipyrromethenes i n  t h e i r  salts, The of  of  more which  g e n e r a l an  s t a b l e  of  a  bromides  p y r r o l e s t r o n g  6  s t r o n g  p r o t o n a t e d  syntheses  a - f o r m y l  presence  the  are  of  a  have  form, been  bases the by  dipyrromethene  6_ w i t h a c i d .  7  an  ct-free  and  are  b e s t  handled  dipyrromethenium f a r  the  i s  the  p y r r o l e  most  p o p u l a r .  c o n d e n s a t i o n 7  i n  the  Por phodimethene  FIGURE 3 : P o r p h y r i n  Porphyrin  Synthesis v i a the 2 + 2 Coupling  Dipyrromethanes  of  13  In a d d i t i o n ,  several  have b e e n d e v i s e d . solution  s p e c i a l i z e d syntheses of S o l v o l y s i s of p y r r o l e s  of hydrobromic  by h e a d - t o - h e a d  and  formic  acids  dipyrromethenes  s u c h as 8 i n a h o t  lead  to  dipyrromethenes  condensation.  Br" _8 X = H. C0 H. C0 t-Bu 2  2  In  the presence of bromine,  in  a head-to-tail  10  and  11.  fashion,  a-methy1-a-free  pyrroles  giving, a mixture of  9  condense  dipyrromethenes  14 Porphyrins 10  have b e e n s y n t h e s i z e d  by r e f l u x i n g  i n formic  from d i p y r r o m e t h e n e s  acid.  The s e l f - c o n d e n s a t i o n i s o f  t h e h e a d - t o - t a i l f a s h i o n and a s s u c h , is  o f "type  I" (Section 1.1).  the r e s u l t i n g  by  the use o f anhydrous f o r m i c  a,  a'-dibromodipyrromethene with  acid. a  the r e a c t i o n mixture  in air.  of  a porphodimethene i n t e r m e d i a t e i n strong acid  This  o f an  a'-dimethyldipyrro-  c o n d i t i o n s i n the presence o f 1  of  slowly  to porphyrins  The c o n d e n s a t i o n  an ,  a l e n t o f bromine producesca p o r p h y r i n  rather  porphyrin  The a-bromo a ' - m e t h y l d i p y r r o -  methene p e r b r o m i d e s 1_1 have a l s o been c o n v e r t e d  methene u n d e r s i m i l a r  such as  o n l y upon  equiv-  evaporation  suggests  the  involvement  which o x i d i z e s to the p o r p h y r i n  medium.  Pipyrroketones Dipyrroketones step  2+2  . syntheses  functionality acidic  u s e among t h e one  The meso  deactivates the dipyrroketone,  i n the usual  component,  condensed w i t h  limited  of porphyrins.  c o n d i t i o n s , and p r e v e n t s  nucleophile philic  have o n l y  i t from b e i n g  coupling reactions.  carbonyl especially  used as the As t h e e l e c t r o -  a., a' - d i f o r m y l d i p y r r o k e t o n e s  a,a'-di-unsubstituted  a f t e r o x i d a t i o n , an o x o p h l o r i n  under  c o u l d be  dipyrromethanes, to give  (oxyporphyrin)  12.  15  The o x o p h l o r i n s acetylation Oxidation  may  be c o n v e r t e d  to porphyrins  f o l l o w e d by h y d r o g e n a t i v e  o f the r e s u l t i n g  r e d u c t i o n and r e -  porphyrinogen.  Dipyrroketones  have been f a r more u s e f u l i n t h e m u l t i s t e p porphyrins discusses  v i a oxobilanes. in detail,  In a r e c e n t  synthesis of  review,  Paine  9  the c o n s t r u c t i o n of the porphyrin  macrocycle using d i p y r r o l i c  1.3  by meso  intermediates.  METALLOPORPHYRINS AS BIOLOGICAL OXYGEN CARRIERS  Porphyrins,  porphyrin  d e r i v a t i v e s and p o r p h y r i n -  l i k e m a t e r i a l s p l a y a l a r g e number o f w e l l d i v e r s i f i e d and  well  established biological  roles.  Of t h e s e ,  one o f t h e most  significant  i s i t s role  of oxygen.  H e m o g l o b i n and m y o g l o b i n combine r e v e r s i b l y  dioxygen  i n the blood  i n the transport,exchange  and t i s s u e s o f a l l v e r t e b r a t e s  o f a "heme" [i i r o n ( I I ) p o r p h y r i n ]  protoporphyrin  by v i r t u e  ion i s chelated  n i t r o g e n atoms o f t h e s p e c i f i c  porphyrin,  IX (Pp) 13.  M = CH  Protoporphyrin  IX  (Pp) 13  I n t h e heme p r o t e i n s o f v e r t e b r a t e s in  with  p r o s t h e t i c g r o u p 14_. F o r  t h i s c l a s s o f r e s p i r a t o r y pigments, t h e Ee(II) to the four core  and s t o r a g e  3  V =  CH=CH  P =  CH CH COOH 2  2  2  Heme = F e ( I I ) P p  the porphyrin  14  i s embedded  a s t r o n g l y non p o l a r h y d r o p h o b i c e n v i r o n m e n t p r o v i d e d  by  the  amino a c i d s a l a n i n e , i s o l e u c i n e ,  and  v a l i n e of the polypeptide  porphyrin being  extend  out of this  leucine,  chains.  The a c i d  pocket.  composed o f o n l y one p r o t e i n c h a i n w h i l e  subunits,  each having  one heme g r o u p .  hemoglobin molecule c o n t a i n s two s u b u n i t s  3-subunit  as deduced  prosthetic non  called  group l i e s  bonding  such  t h e heme i r o n  the 3-chains.  "proximal"  histidine  indicates that the held  the protein.  ition  The s i n g l e  the  phyrins iron  Four o f i t s c o o r d i n a t i o n s i t e s a r e  by t h e i m i d a z o l e  the f i f t h  group.  the  porphyrin,  leads  geometry.  be a t l e a s t  axial  In t h i s  spin state  0.5 A  0  proposal  pos-  conformation with  S t r u c t u r a l s t u d i e s on i r o n  have l e d t o t h e g e n e r a l l y a c c e p t e d  atom w i l l  by c o o r d i n a t i o n  s t a t e t h e f e r r o u s i o n i s found  i r o n h a s been shown t o be i n t h e h i g h  square pyramidal  covalent  nitrogen of the so-called  by t h e p o r p h y r i n m o i e t y w h i l e  i s occupied  i n p l a c e by  residue.  be f i v e - c o o r d i n a t e .  satisfied  heme  v  i n a c r e v i c e , being  In t h e deoxygenated to  polypeptide  The s t r u c t u r e o f t h e  from x - r a y d a t a  to the imidazole  vertebrate  known a s t h e a - c h a i n s  a t t a c h m e n t o f t h e heme t o t h e p r o t e i n o c c u r s of  most  The n o r m a l a d u l t human  two s u b u n i t s  i n t e r a c t i o n s with  groups o f the  M y o g l o b i n s a r e monomeric,  hemoglobins a r e t e t r a m e r i c c o n t a i n i n g four  and  phenylalanine  por-  that the  o u t o f t h e mean p l a n e o f  towards t h e c o o r d i n a t e d  imidazole.  Oxygenation  t o a s i x - c o o r d i n a t e low s p i n system i n which t h e i r o n 11  is  essentially  iron  i n t h e porphyr-ini p^lane-  atom upon o x y g e n a t i o n 1  Fourier  techniques  a n d t h e motion, o f t h e  has been d e m o n s t r a t e d by d i f f e r e n c e  2 .  Although  many d e t a i l s  of the structures  18 o f h e m o g l o b i n and m y o g l o b i n a r e known, t h e n a t u r e o f t h e i r o n - d i o x y g e n bond  h a s been a c o n t r o v e r s i a l  time, p a r t i c u l a r l y  as t o whether  to e i t h e r  one o f t h e s t r u c t u r e s  subject  t h e geometry shown  f o r some  approximates  below:  0=  i i  J  0  •  —  An  Fe  —  —  a c c u r a t e d e t e r m i n a t i o n o f oxyhemoglobin  structures  h a s been d e l a y e d  of o x i d a t i o n o f the i r o n measurements.  and o x y m y o g l o b i n  c o n s i d e r a b l y due t o t h e p r o b l e m  centre  Recent advances  t o F e (III).'  during  i n low t e m p e r a t u r e  ha^ve made t h e s t r u c t u r e d e t e r m i n a t i o n p o s s i b l e 1  Fe —  X-ray techniques  f o r sperm  whale  3  o x y m y o g l o b i n - , w h i c h has shown t h a t o x y g e n  i s bonded  i n the  o end-on  f a s h i o n w i t h an Fe-O-0 a n g l e o f 121 . The most i n t e r e s t i n g  p r o p e r t y o f hemoglobin i s i t s  c o o p e r a t i v e b i n d i n g o f o x y g e n , w h i c h makes i t t h e u n i q u e carrier  i n vertebrates.  The e q u i l i b r i u m u p t a k e o f o x y g e n by  t e t r a m e r i c h e m o g l o b i n t u r n s o u t t o be more complex t h e c a s e o f t h e h e m e - p r o t e i n monomers.  tetramer.  upon t h e number o f o t h e r  than f o r  The a f f i n i t y  s u b u n i t t o add a s i n g l e m o l e c u l e o f o x y g e n dependent  oxygen  of a  i s apparently  subunits oxygenated i n the  T h i s g i v e s hemoglobin the a b i l i t y  t o show  high  affinity low  at high p a r t i a l  affinity  pressures  ( e . g . , i n t h e l u n g s ) and  a t low oxygen p r e s s u r e s  which i s c r i t i c a l  to e f f i c i e n t  oxygen t r a n s p o r t .  operativity  hinges  information  t h a t one heme has been l i g a t e d  utilizing  this  thoseshemes. control is  first  (e.g., i n the t i s s u e s ) ,  upon r e l a y i n g  information to alter  t o t h e o t h e r hemes t h e and s e c o n d ,  the suggestions  by P e r u t z  of W i l l i a m s  1 5  1 0  and H o a r d  state  and a r e l a x e d  (R) state,, f o r t h e h e m o g l o b i n  in  On o x y g e n a t i o n ,  the decrease  "proximal"  i n the s t a b i l i t y  and c a u s e s  model i s b a s e d  the observed  essentially  that other  some s h o r t c o m i n g s mechanism.  1 7  (T)  histidine  than the t h e mean  residue. that  results  cooperativity.  Thus,  on t h e movement o f t h e i r o n  investigators  This  of the T-state r e l a t i v e to  o u t o f t h e mean p o r p h y r i n p l a n e .  noted  a tense  by t h e movement  a change i n t h e s t r u c t u r e o f t h e p r o t e i n  the R - s t a t e  and  t h e heme i r o n moves i n t o  this  atom i n  However, i t s h o u l d be  have c o n c l u d e d  or unresolved d i f f i c u l t i e s  that there are i n this  4  The  tetramer.  t o be more s t a b l e  o f t h e p o r p h y r i n s which i s accompanied  the c o v a l e n t l y l i n k e d  causes  1  t h e T - s t a t e , c h a r a c t e r i z e d by a l a r g e  iron-porphyrin distance i s said  of  .  1 6  o f t h i s model i s t h e e x i s t e n c e o f two s t a t e s ,  plane  accepted  and c o - w o r k e r s ' '  basis  R-state.  might  o f h e m o g l o b i n , t h e most w i d e l y  t h e t r i g g e r mechanism p r o p o s e d  W i t h no o x y g e n p r e s e n t ,  upon  t h e oxygen a f f i n i t y a t  Of t h e many ways i n w h i c h t h e p r o t e i n  the c o o p e r a t i v i t y  following  The c o -  trigger  20 1.4  SYNTHETIC MODELS FOR BIOLOGICAL OXYGEN CARRIERS  T h e r e have been many e f f o r t s Fe(II)  complexes  hope t h a t  t h a t would r e v e r s i b l y  oxygen  give  information  about  o f t h e m e t a l - d i o x y g e n bond and t h e a s s o c i a t e d  kinet  s t u d i e s on s u c h  nature  and  thermodynamic  systems would  factors.  a p r o t e i n - f r e e model  A major problem  Fe^yPjL  base  such  f o r t h e heme p r o t e i n s h a s been t h e d i f f -  complex o f t h e t y p e  nitrogeneous  i n the  i n designing  of synthesizing a suitable high-spin  Fe(II)',  simpler  bind  the  iculty  to synthesize  Fe  I I  (P)L  (P = porphyrin;  s u c h as i m i d a z o l e ) .  usually result  five-coordinate  Low-spin  L =  six-coordinate  and i n c o n t r a s t t o t h e r e v e r s i b l e  . 2  oxygen b i n d i n g porphyrins by  ability  o f heme p r o t e i n s , s u c h  are rapidly  molecular  oxygen.  and i r r e v e r s i b l y  simple  ferrous  oxidized to Fe(III)  The r e v e r s i b l e o x y g e n b i n d i n g  property  o f heme p r o t e i n s d e p e n d s C G ' r i : t r e a l l > y - ~ o , n i ^ h e ^ f a e t t i t h a t - - t h e " i r o n centre this  i s not oxidized.  autoxidation  iron-dioxygen  I t i s now g e n e r a l l y b e l i e v e d  proceeds v i a the formation  adduct, which subsequently  M —peroxo dimer e v e n t u a l l y p r o d u c i n g Fe Fe L(P)Fe  I 3 :  L(P)Fe L  (  P  )  I F  e  V  I 3 :  0  I I I  I 3 :  (P)L +  2  -0 -Fe  (P)L +  Fe I I I  2  _ 0  +  Fe  0 i : [  2  2  (P)L  (P)L I 3 :  (P)L  +  dimerizes  Fe (P)L  +  IJ  J  -  o f t h e monomeric to a  a y-oxocddmer.  l  +  that  L(P)Fe L(P)Fe 2 (P)Fe  i : E I  I 3 :  0  I I I  2  -0 -Fe 2  L(P)Fe  L  I V  i : C I  (P)L  -0  -0-Fe  I I I  (P)  + 2 L  21 R e s e a r c h on s y n t h e t i c m o d e l s f o r t h e n a t u r a l l y occuring and  heme p r o t e i n s has u n d e r g o n e s i g n i f i c a n t  experimental  theoretical  developments w i t h i n the l a s t decade.  c a r b o n monoxide i s n o t a n a t u r a l s u b s t r a t e systems i t s i n t e r a c t i o n  i n biological  has a l s o been w i d e l y  studied.  interest  i n c a r b o n monoxide d e r i v e s  from i t s s t r o n g  to those  metalloproteins  or u t i l i z e  consequent a b i l i t y The  which b i n d  to i n t e r f e r e with  t o be a u s e f u l t e c h n i q u e  or i n h i b i t  t h e work d e s c r i b e d  i n these  some s e l e c t e d m o d e l s w i l l  their  p o i n t o f view.  be d i s c u s s e d  (b)  i n this  area  only a  19  ' •'. have  and t h e r m o d y n a m i c  of research.  two most d e s i r a b l e f e a t u r e s o f a model f o r t h e are:  (a) t h e a b i l i t y  f i v e - c o o r d i n a t e geometry o f t h e type  the suppression  ing dimerization. to prevent  Since  here,"primarily.from  Two e x c e l l e n t r e v i e w s "  n a t u r a l heme o x y g e n - c a r r i e r s stable  i o n s has  f o r model s y s t e m s ,  appeared r e c e n t l y t h a t d i s c u s s the k i n e t i c  The  function.  studies.  18  observations  binding  i n t h i s t h e s i s i s concerned with the  d e v e l o p m e n t o f a new s y n t h e t i c r o u t e  synthetic  This  o x y g e n and i t s  s u b s t i t u t i o n o f i r o n by s e v e r a l d i v a l e n t m e t a l  a l s o proved  Although  of the i r r e v e r s i b l e  t o form a  F e * * ( P ) L and-'  o x i d a t i o n by i n h i b i t -  S e v e r a l o f t h e s y n t h e t i c models  designed  a u t o x i d a t i o n o f t h e f e r r o u s heme have a l s o l e d t o  the  formation  of five-coordinated iron-porphyrin  The  syntheses o f porphyrins  one  face o f the macrocycle appeared  with  to the problem o f d i m e r i z a t i o n .  systems.  protective structures t o be t h e b e s t  covering  solution  Foxr t h i s p u r p o s e two a p p r o a c h e s  22  have b e e n a d v a n c e d . part The  and  the  porphyrin  porphyrin  ring  condensation. with  chains  An  molecule  nucleus  t o form  the  with  cyclized bridge  two  the  are b u i l t  itself.  to the  then  begins  precursors  alternative  introduced  which are  route  is finally  the p o r p h y r i n  groups are  One  by  non-porphyrin  onto  the  two  ends.  intramolecular  forming  method  starts  Appropriate functional  diagonally substituted side  condensed w i t h  another  bifunctional  bridge. 2 0  Traylor the to  and  collaborators  synthesis of a porphyrin inhibit  studies  irreversible  have e v e r  most s i g n i f i c a n t  that u t i l i z e d  oxidation.  been r e p o r t e d w i t h f e a t u r e s of t h i s  of  Cu(II). „. i o n c h e l a t i o n t o f i x t h e  cyclophane biphenyl  1(5 by  two  first  utilizing  of  the  f o l l o w e d by  2 0 was  by  subsequently  through standard  the  (b)  no  succinic  acid  to  the  The  advantage  .  The  starting  reduction),  second  diacid  linked  from  1_7 was  w h i c h was  p y r r o l e 2_5 i n HBr  converted molecules  d i k e tone.  then  to g i v e  the  using  t o two  T h i s was  pyrrole transformations  a-unsubstituted  use  - Crafts paeylation  and  then  2_1  two  (a) t h e  F r i e d e l - C r a f t s aaey.Mvtion. The reduced  binding  The  taking  synthesized  a - f ormy 1 - a ''- cairboxy-py^rorlcel e d i m e r >-24 with  system.  a Wolff-Kishner  c h l o r i d e 1_8_ and  p y r r o l e 19  encumberance  d i p y r r o m e t h e n e ends i n  was  3-carbomethoxypropionyl c h l o r i d e . the b i s a c i d  and  successive Friedel  (each  to  this  to r e p o r t  intramolecular condensation.  s y s t e m 17_ ( F i g u r e 4)  reactions one  intermediates  f o r an  steric  synthesis are,  d i p y r r o m e t h e n e s as  position  first  Unfortunately,  of  proper  were t h e  carried  the condensed  in acetic  acid  to  R =  (CH )^CO^t 2  15  17 : x = O H  16  18  • «•  2  x = ci  18:  'XX  F l N  COjEt  CO^t  -2 l  19  20 21  CH  3  co^t  22  CH  3  COjCHjPh  23  CHO  CO^HjPh  2U  CHO  co^  .QHCH, 24  f l  2  N '  H  „,25  CH,  , . : R = (CH^co^t  26: — 27  R ' = C O , H , R = (cH,),co-,Et 2  : R'= Br  2  ;  3  2  R^ICH^CO-Et  28  R'=  ICHjIjCO^t  FIGURE 4 : S y n t h e s i s o f t h e C y c l o p h a n e P o r p h y r i n o f Traylor  et.  al.  give  the dipyrromethene  group  dimer  o f 2_6 t o bromo g r o u p s  the r e s u l t i n g complex 28. copper  2_6.  After  c o n v e r t i n g the carboxy  by r e a c t i n g w i t h Br^ i n a c e t i c  p y r r o m e t h e n e 2_7 was t r a n s f o r m e d Heating  into  5%.  i t s copper  2_8_ i n x y l e n e w i t h t r i e t h y l a m i n e g a v e t h e  complex o f t h e p o r p h y r i n 1_5 i n a low y i e l d  imately  acid,  The i n a b i l i t y  of  o f t h e a u t h o r s t o improve  approxthe y i e l d  c o u l d be why more work has n o t been r e p o r t e d . Baldwin "capped" up  and c o - w o r k e r s  porphyrin u t i l i z i n g  t h e same s t r a t e g y ,  t h e p o r p h y r i n a t t h e ends o f t h e " c a p " .  was much s i m p l e r a s t h e y u s e d aromatic aldehyde 29  s y n t h e s i z e d a more h i n d e r e d  2 1  the s i n g l e  with pyrrole  (x = 2 o r 3) were p r e p a r e d  (Figure from  (x  acid  approach  The t e t r a a l d e h y d e s  salicylaldehyde  and  condensed  30_ i n r e f l u x i n g  prop-  t o g i v e t h e " c a p " (x — 2) and t h e "homologous c a p "  = 3) p o r p h y r i n s 3_1 i n a p p r o x i m a t e l y  oxygenation  The s y n t h e t i c  s t e p c o u p l i n g o f an  5).  separately with 4 equivalents of pyrrole ionic  i . e . , building  o f the Fe(II) s u b s t i t u t e d  2% y i e l d . capped  Reversible  porphyrin i n 22  pyridine  solution  had been f o l l o w e d s p e c t r o s c o p i c a l l y  at  25°C,, t h e l i f e  be  approximately  5%  1-methylimidazole,  With  the Fe(II)  reported  2 3  time o f the dioxygen  20 h o u r s .  t i m e had d e c r e a s e d  "homologous c a p " s y s t e m  species.  binds dioxygen  (under t h e  They b e l i e v e  reversibly,  recently  suggest the  l - m e t h y l i m i d a z o l ^ e "- l i g a n d  a 6-coordinate  complex so formed  to 5 hours.  these workers  some s p e c t r o s c o p i c o b s e r v a t i o n s t h a t  to y i e l d  was f o u n d t o  In benzene s o l u t i o n s c o n t a i n i n g  the l i f e  weak b i n d i n g o f a s e c o n d cap)  adduct  and  without  that the displacing  25  FIGURE 5  : Synthesis of  t h e Capped P o r p h y r i n o f B a l d w i n e t . a l .  the  weakly  bound l i g a n d . An  m o d e l was also  alternative  reported  utilized  ends of  the  by  2 4  hindered  porphyrin  Baldwin's  the  s t r a t e g y of  strap  (Figure 6).  group,  building The  known as  the  the  a  "strapped"  synthesis of  porphyrin  at  synthesis followed  which  the  the 2  dipyrromethane route The  b i s aldehydes  available  developed  32_ a n d  starting  3_3  dipyrromethanes  3_5  ated  hydrogenation)  the  of  porphyrins  both  (-55°C), a t  and  benzyl  3_6.  ester  porphyrins  and  from  readily  37_ a n d  3_8.  to give  the  subsequently  the  bis debenzyl-  treated with trimethyl  with  trichloroacetic  Although  were oxygenated  25°C t h e y  3_4  These were  i n dichloromethane  produce  obtained  m a t e r i a l s ) were each condensed w i t h  pyrrolyl  orthoformate  K e n n e r and c o l l a b o r a t o r s .  (easily  a-unsubstituted  (catalytic  by  5  the  reversibly  were c o n v e r t e d  acid,  Fe(II)  at  irreversibly  low  to  complexes  temperatures  into  u-oxo  dimers. The hindered i.e.,  more w i d e l y  porphyrins  to condense  a bifunctional  this  approach with of  bridged  approach  been the  second  to  the  route  synthesis mentioned  a d i a g o n a l l y s u b s t i t u t e d preformed  with  series  has  used  molecule.  Battersby  and  of earlier,  porphyrin  co-workers  2 6  s e v e r a l s y n t h e t i c v a r i a t i o n s to produce porphyrin  systems.  used a  27  FIGURE 6  : Synthesis of  the  Strapped  P o r p h y r i n of Baldwin  et. a l .  28  The  bis acid  starting  c h l o r i d e of mesoporphyrin  porphyrin  and  was  reacted with  t h e d i e s t e r 4_0.  T h i s , when s u b j e c t e d  at  with  high d i l u t i o n  copper  and d'emefca-Ma-bed'.d' t o p r o d u c e t h e T h e s e w o r k e r s were a l s o a b l e amide l i n k e d  bridge  1 , i2Vdlfam iinodo'd"ecan ee 1  ,  ;  of  these  The  give  in pyridine-ether  compound 41  was  saturated bridged  hydrogenated system  the p o r p h y r i n  r e a c t i n g 3_9 d i r e c t l y  under h i g h d i l u t i o n .  s y s t e m s were a l s o i r r e v e r s i b l y  temperature.  to  the  t o an o x i d a t i v e c o u p l i n g  to synthesize  s y s t e m by  u s e d as  hex-5-yn-l-ol  (II) a c e t a t e  gave t h e c o p p e r complex o f 4_1.  an  I I 3_9 was  The  Fe(II)  42. 4_3_ w i t h  with complexes  o x i d i z e d a t room  29  Using  similar  m a t e r i a l s O g o s h i and phane p o r p h y r i n s A mixture  8,  9,  with  10,  with in  similar  and  They o b s e r v e d  the  s y n t h e s i s o f the the  side chains.  isobutyl  H N-(CH ) -NH 2 2 n 2  was  (n=6,  7,  cyclophane  t h e -n=6 ^systemu-the-  5-coordinate  and  lengths.  intermediate  irreversibly  oxidized  oxygen.  same l i n e s .  (d-ihexyldeuteroporphyrin  44  chain  tetrahydrofuran  corresponding  p y r i d i n e , b u t was- r a p i d l y  a l s o along  type  that with  complex p r o d u c e d o n l y  The  acid  different  t r i e t h y l a m i n e i n dry  to o b t a i n the  the p r e s e n c e o f  was  produced a s e r i e s of c y c l o -  2 7  t o 43_ w i t h  bis-amines of the  12),  porphyrins. Fe(II)  co-workers  starting  of the p o r p h y r i n - b i s - p r o p i o n i c a c i d ,  chloroformate treated  s y n t h e t i c s t r a t e g y and  "crowned" p o r p h y r i n He  too used a  II) which c a r r i e d  T h i s was  condensed w i t h  c o n t a i n i n g a l a r g e crown e t h e r  group.  by  Chang  porphyrin  two  propionic  the  bis-amine  2 8  30 In  the presence of 1-methylimidazole,' the Fe(II)  of  this  porphyrin  indicating its  that  exhibited  the base  d i o x y g e n complex was  3 minutes  a t room Based  co-workers  2 9  cyclophane"  on  had  the r e g u l a r c r e p t under  found  complex  6-coordinate the s t r a p .  t o have a h a l f - l i f e  spectrum Further,  of  only  temperature. t h e same s y n t h e t i c  recently  synthesized  s y s t e m by c o n d e n s i n g  the  approach  Traylor  and  "anthracene-heme^  a diagonally  substituted  p o r p h y r i n - b i s - a m i n e w i t h t h e b i s a c i d c h l o r i d e 4_5 shown below.  46  47  In  order  to reduce  the f l e x i b i l i t y  these workers performed anthracene  -CH -NH-CO-(CH ) 2  2  linked  -.  t h e "pagoda p o r p h y r i n " ,  t o t h e d i a g o n a l 3 - p o s i t i o n s by  of 1-methylimidazole  have p r o v i d e d  f o r the existence o f a 5-coordinated  s o l u t i o n demonstrating Of  the s t e r i c  effect  i n mimicking  Designing  t h i s model was b a s e d  tetraphenyl-porphyrin to the plane  the phenyl  effectively this  and  on t h e f a c t  (TPP) 1_, t h e p h e n y l o f the porphyrin.  ring, modified  into  the  and c o - w o r k e r s .  t h a t i n mesorings  are perpen-  group c o u l d  b l o c k one f a c e o f t h e p o r p h y r i n m o l e c u l e .  4_8_ by r e a c t i n g  For  meso-tetra(o-nitrophenyl)  o-nitrobenzaldehyde  with pyrrole  by a g/tan'n~o<us5 c h l o r i d e r e d u c t i o n o f 48_, o b t a i n e d meso-  tetra  (o-aminophenyl) p o r p h y r i n  3 0  Thus^an^orthb-substituent  a bulky  purpose these workers prepared  porphyrin  to date,  o x y g e n b i n d i n g p r o p e r t y o f heme p r o t e i n s i s t h e " p i c k e t - f e n c e p o r p h y r i n " o f Collman  on  group.  a l l t h e s y n t h e t i c m o d e l s t h a t have a p p e a r e d  so c a l l e d  dicular  species i n  of the bulky  t h e one t h a t h a s had t h e g r e a t e s t s u c c e s s reversible  with  P r e l i m i n a r y b i n d i n g s t u d i e s o f the Fe(II)  system i n the presence evidence  system,  a D i e l s - A l d e r a d d i t i o n o f 4_6_ on t h e  g r o u p and o b t a i n e d  t h e g r o u p 4_7 b e i n g  of the cyclophane  (H^TamPP) 49.  32  48  :  49: 50  The a , a, a, a a t r o p i s o m e r was c h r o m a t o g r a p h y and  the approach  5_0.  The  of a second  w o r k e r s were a b l e t o i s o l a t e o f F e ( I I ) and One t o mimic  determine  NO  2  R =  N H  2  R =  NHCOC(CH ) 3  the o t h e r s  f r o z e n by  such  g r o u p so w e l l ,  a c r y s t a l l i n e dioxygen  system  a second  Unless  by formgroups  that  these  complex  i n attempting  w i t h most o f t h e model  s p e c i e s i n solution',-  c o o r d i n a t e F e ( I I ) system.  3  structure.  of the b i g g e s t problems encountered  is maintaining a single  the  four bulky pivalamide  i t s crystal  the b i o l o g i c a l  base i s used  from  i t s c o n f i g u r a t i o n was  a t i o n o f the p i v a l a m i d e hinder  separated  :  R =  i . e . , the  a very bulky  ligand molecule  compounds 5-  nitrogeneous  i s observed  to coordinate  33  to the c e n t r a l i r o n atom on the s i d e of the p r o t e c t i v e c o v e r i n g To overcome t h i s problem T r a y l o r and a porphyrin  i n which a nitrogeneous  onto the p e r i p h e r y . 5-coordinate  co-workers base was  covalently linked  These " t a i l - b a s e " p o r p h y r i n s  s p e c i e s as expected.  constructed  31  produced  F u r t h e r , by u s i n g carbon  monoxide to p r o t e c t a g a i n s t o x i d a t i o n and  removing i t q u i c k l y  by f l a s h p h o t o l y s i s these workers were a b l e to use r a p i d s p e c t r o s c o p i c and k i n e t i c methods i n mixtures of CO to study  the s o l u t i o n behaviour of the  o b t a i n a working model f o r the R and  COR  0^  metalloporphyrins.  By v a r y i n g the l e n g t h of the carbon c h a i n t h a t l i n k s base to the p o r p h y r i n p e r i p h e r y i t has  and  the  a l s o been p o s s i b l e to  T s t a t e s of hemoglobin.  1  COR' 51  R =R =0H 1  2  The  R = R 4 = C0 CH Ph 3  :  2  2  53  l a t e s t a d d i t i o n to t h i s long l i s t of s y n t h e t i c  3 2  m o d e l s was The  the doubly  starting  protected  porphyrin  taining diol The R  3  p o i n t of  52 b y  a n t h r a c e n e cap and  R  4  to a c i d  the b i s a c i d (The  bridged  t h i s s y n t h e s i s was  5_1 w h i c h was converting was  functions  c h l o r i d e and  incorporation of  1  (51)  2  inary  solution  binds  dioxygen r e v e r s i b l y  studies with  this with  by  this  been  found  converting obtaining  the d i o l t o be  anthracene cap).  53_  easier Prelim-  s y s t e m have shown t h a t i t  a t the F e ( I I )  s p e c i e s has  to c h l o r i d e s .  introduced  condensing  Hamilton.  p y r i d i n e con-  (by h y d r o g e n o l y s i s ) ,  i n t r o d u c t i o n o f the  the  and  R  and  differentially  to the  t h e m e t a l i o n was  to the  time o f  R  the  linked  subsequently  prior  life  system o f B a t t e r s b y  short.  c e n t r e but  the  35  CHAPTER  RESULTS  AND  2  DISCUSSION  36  2.1  SYNTHETIC OBJECTIVE  One o f t h e most s i g n i f i c a n t metalloporphyrins (M-N) bond.  M-N v a l u e s  and a s i s t h e c a s e  constraints  t o the p o r p h y r i n diaruion l e a d t o v a r y i n g of a l l macrocyclic ligands,  of the porphyrin r i n g  distances.  limit  t o u n d e r g o undue r a d i a l  doming o f t h e p l a n a r  expansion  o f t h e f o u r n i t r o g e n atoms.  Although  to maximizing  conformations  Such a  system would a l l o w t h e i n c r e a s e o f the the metal  planar  or c o n t r a c t i o n i s the  n o r m a l t o t h e mean p l a n e .  d i s t a n c e by p o s i t i o n i n g  unfavourable  the range o f a c h i e v a b l e  In c o n t r a s t t o t h e r e s i s t a n c e o f t h e p o r p h i n a t o  ease o f i t s d e f o r m a t i o n  M-N  nitrogen  The v a r y i n g s i z e s and t h e c o m p l e x i n g powers o f coordinated  core  features of  i s the length of the metal-porphine  the metals  M-N  structural  o u t o f t h e mean  plane  such  deformations are  the d e l o c a l i z e d  IE b o n d i n g , n o n -  a r e known t o e x i s t  in crystalline  pyramidal  (shown below) i s  metalloporphyrins. The very  square  common f o r 5 - c o o r d i n a t e  for  z i n c , magnesium, c o b a l t  The  displacement  a physically class  real  o f the metal  geometry  metalloporphyrins  ( I I ) and h i g h - s p i n i r o n  property of metalloporphyrins  stereochemical  systems.  atom f r o m t h e mean p l a n e i s  and i t s m a g n i t u d e v a r i e s f r o m  Perutz's  especially  of this  0.1 t o >0.5 A  0  .  In  t r i g g e r mechanism f o r c o o p e r a t i v e  37  oxygenation the  o f hemoglobin  (Section 1.3), the primary  l a r g e change i n t h e s t e r e o c h e m i s t r y  g r o u p o f heme w h i c h i s c o n c o m i t a n t from h i g h The  spin 5-coordination  domed p o r p h y r i n  out o f the plane regain  with  of the c o o r d i n a t i o n the transformation  t o low s p i n  system w i t h  trigger i s  the metal  6-coordination. atom p o s i t i o n e d  o f t h e f o u r n i t r o g e n atoms i s t h o u g h t  i t s planarity  upon o x y g e n a t i o n  with  atom back i n t o  plane.  movement o f t h e m e t a l With such  an e m p h a s i s l a i d  of metalloporphyrins  t h e accompanying  on s t e r e o c h e m i c a l  i t was o f i n t e r e s t  to  changes  t o c o n s t r u c t a system  i n which the p o r p h y r i n  i s f o r c e d t o be n o n - p l a n a r  its  T h i s w o u l d a l l o w one t o e s t i m a t e a t  metal  free  state.  least qualitatively,  even i n  t h e i m p o r t a n c e o f t h e phenomenon o f  38 doming i n m e t a l l o p o r p h y r i n c h e m i s t r y e s p e c i a l l y of oxygenation  and c o o p e r a t i v i t y .  c o u l d be s y n t h e s i z e d by c o v a l e n t l y 3 - p o s i t i o n s with a s h o r t carbon ring  to attain  planarity.  bonding could  atoms i n o r d e r orbitals  be e x p e c t e d  Such a n o n - p l a n a r linking  two d i a g o n a l  c h a i n t h a t would n o t a l l o w t h e  o u t o f t h e mean p l a n e o f t h e  t o a t t a i n maximum o v e r l a p w i t h t h e  of nitrogen.  An a r r a n g e m e n t o f t h i s  to favour a 5-coordinate  system  l :  The p o r p h y r i n f i x e d  i n this  Fe  of  t h e cor>e t o a l l o w a s e c o n d  bind.  In a d d i t i o n ,  the s t e r i c  would n o t f a v o u r t h e approach side.  I I  (P)L  domed  c o n f i g u r a t i o n w o u l d n o t be a b l e t o a t t a i n p l a n a r i t y t h e a c c o m p a n y i n g movement o f t h e m e t a l  type  s u c h as  F e ? ( P ) L whereas t h e f o r m a t i o n o f t h e 6 - c o o r d i n a t e w o u l d be m i n i m i z e d .  porphyrin  With such a . p o r p h y r i n the metal i o n  w o u l d have t o be p o s i t i o n e d  nitrogen  i n the context  with  i o n to the centre  ligand molecule  (base) t o  encumberance o f t h e s t r a p of a large  ligand  On t h e o t h e r hand, f o r s m a l l m o l e c u l e s  from  that  s u c h as 0  o  and  'CO- t h e s t e r i c  be  significant  the  hindrance o f the carbon  and i t w o u l d be i n t e r e s t i n g t o s e e what e f f e c t  doming o f t h e p o r p h y r i n  Further, ation  h a s on t h e i r b i n d i n g  i t w o u l d be p o s s i b l e  by c h a n g i n g  would p r o v i d e  s t r a p would n o t  the length  to vary  the extent o f deform-  o f the carbon chain.  systems i n which t h e m e t a l  This  ion i s progressively  removed f r o m t h e mean p l a n e o f t h e p o r p h y r i n  2.2.  properties.  nitrogen  atoms.  SYNTHETIC PLAN  *x The planarity 18  i n order  T-electron  synthetic basic  requirement that  system, imposes a s p e c i a l r e s t r i c t i o n  strategy  f o r the desired  approaches t h a t  involves  porphyrin  product.  have been u t i l i z e d (Section  maintains  on t h e  Of t h e two  f o r the synthesis of  1.4) i t i s c l e a r t h a t  the introduction  o f the strap  t h e one  t o a preformed  c a n n o t be made u s e o f i n t h i s work.  o n c e f o r m e d , c a n n o t be e x p e c t e d chain  macrocycle  t o a t t a i n maximum d e l o c a l i z a t i o n o f t h e  cyclophane porphyrins that  a porphyrin  A  porphyrin  t o condense w i t h a carbon  i f i t w o u l d d e f o r m t h e m o l e c u l e and t h e r e b y c a u s e t h e  reduction  of its. stability.  covalently  linked to a porphyrin  t o be n o n p l a n a r after.  Thus i f a s h o r t i n order  strap  to force  i s t o be the molecule  i t has t o be done b e f o r e c y c l i z a t i o n and n o t  Therefore  the synthetic  building  the porphyrin  followed  by an i n t r a m o l e c u l a r  strategy  precursors  should c o n s i s t of  a t t h e ends o f t h e c h a i n  cyclization.  40  As for of  f o r any  developing the  and  target molecule entire  stituents  double disconnection  a-ho.a-unsubstituted a methene l i n k .  = R 1 leads  would h o l d the  = R  and  R  5  = R 3  chain.  acid  dipyrrolic  The  reverse  o f compound  the  p y r r o l e to 55_ one  methane l i n k a g e s and  intermediate the  two  unstable  rapidly  the  crucial  three d i p y r r o l i c  for this  f o r the  a  the  tetra-  5_5_ i s a t  the would  Such a  Porphodimethenes  a r e known t o  be  porphyrin.  single  success  intermediates  con-  for  of a dipyrromethane r a t h e r than  pyrromethene i n t e r m e d i a t e r e a c t i o n was  such  methene l i n k a g e s .  i n t h e p r e s e n c e o f a i r and  choice  produce  t e t r a p y r r o l e formed  a u t o x i d i z e d t o t h e more s t a b l e The  of  c a t a l y z e d r e a c t i o n of  compound i s r e f e r r e d t o as a p o r p h o d i m e t h e n e . are  , the  four p y r r o l e s i n p o s i t i o n  Since  the  6  to f o l l o w e v e n t u a l l y producing  macroeycle.  the  i n t e r m e d i a t e 5_5_  t o a symmetric  case  b a s e d on  disconnection of  pyrrole withafea-formyl In the  was  W i t h t h e p e r i p h e r a l sub-  2  dipyrromethane o x i d a t i o n l e v e l have two  t h e s i s was  first  , R  4  i s a simple  second condensation pyrrolic  The  a l r e a d y c a r r y i n g the  disconnection  densation  in this  s y n t h e t i c scheme.  1  this  later 7.  synthetic plan that  5_4_ l e d t o t h e most c r u c i a l  c h o s e n as R  intermediate  The  i n Figure  approach  a retrosynthetic analysis  itself.  described  analysis given  the  s y n t h e s i s the b e s t  a s y n t h e t i c r o u t e was  t a r g e t molecule  developed  of  extended o r g a n i c  step  of t h i s  2+2-  a dicoupling  synthesis.  g e n e r a l l y used  for  Of  this  3 type  of  bridging  syntheses  o n l y d i p y r r o m e t h a n e s c o n t a i n s;p-< h y b r i d i z e d  c a r b o n atoms.  The  first  t e t r a p y r r o l e t h a t would  be  FIGURE 7  : A  Retrosynthetic A n a l y s i s of  the  Target  Molecule  formed  from  reactive  a head-to-tail  c o u p l i n g a t any  c e n t r e s o f 55_ would be  which i s a l i n e a r 3 (sjp- ) and  of the  a bilene-b (section  tetrapyrrole with  two  2  one  one  methene b r i d g e (sp-) .  two 1.2)  methane b r i d g e s  Such a s y s t e m  would  be  t h e most f a v o u r e d t o accommodate a d i a g o n a l l y p o s i t i o n e d strap.  With dipyrromethenes  p y r r o l e most commonly  as p r e c u r s o r s , t h e l i n e a r  encountered  with  short  tetra-  i s - the i b i l a d i e n e - a , c  • 2 (Section  1.2)  which would plane with  w i t h two  force  sip  t h e two  hybridized pyrroles  t h e meso c a r b o n .  necessary  f o r the  t o form  a bilene-b  second  the c y c l i c  (the f i r s t  i n each  carbon  half  product  able to a t t a i n  head-to-tail system. from  On  atoms  t o be  Further, a biladiene  w i t h a s h o r t s t r a p w o u l d n o t be juxtaposition  bridging  in  one  system  the  correct  condensation the other  hand,  dipyrromethanes)  with  3 two sjp  hybridized  reacting of  carbon  b r i d g e s should h o l d the o t h e r  groups i n the c o r r e c t o r i e n t a t i o n  a short  even i n the  i m e t h e n e and  the  first  cyclic  not a p o r p h y r i n the  c h a i n w o u l d be  comparatively  w o u l d be more f a c i l e .  The  low  rapid  product strain and  formed  i s a porphod-  imposed by  for this  of  reaction  autoxidation of  to completion.  p l a n a r i t y w o u l d n o t be  a s h o r t carbon  t h a t w o u l d be more t h a n  t o go  f a v o u r e d by  c h a i n i n the molecule  g a i n e d by  sufficient  a short  therefore i t s formation  d i m e t h e n e s t o t h e more s t a b l e p o r p h y r i n w o u l d be  attaining  presence  strap.  Since  force  two  porphothe  driving  Although the  presence  the aromatic  stability  the o x i d a t i o n t o a p o r p h y r i n should  t o overcome i t .  Of  course  a lower  be  limit  43 would be r e a c h e d when t h e c a r b o n c h a i n the  formation  product  in  i n high  be n o t e d .  yield  the intermediate  four  reactions.  fashion  lead  to dimerization  and  could  inter-  eventually since  react  i n an  The i n t e r m o l e c u l a r  reactions under  f u r t h e r i n the r e t r o s y n t h e t i c a n a l y s i s be s e e n t h a t a s i m p l e lead  an c t - c a r b o x y g r o u p .  Compound  common r e a c t i o n i n p y r r o l e c h e m i s t r y . group i n t e r c o n v e r s i o n from a c y c l i c  f u n c t i o n a l group  to the intermediate 5_6 c o u l d  t o 55_ by t h e r m a l d e c a r b o x y l a t i o n  of p y r r o l e s  and/or the  Such  Step  leading  precursors  which 3  t o 5_7.  (Knorr  be  5_6  (step  easily  is a  very  i s another The  7,  favoured  and i f any one d o e s , t h e d e s i r e d  i n t e r c o n v e r s i o n o f 5_5 w o u l d  functional  to Figure  i s n o t t h e most  The c t - f o r m y l  two  dilution.  (Figure 7 ) , i t could  converted  according  by c a r r y i n g o u t t h e c y c l i z a t i o n  Proceeding  2 ) with  undergo  The p r o b l e m becomes more p r o n o u n c e d  be m i n i m i z e d  extremely high  the d e s i r e d  Although  group o f another m o l e c u l e .  p r o d u c t w o u l d n o t be o b t a i n e d . could  55_ s h o u l d  r e a c t i v e groups i n the molecule  intermolecular  2+2  p o s i t i o n o f e a c h h a l f w o u l d be f r e e t o r e a c t  r e a c t i o n s would  polymerization.  this  to obtain  possibility  55_ i n s o l u t i o n .  the appropriate  molecular  In o r d e r  head-to-tail coupling  f o r compound  with  regarding  the c o n f i g u r a t i o n presented  a-unsubstituted  all  feature  seems t o be a r e a s o n a b l e  reality  one  important  should  intramolecular this  even f o r  o f the porphodimethene.  Another condensation  i s too short  synthesis  and r e l a t e d s y n -  44 theses) g e n e r a l l y known t o be  produce the  a-ethyl ester directly  a synthetically useful  A double disconnection produce the basically  pyrrolic  the  of  of  the  conveniently  philic  a-unsubstituted  attack  carbinyl group  of  c a t i o n g e n e r a t e d by  (Section  starting  1.2).  point  An  of  5_8_  59a  and  an  of  5  ) gives  c o n s i s t s of  by  the  H  The the  5 9b  pyrrylleaving  synthetic  functional key  a chain  group  intermediate linked bis-  pyrrole  H  59a  is  nucleo-  a  a good  a-unsubstituted  This  dipyrromethanes.  p y r r o l e on  l o s s of  57_ w o u l d  58_.  a-methyl group i s the  (step  5_9_ w h i c h b a s i c a l l y  formylpyrrole  the  by  prepared  f o r such i n t e r m e d i a t e s .  interconversion system  an  intermediate  synthesis  Dipyrromethanes are  is  substituent.  systems r e p r e s e n t e d  reverse  and  59b.  45 The important  selection  step  c h a i n was t o o  in  the  short  it  would not  it  was b e c a u s e  the  little  no s t r a i n could  product  cannot  careful  study  molecule the  and t h e  of  the  found  to  be t h e  The  strap  dicarboxylic  acid.  acid,  although  to  was t h e  and e i g h t  carbon d i a c i d s  because  of  whether the  strap  with  a  a porphyrin  even  though  planar  dipyrrolic  configuration.  (CPK) m o d e l s  with  of  the  the  A  target  carbon chain would  be  s  porphyrin  the decane,  ed  and  nonane  The e i g h t  the' and  carbon  octane  chain  limit. introduced  commercially  was  i.e.,  that  undecane  The e l e v e n  therefore  failed,  point  thereafter.  be  cause,  a long  the  If the  reaction  r  lower to  or  another  •.>Ther&-f&r.eA§-therIi ' it5,§*f§eP' "  porphyrins  were u n d e r t a k e n  the  hand,  an e l e v e n  starting point.  syntheses  was  that  synthesis.  short  prove  usual  l e n g t h was  cyclization  other  space-filling  synthesized  this  was t o o  its  chain  determine  be c y c l i z e d  porphyrin  straps  to  would not  5_4 i n d i c a t e d  ideal  of  final  On t h e  attain of  ideal  planning  strap  involved.  intermediate  the  be p o s s i b l e  chemistry or  of  synthesized  was r e q u i r e d  carbon d i a c i d  available  from adipic  as a  undecanedioic  was e x p e n s i v e acid.  were r e l a t i v e l y  terminal  and  The t e n ,  cheap and  nine  were  purchased. The s y n t h e t i c used t o  construct  results  obtained  1.4), and p r o v i d e  route  a model with  that  other  a better  developed  h e r e was  would help  synthetic  supplement  model  understanding  subsequently  of  systems the  the (section  natural  system.  46  The  biggest  ability  to maintain  Even w i t h of  the  a 5-coordinate  intermediate  large protective structures covering  porphyrin,  a second  l i g a n d had  i t t o form a 6 - c o o r d i n a t e  under  synthetic it  drawback o f most s y n t h e t i c m o d e l s was t h e i n -  route  i s capable  would a l l o w to prevent  has  over  the  space under the  large  the  bulky  ligand molecules  indicated  group f o r the  reasonably available  small 1;4--fej..§:  give  " h o l e " under the  in  f o r the  order  2.3  chemical  to o b t a i n  shorter  this  i s that  straps.  under  in the  This order strap.  (durene) was u s e d models  on e i t h e r s i d e o f the porphyrin  strap.  - 2 , 3 .;• 5 ,  The  with a  commercially  6-teferamefehylbenzene •..  the  m o d i f i c a t i o n o f the required chain  para  positions  length.  SYNTHESIS OF UNDECANEDIOIC ACIB  The .8,.  creep  \«^sj - i s ^ e i asj ^hi%. .sjtar-tingj. mat-  [(3S,y6;-b>is;(ch^ erial  reported,  from b i n d i n g  an u n s t r a i n e d  (chloromethyl)  to  advantage  p r o t e c t i v e s t r u c t u r e . CPK  that a five, carbon chain  durene m o i e t y would  f a c e .-  s t r a p t o be m i n i m i z e d  1", I , 2 # 4 / 5 - T e t r a m e t h y l b e n z e n e as  The  already  ofintroducing relatively  the  one  been o b s e r v e d  species.  others  in solution.  TMee key  dioic  acid  outline ofthis  synthesis  i s given  in Figure-8.  s t a r t i n g m a t e r i a l was t h e m o n o e s t e r o f h e x a n e (adipic  acid)  6_2.  The  diethyl  ester  6 1 was f i r s t  FIGURE 8  :  Synthesis of Undecanedioic  Acid  48 obtained of  i n g r e a t e r than  adipic  sulfuric  acid acid  60_ w i t h  equimolar  in  the presence  excess  ethanol, using The  concentrated  diester  and  was  the  i n an  inert  atmosphere  After  fractionally  diacid  several  distilled  substantial  amount o f u n r e a c t e d  off first,  f o l l o w e d by  the monoester.  the unreacted This process  diacid  yield,  t h e d i e s t e r was  o f h e a t i n g and  t h e h e a t i n g was  distillation was  observed  reduced  pressure  yield.  In a n t i c i p a t i o n  quantities It  diester order  repeated  1.5  o f low  overall  mole s c a l e ,  yield,  so as  the  twice.  progress-  stage.  redistilled  The under 56%  reaction  to obtain  sufficient  62.  s h o u l d be  noted  that recently,  B a b l e r and  Moy  have r e p o r t e d a s e l e c t i v e m o n o e s t e r i f i c a t i o n p r o c e d u r e diacid  ( s e b a c i c a c i d ) u s i n g aqueous e t h a n o l  of a strong a c i d yields  could  be  i t was  converted  the presence of  catalyst.  g r e a t e r than  m o n o e s t e r as  with  reheated.  t o o b t a i n t h e p u r e m o n o e s t e r 62_ i n  o u t on of  was  to darken  discontinued at this  m o n o e s t e r f r a c t i o n s were combined and  carried  was  In  under  recombined  i n t h e r e a c t i o n v e s s e l and  Since the r e a c t i o n mixture  was  esterification  A  t o improve the o v e r a l l  ively,  the  o f tolLue-ne— p—su']!fondle; a c i d .  pressure.  distilled  by  q u a n t i t i e s , were h e a t e d  the r e a c t i o n mixture  reduced  yield,  as the c a t a l y s t .  in  hours,  7 5%  96%,  by  formed  i n the  T h e s e w o r k e r s have the continuous  to the d i e s t e r .  presence  obtained  o f a l a r g e amount o f w a t e r p e r m i t s and  the  before i t  They have o b s e r v e d  t h e m o n o e s t e r t o o c c u r more r e a d i l y  for a  e x t r a c t i o n of  (using cyclohexane),  3 4  the  that  extraction  a l s o reduce  the  49 d i e s t e r formation. The monoester 6_2 was  next converted to the c o r r e s -  ponding a c i d c h l o r i d e 63_ by h e a t i n g with t h i o n y l The excess reagent was  chloride.  removed by e v a p o r a t i n g (under reduced  pressure) w i t h carbon t e t r a c h l o r i d e and the product was f o r the next r e a c t i o n without f u r t h e r  used  purification.  The c o n v e r s i o n of the a c i d c h l o r i d e 63_ to the keto diacid  64_ was  c a r r i e d out a c c o r d i n g to the method  suggested  '•35  by Durham, Mcleod and Cason-.,,. with c e r t a i n m o d i f i c a t i o n s . The treatment of the a c i d c h l o r i d e w i t h t r i e t h y l a m i n e f o l l o w e d by s a p o n i f i c a t i o n i n aqueous potassium hydroxide  produced  the d e s i r e d product 64 i n y i e l d s comparable w i t h those reported.  The r e a c t i o n proceeds v i a an i n i t i a l  h a l o g e n a t i o n of 63_ by t r i e t h y l a m i n e t o produce  dehydroa ketene,  50 which subsequently undergoes d i m e r i z a t i o n .  I t i s essential  that both t r i e t h y l a m i n e  and t h e s o l v e n t  absolutely  t o p r e v e n t any h y d r o l y s i s o f t h e  ketene. opening  dry i n order  (toluene) a r e  Base h y d r o l y s i s o f t h e k e t e n e d i m e r followed  by t h e d e c a r b o x y l a t i o n  the of  2.4  i n 60% o v e r a l l y i e l d  amount o f m o n o e s t e r the ketoacid  6_2 u s e d ) .  Wolff-Kishner  produced undecanedioic  O n l y two p y r r o l e s were s y n t h e s i z e d the 3-unsubstituted  The k e t o d i a c i d 6_4 was  ( c a l c u l a t e d on t h e b a s i s o f  pyrrole  reduction  3 6  a c i d 6_5 i n 92% y i e l d .  MONOPYRROLTC STARTING MATERIALS AND  precursors.,  to ring  o f the r e s u l t i n g  3-keto a c i d u n d e r t h e r e a c t i o n c o n d i t i o n s . isolated  leads  INTERMEDIATES  from  acyclic  6_6_ and t h e g - a c e t y l -  p y r r o l e 67.  67  66  The  s e l e c t i o n o f t h e s e two a s t h e k e y p y r r o l i c  materials,  was n o t a r b i t r a r y .  unsubstituted  Compound  S - p o s i t i o n was u s e d  starting  66, w i t h  to l i n k  i t s single  two s u c h m o l e c u l e s  to  t h e two t e r m i n i  not  used  o f the carbon  directly,  monopyrrolic  the ethyl The  intermediates  discussed significant  ester  in  pyrrole  of  the increase  on  the pyrrole  work.  The a c e t y l  b u t was t h e p r e c u r s o r  i n both  66 and 67  and p r o t e c t i n g  group  c h e m i s t r y , by v i r t u e o f t h e e a s e o f r e m o v a l and  merization.  i n stability  that  such a s u b s t i t u e n t  nucleus, with respect  The most common p y r r o l e  and i t s v a r i a t i o n s , l e a d  to oxidation synthesis,  confers  and p o l y -  the Knorr  t o such e s t e r s  (vide  infra).  SYNTHESES OF PYRROLES FROM ACYCLIC PRECURSORS  The of  f o ra l l other  i n this  f u n c t i o n a l i t y present  by f a r t h e most i m p o r t a n t b l o c k i n g  2.4.1  67_, a l t h o u g h  group.  is  synthesis  The p y r r o l e  was t h e s t a r t i n g m a t e r i a l  g r o u p was n o t c h e m i c a l l y to  strap.  pyrroles  the Knorr r e a c t i o n .  66_ and 6_7 were s y n t h e s i z e d In the c l a s s i c a l  9) , e t h y l o x i m i n o a c e t o a c e t a t e k e t o n e 7_0 w i t h another  by v a r i a t i o n s  Knorr r e a c t i o n  6J9 i s r e d u c e d  (Figure  t o t h e a-amino  z i n c and a c e t i c a c i d w h i c h i s t h e n r e a c t e d  equivalent  of ethyl acetoacetate  with  68_.  The r e a c t i o n i s  t h o u g h t t o p r o c e e d v i a t h e S c h i f f s b a s e 7_1.  In the o r i g i n a l  3 7  Knorr r e a c t i o n equivalent mixture zinc  , ethyl acetoacetate  o f aqueous s o d i u m n i t r i t e  o f 68_ and 6_9, t h e l a t t e r  and a c e t i c a c i d .  was t r e a t e d to give  a half  an e q u i m o l a r  being reduced  Unfortunately,  with  i n s i t u , by  t h e ct-amino  ketone  Aq. NaN0 0  /  2  0  CH-.CO 300^  0  68  0  69 Zn / CH C0 H 3  0^/  C H  H  NH,  0  0  70  3  HC 3  71  =0  72  FIGURE 9 :  Synthesis of Knorr's  Pyrrole  2  so  formed, s e l f - c o n d e n s e d  bases, e v e n t u a l l y minimize  this,  This  leading  the  to a mixture of  low,  oxime i s now  the  reducing  compared  The  B-diketone  the  oxime c a n  systems.  In  the  ketone i n the  synthesis 3 8  , who  o x i m i n o m a l o n a t e 7_5 of  nitrogen,  the  deduced  f o r the reacted  to  the  that  pyrrole  corresponding  pyrrole  the  lead  to  the  the  synthesis of  the  The  6_6 was  due  to the  r e a c t i o n was  67_,  desired  amino reaction  (Figure  10)  developed  69_ i n  product  the  (Figure not  as  e t h y l aeetoacetate.-  were u s e d p e r evolution  c a r r i e d out  ethyl  s u b s t i t u t i o n of d i e t h y l  oximinomalonate,  sodium n i t r i t e  Further, the  of  keto e s t e r  are  with different-  Knorr r e a c t i o n  3-free  amino  Knorr r e a c t i o n  of the  the  the  ester.  for ethyl oximinoacetoacetate  that of  3 equivalents malonate.  3-keto  synthesis  reduced  of  6_7_, w o u l d  as  Thus i n t h e  the  of  slowly  ester.  n i t r o s a t i o n o f d i e t h y l m a l o n a t e 74_ was  initial  efficient  keto  p r e s e n c e o f p e n t a n e - 2 , 4 - d i o n e 7_3.  Kleinspehn  synthesis  be  i n a manner s i m i l a r t o The  the  to  added  concentration  to that of  o x i m i n o a c e t o a c e t a t e was  proceeds  a g e n t and  the  In o r d e r  i s o l a t e d and  variations possible  numerous s i n c e  The  to by-products.  e f f e c t i v e l y maintains  ketone  by  to produce a mixture of S c h i f f ' s  of  approximately equivalent  the  i n the  . -  oxides  fumehood.  of  of  10)  54  H  o o  0  67  68  t t  OH CH, 0  0  Zn / CH C0 H 3  2  69  HC  0  3  H  3  C  \ ^ y 0 0 |  /  C  H  3  f  73  .CH. Zn / CHgCOjH  N-° N/  H3c7^  H  1  0  0  75 Aq.  NaN02  H  \  /CH  3  CHgCOjH H  3  L  o o  H  0  66  IU  FIGURE 10  :  S y n t h e s e s o f M o n o p y r r o l e s 66_ and Variations  o f the Knorr Reaction  6_7 by t h e  55 2.4.2  PREPARATION  OF SYNTHETICALLY- USEFUL PYRROLES V I A  TRANSFORMATIONS  The pyrroles  OF a-SUBSTITUENTS  construction of a porphyrin  i n v o l v e s the manipulation  The g r e a t e r  u e n t o v e r t h e 3, c h a r a c t e r i s t i c in  s e l e c t i v e l y modifying  67 w i t h o u t  affecting  Wifchiy.the e x c e p t i o n synthesized  represented  the  i n Figure  t o be c a r r i e d  o f p y r r o l e s , was made u s e o f g r o u p i n b o t h 6_6 and  p y r r o l e 6_6 (which  by t h e c h e m i c a l  Catalytic until  are schematically  11.  o f an e t h y l s i d e c h a i n out while  blocked.  KOH)  was  m o d i f i c a t i o n of the  transformations  and t h i s  conversion  The r e d u c t i o n o f t h e c a r b o n y l  Whitlock  had b e e n u s e d  and H a n a u e r  conditions  3 9  reported  for this  (^NNH-^.  of the 3,4-diethyl  of  3-acetylpyrrole.  7_6_ f r o m t h e c o r r e s p o n d i n g  r e d u c t i o n o f 67_ p r o d u c e d  chain.  transformation  t h a t the use of  produced q u a n t i t a t i v e y i e l d s  work, t h e d i b o r a n e  had  t o methylene  due t o t h e s a p o n i f i c a t i o n o f t h e e s t e r s i d e hydrogenation  was  t h e more r e a c t i v e c t - p o s i t i o n s were  c a n n o t be p e r f o r m e d u n d e r W o l f f - K i s h n e r and  of the ct-substit-  3 - a c e t y l g r o u p o f 67_, as m e n t i o n e d e a r l i e r ,  precursor  already  carried  a l l other monopyrroles required i n  The d i f f e r e n t  The  reactivity  t h e ct-methyl  of the 3-free  directly),  67_.  are generally  the methyl group a t the 3 - p o s i t i o n .  t h i s work were p r e p a r e d pyrrole  f r o m mono-  of the a - s u b s t i t u e n t s of  p y r r o l e s , whereas t h e 3 - s u b s t i t u e n t s through unchanged.  nucleus  diborane  analogue In the present  t h e compound 7_6  FIGURE  11  P r e p a r a t i o n of via  Synthetically  Transformations of  Useful  Monopyrroles  a-Substituents  57  in  over  8 0% y i e l d .  boron t r i f l u o r i d e borohydride,  The r e a c t i o n was c a r r i e d o u t by a d d i n g etherate,  t o a d i s p e r s i o n o f 6_7 and sodium  i n tetrahy.drofuran,  u n d e r an i n e r t  added a t s u c h a r a t e  atmosphere.  The  b o r o n t r i f l u o r i d e was  the  t e m p e r a t u r e o f t h e r e a c t i o n m i x t u r e b e l o w 2 0°C. . of the p y r r o l e  In  order  to a v o i d  the e t h y l e s t e r  attacked  by t h e e x c e s s r e a g e n t u s e d , t h e r e a c t i o n was c a r r i e d  out  side chain  as t o m a i n t a i n  i n the presence o f e t h y l acetate.  commonly being  The compound  r e f e r r e d t o as t h e c r y p t o p y r r o l e  cryptopyrrole It  should  mediates r e q u i r e d a-unsubstituted  f o r the synthesis  pyrrole  59b  (Figure  of the porphyrin  (Section  2.2).  This  inter-  was t h e  i s equivalent  b  79 —  and  R = C^Hi^ .  The c o n v e r s i o n  the  s y n t h e t i c a l l y u s e f u l 'a - u n s u b s t i t u t e d  out  v i a a.-carboxypyrrole was  e t h y l e s t e r , 8JL  be r e c a l l e d t h a t one o f t h e two k e y  to the p y r r o l e  step  7_6 i s  itself.  59  first  being  11) when R =R-» =C_H_ C M-.^R^CH 5 -2 5 •' 3 6 3. ?  o f the a -methylpyrrole pyrrole  11_ and t h e a - i o d o p y r r o l e  the t r i c h l o r i n a t i o n  - '  7_6_ t o  79^ was c a r r i e d 78_.  The  o f t h e a.-methyl;jgr.oup..of  58  7 6 with  3 e q u i v a l e n t s of s u l f u r y l  subsequently  to the  major concern  acid.  in this  Ether  carbon  product  either  i s damaged by ether  enhancing  the product The  was  76 was  fails the  sulfuryl  chloride,  to avoid t h i s  to proceed  problem but  to completion  stability  Battersby  was  carried  and  co-workers'*  solvents.  f o r p y r r o l e s ) and  t h e volume) was  The  out  addedy. j u s t p r i o r  c h l o r i d e , was  added r a p i d l y  a period of  chloride, diluted  ether.  to the with  using a dropping  30-60 s e c o n d s ) i n o r d e r With the  funnel  t o make s u r e  would n o t o v e r f l o w  the  The  the  the  intermediate  solvent, for  the  o f i n c r e a s e d amounts o f  r e a c t i o n was  t h a t the v i g o r o u s  contents  (usually  to minimize i t s  t o compete as w e l l as  thehby-product.  good  slow a d d i t i o n p r o c e d u r e s ,  formation  best  methylene  able  i n the  the  a d d i t i o n of  m i g h t n o t be  resulting  to  (approximately  reactive d-dichloromethylpyrrole  a large flask  By  ct-methylpyrrole  less  a l d e h y d e as  the  , where t h e  0  and  oxidant,  or  according  starting  anhydrous e t h e r  Sulfuryl  hindered  the  under the r e a c t i o n c o n d i t i o n s .  d i s s o l v e d i n m e t h y l e n e c h l o r i d e (a u n i f o r m l y  reaction with  Chloro-  hydrogen c h l o r i d e e v o l v e d .  the r e a g e n t .  over  the  solution with highly v a r i a b l e  the major cause f o r t h i s .  trichlorination  made o f b o t h  solvent twice  s o l v e n t was  seems t o s o l v a t e t h e h y d r o g e n c h l o r i d e f o r m e d ,  method r e p o r t e d by use  i n ether  t o be  contrast,  hydrolysed  :?_  s o l v e n t s have b e e n u s e d  trichlorination  c h o i c e of the  i s known t o r e a c t w i t h  which i s c o n s i d e r e d  t o be  r e a c t i o n . ot-Methylpyrrole-c m6h6es"r.ers. *.  have b e e n t r i c h l o r i n a t e d results.  The  chloride,  performed  in  effervescence  from the r e a c t i o n v e s s e l .  Once t h e a d d i t i o n was i n v a c u o , and  complete,  the s o l v e n t s were removed  t h e r e s u l t i n g r e d o i l was  r e f l u x i n g aqueous a c e t o n e . i n g r e a t e r t h a n 80%  yield  The  hydrolysed  in  a - c a r b o x y p y r r o l e was  after  /  obtained  purification.  H00C  76  77  The  79  t r a n s f o r m a t i o n of the a - c a r b o x y p y r r o l e  77_ t o  t h e a - u n s u b s t i t u t e d p y r r o l e 7_9 b a s i c a l l y  i n v o l v e s a decarboxy-  lation.  t h e r m a l l y , i t has  Although  been o b s e r v e d  4 1  t h i s c o u l d be  earlier  t h a t an i n d i r e c t i o d i n a t i o n  ( v i a 78_) g i v e s h i g h y i e l d s and the carboxypyrrole moiety The  achieved  purer product  bears  decarboxylative iodination  procedure  e s p e c i a l l y when  e l e c t r o n withdrawing [TT_^ 78_) was  the two-phase system of 1 , 2 - d i c h l o r o e t h a n e  groups.  c a r r i e d out i n and w a t e r ,  using  s o d i u m b i c a r b o n a t e t o s o l u b i l i z e t h e s t a r t i n g m a t e r i a l as i t s "anion.  The  d i c h l o r o e t h a n e e x t r a c t s t h e i o d o p y r r o l e 7_8_  as i t i s f o r m e d , p r e v e n t i n g t h e f o r m a t i o n o f s o l i d i o d i n e charge t r a n s f e r complexes.  This also  pyrrole-  reduces.the  time a v a i l a b l e f o r the s a p o n i f i c a t i o n of the e s t e r s i d e c h a i n by t h e b i c a r b o n a t e s o l u t i o n . complexes cannot form,  Since the molecular  the i o d i n e taken  i n excess  iodine ( i n aqueous  60 potassium  i o d i d e ) , was  time the  ester  isolated  from the  added r a p i d l y , t o  i s exposed organic  t o aqueous b a s e .  sodium b i s u l f i t e .  p r o d u c t was  approximately  hydroiodic  removal of  acid instead  of potassium used  iodide  for this  and  94%  by  The  yield  i o d i n e was  product the  the  e f f e c t e d by  was  excess  recrystallized  the  use  of c a t a l y t i c  hydrogenation.  concentrated  hydrochloric  p u r p o s e and  the  iodine  The  c h r o m a t o g r a p h y , was  obtained  A  of mixture  acid  l i b e r a t e d was  a-unsubstituted  was  destroyed  pyrrole  i n greater  79,  than  yield.  80  79  The used  compound  i n t h i s work.  8_0 was  another  a-unsubstituted  With the  pyrrole  7_9,  were e n c o u n t e r e d  i n attempting  chain  latter  2.6).  during To  since  the  overcome t h i s ,  substituting 8 0,  of  the  90%.  w i t h hypophosphorous a c i d . purified  The  phase a f t e r d e s t r o y i n g  iodine with  The  f u r t h e r reduce  the  hydrogenolysis  the  an  the  ester  .followed  by  ethyl ester  synthesis  (see  a l t e r n a t i v e ..route was  p y r r o l e 7_9 w i t h t h e  benzyl  c e r t a i n problems  t o remove t h e  stages of  group can  benzyl be  pyrrole  ester  Section  considered analogue  removed e a s i l y  decarboxylation.  The  side  by  pyrrole  80  was  obtained  ication  i t s ethyl  e s t e r a n a l o g u e by  a  transesterif  i n b e n z y l a l c o h o l , u s i n g sodium b e n z y l o x i d e as  catalyst.  I t s h o u l d be  a very useful yields  from  and  reaction  emphasized  the  that transbenzylation i s  i n p y r r o l e chemistry  due  to i t s high  t h e e a s e o f r e m o v a l o f t h e b e n z y l e s t e r when r ?  required. The  compounds 8_6  and  8_7_ a r e two  p y r r o l e s used  simple models f o r the c h a i n l i n k e d d i m e r i c systems. were p r e p a r e d  84  and  by  treating  8_5 w i t h one  compounds 8_4 and They had  the c o r r e s p o n d i n g  equivalent of s u l f u r y l  8_5 were o b t a i n e d  been p r e p a r e d  by  from  Dr.  the t r a d i t i o n a l  as  They  a-methylpyrroles  chloride. J o h n B. route  The Paine  starting  III  from c r y p t o p y r r o l e e t h y l e s t e r 7_6 (Figure 1 1 ) . step o f t h i s s y n t h e s i s i s the c o n v e r s i o n 81.  The f i r s t  of 7_6_ to c r y p t o p y r r o l e  This i s e f f e c t e d by the s a p o n i f i c a t i o n o f the e t h y l e s t e r  83 ~  82_  with aqueous base, f o l l o w e d by the n e u t r a l i z a t i o n o f the hot s o l u t i o n with a s l i g h t d e f i c i e n c y o f a c e t i c a c i d . conditions r e s u l t i n decarboxylation p y r r o l e 81_ i s steam d i s t i l l e d  These  and the v o l a t i l e a - f r e e  away from the t a r r y  by-products.  T h i s i s then taken up i n dimethylformamide and t r e a t e d with phosphorus's- o x y c h l o r i d e and the r e s u l t i n g iminium s a l t 8_2 i s hydrolysed  i n aqueous sodium bicarbonate  a-formylpyrrole  8_3.  to g i v e the  The a - f o r m y l p y r r o l e when r e a c t e d  with  m a l o n o n i t r i l e i n the presence of an amine produces the a-dicyanoy in.ylpyrrole 8_4. r  a c e t a t e the a - c y a n o a c r y l a t e  A l t e r n a t i v e l y , with methyl cyano8_5 i s formed.  The f o r m y l a t i o n  63 o f an o t - f r e e p y r r o l e and i t s s u b s e q u e n t p r o t e c t i o n as a cyanovinyl value in  d e r i v a t i v e a r e two r e a c t i o n s o f immense  i n p y r r o l e chemistry  the following  2.5  and w o u l d be d i s c u s s e d  synthetic in detail  section.  CHAIN LINKED BIS PYRROLES  AND  THEIR CHEMICAL  MODIFICATIONS  W i t h t h e i m p o r t a n t m o n o p y r r o l e s i n hand, i t now necessary  to consider  formylpyrrole  the synthesis  d i m e r 59a.  retrosynthetic  I t should  a n a l y s i s presented  of the chain be r e c a l l e d  i n s e c t i o n 2.2  became  linked athat the suggested  59a  this  compound t o be a k e y s y n t h e t i c  target molecule. 59a  When b o t h R-^ and R^ a r e m e t h y l  becomes e q u i v a l e n t  to the b i s formylpyrrole  of which i s o u t l i n e d i n F i g u r e The the of  initial  acylation  f o r the groups, 9_3, t h e s y n t h e s i s  12.  step of t h i s  t e r m i n i of the r e q u i r e d two p y r r o l e s .  intermediate  s y n t h e s i s was t h e l i n k i n g o f  carbon chain  T h i s was a c h i e v e d  by t h e s i m u l t a n e o u s b i s  o f two m o l e c u l e s o f t h e 3 - f r e e  b i s a c i d c h l o r i d e of the appropriate  to the 3-positions  pyrrole  diacid.  6_6 w i t h t h e  T h i s r e a c t i o n had  H00C(CH ) _ C00H 2  FIGURE 12  :  n  2  Syntheses of Chain Intermediates  SOCI  2  ClOCICHjl^COCI  Linked Bis P y r r o l i c  been d e v e l o p e d  as  the  first  step  i n a general  route  to  the  4 2  synthesis milder used  of c o v a l e n t l y l i n k e d  acylation catalyst,  i n these  dimeric  porphyrins.  anhydrous s t a n n i c c h l o r i d e  substitution  than  The  c h l o r i d e was  prepared  The  of  3-free  was  pyrrole  i n c r e a s e the  with  6j5.  over  the  dilute  and  compounds.  i n the  usual  thioniyl c h l o r i d e .  out  more t h a n  A mixture  u s e d as  a t 0°C two  under  an  equivalents  of methylene c h l o r i d e  s o l v e n t , the  of the product The  latter  and  acid  helping  thereby  avoid-  c h l o r i d e and  f o u r e q u i v a l e n t s of anhydrous  a period of  3-4  o u t when t h e  aqueous  During  the  hours.  the course  the  was  p o s s i b l e to i s o l a t e realized  c h l o r i d e was c o u l d be hours).  diketo bis pyrrole  r e a c t i o n mixture  was  hydrolysed  o f t h i s work d i a c i d s w i t h  9 were u s e d , e a c h p r o d u c i n g 1st crop.  The  stannic  acid.  for  3-4  excess  carried  slightly  solubility  approximately  crystallized  with  it  first  benzenoid  p y r r o l e , i n t h e .above s o l v e n t s y s t e m , were t r e a t e d  chloride  ly  with  i t s premature c r y s t a l l i z a t i o n .  3-free  10  the d i a c i d  n i t r o m e t h a n e was  ing  88  heating  atmosphere, u s i n g  the  and to  bis acid  acylation. i t s e l f  inert  was  r e a c t i o n s s i n c e p y r r o l e s a r e more r e a c t i v e  towards e l e c t r o p h i l i c  manner by  The  By  greater  concentrating  over  two  for this  added r e a s o n a b l y  equivalents  F u r t h e r , c a r r y i n g out  of  yields  subsequentstannic  in addition,  (30 m i n u t e s as these  11,  phase, i t  I t was  a c y l a t i o n and  fast  7 0%  organic  a f u r t h e r 10-15%.  that s l i g h t l y sufficient  the  than  h =  opposed  to  r e a c t i o n s a t room  temperature d i d n o t have any h a r m f u l e f f e c t s .  In f a c t ,  in  most i n s t a n c e s , these changes r e s u l t e d i n improved y i e l d s . The monoacylated d e r i v a t i v e i s a by p r o d u c t o f r e a c t i o n and p r e v i o u s work has shown  this  , t h a t when n = 4 or 5,  t h i s becomes t h e major or even the o n l y p r o d u c t .  It  has  been suggested t h a t t h e i n t e r m e d i a t e p y r r o l y l k e t o a c i d c h l o r i d e c o u l d c y c l i z e t o an e n o l l a c t o n e , which upon work up would h y d r o l y s e t o the p y r r o l y l k e t o a c i d as shown below:  I t would be n o t i c e d t h a t when h = 4 and 5, the l a c t o n e s are 5 and 6 membered r i n g systems r e s p e c t i v e l y , and the  stability  o f such systems would be the d r i v i n g f o r c e f o r the predominant f o r m a t i o n o f the m o n o p y r r o l i c by p r o d u c t .  67 The of  next step  t h e two k e t o n i c  s y n t h e s i s was t h e r e d u c t i o n  groups t o methylenes.  was  used  was  m o n i t o r e d b y t'|>e a n a l y s i s .  the  slowest  with  for this  i n this  p u r p o s e and t h e p r o g r e s s  moving spot  and t h e f u l l y  d i d not dissolve f u l l y  hydrofuran) but the product c a r e f u l l y destroyed crystallized  using  is  best  carried  f l a s k was.cooled with  intermediate.  did.  in  a very  I t should  be n o t e d  that this  o u t a t room t e m p e r a t u r e . i n i c e , very  remained u n d i s s o l v e d .  little  was 8_9 was  varied reaction  When t h e r e a c t i o n  product  was f o r m e d  even  most o f t h e s t a r t i n g  On a l l o w i n g  the r e a c t i o n  the s o l i d  was  t o go i n t o s o l u t i o n and t h e r e a c t i o n was c o m p l e t e short  time.  With the appropriate the  (tetra-  a c e t i c a c i d and t h e p r o d u c t  m i x t u r e t o warm up t o room t e m p e r a t u r e , observed  the fastest,  The e x c e s s d i b o r a n e  The y i e l d s  n e x t t a s k was t o m o d i f y  carbon chain  the e t h y l ester  securely i n place, functionalities  o f 8_9^ t o o b t a i n t h e s y n t h e t i c a l l y u s e f u l b i s f o r m y l p y r r o l e 93.  was  The s t a r t i n g  i n t h e s o l v e n t used  the additionoof excess reagent;  material  of the r e a c t i o n  reduced product  by t h e a d d i t i o n o f w a t e r .  between 75 and 85%.  diborane  As e x p e c t e d , t h e d i k e t o n e  t h e monoketo d e r i v a t i v e b e i n g  material  Once a g a i n ,  As f o r t h e model s y s t e m d i s c u s s e d  (conversion  o f 7_6 t o 83_) , t h i s  removal o f the e s t e r f o l l o w e d  i n s e c t i o n 2.4.2  had t o i n v o l v e t h e c o m p l e t e by t h e i n t r o d u c t i o n o f t h e  68  formyl the in  group.  simple this  could  trialkyl  case.  of  the d e s i r e d  are  known  itate  11) were n o t  of the type  involve  8_9 i n s t r o n g  Pyrrole  81 ,-£b,e'.Jbng yyjo.l-a t i le,,  92_ c o u l d  91  decarboxy-  the s a p o n i f i c a t i o n of  base f o l l o w e d  acids  chain  n o t be e x p e c t e d  to thermal  91 by a c i d i f i c a t i o n  carboxylic  by t h e p r e c i p i t a t i o n a t room  obtained  t o cause problems i n h a n d l i n g .  o u t as g e l a t i n o u s  appropriate  the a-carboxypyrrole  and t h e n s u b j e c t e d  product  described f o r  out of the r e a c t i o n mixture, a  T h i s would u s u a l l y  ethyl ester  or below.  (Figure  T h i s meant t h a t  t o be i s o l a t e d  lation.  the r e a c t i o n s  Although cryptopyrrole  bis- a -free pyrrole  t o do t h e same.  the  pyrrole  be steam d i s t i l l e d  linked  had  Unfortunately,  temperature  i n this  manner  They u s u a l l y  s o l i d s w h i c h maiie t h e  precip-  filtration  extremely  tedious.  F u r t h e r , they  days over  potassium  hydroxide,  Considering s y n t h e s i s was  these  to convert  catalytic  factors,  the e t h y l  effected  by  procedure alcohol tilled  hydrogenation. a high  ethyl  best approach to  e s t e r 8_9 t o t h e  removed c l e a n l y  by  Kenner and  sodium b e n z y l o x i d e .  heated  A vigorous  reflux  temperature.  with  The  any  , using  4 4  benzoic  to r e f l u x  product  9£ was  carbonate acid  dis-  i n order  present.  i n benzyl alcohol added i n  isolated  f o l l o w e d by  and  ISTIIL  lowering  to methanol c o n t a i n i n g catalyst,  benzyl  of  by  observed the  adding  sufficient dilution  water.  ethyl  eleven,  e s t e r s 8 9a,  the  course  95%  were o b t a i n e d .  8 9d had  t e n and  89b  and  The  nine  89c  o f t h i s work and  g r e a t e r than  95%  carbon  in general, yields  e i g h t carbon  yield)  linked  as an  by  linked Dr.  during  greater  than  dibenzyl ester  J.B.Paine  intermediate  dimeric porphyrins.  t h i s m a t e r i a l were o b t a i n e d  bis pyrrole  were t r a n s b e n z y l a t e d  p r e v i o u s l y been p r e p a r e d  of c o v a l e n t l y l i n k e d of  {  b e n z y l a l c o h o l was  the concomitant  t o quench the  The  in  The  r e a c t i o n mixture acid  conveniently  e v o l u t i o n o f e t h a n o l v a p o u r s was  the r e a c t i o n , w i t h  acetic  43  co-workers  from anhydrous potassium  during  hot  and  the  a s o l u t i o n o f s o d i u m i n b e n z y l a l c o h o l was  the  corresponding  t e m p e r a t u r e m o d i f i c a t i o n ^5).-.. -' o f  e s t e r 8_9 was  portions.  this  was  t o remove most o f t h e w a t e r and The  the  4  beforehand,  for several  This t r a n s e s t e r i f i c a t i o n  developed  and  dried  u n d e r vacuum.  b e n z y l e s t e r 90^ w h i c h c o u l d be by  have t o be  III  i n the  (also synthesis  Sufficient quantities  for further modifications.  70 It  should  transformations  be e m p h a s i z e d  were c a r r i e d  one t o be s t u d i e d ,  stage  out i n a l l four  b n = 10, c n = 9 and d n = 8. first  at this  ( F i g u r e 12).  the others  that  subsequent  series;  a n  = 11,  S e r i e s a was t h e  were a t t e m p t e d o n l y  after  the  c o n d i t i o n s o f a l l t h e r e a c t i o n s were o p t i m i z e d .  Except f o r  the  final  observed  in  cyclization  experimental The  genation was  using the  no m a j o r v a r i a t i o n s were  yields.  b i s benzyl  i n order  carried  step,  ester  90_ was  t o citeav/e t h e b e n z y l  o u t a t room t e m p e r a t u r e  approximately  catalyst.  next subjected e s t e r group.  pale  In each case,  i n vacuo t o o b t a i n  yellow  pressure  10% b y w e i g h t o f 10% p a l l a d i z e d c a r b o n as  removal o f the c a t a l y s t ,  evaporated  The r e a c t i o n  and 1 a t m o s p h e r e  the uptake o f hydrogen  when t h e c a l c u l a t e d amount o f h y d r o g e n was the  to hydro-  the solvent  ceased  absorbed.  Following  (tetrahydrofuran)  the b i s carboxypyrrole  was  9J_ a s a  solid.  The  crude carboxypyrrole  thermal decarboxylation high b o i l i n g  solvents  without  d i m e r s were s u b j e c t e d  further purification.  are g e n e r a l l y used  w h i c h d i m e t h y l f o r m a m i d e had a d i s t i n c t  to Several  f o r t h i s purpose o f  advantage over the  o others  f o r t h i s work.  sufficient  not only  to decarboxylate  remove any r e m a i n i n g (toluene  i s the other  ester).  Further,  used  I t s r e f l u x t e m p e r a t u r e o f 153  toluene product  c  was  the p y r r o l e but a l s o to  from the crude  starting  of hydrogenolysis  d i m e t h y l f o r m a m i d e was  material  o f the benzyl  one o f t h e  reagents  i n t h e n e x t r e a c t i o n , i . e . t h e V i l s m e i e r f o r m y l a t i o n and  71 therefore  i t was-not n e c e s s a r y  to-isolate  the  decarboxylated  product f ; The in  d e c a r b o x y l a t i o n o f t h e a - c a r b o x y p y r r o l e dimer-;:91  dimethylformamide  were f o l l o w e d by uv  starting material exhibited approximately observed  285  t o be  nm.  a single  After  reduced  2 hours  to j u s t  removed c o m p l e t e l y  even a f t e r  In o r d e r  the time  to reduce  higher b o i l i n g no  decarboxylation,  the  i n dimethylformamide  at r e f l u x ,  band  for this  was  tried  observed.  f o r the  was  never  hour o f h e a t i n g . reaction,  as  On  solution,  i n t r o d u c t i o n of the  this  s h o u l d e r b u t was  c o o l e d and  the  the s o l v e n t but  completion  of  the  t h e p r o d u c t was  used,  formylation reaction.  f o r m y l g r o u p i s now  effected  5  the V i l s m e i e r r e a c t i o n  pyrrole  at  f l a s k was  i+  by  taken  The  a b s o r p t i o n band  a f u r t h e r one  diethylformamide  a p p r e c i a b l e r e d u c t i o n was  The  a  spectroscopy.  i n dimethylformamide  , whereby t h e a - u n s u b s t i t u t e d solution  i s treated with  phos-  46  phorous o x y c h l o r i d e or benzoyl  chloride  to proceed  o f the type  v i a an  iminiium s a l t  .  T h i s i s known 8_2.  The  iminium  72 s a l t could pyrroles  be  isolated in crystalline  i f benzoyl c h l o r i d e  hydrolysed  pyrrole  often  crystallize  formylation  aldehydes are  of  well  the  iminium  s a l t was  aqueous  base.  During  the  base used  crucial,  not  course of  the  product turned one  separated  i t . as  i n water,  solution.  the  and  the  iminium  o i l w h i c h on  eventually  coagulated this  showed v e r y is  the  salts, results  few  as  a pale  i m p u r i t i e s on  base g e n e r a l l y  used  tic.  f o r the  t h i s work i n d i c a t e d t h a t i n a purer  product.  the  the  into  material  colors in addition  using  the  heating,  A l t e r n a t i v e l y , when a w e a k l y b a s i c medium  out  was  used,  product.  product c r y s t a l l i z e d  that  appearance of  l a y e r chromatography of  h y d r o l y s i s by  in  salt  s e v e r a l bands o f v a r y i n g  f o r the  phos-  the  observed  exhibited  provided  The  directly  When aqueous ammonia was a reddish  they  effected using  t h i s work, i t was  i n t o d a r k brown lumps and Thin  a-formylpyrroles.  hydrolysed  h y d r o l y s i s of  out  s t i c k y mass.  9_2 was  trialkyl-  subsequently  o f b e n z o y l c h l o r i d e , and  purity, yield  p r o d u c t d e p e n d e d on  the  is  hydrolysis  i s o l a t e d but  f o r the  since  from the  instead  This  somewhat s o l u b l e  p y r r o l e dimer  phorous o x y c h l o r i d e  the  i s used.  i n aqueous b a s e t o g i v e  Since  form f o r simple  to  the  was  sodium b i c a r b o n a t e ,  the  g r e y powdery s o l i d  which  A l t h o u g h aqueous  ammonia  hydrolysis use  of  of  sodium  the  iminium  bicarbonate  73  I t w o u l d be n o t i c e d ester  that  9_0, e s s e n t i a l l y 3 r e a c t i o n s  purification a-free  s t a r t i n g from  had been c a r r i e d o u t w i t h o u t  o f t h e two i n t e r m e d i a t e  pyrrole  purification  dimer  t o g r a p h y was n o t p o s s i b l e adsorbed  for this  generally  the  p o l a r i t y of the e l u t i n g solvent  strongly  t o move.  purpose,  this  separation  problem,  almost  onto  silica  g e l and  i s increased  This  impossible.  the b i s - f o r m y l p y r r o l e  In order  t o overcome  93_ was c o n v e r t e d  made i t s p u r i f i c a t i o n  also  i n protecting  the s e n s i t i v e aldehyde  (videvinfra).  considerably  the chromatro-  which not only  alities  unless  of course r e s u l t s i n the  derivative, served  Although a  a-Formylpyrroles  movement o f t h e i m p u r i t i e s a s w e l l , r e n d e r i n g graphic  In f a c t , the  a t t h i s . s t a g e , t h e u s e o f chroma-  are  t h e y c a n n o t be f o r c e d  products.  92_ was n o t e v e n i s o l a t e d .  was n e c e s s a r y  the b i s benzyl  to a  easy b u t function-  a-Formylpyrroles, and  ©annizzaro d i s p r o p o r t i o n a t i o n ,  decomposition of  although r e s i s t a n t  under a c i d i c  conditions  t h e r e a g e n t s commonly u s e d  the  next stage of t h i s  synthesis  formyl used  required  for this  sulfuryl (for  9^  w  a  Several but  n o t be e x p e c t e d  formation  to survive  and t h e  the reagents  tetraacetate-  f o r aldehydes  i n p y r r o l e chemistry are the  cyanovinyl  groups:  H.  NC  //  \^  CN  DICYA NOVINYL  groups  mandatory.  p r o t e c t i n g g r o u p s a r e known  t h e most u s e f u l  o f the  The p r o t e c t i o n o f t h e two f o r m y l  therefore  s  In f a c t ,  (for bromination),  ( f o r c h l o r i n a t i o n ) and l e a d  acetoxylation).  o f compound  chemistry.  a source o f p y r r y l c a r b i n y l  purpose, i . e . , bromine  chloride  susceptible to  was t h e o x i d a t i o n  f o r the dipyrromethane  groups c o u l d  autoxidation  and i n t h e p r e s e n c e  i n pyrrole  a - m e t h y l g r o u p s o f 93^ t o p r o v i d e cations  are very  to  CYANOACRYLATE  75  The  cyanovihyl  and  later  protecting  • --  '  •-  h  g r o u p s - w e r e • f i r s t u s e d by F i s c h e r  i  h8  Since  by Woodward  i n his total  synthesis  of chlorophyll.  then, t h e use o f t h i s group f o r t h e p r o t e c t i o n o f a l d e h 9  h y d e s h a s been e x p l o r e d  further.  p r e p a r e d by t h e K n o e v e n a g e l malononitrile of  a basic  required with  or esters  reaction of -formylpyrroles  of cyanoacetic  to generate the protected  the s u b s t i t u t i o n pattern  1  esters  tend  a few s e c o n d s w h i l e  with  a  c a t a l y s t , u s u a l l y a n amine.  a -carboxylate in  Cyanovmyl derivatives are  a c i d , i n the presence The r e a c t i o n  a l d e h y d e a r e known t o v a r y  o f the p y r r o l e .  to give  conditions  Thus ,'a-^-formyl-  almost q u a n t i t a t i v e  trialkylpyrroles  require  yields  prolonged  treatment. In a d d i t i o n t o b e i n g  usually well  these d e r i v a t i v e s are l e s s s o l u b l e  crystallized,  and-ITigy§. f a s t e r on  These f e a t u r e s  gel  than the parent aldehydes.  the  use o f the Knoevenagel r e a g e n t t o scavenge t h e crude  a l d e h y d e and a l s o p u r i f y i t by c h r o m a t o g r a p h y . extended c o n j u g a t i o n , in  the range  in  s o l u t i o n as w e l l The  tecting strong  bearing as  390-410nm, r e s u l t i n g i n y e l l o w as i n the s o l i d  Due t o t h e maxima  t o orange  colors  state.  main disadvantage o f the u s e o f c y a n o v i n y l  aqueous a l k a l i  This  chemistry,  i s the necessity  f o r the regeneration  This obviously  substituents  esters.  possible  t h e s e compounds have a b s o r p t i o n  groups i n p y r r o l e  function.  make  silica  limits  t o use  o f the aldehyde  i t s usefulness  which a r e base i n e r t  pro-  to pyrroles  or else  reparable  was n o t a m a t t e r o f c o n c e r n i n t h i s work  76 since this  the 3-substituents synthesis  ment o f s t r o n g  c h o s e n were a l k y l  was d e s i g n e d  group i s c a r r i e d  was  the use o f a l k a l i  aldehydes but a l s o saponify the  intermediate The  solubility the  less  'When t h e  t h e d i p y r r o m e t h a n e d i m e r 57_  would n o t o n l y t h e two e s t e r  regenerate the  functions  and produce  56.  choice  to •cyanoacrylates  until  In f a c t  use o f the r e q u i r e -  base f o r t h i s d e p r o t e c t i o n .  protecting formed  t o make b e s t  groups.  of dicyanovinyl  p r o t e c t i n g g r o u p as o p p o s e d  f o r t h i s work, was i n p a r t d i c t a t e d b y  considerations.  Malononitrile  i s known t o p r o d u c e  s o l u b l e d e r i v a t i v e s and i s g e n e r a l l y  systems o f i n h e r e n t l y  low s o l u b i l i t y .  systems encountered h e r e ,  avoided i n  In the b i s p y r r o l i c  the long methylene chains  were  expected  t o overcome t h i s  problem a t l e a s t  o t h e r hand, t h e l o w e r s o l u b i l i t y was t h o u g h t t o h e l p thereby  increasing  cis-trans  scavenge  to the p y r r o l e  Since  two s u c h g r o u p s would  t h e number o f p o s s i b l e systems would  The nitrile  was  94 chloride Thin  t o improve  layer  monitor faster  linked  bis-pyrrolic  T h i s was e x p e c t e d t o c a u s e  o f the subsequent  problems  reaction products.  i n h o t methanol  93. and m a l o n o -  using  some  A  a  n = 11  CHO  b  n=10  c  n= 9  d  n= 8  methylene  C(H)=C(CNL the s o l u b i l i t y  chromatography  the r e a c t i o n .  of the s t a r t i n g  material.  ( i n 2% CH OH-CH^C^) was u s e d t o 3  The m o n o p r o t e c t e d  than the d i a l d e h y d e s t a r t i n g  diprotected  ester  be p r e s e n t i n a s i n g l e m o l e c u l e ,  isomers o f the c h a i n  attempted  93  efficiently,  (with t h e b u l k y  r e a c t i o n o f the crude b i s aldehyde first  derivative  n u c l e u s ) i s known t o p r e d o m i n a t e .  be i n c r e a s e d .  the c r y s t a l l i z a t i o n  On t h e  The c y a n o a c r y l a t e s e x i s t a s  i s o m e r s a l t h o u g h one i s o m e r  trans  in  of the d i c y a n o v i n y l  t h e c r u d e a l d e h y d e more  the y i e l d s .  group  partially.  d e r i v a t i v e moved w e l l  derivative  moved  m a t e r i a l , whereas t h e  ahead  of both.  The r e a c t i o n  78  appeared  t o t a k e o v e r two h o u r s and e v e n then  compound c o u l d and  pyridine  difference  (in  be o b s e r v e d on t i g . T r i e t h y l a m i n e ,  were t r i e d  could  The  biggest  crystallization  by  as base c a t a l y s t s ;  be o b s e r v e d  solvent  series).  times.  in this  solution  o f more s o l v e n t  reaction  s y s t e m ) , was t h e p r e m a t u r e  o f the monoprotected aldehyde.  t o g e t i t back i n t o  the a d d i t i o n  cyclohexylamine  n o t much o f a  i n the r e a c t i o n  problem encountered  t h e above m e n t i o n e d  icult  some m o n o p r o t e c t e d  for further  I t was  diff-  reaction,  ( e s p e c i a l l y f o r t h e c and d  The u s e o f l a r g e r v o l u m e s o f s o l v e n t  appeared t o  h e l p keep t h e m o n o a l d e h y d e i n s o l u t i o n b u t t h e r e a c t i o n could  n o t be r e d u c e d .  reaction  solvent water  1 hour.  In f a c t ,  for this reaction.  vinylpyrrole The purified  catalyst-  Azeotroping o f f the the r e a c t i o n to  E v a p o r a t i o n o f t h e t o l u e n e and t h e a d d i t i o n o f i n the c r y s t a l l i z a t i o n  9_4 a s a y e l l o w brown bis dicyanovinyl-  of the b i s dicyano-  solid.  d e r i v a t i v e was  conveniently  by c h r o m a t o g r a p h y on s i l i c a g e l ( a c t i v i t y  approximately dissolve  reduced the  cyclohexyl-  t o be t h e b e s t  f o r m e d w i t h t o l u e n e a l s o .helped d r i v e  methanol r e s u l t e d  of  p r e v e n t e d t h e prem-  o f t h e monoaldehyde, b u t a l s o  t o l u e n e was f o u n d  combination  completion.  the  toluene, not only  time t o a p p r o x i m a t e l y  amine i n r e f l u x i n g  times  On t h e o t h e r hand, t h e u s e o f t h e  higher b o i l i n g solvent ature c r y s t a l l i z a t i o n  even  4 00mL o f m e t h y l e n e c h l o r i d e  15g o f t h i s m a t e r i a l  was r e q u i r e d  (the s o l u b i l i t y  This  Although to  was l o w e r f o r  c and d s e r i e s ) , t h e p u r i f i c a t i o n was e f f e c t e d s i l i c a gel.  I).  was e s s e n t i a l l y a p r o c e s s o f  on lOOg filtration.  79 The  dark colored  i m p u r i t i e s were a d s o r b e d on t h e column and t h e  only  compound t o move, i n m e t h y l e n e c h l o r i d e , was t h e p r o d u c t  94.  This  ethyl the  t o o moved r a t h e r  acetate  a t the i n i t i a l  impurities  possible. during  slowly  b u t the a d d i t i o n o f even  s t a g e s had r a t h e r  s t a r t e d m o v i n g and a good  In order  separation  t o minimize waste, the s o l v e n t  b i s dicyanovinyl  d e r i v a t i v e was  from methanol, f o l l o w i n g chromatography. this  analytically  benzylester  2.6  p u r e sample  9_0_) was g r e a t e r  DIPYRROMETHANES  (starting  than  was  recycled  required  two  a-methyl groups o f the p y r r o l e  cations stituted  p o s i t i o n s , the next task  The o v e r a l l y i e l d from t h e b i s -  groups i n t r o d u c e d was t o t r a n s f o r m  at  the  nuclei to p y r r y l c a r b i n y l  f o r the subsequent c o n d e n s a t i o n w i t h t h e a-unsubpyrrole.  oxidation,  selected  recrystallized  THEREFROM  formyl  the  the  was n o t  60%.  AND PORPHYRINS  W i t h t h e two p r o t e c t e d  this  adverse e f f e c t s ;  chromatography. The  of  1%  Of t h e t h r e e  c h l o r i n a t i o n with  f o r t h i s work.  transformation  Figure  sulfuryl  available for  c h l o r i d e was  13 s c h e m a t i c a l l y  of the b i s d i c y a n o v i n y l p y r r o l e  dipyrromethane dimer It  ways g e n e r a l l y  represents 94_ t o t h e  96.  i s known t h a t  the pyrrole-a-methyl  groups a r e  FIGURE 13  : S y n t h e s i s o f t h e D i p y r r o m e t h a n e Dimer  96  81 s e l e c t i v e l y c h l o r i n a t e d o v e r t h e 3 - m e t h y l g r o u p s by chloride.  sulfuryl  In a d d i t i o n , a stepwise c h l o r i n a t i o n could  be  e f f e c t e d by t h e u s e o f c a l c u l a t e d amounts o f t h e r e a g e n t . It  should  be n o t i c e d  monochlorinations  that i n the conversion  o f 94_ t o 9_5, two  w e r e r e q u i r e d , and a d i c h l o r i n a t i o n a t  one m e t h y l g r o u p w o u l d r e n d e r t h a t p o s i t i o n u s e l e s s subsequent c o u p l i n g  reaction.  t h a t i f s u c h a b y p r o d u c t was amounts, the s e p a r a t i o n  I t should  a l s o be  solvents for  and p u r i f i c a t i o n o f t h e d e s i r e d  are not very  Fortunately,  slower than monochlorination forcing conditions. of the c y a n o v i n y l  since the c h l o r o -  s o l u b l e i n t h e commonly u s e d  and a r e e a s i l y h y d r o l y s e d  chromatography.  e v e n on s i l i c a  g e l used  dichlorination i s generally  and i s known t o r e q u i r e more  Further,  the large d e a c t i v a t i n g e f f e c t  group would a l s o reduce the p o s s i b i l i t y  a s e c o n d c h l o r i n a t i o n a t t h e same p y r r o l e A t e s t r e a c t i o n was compound 9_4.  emphasized  t o be p r o d u c e d i n s i g n i f i c a n t  p r o d u c t 9_5 w o u l d be e x t r e m e l y d i f f i c u l t , methylpyrroles  f o r the  first  of  ring.  c a r r i e d out with  lOOmg o f  S u l f u r y l c h l o r i d e i n methylene c h l o r i d e  was  a d d e d d r o p w i s e , t o a s o l u t i o n o f 94_ i n m e t h y l e n e c h l o r i d e , a t room t e m p e r a t u r e and t h e s o l v e n t was  boiled o f f while  constantly replenishing with d i e t h y l ether. s o l i d p r e c i p i t a t e d o u t , w h i c h was and d r i e d .  The p r o t o n nmr  deuter'ochloroform) f r o m TMS,  A yellow  c o l l e c t e d by  powdery  filtration  spectrum of t h i s m a t e r i a l ( i n  showed a s i n g l e t a t ^  4.62(2 H)  downfield  c h a r a c t e r i s t i c of a-monochloromethyl protons.  There  82 was  no i n d i c a t i o n of d i c h l o r i n a t i o n .  As expected f o r compound  95,  o n l y a s i n g l e methyl resonance was  observed  ( 6 = 2.16ppm).  The s t a r t i n g m a t e r i a l 94_ e x h i b i t e d two methyl resonances a t <5  2.26  and  2.12.  Since the c h l o r i n a t i o n appeared as expected, the next step was d e r i v a t i v e w i t h the methane dimer  9_6.  a  to have taken p l a c e  to condense the c h l o r o m e t h y l  - f r e e p y r r o l e 7_9 to produce  the d i p y r r o -  For the r o u t i n e c o u p l i n g of p y r r o l e mono-  e s t e r s , a v a r i e t y of c o n d i t i o n s have been r e p o r t e d .  Paine  has shown t h a t c h l o r o m e t h y l p y r r o l e monoesters r e a c t t a n e o u s l y , a t room temperature  with c e r t a i n a - f r e e  sponpyrroles  i n methylene c h l o r i d e , r e s u l t i n g i n the e v o l u t i o n of chloride.  Although compound 9J3 was  i n t h i s s o l v e n t u s i n g approximately 2.2  first  the mixture was  n i t r o g e n f o r 2 hours.  attempted  e q u i v a l e n t s of the  Since no a p p r e c i a b l e change c o u l d be  a t room temperature,  hydrogen  not v e r y s o l u b l e i n  methylene c h l o r i d e , the c o u p l i n g r e a c t i o n was  pyrrole 79.  4 3  observed  heated a t r e f l u x under  A y e l l o w s o l i d was  isolated  from the  r e a c t i o n mixture by r e p l a c i n g the methylene c h l o r i d e w i t h methanol.  U n f o r t u n a t e l y , the proton nmr  spectrum of t h i s  m a t e r i a l d i d not e x h i b i t a s i g n a l near 6„. 4.0  ppm,  the  the c h a r a c t e r i s t i c s i g n a l of the methylene b r i d g e protons of dipyrromethanes.  F u r t h e r , the q u a r t e t and the  expected f o r the e t h y l groups of 9_6 were not observed.  triplet  ( o r i g i n a t i n g from 7 9)  T h i s c l e a r l y i n d i c a t e d t h a t the r e a c t i o n  83 had  not  worked. At  would h e l p workers a-free  this  a catalytic  reported  pyrroles  a t 35°C  unsymmetrical  had  been h i g h  i n methanol or amount o f  the  work-up, f a c i l e . containing  acid  and  the  r e a c t i o n was  -15°C  or  Battersby  frequently  c a r r i e d out  co-workers  i n dry  used  similar reactants  observed  that  the  acid  (TFA)  as  r e a c t i o n p r o c e e d s c l e a n l y and  such b y - p r o d u c t s .  s y s t e m was  the  the  reaction.  2%,  up  to  longer  The  the  optimal  TFA  been r e q u i r e d  at  catalyst  chloride  f o r the  He  also under  reaction this  completion  concentration in certain  had  quantitatively  m a j o r drawback w i t h  times r e q u i r e d  With the  6 d a y s had  stannic  when  dipyrromethanes.  i n m e t h y l e n e c h l o r i d e and  whereas t h e  that  Instead,  m o n o p y r r o l i c b y - p r o d u c t s were f o r m e d  these c o n d i t i o n s , produced  propionic  observed  t o d i p y r r o m e t h a n e p r o d u c t s a t room t e m p e r a t u r e . n o t e d t h a t no  other  c h l o r i d e as c a t a l y s t ,  Paine  trifluoroacetic  to  yields  methylene c h l o r i d e  good y i e l d s o f u n s y m m e t r i c a l  to couple  5 1  the  the  gave poor r e s u l t s .  they obtained had  On  with  acid  the  a c e t i c and  below, w i t h anhydrous s t a n n i c  '  co-  acetic acid in  In g e n e r a l ,  hand, w o r k i n g w i t h p y r r o l e s  Kenner's procedure  that  Kenner and  toluene-p-sulfonic  dipyrromethanes.  (90+%) and  side chains,  sought  that acetoxymethylpyrroles reacted  presence of a c a t a l y t i c give  s y s t e m was  t h i s dipyrromethane synthesis. had  5 0  stage,  of  0.5  instances.  of to  84  Of  the d i f f e r e n t c a t a l y s t s reported  methane c o u p l i n g  reactions,  tried  this  first  with  anhydrous  system.  A fresh  9jp_ was p r e p a r e d  chloromethylpyrrole  methylene c h l o r i d e with  f o r the dipyrro-  stannic  chloride  was  sample o f t h e b i s  and was t a k e n up i n  t h e ct - f r e e p y r r o l e  7_9.  Maintaining  o the  temperature  a t approximately  10 C, a n h y d r o u s  stannic  c h l o r i d e was a d d e d , when t h e r e a c t i o n m i x t u r e  turned  almost  a c i d was  immediately.  When d i l u t e h y d r o c h l o r i c  to quench the c a t a l y s t , the s o l u t i o n turned to  i s o l a t e the product  resulted  red.  green  An  from t h e methylene c h l o r i d e  attempt  solution  i n an i n t r a c t a b l e t a r . The  above r e s u l t s u g g e s t e d  that  this  r e a c t i o n had  t o be c a r r i e d o u t u n d e r more c o n t r o l l e d c o n d i t i o n s . it  appeared a p p r o p r i a t e  to substitute  the valuable  linked  b i s - p y r r o l i c s y s t e m by a s i m p l e m o n o p y r r o l i c  system  i n the search purpose,  f o r the i d e a l r e a c t i o n  the ct-chloromethylpyrrole  Further, chain model  conditions. 8j6 was  For  this  and  i t s c o n d e n s a t i o n w i t h t h e same c t - f r e e p y r r o l e was  (The  added  synthesis  o f 8_6 was d e s c r i b e d  i n section  2.4).  selected studied.  Equimolar were m i x e d stir  • quantities  o f t h e two  i n methylene c h l o r i d e ,  f o r 2 hours exhibited  colored  r e d w i t h bromine vapour  the o x i d a t i o n sible that the  color  s o l u t i o n was  and  and  change).  heated  (a t e s t  for  reaction being  dipyrromethanes;  S i n c e t h i s was  added.  then red.  an  indication  to r e f l u x  to d r i v e  slowly,  the r e a c t i o n  2 hours  very  to  little  observed.  s t a g e , t h e r e a c t i o n m i x t u r e was  approximately  0.5 The  cooled to  e q u i v a l e n t s of anhydrous solution  immediately  stannic  turned  green  F o l l o w i n g t h e work-up d e s c r i b e d e a r l i e r ,  dipyrromethane isolated  to  taking place, although rather  c o u l d be  this  c h l o r i d e was  allowed  A t i c of the  U n f o r t u n a t e l y , even a f t e r  dipyrromethane  0°C  7_9  2 y e l l o w s p o t s , t h e f a s t e r m o v i n g one  t h e r e a c t i o n was  At  and  8_6 and  o f t h e methane b r i d g e t o a methene i s r e s p o n -  for this  completion.  under argon  a t room t e m p e r a t u r e .  mixture  pyrroles  product  by c a r e f u l  (the o n l y y e l l o w s p o t on  chromatographic  gel  and  crystallized  and  t h e mass s p e c t r u m  t i c ) was  s e p a r a t i o n on  from methanol.  The  the  silica  p r o t o n nmr  spectrum  o f t h e p r o d u c t were c o n s i s t e n t w i t h  the  structure  f o r the expected dipyrromethane  97_.  Unfortunately,  the y i e l d  was  that  stannic  was that  just  over  25%.  c a u s i n g the d e s t r u c t i o n this  r e a g e n t s h o u l d be In  an a t t e m p t  refluxing  t o l u e n e was  potassium  carbonate  liberated.  The  I t appeared of the r i n g  as  the y i e l d  was  of t h i s  the s o l v e n t w i t h  b e i n g added t o a b s o r b  yield  suggesting  avoided.  t o improve used  system,  chloride  improved  reaction,  some a n h y d r o u s  the hydrogen  to almost  4 6%  chloride  but once  again  86 c h r o m a t o g r a p h y was  r e q u i r e d f o r the p u r i f i c a t i o n  of  the  product. 5  For had  the' c o u p l i n g ,o.f p y r r o l e monoes-ter-srMacDonald ' s g r o u p  devised a procedure,  acetoxymethylpyrrole in  whereby a b r o m o m e t h y l p y r r o l e  was  refluxed  with  by-product  conditions.  f o r m a t i o n had  E.g.,  the d e s i r e d product  been o b s e r v e d  under  symmet-  these  the  s t a r t i n g m a t e r i a l s shown b e l o w ,  100  had  been o b t a i n e d  yield,  contaminated  101  t o t h e e x t e n t o f 10%.  102  (the d i - t - b u t y l liquors.  Considerable  with  70%  mother  an  an be-free component  sodium a c e t a t e b u f f e r e d a c e t i c , a c i d .  rical  or  by  the  symmetrical  The  other  e s t e r ) had  in  approximately  dibenzyl ester  symmetrical  probably  been l o s t  by-product i n the  87 Acetic  acid  had n o t been u s e d b e f o r e  to couple  c h l o r o m e t h y l p y r r o l e s bearing c y a n o v i n y l groups; common s o l v e n t u s e d b e i n g m e t h y l e n e c h l o r i d e , a catalyst. iably was  order  even w i t h  in glacial  86 was s u s p e n d e d pyrrole  to prevent  in glacial  produced single vapour. and  acetic  minimal. addition  together  with  the a - f r e  was warmed on a w a t e r b a t h .  When t h e t e m p e r a t u r e  In  reached  f o r the 7 0°C  ,the  compound began t o d i s s o l v e and w i t h i n 2 0 m i n u t e s , orange s o l u t i o n .  spot  ;  A t i c exhibited only a  and was c o l o r e d r e d d i s h v i o l e t  This indicated :  i m p u r i t i e s remaining Concentration  by b r o m i n e  t h a t t h e r e a c t i o n had gone t o c o m p l e t i o  only a single dipyrromethane  reddish  acid  condensation  a-chloromethylpyrrol  The  a n i t r o g e n a t m o s p h e r e was p r o v i d e d  a clear  yellow  acid.  apprec-  any o x i d a t i o n o f t h e a - f r e e p y r r o l e a t h i g h  r e a c t i o n mixture. chloromethyl  or without  t h e model system, t h i s  acetic  7_9 and t h e m i x t u r e  temperatures,  with  S i n c e m e t h y l e n e c h l o r i d e had n o t p r o d u c e d  high y i e l d s  attempted  t h e most  product  had f o r m e d .  a t the o r i g i n  of the s o l u t i o n  The  o f t h e t i c were  f o l l o w e d by t h e  o f m e t h a n o l p r o d u c e d an o r a n g e - y e l l o w  crystalline  88 solid  w h i c h was  earlier. a  A yield  f u r t h e r 8%  overall  identical  was  yield  ucible with  87+%  was  isolated  of  the  of  t o t h e d i p y r r o m e t h a n e 97_  95+%.  obtained  from  system c o n s i d e r e d  similar  c o u p l i n g r e a c t i o n s between  bearing  cyanovinyl  functions.  Further,  dipyrromethane products the  yield,  porphyrin  isolation  of  with  syntheses,  the  s t e p was deprotect ethyl  ester.  ethanol, of  the  the  T h i s was  w h i c h was proton  nmr,  isolated  carried  solid  c a r b o n nmr  as w e l l in  as  high  2+2  dipyrromethane i t s conversion  t o r e s u m i n g work  Figure  14  provides  synthetic plan. 97_ w i t h  same t i m e ,  out  The  saponify  approximately ethanol  separated  out  was of  the  equivalents  boiled  off  after  solution,  (by e l e m e n t a l  mass s p e c t r o m e t r y )  to  aqueous  10  the  a  first  aqueous b a s e  in refluxing  characterized and  the  prior  system.  a t the  When t h e  and  106,  the  under n i t r o g e n , u s i n g  tan  rearranged  u s e f u l i n the  to attempt  dipyrromethane  a l d e h y d e and  a pale  no  uncontaminated product  porphyrin  sodium h y d r o x i d e .  3 hours,  other  only  s h o r t r e a c t i o n times  reasonable  representation of to t r e a t  also for  d e s i r e d product;  chain-linked dimeric  schematic  reprod-  a-free pyrroles carrying ester  the The  an  v i a dipyrromethanes.  corresponding  the  only  and  chloromethylpyrroles  t h i s method e x t r e m e l y  9 7 i n hand, i t a p p e a r e d the  not  above b u t  With s u f f i c i e n t q u a n t i t i e s of  to  was  1  formed was  rendered  yield  for  u n l i k e M a c D o n a l d s work, t h e  were o b s e r v e d .  facile  1st crop  the mother l i q u o r s  This high  g r o u p s and  f o r the  prepared  as  analysis,  the  deprotected,  89 ClHjC NC  H  CN  6  79  86  CH C0 H 3  2  70° C V  o'  \_  a) Aq. KOH  b) CH C0 H 3  2  V  Heat  0  o  105  106  FIGURE 14 : S y n t h e s i s o f the Model P o r p h y r i n - E t i o p o r p h y r i n I I  90 unsaponified filtrate the  d i p y r r o m e t h a n e 104.  with  a c e t i c a c i d gave a g e l a t i n o u s  d e s i r e d product The  letely  fact  under the  g r o u p , was a-ester  N e u t r a l i z a t i o n of  not  p r e c i p i t a t e of  103.  t h a t the  e t h y l e s t e r was  c o n d i t i o n s which c l e a v e d  surprising.  The  greater  g r o u p t o h y d r o l y s i s c o u l d be  not the  removed compdicyanovinyl  resistance of  due  a weaker e l e c t r o p h i l e t h a n a s i m p l e  a r e s u l t of  i t s conjugation  p y r r o l e nucleus.  t i m e s and  67%  In f a c t ,  somewhat h i g h e r  to i s o l a t e  the  with  the  by  1  system  of  shorter reaction  base c o n c e n t r a t i o n s ,  a-formyl-a -ethyl  ethyl ester;  d o u b l e bond  using  the  to i t s c a r b o n y l  group b e i n g  the  the  e s t e r 104  i t was  in  possible  approximately  yield. The  obtained imately  a-formyl-  a - c a r b o x y d i p y r r o m e t h a n e 103  in essentially 50  equivalents  was  f o u n d t o be  any  decarboxylation  was  cooled  quantitative yields of  complete  last  two  i n 1%  the  methane 105. could  be  steps  the  of t h i s and  using  The  In o r d e r  reaction t o atyoid  acetic acid.  sequence are  the  the  de-  acid catalyzed  2+2  r e s u l t i n g a-formyl-a ' -unsubstituted encountered p r e v i o u s l y , the  acid)  (using dimethyl  formamide), b u t  conditions  or weakly b a s i c the  dipyrro-  decarboxylation  under m i l d l y a c i d i c  or u n d e r - n e u t r a l  approx-  r e a c t i o n mixture  n e u t r a l i z i n g with  effected thermally,  (using.acetic itions  As  hours.  stage,  c a r b o x y l a t i o n o f compound 103 coupling of  by  sodium h y d r o x i d e .  at this  i n i c e before  The  was  1  choice  of  cond-  the  solvent  h e r e depends on t h e a c i d - c a t a l y s t s y s t e m t o be u s e d subsequent c y c l i z a t i o n  reaction.  105,  with  ring  t h a t has an u n s u b s t i t u t e d  high b o i l i n g  hence t h e i r solutions  if  acidic  s o l v e n t s used  group  t o be v e r y  soluble i n  f o r the decarboxylation  s m a l l volume.  o f the °t-formyl  This  could r e s u l t  and o f the  i n the  and a - f r e e p o s i t i o n s , e s p e c i a l l y  c o n d i t i o n s a r e used  linked dimeric  on_the  was n o t c o n s i d e r e d .  i s o l a t i o n would r e q u i r e the c o n c e n t r a t i o n  premature condensation chain  i t sisolation  s u c h compounds t e n d  to a very  condensation  product  a - p o s i t i o n , was n o t e x p e c t e d  s t a b l e and t h e r e f o r e  Further, the  The d e c a r b o x y l a t e d  t h e a b s e n c e o f an e l e c t r o n - w i t h d r a w i n g  t o be v e r y  i n the  f o r decarboxylation.  Such a  w o u l d be h i g h l y u n d e s i r a b l e  f o r the  system, s i n c e i n c o n c e n t r a t e d  solution,  t h i s w o u l d l e a d t o i n t e r m o l e c u l a r c o u p l i n g , w h i c h would n o t produce the d e s i r e d product The cyclization  acid catalyst step,  (see S e c t i o n 2.2). s y s t e m t o be u s e d  f o r the f i n a l  had t o be s e l e c t e d c a r e f u l l y .  Acid-catalyzed 5 3  r e a r r a n g e m e n t o f d i p y r r o m e t h a n e s i s a w e l l known phenomenon e s p e c i a l l y when t h e p y r r o l e s l a c k e l e c t r o n - w i t h d r a w i n g stituents. reactions fashion,  Such r e a c t i o n s a r e shown i n F i g u r e s h u f f l e the p y r r o l e s around  until  (dipyrromethenes)  attack.  P y r r o l e s 'bearing  although  more r e s i s t a n t  less  produces  susceptible to e l e c t r o p h i l i c  electron-withdrawing  to e l e c t r o p h i l i c  rearrangements.  These  i n a truly reversible  o x i d a t i o n o f t h e methane b r i d g e s  species  immune t o t h e s e  15.  sub-  Since  substituents,  attack,  such  are not  rearrangements  ,  FIGURE 15  : Acid-Catalyzed  Rearrangements  of  Dipyrromethanes  lead  to unexpected  proper acid  c a t a l y s t was  Of for of  i s o m e r i c p r o d u c t s , the s e l e c t i o n  the s e v e r a l  the dipyrromethane particular  co-workers  5 k  crucial. acid  catalysts  coupling  importance. , who  The  t h a t have been  reactions, first  two  i s by M a c D o n a l d  d e v e l o p e d a p r o c e d u r e f o r t h e one  fairly  pyrromethane.  high d i l u t i o n  in glacial  solution  of hydroiodic  solution  o f t h e two  in  order to o b t a i n  0.4%.  The  acid,  was  sodium the  acid  These  promoted  to  very  was  was  added  ( i n the  at  to a  dark)  formed.  T h i s was  r e d as  the  subsequently  the a c i d  with  leading  systems  to isomeric  studied,  por-  they obtained  65%. s e c o n d method was  , who  low y i e l d s  dipyrromethane p-sulfonic  dilute  acid  neutralizing  rearrangements  y i e l d s up  5 5  bis-a-  c o n d i t i o n s were shown t o m i n i m i z e  In t h e p a r t i c u l a r  workers  step  A  o b s e r v e d t o t u r n burgundy  phyrins.  The  and  performed  acid.  in acetic  to theporphyrin a f t e r  acetate.  acetic  was  are  HI c o n c e n t r a t i o n o f a p p r o x i m a t e l y  i n t e r m e d i a t e porphodimethene oxidized  reaction  i n acetic- acid,  reactants a final  solution  The  used  systems  condensation of a dipyrromethane dialdehyde with a unsubstituted  o f the  acid  obtained y i e l d s  d e v e l o p e d by Kenner  and  o b s e r v e d t h a t MacDonald's c o n d i t i o n s for similar systems.  However, i n t h e p r e s e n c e o f  t o 40%.  l e d to  condensations with d i f f e r e n t  i n methanol-methylene up  co-  The  chloride  p o r p h y r i n was  toluene-  solution, isolated  as  they the  94 zinc  salt  w h i c h was 5%  (zinc  a c e t a t e was  purified  sulfuric  by  added t o n e u t r a l i z e  c h r o m a t o g r a p h y and  the a c i d )  demetallated i n  acid-methanol.  0  0  103  W i t h -"the a - f o r m y l - a ' - c a r b o x y - d i p y r r o m e t h a n e it  was  acetic  noted  that  a c i d , MacDonald's c y c l i z a t i o n  preferred  since  Alternatively, cyclization, as  t h e same s o l v e n t 1  the s o l v e n t .  t o be  c o n v e n i e n t to use  important  i f acetic  Such p r e m a t u r e  c e s s i v e by-product  2.2).  reactions. f o r the  dimethylformamide  s t a g e was  the  poss-  acid  was  t o be  used  condensations, although would  lead  as  not to  ex-  f o r m a t i o n i n the c o r r e s p o n d i n g c h a i n -  d i m e r i c system,  (section  used  be  condensation during decarboxylation,  s i g n i f i c a n t w i t h the model systems,  linked  f o r both  point considered at this  of p a r t i a l  w h i c h w o u l d be  would  out i n  for decarboxylation.  Another ibility  carried  procedure  i s used  i f K e n n e r s method was  i t w o u l d be  the s o l v e n t  very  i f t h e d e c a r b o x y l a t i o n was  103 ,  due  to i n t e r m o l e c u l a r condensations  In o r d e r t o minimize  this,  the d e c a r b o x y l a t i o n  95 could  be c a r r i e d  doubtedly  lead to experimental The  if  o u t under h i g h  cyclization  hydroiodic  cyclization  acid  leave  exposed would  increase  the  slowly  catalyst  a c i d was n e u t r a l i z e d w i t h acid  unsuitable  over  a s an a c i d  long periods  o f time.  mineral  t h a t M a c D o n a l d had  i n a i r , which would  of time. a l l these  factors,  the decarboxylation  103 was c a r r i e d  When t h e r e a c t i o n was c o m p l e t e ,  concentrated,  outi n  The r e a c t i o n  water.  subjected  band  t h e s o l u t i o n was  i n v a c u o , s u f f i c i e n t m e t h y l e n e c h l o r i d e added and  most o f t h e r e m a i n i n g with  make  f o r reactions carried out  dimethylformamide, under n i t r o g e n .  280nm.  which  In a d d i t i o n ,  was m o n i t o r e d by t h e d i s a p p e a r a n c e o f t h e uv a b s o r p t i o n at  This  (of the type  when  sodium a c e t a t e .  catalyst  which  as t h e i n t e r m e d i a t e  10 t o 15 m i n u t e s , a f t e r  the-a^fqrmyl--.a ' - c a r b o x y p y r r o l e  refluxing  catalyst),  o f rearrangements  i s oxidized rapidly  Considering of  t o the acid  be e m p h a s i z e d  dilution  s e v e r a l days (the  15) t a k i n g p l a c e , e s p e c i a l l y I t should  problems  The h i g h  f o r long periods  r e a c t i o n times of only  hydroiodic it  out over  the p o s s i b i l i t y  i s used.  employed  difficulties.  t h e s t a r t i n g m a t e r i a l as w e l l  to the acid  would un-  i t s e l f may have c a u s e d  h a s t o be c a r r i e d  shown i n F i g u r e acid  but this  was u s e d a s t h e c a t a l y s t .  r e a c t a n t h a s t o be added would  step  dilution  d i m e t h y l f o r m a m i d e removed by e x t r a c t i o n  The r e a c t i o n p r o d u c t  to acid  was n o t i s o l a t e d  catalyzed cyclization.  b u t was  The above s o l u t i o n  was a d d e d , d r o p w i s e , t o a s o l u t i o n o f t o l u e n e - p  -sulfonic  acid,  in  methanol-methylene c h l o r i d e  was a l l o w e d  to s t i r  f o r a further  somewhat d i f f e r e n t f r o m t h a t the as  over a p e r i o d  the a c i d n e u t r a l i z e d  106  crystallized  yield  as s h i n y  attempted  in glacial  further  solution exhibited light,  both being  and t r e a t e d  acetic acid.  forming near  some f l u o r e s c e n c e  moiety).  A t t h i s stage,  comp-  420nm.  In a d d i t i o n ,  under l o n g  wavelength  the s o l u t i o n  with a d i l u t e s o l u t i o n of hydroiodic  After  allowing  the r e a c t i o n  20 m i n u t e s , t h e a c i d was n e u t r a l i z e d  the  work up was a s d e s c r i b e d the p u r i f i e d porphyrin The  A  i n d i c a t i o n s o f e x t e n d e d c o n j u g a t i o n due  for  of  t o a shoulder of the  45 m i n u t e h e a t i n g d i d n o t remove t h e s h o u l d e r started  acid,  diminished i n  ( r e s u l t i n g from t h e f o r m y l p y r r o l e  b u t a new band  also  the r e a c t i o n  On r e f l u x i n g i n a c e t i c  band a t 28 0nm p r o g r e s s i v e l y  to premature c y c l i z a t i o n .  in  o f 103 was  acetic acid, monitoring  and i n 4 5 m i n u t e s , was r e d u c e d  band a t 320nm  cooled  amine, t h e p o r p h y r i n  comparison, the decarboxylation  absorption  intensity  uv  concentrated  p u r p l e c r y s t a l s , i n an o v e r a l l  o n c e a g a i n b y uv s p e c t r o s c o p y .  the  ;  s a l t but d i r e c t l y  m i x t u r e was  with t r i e t h y l  5 5  o f a l m o s t 48% (from t h e p r e c u r s o r 1 0 3 ) . For  letely  The work-up was  u s e d by Kenner and c o - w o r k e r s  When t h e r e a c t i o n  and  the  15 h o u r s .  p o r p h y r i n was n o t i s o l a t e d a s t h e z i n c the f r e e base.  o f 2 h o u r s and .  with  mixture sodium  by MacDonald e t a l .  5  4  was acid  to s t i r acetate; The y i e l d  106 was 42% ( o v e r a l l f r o m 1 0 3 ) .  above r e s u l t s f u r t h e r  supported  t h e arguments  presented  earlier  on  decarboxylation.  the  The  cyclization  c a r b o x y l a t i o n would not porphyrin, strapped was by  but  Further,  All  this  coupled  considered, with  the  chosen f o r the  prepare  stituted  p y r r o l e 7_9  linked  four 85%  required. series,  acetic the  Each time a t o d)  (starting  to i s o l a t e  bringing  up  the  The  the  109  the  from the  possible  porphyrin  dimeric  than  model  that  the  obtained  this first  no  cyclization  t o as  9_5 w i t h  described  of  attempted  was  yield  same r e a c t i o n s c a r r i e d  95%  out  f o r m e d as  the  purification  94).  It  than  was  liquors,  in certain  the model  (in a l l  greater  outlined i n Figure on  by  model  prepared was  was  carried  instances.  the dipyrromethane dimer as  task  f o r the  from the mother as  was  t h e .'a-unsub-  r e a c t i o n was  compound was  high  first  chromatographic  crop  step).  96_ i n h i g h y i e l d ,  d e s i r e d product and  cyclization  systems.  The as  for  decarboxylation,  bis-a-methylpyrrole  conversion was  acid,  a second crop  yield  the  the MacDonald  system, the  ( F i g u r e 13) .  Once a g a i n ,  de-  involved a decarboxylation  only dipyrromethane product was  of  b i s - a -chloromethylpyrrole  i n warm g l a c i a l  of  acid  the  e f f e c t with  significant)  the dipyrromethane dimer  the  system.  yield  to the d i m e r i c  coupling  out  adverse  yield  the dimethylformamide  chain  acetic  indicated during  toluene- p - s u l f o n i c acid  Returning to  (both  an  the  (though not v e r y  K e n n e r ' s method  of using  have a f f e c t e d t h e  w o u l d h a v e had  system.  lower  disadvantages  9_6 t o  16,  the  using  dipyrromethane  FIGURE 16  : Conversion Strapped  of the Dipyrromethane  Porphyrin  109  Dimer  96 t o t h e  system. using  The  first  s t e p h e r e was  s t r o n g aqueous b a s e .  more c l o s e l y , spectroscopy.  the  In o r d e r t o f o l l o w  t h e d e p r o t e c t i o n was The  (due  a band o f medium i n t e n s i t y (a s h o u l d e r ) a t 315nm. e t h a n o l i c potassium  a t 27 5nm  t o lower wavelengths)  3 hours,  t h e e t h a n o l was  ition  the a d d i t i o n of water. t h e model s y s t e m ,  hours. cooled  equivalents),  ( a l s o moved  increase i n  to p y r r o l e  off.  aldehyde).  At this point,  this  i n f a c t more s o l i d Due solid  was  ethyl  a d d i n g e t h a n o l and  t o room t e m p e r a t u r e ,  boiled  s o l u t i o n was  with a c e t i c  over potassium  o f f and  a brown o i l y  on  g e l a t i n o u s p r e c i p i t a t e was  The  addwith  the  solid  was  unre-  c o n t i n u e d h e a t i n g f o r 3 more  out, which r e d i s s o l v e d acidified  on  experience with  s u s p e c t e d t o be ester.  a brown  separated out  to the s i m i l a r  When t h e e t h a n o l was  desiccator  i n aqueous  t o have gone t o c o m p l e t i o n i n  boiled  s a p o n i f i e d dipyrromethane by  refluxed  in intensity  (due  group),  separated out which d i d not r e d i s s o l v e  o f more w a t e r ;  dissolved  a strong  a weak a b s o r p t i o n  simultaneous  o f t h e band a t 315nm  powdery s o l i d  and  reaction  uv-visible  ( a p p r o x i m a t e l y 100  with the  appeared  by  9_6_ e x h i b i t e d  When t h i s was  hydroxide  this  to the d i c y a n o v i n y l  t h e a b s o r p t i o n a t 407nm d e c r e a s e d  Since the r e a c t i o n  monitored  starting material  a b s o r p t i o n band a t 4 07nm  intensity  deprotection-saponification,  the a d d i t i o n acid  filtered hydroxide.  and  the  product  solution separated  o f more w a t e r . and  the dark  dried  The brown  i n a vacuum  100 The  p r o t o n nmr  spectrum  (in dimethyl sulfoxide-d^) 6  of  this  solid  product exhibited  certain  0  features that  were  0'  107  i n c o n s i s t e n t with the s t r u c t u r e The  signal  a t <5.; 3.82 ppm,  of the expected  characteristic  product  107.  o f the methylene  b r i d g e p r o t o n s , c o n t a i n e d a "hook" a t 6 ... 3.77, i n d i c a t i n g t h e presence  o f two t y p e s o f d i p y r r o m e t h a n e s .  supported  by t h e p r e s e n c e  o f t h e two e x p e c t e d  for this  6,- 11.45) were o f e q u a l two N-H 103  resonances  pair. 6  proton  compound.  intensity  but l e s s  The two p y r r o l e r i n g m e t h y l  2.17 were n o t o f e q u a l  signals,  instead ( 6 , 11.00;  and compared w a l l w i t h t h e s i m p l e model  The o t h e r two, a t 6  intensity  further  Two o f t h e s e  of the corresponding  (6 - 11.00; 1 1 . 4 2 ) .  were a l s o o f e q u a l  o f f o u r N-H  T h i s was  intensity  9.87  i n t e n s e than  singlets  at 6  and a n o t h e r  system  and 6 the  11.24  former  2.15 and singlet  was  101 observed  at  with  s t r u c t u r e o f compound. 107.  the  6 1.91.  A l l the  happened came f r o m t h e  above f e a t u r e s were i n c o n s i s t e n t  broad  A c l u e t o what may  singlet  at  here i s i n d i c a t i v e  o f an  suggested  a-carboxy group of  t h a t the  partial  decarboxylation  prising  s i n c e the  6  a - p r o t o n on  during  6 6.33.  A  have  resonance  a pyrrole nucleus. 107  w o u l d have u n d e r g o n e  h y d r o l y s i s , w h i c h was  r e a c t i o n m i x t u r e had  This  not  sur-  been r e f l u x e d f o r o v e r  hours. If decarboxylation  t o have t a k e n p l a c e , concern  s i n c e the  decarboxylation porphyrin  109  was  i t would n o t  (Figure 16).  As  was  of  decarboxylation  although  the  one  and  2 hours.  a  synthesis  t h i s m a t e r i a l as above s o l i d  was  followed  (due  to the  formyl  r e a c t i o n appeared  When most o f  m e t h y l e n e c h l o r i d e was  the  s o l v e n t was  added,  108  in  great  of  the  planned.  taken  up  Once  uv-spectroscopy.  r a p i d l y decreased  a t 32 0 nm The  by  of  thermal  r e f l u x e d under n i t r o g e n .  band a t 28 0 nm  remained unchanged. in  was  the  s y n t h e s i s was  such, the  attempted with 50 mg  unexpected r e a c t i o n  have been a m a t t e r  i n the  i n d i m e t h y l f o r m a m i d e and  absorption  only  next step  Approximately  the  the  again,  The  intensity groups)  t o be  complete  evaporated  off  102 some s o l i d since  separated  out of solution.  the decarboxylated  i n methylene c h l o r i d e . attempted  with The  product  then  t o be s o l u b l e  the c y c l i z a t i o n  was  this material.  above s o l u t i o n was d i l u t e d  toluene-p -sulfonic  was a l l o w e d  surprising,  108 was e x p e c t e d  Nevertheless,  600mL w i t h m e t h y l e n e c h l o r i d e of  T h i s was  to s t i r  concentrated,  acid  to approximately  and was t r e a t e d w i t h  i n methanol.  solution  The r e a c t i o n  o v e r n i g h t i n the dark. the a c i d  a  The s o l u t i o n  removed by e x t r a c t i o n w i t h  urated  s o d i u m b i c a r b o n a t e and t h e o n l y f l u o r e s c i n g  (under  365nm l i g h t )  was i s o l a t e d  by c h r o m a t o g r a p h y .  109a  mixture was  sat-  material The mass  n =11  s p e c t r u m o f t h i s m a t e r i a l e x h i b i t e d t h e p a r e n t peak a t m/e as e x p e c t e d  = 574,  f o r t h e d e s i r e d p o r p h y r i n 109 and t h e h a l f mass peak  103 a t m/e  = 287.  Since  t h e r e was t h e p o s s i b i l i t y  linked  dimeric porphyrin being  1200 mass u n i t s was c h e c k e d such  a compound.  alize  t h e low y i e l d  Since  on  the c y c l i z a t i o n  f o r m e d , t h e mass r a n g e up t o  yield  of t h i s product  starting  i t was n o t p o s s i b l e t o r a t i o n -  obtained  t h e model system) as b e i n g  doubly  b u t t h e r e was no i n d i c a t i o n o f  The o v e r a l l  f r o m 107 was o n l y 7%.  of a  (compared  to almost  48% w i t h  due t o t h e r e s t r i c t i o n s  by t h e s h o r t s t r a p , a f r e s h  s t a r t i n g m a t e r i a l 107 was p r e p a r e d  i n order  imposed  sample o f t h e  to.repeat the  cyclization. The  deprotection - saponification  96 was c a r r i e d  o u t once a g a i n , a s d e s c r i b e d e a r l i e r .  t h e d e p r o t e c t i o n was c o m p l e t e by  uv-visible  the time boiled  spectroscopy)  taken  i n just  saponification.  separated  The p r o d u c t  reaction.  similar  to t h a t of the previous  This material exhibited a proton  i n t e n s i t i e s o f the e x t r a peaks subjected  those  decarboxylated s o l u t i o n over night.  (not expected  as p r e nmr  that the r e l a t i v e f o r 107) v a r i e d .  to d e c a r b o x y l a t i o n i n dimethylformamide  cyclized  used e a r l i e r .  sample e x c e p t  was  incomplete  was e v e n t u a l l y i s o l a t e d  described.  subsequently  (as i n d i c a t e d  When e t h a n o l  out, indicating  viously  and  3 hours  Although  i t was n o t p o s s i b l e t o r e d u c e  f o r the o v e r a l l  off, a solid  T h i s was t h e n  r e a c t i o n o f compound  u n d e r more d i l u t e  conditions  The m e t h y l e n e c h l o r i d e s o l u t i o n  m a t e r i a l was added d r o p w i s e  The s o l u t i o n d i d n o t e x h i b i t  o f the  to the acid  a p e r i o d o f 6 h o u r s and was a l l o w e d  than  catalyst  to s t i r  over-  any f l u o r e s c e n c e u n d e r  104 365nm l i g h t and  ( a l l porphyrins  no p o r p h y r i n  these  product  times,  with  from i t .  o f 107 -> 108 ->- 109,  o f compound 108 t o t h e p o r p h y r i n  Since  m o l e c u l e be a v a i l a b l e f o r t h e 2+2 c o u p l i n g .  It  should  polymerization  be r e c a l l e d  times r e q u i r e d  lation. by  at this  since  stage  p o s i t i o n with  e a c h o f two m o l e c u l e s ,  cyclization Of  o f 9_6 t o 107 had been a  could  be  o f the r e s u l t i n g  group, thereby  decarboxyfollowed a-free  b l o c k i n g one p o s i t i o n  towards i n t r a m o l e c u l a r  T h i s w o u l d have l e d t o e x t e n s i v e final  reaction  i t may have l e d t o p a r t i a l  condensation  an a - f o r m y l  S h o u l d any one  that the long  Such a p r e m a t u r e d e c a r b o x y l a t i o n  an i n t e r m o l e c u l a r  o f t h e same  i s a l l t h a t c o u l d be e x p e c t e d .  f o r the conversion  matter o f concern,  the con-  109 i s i n t r a m o l e c u l a r ,  i s e s s e n t i a l that a l l four reactive centres  blocked,  repeated  result.  i n t h e r e a c t i o n t h a t made 107 i t s e l f .  be  Both  t o assume t h a t t h e m a j o r c a u s e f o r  p r o b l e m was n o t i n t h e c o n v e r s i o n  version it  be i s o l a t e d  t h e same d i s a p p o i n t i n g  I t was r e a s o n a b l e  but  could  conditions)  r e a c t i o n s , 9_6 -> 107 and 107 -> 108 -> 109 were  several  this  f l u o r e s c e under these  cyclization.  polymerization  during the  step.  t h e two r e a c t i o n s t h a t t a k e  treatment o f the dipyrromethane  9_6 w i t h  base, the d e p r o t e c t i o n  of  the cyanovinyl  as  i n d i c a t e d by t h e c h a n g e s i n t h e u v - v i s i b l e s p e c t r u m .  the  other  monitored. resistant  group appeared  place during the  to proceed  reasonably  hand, t h e s a p o n i f i c a t i o n o f t h e e s t e r c o u l d  well,  n o t be  I t i s known t h a t p y r r o l e - a - e s t e r s a r e more t o base h y d r o l y s i s than a l i p h a t i c  esters.  On  One  105 solution  to  could  removed by  The  be  t h i s p r o b l e m was  a reaction, other  most o b v i o u s c h o i c e  removed e a s i l y this  by  be  was  the  benzyl  ester  synthesized  by  i n the  first,  i n order Figure  17  an  benzyl 86  ester  8_0 was  under the  work.  The  benzyl  ester  as  yield.  The  This  charcoal  as  moderate a t third of  the  of  the  the  but  unreacted  the  rate  indicated  f r e s h c a t a l y s t , but required  amount.  a-free  the  to produce  this  the then  to cleave  c a r r i e d out 10%  of uptake of  in  A  was one  t i c analysis a  reaction  once a g a i n  tetra-  hydrogen  the'".presence o f The  the  palladized  after absorbing  amount.  Another  that  pyrrole-  course of  i n order  starting material.  used  reactions  hydrogen u s i n g  t h e o r e t i c a l l y required  continued with up  The  13).  conditions.  compound was  stopped completely  r e a c t i o n mixture  amount o f  taking  catalyst.  first  (Figure  a-chloromethylpyrrole  r e a c t i o n was  h y d r o f u r a n under 1 atmosphere of  the  The  before,  hydrogenation  function.  reaction  o u t l i n e of  developed during  i n 88%  to c a t a l y t i c  a-unsubstituted  optimum r e a c t i o n  condensed w i t h the  r e a c t i o n proceeded 110  required,  for i t s ethoxycarbonyl  model systems.  conditions  dipyrromethane subjected  provides  using  9j) was  be  For  m o n o p y r r o l i c m o d e l s y s t e m was the  were c a r r i e d o u t  a t room t e m p e r a t u r e .  8_0  t o work o u t  that  e s t e r , which can  pyrromethane c o u p l i n g  Once a g a i n a c h a i n - f r e e  function  saponification.  substituting  1  7_9  than  analogue of  - . a -benzyloxycarbonylpyrrole analogue  ester  benzyl  hydrogenation  purpose, the  which c o u l d  t o have an  substantial was  i t stopped  attempt  to d r i v e  before the  An  Alternative Synthetic  Route t o E t i o p o r p h y r i n  II  107 reaction order  to completion  t o make s u r e  contaminated with a  using  that  fresh catalyst, failed.  the s t a r t i n g m a t e r i a l  some m a t e r i a l  that  In  110 was n o t  poisoned  the c a t a l y s t ,  f r e s h sample was p r e p a r e d and i t s h y d r o g e n a t i o n was  empted;  t h e r e s u l t was This  since  t h e same.  was a r a t h e r  unexpected  successful hydrogenolysis  containing  both benzyl  att-  ester  result, especially  of simple  monopyrroles  and a c y a n o v i n y l  protecting  group,  4 9  have been r e p o r t e d abandoning able  this  to attempt  cyanoacrylate  previously.  route  altogether,  rather  i t appeared  than  t o be r e a s o n -  the hydrogenation of the corresponding  d e r i v a t i v e 112, w h i c h was p r e p a r e d  manner u s i n g  the appropriate  17).  indeed a pleasant  I t was  Therefore,  in a similar  c h l o r o m e t h y l compound  87_  (Figure  s u r p r i s e t o o b s e r v e . t h a t the.  h y d r o g e n a t i o n o f 112 p r o c e e d e d w i t h o u t any p r o b l e m s a t a l l . The  r e a c t i o n was m o n i t o r e d c a r e f u l l y i n o r d e r  to avoid  any  o v e r h y d r o g e n a t i o n which might r e s u l t from the a t t a c k  of the  cyanovinyl  was  plotted  protecting  group.  The u p t a k e o f h y d r o g e n  as a f u n c t i o n o f t i m e and was f o u n d  linear.  Further,  i t stopped a f t e r only  h y d r o g e n had b e e n a b s o r b e d .  for  113 was  tetrahydrofuran  of  crystallized  (the s o l v e n t  the hydrogenation) with methanol, a f t e r removing the  catalyst. was  one e q u i v a l e n t  The p r o d u c t  f r o m t h e s o l u t i o n by r e p l a c i n g  t o be r a p i d and  The y i e l d  j u s t under  benzyl  ester  90%.  of this  analytically  I t i s n o t c l e a r why  110 was n o t h y d r o g e n a t e d  a c r y l a t e ..analogue 112  was.  pure  material  the d i c y a n o v i n y l -  f u l l y when t h e c y a n o -  108 The  d e c a r b o x y l a t i o n o f 113  trifluoroacetic' acid which simply in  osition of  stirring  during  evaporating  i t was  bicarbonate  An  by  Since  yield  of  92%  decomp-  o x y g e n was  minimal  was  removed  e x t r a c t i n g the  114  obtained  was  sodium found  used to i n two  first  methylene  a saturated  the p r o d u c t  was  to avoid  found  exposure  s o l u b l e i n m e t h a n o l , hexane was  overall  was  t h a t the  acid  of the r e s i d u e w i t h  solution.  reasonably  then  t i c and  In o r d e r  The  neat  starting material  by  essential  t h e work-up.  in  The r e a c t i o n ,  the  to atmospheric  i n v a c u o and  solution  of  monitored  5 minutes.  the r e a c t i o n mixture  chloride  it.  in just  of the product,  especially by  i n v o l v e d the  complete  performed  a t room t e m p e r a t u r e .  a c i d , u n d e r n i t r o g e n , was  t o be  was  to  be  crystallize  crops,  for  this reaction. The  next  step  in this  s y n t h e t i c r o u t e was  of  t h e c y a n o a c r y l a t e p r o t e c t i n g g r o u p , w h i c h was  in  aqueous p o t a s s i u m  methanol to get  hydroxide  the  d i p y r r o m e t h a n e 105 colored  solid  the product,  separated  i n an  removal  carried  out  u s i n g t h e minimum amount o f  starting material into  15 m i n u t e s o f r e f l u x i n g ,  the  out of  solution.  Within  a - f o r m y l - a ' T u n s u b s t i t u t e d  solution  a n a l y t i c a l l y pure s t a t e ;  as a l i g h t the  yield  tan was  almost q u a n t i t a t i v e . The carried  out  2+2  i n methylene c h l o r i d e - m e t h a n o l  toluene-p-sulfonic conditions  c o u p l i n g o f the dipyrromethane  for this  acid  as  the  cyclization  catalyst. were t h e  t h e model p o r p h y r i n , e t i o p o r p h y r i n I I 106  105  solution The  using  experimental  same as b e f o r e was  was  isolated  and in  109 68%  yield. It  in  this  the  should  work  that i n both  and  17),  t h e a-formyl-a  lation  obtained  product  b u t was  1  isolated.  ester route,  characterized, prior feature of  this  in solution,  developed  immediate p r e c u r s o r  —unsubstituted  as  the  dipyrromethane  (Figure 14),  thermal  to  this  decarboxy-  o f t h e ct - f ormyl-ct ' - c a r b o x y d i p y r r o m e t h a n e  not  acrylate-benzyl  On  the other  this  l a t t e r r o u t e was  carried  out with  the  r e a c t i o n s t o be m o n i t o r e d ;  hand, i n t h e  compound was  to c y c l i z a t i o n .  was  by  the  routes  In the d i c y a n o v i n y l - e t h y l e s t e r r o u t e  compound was  103,  noted  ( F i g u r e s 14  p o r p h y r i n was  105.  be  The  most  t h a t o n l y one  each reagent,  thereby  isolated  and  important deprotection  making  i t easy  t h e d e b e n z y l a t i o n was  t h e u p t a k e o f h y d r o g e n , d e c a r b o x y l a t i o n by  cyano-  for  followed  t i c a n a l y s i s and  110 the  removal of the c y a n o a c r y l a t e  visible for  spectroscopy.  the l a t t e r  p r o t e c t i n g g r o u p by u v -  Although this  route,  the high  i n t r o d u c e d more  yields  obtained  steps  throughout the  106  s e q u e n c e were more t h a n  sufficient  lowering  In f a c t ,  tained  of the y i e l d .  i n an o v e r a l l  methylpyrrole while  yield  to offset  the  the porphyrin  o f 4 9% s t a r t i n g  106 was o b -  from t h e a - c h l o r o -  87_ and t h e a - f r e e - p y r r o l e 8_0 (5 r e a c t i o n s )  the y i e l d  o f t h e same p o r p h y r i n ,  synthesized  o t - c h l o r o m e t h y l p y r r o l e 8_6 and t h e a - u n s u b s t i t u t e d was o n l y  43%  overall  ( f o r 4 r e a c t i o n s ) .•  from t h e  p y r r o l e 7j)  Ill The t o be  a very  porphyrin ality  cyanoacrylate-benzyl promising  109.  Since  alternative the  i s e f f e c t e d while  w o u l d n o t be  ester route  removal of  the  aldehyde  involves only  the  is still  cyanoacrylate  major concern  starting material.  s e q u e n c e was  the  The  strapped  protected, i t position  s i n c e the  to penultimate  the p r o t e c t i n g group,  the  -unsubstituted dipyrromethane i s  the d i c y a n o v i n y l group should The  seemed  ester function-  t o s t r o n g b a s e w o u l d be - g r e a t l y r e d u c e d .  removal of the  of  the b e n z y l  Further,  removal of  time t h a t the a-formyl-a' exposed  f o r the  p o s s i b l e f o r the a - u n s u b s t i t u t e d  undergo a premature c o n d e n s a t i o n . step  route  therefore  The  p r o t e c t i n g g r o u p compared help reduce t h i s  at this  stage  was  ease  of  to  time f u r t h e r .  the  availability  branch o f f p o i n t i n t h i s r e a c t i o n  a-formylpyrrole  dimer  93 w h i c h had  to  be  112 converted vinyl  to i t s b i s cyanoacrylate  d e r i v a t i v e 94_.  purified  only  reasonably but  very  order  o f 9^3 i t s e l f  little  intermediate  t h e new  9_3.  ester  available. i t was  dicyanovinylpyrrole  necessary  t o go  in back  formylpyrrole derivative  w i t h b a s e and t h e b i s a l d e h y d e s o as t h e b i s  cyanoacrylate.  o f l a r g e q u a n t i t i e s of the b i s  9j4 n e c e s s i t a t e d  forced  stage  Therefore,  A l t e r n a t i v e l y , the b i s d i c y a n o v i n y l  be r e - p r o t e c t e d  be abandoned;  was  derivative,  at this  9J) and make more o f t h e  had t o be d e p r o t e c t e d  reaction that  was  i t to i t s dicyanovinyl  sequence  The a v a i l a b i l i t y  the  dimer  l a r g e q u a n t i t i e s o f 94_ were i n hand  to follow  obtained  of the b i s d i c y a n o -  the formylpyrrole  after converting  to the b i s benzyl  94  Since  instead  the r e i n v e s t i g a t i o n o f  the d i c y a n o v i n y l - e t h y l  i . e . , the conversion  o f 9_6 t o 107.  ester As  route  to  mentioned  113  earlier, it  was  t h e main c o n c e r n h e r e was  r e a s o n a b l e t o assume t h a t  increasing solvent by was  the r e a c t i o n  used  i n this  a higher b o i l i n g aqueous b a s e  water,  reaction  reduced  this  ( e t h a n o l ) had  t o be  had  the  replaced  t o be m i s c i b l e  deprotection-saponification  therefore  reattempted  as t h e b a s e .  monitored  by uv  attributed  was  here with  t h e most  indicating  The  strong  group,  was  c o m p l e t e l y removed deprotection.  o f f a brown o i l s e p a r a t e d o u t  rather  on  the p r o d u c t s e p a r a t e d o u t once a g a i n  suction addition  and  easily  when d i l u t e d  The  w i t h water.  s o l u t i o n was  the product d i s s o l v e d  on  the f i l t e r  t h e most c o n v e n i e n t way  of d i s s o l v i n g  N e u t r a l i z a t i o n of the s o l u t i o n w i t h a c e t i c a-formyl- a V-carboxy-dipyrromethane ;  yield.  nmr  spectrum  The was  p r o d u c t was  dimer  (partially)  by  found  the to  material.  acid 107  under  paper  T h i s was this  which  However,  filtered  o f t h e minimum amount o f w a t e r .  95%  was  a b s o r p t i o n a t 4 07nm,  the c o m p l e t i o n o f the  boiled  as a brown s t i c k y mass.  compound  using potassium  redissolved cooling,  of  Once a g a i n , t h e d e p r o t e c t i o n  to the d i c y a n o v i n y l  hours  reaction  i n n-propanol  spectroscopy.  When p r o p a n o l was  be  and  by  purpose,  S i n c e the r e a g e n t used  the s o l v e n t  hydroxide  2.5  For  be  times  choice. The  in  could  reaction  t h e n e x t h i g h e r ;homologue, n - p r o p a n o l  obvious  9 6 was  this  temperature.  solvent.  and  the long  produced  i n greater  p a l e brown i n c o l o r  consistent with i t s structure;  and  the than  i t s proton  unlike  the  114 previous with  batches,  the a  product  no e x t r a n e o u s s i g n a l s were o b s e r v e d .  (n = 1 1 ) , b  (n = 10) and d  was a n a l y t i c a l l y  On t h e o t h e r  (n = 8) s e r i e s ,  pure, without  hand, compound 107c  Further, the r e a c t i o n  any r e c r y s t a l l i z a t i o n .  (n = 9 s e r i e s ) d i d n o t g i v e  a good a n a l y s i s b u t no r e c r y s t a l l i z a t i o n was a t t e m p t e d due to  the p o s s i b i l i t y o f The  in  refluxing  being  o f compound 107 was c a r r i e d  by uv s p e c t r o s c o p y .  i n 2 hours w h i l e  formylpyrrole taken  The a b s o r p t i o n band a t  g r o u p ) was r e d u c e d  t h e band a t 3 2 0nm  group) remained unchanged.  The p r o d u c t  was  and was  r e a c t i o n without  isolation.  It  was  of  t h e two a b s o r p t i o n b a n d s , .A^'Q ^ / A ^ Q , o f t h e s t a r t i n g  the be  interesting  to a  (due t o t h e  up i n m e t h y l e n e c h l o r i d e a s d e s c r i b e d b e f o r e i n the subsequent c y c l i z a t i o n  erial  related  final  largest  p r o d u c e d when t h i s previous  step.  r e a c t i o n was o b t a i n e d (closer  t o 1.5), while  r a t i o was  b a t c h e s o f 107, t h i s  this  observation  smaller. ratio  was  The o n l y  mat-  f o r each o f  T h i s appeared t o produced  The maximum y i e l d  o r no p o r p h y r i n was p r o d u c e d . for  1.  t o t h e amount o f t h e p o r p h y r i n  cyclization  was  1.5 w h e r e a s t h e r a t i o  b a t c h e s was a p p r o x i m a t e l y  lation-cyclization ratio  to note t h a t the r a t i o o f the i n t e n s i t i e s  was a p p r o x i m a t e l y  previous  out  dimethylformamide, under n i t r o g e n , the r e a c t i o n  (due t o t h e c a r b o x y p y r r o l e  shoulder  used  decarboxylation  monitored  280nm  decomposition.  i n the  f o r the decarboxy-  when t h e A 8 d / 3 2 0 A  2  lower y i e l d s  In f a c t ,  with the  1 or less logical  i s t h a t a lower r a t i o  were  and  little  explanation  c o u l d be an  indie-  ation of a partial of  9^6.  very  decarboxylation  thes a p o n i f i c a t i o n  T h i s may have l e d t o s u b s e q u e n t m o d i f i c a t i o n o f t h i s  reactive centre,  thereby  u n d e r g o i n g an i n t r a m o l e c u l a r The  The  during  cyclization  preventing  the molecule  from  cyclization.  itself  was e f f e c t e d a t h i g h  dilution.  m e t h y l e n e c h l o r i d e s o l u t i o n o f 108 was added t o t h e a c i d  catalyst  (toluene- p - s u l f o n i c a c i d i n methanol-methylene  chloride  solution) extremely  This rate,  i s a device  t h a t i s used  through a hypodermic  operation,  slowly,  t h e pump e m p t i e d  using  a syringe-pump.  t o add a s o l u t i o n a t a  syringe.  A t the slowest  a 20mL s y r i n g e  in  constant speed o f  approximately  7 hours.  I t was  constant of  the  precursor  out  approximately  i n 15 0mL  500mL.  added  (700mg o f  acid  of  the  used here In  two  two  less  polar  of  acid.  I t was nine the in  Under t h e  carbon  dilution  product  monoporphyrin  109  strapped  cyclization  porphyrins,  and  recalled  yield  106,  t h a t the  synthesized  109a,  by  26.8%  the  of  of  was  adjusted was  just  An  was  t o a minimum. sufficient  conditions was  was the  to  specified  the  desired  convenient. eleven,  109b  above.  reaction obtained  were 39.6%, 37.3%  volume  t h e r e f o r e i t s chromato-  synthesize  r e a c t i o n sequence d e s c r i b e d the  and  carried  (600mL).  acid  obtained  (discussed later)  p o s s i b l e to  amount  toluene- p - s u l f o n i c  the  the  porphyrin  of  starting  s o l v e n t , methylene c h l o r i d e  the d i s s o c i a t i o n  purification  the  solution  methylene c h l o r i d e  dissolve  graphic  final  syringes, this  amount o f m e t h a n o l u s e d was  bridged  flasks  experiment  the  the  singly  dilution  d e c a r b o x y l a t i o n was  fact,  only  number o f  e a c h c o n t a i n i n g 4g  (25mL) and  to hold  above, the  The  i n methylene c h l o r i d e ,  separate  flasks,  i n methanol  excess  107a), the  product,  and  t h e ' a - f ormyl'-a ' - c a r b o x y - d i p y r r o -  o f d i m e t h y l f o r m a m i d e and  Using  into  the  In a t y p i c a l  1 mmol'of  the d e c a r b o x y l a t e d to  funnel.  u s e d , were v a r i e d d e p e n d i n g on  m a t e r i a l used.  methane d i m e r  such a slow  a dropping  s o l u t i o n , as w e l l as  solution  starting  with  p o s s i b l e to o b t a i n  a d d i t i o n rate with  catalyst of  not  and  The  three  ca.48%.  and  using yields porphyrins  I t should  the model p o r p h y r i n ,  same method, was  109c  highest  f o r the  respectively.  ten  be  etioporphyrin II If  one  considers route,  this  the reduced  reflect  the strapped  o f the chain  the chain  carbon  systems  s t r a p was i n t r o d u c e d  but the r e d u c t i o n  l e n g t h by one c a r b o n d i d n o t seem t o a f f e c t t h e  significantly.  On t h e o t h e r  hand, t h e r e d u c t i o n o f  c h a i n by one more c a r b o n had a more p r o n o u n c e d  the  yield  the  nine  d r o p p e d by a l m o s t 1 0 % . carbon chain,  intramolecular  eight  carbon  every  intermediate  in  spectral  spectra the  first  '2+2  initial  product  reached f o r  absorption  be e m p h a s i z e d  that  (the porphodimethene) flexibility  porphodimethene i n t e r m e d i a t e  to gain  deserves a s p e c i a l mention.  the aromatic of the  I t was o b s e r v e d  was  have  Further, i f  was f o r m e d ,  to a t t a i n  chromatographic p u r i f i c a t i o n  although  to f a c i l i t a t e  even t o such a s p e c i e s .  near p l a n a r i t y ) i n order  well  o n e s i n t h e a,  c o u p l i n g , an e i g h t c a r b o n c h a i n may strain  although  m a t e r i a l was i s o l a t e d i n  I t should formed  with  was o b t a i n e d  which e x h i b i t e d p e c u l i a r  product  that  In the case o f the  the corresponding  A non-fluorescent  effect;  ( s e r i e s d) compared  i t would n o t have been a b l e  The  suggested  l i m i t was b e i n g  synthesis  to possess the necessary  initial  strained, (or  i n this  low y i e l d  cyclic  This  condensation.  p r o p e r t i e s with  imposed e x c e s s i v e the  ,<2+2  (see C h a p t e r 4 ) .  expected the  the lower  s t r a p , no p o r p h y r i n  b and c s e r i e s . extremely  should  8% d r o p i n t h e y i e l d  the  this  for this  l e n g t h on t h e c y c l i z a t i o n  T h e r e was an a p p r o x i m a t e l y  when an e l e v e n  yield  as t h e maximum p o s s i b l e y i e l d  y i e l d s with  the e f f e c t  reaction.  of  value  already  planarity stability. porphyrins  that the strapped  118 porphyrins  do n o t move on a c t i v i t y  m e t h y l e n e c h l o r i d e as t h e e l u t i n g of  the non-porphyrin  ing  by-products  the concentrated  acid gel.  I silica solvent.  (after  colorless,  most  removed by p a s s removing the  a small quantity of a c t i v i t y  When t h e e l u a t e was a l m o s t  pure  Therefore,  were f i r s t  r e a c t i o n mixture  c a t a l y s t ) through  g e l with  I  silica  2% m e t h a n o l was  added t o m e t h y l e n e c h l o r i d e a n d t h e p o r p h y r i n was e l u t e d out.  T h i s was e f f e c t i v e l y  was c o n c e n t r a t e d gel.  After  a filtration  the l a s t  again eluted with  the  was on b a s i c a l u m i n a .  especially partially  I t was o b s e r v e d the nine  carbon  protonated  The o n l y m a t e r i a l t o move  the i m p u r i t i e s remaining a t  that a l l three  strapped  on s i l i c a  The f i n a l  porphyrins,  porphyrin  1 0 9 c , were  g e l a n d c o u l d n o t be made t o  move u n l e s s  the solvent p o l a r i t y  In t h e case  o f 109c up t o 5% o f m e t h a n o l was r e q u i r e d .  always r e s u l t e d and  essential.  silica  on b a s i c a l u m i n a  purification),  move ahead o f and a l m o s t the  purification  s e p a r a t i o n almost  methanol. This  the porphyrin  on b a s i c a l u m i n a  I f t h e e l u a t e from t h e f i r s t  graphed d i r e c t l y IV  was i n c r e a s e d w i t h  i n some i m p u r i t i e s c o n t a m i n a t i n g  t h e r e f o r e the f i n a l  silica  t h e p o r p h y r i n was once  2% m e t h a n o l - m e t h y l e n e c h l o r i d e .  t h e c o l u m n was t h e p o r p h y r i n , origin.  IV  t r a c e s of the f o r e r u n n i n g  i m p u r i t i e s with methylene c h l o r i d e ,  on  The e l u a t e  and r e c h r o m a t o g r a p h e d on a c t i v i t y  removing  purification  process.  was  c o l u m n was r e c h r o m a t o -  (without  subjecting to a c t i v i t y  a d a r k y e l l o w band was o b s e r v e d with  the porphyrin product  impossible.  to  w h i c h made  119 I t was porphyrins  also interesting  to note  were more s o l u b l e i n m e t h y l e n e c h l o r i d e t h a n  model p o r p h y r i n , e t i o p o r p h y r i n I I . since  the molecules  inherently  By  low  c o v e r i n g one  carbon  chains  aggregation, that result  effect  best  These alkane  the  c o u l d g r e a t l y reduce the  exhibiting  of these  extent of  also porphyrins.  i n lower  solubilities.  to c r y s t a l l i z e  109a  and  10 9b,  The  these  these  molecular  a w e l l known phenomenon i n p o r p h y r i n  For  are  c h a i n s may  solubilities  the  surprising,  chains which  of molecules  increased  chemistry, solubilities  compounds f r o m m e t h y l e n e  nitromethane  solvent for r e c r y s t a l l i z a t i o n  proved  was  found  whereas f o r 109c,  t o be  the  methanol  t o be b e t t e r . Although  the  had  been s u c c e s s f u l l y  was  of  interest  sequence developed of  on  not  f a c e of the p l a n a r p o r p h y r i n m o l e c u l e ,  made i t d i f f i c u l t chloride.  solubility  solubilities.  indirect  T h i s was  c o n t a i n long alkane  known t o i n c r e a s e t h e  have an  that a l l three  syntheses  accomplished  to study  the  ( v i a the b e n z y l on  t h e p o r p h y r i n 10 9. had  studies,  s e q u e n c e was  series  (series  yields  of  two  the  chain-linked  feasibility  of  (Figure 17),  been p r e p a r e d  a).  the  planned,  i t  second s y n t h e t i c  i n the  l g . of each of  only with  Further, i n order  e s t e r 9_0  synthesis  f o r m e t a l l a t i o n and  attempted  pathways, the  b i s benzyl  porphyrins  as o r i g i n a l l y  Since approximately  three porphyrins  carbon  strapped  e s t e r - c y a n o a c r y l a t e dipyrromethane)  t h e model s y s t e m  t h e new  of the  s y n t h e s i s was stage.  the  binding eleven  t o compare started  the  at  the the  120  X 90a  CO CH C H 2  93 a  crude bis  a  C(H)=^C(CN)  9 0a was  first  of methylcyanoacetate After  was  i n approximately 90a.  70.2%  60-65%.  3  subsequently  chromatographic  to the b i s  (Figure 12).  amounts  purification,  The h i g h e s t y i e l d  yield,  recorded  series  The  p r o t e c t e d as t h e  i n toluene with  76% o v e r a l l  sequence, f o r the c o r r e s p o n d i n g was  2  and c a t a l y t i c  hexylamine.  benzyl ester  CO CH  93a as d e s c r i b e d e a r l i e r  f o r m y l p y r r o l e d i m e r was  isolated  2  converted  c y a n o a c r y l a t e 115a by r e f l u x i n g  lents  5  C(H)=C(CN)  The compound formyl d e r i v a t i v e  6  CHO  94a 115  2  two  of  cyclo-  the product from  the  i n the c y a n o v i n y l  o f r e a c t i o n s (90  ( f o r 94b) b u t i n g e n e r a l , t h e y i e l d s  equiva-  varied  94)  between  121 The  r e a c t i o n s e q u e n c e t h a t was u s e d  cyanoacrylate  115a t o t h e p o r p h y r i n  i n F i g u r e 18.  was c a r r i e d  o u t as b e f o r e , u s i n g s u l f u r y l  of  The b i s - m o n o c h l o r i n a t i o n  1  117a.  c h l o r i d e and t h e  condensed w i t h  t h e a - f r e e p y r r o l e ;a - b e n z y l  dipyrromethane dimer  o f 115a  a  116a was s u b s e q u e n t l y  the b i s  109a i s s c h e m a t i c a l l y  represented  product  to convert  two e q u i v a l e n t s  e s t e r 8_0 t o p r o d u c e t h e  The p r o d u c t  d i d not c r y s t a l l i z e  when t h e r e a c t i o n m i x t u r e  was c o n c e n t r a t e d  added.  Instead,  out.  of  d i p y r r o m e t h a n e d i d n o t a i d i t s c r y s t a l l i z a t i o n . When  this  the  i toiled  The m a t e r i a l s o o b t a i n e d  b i s - p y r r o l e 1X5a) was f o u n d used  purification  ( i n 81% y i e l d  t o be a n a l y t i c a l l y  i n the subsequent r e a c t i o n s .  The f a i l u r e  a t the c y a n o a c r y l a t e groups The  as u s u a l the  hydrogenation  of this  catalyst.  10% p a l l a d i z e d  was e v i d e n t .  1X8a  o u t i n an a n a l y t i c a l l y  hydrof uran  The  and u n i f o r m  The c a r b o x y p y r r o l e  was r e p l a c e d b y m e t h a n o l .  was o b t a i n e d  c h a r c o a l as  m o d e l s y s t e m 112 and o n c e a g a i n , no  overhydrogenation crystallized  geometric  117a was c a r r i e d o u t  The u p t a k e o f h y d r o g e n was f a s t  f o r the corresponding  of  compound  (see C h a p t e r 4 ) .  o f compound  i n tetrahydrofuran using  from t h e  p u r e and was  c r y s t a l l i z e c o u l d w e l l be due t o t h e p r e s e n c e  isomers  as  The c h r o m a t o g r a p h i c  s o l v e n t was removed on t h e v a c u u m - l i n e , t h e compound  glassified.  to  and m e t h a n o l was  product  p u r e f o r m when  An o v e r a l l  yield  tetrao f 84%  i n two c r o p s . d e c a r b o x y l a t i o n o f 118a was p e r f o r m e d i n n e a t  trifluoroacetic  acid  and a s i n t h e c a s e  o f t h e model  compound  122  FIGURE 18  :  An  Alternative  Porphyrin  10 9  Synthetic  Route t o  the  Strapped  123 113,  t h e r e a c t i o n was  work up in  of the  92%  deprotected being  material.  On  out  solution  that  unsubstituted  ester  of  109a  was  this  i t was 108  noted  a-formyl-a'  was  never  was  the  -  immediate  isolated.  The  performed under  above  The  yield  clearly has  compensated  Starting  109a  was  The  of  precisely the  indicate  that  great potential  yields  f o r the  as  produced  extra steps  same p o r p h y r i n was  i n an o v e r a l l produced o n l y  d i c y a n o v i n y l - b i s - p y r r o l e 94_) .  i s not very  synthesis of  115a  overall  significant, from the  yield  i t should  b i s benzyl  o f 76%  yield i n 28%  (starting  compared  involved  31%  yield,  from  the this  recalled  e s t e r 9_0 was to the  were  115a,  of  Although be  head-  obtained  from the b i s - c y a n o a c r y l a t e  the d i c y a n o v i n y l - e t h y l e s t e r r o u t e  a higher  be  s y n t h e t i c pathway f o r p o r p h y r i n s , v i a t h e  sequence.  difference  separated  51.5%.  presented  t h e y more t h a n  corresponding  starting  i n the d i c y a n o v i n y l - e t h y l  c o u p l i n g of dipyrromethanes.  whereas t h e  in  although  results  the p o r p h y r i n  the  109a  the  I t should  119a  with  the product  yield.  usual  This material  hydroxide,  above r e a c t i o n , t h e  cyclization  porphyrin  alternative  h i g h and  via  of the  95%  crops).  to s o l u b i l i z e  cyanoacrylate-benzyl ester route  to-tail  in  i n over  as w e l l ,  The  an  again  The  t h e compound  ( i n two  same c o n d i t i o n s m e n t i o n e d e a r l i e r .  purified  the  yield  d i p y r r o m e t h a n e d i m e r 108a  intramolecular the  used once  to the p o r p h y r i n  route  produced  removal of the a l c o h o l ,  the product  precursor  overall  5 minutes.  u s i n g aqueous p o t a s s i u m  n-propanol  of the  i n just  r e a c t i o n mixture  g r e a t e r than  was  complete  60-65%  that  effected yields  124 generally other the  obtained  hand, t h e  f o r the c o n v e r s i o n of  s y n t h e s i s of  79,  the  transesterification  w h i c h was  effected  When one the  corresponding  above seem t o be porphyrin. thesis  The  should  u s e d , on  the  c o n s i d e r s t h e number o f obtained,.both  b a s e d on  the  the  where t h e here  ethyl  ester  steps  involved  and  pathways d e s c r i b e d s y n t h e s i s of a  f o r any  particular  possible effects the  strapped  of  the  syn-  reagents  intermediates  and  ITS  INCORPORATION  aim  was  of  the  to build was  the p o r p h y r i n .  porphyrins a distorted  co-ordinate  l e a v i n g a vacant  work was  109b  porphyrin  to introduce a bulky  of a nitrogeneous  durene-bis-pentane  109a,  Such a s y s t e m was  of a f i v e  the presence  in this  used  m o d e l s y s t e m f o r heme p r o t e i n s .  site  binding of a small molecule. was  one  s y n t h e t i c route developed  syntheses  formation  thereby  step;  PORPHYRIN  the main c o n c e r n  face of  in  porphyrin.  to c o n s t r u c t y e t another Unlike  the  yield.  choice of e i t h e r  be  On  extra  corresponding  e q u a l l y u s e f u l f o r the  the  The  in  the  DURENE-BIS-PENTANOIC ACID AND INTO A  the  of  i n v o l v e d an  r e q u i r e d B-substituents of  therefore of  2.7  i n 84%  yields  94_.  t h e a - f r e e - p y r r o l e 8_0 u s e d  cyanoacrylate-benzyl ester route  i.e.,  9_0 t o  109c  molecule,  g r o u p above  expected  to  base  (due  to s t e r i c centre  s t r a p chosen  ( S e c t i o n 2.2),  w h i c h was  for  one  favour  s p e c i e s as o p p o s e d  a t the metal The  and  to s i x , reasons), the  for this required  work as  125  the  b i s pentanoic  durene  available  as t h e s t a r t i n g m a t e r i a l .  of the b i s pentanoic  methyl d e r i v a t i v e incorporation trivial  discussion of  into  i s discussed  acid  s t a r t i n g from the c h l o r o -  i n section  the porphyrin  The  2.7.1 whereas i t s  i s given  i n section  name, d u r e n e , i s commonly u s e d  2.7.2.  throughout the  b u t t h e s e compounds have been named  as d e r i v a t i v e s  2,3,5,6-tetramethylbenzene.  2.7.1  SYNTHESIS OF DURENE-BIS-PENTANOIC  The  synthetic  durene i s o u t l i n e d  19.  bis(chloromethyl)  I t was a p p a r e n t t h a t t h e  e x t e n s i o n method w o u l d be two m a l o n a t e  syntheses, each c o n d e n s a t i o n e l o n g a t i n g carbon  ACID  scheme, s t a r t i n g f r o m  i n Figure  most c o n v e n i e n t c h a i n  the chain  by two  atoms. The  most s u i t e d are  Bis(chloromethyl)  ( A l d r i c h C h e m i c a l Co.) a t a r e a s o n -  p r i c e and was s e l e c t e d  synthesis  The  f o r the synthesis.  , [1,4-bis(chloromethyl)-2,3,5,6-tetramethylbenzene]  was c o m m e r c i a l l y able  acid  commercially  available  f o r the i n i t i a l  starting material  malonate r e a c t i o n .  Although  the l e a s t r e a c t i v e o f the a l k y l h a l i d e s , towards  philic  s u b s t i t u t i o n , the s t a b i l i t y  of the benzyl  ion  i s known t o a i d i n t h e r e a c t i o n s  The  extra  a c t i v a t i o n provided  involving  by t h e f o u r  was chlorides  nucleo-  carbpnium  such  groups.  methyl groups  was  126  COjH BIS(CHLOROMETHYL) D U R E N E  COJC^J 121  120  t  Ouinoline heat  COjH  122  EtOH / H SO 2  V  C02C H 2  123  FIGURE 19 : S y n t h e s i s o f D u r e n e - B i s - P e n t a n o i c  Acid  130  5  A  127 expected the  to favour  ethanol  sodium e t h o x i d e  the d i s s o l u t i o n the  in this  of  excess  obtained  in situ,  of  dissolution  the  was  not  order  equivalents)  with  When  the r e a c t i o n mixture  observed;  the white  the  malonate  s t a r t i n g m a t e r i a l and  reflux,  starting material within  observed  t h a t t h e change i n t h e  re-  bis(chloro-  Nevertheless,  had  had  5 6  brought to  solid  of  equimolar  chloride, Marvel  s o d i u m c h l o r i d e (the o t h e r p r o d u c t )  the  on  half  a tic.  precipitation  occurred  so  fast  reaction  mixture  observable. The  12 0 was  (4  added t o t h e m o n o s o d i o d i e t h y l  of the  simultaneously,  In  b e n z y l malonate u s i n g  d i b e n z y l malonate.  and  prepared  analogous conversion  s t a r t i n g m a t e r i a l c o u l d be  and  not  reaction,  product isolated  to the  of but  distilled  this  o f f and  r e a c t i o n , the  tetraethyl  saponified directly  tetraacid  complete, approximately was  t h e b a s e , w h i c h was  I n an  to remain u n d i s s o l v e d .  an h o u r , no The  was  change c o u l d be  appeared  i n anhydrous  51-57% o f t h e d e s i r e d p r o d u c t ,  methyl)durene"  on  the d i a n i o n of malonate l e a d i n g  reaction.  mainder b e i n g d i e t h y l  no  performed  sodium i n e t h a n o l .  o f t h e m a l o n a t e and  only  generated  as  synthesis  observed.  d i e t h y l malonate  b e n z y l c h l o r i d e to d i e t h y l quantities  b i s malonate  t h i s was  of m e t a l l i c  formation  to b i s a l k y l a l i o n , used  indeed  m a l o n a t e r e a c t i o n was  using  to prevent  was  simultaneous  starting material; The  by  the  one  121. third  Once t h e of the  t h e r e m a i n d e r was  ester  in a single-pot  alkylation solvent  was  (ethanol)  treated with  aqueous  128 potassium  hydroxide  saponification  solution.  of a l l ester  o f b a s e were u s e d . and  the remaining  temperature hydrochloric caused  In order to ensure  groups,  approximately  The m i x t u r e was  refluxed  e t h a n o l was b o i l e d  reached acid  100°C  .  with concentrated  acid  vigorous evolution expected  white  solid  of gas.  was  than  found  product i s o l a t e d  95% o v e r a l l  compound  decarboxylation. t h i s purpose  from  the b i s malonic  with the acid  the r e a c t i o n mixture  The b i s m a l o n i c yield  t o be a n a l y t i c a l l y The  formed,  from  t o d e c a r b o x y l a t e under t h e s e c o n d i t i o n s , t h e  no d e c a r b o x y l a t i o n . greater  Although  at reflux,  (resulting  t h e e x c e s s d i e t h y l m a l o n a t e used) as i t was  was  the r e f l u x  while m a i n t a i n i n g the s o l u t i o n  the d e c a r b o x y l a t i o n of malonic  12 e q u i v a l e n t s  f o r a s h o r t time  off until  Acidification  complete  acid  121 o b t a i n e d i n  from - b i s ( c h l o r o m e t h y l ) d u r e n e , -  pure.  121 was n e x t  Q u i n o l i n e was  subjected to thermal  selected  as t h e s o l v e n t f o r  n o t o n l y due t o i t s h i g h b o i l i n g  b u t a l s o due t o i t s a b i l i t y  indicated  to f a c i l i t a t e  point  (237°C) ,  the process of  d e c a r b o x y l a t i o n by t h e f o r m a t i o n o f t h e c a r b o x y l a t e a n i o n . In r e f l u x i n g aneous.  quinoline,  The p r o d u c t 122 was  r e a c t i o n mixture by  filtration.  the f i l t r a t e ether. darkened  t h e d e c a r b o x y l a t i o n was  into dilute  Although  by p o u r i n g t h e h o t  hydrochloric  acid  and c o l l e c t e d neutralizing  s o d i u m h y d r o x i d e and e x t r a c t i n g  q u i n o l i n e was  d u r i n g the r e a c t i o n  instant-  crystallized  The q u i n o l i n e was r e c o v e r e d by  with s o l i d  almost  redistilled  prior  into  to use, i t  (even u n d e r n i t r o g e n ) ,  causing  the product had  to be c o l o r e d brown.  T h e r e f o r e , the crude  product  to be p u r i f i e d by d i s s o l v i n g i n hot aqueous sodium b i -  carbonate,  f i l t e r i n g through a c e l i t e plug and  by a c i d i f i c a t i o n . g r e a t e r than  The  y i e l d of the p u r i f i e d product  was  96%.  With the c h a i n extended by two task was  reprecipitating  carbons,  the  next  to convert the c a r b o x y l i c a c i d f u n c t i o n a l i t i e s of  CO^  122  CH^H  122 to groups s u i t a b l e f o r the second malonate s y n t h e s i s . first was  step was  the r e d u c t i o n to hydroxymethyl groups, which  performed i n the u s u a l manner u s i n g diborane.  m a t e r i a l 122'did hydrofuran,  The  not d i s s o l v e completely  The  starting  i n the s o l v e n t , t e t r a -  but appeared to d i s s o l v e d u r i n g the r e a c t i o n .  Since a t i c of the r e a c t i o n mixture  i n d i c a t e d some s t r e a k i n g  behind  the f a s t moving product  (no s t a r t i n g m a t e r i a l  left),  i t was  allowed  spot  to s t i r f o r 10 minutes a f t e r the a d d i t i o n  of boron t r i f l u o r i d e e t h e r a t e .  U n f o r t u n a t e l y , the  turned g e l a t i n o u s and e v e n t u a l l y hardened. been due  solution  T h i s may  to the formation of i n s o l u b l e borates of the  have product.  130 Since s t i r r i n g excess  was  virtually  impossible at this  d i b o r a n e was q u e n c h e d w i t h a c e t i c  was  diluted  w i t h water which r e s u l t e d  The  product  124  in  v a c u o and  was  was  isolated  spectrum  a t m/e  a n a l y s i s was 2%  = 250  t h e s t r u c t u r e 124 integrated was  due  was  dried  hydroxy  but  on  The  i n t h e nmr  unchanged.  p r o t o n nmr  t h e two  subsequent  next  hydroxy  consistent  proton resonance  but  with  a t 6' 1*47  Assuming t h a t  this  o u t as a h y d r a t e , a samplehours.  the carbon  This  analysis  N e v e r t h e l e s s , t h i s p r o d u c t was  s t e p i n the  s y n t h e s i s was  g r o u p s t o good l e a v i n g  g r o u p was  of the carbonium  the  remained used  for  Two  g r o u p and  t h e bromo g r o u p .  the c o n v e r s i o n  groups f o r the  S i n c e the i n f l u e n c e o f  not a v a i l a b l e  i o n , t h e use  avoided.  f o r the  chloride  and  m a t e r i a l 124  b r o m i n a t i o n was  Since mesylation  p y r i d i n e ) s h o u l d be  was  attempted  stabil-  in a partially  was  methanesulfonyl ( u s i n g methane-  carried  t h e r e were i n d i c a t i o n s  first.  the  of a c h l o r o group  g r o u p s c o n s i d e r e d h e r e were t h e  a n h y d r o u s c o n d i t i o n s and starting  was  o f the h i g h i n t e g r a t i o n o f  malonate s y n t h e s i s .  tetramethylbenzene  sulfohyl  approximately  modification. The  ization  Although  f o r 124, i t s e l e m e n t a l  a t 80°C f o r 24  to s o l v e the problem  solution.  aqueous e t h a n o l .  Carbon a n a l y s e d  the hydroxy  the vacuum-line  solution  the t e t r a h y d r o f u r a n  somewhat h i g h e r t h a n e x p e c t e d .  protons  further  of  as e x p e c t e d  value.  the  the  s t r o n g p a r e n t peak i n t h e mass  to the p r o d u c t c r y s t a l l i z i n g  appeared  almost  a very  not acceptable.  below the e x p e c t e d  from  and  in a clear  by r e m o v i n g  recrystallized  this material exhibited  acid  stage,  out  that  hydrated  under the  form,  A t e s t r e a c t i o n was c a r r i e d out on a r e l a t i v e l y small s c a l e  (0.02 M) u s i n g the b i s ( h y d r o x y p r o p y l ) d u r e n e  CH^H  CH Br 2  m 124  V27  sample prepared above.  The s t a r t i n g m a t e r i a l was heated,  under n i t r o g e n , with a mixture of 48% aqueous hydrobromic a c i d and c o n c e n t r a t e d s u l f u r i c a c i d .  The s o l i d s t a r t i n g m a t e r i a l  turned i n t o an o i l and l a t e r produced aqueous reagent.  Within 30 minutes,  an emulsion with the the t i c o f an a l i q u o t  e x t r a c t e d i n t o methylene c h l o r i d e e x h i b i t e d a s i n g l e moving ahead o f the s t a r t i n g m a t e r i a l (some products- were observed  a t the o r i g i n ) .  i s o l a t e d i n approximately  spot,  decomposition  T h i s m a t e r i a l was  90% y i e l d , the s p e c t r o s c o p i c as  w e l l as a n a l y t i c a l data being c o n s i s t e n t with the s t r u c t u r e of bis(bromopropyl)durene  127.  These r e s u l t s were  reproduced  when the r e a c t i o n was repeated on a l a r g e r s c a l e u s i n g the same stock of b i s ( h y d r o x y p r o p y l ) d u r e n e 124 .  132 Before proceeding and  c a r r y out the  first 122  last  two  s t e p , the d i b o r a n e  was  r e p e a t e d on  i o n of boron again  0.2  described before.  M.  ever,  its  1 3  C  nmr  The  A  product  product  Even a f t e r icant  darkened  earlier.  c o n s i d e r a b l y by  The  t i c taken  appeared  sample.  time  After  30  and  i t was  allowed  min-  the  behind  the  decomp-  show a  signif-  i n approximately  i t was  removing  of methanol.  out under these c o n d i t i o n s ,  under  after  Since the r e a c t i o n mixture  this  How-  t o be more i n t e n s e .  the t i c d i d not  the  had  c o o l e d and e x t r a c t e d the a c i d  sodium b i c a r b o n a t e , the methylene c h l o r i d e  and  as  low.  bands were a l s o o b s e r v e d  intensities.  methylene c h l o r i d e  almost  isolated  f a s t moving s p o t , almost  of r e f l u x i n g  i n the presence  was  to the spot corresponding to  another  w i t h methylene c h l o r i d e .  orated  addit-  an anomalous peak a t 6 33.77,  change, the e x t r a s p o t s r e m a i n i n g  same r e l a t i v e  the  once  subjected to bromination  spot a t the o r i g i n  3 hours  Since s t i r r i n g  t h e p r o d u c t was  exhibited  i n addition  series of f a i n t  osition  and  o f t h i s peak was  127,  As  o f the  of the p r e v i o u s l y p r e p a r e d  the e x a c t c o n d i t i o n s used  expected  Towards t h e end  hardened.  above p r o d u c t was  utes exhibited,  scale.  back  spectroscopic properties of this material  spectrum  the i n t e n s i t y  a larger  t o go  e t h e r a t e , the r e a c t i o n mixture  compared w e l l w i t h t h o s e  it.  scale.  worked up  The  necessary  reduction of durene-bis-propionic acid  trifluoride  t h i s was  i t was  r e a c t i o n s on  t u r n e d g e l a t i n o u s and  impossible,  but  further,  with  s o l u t i o n was  S i n c e the p r o d u c t redissolved  t o stand i n the  in  aqueous evapoiled  sufficient  refrigerator  133 o v e r n i g h t , when c r y s t a l l i z a t i o n c o n s i s t e d m a i n l y o f the very  little  occurred.  This  ; b i s ( b r o m o p r o p y l ) d u r e n e .\ 127,  o f the i m p u r i t y .  Recrystallization  l e n e c h l o r i d e - m e t h a n o l removed t h i s m a t e r i a l . disappointing  to note  that  mother l i q u o r s  the s o l i d s was  This produced imately for  65%  i n methylene  the pure and  characterization  purposes.  The  and and  quantity  a  was  to dryness, separation  crystallizations. 127  of the  lower y i e l d  in  compounds a p p e a r e d properties  and  o f 127  was  by-  of p u r i f i c a t i o n .  t o have v e r y s i m i l a r as  approx-  by-product  t o t h e f o r m a t i o n o f t h e above m e n t i o n e d to the d i f f i c u l t y  methy-  t h e unknown i m p u r i t y .  bis(bromopropyl)durene a sufficient  p r o d u c t , b u t a l s o due  tion  chloride  by r e p e a t e d c h r o m a t o g r a p h y  yield  n o t o n l y due  by  with  contained a  and w a s h i n g s were e v a p o r a t e d  t a k e n up  attempted  contaminated  from It  t h e mother l i q u o r s  c o n s i d e r a b l e amount o f 127 The  material  solubility  s u c h , t h e s e p a r a t i o n was  and  Both  adsorp-  not very  efficient. 13 The  a n a l y s i s of the  product provided s u f f i c i e n t structure istic  for this  .: C-nmr s p e c t r u m  by-  i n f o r m a t i o n i n order to.propose  compound.  of a c a r b o n y l carbon  of the  A resonance  and  a t 6 173.09,  a  character-  a n o t h e r a t 6 64.47 i n d i c a t i v e  3. a carbon  a t t a c h e d t o an  sp  hybridized  t h e m o l e c u l e p o s s e s s e d an e s t e r resonances carbons  a t 6 16.41  and  oxygen, suggested  linkage.  T h e r e were  two  6 16.31, e a c h c o r r e s p o n d i n g t o  (four methyls), i n s t e a d  o f the s i n g l e  that  resonance  four near  of  6  16  observed  suggesting In  f o r a l l other symmetrical  t h e e x i s t e n c e o f two  support of t h i s  was  the aromatic r e g i o n . mediates  exhibited  durene i n t e r m e d i a t e s ,  durene m o i e t i e s i n the  t h e o c c u r r e n c e ;of s e v e n  The  resonances  s y m m e t r i c a l monomeric d u r e n e  o n l y two  resonances  molecule. in  inter-  i n the a r o m a t i c r e g i o n , 13  in nmr  a ratio  o f 2:1.  spectrum  assigned  The  o f 127,  three resonances  a t <5 33 . 90,  to the t h r e e carbons  6  observed  32 .72  and  in this  and <$ 29.39.  o f t h e s e r e p r e s e n t e d two  Each  by-product  compared w i t h t h e o t h e r f o u r ene  128  was  on  proposed  reaction.  The  carbon  f o r the by-product hydrogen  and  isolated  and  32.71  atoms  i n the  as methyl-  each.  the a n a l y s i s p r e s e n t e d above, the  carbon,  as t h e p r o t o n nmr  t o one  carbon  observed  C-  side chain,  ; a t 6 33.89, 6  resonances  r e g i o n , which corresponded  Based  <S 29.40,  o f . t h e bromopropyl  were a l s o o b s e r v e d  i n the  i n the  structure bromination  b r o m i n e a n a l y s e s as  s p e c t r a l d a t a were c o n s i s t e n t w i t h  the  well  135 proposed  structure.  mass c o m b i n a t i o n  The mass s p e c t r u m  o f m/e  = 620-622-624 was added  With the i d e n t i t y established, order  m i z e d . I t was contained  In o r d e r  t o assume t h a t  125 w h i c h ,  the e s t e r  the i s o l a t e d  to r a t i o n a l i z e  support.  by-product i t s origin in  126.  by-product  the r e a c t i o n  i n t h e a c i d medium  mixture  reacted with  T h i s on b r o m i n a t i o n would have p r o 128.  to e l i m i n a t e the p o s s i b i l i t y  the p a r t i a l  a parent  i t s f o r m a t i o n c o u l d be a v o i d e d o r m i n i -  reasonable  compound  124 t o p r o d u c e duced  o f the r e a c t i o n  i t was n e c e s s a r y  t o work o u t how  exhibiting  o f 125 b e i n g  f o r m e d by  o x i d a t i o n o f 124 i n c o n c e n t r a t e d s u l f u r i c  acid,  t h e b r o m i n a t i o n was r e p e a t e d u s i n g 48% hydrobromic- a c i d The  r e s u l t was  t h e same as b e f o r e ;  i . e . , both  alone.  127 and 128 were  formed. This propyl)  suggested  d u r e n e 124 u s e d  been c o n t a m i n a t e d  with  that  the p a r t i c u l a r  i n this  sample o f b i s ( h y d r o x  b r o m i n a t i o n r e a c t i o n may  the p a r t i a l l y  reduced  product  125.  have  136 Although  at f i r s t ,  t h i s was  r e d u c t i o n o f carboxy facile  surprising,  to hydroxymethyl  i s known  t o be a  r e a c t i o n , i t c o u l d n o t be r u l e d o u t , c o n s i d e r i n g  t h e manner i n w h i c h t h e r e a c t i o n 122 should  s i n c e the diborane  be r e c a l l e d  was n o t v e r y expected  124 p r o c e e d e d .  It  t h a t the d u r e n e - b i s - p r o p i o n i c a c i d  122  s o l u b l e i n t e t r a h y d r o f u r a n and a l t h o u g h  t o go i n t o  solution during  b e i n g more s o l u b l e ) , partially  reduced  the r e a c t i o n (the product  the premature c r y s t a l l i z a t i o n  product  125 may  have p r e v e n t e d  from g o i n g  to completion.  gelatinous  and e v e n t u a l l y h a r d e n e d e v e n b e f o r e  o f boron t r i f l u o r i d e  The r e a c t i o n m i x t u r e  o f the  the r e a c t i o n turned  the a d d i t i o n  e t h e r a t e was c o m p l e t e , and t h i s  have l e d t o t h e e x i s t e n c e o f t h e p a r t i a l l y 125 i n t h e i s o l a t e d  i t was  reduced  may material  sample o f 124. The anomalous peak  observed  13 a t 6 33.77 i n t h e attributed a  C-nmr s p e c t r u m o f t h i s m a t e r i a l c o u l d be  to the presence  to a carboxy  o f compound 125;  g r o u p a r e known t o a p p e a r i n t h i s  In o r d e r  to avoid  the formation  the d u r e n e - b i s - p r o p i o n i c a c i d ester  before  ester  123 was o b t a i n e d  of  122 w i t h  acid.  methylene  s u b j e c t i n g to the diborane  ethanol  i n approximately  i n the presence  region.  of t h i s  122 was c o n v e r t e d  carbons  by-product,  to i t s d i e t h y l  reduction. 90% y i e l d  The d i e t h y l by t h e r e a c t i o n  of concentrated  sulfuric  137  Hf CH  H3C  123  122 The  prior  esterification  the  s t a r t i n g m a t e r i a l i n t e t r a h y d r o f u r a n and  reduction  (123 V  relatively  124  124)  greatly  proceeded  improved  without  l a r g e volume o f s o l v e n t was  crystallization isolated  3  was  observed.  i n g r e a t e r than  The 95%  the  any used  solubility the  diborane  problems. and  of  no  A  premature  b i s ( h y d r o x y p r o p y l ) d u r e n e •"  yield  gave an  acceptable  13 carbon of  and  hydrogen a n a l y s i s .  F u r t h e r , the  t h i s m a t e r i a l d i d not e x h i b i t  subsequently The  brominated  r e a c t i o n was  complete  reaction mixture dimeric isolated into  u s i n g 48%  indicated  i m p u r i t y 128.  The  spectrum  a peak a t <5 33 .77 . T h i s aqueous h y d r o b o m i c  i n 3 0 m i n u t e s and no  C nmr  acid.  the t i c o f  spot corresponding  to  bis(bromopropyl)durene''  was  the  the 127  was  i n a p p r o x i m a t e l y 90% y i e l d . A l t h o u g h t h i s m o d i f i c a t i o n i n t r o d u c e d an e x t r a s t e p  the r e a c t i o n  to the o r i g i n a l  s e q u e n c e , t h e new  one  due  separation of products  route proved  to the e l i m i n a t i o n after  bromination.  of the But  t o be s u p e r i o r cumbersome  i t should  be  138 emphasized t h a t i f problems were a n t i c i p a t e d i n the r e d u c t i o n of d u r e n e - b i s - p r o p i o n i c a c i d 122, could have been obtained d i r e c t l y without the d i a c i d .  diborane  the d i e s t e r 123  passing  through  For t h i s purpose, the t e t r a e t h y l e s t e r  120  C0 C H 2  C C H  CH Cl  U 2  2  2  5  5  2  ^2°2'  H  CH Cl 2  BIS(CHLOROMETHYL) DURENE  120  should have been i s o l a t e d f o l l o w i n g the malonate r e a c t i o n of b i s (chloromethyl) durene-: - without 5  esters.  the h y d r o l y s i s of  the  T h i s i s e a s i l y achieved by the a c i d i f i c a t i o n of  r e a c t i o n mixture w i t h water.  (with g l a c i a l a c e t i c acid) followed by  The d e c a r b e t h o x y l a t i o n s  to 12 0 have been e f f e c t e d i n dimethyl or without  added s a l t s .  the dilution  of geminal d i e s t e r s r e l a t e d s u l f o x i d e by water, with  T h i s type of d e c a r b a l k o x y l a t i o n s of  geminal d i e s t e r s have been s t u d i e d by Krapcho and  co-workers  u s i n g a v a r i e t y of s u b s t r a t e s and d i v e r s e s a l t s .  They have  observed  57  t h a t s u b s t r a t e s w i t h e l e c t r o n withdrawing s u b s t i t u e n t s  such as d i e t h y l phenylmalonate and d i e t h y l benzylmalonate undergo d e c a r b e t h o x y l a t i o n s  f a i r l y readily in  water-dimethyl  139 sulfoxide react the  whereas n - a l k y l  slowly  latter  under the  group of  accelerated  by  the  substituted  d i e t h y l malonates  above c o n d i t i o n s .  geminal d i e s t e r s addition  of  The  has  reaction  with  been o b s e r v e d  s a l t s s u c h as  KCN,  to  NaCl-  be  and  LiCl. The to  the  b i s ( b r o m o p r o p y l ) d u r e n e 127  malonate  previously.  synthesis  The  under the  starting material  CH  was  then-  conditions went i n t o  subjected  described  solution at  the  3  130 onset of out  of  r e f l u x and  solution.  isolation overall  and  yield  tetraacid  The  the of  within  m i n u t e s sodium bromide  b i s malonate e s t e r  tetracarboxylic 95%  (from 1 2 7 ) .  in refluxing quinoline  durene-bis-pentanoic acid as  10  i t s dimethyl  ester.  130  acid  was  129  saponified  was  obtained  Decarboxylation of produced  i n 95%  yield  crystallized  the and  desired was  the  without in  an  .  product,  characterized  140 2.7.2  INCORPORATION OF THE  PORPHYRIN  The the  durene-bis-pentanoic  r e a c t i o n sequence developed  linked  series,  main c o n c e r n as  compared w i t h  the  the  initial  Figure  20.  of  the  in  t h e u s u a l manner by  pyrrole  The  low,  67%.  The  with  diborane  s o l v e n t was  solvent  of  this  the  first  two  two  yield  of  carried  through  aliphatic  chain  porphyrin. of  linked  the  used, the  analogues.  s t e p was  the  pyrroles. the  acid  10 m i n u t e s .  The  linking  T h i s was  130  ;  moles of  the d i k e t o n e  When t h e  r e a c t i o n d i d not excess  go  of diborane  and  3 v o l u m e s ) was the  the 132  3-unsubstituted was  product  133  was  u s u a l volume  to completion and  a  of even  considerable  complete  isolated  relatively  reduced  When more  added, a l l the  r e a c t i o n was  effected  to i t s bis 'acid  s t a r t i n g m a t e r i a l remained u n d i s s o l v e d .  solution  intermediates  k e t o n i c g r o u p s were s u b s e q u e n t l y  in tetrahydrofuran.  The  sequence are o u t l i n e d  t o v ' a e y l a t e two  overall  (approximately  went i n t o  chain  converting  this  t h e p r e s e n c e o f an  amount o f  was  simple  solubility  g - p o s i t i o n s of  using  6_6.  stages  Once a g a i n ,  s t r a p to  and  130  f o r the  lower  aliphatic  in  chloride  acid  to produce the c o r r e s p o n d i n g  h e r e was  The  in  DURENE-BIS-PENTANOIC ACID INTO  solid  in less  i n greater  than  yield. The produced  t r a n s b . e n z y l a t i o n of the  t h e b i s b e n z y l • e s t e r 134  bis ethyl ester  i n over  98%  yield-.  133 -The  than 87%  141  FIGURE  20  : Syntheses  of  Intermediates  Durene-Bis-Pentane  Linked  Bis  Pyrrolic  higher y i e l d here c o u l d be due  to the ease of c r y s t a l l i z a t i o n ;  a consequence of i t s lower s o l u b i l i t y . the benzyl e s t e r (135  136)  conditions  (134 -> 135) , the d e c a r b o x y l a t i o n of the  of  product  and the subsequent f o r m y l a t i o n under V i l s m e i e r (136 -f 137)  a l l proceeded without  The b i s f o r m y l p y r r o l e 137 was d i c y a n o v i n y l d e r i v a t i v e 138 of 138  The h y d r o g e n o l y s i s  any  complications.  once again converted  and p u r i f i e d .  from the b i s benzyl e s t e r 134 was  to i t s  The o v e r a l l  yield  over 6 0%.  With the p r o t e c t e d formyl groups i n p l a c e , i t was necessary  to monochlorinate  of compound 138  each of the two a-methyl groups  i n order to condense with two moles of the  a-unsubstituted pyrrole.  U n l i k e the p r e v i o u s examples where  the " s t r a p " c o n s i s t e d of simple methylene groups, the  presence  of an a c t i v a t e d benzene r i n g i n t h i s case, made t h i s  chlorin-  a t i o n the most c r u c i a l step i n the e n t i r e r e a c t i o n sequence. Since s i d e c h a i n halogenations  are known to occur with  such  systems s t r i c t c o n t r o l of r e a c t i o n c o n d i t i o n s appeared to be of importance i n d r i v i n g the r e a c t i o n to the d e s i r e d product. Side c h a i n halogenations  of p o l y s u b s t i t u t e d ct-methyl5 8  p y r r o l e s have been known f o r a long time  and have been  recognized as i n t e r m e d i a t e steps i n the p r e p a r a t i o n of a number of p y r r o l e oligomers methenes -and  porphyrins.  such as dipyrromethanes,  dipyrro-  However, very l i t t l e a t t e n t i o n has  been p a i d to the mechanism of these r e a c t i o n s .  In one  the s i d e c h a i n c h l o r i n a t i o n with s u l f u r y l c h l o r i d e was  instance, assumed  143 to occur by a f r e e r a d i c a l mechanism  5  9  ;  i n f a c t t h i s seems to  be the g e n e r a l b e l i e f although the mechanism has not been e s t ablished.  Conversely, a c o n s i d e r a b l e amount of work has been  c a r r i e d out on the h a l o g e n a t i o n of alkylbenzenes and appears  to be two d i s t i n c t mechanisms.  One  there  i s the w e l l known  6 0  f r e e r a d i c a l mechanism  which i s most l i k e l y to occur i n the  r e a c t i o n of the lowest a l k y l a t e d benzenes, with i n non-polar, non-hydroxylic media.  halogens,  The other i s e l e c t r o -  p h i l i c i n nature, and i s favoured i n the dark r e a c t i o n of the higher a l k y l a t e d benzenes i n non-polar and/or h y d r o x y l i c 62  6 1  media.  In a c l o s e r examination  of the l a t t e r mechanism  the c h l o r i n a t i o n of h e x a s u b s t i t u t e d benzenes i n a c e t i c s o l u t i o n proved  to be q u a n t i t a t i v e l y analogous  p h i l i c n u c l e a r s u b s t i t u t i o n by Cl^  ' acid  to e l e c t r o -  i n the same s o l v e n t .  The evidence i n v o l v e s the k i n e t i c form, the magnitude of the a c t i v a t i o n parameters,  the r e a c t i o n s e l e c t i v i t y , the i n f l u e n c e  of c a t a l y s t s and the i n s e n s i t i v i t y to l i g h t . philic  s i d e c h a i n a t t a c k " was  The  "electro-  thus shown to proceed v i a an  e l e c t r o p h i l i c n u c l e a r a t t a c k of c h l o r i n e and have i d e n t i c a l k i n e t i c behaviour  to aromatic n u c l e a r c h l o r i n a t i o n .  a t t r i b u t e d to the s i m i l a r i t y of the benzenonium ions below) i n the r a t e determining  R  step.  Cl  This i s (shown  144  When R=H,  the decomposition  expulsion of the proton but  i n a polyalkylated  of the i o n r e s u l t s  and t h e f o r m a t i o n o f t h e a r y l benzene, t h i s would  arrangement o f the halogen  from  anism.  are of l i t t l e I t i s clear  help  l o s s o f a p r o t o n , b u t whether t h i s a t t a c k by C l  +  to the side chain.  step,  f o r the e l u c i d a t i o n  that the o v e r a l l  reaction  reaction o f i t s mech-  i n v o l v e s the  takes p l a c e p r i o r  o r as a c o n c e r t e d p r o c e s s  halide,  i n v o l v e the r e -  the nucleus  Since t h i s m i g r a t i o n i s a subsequent f a s t kinetics  i n the  i s a matter  to the of great  interest. The reaction  special  course  taken  by t h e c h l o r i n a t i o n  o f 2 , 4 , 6 - t r i m e t h y l - 3 , 5 - d i c h l o r o a n i s o l e and t h e  c  failure  of this  suggested  to y i e l d  a proton  i s lost  attack.  6 3  a t the a d j a c e n t methyl group p r i o r to  t h e benzenonium i o n w i t h  derivative:  derivative  o f a methyl group a t  to the p o i n t of e l e c t r o p h i l i c  the rearrangement o f c h l o r i n e , of  a 4-chloromethyl  the n e c e s s i t y f o r the presence  a p o s i t i o n ortho If  compound  i t would l e a d  the corresponding  to equilibration methylene  145  This  should  During with  result  i n e x t e n s i v e hydrogen i s o t o p e exchange.  the c h l o r i n a t i o n  o f hexamethylbenzen'e,  t h e medium c o u l d be d e t e c t e d and t h i s  no  exchange  experimental 63  result that  has been u s e d by B a c i o c c h i and  the proton  process  involving  The sulfuryl  loss  i s probably  engaged  to suggest  i n a concerted  an i n t r a m o l e c u l a r m i g r a t i o n :  light  induced  c h l o r i d e h a s been  r e a c t i o n s had been c a r r i e d at  Illuminati  40°C u s i n g a 275 Watt  chlorination  of a l k y l  studied i n d e t a i l  b e n z e n e s by  by L e e  6 4  out i n carbon t e t r a c h l o r i d e  sunlamp  for irradiation.  .  The solution  Under  these  146 conditions, and  the  the r e a c t i o n proceeded v i a a r a d i c a l  suggested  course  R-H  +  'S0 C1  R*  +  S0 C1  of the  2  2  2  *soci The  evidence  been p r o v i d e d  2  that  Lee  has  i n non  mainly  by  ->  R'  +  -»•  RC1  +  HC1  concluded  complexing  the  +  S0  2  *S0 C1 2  so + Cl" 2  f o r the e x i s t e n c e of the  (*S0 C1) had 1951.  r e a c t i o n i s shown b e l o w :  t  2  mechanism  by  chlorosulfinyl  K h a r a s c h and  Zavist  from h i s e x p e r i m e n t a l  radical , in  6 5  observations  s o l v e n t s , the hydrogen a b s t r a c t i o n i s  chlorosulfinyl  radical. 66  Recently, very  interesting  substituted  with  results  steps,  and  suggest  polyalkylated  of  poly-  the  the  s i d e c h a i n was  The  halogen  found  a d j a c e n t 3 - p o s i t i o n or  and  in  two  r e a c t i o n of c h l o r i n e with electrophilic  migration  t o be  c o n s i s t s of  nuclear  the halogen  to  from the n u c l e u s  possible either  from  to  the  from the v i n y l o g o u s a ' . p o s i t i o n .  f o r e g o i n g d i s c u s s i o n p o i n t s towards the  a competition  mechanisms o f  i . e . , the  process  subsequent rearrangement of  side chain.  The  temperatures  chlorine  selected a-methylpyrroles.  t h a t the o v e r a l l  benzenes;  some  i n v e s t i g a t e d the  c h l o r o f o r m a t low  to the c o r r e s p o n d i n g  the  that  reported  the h a l o g e n a t i o n  They had  four c a r e f u l l y  similar  a t t a c k and  co-workers  the a-methyl c h l o r i n a t i o n w i t h m o l e c u l a r  i n dichloromethane  The  and  o b s e r v a t i o n s on  a-methylpyrroles.  mechanism o f  the dark,  Illuminati  between e l e c t r o p h i l i c  side chain halogenations  and  free  fact  radical  could r e s u l t  from  a  combination the  of  several  substrate,  evident  that  selective attack that  solvent  since  and  the  very  highly  and  free radical  r e a c t i v e towards e l e c t r o p h i l i c  electrophilic  the  f r e e r a d i c a l mechanism i n c a r b o n  under i l l u m i n a t i o n It for  an  ation  6 3  appeared  the  substrate  been o b s e r v e d  that  the  vinylpyrrole  mechanism may  i n the  138  present  (Figure  w h i c h was  highly  expected  a-methyl group o f of  138  ion,  was  the  solvent  79.  to  21).  favour  the  The  i n the  13 9 was  dipyrromethane  desired  p r o d u c t 140  the  overall reaction the  high  and  halogen-  the  bis  dicyano-  pyrrole  nucleus  contained  is  attack  c h l o r i n a t i o n at  Therefore  the  the b i s - c h l o r i n a t i o n  dark, i n methylene c h l o r i d e  equivalents  the  confirmed  favourable  case of  i . e . , the  exclusive  two  equivalents  i s o l a t e d , as  (methylene c h l o r i d e )  only  with  Although t h i s molecule  pyrroles.  product  c o n d e n s e d w i t h two  t o compete  to e x c l u s i v e  i n the  work;  a t room t e m p e r a t u r e u s i n g The  halogenation  r e a c t i v e towards e l e c t r o p h i l i c  c a r r i e d out  chloride.  In  t e t r a c h l o r i d e even  lead  a p o l y a l k y l a t e d benzene m o i e t y , the known t o be  reagents.  reaction conditions  p y r r o l e methyl groups,  used  substrates  .  electrophilic on  had  side chain  via  un-  electrophilic  i t , especially in  w i t h hexamethyl benzene, the  of  It is  reaction i s rather  dark, the  competes w i t h  attack  structure  reaction conditions.  slow i n the  effectively  are  fact,  the  f a c t o r s , i n c l u d i n g the  of  sulfuryl  before,  with d i e t h y l ether  of  the  solut-  a-unsubstituted  by  replacing  and pyrrole  formed under t h e s e c o n d i t i o n s the  usual  high  yield  of  ca.  90%  was for  (a-methyl+a-chloromethyl+dipyrromethane)  regioselectivity  of  the  chlorination  step.  148  149  When t h e r e a c t i o n illumination Although that  was r e p e a t e d u n d e r  no change was o b s e r v e d  this  does n o t c o n s t i t u t e  i n t h e absence  chloride  alcohol  o u t i n aqueous p o t a s s i u m  to solubilize  was b o i l e d  off after  dimer  decarboxylation  hydroxide, using  of this  9 0%  chain analogues.  was  found  and  a s such,, was c r y s t a l l i z e d  t o be more s o l u b l e  yield.  o u t as d e s c r i b e d  The " d u r e n e - c a p p e d  i n nitromethane from  The  cyclization of  142 were c a r r i e d  the s t r a i g h t  solution  1  o f 141 a n d t h e s u b s e q u e n t  for  dispersed  of a-formyl-a -carboxy-  141 i n . g r e a t e r t h a n  the l a t t e r  p r e p a r a t i o n s , t h e maximum y i e l d  decarboxylation-cyclization  When t h e  I n s t e a d , i t remained  Acidification  the d e c a r b o x y l a t e d product  dimer  the completion o f the r e a c t i o n ,  i n the p r e c i p i t a t i o n  dipyrromethane  several  proceeds  the starting material.  w a t e r as an e m u l s i o n .  resulted  sulfuryl  mechanism.  the product d i d n o t o i l out. in  c o n c l u s i v e p r o o f , i t appears  base h y d r o l y s i s o f t h e dipyrromethane  was c a r r i e d  n-propanol  of laboratory  results.  o f p y r r o l e - a - m e t h y l groups  m a i n l y v i a an e l e c t r o p h i l i c  140  i n t h e above  of intense irradiation,.the  chlorination  The  the conditions  than  porphyrin"  i n methanol  solvent.  In  obtained f o r the  s t e p was 31.4%.  CHAPTER 3  EXPERIMENTAL  151  3.1  GENERAL METHODS  Melting  Point  Determinations  M e l t i n g p o i n t s were o b t a i n e d w i t h a Thomas-Hoover Unimelt,  a capillary/oil  are presented  immersion  apparatus;  the r e s u l t s  uncorrected.  E l e m e n t a l Ana1y s i s E l e m e n t a l a n a l y s e s were p e r f o r m e d by Mr. P. B o r d a of  the M i c r o a n a l y t i c a l  L a b o r a t o r y , U.B.C.  N u c l e a r M a g n e t i c Resonance  Unless obtained  otherwise  Spectroscopy  stated,  a l l p r o t o n nmr s p e c t r a were  a t 100 MHz w i t h a V a r i a n HA-100 s p e c t r o m e t e r f o r  continuous  wave s p e c t r a and V a r i a n XL-100 s p e c t r o m e t e r f o r  Fourier-transform  spectra.  In c e r t a i n  instances, spectra  were r e c o r d e d a t 270 MHz w i t h a U.B.C. NMR Nicolet-Oxford recorded (6  =0)  H-270 s p e c t r o m e t e r .  i n t h e <S (ppm) s c a l e w i t h a s an i n t e r n a l  standard.  Centre  The c h e m i c a l  modified shifts are  t e t r a m e t h y l s i l a n e (TMS) The p r o t o n nmr s p e c t r a  of  t h e s t r a p p e d p o r p h y r i n s 109a, 109b and 109c were o b t a i n e d  in  deuterochloroform solution  400 s p e c t r o m e t e r .  a t 4 00 MHz w i t h a B r u k e r WH -  T h i s i n s t r u m e n t was c a l i b r a t e d  with  TMS  as an e x t e r n a l s t a n d a r d . The  c a r b o n - 1 3 nmr s p e c t r a were o b t a i n e d w i t h a V a r i a n  CFT  - 2 0 spectrometer  standard.  u s i n g TMS  The c h e m i c a l  shifts  (6 = 0) as t h e i n t e r n a l a r e r e c o r d e d i n t h e 6(ppm)  scale.  Mass  Spectrometry Mass s p e c t r a were r e c o r d e d on a V a r i a n MAT  4-B s p e c t r o m e t e r  CH  o r a K r a t o s / A E I MS-902 s p e c t r o m e t e r .  High  r e s o l u t i o n measurements were o b t a i n e d on a K r a t o s / A E I MS-50 spectrometer.  Infrared  Spectroscopy The  using the  infrared  s p e c t r a were o b t a i n e d f r o m KBr d i s c s  a P e r k i n - E l m e r M o d e l 457 g r a t i n g  f r e q u e n c y r a n g e 4000-250 cm  rated with polystyrene film  'Electronic  The s p e c t r a were  a t 1601.4  calib-  cm  Spectroscopy  A Cary to  spectrometer covering  r e c o r d i n g spectrometer  o b t a i n uv and v i s i b l e  (Model 17) was  used  spectra.  C h r o m a t o g r aphy Column c h r o m a t o g r a p h y was p e r f o r m e d obtained  from  ICN P h a r m a c e u t i c a l s  I) and Camag aluminum o x i d e Chromatography plates  (Woelm, 70-150 mesh,  (basic, a c t i v i t y  ( t i c ) was p e r f o r m e d  using s i l i c a g e l  I).  using precoated  Thin  activity Layer  silica gel  ( A n a l t e c h - U n i p l a t e , 250 V) and t h e compounds were  detected  by uv l i g h t  (254 nm).  153 Starting  Materials As  none o f t h e p y r r o l e s r e q u i r e d  commercially pyrrolic  a v a i l a b l e a t a reasonable  starting materials  most o f t h e s e literature,  f o r t h i s work was  price,  a l l of the  had t o be s y n t h e s i z e d .  Although  compounds have a p p e a r e d p r e v i o u s l y i n t h e  their  s y n t h e s e s have been i n c l u d e d h e r e f o r  c o m p l e t e n e s s , and t h e c o n v e n i e n c e o f any who m i g h t w i s h t o make u s e o f t h e i n f o r m a t i o n  contained  herein.  I n some  cases,  u s e f u l m o d i f i c a t i o n s have been made.  R e a g e n t s and S o l v e n t s All unless  3.2  chemicals  otherwise  and s o l v e n t s were r e a g e n t  indicated.  NOMENCLATURE OF PORPHYRINS AND THEIR The  INTERMEDIATES  nomenclature of a l l porphyrins  synthesized  t h i s work h a s been b a s e d on t h e IUPAC n u m b e r i n g in Figure numbered bridged on  IB.  in  scheme  during given  The p y r r o l e n u c l e i o f d i p y r r o m e t h a n e s were  i n s u c h a way a s t o a s s i g n  a positions.  one p y r r o l e r i n g  distinguishing  grade  2 and 2' t o t h e methane  The numbers 2', 3' e t c . have been ( i n t h e f i g u r e s ) only"-  f o r the purpose o f  t h e .analogous p o s i t i o n s on the .two r i n g s  s p e c t r a l assignments.  used  :  -  154  Following  the Chemical A b s t r a c t s  have been named as s u b s t i t u t e d  nomenclature, these compounds (pyrrol-2-yl)methyl-pyrroles..  For the c h a i n - l i n k e d d i m e r i c considered  as the parent compound and they were named as term-  i n a l l y b i s - s u b s t i t u t e d alkanes. has  systems, the alkane was  Further,  the p y r r o l e nucleus  been numbered as shown below, so as to a s s i g n the c h a i n  linked  3 - p o s i t i o n the lower number p o s s i b l e .  To avoid c o n f u s i o n ,  t h i s numeration scheme has been maintained  f o r every b i s - p y r r o l e and bis-dipyrromethane  intermediate.  155  3.3  SYNTHESES QF  Diethyl  95%  hexanediote  (Diethyl  Hexanedioic  acid  ethanol  toluene fitted The  ACYCLIC PRECURSORS  (650 mL),  (360 mL)  (adipic  w i t h a Dean-Stark  the Dean-Stark  trap  (2x200 mL) distilled  heated  (m,  apparatus.  under reduced  4H,  (6,  CDC1 )  C-3,  3  C-4,  and flask  condenser. h. d u r i n g  l a y e r was The  con-  reaction  e x t r a c t e d w i t h water and  the o r g a n i c phase and  t h e p r o d u c t was 308  g;  collected  75.5%.  Torr  ( t , 6H,  J=7  methylene protons)  m e t h y l e n e p r o t o n s ) , 4.06  f o r 16  flask).  145°C/20 T o r r , y i e l d ,  : 1.23  a reflux  Ethanol, toluene  o v e r b e l o w 30°C and  and  (20 mL)  l a y e r were removed  (The u p p e r  acid  moi),  round-bottomed  o f lower  pressure.  6 7 0 ( L i t . • ) : 136-137 C/19  NMR  mL  t o remove t h e s u l f u r i c  between 139°  H  350  2.02  acid  under r e f l u x  c o o l e d t o room t e m p e r a t u r e ,  water d i s t i l l e d  1  (295 g,  surmounted by  r e i n t r o d u c e d to the r e a c t i o n  m i x t u r e was  BP  acid)  were p l a c e d i n a 2 - l i t e r  which time, approximately  stantly  6_1  concentrated s u l f u r i c  r e a c t i o n m i x t u r e was  from  adipate)  (q, 4H,  J=7  Hz,  -0-CH -CH_ ), 2  3  2.05-2.50 Hz,  (m,  4H,  -0-CH ~CH ) 2  3  1.42-1.81 C-2,  C-5,  156 Monoethyl  hexanediote  adipate) 62_  (Ethyl hydrogen  D i e t h y l hexanedioate 6_1 (303.0 g, 1.5 moi), hexanedioic acid  (219.0 g, 1.5 moi) and t o l u e n e - p - s u l f o n i c  (2.0 g) were p l a c e d i n a 1 - l i t e r 3-neck f l a s k f i t t e d thermometer, a n i t r o g e n a t r e f l u x temperature of  inlet  acid  with a  tube and a condenser and heated  f o r 15 h.  Fractional  distillation  the r e a c t i o n mixture under reduced p r e s s u r e (13 t o r r ) gave  two f r a c t i o n s ; I a , c o n t a i n i n g mainly the d i e s t e r and I l a , the monoester  (bp 152-170°C).  combined with the r e s i d u e i n the f l a s k f l u x e d f o r a f u r t h e r 15 h  period.  (bp 128-152°C)  The f r a c t i o n Ia was (the d i a c i d ) and r e Another reduced p r e s s u r e  (6 t o r r ) d i s t i l l a t i o n gave the d i e s t e r f r a c t i o n l b (bp 120-145°C) and the monoester f r a c t i o n l i b (bp 145-165°C).  Ib was recombined  w i t h the r e s i d u e and the processes o f r e f l u x i n g f o l l o w e d by f r a c t i o n a l d i s t i l l a t i o n were repeated once more. The monoester f r a c t i o n l i e was combined with the p r e v i o u s f r a c t i o n s I l a and l i b and r e d i s t i l l e d  under  reduced  p r e s s u r e to g i v e 294.2 g (56.3%) of the pure hexanedioic a c i d , monoethyl  ester.  (BP : 150-153°C/6 Torr)  o . MP : 27.5 - 28.5 C; L i t . 6  BP  69  8  o : 28-29 C  0  : ( L i t : ' ) : 163 C(10 Torr)  H NMR  (6, CDC1 ) : 1.26(t, 3H, J=7 Hz-, -0-CH ~CH ) •; .'1. 42-192 3  2  3  157 (m,  4H,  C-5,  C-3,  C-4,  methylene  methylene  p r o t o n s ) , 4.14  6-0xoundecanedioic Monoethyl thionyl  acid  (140 mL,  flask  1.5  h) .'  The  tube.  (5x50 mL)  [NOTE 2]  three-necked ometer, a drying  tube  prepared  above was  maintaining 25°C.  chloride  and 1-liter and  a a  (approximately  removed w i t h  carbon  reduced pressure.  used  i n the  (210 mL,  1.5  moi)  and  next  dry  were c o o l e d t o 3-5°C i n a  the l i q u i d )  the temperature  and  stirrer, a  acid  stirred  r e a c t i o n had  solid  was  therm-  chloride  liquid, below  subsided, the  bath to r a i s e  t o 35°C and  A t h i c k white p r e c i p i t a t e The  The  o f the r e a c t i o n mixture  by a warm w a t e r  2-liter  a d r o p p i n g f u n n e l (with  to the w e l l  exothermic  separated out.  3  h e a t e d on  ceased  c h l o r i d e was  e r a t u r e of the r e a c t i o n mixture 30 m i n u t e s .  moi)  condenser  f l a s k was  of gases  added r a p i d l y  replaced  2  with calcium c h l o r i d e ) .  When t h e ^ m i l d l y  i c e - b a t h was  -0-CH_ CH )  1.06  f i t t e d with a mechanical  filled  C-2,  purification.  [NOTE 1]  (extending i n t o  4H,  were p l a c e d i n a  t h u s o b t a i n e d was  (900 mL)  flask  Hz,  by e v a p o r a t i n g u n d e r  reaction without further Triethylamine  moi)  The  the e v o l u t i o n  The m o n o a c i d c h l o r i d e  toluene  6_2_ (184.0 mL,  1.95  excess t h i o n y l  tetrachloride  J=7  f i t t e d with a reflux  calcium chloride drying steam b a t h u n t i l  (q, 2H,  (m,  64  hexanedioate  chloride  round-bottomed  p r o t o n s ) , 1.92-2.14  the  temp-  allowed to s t i r  of triethylamine dissolved  for  hydro-  i n water  (3 00  mL),  158 the o r g a n i c phase separated and the s o l v e n t (toluene) removed by e v a p o r a t i n g under reduced  pressure.  A s o l u t i o n of potassium (450mL) and ethanol heated  off  t o g i v e a completely  Ethanol and the excess  under reduced  (120g) i n water  (lOOmL) was added t o the r e s i d u e and  under r e f l u x f o r 2 h  solution.  hydroxide  toluene were  homogeneous  evaporated  pressure and the aqueous s o l u t i o n was  a c i d i f i e d w i t h concentrated h y d r o c h l o r i c a c i d  (approximately  200mL) when the product c r y s t a l l i z e d out as a t h i c k white precipitate.  The s o l u t i o n was c o o l e d i n i c e o v e r n i g h t and  the s o l i d was c o l l e c t e d by s u c t i o n f i l t r a t i o n , washed with ice-water and d r i e d i n a i r . a c i d was 72.9g  (60.0%, s t a r t i n g from monoethyl  MP : 107.5-109.0°C,  NMR  The y i e l d of 6-oxoundecanedioic  Lit.:  108-109°C  hexanedioate).  , 111°C  1  (6, DMSO-d ), 1.28-1.52 (m, 8H, C-3, C-4, C-8, C-9 j  methylene p r o t o n s ) , 1.98-2.32(m, 4H, C-2, C-10 methylene p r o t o n s ) , 2.32-2.68 (m, 4H, C-5, C-7 methylene p r o t o n s ) , 10.93 NOTE 1  (br, 2H, -COOH) T r i e t h y l a m i n e was p u r i f i e d i n the f o l l o w i n g manner. F i s h e r reagent grade t r i e t h y l a m i n e was f r a c t i o n a l l y distilled  through  a 2 0cm.  Vigreux column and the  f r a c t i o n c o l l e c t e d over the range 88.5-90°C was then  159 r e f l u x e d with p h t h a l l i c anhydride and r e d i s t i l l e d . T h i s was d i s t i l l e d once more from 1 - n a p h t h y l i s o cyanate, b e f o r e use.  NOTE 2  A q u a n t i t y of reagent grade toluene was d r i e d by distilling ing  about o n e - f o u r t h o f i t and then c o o l -  the r e s i d u e with p r o t e c t i o n from moisture by  the use of a c a l c i u m c h l o r i d e  Undecanedioic a c i d i  tube.  6_5  Diethylene g l y c o l  (340mL) and potassium  (60g, 0.91 moi) were p l a c e d i n a 1 - l i t e r f i t t e d with a C l a i s e n head condenser.  The mixture was m a g n e t i c a l l y s t i r r e d  completely d i s s o l v e d .  6-oxoundecanedioic zine  erlenmeyer  flask  (side-arm stoppered) and a r e f l u x  f u l l y heated on a hot p l a t e u n t i l was  hydroxide  the potassium  and c a r e hydroxide  The s o l u t i o n was c o o l e d t o 8 0°C,  a c i d 64_ (70.0g,  0.30 moi) and 95% hydra-  (32g, 0.95 moi) added and heated under r e f l u x f o r 1 h. The r e f l u x condenser was removed, a thermometer  suspended  i n the heated l i q u i d  and the mixture was d i s t i l l e d  through the s i d e arm of the C l a i s e n head. temperature  reached 205-210°C  When the l i q u i d  (approximately 52mL of d i s -  t i l l a t e was c o l l e c t e d ) , the thermometer was removed, the s i d e arm stoppered and heated under r e f l u x f o r 3 h. The  reaction  mixture  was c o o l e d t o 1 1 0 C and p o u r e d U  (300 mL), an a d d i t i o n a l reaction  flask. acid  product  was f i l t e r e d ,  water acid and  MP  1  H  (250 mL) and a l l o w e d  on c o o l i n g ,  r e c r y s t a l l i z e d from  : 1 1 0 - 1 1 1 . 5 ° C •" L i t .  NMR  (6, DMSO-d ) 6  protons)  11.94  1.34-1.70  water  to r i n s e the  with  6M  to stand o v e r n i g h t .  hydroThe  washed w i t h w a t e r and r e m e l t e d i n  (550 mL) t o remove o c c l u d e d was r e s o l i d i f i e d  2.19  200 mL o f w a t e r was u s e d  T h i s s o l u t i o n was a c i d i f i e d  chloric  into  3 5  impurities.  Undecanedioic  c o l l e c t e d by f i l t r a t i o n  hot toluene  t o g i v e 60.7 g  (92.3%).  : 110 .-5-112°C  : 1.06 ( b r , 10H, C-4 t o C-8 m e t h y l e n e (m, 4H, C-3, C-9 m e t h y l e n e p r o t o n s ) ,  ( t , 4H, J=7.5 Hz, C-2, C-10 m e t h y l e n e p r o t o n s ) , ( b r , 2H, -COOH)  161  3.4 SYNTHESES OF MONOPYRROLES  2-Ethoxycarbonyl-3,5-dimethylpyrrole  66  66 D i e t h y l malonate acid  (128 0 g, 8.0 moi)and g l a c i a l  acetic  (1440 g, 24.0 moi), s t i r r e d m a g n e t i c a l l y i n a 1 2 - l i t e r  f l a s k , were t r e a t e d dropwise w i t h a s a t u r a t e d s o l u t i o n of sodium n i t r i t e 12 h. (NOTE 1 ) .  (1656 g, 24.0 moi) i n water, over a p e r i o d o f The s o l u t i o n turned b l u e , then green and  f i n a l l y yellow and the i n t e r n a l temperature  reached  The r e a c t i o n mixture was allowed t o s t i r o v e r n i g h t .  45°C. Diethyl  oximinomalonate separated out as a dark yellow v i s c o u s o i l and was used i n the next stage without Pentane-2,4-dione  purification.  (900 g, 9.0 moi)  and a c e t i c  (4020 g, 67.0 moi), were m e c h a n i c a l l y s t i r r e d  acid  i n a 12-liter  3-neck f l a s k as the oxime prepared above was added, r a p i d l y dropwise, (NOTE 2 ) .  along w i t h f i n e l y ground z i n c dust  (1246 g, 19.0 moi)  The e x o t h e r m i c i t y of the r e a c t i o n brought the  s o l u t i o n t o near r e f l u x but was not c o o l e d  (NOTE 3).  The hot  162 s o l u t i o n was decanted  from the unreacted z i n c i n t o  several  f l a s k s and s l o w l y d i l u t e d with two or three times of water. 2-Ethoxycarbonyl-3,5-dimethylpyrrole c r y s t a l l i z e d  as a y e l l o w  s o l i d , was c o l l e c t e d by f i l t r a t i o n and washed with hot water. The  s o l i d was r e d i s s o l v e d i n dichloromethane, the  d i s s o l u t i o n being f a c i l i t a t e d by h e a t i n g on a steam bath. When the p y r r o l e went i n t o s o l u t i o n , a c o n s i d e r a b l e amount o f water trapped w i t h i n the s o l i d , separated o f f as a l a y e r . The o r g a n i c phase was g r a v i t y f i l t e r e d and the product crystallized  o u t from methanol.  The s o l i d was s u c t i o n f i l t e r e d ,  washed w i t h methanol and a i r d r i e d t o g i v e 373.1 g (27.9%). The mother l i q u o r s were c o n c e n t r a t e d t o g i v e a second of  crop  130.1 g (9.7%) (NOTE 4 ) .  MP : 121.0-122.5°C ; L i t  .Anal.Calcd. f o r C H 9  1 3  0 N 2  124.0 - 124.5°C  3 8  : C, 64.65; H, 7.84 ; N, 8.38. Found :  C, 64.35; H, 7.90; N, 8.28  1  H NMR 3H,  (6, CDC1 ) : 1.36 ( t , 3H, J=7 Hz, -0-CH -CH_ ), 2.26 3  2  3  5-CH ), 2.32 (s, 3H, 3-CH ), 4.34 (q, 2H, 3=1 Hz, 3  3  0-CH -CH ) 5.82 (d, IH, J=2.6 Hz, 4-H), 9.40 (bs, IH, N-H) 2  1 3  C  NMR  128.97  3  (6, CDC1 ) : 162.34 (C=0), 133.00 ( p y r r o l e 5-C), 3  ( p y r r o l e 3-C), 117.93  ( p y r r o l e 2-C), 111.34 ( p y r r o l e 4-C),  59.68 (0-CH -CH ), 14.57 (0-CH -CH ), 12.90 (3-CH , 5-CH ) 2  3  2  3  3  3  163  Notes  1.  Since n i t r o g e n oxides are evolved d u r i n g the n i t r o s a t i o n , the r e a c t i o n  was c a r r i e d out i n the fume-hood.  2.  The z i n c dust i s best added as a t h i c k s l u r r y i n water.  3.  C o o l i n g tends to s e t i n premature c r y s t a l l i z a t i o n .  4.  R e f l u x i n g the s o l u t i o n  f o r 90 minutes a f t e r the  addition  of the reagents has been shown to improve the y i e l d .  4-Acetyl-2-ethoxycarbonyl-3,5-dimethylpyrrole  70  67  .CH  67 Ethyl acetoacetate acid  (1040 g, 8.0 moi) and  acetic  (1080 g, 18.0 moi) were i c e cooled and m a g n e t i c a l l y s t i r r e d  164 in a 5-liter flask. (560 g, 8.1 moi)  A s a t u r a t e d s o l u t i o n of sodium n i t r i t e  i n water was  v i s c o u s product was  added, r a p i d l y dropwise  (4 l i t e r s ) and pentane-2,4-dione  (900 g , ) , a c e t i c  (850 g, 8.5  moi)  (1046 g, 16.0  moi).  added dropwise  The temperature  mixture was maintained between 75 - 80°C.  were s t i r r e d  mixture poured c o l l e c t e d by  along w i t h of the  reaction  S t i r r i n g was  inued f o r 3 0 minutes a f t e r the a d d i t i o n was  complete,  cont-  the  i n t o water arid'-the c r y s t a l l i z e d product  filtration.  The  s o l i d was  dissolved  i n chloroform  (by warming  on a steam bath) to separate the trapped water. phase was  acid  i n a 1 2 - l i t e r 3-neck f l a s k as the above s o l u t i o n  of e t h y l oximinoacetoacetate was z i n c dust  the  s u i t a b l e f o r immediate use.  Anhydrous sodium carbonate  vigorously  and  suction  The organic  f i l t e r e d and evaporated under reduced  p r e s s u r e a f t e r adding methanol.  4-Acetyl-2-ethoxycarbonyl-3,  5 - d i m e t h y l p y r r o l e c r y s t a l l i z e d as white needles and was c o l l e c t ed by f i l t r a t i o n to g i v e 910.2  g.  (54.-4%).  The mother l i q u o r s  were c o n c e n t r a t e d f o r the second and t h i r d crops of 324.4 g (19.4%).  MP  1  H  : 142.5°-143.5°C; Lit'.  7 1  NMR  (6, CDC1 ) : 1.37 3  (s, 3H, COCH_ ), 2.52 3  143-144°C  ( t , 3H,  (s,, 3H,  J=7  Hz, -O-CH^CH^),  3-CHg), 2.57  (s., 3H,  2.42  5-CH_ ), 3  1 6 5  4.33  1 3  C  (q, 2H, J=7 Hz, 0-CH_ -CH ), 2  NMR  144.42  (6, 10% TFA-CDC1-) J  9.62  3  : 201.62  ( p y r r o l e 5-C) , 133.48  (bs, IH, N-H).  (COCH-)/ 164.30 (CO-C H.-), — 3 — Z Z D n  ( p y r r o l e 3-C) , 122.76  119.31 ( p y r r o l e 2-C), 62.89 (-0-CH -) , 29.53 2  14.27 (0-CH -CH ), 13.28 2  3  Mass spectrum  : m/e,  (5-CH ),  3  3  3  209 (M ,), 194 +  +  2  (COCH ), 15.84  (3-CH ).  (M-CH ) , 164 +  3  163 (M-CH CH OH) , 162 [M-(CH CH OH+H)] , 3  ( p y r r o l e 4-C) ,  +  3  2  (M-C H 0) 2  +  5  148 [M-(CH CH OH + C H ) ]  2-Ethoxycarbonyl-4-ethyl-3,5-dimethylpyrrole  3  2  76  76  4-Acetyl-2-ethoxycarbonyl-3 ,5-dimethylpyrrole 67_ (836.7 g, 4.0 moi), sodium borohydride (160.1 g, 4.2 moi) and e t h y l a c e t a t e  (14 00 mL) i n t e t r a h y d r o f u r a n  (4 l i t e r s )  under n i t r o g e n , were t r e a t e d dropwise w i t h boron etherate vigorously 15-20°C.  (700 mL).  trifluoride  Throughout the a d d i t i o n , the s o l u t i o n was  s t i r r e d and the temperature was maintained between When the a d d i t i o n was complete, an a l i q u o t of the  3  +  166 r e a c t i o n m i x t u r e was  removed, quenched w i t h  tic  f o r any  unreacted s t a r t i n g material.  was  d e s t r o y e d by  and  water  the  solution followed  the  cautious  (2-liters).  (1 l i t e r )  s o l u t i o n of  organic  p h a s e was  extracts  of  the  The the  ensued.  (S,  The  (6,  4.26  1 3  C  yield  CDC1 ) 3  J=7  J=7  a q u e o u s p h a s e and  dissolved  with  cooled  a  evaporated  to  i n hot  ethanol  water u n t i l and  (56.2%).  the  acid.  The  mother l i q u o r  38/  (q,  2H,  3  J=7.5 Hz,  - 0 - C H _ - C H ) , 8.83 2  3  123.83  ( - 0 - C H - ) , 17.41  108.7  3  4-ethyl  CH_ -CH ),  3  2  2.24  3  N-H)  ( p y r r o l e 5-C) , 126.69  116.94 3  2  5-CH_ ),  (pyrrole  ( 3 - e t h y l C H - C H ) , 15.45 2  CH -CH ),  ( s , 3H,  (C=0) , 130.23  ( p y r r o l e 4-C),  was  (13.9%).  4-ethyl  (bs, IH,  3  g.  by  72  J=7.5 Hz,  - 0 - C H - C H ) , 2.16 2  crystallization  product c o l l e c t e d  second c r o p of  ( t , 3H,  95%  the  90-91°C ', 9 5 - 9 6 ° C  (<5;CDC1 ) : 162.71  2  and  ethyl  : 1.02  Hz,  an  the  treated  2.36  3  ( p y r r o l e 3-C), 59.74  water  i s o l a t e d , combined w i t h  438.8 g.  Hz,  3-CH ),  ( q , 2H,  NMR  and  into  some b o r i c  s o l u t i o n was  ( t , 3H, 3H,  stirred  product i n tetrahydrofuran  c r u d e p r o d u c t was  : 90-91.5°C; L i t . .  1.30  (1 l i t e r )  mL)  and  concentrated to obtain  '''H NMR  was  (300  pressure.  s o l u t i o n was  filtration,  MP  g)  by  diborane  sodium f l u o r o b o r a t e  the  dryness under reduced  and  (250  ethyl acetate  lower aqueous s o l u t i o n o f  acetate  excess  c a u s i n g the r e a c t i o n m i x t u r e tp separate i n t o  upper o i l y  The  The  checked  a d d i t i o n of a c e t i c a c i d  Sodium c h l o r i d e by  w a t e r and  2-C),  (4-ethyl  CH -CH ), 2  3  167 14.66  (-6-CH -CH ), 11.12 (5-CH ), 10.72 (3-CH ). 2  3  3  3  Mass spectrum : m/e, 195 (M ), 180 (M-CH ) , 166 ( M - C H ) , +  +  +  3  2  5  150 (M-C H 0) , 149 (M-CH CH OH) , 148 [M-(CH CH OH+H) ] , 134 +  2  +  5  3  [M-(CH CH OH+CH )] 3  2  +  2  3  2  +  3  5-Ethoxycarbonyl-3-ethyl-4-methylpyrrole-2-carboxylic  acid'  77  HOOC  77 2-Ethoxycarbonyl-4-ethyl-3,5-dimethylpyrrole 7_6 (58.5 q,  0.30 moi) was d i s s o l v e d  i n methylene c h l o r i d e  i n a 5 - l i t e r round-bottomed f l a s k . s t i r r e d and ether  (300 mL)  The s o l u t i o n was m a g n e t i c a l l y  (500 mL) was added, immediately followed by  the r a p i d dropwise a d d i t i o n o f a s o l u t i o n of s u l f u r y l  chloride  (128.36 g, 0.95 moi) i n methylene c h l o r i d e  (200 mL).  s o l u t i o n was allowed t o s t i r  10 minutes and  evaporated o f f the s o l v e n t s  f o r a further  The  under reduced p r e s s u r e .  The r e s i d u a l r e d o i l was added i n t o hot 20% wateracetone and the r e s u l t i n g dark yellow s o l u t i o n was heated under r e f l u x f o r 5 minutes causingcthe product-to out as a p a l e y e l l o w s o l i d .  crystallize  The s o l i d was c o l l e c t e d . .'  168 by  f i l t r a t i o n , washed w i t h  then w i t h  a  .1:1  water-acetone  m i x t u r e and  water. The  crude  a-carboxypyrrole  was r e d i s s o l v e d i n  m e t h a n o l a n d s a t u r a t e d aqueous s o d i u m b i c a r b o n a t e b y warming on  a steam b a t h .  The u n d i s s o l v e d s o l i d  was e x t r a c t e d  e t h e r and t h e aqueous p h a s e was c a u t i o u s l y a c i d i f i e d concentrated as  a white  dried  MP  1  H  solid  i n a i r t o g i v e 54.1 g  NMR  reprecipitated  7  3  (80.2%).  : 211°C  (6, DMSO-d ) : 1.06 ( t , 3H, J=7 .5 Hz, 3-CH -CH_ ), 6  2  3  ( t , 3H, J=7 Hz, OCH -CH_ ) , 2.24 (s , 3H, 4-CH_ ), 2.72 2  3  2H, 3=1.5 Hz, 3 - C H - C H ) , 4.2 9 2  I I . 18  3  3  ( q , 2H, 3=1 Hz, -O-CHj-CILy) >  ( b s , I H , N-H), 12.62 ( b s , I H , -COOH)  Mass s p e c t r u m 180  The p r o d u c t  with  and was f i l t e r e d , washed w i t h w a t e r and  : 210-211°C; L i t  I . 33 (q,  hydrochloric acid.  into  : m/e, 225 ( M ) , 210 ( M - C H ) , 196 +  +  3  (M-C H ) , +  2  5  (M-C H 0) , 178 [ M - ( C H C H O H + H ) ] , 164 [M-(CH CH OH+CH ) ] • +  2  5  +  3  2  +  3  2  3  169  2-Ethoxycarbonyl-4-ethyl-5-iodo-3-methylpyrrole  78  78  5-Ethoxycarbonyl-3-ethyl-4-methylpyrrole-2-carboxylic a c i d 77_ (22.5 water  (250 mL)  g, 0.10 and  moi),  sodium b i c a r b o n a t e  !dichloroethane  (15 0 mL)  1 - l i t e r erlenmeyer f l a s k and heated  (33.0  g, 0.39  moi),  were p l a c e d i n a  on a steam bath.  s t a r t i n g m a t e r i a l d i s s o l v e d with effervescence.  The  The  flask  was  removed from the steam bath and with the a i d of a dropping f u n n e l , a s o l u t i o n of i o d i n e (29.0 g, 0.11 iodide  (45.1 g, 0.27  2 minutes throughout minutes and sulfite  moi)  i n water  (150 mL)  (the r e a c t i o n mixture was the a d d i t i o n ) . the excess  The  was  magnetically  s o l u t i o n was  i o d i n e was  moi)  and  potassium  added w i t h i n stirred  refluxed for 3 0  destroyed with sodium b i -  (a p a l e y e l l o w c o l o r remained i n the o r g a n i c l a y e r  while the aqueous l a y e r turned c o l o r l e s s ) . c o o l e d , methylene c h l o r i d e (200 mL) separated and g r a v i t y f i l t e r e d . evaporated  to dryness  hot a b s o l u t e e t h a n o l  The  flask  was  added, the o r g a n i c phase  The c l e a r y e l l o w s o l u t i o n  was  and the crude product r e d i s s o l v e d i n (200 mL).  The  s o l i d was  reprecipitated  by adding water, c o l l e c t e d by f i l t r a t i o n and washed with  50%  ethanol-water  f o l l o w e d by w a t e r t o g i v e  mother l i q u o r s were c o n c e n t r a t e d  21.5 g  (7 0 . 0 % ) .  The  f o r a s e c o n d c r o p o f 5.9 g  (19.2%)  MP  1  H  : 114.0-115.5°C; L i t .  NMR  (t,  (<5, C D C 1 )  : 1.03  3  2  2  (bs,  C  ( t , 3H, J=7 .5 Hz, 4-CH CH_ ), 2  3H, J=7 Hz,-0-CH -CH ) , 2.27  J=7.5 Hz, 4-CH_ CH ),  1 3  : 114-115°C  7 4  (s , 3H, 3-CH_ ), 2.37  3  4.31  3  ( q , 2H,  3  ( q , 2H, J=7 Hz ,-0-CH_ CH ) , 2  9.02  3  IH, N-H),  NMR  126.05 60.42  (6, C D C 1 ) 3  (pyrrole  : 161.38  ( 0 - C H C H ) , 20.00 2  2  (C=0), 131.88  3 - C ) , 123.96  3  ( 6 - C H - C H ) , 10.98 3  (pyrrole 2  ( 4 - C H - C H ) , 14.60 2  3  3  ( M - C H C H O H ) , 260  ( M - C H 0 ) , 261 +  ( M ) , 292 +  +  5  3  [M-(CH CH OH+CH )] 2  ( p y r r o l e 5-C),  (3-CH )  262  3  2 - C ) , 73.42  3  307  2  ( p y r r o l e 4-C),  ( 4 - C H - C H ) , 14.81  Mass s p e c t r u m : m/e,  246  1.33  3  3  +  2  ( M - C H ) , 278 +  3  (M-C H ) , +  2  5  [M-(CH CH OH+H)] / +  3  2  171 2-Efchoxycarbonyl-4-ethyl-3-methylpyrrole  79  79 2-Ethoxycarbonyl-4-ethyl-5-iodo-4-methylpyrrole (30.7 g, 0.10  moi)  was  dissolved  in  95% e t h a n o l  by warming on a steam b a t h . When a b s o l u t i o n i o d i d e ;.(26 .5 .g, 0.16  moi)  hydrochloric  acid  50% Aqueous  hypophosphorus. a c i d  the  iodine  added for  and  color.  was  A further  added,  25 mL  The  and w a t e r  s o l u t i o n was  (150 mL)  of  was  oil  dissolved  on s i l i c a the  heated  at  the o r i g i n  a pale product of  g e l (85 g, a c t i v i t y  yellow  liquid.  transferred  solvent  The y i e l d  pressure,  methylene  The  I) u s i n g  solvent  i n t o a weighed  was  p y r r o l e was  was  bath  chloride  phase i s o l a t e d solvents  were  and  chromatographed  methylene c h l o r i d e impurities  eluted  as  remained  out clean  as  e v a p o r a t e d , .-the  f l a s k and  removed on t h e vacuum l i n e of the a-free  The  (25 mL)  pyrrole  discharge  the r e s i d u a l dark red  A l l o f the c o l o r e d  and t h e a - f r e e  to  on t h e steam  cooled,  i n methylene c h l o r i d e  eluting solvent.  added  added, the o r g a n i c  ----- u n d e r r e d u c e d  liberated-.  hyppphosphoru-S; a c i d  and d r i e d w i t h a n h y d r o u s s o d i u m s u l f a t e . evaporated  concentrated  i o d i n e was  (25 mL)  mL)  of. p o t a s s i u m '  (20; mL);. and  t h e r e a c t i o n m i x t u r e was  15 m i n u t e s .  (250 mL)  (40 mL)  i n water  (250  7_8  the l a s t  traces  a t room t e m p e r a t u r e .  17.2  g  (94.9%).  172 MP  : 22.0-23.0°C  '''H NMR  ; Lit.  25°C  7 5  (6 , CDC1 ) : 1.14  ( t , 3H, J=7 .5 Hz, 4-CH CH ),  3  2  ( t , 3H, J=7.2 Hz, -0-CH CH ), 2.24 2  3  (q, 2H, J=7.5, 4-CH CH ), 2  6.61  1 3  C  3  4.27  125.92  (6, CDC1 ) : 162.44  ( s , 3H, 3-CH ), 2.40 3  2  ( p y r r o l e 3-C), 119.82  ( b s , IH, N-H).  ( p y r r o l e 5-C), 119.52  59.94  (-o-CH CH ), 18.41 (4-CH CH ), 14.58  14.58  (4-CH CH ), 10.34  3  2  2  3  M a s s Spectrum  m/e  120  [M-(CH CH OH+CH )] 2  3  ( M - C H ) , 152  (M-C H ) ,  +  +  3  2  +  5  3  3  5  (M-CH CH OH) , 134 [M-(CH CH OH+H)] ,  +  2  2  (3-CH )  +  ( M - C H 0 ) , 135  ( p y r r o l e 2-C),  (-0-CH CH ),  3  : 181 ( M ) , 166  136  3  (C=0), 127.39 ( p y r r o l e 4-C),  3  2  1.32  (q, 2H, J=7 . 2 Hz, -0-CH CH ),  (d, IH, J=2.8 Hz, 5-H), 8.88  NMR  3  3  +  2  3  2  +  3  2 - Be n z y 1 oxy c ar bony 1 - 4- e t h y l - 3 -me t h y l p y r r o l e  ';8 0  80  2 - E t h o x y c a r b o n y l - 4 - e t h y l - 3 - m e t h y l p y r r o l e 7_9 (5.0 g, 0.028 moi) was heated, under n i t r o g e n ,  in redistilled  benzyl  173 (30 mL, 31.2 g , 0.29 m o l s ) , t o r e f l u x a t 209°C t o e n s u r e  alcohol the  complete  centrated  removal o f water.  solution  1 mL p o r t i o n s , vapours  resulting  temperature, a con-  i n b e n z y l a l c o h o l was added  o f 3 mL, t h e r e a c t i o n  temperature.  appeared  stirred Water  h o t s o l u t i o n was p o u r e d  mixture of acetic  (250 mL) was added  orange-brown  at  into  209°'C.  a magnetically  (10 mL) and m e t h a n o l  acid  when t h e s o l u t i o n  o i l separated out.  With the  t o be c o m p l e t e a n d  r e a c t i o n mixture continued to r e f l u x The  in  i n the vigorous evolution of ethanol  and t h e l o w e r i n g o f t h e r e f l u x  addition the  o f sodium  At this  (200 mL).  turned turbid  The o i l was e x t r a c t e d  and an  into  (250 mL) a n d t h e s o l v e n t was e v a p o r a t e d  methylene  chloride  off  r e d u c e d p r e s s u r e (an o i l pump had t o be c o n n e c t e d  to  under  the r o t a r y The  e v a p o r a t o r t o remove t h e e x c e s s b e n z y l a l c o h o l ) . residual  d a r k brown o i l was d i s s o l v e d  chloride  (5 mL) a n d c h r o m a t o g r a p h e d  activity  I) u s i n g m e t h y l e n e  chloride  Most o f t h e d a r k brown i m p u r i t i e s a d a r k y e l l o w band  eluted  on s i l i c a  out s l i g h t l y  p r o d u c t a n d c o u l d n o t be s e p a r a t e d . and  the  solid  was r e c h r o m a t o g r a p h e d  all  the colored  impurities  a t the o r i g i n but  ahead  of the c o l o r l e s s  i n the freezer f o r  t u r n e d d a r k brown.  on s i l i c a  remained  solvent.  The s o l v e n t was removed  t h e a - f r e e b e n z y l e s t e r was s t o r e d  10 d a y s when t h e p a l e y e l l o w s o l i d  g e l (4 0 g ,  as t h e e l u t i n g  remained  i n methylene  When  g e l (30 g , a c t i v i t y I ) ,  a t the o r i g i n .  The  s o l v e n t was removed and t h e b e n z y l e s t e r was o b t a i n e d a s a pale yellow o i l , y i e l d  5.6  g,  (83.6%).  174 MP  : 26.5-28.0°C  Mol.Wt.  Anal.  Caicd.  Found  : C, 74.06; H, 7.16; N,  1  H  NMR  (s,  1  H 1  C  '  7 4  - /" H, 7.04; N,  5.76;  05  5.63.  ( t , 3H, J=7 . 5 Hz, 4 - C H C H ) , 2  2  : 161.91  3  128.54/128.04  65.63  :  2.30  3  5.31  3  ( s , 2H,  (m, 5H, C , H ) , C  N-H)  (6, C D C 1 )  (pyrrole  2  ( d , IH, J=2.8 Hz, 5-H), 7.38  ( b s , IH,  NMR  N 0  ( q , 2H, J=7 .5 Hz, 4-CH_ CH ),  3  6.64  7  : 1.16  3  3H, 3-CH_ ) , 2.43  9.00  C  5  C  (6, C D C 1 )  -0-CH„),  1 3  for  : 243.31  (C=0), 136.80  (benzene r i n g ) ,  3-C.) , 120.02  127.46  (pyrrole  (-0-CH ~), 18.29 2  (pyrrole  5-C) , 119.09  ( 4 - C H C H ) , 14.62 2  (benzene 1 - C ) ,  3  4 - C ) , 126.35  (pyrrole  2-C) ,  ( 4 - C H C H ) , 10.41 2  3  (3-CH ) 3  Mass s p e c t r u m 136  (M-C H CH 0) , +  6  5  (C H CH ) , +  6  : m/e  5  3  2  91  243 (M ) , 228 (M-CH_.) , j +  108  (C H 7  + y  +  (C H CH OH) , +  6  )  5  2  107  152  (M»C,H CH ) , o b 2. +  c  n  ( C H C H 0 ) , 92 +  6  5  2  175 5-Chloromethyl-2-(2,2-dicyanovinyl)-4-ethyl-3-methylpyrrole  - 86  86 2- (2 , 2 - D i c y a n o v i n y l ) - 4 - e t h y l - 3 , 5 - d i m e t h y l p y r r o l e 8_4 (3.98  g, 0.02 moi) i n d r y m e t h y l e n e c h l o r i d e  treated with  a solution  of s u l f u r y l  0.02 moi) i n m e t h y l e n e c h l o r i d e (sulfuryl  c h l o r i d e was  magnetically allowed was  stirred  added r a p i d l y  t o b o i l down c a r e f u l l y  yellow needles,  yield  An a n a l y t i c a l methylene  1  H  a t room  The s t i r r e d  temperature  solution  was  w h i l e anhydrous d i e t h y l  4.1 g  of the product  ether as  (87.8%).  sample was  : 1 7 6 . 0 - 1 7 8 . 0 ° C (dec)  15.17;  NMR  (2.75 g, 2.70 g  recrystallized  from  chloride-methanol.  Anal. Calcd. Cl,  was  and d r o p w i s e t o a  added, c a u s i n g the c r y s t a l l i z a t i o n  fluffy  MP  chloride  (50 mL)  solution).  (75 mL)  for  c  H 1  Found  2  i 2  C  l  Mol.Wt  N  3  (s,  3H, 3 - C H ) ,  (s,  2H, C H C 1 ) , 7.46 2  :  C  '  6 1  : C, 61.38; H,  : (6, C D C 1 ) : 1.11 3  3  2.48  -  6 7  : 233.70  '" / H  5.18; N,  17.98;  5.30; N, 17.73; C l , 15.00  ( t , 3H, J=7.5  (q, 2H, J=7.5  Hz, 4 - C H C H ) , 2  Hz, 4-CH_ CH ), 2  ( s , IH, CH=C(CN) ), 2  9.52  3  3  2.17  4.61  ( b s , IH,  N-H)  :  176  Mass s p e c t r u m ,  m/e  184  (M-C1-CH +H)  IR  (v^ ,  : 233  (M , v e r y weak), +  199  (M-C1+H) , +  +  3  KBr)  v  : 3340  (N-H), 2220  (C=N) , 1595  T h i s compound had p r e v i o u s l y been p r e p a r e d  (C=C)  by R.B.  Woodward  as an i n t e r m e d i a t e i n t h e s y n t h e s i s o f c h l o r o p h y l l the e x p e r i m e n t a l  details  nor i t s s p e c t r a l  cm"  but neither  p r o p e r t i e s have  been r e p o r t e d . .  5-Chloromethyl-2-(2-cyano-2-methoxycarbonylvinyl)-  2-(2-Cyano-2-methoxycarbonylvinyl)-4-ethyl3,5-dimethylpyrrole chloride  (7 0 mL)  while being  8_5 (5.0 g , 21.6 mmol) i n d r y m e t h y l e n e  was c o o l e d i n i c e and m a g n e t i c a l l y  t r e a t e d , dropwise, with a s o l u t i o n  of  75  stirred  sulfuryl  177 chloride (20  mL)  was  (3.05 g, 2.92 over a p e r i o d  allowed  to s t i r  g = 21.6 mmol) i n d r y m e t h y l e n e o f 30 m i n u t e s .  for a further  M e t h y l e n e c h l o r i d e was  The r e a c t i o n  product  isolated  (42.2%).  MP  Cl,  1  H  Calcd.  a first  Found  reduced  and t h e  c r o p o f 2.42  g.  to obtain a  (42.0%).  Mol.Wt  for C ^ H ^ C I N ^  13.29;  NMR  ether  The m o t h e r l i q u o r s were c o n c e n t r a t e d  : 157.0 - 1 5 9 . 0 ° C (dec.)  Anal  temperature.  e v a p o r a t e d o f f under  from hexane, t o g i v e  s e c o n d c r o p o f 2.41 g.  mixture  3 0 m i n u t e s a t room  p r e s s u r e , r e p l a c e d w i t h anhydrous d i e t h y l  chloride  =  266.73  : C, 58.54; H,  5.67; N,  10.50;  : C, 58.64; H, 5.66; N, 10.42; C l , 13.19  , ( 6 CDC1 ) 3  : 1.09  ( t , 3H, J=7.5 Hz, 4 - C H C H ) , 2  3  2.18  (s,  3H, 3 - C H ) , 2.46  ( q , 2H, J=7.5 Hz, 4-CH_ CH ),  3.86  (s,  3H, 0 - C H ) ,  ( s , 2H, CH_ C1), 8.00  CH=C (CN) C C ^ C H ^ ,  3  3  4.60  2  2  3  [ s , 1H,  9. 64- ( b s , IH,- N-H) .  Mass S p e c t r u m , 217  m/e  : 266  (M-C1-CH +H) , 199  IR (C=C)  +  3  P ') .  K v  cm  - 1  r  = 3300  ( M ) , 232  (M-C1+H) ,  +  (M-C1-CH 0H) 3  (N-H) , 2220  +  +  231  (M-C1) , +  185 [M-(Cl+CH OH+CH )+H] 3  (C=N) , 1725  3  (C=0) , 1595  +  178 3.5  SYNTHESIS  OF THE MODEL PORPHYRIN AND  ITS DIPYRROMETHANE  PRECURSORS  5-(2,2-Dicyanovinyl)-2-[(5-ethoxycarbonyl-3-ethyl-4-methylpyrrol2-yl)methyl] -3-ethyl-^-methylpyrrole  97  5 - C h l o r o m e t h y l - 2 - (2 , 2 - d i c y a n o v i n y l ) - 4 - e t h y l - 3 - " ' methylpyrrole  8_6_ (3.57 g , 15.3 mmol) and  ethyl-3-methylpyrrole in  glacial  acetic  a water bath dissolved  acid  a t 7 0°C.  giving  7_9 (2.87 g, 15.8 mmol) were (150 mL) Within  a clear  methylene c h l o r i d e ,  2-ethoxycarbonyl-4-  u n d e r n i t r o g e n and warmed i n  0.5  orange  suspended  h  the s t a r t i n g m a t e r i a l s  solution.  A d r o p removed  washed w i t h w a t e r , showed a s i n g l e  s p o t on t i c (2% C H 0 H - C H C 1 ) , c o l o r e d v i o l e t 3  2  2  with  into  yellow  bromine  vapor. The orated  solution  was  c o o l e d t o room t e m p e r a t u r e ,  down t o a p p r o x i m a t e l y  2 0 mL,  treated  with  evap-  methanol  179  (80 mL)  and a l l o w e d  crystalline  solid  to stand overnight.  The y e l l o w  was c o l l e c t e d by f i l t r a t i o n ,  m e t h a n o l and d r i e d  i n a i r to give a f i r s t  finely  rinsed  crop  with  o f 5.05 g  (87.4%). The solids with  taken  m o t h e r l i q u o r s were e v a p o r a t e d up i n methylene, c h l o r i d e  s a t u r a t e d sodium b i c a r b o n a t e  (8 0 mL), and washed  (2x20 mL)  A s e c o n d c r o p was o b t a i n e d by e v a p o r a t i n g chloride 482 mg  s o l u t i o n a f t e r the a d d i t i o n  (8.3%).  methylene  MP  : 186.0-187.0°C;  Mol.Wt.  : C, 69.66; H, 6.84; N, 14.80.  H  N  C  /  6  9  ,  (6, C D C 1 ) 3  : 1.05  2.17  ( s , 3H, 4 - C H ) , 2.30  2  3  3'-CH CH ), 2  2.46  3  b r i d g e CH_ ), 4.30 2  C H = C ( C N ) ) , 8.7 6 2  C  NMR  (pyrrole  of methanol,  4  ;  (6,CDC1 ) 3  H  '  6  - '* > 8 8  yield  3  1.35  3 -CH CH ), ,  2  ( s , 3H, 4'-CH  ) , 2.44  ( q , 2H,  ( q , 2H, J=7 .5 Hz, 3-CH_ CH ), 2  2  ( b r , IH, l ' - N H ) ,  : 162.15  9.2 0  3  ( t , 3H, J=7 Hz,  ( q , 2H, J=7 Hz, - 0 - C H C H ) ,  C - 2 ) , 136.06  14.81;  N  ( t , 3H, J=7.5 Hz,  ( t , 3H, J=7.5 Hz, 3-CH CH_ ),  1 3  8  2  1.08  Hz,  the methylene  : 378.48  Found  C  NMR  (20 mL).  chloride-methanol.  Calcd. f o r 2 2 6 4 ° 2  H  and w a t e r  An a n a l y t i c a l sample was r e c r y s t a l l i z e d f r o m  Anal.  1  to dryness, the  3  3.98  3  7.34  -0-CH CH ), 2  J=7.5 ( s , 2H,  ( s , IH,  ( b r , I H , 1-NH).  (C=0) , 140.78 [ CH=C (CN) ] , 140.44  (pyrrole  2  C - 4 ) , 127.11, 126.41, 126.21,  3  180 125.15  ( p y r r o l e C-3, C-2', C-3', C - 4 ' ) , 124.16  118.93  (pyrrole  [CH=C(CN) ] 2  C - 5 ' ) , 116.78  , 59.96  ( 3 ' . C H C H ) , 17.12 2  3  ( 3 - C H „ C H _ ) , 14.48  Mass  ( 0 - C H C H ) , 23.75 2  2  O-CH  IR  CH  ) , 10.52  17.34  2  (3 "-^CI^CI^) , 14.67 (4 -CH-), 1  9.38  (4-CH_)  Spectrum Relative Intensity  Assignment  37 9  27  378  99  363  13 .".  (M-CH )  333  34  (M-C H 0)  332  100  317  42  197  44  ( v ; ^ KBr)  1665  3  (C=N) , 64.11  (bridge C H ) ,  3  ( 3 - C H C H ) , 15.36  m/e  —~—  (C=N), 115.99  (pyrrole C-5),  : 3400  (N-H), 3280  IuclX  (C=0), 1585  (C=C)  cm" . 1  M' + H +  M  +  +  3  2  +  5  (M - C H O H ) 2  +  5  (M- C H O H - C H ) 2  (N-H), 2220  (C=N) ,  5  3  +  181  2-[(5-Carboxy-3-ethyl-4-methylpyrrol-2-yl)methyl]-3-ethyl 5-formyl-4-methylpyrrole  103  5-(2,2-Dicyanovinyl)-2-[(5-ethoxycarbonyl-3-ethyl4-methylpyrrol-2yl)methyl]-3-ethyl-4-methylpyrrole 1.32 mmol) d i s s o l v e d i n r e f l u x i n g ethanol w i t h sodium hydroxide  (2.5 g) i n water  (25 mL) was t r e a t e d  (10 mL).  was r e f l u x e d under n i t r o g e n f o r 0.5 h, water and continued r e f l u x i n g f o r 1 h. ( r e f l u x temperature reached  9_7 (500 mg ,  The mixture  (50 mL) was added  Ethanol was b o i l e d o f f  100°C), more water  added and c o o l e d to room temperature. dropwise u n t i l the s o l u t i o n was a c i d i c  (50 mL)  was  A c e t i c a c i d was added (pH~5) and the grey  g e l a t i n o u s p r e c i p i t a t e was f i l t e r e d , washed w i t h water and d r i e d over potassium 380.7 mg  (95.3%).  hydroxide  i n a vacuum d e s s i c a t o r , y i e l d  F u r t h e r d r y i n g on the vacuum l i n e  (0.2 t o r r )  at room temperature f o r 18 h-_, gave an a n a l y t i c a l l y pure sample.  The r e a c t i o n was repeated with 2.5 g of s t a r t i n g  m a t e r i a l t o g i v e the product i n e s s e n t i a l l y q u a n t i t a t i v e yield.  182 MP  : 188.0 - 1 9 0 . 0 ° C  Mol.Wt.  Anal.  Calcd.for  Found  : C, 67.26; H, 7.32; N, 9.35.  C 1  7  (dec.)  'H NMR (6, DMS0-d )  H  3- and 3'- C H - C H ) , 2.29,  (br,  C  '  6  7  '  5  3  ;  H  '  7  -  3  3  " N, 9.26  3  6H, J=7.5 Hz,  2.11 ( s , 3H, 4-CH >, 2.15 ( s , 3H, 4 ' - C H ) , 3  3  2.31 (two q u a r t e t s masked by DMSO-d^ s i g n a l ,  CH CH ), 2  0  : 0.83, 0.85 (two t r i p l e t s ,  6  2  2 2 3 N  2  : 302.37  3  3.77 ( s , 2H, b r i d g e  CH ) 2  f  3- and 3'-  9.46 (s , I H , .CHO)',, 11.00 ;  I H , 1-NH), 11.42 ( b r , I H , l'-NH)  Mass s p e c t r u m : m/e  Relative Intensity  Assignment  3 02  18  M  258  74  (M- C 0 )  1  4  9  1  0  0  2  i  HXX NA' X  U  N  "  H  \  122  32  121  25  1 0 9  108  1 4  +  0  /CH  3  HX  , H" . i HNX^  35. H  3 H  +  183  I  R  (  v ma  -  K B r v  )  :  3  2  6  (broad, N-H), 1670  5  (broad, C=0)  cm - . 1  2- [ ( 5 - E t h o x y c a r b o n y l - 3 - e t h y l - 4 - m e t h y l p y r r o l - 2 - y l ) m e t h y l ] 3- e t h y l - 5 - f o r m y l - 4 - m e t h y l p y r r o l e  104  5-(2,2-Dicyanovinyl)-2-[(5-ethoxycarbonyl-3-ethyl - 4 - m e t h y l p y r r o l - 2 - y l ) m e t h y l ] - 3 - e t h y l - 4 - m e t h y l p y r r o l 97_ (502 mg,  1.33 mmol) i n ethanol  (2 g) i n water  (10 mL)  and potassium  (2 0 mL) were heated on a steam bath.  hydroxide Within 1 h  the f l u f f y y e l l o w s t a r t i n g m a t e r i a l changed i n t o a l i g h t t a n , powdery  solid.  More water  (50 mL) was added, c o o l e d , f i l t e r e d ,  washed with water and d r i e d to g i v e 275 mg r e p i t i t i o n of the s y n t h e s i s gave a y i e l d  MP  : 167.5 - 168.0°C  Anal. Calcd. f o r  C  Moi. Wt.  H 1  9  N 2  6  C, 68.75; H, 8.01; N,  0 2  3 ' :  8.42.  c  >  69  • '" 06  H  (62.7%).  of 305 mg  A (69.7%).  : 330.43  ' - 9 3 , N, 8.48, 7  Found  1  H  NMR  (6, C D C 1 ) 3  3'-CH CH ), 2  3  (two t r i p l e t s ,  6H, J=7.5 , 3-,  1 . 2 5 ( t , 3H, J=7 H z , - 0 ~ C H C H ) , 2.25  4 ' - C H ) , 2.44 3  4.19  : 1.04, 1.05  2  ( q , 4H, 3-, 3 ' - C H C H ) , 2  3  (q, 2H, J=7 Hz, -OCH_ CH ) , 9.45 2  ( b r , 1, l ' - N H ) , 10.68  Mass s p e c t r u m  3  6H,4-,  3  3.89  (s , 2H, b r i d g e  ( s , I H , CHO),  CH )  9.97  ( b r , I H , 1-NH).  : Relative  m/e  Intensity  Assignment  330  97  M  315  17  (M-CH )  301  17  (M-C„H )  193  31  -149  100,  (v ^ .. m  x  KBr) : 3265 ( b r o a d , N-H), 1680  +  3  +  C  J^..\ ~  IR  +  H  0  (C=0) , 1625 (C=0) cm  2  185 2-[(5-Benzyloxycarbonyl-3-ethyl-4-methylpyrrol-2-yl)methyl]5- ( 2 , 2 - d i c y a n o v i n y l ) - 3 - e t h y l - 4 - m e t h y l p y r r o l e .  110  5-Chloromethyl-2-(2,2-dicyanovinyl)-4-ethyl-3methylpyrrole  8_6 (1.02 g , 4.37 mmol) and  4-ethyl-3-methylpyrrole acetic  acid  0.5h..  particles itself. and  80_ (1.103 g , 4.54 mmol) i n g l a c i a l  (7 0 mL) were warmed i n a w a t e r b a t h  The c l e a r  temperature  orange c o l o r e d  and s u c t i o n  filtered  when t h e p r o d u c t The f l u f f y  solution  The  allowed  solid  mother l i q u o r s  to stand  (10.3%) was An  t o room  insoluble  c r y s t a l l i z e d out i n the f i l t e r  yellow  to approximately  a t 7 0°C f o r  was c o o l e d  t o remove any  was c o l l e c t e d  washed w i t h m e t h a n o l t o g i v e 1.5 g  pressure  2-benzyloxycarbonyl-  filtration  (78.0%).  were e v a p o r a t e d  under  10 mL, added m e t h a n o l  overnight,  by  flask  reduced  (3 0 mL) and  from which a second c r o p  o f 197 mg  isolated. analytical  chloride-methanol.  sample was r e c r y s t a l l i z e d f r o m m e t h y l e n e  186  192.0-193.0 C  MP  Anal.  Calcd.  Found  1  for 7 2 8 4 ° 2 C  H  N  :  C  2  '  7 3  Wt.  '  6 1 ;  : 44 0.55  H  ' 6.41; N, 12.72;  : C, 73.70; H, 6.37; N, 12.66.  H NMR  : (6, CDC1 ) : 1.02, 1.04 3  C H C H ) , 2.12 2  Moi.  3  ( t , 6H, J=7.5 Hz, 3- and 3'-  (s, 3H, 4-CH.j), 2.28  (s, 3H, 4'-CH_ ), 2.40 (q, 3  4H, J=7.5 Hz, 3- and 3'- CH_ CH ), 3.93 2  5.21  (s, 2H, - 0 - C H C H ) , 7.21 2  (m, 5H,  1 3  C  3  NMR  C  E  b—b  r  c  6  9.00  ) ,  5  (s, 2H, b r i d g e CH ) , 2  (s, IH,-CH=C(CN) ), 7.22-7.37 2  (br, IH, 1V-NH), 9.17 ' —  (6, CDC1 ) : 162.64 3  ( p y r r o l e C-2), 136.44  (br, IH, 1-NH) —  (C=0), 140.87[CH=C(CN) ], 139.79 2  (benzene C - l ) , 135.91 ( p y r r o l e C-4),  128.56/128.01 (benzene r i n g ) , 127.81, (hook), 126.32, 125.41 ( p y r r o l e C-3, C-2', C-3', C-4'), 124.24 ( p y r r o l e C-5'), 116.76  (C=N), 115.79 (C=N), 65.75  64.68 [CH=C (CN) ) ] , 23.82 2  17.13 (3-CH CH ), 15.33 2  3  ( p y r r o l e C-5), 118.62  (bridge  C H ) , 17.32 2  P ' - C H ^ H ^ , 14.68  (-0-CH C H ), 2  P'-CH^H^,  (3-CH CH ), 10.60 2  3  (4'-CH ), 9.41(4-CH ). 3  6  3  Mass Spectrum : Relative ion  m/e  Intensity  Assignment  1  440  27  2  349  18  (M-C,H .CH,J  3  199  21  ( i o n 4 + H)  M  +  +  [  5  187 ion  Relative Intensity  m/e  Assignment  NC  6  9  100  1  C H U  —  :  1660  (v  max  K  B  r  )  :  (0=0), 1595  3  3  8  0  (C=C)  (N-H), 3320  (N-H), 2220  CN  T  7 7 H  (C=N),  cm" . 1  2-[(5-Benzyloxycarbonyl-3-ethyl-4-methylpyrrol-2-yl)methyl]5-(2-cyano-2-methoxycarbonylvinyl)-3-ethyl-4-methylpyrrole  112  188 5-Chloromethyl-2-(2-cyano-2-methoxycarbonylvinyl) -4-ethyl-3-methylpyrrole glacial  acetic  acid  3 - m e t h y l p y r r o l e 8_0 stirred  in.  nitrogen cooled  was  (4 0 mL)  to give  methylene  and  1.86  g  c  8 3l 3°4 H  2  N  71.09; H,  0-CH C H ), 8.82  :  6.58;  mL)  orange s o l u t i o n  under  suction. t o 10  (10 mL).  was  The  mL,  The p r o d u c t  finely crystalline solid  and  washed w i t h m e t h a n o l and a i r -  -0-CH ), 3  7.12-7.40  3.87 (m,  ( b r , IH, l ' - N H ) , 9.28  C  '  N,  : 1.00,  (two q u a r t e t s ,  ( s , 3H, 5  then water  was  Mol.Wt.  3  6  the c l e a r filtered  a n a l y t i c a l sample  (6, CDC1 )  2.39  2  (20  (88.1%).  3- and 3 '-CH^CHLj) , 2.08  3.77  acid  r e c r y s t a l l i z e d from  chloride-methanol.  : C,  NMR  2.35,  and  by f i l t r a t i o n ,  Anal. Calcd.for  E  added  : 168.0-169.0°C  Found  mmol) i n a c e t i c  warmed i n a w a t e r b a t h u n d e r  o u t as a y e l l o w  collected  An  X  h  suspended i n  2-benzyloxycarbonyl-4-ethyl-  (1.15 g, 4.73  f o r 0.5  mmol) was  e v a p o r a t e d under reduced p r e s s u r e  crystallized  MP  and  t o room t e m p e r a t u r e and  methanol  dried  (60 mL)  The m i x t u r e was  a t 70°C  filtrate  was  87_ '(1.19 g, 4.46  7 1  -  0 2  '"  (s , 3H,  >  6.60;  N,  (two t r i p l e t s , 4-CH.j), 2.27  J=7.5 Hz,  (s , 2H, 5H,  H  8.87;  8.87.  1.02  4H,  473.57  3- and  6H,  (s , 3H,  , 7.77  ( b r , IH, 1-NH).  Hz,  4'-CH_ ), 3  3'-CH CH ),  b r i d g e C H ) , 5.20 2  J=7.5  2  3  (s ,  2H,  ['s , IH, CH=C (CN) ^ ,  189 1 3  C  NMR, : (6, C D C 1 ) 3  : 165.19  (C0 CH ), 2  138.32 [ C H = C ( C N ) C 0 C H ] , 137.70 2  C-l),  135.38  127.98  123.65  ( p y r r o l e C-4)>  (pyrrole  (pyrrole  3  3  161.64  (CC> CH C H ) , 2  ( p y r r o l e C - 2 ) , 136.54  128.45  (benzene  (pyrrole  (pyrrole  C - 5 ) , 119.42  (C=N), 118.43  86.14  [C (H)=C (CN) C 0 C H ] , 65.57  23.62  ( b r i d g e C H ) , 17.32  15.35  ( 3 ' - C H C H ) , 14.72  2  C - 3 ) , 125.23  5  carbons),  127.09  (pyrrole  (pyrrole  C-3'),  C-5'),  (-O-CH^-CgB^) , 52.38 (O-CH^),  3  2  6  (benzene  ring-two  C-2', benzene r i n g - t h r e e . c a r b o n s ) ,  C - 4 ' ) , 125.71  2  ( 3 ' - C H C H ) , 17.13 2  3  (3-CH CH ), 2  3  ( 3 - C H C H ) , 10.57  (4'-CH ),  m/e  Relative Intensity  Assignment  474  33  473  100  382  20  365  49  (M-C H CH-.sOH)  364  40  (M-C H CH OH-H)  231  18  230  19  91  65  2  3  2  3  9.16  3  (4-CH ). 3  Mass s p e c t r u m :  (M+H) +  M  +  (M-C H CH ) 6  r  5  c  6  5  +  2  2  +  [ +  190 IR 1685  (v  -  KBr)  : 3380  ( b r o a d , C=0),  (N-H), 3310  1590  (C=C)  ( b r o a d , N-H),  2205  (C=N),  cm" . 1  2-[ ( 5 - C a r b o x y - 3 - e t h y l - 4 - m e t h y p y r r o l - 2 - y l ) m e t h y l ]  -5-(2-cyano-  2-methoxycarbonylvinyl)-3-ethyl-4-methylpyrrole  113  113  2-[(5-Benzyloxycarbonyl-3-ethyl-4-methylpyrrol-2-yl) methyl]-5-(2-cyano-2-methoxycarbonylvinyl)-3-ethyl-4-methylpyrrole 112  (1 g,  2.12  palladized  charcoal  u n d e r 1 atm and  linear  a further  mmol) i n t e t r a h y d r o f u r a n (35 mL)  of hydrogen. with  time  10 min  h y d r o g e n was  solution  finely  a p l a t e a u i n 25 min.  showed no  crystalline  After more  o f f and  starting  material.  crystallized The  rapid  filtered  o f f under reduced  solid.  10%  temperature  o f h y d r o g e n was  t h e c a t a l y s t was  evaporated  a t room  ( d u r i n g w h i c h p e r i o d no  m e t h a n o l added when t h e p r o d u c t yellow  stirred  uptake  reached  of s t i r r i n g  of the  s o l v e n t was  was  The  and  taken up),  a t i c analysis The  (101 mg)  with  solid  pressure  and  o u t as a lemon was  collected  by  filtration,  washed  This  w i t h m e t h a n o l and e t h e r ,  to give  r e a c t i o n was r e p e a t e d w i t h 3.01 g  t h e d i p y r r o m e t h a n e 112 and 3 00 mg o f c a t a l y s t (80 mL). 0.64  g  The f i r s t  c r o p weighed  (26.3%) f o r a t o t a l  progressively  above  1.55 g  yield  681 mg  (84.1%).  (6.36 mmol) o f  i n tetrahydrofuran  (63.6%) and t h e s e c o n d ,  o f 89.9%.  The sample d a r k e n e d  205.0°C and m e l t e d a t 2 1 6 . 0 ° C . (dec.)  An a n a l y t i c a l  sample was r e c r y s t a l l i z e d  from  tetrahydrofuran-methanol.  M o i . Wt. : 383.45  Anal.  Calcd. for  Found  : C, 65.73;  -"H NMR  i 25 3°4 H  2  N  3  :  C  '  6 5  -  7 8  "  H  ' 6.57; N, 10.96  H, 6.46; N, 10.89.  : (6, DMSO-d )  CH CH ), 2  c  g  : 0.8 9  ( t , 6H, J=7 .5 Hz, 3- and 3'-  2.14 ( s , 3H, 4 - C H ) , 2.20 ( s , 3H, 4 - C H ) , 2.39 1  3  3  (two q u a r t e t s masked by t h e DMSO-d^ s i g n a l , CH CH ), 2  3  3- and 3'-  3.80 ( s , 3 H , - 0 - C H ) , 4.04 (s , 2H, b r i d g e CH_ ), 7.87 3  2  [ s , l H , C H = C ( C N ) C 0 C H ] , 10.39 ( b r , I H , 1-NH), 11.05 2  3  IH, l ' - N H ) , 11.84 ( b s , I H , C 0 H ) . 2  Mass s p e c t r u m Relative m/e  Intensity  Assignment  384  25  (M+H)  383  100  M  +  +  (br,  Relative m/e  Intensity  Assignment  365  24  (M-OH-H)  339  28  (M-C0 )  231  28  +  +  2  •OCH,  26  230  OCH,  I  R  ( ™ =„ v  KBr) : 3380  (N-H), 3265  ( b r o a d , N-H), 2200 (C  IllciX  1690  (C=0), 1640  (C=0), 1580  (C=C)  cm" . 1  5-(2-Cyano-2-methoxycarbonylvinyl)-3-ethyl-2-[ (3-ethyl4-methylpyrrol-2-yl)methyl]-4-methylpyrrole  114  114  193  2-[ ( 5 - C a r b o x y - 3 - e t h y l - 4 - m e t h y l p y r r o l - 2 - y l ) m e t h y l ] - 5 (2-eyano-2-methoxycarbonylvinyl)-3-ethyl-4-methylpyrrole (1.01 g, 2.64 stirred  mmol) and t r i f l u o r o a c e t i c a c i d  under n i t r o g e n f o r 5 min.  methylene c h l o r i d e revealed No  and c h e c k i n g  a single  yellow  Removal  on t i c ( i n m e t h y l e n e  spot, colored  pressure,  and w a t e r  solution  was  and d r i e d  mother  and a i r d r i e d  after  MP  :  156.0  122 mg  Found  1  H  2  : C, 70.79;  NMR  2.02  c  (6, CDC1 ) 3  ( s , 3H,  (13.6%),  H  N  H,  7.54;  : 1.05  :  C  N,  2  7.78  6.41  -  7  3  ( d , IH, J=2 2  3  mL)  sulfate. of  hexane  filtered,  washed  (78.4%).  The  ;  H  '  of  92%.  339.44  -  7  4 2  ;  N,  12.38;  Hz,  3- and  4 - C H ) , 2.40 3  3'-CH CH ), 2  3  Hz,  5'-H),  7.63  3  ( q , 4H,  ( s , 3H, 0 ~ C H ) , 3.87  [ , IH, C H = C ( C N ) C 0 C H ] , 9.31 s  7  :  J-7.5  ( s , 3H,  3  J=7.5, 3- and 3' -CH' CH ) , 3.77 bridge CH ),  0  mL)  12.36.  ( t , 6H,  4 ' - C H ) , 2.12 2  7  (50  (2x2 0  f o r an o v e r a l l y i e l d  '  reduced  and c o o l e d i n i c e , t o o b t a i n  Mol.Wt.  o 25 3°2  was  t o g i v e 701 mg  - 157.0°C  Anal.Calcd. for  the a d d i t i o n  solid  l i q u o r s were c o n c e n t r a t e d  an a d d i t i o n a l  solution  w i t h anhydrous sodium  concentrated  tri-  i n methylene c h l o r i d e  and t h e o r a n g e m i c r o c r y s t a l l i n e w i t h hexane  Most o f t h e  s a t u r a t e d sodium b i c a r b o n a t e  (20 mL)  chloride)  the complete  by e v a p o r a t i n g u n d e r  t h e r e s i d u e t a k e n up  washed w i t h  The  removed  into  r e d by b r o m i n e v a p o u r .  disappearance of the s t a r t i n g m a t e r i a l . a c i d was  were  o f an a l i q u o t  spot remained a t the o r i g i n , i n d i c a t i n g  fluoroacetic  ( 8 mL)  113  (s', 2H  ( b r , IH, l ' - N H ) ,  ( b r , IH, 1-NH).  "^C NMR 137.63  (6, C D C 1 )  : 165.29  3  (CC> CH ), 140.47 2  [ C H = C ( C N ) C 0 C H ] , 135.56 2  C - 3 ) , 123.54  (pyrrole C-2),  3  ( p y r r o l e C - 4 ) , 125.52  3  ( p y r r o l e C - 5 ) , 122.47 . ( p y r r o l e C - 2 ' ) ,  (pyrrole  C - 3 ' ) , 119.61  (pyrrole  C - 5 ' ) , 85.55  (0=N), 118.43  (-CH=C(CN)C0 CH ),  23.68  (bridge C H )  15.63  ( 3 ' - C H C H ) , 14.78  2  2  3  f  (pyrrole  17.62  2  3  p'-CI^CB^),  17.12  ( 3 - C H C H ) , 10.33 2  3  120.71  C-4'),  52.37  115.19  (0-CH ), 3  (3-CH CH ), 2  3  (4'-CH ),  9.30  3  (4-CH ). 3  Mass  spectrum m/e  Relative Intensity  340  23  339  100  307  16  231  41  Assignment (M + H)  +  M (M-CH OH) + 3  CH,  230  57 • 0CH NC  \ _ / C H  122  59  (pyrrole  f  t  H X ^ N ^ H  3  3  Relative m/e  IR 2200  (v  m a x  KBr)  (C=N), 1690  Intensity  : 3410  (N-H),  (C=0), 1590  3400 (C=C)  Assignment  (v.weak), cm" . 1  3360  (N-H)  196 3- E t h y l - 2 - [ ( 3 - e t h y l - 4 - m e t h y l p y r r o l - 2 - y l ) m e t h y l ] - 5 - f o r m y l 4- m e t h y l p y r r o l e  105  5-(2-Cyano-2-methoxycarbonylvinyl)-3-ethyl-2-[(3ethyl-4-methylpyrrol-2-yl)methyl]-4-methylpyrrole  114  (503  1.48  (20  mL)  mmol) and  were h e a t e d the  yellow  within out  of heating,  solution.  sulfate  dried  to g i v e  analytically  380  f o r 2h  : 137.0  pure.  - 137.5°C  Anal. Calcd: Found C,  i n water  (15 mL)  was  added  for C  74.30; H,  1 6  was  and  2 2  mg  The  filtered.  2  N,  g  The  solid  : C,  repeated  Wt  :  74.38 ; H,  10.7 2  was  dried found with  product.  258.37  8.58;  N,  more  over  sample,  (97.1%) o f t h e  Moi.  separated  f o r 3 0 min,, The  r e a c t i o n was  causing  and  needles  continued  (99.2%).  1.05  N 0  8.33;  fluffy  i n a vacuum d e s s i c a t o r  (dec.)  H  tan  a t room t e m p e r a t u r e , was  s t a r t i n g m a t e r i a l to give  MP  light  added, c o o l e d  the vacuum-line  t o be  Methanol  Heating  washed w i t h W a t e r and  on  (2 g)  s t a r t i n g m a t e r i a l to d i s s o l v e completely  (30 mL)  calcium  hydroxide  under n i t r o g e n .  15 min.'  of the  water  potassium  mg,  10.84,'  1.43  g  197 1  H  NMR  : (6, C D C l ) , 1.06, 1.07 3  3- and 3'- CH CH_ ) , 2.02 2  2.43  1 3  C  3  6.36' ( d , I H , J=2 Hz, 5'-H), 8.4 6 IH, l ' - N H ) ,  NMR  9.99  (6, C D C 1 ) 3  : 175.91  C - 4 ) , 128.43  122.75  (pyrrole  C-2'),  120.98  (pyrrole  C-4'),  114.78  (pyrrole  C-5'),  22.74  CH CH ), 2  Mass  3  3  10.36  spectrum  ( s , 2H,  (s , IH CHO),  (CHO), 138.81  (pyrrole  2  3.83  9.38  (pyrrole  (4'-CH ), 3  C-3'),  (pyrrole C-3), (pyrrole  17.70  ( 3 ' C H C H ) , 15.21 ( 3 2  3  (4-CH ). 3  Relative Intensity  258  86  243  13  (M-CH )  229  22  (M-C„H )  Assignment M  C  0CH3  100  33  +  +  3  ~  122  C-2) ,  117.53 2  3  8.76  C - 5 ) , 124.85  (bridge C H ) ,  ( 3 - C H C H ) , 15.83 2  (pyrrole  m/e  149  bridge  ( b r , IH, 1-NH).  133.58  ( 3 ' - C H C H ) , 17.03  Hz,  ( s , 3H, 4-CH.j) ,  3  2  2  6H, J=7.5  ( s , 3H, 4 ' - C H ) , 2.23  3  (q, 4H, J=7.5 Hz, 3- and 3'- CH_ CH ),  CH ), (br,  (two t r i p l e t s ,  H  f t  N  0  +  198 Relative m/e  Intensity  121  28  Assignment  \_v  IR  ( v - V - . K B r ) : 3330 ITlciX  (N-H), 3270  C H  3  J = \  (N-H), 1610  (C=0) cm  1  ,  199  3,7,13,17-Tetraethyl-2,8,12,18-tetramethylporphyrin (Etioporphyrin  II)  106  Method A  2-[(5-Carboxy-3-ethyl-4-methylpyrrol-2-yl)methyl]-3-ethyl-5formyI-4-rmethylpyrrole N,N-dimethylformamide gen.  The  103  (1.013 g, 3.35  (100 mL)  disappearance  and  heated  mmol) was  to r e f l u x under  25 mL, water  evaporated  The p r o d u c t 105 was and  under reduced  added t o m e t h y l e n e c h l o r i d e (2x50 mL)  After  methylene c h l o r i d e  3 h,  was  the  pressure to approximately  (150 mL)  and  t o remove m o s t o f t h e r e m a i n i n g  extracted with dimethylformamide.  s o l u t i o n of the d e c a r b o x y l a t e d  d r i e d w i t h anhydrous sodium s u l f a t e ,  added d r o p w i s e  nitro-  o f t h e uv a b s o r p t i o n band a t 28 0 nm  t a k e n as an i n d i c a t i o n o f d e c a r b o x y l a t i o n . s o l u t i o n was  dissolved i n  filtered  to a s o l u t i o n of t o l u e n e - p - s u l f o n i c acid  200 (4.0 g)  i n methanol  over a p e r i o d dark to  (25 mL)  o f 2 h.  for a further  was  allowed solid  neutralized to stand  was  Moi.  allowed  M e t h a n o l ( 7 5 mL)  with  triethylamine  i n the r e f r i g e r a t o r  filtered  : > 280°C  s o l u t i o n was  (450  mL)  to s t i r  i n the  16 h and t h e n e v a p o r a t e d u n d e r vacuum was and  f o r 0.5  added,  the  the m i x t u r e h.  The  was  purple  o f f f r o m t h e g r e e n i s h brown s o l u t i o n  washed w i t h m e t h a n o l  MP  The  a p p r o x i m a t e l y 25 mL.  acid  - methylene c h l o r i d e  to give  7- 7 .-Lit. .  Wt.Calcd. f o r C  382 mg  and  (47.7%).  : 360-366°C  3 2  H gN 3  : 478.3097  4  Found,  by  high  r e s o l u t i o n mass s p e c t r o m e t r y : 478.3093  Anal.Calcd. Found  1  H (s,  NMR  C  NMR  142.29  3 2  H  80.00; H,  : (6, C D C l ) 3  12H,  10.12  1 3  : C,  for C  2-,  8-,  3 g  N  4  : C, 80.29; H,  7.93;  N,  : 1.89  12-,  ( s , 4H, m e t h i n e  N,  11.70;  11.56.  ) t , 12H,  1 8 - C H ) , 4.12 3  J=7.5 Hz, C H C H ) , 2  (q, 8H,  3.66  3  J=7.5 Hz,  CH CH ), 2  3  CH).  : (6, 10% TFA-CDC1 ) 3  : 143.54  ( 1 - , 9-,  11-,  1 8 - C ) , 141.53  97.95  ( 5 - , 10-,  15-,  20-C) , 20.11  11.67  (CH ). 3  8.00;  ( 3 - , 7 - , 13-,  (4-, 6-, (CH CH ), 2  3  14-, 16.42  17-C) ,  16-C),  98.39,  (CH CH ), 2  3  201 Method  B  3-Ethyl-2-[ (3-ethyl-4-methylpyrrol-2-?yl)methyl] -4-methylpyrrole  105  methylene c h l o r i d e of  (200 mL)  s o l u t i o n was under reduced the  acid  filtered  MP  over  to s t i r  pressure  mmol) was  dissolved in  i n methanol  (25  a p e r i o d o f 2 h.  triethylamine.  and washed w i t h m e t h a n o l , y i e l d  solution mL)The  f o r a f u r t h e r 16 h,  t o 50 mL. , m e t h a n o l  n e u t r a l i z e d with  evaporated  (7 5 mL)  added  The p u r p l e 447 mg  and  solid  was  (68.4%).  : > 280°C  Anal. Calcd. Found  E  : C,  (<S,  NMR  (S , 12H, 1  10.13  1 3  (4.3 g)  (475 mL)  allowed  2.74  and added d r o p w i s e t o a  toluene-p-sulfonic acid  methylene c h l o r i d e  1  (706 mg,  -5-formyl  C  NMR  142.29  C  H 3 2  38 4  80.04; H,  N  3  2-,  8-,  :  C  7.91;  C D C 1 ) , 1.89 12-,  '  80-29; H,  N,  8.00;  N,  11.70;  11.76.  ( t , 12H,  J=7 .5 Hz, CH CH_ ),  1 8 - C H ) , 4.12 3  2  (q, 8H,  3.65  3  J=7.5 Hz,  CH CH ), 2  3  (s., 4H, m e t h i n e CH) .  : (6, 10% TFA-CDC1 ) 3  ( 1 - , 9-,  98.35, 97.91 11.67  for  (CH ). 3  11-,  : 143.46  1 8 - C ) , 141.52  ( 5 - , 10-,  15-,  ( 3 - , 7-,  (4-, 6-,  2 0 - C ) , 20.10  13-,  14-,  16-C),  (CH CH ), 2  3  17-C) ,  16.45  (CH CH ), 2  3  202 3.6  SYNTHESES OF CHAIN LINKED B I S PYRROLES  3.6.1  BIS PYRROLE  DIKETONES  88  1,ll-Bis(5-ethoxycarboriyI-2> 4 - d i m e t h y l p y r r o l - 3 - y l ) 1,11-d i oxoundec ane  (n=ll)  Undecanedioic chloride flask  min.  acid  without  a reflux  The m i x t u r e  the vigorous  thionyl  reduced bis  with  tube.  until  excess  (21.4 g , 0.10 moi) and t h i o n y l  (46.3 g, 0.39 moi) were p l a c e d i n a r o u n d  fitted  drying  acid  88a  on a steam b a t h  e v o l u t i o n o f gas s u b s i d e d .  carbon  c h l o r i d e was u s e d  In  was h e a t e d  chloride for 30 The  c h l o r i d e was d r i v e n o f f by e v a p o r a t i o n  pressure with  further  c o n d e n s e r and a c a l c i u m  bottomed  tetrachloride  i n the next  (4x3 0 mL)  under and t h e  stage o f the s y n t h e s i s  purification.  an i c e - c o o l e d 1 - l i t e r  erlenmeyer  flask  fitted  with  203 a Claisen  head, a n i t r o g e n i n l e t  (pressure-equalizing  type)  tube,  a dropping  and a d r y i n g t u b e ,  funnel  were p l a c e d ,  - 2 - e t h o x y c a r b o n y l - 3 , 5 - d i m e t h y l p y r r . o l e (35 g, 0.21 m o i ) , methylene c h l o r i d e  (250 mL) and n i t r o m e t h a n e  (200 mL).  s y s t e m was f l u s h e d w i t h n i t r o g e n and t h e a c i d prepared  (50 mL).  the r e a c t i o n mixture  the a i dof  Anhydrous s t a n n i c c h l o r i d e  (104.2 g , 0.40 moi) was added d r o p w i s e o v e r and  chloride  above was i n t r o d u c e d t o t h e f l a s k w i t h  methylene c h l o r i d e  The  was a l l o w e d  a period of 3 h  to s t i r  f o r a further  4 h  period. The acid  s o l u t i o n was p o u r e d  (10 mL c o n c e n t r a t e d  to  stir  an  emulsion  with  t h e o r g a n i c s o l v e n t s and w a t e r .  allowed  filtrate  set  aside to isolate  (which  w i t h methanol (73.5% f r o m  had now s e p a r a t e d a second  (under  the d i a c i d ) .  to isolate This  under i d e n t i c a l  crop.  solid  and e v a p o r a t e d  a second  reaction  The s o l i d  layers)was was washed  t© g i v e 37.8 g  down u n d e r  c r o p o f 6.3 g  conditions.  and 75.1% were o b t a i n e d ; analytical  two  The o r g a n i c p h a s e o f t h e mother  s y n t h e s i s was r e p e a t e d  hydrof uran-methanol .  into  suction) and.air dried  l i q u o r s was s e p a r a t e d  An  The  form  washed w i t h w a t e r and m e t h y l e n e c h l o r i d e a.nd  the  71.6%  i n 350 mL w a t e r ) and was  f o r 15 m i n c a u s i n g ..the p r o d u c t ..to . s e p a r a t e b u t and  was f i l t e r e d ,  pressure  acid  into dilute hydrochloric  reduced  (12.3%).  twice  on t h e same  First  crop y i e l d s of  a second  scale  c r o p was n o t i s o l a t e d .  sample was c r y s t a l l i z e d  from  tetra-  204  MP  :  Moi.  173.5 - 175.0°C  Wt.Calcd. f o r ^ 9 4 2 2 ° 6 H  N  :  5  1  -  4  2  r e s o l u t i o n mass  spectrometry  Calcd.. f o r C „ H . „ N „ 0 v 2a 42 2 6  Found  : C, 67.71; H, 8.12; N, 5.68.  1  H  NMR  (6, 10% TFA-CDC1 ) 3  protons  : 1.33  3  3  F o u n d , by h i g h  ( b r , 10H, c h a i n 2  2.57  methylene protons  1  3  ;  3  : 204.07  ( e s t e r C=0) , 142.31  ( p y r r o l e C - 4 ) , 122.80  ( q , 4H,  10.15 ( b s , 2H, NH).  (6, 1C% TFA-CDC1 ) 164  2  ( t , 4H, J=7 . 5  3  2  2  C-ll ),  3'-, 9 ' - C H ) ,  m e t h y l e n e p r o t o n s 2'- and 1 0 ' - C H ) , 4.46  J=7 Hz, - 0 - C H - C H ) ,  NMR  methylene  ( t , 6H, J=7 Hz,  ( s , 6H, 4-CH ) , 2.59 ,(s , 6H, 2-CH_ ), 2.86  Hz, c h a i n  C  '  3  4'-, 5'-, 6'-,. 7'-, 8 ' - C H ) , 1.43 (m, 4H, c h a i n  1 3  4  : C, 67.7 0; H, 8.17; N, 5.48;  - Q - C H C H ) , 1.6 9 2  0  : 514.3060.  Anal.  o  3  ( c h a i n C=0, C - l ' and  ( p y r r o l e C - 2 ) , 132.26,  ( p y r r o l e C - 3 ) , 118.49  (pyrrole C-5),  62.34  (ester-6-CH ),  29.37  ( c h a i n m e t h y l e n e s , C - 4 , C-5', C-6', C - 7 , C - 8 ) ,  25.74  (chain methylenes  2  42.27  ( c h a i n CO-CH 1  ( e s t e r - 0 - C H C H ) , 12.94 2  3  2  C-2' and C - 1 0 ' ) , 1  1  C-3' and C - 9 ' ) , 15.43 ( 2 - C H ) , 14.23 3  (4-CH ). 3  205 Mass  spectrum  Relative  m/e  Intensity  514  (%)  Assignment  23  M  +  OH  72  209  H  J  L  0C\  194  148  R  K B r  )  0  ^CH  3  100  oc  I  H  CH->  87  :  3290  (N-H), 1650  (C=0) cm  1  .  1 , 1 0 - B i s (5-e t h o x y c a r bony 1 - 2 ,4-d ime t h y l p y r r o 1- 3-y 1)' 1,10-dioxodecane  (n=10)  Decanedioic Eastman Kodak C h e m i c a l  acid  88b  (sebacic  Company  a c i d ) was o b t a i n e d  and was  found  t o be  from  suitable  206 for  use without The  further p u r i f i c a t i o n .  b i s acid  were s y n t h e s i z e d  chloride  according  to the procedure given  analogous undecane d e r i v a t i v e stannic and  chloride  the y i e l d  A second  and t h e b i s p y r r o l y l  were u s e d  88a.  f o r the  Four e q u i v a l e n t s of  f o r the a c y l a t i o n  of the f i r s t  diketone  c r o p was 79.2%  reaction  (from  the d i a c i d ) .  c r o p was n o t i s o l a t e d . An a n a l y t i c a l sample was c r y s t a l l i z e d  from t e t r a -  hydrofuran-methanol.  MP  :  158.5 - 159.5°C  Anal.Calcd. Found  1  H  4.'-, 5'-, 6'-,  3  0 - C H - C H ) , 10.15 2  C  ( b r , 8H, c h a i n  7 ' - C H ) , 1.43 2  (m, 4H, c h a i n m e t h y l e n e p r o t o n s 6H, 4 - C H ) , 2.59  (pyrrole 62.16  1  1  2  3  Hz,-0-CH CH ), 2  2  : 203.68  ( e s t e r C=0), 141.94  C - 4 ) , 122.79  (pyrrole  0 - C H ) , 42.27 0  (chain  (pyrrole  C - 3 ) , 118.42  (chain  C0CH  2.57  ( q , 4H, J=7 Hz,  C=0) , C - l ' and C - 2 ) , 131.96 (pyrrole C-5),  C-2' and C - 9 ) , 1  o  3  ( t , 4H, J=7.5 Hz,  2'- and 9 ' - C H ) , 4.45  3  (ester  3 -,8 -CH ),  ( s , 6H, 2-CH >, 2.86  (6, 10% TFA-CDC1 )  C - 1 0 ' ) , 163.76  ( t , 6H, J=7  methylene  ( b s , 2H, NH).  3  NMR  5.59  5.55.  : 1.33  3  c h a i n methylene protons  1 3  : C, 67.18; H, 8.05; N,  N  .. (6, 10% TFA-CDC1 )  protons  (s,  H  2  : C, 67.07; H, 7.88; N,  NMR  1.66  for C 8 40 2°6  207 29.41  (chain  C-4' and C-7 ' ) , 29.24  25.58  (chain  C - 3 , C - 8 ) , 15.39  12.89  (4-CH ).  1  1  (chain  (2-CH ), 3  C-5',  14.23  C-6'),  (ester  -0-CH -CH ),  3  Mass s p e c t r u m  : Relative  m/e  Intensity  500  26  (%)  Assignment M  +  ®  OH  20 9  71  H  2  C -  A  C  X /  Y  c  h  3  -  194  148  1, g-Sl-s'T'S-'-'e't-hd'xyc-'arrKDny 1-2,4 -dime t h y l p y r r o 1 -3 -y 1) -1,9dioxononane  (n=9)  Technical mp  88c  grade n o n a n e d i o i c a c i d  93-96°C) was o b t a i n e d  (azelaic acid,  f r o m Eastman Kodak C h e m i c a l  Company  2  3  208 and  recrystallized  p o i n t of the literature  value  of  the  as  yield  diacid.  described  (1 moi  of  of  The  equivalents  sample was  of  the  instances,  bis pyrrolyl  undecane  first  crop  was  first  crop  repeated  using  c h l o r i n e of  yield  analogue,  only  the  o f 7 9.6%.  were n o t  analytical  diketone  from  two  a c y l a t i o n step  each showing a s i n g l e spot  second c r o p s An  the  69.1%, s t a r t i n g  of s t a n n i c c h l o r i d e f o r the  were i d e n t i c a l ,  melting  s t a n n i c c h l o r i d e f o r the a c y l a t i o n  s y n t h e s i s was  i n the  The  1 0 1 ° C , 5° below  the  f o r the  stannic chloride/atom  resulting  acid.  106°C.  four equivalents The  formic  b i s a c i d c h l o r i d e and  were s y n t h e s i z e d  step.  from hot  recrystallized  The  using  twice  acid chloride)  The on  two  tic.  samples In  both  isolated.  sample was  crystallized  from  hot  dimethylformamide.  MP  : 173.0  -173.5°C  "- _  Anal.  Calcd.. f o r 2 7 3 8 2 ° 6  Found  : C,  C  NMR  1.69 (s,  66.34; H,  (6, 10%  protons  1  (m, 6H,  H  N  7.82;  :  C  '  N,  TFA-CDC1 ) 3  6  '  6  4  H,  ;  : 1.36  2  ( b r , 6H, ( t , 6H,  c h a i n methylene protons  4 - C H ) , 2.59 3  ( s , 6H,  c h a i n methylene protons  2'-  7.87;  N,  5.76.  5.69.  4'-,5'-, 6 ' - C H ) , 1.43 4H,  6  2-CH ) 3  and  #  J=7  - 3'2.87  chain Hz, and  0-CH CH ), 2  3  7'-CH ), 2  ( t , 4H,  8 ' - C H ) , 4.46 0  methylene  J=7.5  (q, 4H,  J=7  2.57 Hz, Hz  -0-CH CH ), 2  1 3  C  NMR  3  10.15  ( b s , 2H, NH).  (<5, 10% TFA-CDC1 ) 3  : 203.79  163.95  ( e s t e r C=0) , 142.25  122.78  ( p y r r o l e C - 3 ) , 118.49  0 - C H ) , 42.23 2  C-5', C - 6 ' ) , 14.23  ( p y r r o l e C - 2 ) , 132.19  (pyrrole  ( p y r r o l e C - 5 ) , 62.32  (chain  2  25.57  ( c h a i n - C-3' and C-7') , 15.44 2  3  12.94  (2-CH ), 3  (4-CH ). 3  : Relative  m/e  Intensity  486  24  209  77  (%)  Assignment M  +  ®  0 H  H C^ \  ^CH  C  2  H  148  87  0  C-4)  (ester  ( c h a i n C 0 C H . C-2' and C-8 ' ) , 29.32  (ester -0-CH -CH ),  Mass s p e c t r u m  ( c h a i n C=0, C - l ' and C-9*)  3  C-4',  210 3.6.2  BIS PYRROLE ETHYL ESTERS  69  1 , 1 1 - B i s ( 5 - e t h o x y c a r b o n y l - 2 4 - d i m e t h y l p y r r o l - 3 - y l ) undecane ;  /  (n=ll)  89a  1,11-Bis(5-ethoxycarbonyl-2,4-dimethylpyrfol-3-yl) 1 , 1 1 - d i o x o u n d e c a n e 8_8 (32.0 g , 62.3 mmol) a n d d r y t e t r a d hydrofuran fitted  (300 mL) were p l a c e d  with  in a 1-liter  a C l a i s e n adapter, a nitrogen  erlenmeyer  inlet  (connected  t o t h e s i d e arm o f t h e C l a i s e n a d a p t e r ) ,  a dropping  (pressure  chloride  tube.  e q u a l i z i n g t y p e ) and a c a l c i u m  drying  The f l a s k was i c e - c o o l e d and t h e m i x t u r e was  stirred  under n i t r o g e n .  (The s t a r t i n g m a t e r i a l  funnel  magnetically  d i d not dissolve  fully).  Sodium b o r o h y d r i d e  (5.0 g , 132.3 mmol) was a d d e d ,  followed  by t h e c a r e f u l d r o p w i s e a d d i t i o n o f b o r o n  fluoride  etherate  (30 mL, 238.1 mmol).  tri-?  The r e a c t i o n m i x t u r e  appeared as a b u f f c o l o r e d  e m u l s i o n and was c h e c k e d by t i c  for  material.  any u n r e a c t e d  starting  211 Acetic diborane water  (200 mL).  crude  (100 mL)  (carefully, while  went c l e a r  was  acid  As w a t e r was  crystallized  gravity  the s o l u t i o n  g,  give  a f u r t h e r 1.2  filtered  and c o n c e n t r a t e d  (82.9%).  undecane  The mother g,  yield  o f 83.5% was  was  recrystallized  MP  :  was  solid  phase  after  adding  collected  by  i n a i r to give  l i q u o r s were c o n c e n t r a t e d  repeated  to  on t h e same s c a l e and  obtained.  from methylene  An a n a l y t i c a l  an  sample  chloride-methanol.  11.5.0 -116. 5°C  Wt.Calcd.  for  C  9 46 2°4 H  2  N  :  r e s o l u t i o n mass s p e c t r o m e t r y  Anal. Calcd. Found  : C,  NMR  5'-,  first  (4.0%).  T h i s r e a c t i o n was  'MoT.  excess  by  The  the o r g a n i c  washed w i t h m e t h a n o l and d r i e d  25.1  (6, C D C 1 ) 3  9.54;  N,  8'-,  9'-,  CH -CH ),  2.14  ( s , 6H,  6  -  3  4  5  8  "  F o u n d , by  high  71.60; H,  (m, 18H,  10'-CH ), 2  2-CH ), 3  9.47;  N,  5.76;  5.85.  : 1.08-1.58  7'-,  3  8  : C,  n  71.60; H,  4  : 486.3452  for C„ H N O. zy 46 2 4  6'-,  2  added,  the  followed  o u t as a w h i t e s o l i d .  The b i s ( p y r r o l y l )  filtration,  overall  to destroy  passing nitrogen)  d i s s o l v e d i n methylene c h l o r i d e ,  methanol.  H  added  ( p a l e brown c o l o r ) and w i t h more w a t e r , t h e  product  isolated,  1  was  2.22  1.31  chain  2'-,  ( t , 6H,  ( s , 6H,  J=7  3'-, Hz,  4 - C H ) , 2.18 3  4'-, -0~ -  212 2.44  (m, 4H, c h a i n  1 -CH 1  2  and l l ' - C F ^ ) ,  4.25  (q, 4H, J=7 Hz,  -6CH CH ), 8.7 3 ( b s , NH). 2  1 3  C  3  NMR  126.99  (6, C D C 1 ) 3  (pyrrole  : 162.24  (C=0), 130.04  4 - C ) , 122.36  (pyrrole  59.56  (-OCH CH ), 30.95  (chain  3'-C,  4'-C,  5*-C,  6'-C,  7'-C,  ll'-C),  14.64  (-o-CH -CH ),  and  Mass  2  3  2  3  2 -C 1  3 - C ) , 116.76 and l O ' - C ) ,  8 '-C, 9'-C), 11.41  ( p y r r o l e 2-C),  29.69  24.10  (chain  (chain  ( 2 - C H ) , 10.73  1 -C 1  (4-CH ).  3  3  spectrum Relative Intensity  m/e 486  65  440  86  180  100  (%)  Assignment M  +  (M-CH CH OH) 3  2  0  134  IR  ( p y r r o l e 5-C),  K B r  )  :  3330  (N-H), 1675  (C=0) cm  +  213 1 , 1 0 - B i s (5-ethoxycarbony!-2">4.-d^ (n=10)  89b  The  diketone  88b  (38.0 g, 7 6 mmol) was r e d u c e d  d i b o r a n e , g e n e r a t e d by sodium b o r o h y d r i d e boron t r i f l u o r i d e the  etherate  procedure given  (40 mL,  an  overall  MP  :  yield  Found  first  c r o p o f 0.7 g were o b t a i n e d f o r  .  for C 8 44 2°4 H  N  2  3  7'-, 8'-,  : C, 71.15; H, 9.138; N,  : 1.12-1.60  5.92  8.81  ( b s , NH).  NMR  127.05 5-C),  : (6, CDC1 ) (pyrrole  (chain  3'-C, 4'-C,  (m, 4H, 2  (C=0), 129.49 (pyrrole  (-OCH CH ), 30.88  and l O ' - C ) ,  (4-CH ).  4 - C ) , 122.42 2  3  (chain  3  2.14 chain  (-0-CH CH ), 2  3  3  ( p y r r o l e 2-C),  3 - C ) , 116.79  (pyrrole  2'-C and 9'-C),  5 *-C , 6 '-C, 7 *-C, 8'-C), 24.06  14.62  4'-  ( q , 4H, J=7 Hz, -0-CH_ -CH ),  : 161.84  3  59.52  3  3  2  3'-,  1  2  (s , 6H, 4 - C H ) , 2.20-2.48  and 1 0 ' - C H ) , 4.26  2" ,  ( t , 6H, - 0 - C H - C H ) ,  2  3  2  (m, 16H, c h a i n  9 ' - C H ) , 1.30  6H, 2 - C H ) , 2.20  l'-CH  l'-C  A  o f 85.9%.  : (6, CDC1 )  5'-, 6'-,  C  88a.  : C, 70.89; H, 9.41; N, 5.70.  '''H NMR  1 3  317 mmol), a c c o r d i n g t o  143.0 - 144.0°C  Anal.Calcd.  (s,  (7.5 g , 198 mmol) and  f o r t h e undecane analogue  c r o p o f 3 0.1 g and a s e c o n d  with  11.47  (2-CH ), 3  29.62  (chain 10.62  214 Mass  Spectrum  Relative  m/e  Intensity  472  62  426  88  180  (%)  Assignment M  +  (M-CH CH OH) 3  100  H  2 C \ _ - ^  +  2  C  H  3  134  1, 9 - B i s ( 5 - e t h o x y c a r b o n y l - 2 , 4 - " d i m e t h y l p y r r o T - 3 - y I ) nonane(n=9)  89c  The  diketone  88c (30.3 g , 62.3 mmol) was  as d e s c r i b e d f o r t h e undecane a n a l o g u e borohydride  (5.0 g, 132.3 mmol) and b o r o n  (30 mL, 238.1 mmol). crystallized (69.3%). of  The c r u d e  sodium  trifluoride  p r o d u c t was i s o l a t e d  etherate and r e -  from m e t h y l e n e c h l o r i d e - m e t h a n o l t o g i v e 19.8 g .  The r e a c t i o n was r e p e a t e d w i t h  the diketone  obtained.  88a, u s i n g  reduced  88c and an o v e r a l l  yield  77.0 g  (158.4 mmol)  o f 55.1 g  (75.9%) were  215 MP  :  Anal  132.0 - 133.0°C  : Calcd.  Found  1  H  (s,  : ( 6 , CDC1 ) 3  N  :  C  : 1.12  7 0  -  7 0  '*  H  '  9  -  2 3  "  '  N  - 1.60  (m, 14H, c h a i n 2  3'-, 2.14  3  (m, 4H,  3  2  2'-,  ( t , 6H,-0-CH CH ),  ( a , 6H, 4 - C H ) , 2.18-2.48  and 9 ' C H ) , 4.26  6.11.  6.04.  2  3  2  '  7'-, 8 ' - C H ) , 1.29  6H, 2 - C H ) , 2.22  (bs,  C  H  2  5'-, 6'-,  l'-CH  1 3  C  : C, 7 0.4 0; H, 9.22; N,  NMR  4'-,  for 7 42 2°4  ( q , 4H, J=7 Hz, O - C H - C H ) , 2  chain  8.77  3  NH).  NMR  127.00  : ( 6 , CDC1 ) 3  (pyrrole  : 162.04  4 - C ) , 122.37  (C=0), 129.75 (pyrrole  59.55  (-OCH_ CH ), 30.90  (chain  3'-C,  4"-C,  7 ' - C ) , 24.06  14.59  (-0-CH -CH ),  2  3  5'-C, 2  Mass s p e c t r u m  3  6'-C,  11.43  ( p y r r o l e 2-C),  3 - C ) , 116.78  ( p y r r o l e 5-C),  2 '-C and 8 ' - C ) , 29.61 (chain  (2-CH >, 10.66 3  1 -C  and  1  (chain 9'-C),  (4-CH ). 3  : Relative  m/e  Intensity  458  61  412  87  134  86  (%)  Assignment M  +  (M-CH CH OH) 3  2  +  216  3.6.3  B I S PYRROLE  BENZYL  ESTERS  90  1,ll-Bis(5-benzyloxycarbonyl-2,4-dimethylpyrrol-3-yl)undecane  (n=ll)  90a  1,ll-Bis(5-ethoxycarbonyl-2,4-dimethylpyrrol-3-yl)undecane  89a  (125  were heated  in  mL)  a 5 0 0 mL  reached in  (24 g , 4 9.4  benzyl steady  a  simultaneous  flask.  temperature,  flow of nitrogen. drop  ion  o f 3 mL  When t h e b e n z y l  a concentrated  and  t h e r e a c t i o n was The methanol  stirring,  solution  vapours were  temperature.  of  sodium  maintaining  liberated After  c o u l d be  with  the addit-  observed  complete. was p o u r e d  t o quench  flask  was w a s h e d w i t h b e n z y l  until  the i n i t i a l  for" 5 min causing  alcohol  alcohol  portions while  no e f f e r v e s c e n c e  hot solution ( 5 0 0 mL)  Ethanol  i n the reflux  of catalyst,  benzyl  n i t r o g e n , with magnetic  a l c o h o l w a s a d d e d , i n 1 mL  a  in  under  erlenmeyer  reflux  mmol) a n d r e d i s t i l l e d  solid  into  acetic  the catalyst  alcohol.  was o b s e r v e d  the precipitate  acid  ( 2 0 mL)  and t h e r e a c t i o n  W a t e r was a d d e d and then  allowed  t o thicken.--More  slowly, to  water  stir  217 was a d d e d , s t i r r e d by  filtration  (the s o l i d  to darken with washed w i t h  f o r 5 m i n u t e s and t h e p r o d u c t was was p a l e  pink  i n color  time, p r i o r to f i l t r a t i o n ) .  collected  and was  observed  The d i b e n z y l  50% m e t h a n o l - w a t e r and a i r d r i e d , w e i g h e d ,  ester,  28.4 g .  (94.3%) . This ester  reaction  89a t o y i e l d  was r e p e a t e d w i t h  89.3% o f t h e d i b e n z y l  sample was r e c r y s t a l l i z e d f r o m  MP  :  C  r e s o l u t i o n mass  A n a l .-Calcd.. Found  H  N 0  2 4 O  :  spectrometry  for  . C  (6, CDC1 )  H  3 9  7'-, 8'-,  9'-,  2.20-2.52  3  ( s , 4H, O-CH  NMR  5 Q  6 1  0 .37-71; .Found"-by h i g h  N 0 2  :  4  (pyrrole  H, 8.25;  N,  ( b r , 18H, c h a i n 2  2'-, 3'-, 4'-,  ( s , 6H, 2 - C H ) , 2.29 3  1 -CH  5'-, ( s , 6H,  and l l ' - C B ^ ) , 5.31  1  2  (m, 10H, C , H ) , 8.67 C  ( b s , NH).  D—~> : 161.68  (C=0), 136.77  2 - C ) , 128.46, 127.91 (pyrrole  (-OCH_C,H ) , 30.85  3'-C,  4'-C,  5'-C,  6'-C,  ll'-C),  11.37  ( 2 - C H ) , 10.84  c  (chain 7'-C,  3  2 -C 1  8'-C,  -•  (benzene C - l ) ,  (benzene r i n g ) ,  3 - C ) , 116.37  65.30  Z o o  4.59,  4.69.  1 0 ' - C H ) , 2.18  4 - C ) , 122.50 —  C, 76.69;  b 5  3  rr -  : 610.3790  ) , 7.22-7.56  (6, CDC1 )  (pyrrole  and  An a n a l y t i c a l  tetrahydrofuran-methanol.  (m, 4H, c h a i n  -C,H  —z  130.37  : 1.27  3  4-CH ),  C  H  : C, 76.61; H, 8.29; N,  NMR  6'-,  1 3  ester.  108.5 - 110.5°C  Moi .Wt.- C a l c d . ' f o r 3 9 5  1  23 g. o f t h e e t h y l  ( p y r r o l e 5-C),  and l O ' - C ) , 9'-C), 24.02  (4-CH ). 3  127.52  29.61 (chain  (chain 1'-C  218 Mass  spectrum  :  Relative Intensity  m/e 610  37  502  22  242  19  (%)  Assignment M  +  (M-C H CH OH) 6  H  —  (v  'max  108  22  91  100  K  B  r  )  :  3  3  2  0  (  N  -  H  )  '  1  6  7  5  0  (C H CH OH) 6  5  C  0  (  C  =  0  )  c  m  +  2  +  2  7 7 H  +  1  1,10-Bis(5-benzyloxycarbonyl-2,4-dimethylpyrrol-3-yl)-Decane (n=10)  90b  The benzylated described was 28.9 g from  ethyl  e s t e r 8 9b  (24.0g,  i n r e d i s t i l l e d benzyl previously. (95.4%).  The y i e l d  a l c o h o l (125ml)  trans-  i n t h e manner  o f t h e b i s b e n z y l e s t e r 90b  An a n a l y t i c a l  tetrahydrofuran-methanol.  50.8 mmol) was  sample  was  recrystallized  219 MP  142.5-144.0 C  A n a l . Calc.d.Found  1  H  C  H 3  8  N 4  8  :C,76.59;H,  NMR-,  6'-,  for  0  :  C  '  76.48; H, 8.11; N, 4.69;  8.30;N,'4.60.  (6, CDC1 )  : 1.27  3  7'-, 8'-,  2 4  9'-CH  ( b r , 16H, c h a i n  ) , 2.17  (s , 6H, 2-CH  ^ 4-CH ), 3  2.18-2.55  4H,  1 3  C  (m, 4H, c h a i n  ) , 7 .25-7.55  NMR  1'-CH  (s , 6H,  and 1 0 ' - C H ) , 5.31 (S,  2  2  (m, 10H, C H .) , 8.63 r  (bs,-NH).  c  D—D  (6, CDC1-J  : 161.53  (C=0), 136.83  ( p y r r o l e 2 - c ) , 128.49, 128 .01 122.57  ) , 2.29  (pyrrole 3-c),  116.41  (benzene 1 - C ) , 130.05  (benzene r i n g ) , (pyrrole  127.64  5 - C ) , 65.37  (pyrrole  (chain  6'-C,  7'-C,  10.78  2'-c 8'-C),  and 9'-C), 24.04  29.61  (chain  (chain  1'-C  3'-C,  c  4'-C,  and l O ' - C ) ,  Z  O  11.48  (2-CH ), 3  3  Mass s p e c t r u m m/e 596  43  488  29  24 2  21  (%)  Assignment M  +  (M-C H CH OH) 6  ^CH  i  H  108  27 100  2  3  0  (C H CH 0H) c  D  91  5  c  o  D C  Z  7 7 H  +  3  5'-C,  (4-CH ).  Relative Intensity  4-C) ,  (-OCH„C,H ), —  30.88  5'-,  3  O D  —Z  2'-, 3'-, 4'-,  +  +  220  1-9-Bis(5-benzyloxycarbonyl-2,4-dimethylpyrrol-3-yl)-nonane (n=9)  90c  The  b i s ethyl ester  transesterified  i n benzyl  the  undecane analogue.  was  18.0 g ,  of  MP  :  Anal.  E  This  120-121. 5°C  as d e s c r i b e d f o r  o f the b i s benzyl  and 2 50 mL b e n z y l  alcohol  for  y _•  C  7 46 H  3  N  0 2  4  :  c  (<5, C D C 1 )  : 1.28  3  >  7 6  - 2 6 ; H, 7.96; N,  ( b r , 14H, c h a i n  2.24-2.50  (m, 4H, c h a i n  l'~CH  :  2  0-CH--C.HJ , 7.28-7.52  NMR  (6, CDC1 ) 3  (chain  2  and 9 ' - C H ) , 2  (m, 10H, C H ) e  c  (C=0),  4 - C ) , 122.52  3'-C,  9'-C), 11.44  6  5  4 -C,  5'-C,  1  (chain 6'-C,  ( 2 - C H ) , 10.77 3  8.62  2'-C  3  5.31  5'-,  4-CH ), 3  ( s , 4H,  ( b s , NH).  (benzene 1 - C ) , 127.61  ( p y r r o l e 5-C),  and 8'-C),  7 ' - C ) , 24.03  (4-CH ).  ( s , 6H,  (benzene r i n g ) ,  ( p y r r o l e 3 - C ) , 116.39  ( 0 - C H C H ) , 30.84 2  f  136.85  ( p y r r o l e 2 - C ) , 128.49, 127.93  (pyrrole 65.33  3  : 161.57  4.81.  2'-, 3'-, 4'-,  ( s , 6H, 2 - C H ) , 2.29  130.16  to give  4.79.  8 - C H ) , 2.18  C  55.0 g  ..  7'-,  1 3  ester  r e a c t i o n was r e p e a t e d w i t h  : C, 7 6.18; H, 7.99; N,  NMR  6'-,  (120 mL)  (94.0%) o f t h e t r a n s e s t e r i f i e d p r o d u c t .  Calcd.  Found  (16.0 g , 34.9 mmol) was  alcohol  The y i e l d  the s t a r t i n g m a t e r i a l  65.7 g  X  (88.7%).  8 9c  29.53  (chain  1 -C 1  and  Mass  spectrum  Relative  m/e  Intensity  582  39  474  27  (M-C H CH OH)  24  22  Hjtx  2  Assignment M  +  6  /CH  H  108  26  91  100  5  2  3  0  (C H CH OH) 6  C  7 7 H  5  +  2  +  222 1,ll-Bis(5-formyl-2,4-dimethylpyrrol-3-yl)undecane  The bis  benzyl  benzyl  ester  90a  of  intermediate  the  i n the The  the  resulting  and  techniques  a much h i g h e r r ^ v a l u e  fore  the  sample o f  dicyanovinylpyrrole sample o f p u r e  94a  hydroxide  using  material,  yield  t h i s manner was  MP  :  133.5  -  94a. was  92a  the  were n o t  i s not  isolated.  The  r e a c t i o n s are  des-  readily  93c.  purified  purified.  converted  by  derivative,  There-  was  For  c h a r a c t e r i z a t i o n purposes,  deprotected  to the  i n aqueous  to s o l u b i l i z e  •••  bis a  potassium  the  bis formylpyrrole  analytically  Vilsmeier  The  93a  The  the  the  and(iii)the  nonane a n a l o g u e  is easily  a n-propanol 98%.  of  whereas i t s d i c y a n o v i n y l  with  from  p y r r o l e 92a.  c o n d i t i o n s f o r these  crude dialdehyde  entire  above p r o d u c t  bis-a-free  preparation of  chromatographic  compound, s t a r t i n g  starting  93a  prepared  pure.  135.0°C  Mol.Wt.Calcd.  for  C  5 38 2°2 H  2  N  r e s o l u t i o n mass s p e c t r o m e t r y  Anal.  Calcd. for C ^ H ^ N ^  Found  : C,  75.27; H,  9.88;  93a  bis-carboxypyrrole 91a,(ii)the  of  compounds 91a  experimental  cribed  the  decarboxylation  formylation  this  involved,(i)the hydrogenolysis  e s t e r to produce  thermal  ideal  preparation of  (n=ll)  :  3  9  8  -  2  9  3  3  ;  F o u n d , by  high  : 398.2934  : C, N,  75.33; H,  7.20.  9.61;  N,  7.03;  in  223  1  H  NMR. , (6, CDC1 ) 3  : 1.26  ( b r , 18H, c h a i n  5'-, 6'-, 7'-, 8'-, 9'-, 1 0 ' - C H ) , 2.27  ( a , 12H, 2-CH  2  4-CH ), 3  (s,  1 3  2.27 - 2.49  2H, HCO),  C  NMR  132.71  -  9.84  (m, 4H, c h a i n  2  3  and l l ' - C B ^ ) ,  and 9.50  ( b s , 2H, NH).  (6, C D C 1 ) 3  (pyrrole  1'-CH  2'-, 3'-, 4'-,  : 175.52  4 - C ) , 127.87  (C=0), 136.74  (pyrrole  ( p y r r o l e 2-C),  5 - C ) , 123.44  ( p y r r o l e 3-C),  30.61  (chain.  2 - C and l O ' - C ) ,  29.59  (chain  3'-C, 4'-C,  5'-C,  6'-C, 7'-C, 8'-C, 9'-C),  23.76  (chain  1'-C and  11,61  (2-CH ),  Mass  3  1  8.87  (4-CH ). 3  spectrum Relative m/e  Intensity  (%)  398  22  M  370  23  (M-CO)  108  IR  (v•  Assignment  , KBr)  : 3240  (N-H),  1640 (C=0) cm  +  +  ll'-C),  224  1,10-Bis(5-formyT-2,4-dimethylpyrrol-3-yl)decane  (n=10)  93b  1,10-Bis(5-benzyloxycarbonyl-2,4-dimethylpyrrol-3yl)  d e c a n e 9Ob was c o n v e r t e d  t o the dialdehyde  manner d e s c r i b e d f o r t h e nonane a n a l o g u e . sample was p r e p a r e d anovinylpyrrole  MP  ':  Moi.  by t h e d e p r o t e c t i o n o f t h e p u r e b i s d i c y -  94b i n a q u e o u s p o t a s s i u m  Calcdi, for 4 3 6 2 ° 2 C  N  mass s p e c t r o m e t r y  • A n a l . •. C a l e c k - ' f o r C  H  H  :  H 2  4  :  N 3  6  2  °  ; (6, C D C 1 ) 3  : 1.27  (m, 4H, c h a i n 1'-CH  HC=0), 9.98  ( b s , 2H, NH).  NMR  •••  (<5, C D C 1 ) 3  :  2 7 7 7  "  F o u n d , by h i g h  ( s , 12H, 2-CH  (chain  and 4 - C H ) , 3  2  (C=0) , 136.51  (chain  (chain  ( s , 2H,  ( p y r r o l e 2-C),  ( p y r r o l e 5 - C ) , 123.46  2'-C and 9'-C), 29.58  (4-CH-,) .  3  and 1 0 ' - C H ) , 9.44  2  175.53  ( p y r r o l e 4 - C ) , 127.88  6'-C, 7'-C, 8 ' - C ) , 23.77 8 . 87  •  ( b r , 16H, c h a i n 2'-, 3'-, 4'-,  2.26 - 2.48  30.60  4  : C, 74.66; H, 9.57; N, 7.15.  NMR  132.63  8  : C , 74.96; H, 9.44; N, 7.28;  2  2  C  hydroxide.  384.2773  5'-, 6'-, 7'-, 8'-, 9 ' - C H ) , 2.20  1 3  3  2  resolution  1  analytical  170.0 - 170. 5°C  Wt.  Found  An  93b i n t h e  ( p y r r o l e 3-C),  3'-C , 4'-C , 5 ' -C ,  1'-C and l O ' - C ) , 11.63  (2-CH ), 3  225 Mass  spectrum Relative m/e  Intensity  384  29  356  31  136  100  (%)  Assignment M  +  (M-CO)  Vx/" 3  H  +  3  Q  70  108  HjC  1,9-Bis(5-£ormyl-2,4-dimethylpyrrol-3-yl)nonane  (i)  (n=9)  93c  Debenzylation 1,9-Bis(5-benzyloxycarbonyl-2,4-dimethylpyrrol  -3-yl)  nonane  charcoal  ( 1 . 5 g) w e r e  atmosphere) of  9 0 c ( 2 0 . 0 g , 34.4 mmol) a n d 1 0 % p a l l a d i u m o n  i n tetrahydrofuran  triethylamine.  catalyst checked  stirred  When  was f i l t e r e d  o v e r n i g h t under  hydrogen  (1  ( 1 5 0 mL) c o n t a i n i n g 5 d r o p s  the uptake  o f hydrogen  through a c e l i t e  by t i cf o r any unconverted  plug  starting  s o l v e n t was e v a p o r a t e d o f f , i n v a c u o ,  ceased, the  and t h e s o l u t i o n material.  The  leaving the b i s carboxy-  226 pyrrole  91c  as a p a l e  yellow s o l i d .  u s e d , as i s , i n t h e n e x t  (ii)  dissolved  nitrogen  showing  crude b i s - c a r b o x y p y r r o l e  flask  inlet.  methylene  chloride  and  two  this  hours but a f u r t h e r  the next  (iii)  Vilsmeier  half  hour  with recorded,  dimethyl-  temperature  e v e r y 0.5 t h e uv  was  s o l u t i o n was  h, a d r o p  (153°C) was  spectrum r e c o r d e d .  reduced  to j u s t  a shoulder  o f h e a t i n g d i d n o t remove  cooled  i n i c e and  used i n  formylation. ice-cooled  i n d r y methylene  oxychloride  (35 mL)  The V i l s m e i e r  was  solution  chloride added  the b i s a - f r e e complete,  of  dimethylformamide  (150 mL),  pyrrole  stirred.  treated,  dimethylformamide  92c p r e p a r e d a b o v e .  t h e s o l u t i o n was  phosphorous  and m a g n e t i c a l l y  r e a g e n t p r e p a r e d t h u s , was  and d r o p w i s e , w i t h t h e c h i l l e d  was  and  The  a  reaction.  To an (40 mL)  chloride  a t A - 2 8 6 nm.  The  s p e c t r u m was  heated a t i t s r e f l u x  i n t o methylene  diluted  nm.  was  i n a 5 00  a d a p t e r and  a t A 286  t u r n e d d a r k brown) and  completely.  placed  s o l u t i o n was  a b s o r p t i o n band  a b s o r p t i o n band  and  with a Claisen  a uv a b s o r p t i o n  s o l u t i o n was  (the s o l u t i o n removed  fitted  p r e p a r e d above  (15 0 mL)  A drop of t h i s  a single  formamide  in  was  reaction.  i n dimethylformamide  erlenmeyer  The  crude product  Decarboxylation. The  mL  The  stirred  rapidly solution  Once t h e  for a further  of  addition half  227 hour  to ensure  chloride and  was  the c o m p l e t i o n of the r e a c t i o n .  removed by  the s o l u t i o n  stirring, and  was  e v a p o r a t i o n under r e d u c e d  poured  onto  crushed  Solid  s o d i u m b i c a r b o n a t e was  until  the  then heated  on  The  solution  was  (500  g.).  t o pH-paper  (the s o l u t i o n  t o be  pressure  added, c a r e f u l l y , w i t h  weakly b a s i c  t h e steam b a t h  a g a i n and more b i c a r b o n a t e had  ice  methylene  added).  became a c i d i c  A dark  brown  phase s e p a r a t e d o u t a t the bottom, c o n t a i n i n g the p r o d u c t , i n dimethylformamide was  c o n t i n u e d on  evaporated  particles, on  t h e steam b a t h and  hot  t h e steam b a t h . turned t u r b i d  The  h e a t i n g was  solid  was  filtered  was  was  filtered  t o remove a few  dried  When t h e t e m p e r a t u r e and  a grey colored  washed w i t h w a t e r .  i n a i r over  several  brown  w i t h w a t e r and reached  solid  continued for a further  and  chloride  brown s o l u t i o n (one "phase) was" o b t a i n e d .  solution  out.  Heating  as t h e m e t h y l e n e  t h e volume a d j u s t e d t o 14 00 mL  the s o l u t i o n  93c  unremoved m e t h y l e n e c h l o r i d e .  off, a clear The  heated  and  crude  d a y s t o g i v e 11.8  7 5°C,  separated  3 0 min,  The  re-  the product  g.  (93%) . In  several  p r e p a r a t i o n s , the y i e l d s  p r o d u c t were between 90-100%. crude of  solid  was  the aldehyde  sample was  used  The  dicyanovinylpyrrole  sample o f  f o r the next r e a c t i o n ,  as t h e d i c y a n o v i n y l  prepared  entire  by 94c  of the  the  derivative.  crude the  protection An  analytical  the d e p r o t e c t i o n of the pure b i s i n aqueous p o t a s s i u m  hydroxide.  228 MP  :  165.0 - 165.5°C  Moi.  Wt.  Calcd.  high  r e s o l u t i o n mass s p e c t r o m e t r y  A n a l . •-. C a l c d ; Found  E  :  NMR  1  for23 34 C  (6, C D C 1 ) 3  (m, 4H, c h a i n  9.96  ( b s , 2H, NH).  NMR  132.60  (5, C D C 1 ) 3  (pyrrole  (pyrrole (chain 11.60  0 2  2  370.2620;  :  F o u n d , by  : 37 0.2625  : C, 74.56; H, 9.25; N, 7.56;  C, 74.57; H, 9.21; N, 7.64.  2.42  C  N  forC ^ H ^ N ^  5'-, 6'-, 7'-, 8'-CH  1 3  H  :  1.26  ) , 2.21  1'-CH  ( s , 12H, 2-CH 2  : 175.52  3 0.58  3  Mass s p e c t r u m m/e  3  ( s , 2H, HC=0),  (C=0), 136.61  (pyrrole (chain  ( p y r r o l e 2-C),  5 - C ) , 123.43 •  2'-C and 8 ' - C ) , 29.51  3'-, 4'-, 5'-, 6'-, 7 ' - C ) , 23.74 ( 2 - C H ) , 8.86  2'-, 3'-, 4'-,  and 4 - C H ) , 2.22 -  3  and 9 ' - C H ) , 9.38  2  4 - C ) , 127.89  3-C),  ( b r , 14H, c h a i n  (chain  1'-C and 9'-C),  (4-CH ). 3  : Relative Intensity  370  26  342  25  (%)  Assignment M  +  (M-CO)  +  229 Relative m/e  Intensity  108  (%)  Assignment  73  Ti  1,8-Bis(5-formyl-2,4-dimethylpyrrol-3-yl)octane  (n=8)  93d  1,8-Bis(5-benzyloxycarbonyl-2,4-dimethylpyrrol -3-yl)  o c t a n e . 9 0 d u s e d as t h e s t a r t i n g  provided  b y Dr. J . B . P a i n e  out  as d e s c r i b e d  MP  :  185.5  III.  high  r e s o l u t i o n mass s p e c t r o m e t r y  ••Calcd. - f o r 2 2 3 2 2 ° 2 C  -.-Calcd.;. f o r C :  The r e a c t i o n s were  carried  - 187.0°C  Wt.  Found  kindly  f o r t h e nonane a n a l o g u e .  Moi.  Anal.  m a t e r i a l was  2 2  H  H  C, 74 . 22 ; H,  3 2  N  N 0 2  9.23;  2  :  : N,  3  5  6  :  *  2  4  6  '*  F  o  u  n  d  '  Y  h  356.2463.  C, 74.12; 7.90.  4  H,  9.05;  N,  7.86;  230 "'"H NMR  (6, C D C 1 ) 3  : 1.30  ( b r , 12H, c h a i n  5'-, 6'-, 7 ' - C H ) , 2.22, 2.24  ( s , s , 12H, 2-CH  2  2.22-2.42  (m, 4H, c h a i n  HC=0), 9.90  13  C  NMR  132.58 30.57 6'-C),  1'-CH  9  and 4 - C H ) ,  3  3  and 8'-CH^), 9.48  ( s , 2H,  ( b s , 2H, NH).  (6, C D C 1 )  ;  2'-, 3'-, 4'-,  3  (pyrrole (chain 23.76  Mass s p e c t r u m  :  175.56  4 - C ) , 127.96  2'-C and 7 ' - C ) , (chain  (C=0), 136.55  (pyrrole  ( p y r r o l e 2-C),  5 - C ) , 123.38  29.51, 29.35  (chain  (pyrrole  3'-C, 4'-C, 5'-  1'-C and 8 ' - C ) , 11.61 ( 2 - C H ) , 8.89 3  : Relative  m/e  Intensity  (%)  Assignment M  356  43  328  32  (M-CO)  136  100  H C _^CH  108  57  2  +  N  +  3  CH3 HX  3-C)  Il \ H  (4-CH >. 3  231  3.6.5. BIS CYANOVINYLPYRROLES  l , l l - B i s [ 5-(2,2-dicyanovinyl)-2,4-dimethylpyrrol-3-yl] (n=ll)  undecane  94a  The  crude b i s f o r m y l p y r r o l e  bis dicyanovinyl  d e r i v a t i v e by h e a t i n g  93a was c o n v e r t e d  to i t s  w i t h m a l o n o n i t r i l e and  * triethylamine  i n methanol-methylene c h l o r i d e . "  preparations,  the o v e r a l l y i e l d s  90a)  of the p u r i f i e d  In s e v e r a l  (from t h e b i s b e n z y l e s t e r  p r o d u c t v a r i e d between 4 0%  and 67%.  y i e l d was f o u n d t o be d e p e n d e n t p r i m a r i l y on t h e p u r i t y o f the  b i s formypyrrole  are  described  93a.  The optimum r e a c t i o n  f o r the synthesis  o f t h e decane  conditions  analogue.  * T o l u e n e was s u b s e q u e n t l y f o u n d - t o be a b e t t e r this  r e a c t i o n . At the r e f l u x temperature,  cause the premature c r y s t a l l i z a t i o n derivative. MP  : 153.0 - 1 5 4 . 5 ° C  solvent f o r  toluene  d i d no't  o f the monoprotected  The  232 MoT.Wt.  -caicd...  for C^H^Ng  r e s o l u t i o n mass spectrometry  .Calcd:  Found  : C, 75.28; H, 7.46; N, 16.80.  H NMR  C  H 3  1  ; (6, CDC1 )  N 3  8  :  3  6-, 7-, 8-, 9-, 10-CH ); 2  2-CH ), 2.27-2.47 3  :  75.27; H, 7.74; N, 16.98;  1-CH  2  2  (bs, 2H, NH).  (6, CDC1 )  :  •[ C(H)=C (CN)  '] , 136.44  ( p y r r o l e 4-C) , 125.82  124.14  3  (s , 6H,  and 11-CH ), 7.27  ;:  1 3  2-, 3-, 4-, 5-,  (s , 6H, 4-CH ), 2.27  (m, 4H, chain, 2  NMR  >  (br, 18H, c h a i n  2.10  [ s , 2H, C(H)=C(CN) ], 9.35  C  c  6  1.24 f  Found, by high  : 494.3167.  Anal.  1  for  : 494.3158 :  141.37  ( p y r r o l e 5-C), 117.64  ( p y r r o l e 2-C) , 140.48 ( p y r r o l e 3-C) ,  (C=N), 116.26 (C=N), 62.51  [CH=C(CN) ], 30.25 (chain 2-C and 10-C), 29.59 (chain 2  3-C,  4 - C , v 5 - C , 6-C, 7-C, 8-C, 9-C) , 23.92 (chain 1-C and 11-C) , 12.56  (2-CH ), 9.64 3  (4-CH >. 3  Mass spectrum: Relative m/e  Intensity  (%)  Assignment  495  24  (M+H)  494  68  M  184  100  +  +  233 —  :  (v  1595  max  K B r )  (C=C)  3200-3600. (broad, N-H),  :  2205 (C=N),  CM . -1  1,10-Bisr 5-(2,2-dicyanovinyl)-2,4-dimethylpyrrol-3-yl]decane  (n=10)  '94b  The  crude 1 , 1 0 - b i s ( 5 - f o r m y l - 2 , 4 - d i m e t h y l p y r r o l - 3 -  y l ) decane (5.01 chloride  g, 13.0  (100 mL)  and methanol  bath; and the volume was c  The  s o l u t i o n was  triethylamine and  mmol) was  d i s s o l v e d i n methylene  (20 mL),  reduced to approximately 50  cooled, m a l o n o n i t r i l e  (1 mL)  and  by heating  (2.0 g, 3 0.3  more methanol  (250 mL)  on a steam mL. mmol),  were added  reheated on the steam bath w i t h o c c a s i o n a l s w i r l i n g .  I t was  p o s s i b l e to monitor the r e a c t i o n by t i c , s i n c e  mono and  the  b i s - d i c y a n o v i n y l d e r i v a t i v e s were e a s i l y d i s t i n g u i s h e d  from each other  as w e l l as from the s t a r t i n g m a t e r i a l .  In  2% methanol-methylene c h l o r i d e , the b i s - p r o t e c t e d d e r i v a t i v e had 0.45  an  r  and  of 0.65-0.70, the mono-protected, an  f  the s t a r t i n g m a t e r i a l , an The  and  cooled  s o l u t i o n was  r  f  r ^ of 0.4 0-  of 0.10-0.20.  b o i l e d down to approximately 100  to room temperature when a yellow-brown  c r y s t a l l i z e d out.  T h i s was  washed with methanol, y i e l d were concentrated  c o l l e c t e d by f i l t r a t i o n 5.05  g.  The  on the steam bath and  solid and  mother l i q u o r s cooled  to g i v e  an  mL  234 a d d i t i o n a l 0.45 g. The combined i n methylene c h l o r i d e  crude product (5.5 g) was d i s s o l v e d (150 mL) and chromatographed  s i l i c a g e l (45 g, a c t i v i t y the e l u t i n g s o l v e n t .  on  I) u s i n g methylene c h l o r i d e as  The dark c o l o r e d i m p u r i t i e s remained  a t the o r i g i n and the pure b i s d i c y a n o v i n y l d e r i v a t i v e e l u t e d out as a yellow by evaporating  solution.  The product was c r y s t a l l i z e d  the methylene c h l o r i d e , i n vacuo, a f t e r the  a d d i t i o n o f methanol.  The lemon yellow  s o l i d thus  obtained,  was a n a l y t i c a l l y pure, y i e l d , 4.59 g •: (73.3% from the crude b i s aldehyde; 70.2% from the bis';:benzyl e s t e r ) .  MP  :  186.0 - 186.5°C  Anal.  Calcd..  Found  : C, 74.76; H, 7.57; N, 17.46.  1  H NMR  :  for  C  H 3 0  36 6  :  N  (6, CDC1 )  :  3  1.28  5-, 6-, 7-, 8-, 9-CH ), 2.15 2  2-CH ), 2.26-2.50  [a, 2H, C(H)=C(CN) ],  9.56  2  C  NMR  124.11  (s , 6H, 4-CH ), 2.33 2  (a, 6H,  and 10-CH ), 7.34 2  (bs, 2H, NH).  3  2  , 136.38  ( p y r r o l e 4-C), 125.79  ( p y r r o l e 5-C), 117.61 (G=N), 116.18  [C(H)=C(CN) ] 2  /  30.27  (2-CH ), 9.64  (4-CH ). 3  ( p y r r o l e 3-C), (C=N) , 62.62  (chain 2-C and 9-C) , 29.61, .29.49 (chain 3-C,  4-C, 5-C, 6-C, 7-C, 8-C), 23.93 3  3  (6, CDC1 ) : 141.25 ( p y r r o l e 2-C), 140.48  (  C(H)=C(CN)  (br, 16H, c h a i n 2-, 3-, 4-,  (m, 4H, c h a i n 1-CH  3  1 3  C, 74.97; H, 7.56; N, 17.48.  (chain 1-C and 10-C), 12.56  235 Mass s p e c t r u m  : Relative  m/e  Intensity  481  22  480  65  184  100  Assignment (M+H) M  +  +  H#.  // W NC'  "CN  1,9-Bis[5-(2,2-dicyanovinyl)-2,4-dimethylpyrrol-3-yl]nonane (n=9)  94c  The corresponding  crude  dialdehyde  93c  f o r the decane analogue.  yields  55.8%, 67.1%  of  MP  the p u r i f i e d  :  product  and  68.6%  were  i n the  manner  the b i s b e n z y l  overall ester)  :  form changed a t  169°C)  :  C,  Found  N,  18.05.  74.87; H,  the  obtained.  A n a l . C a l c d . .- f o r C ^ H ^ N g : C,  94c  to  In t h r e e attempts,  (from  182.0-182.5°C  (crystalline  converted  bis dicyanovinyl derivative  described of  was  7.33;  74.65; H,  7.34;  N,  18.01;  236 1  H NMR  (6, CDC1 )  :  3  7-, 8-CH ), 2.15 2  3  (m, 4H, c h a i n ,  9.36  (bs, 2H, NH).  C  NMR  136.36  1-CH  2  (s, 6H, 2-CH ), 2.263  and 9-CH ), 7.35 [ s , 2H, C(H)=C(CN) ], 2  2  3  2  ( p y r r o l e 4-C), 125.82  (chain,  2-, 3-, 4-, 5-, 6-,  (6, CDC1 ) : I'41.31 ( p y r r o l e 2-C), 140.49 [C(H)=C(CN) ],  5-C), 117.54  23.93  (br, 14H, c h a i n  (s, 6H, 4-CH ), 2.33  2.52  1 3  1.29  (C=N), 116.18  2-C and 8-C), 29.47  (chain,  ( p y r r o l e 3-C), 124.14  (pyrrole  (G=N), 62.55 [C(H)=C(CN) ]  , 30.24  2  (chain, 3-C, 4-C, 5-C, 6-C, 7-C),  1-C and 9-C), 12.51  (2-CH ), 9.64  (4-CH ).  3  3  Mass spectrum :  m/e  Intensity  467  27  466  71  184  100  (%)  Assignment (M+H) M  +  +  CH,  NC  CN  1,8-Bis[ 5- (2 , 2 - d i c y a n o v i n y l ) -2 , 4 - d i m e t h y l p y r r o l - 3 - y l ] octane (n=8)  94d  The crude d i a l d e h y d e 93d (6.03 g. 16.9 mmol) was  237  reacted of  with malononitrile  triethylamine  the  (2.57 g , 38.9 mmol) i n t h e p r e s e n c e  according  decane analogue.  t o 'the p r o c e d u r e g i v e n f o r  The c r u d e b i s - d i c y a n o v i n y l  obtained  (7.0 g . i n two c r o p s ) was d i s s o l v e d  chloride  (250 mL)  activity  I) t o g i v e  benzyl ester)  MP  :  i n methylene  and c h r o m a t o g r a p h e d on s i l i c a 5.38 g  (65.7% o v e r a l l  of the a n a l y t i c a l l y  pure  derivative  g e l (80 g .  yield  from the b i s  product.  216.5 - 217.5°C  Anal.  Calcd  Found  f o r C^gH^Ng  ;  :  C, 74.31; H, 7.13; N, 18.57.  : C, 74.41; H, 7.00; N, 18.65.  NMR  '  5-, 6-,  (6, C D C 1 ) 3  7 - C H ) , 2.15 2  2.30-2.50  :  2  ( b r , 12H, c h a i n  ( s , 6H, 4 - C H ) , 2.33 3  (m, 4H, c h a i n  C ( H ) = C ( C N ) ] , 9.36  1.30  1-CH  2  2-, 3-,  ( s , 6H,  and 8 - C H ) , 7.36[s  4-,  2-CH ), 3  2  , 2H,  145.85  ( p y r r o l e 2-C),  ( b s , 2H, NH) .  13 C NMR  (6,.10% TFA-CDC1 ) 3  :  140.49  [C(H)=C(CN) ] , 139.19  ( p y r r o l e 4 - C ) , 127.29  125.22  ( p y r r o l e 5-C) , 117.12  (C^N) , 116.21  [C(H)=C(CN) ] , 30.26 4-C, 9.80  5-C,  6-C), 24.03  (4-CH ). 3  (chain (chain  ( p y r r o l e 3-C),  (C*=N) , 57.97  2-C and 7 - C ) , 29.61 1-C and 8-C), 12.57  (chain  3-C,  (2-CH ), 3  238 Mass s p e c t r u m : Relative m/e  Intensity  (%)  Assignment  453  21  (M+H)  452  66  M  +  +  1 ,T1-Bis[5 - ( 2 - c y a n o - 2 - m e t h o x y c a r b o n y l v i n y l ) - 2 , 4 - d i m e t h y l p y r r o l 3-yl] undecane  115  1,11-Bis(5-benzyloxycarbonyl-2,4-dimethylpyrrol3-yl)  u n d e c a n e 90a  (9.5 g . 15.6 mmol) was i n i t i a l l y  t o t h e b i s f o r m y l p y r r o l e 93a i n t h e manner d e s c r i b e d The  entire  sample o f t h i s  crude  solid  was  converted previously.  t a k e n up i n t o l u e n e  (260 mL) w i t h m e t h y l cyclohexylamine plate.  cyanoacetate  (3.2 g . 36.8 mmol) and  (3 mL) and h e a t e d  a t r e f l u x on a  The r e a c t i o n was m o n i t o r e d  by t i c and was f o u n d t o  be  complete  in  v a c u o , t h e r e s i d u e t a k e n up i n m e t h y l e n e c h l o r i d e  solution The  i n approximately  stirrer-hot  allowed  by f i l t r a t i o n  by c o n c e n t r a t i n g t h e m o t h e r The  total  methylene c h l o r i d e gel  crude  product  as t h e s o l v e n t .  to  first  facilitate  move.  eluted  from  MP  158.0 - 159.5°C  Found  Calcd-. :  C,  forC 70.44;  H  on  was g r a d u a l l y  1% e t h y l  acetate  causing the impurities t o from  the chromatographed of methanol,  the b i s benzyl ester  y e l l o w powdery s o l i d  Anal.  silica  o u t , c l e a n , w i t h methylene  0.5% and t h e n w i t h  e l u t i o n without  overall  crop  liquors.  The s o l v e n t p o l a r i t y  bright  :  methanol.  and a s e c o n d  by c o n c e n t r a t i n g i n t h e p r e s e n c e  (75.9%  and t h e  (7.6 g) was d i s s o l v e d i n  The p r o d u c t was c r y s t a l l i z e d  solution 6.6 g  with  evaporated,  The i m p u r i t i e s were a d s o r b e d  t h e c o l u m n and t h e p r o d u c t  increased,  adding  (100 mL) a n d c h r o m a t o g r a p h e d o n  (100 g , a c t i v i t y . I ) .  chloride  The s o l v e n t was  t o stand overnight a f t e r  p r o d u c t was i s o l a t e d  obtained  2 h.  yield  9 0 a ) . The  o b t a i n e d was a n a l y t i c a l l y  pure.  " -  ^  N  ^ :  C, 7 0 . 6 9 ;  H, 8 . 0 6 ; N , 9 . 8 0 .  H, 7 . 9 1 ; N ,  9.99.  NMR '• (6, C D C 1 )  :  3  6-,  ( b r , 18H, c h a i n  7-, 8-, 9-, 10-CH ) , 2.19  1-CR" and 1 1 - C H ) , 3.88 2  2  6H, -QCH ) , 7.95  [ 5 , 2H, C (H) =C (CN) ] , 9.51  NMR  :  3  5-,  (s , 6H,  3  (m, 4H, c h a i n  3  2-, 3-, 4-,  (s , 6H, 4-CH ) , 2.32  2  2-CH ) , 2.26-2.50 (s,  1.28  ( b s , 2H,  2  NH) .  1 3  C  (6,, C D C L ) 3  165.15  135.62  (pyrrole  120.29  (C=?N) , 84.85  (chain  2-C and 10-C) , 29.54  8-C,  9-C), 24.01  4 - C ) , 125.01  (C=0) , 139.16  (pyrrole  3 - C ) , 123.46  (CH=C (CN) C 0 C H ) , 52.38  (chain  2  (chain  30.41  3  3-C, 4-C, 12.38  5-C,  2-C)  (pyrrole  (0-CH ),  3  1-C and 11-C),  (pyrrole  6-C,  (2-CH ),  7-C, 9.66  3  (4-CH ). 3  Mass  spectrum m/e  Relative Intensity  560  39  528  11  496  16  217  89  (%)  Assignment M  +  (M-CH OH)  +  3  (M-2  CH OH)  H  3  OCH,  185  100 CN  5-C)  241 3.7  SYNTHESES OF CHAIN LINKED DIPYRROMETHANE DIMERS  1,T1-Bis{5-(2,2-dicyanovinyl)-2-[(5-ethoxycarbonyl-3-ethyl4-methylpyrrol-2-yl)methyl]-4-methylpyrrol-3-yl> (n=ll)  (i)  96a  Monochlorination  1,11-Bis yl]undecane chloride  undecane  o f the a-methyl  groups.  [5-(2,2-dicyanovinyl)-2,4-dimethylpyrrol-3-  94a (2.05 g , 4.15 mmol), d i s s o l v e d  (80 mL), was s t i r r e d  in  an e r l e n m e y e r  of  sulfuryl  flask,  chloride  on a m a g n e t i c  and t r e a t e d  i n d r y methylene  stirrer/hot  dropwise with a s o l u t i o n  (1.13 q> 8.37 mmol) i n m e t h y l e n e  (50 mL), a t room t e m p e r a t u r e .  plate  The p a l e y e l l o w  chloride  solution  turned  orange  during  the a d d i t i o n .  away and r e p l a c e d product  w i t h anhydrous  to c r y s t a l l i z e .  was c o l l e c t e d chloride-ether  (ii)  diethyl  f o l l o w e d by e t h e r , and d r i e d was u s e d  glacial  acetic  compound acid  i n the next r e a c t i o n  The lemon  without  (30 mL).  color).  95a p r e p a r e d above was s u s p e n d e d i n  7_9 (1.8 0 g , 9.94 mmol)  solution.  methanol-methylene  (The s o l u t i o n  chloride)  s o l u t i o n was c o o l e d  by b r o m i n e t o room  vapour.  temperature, reduced p r e s s u r e ,  and a l l o w e d t o s t a n d o v e r n i g h t i n  the  refrigerator.  out  as a d a r k y e l l o w s o l i d  The d i p y r r o m e t h a n e  and washed w i t h m e t h a n o l . sample was 3.04 g  ( i n 2%  the p r o d u c t as a  e v a p o r a t e d down t o a p p r o x i m a t e l y 2 5 mL u n d e r (100 mL) added  reacted  turned orange-red i n  indicated violet  acetic  n i t r o g e n , on a  of the r e a c t i o n mixture  yellow spot, colored  methanol  in glacial  f o r 1 h . when t h e s t a r t i n g m a t e r i a l  A t i c analysis  The  i n , 2-ethoxycarbonyl-4  The m i x t u r e was warmed, u n d e r  b a t h a t 7 0°C  and went i n t o  dimer  (120 mL) and s t i r r e d  ethyl-3-methylpyrrole  single  in air.  purification.  The  water  ether causing the  washed w i t h 10% m e t h y l e n e  P r e p a r a t i o n of the dipyrromethane  acid  boiled  The a - c h l o r o m e t h y l d e r i v a t i v e 95a  by f i l t r a t i o n ,  y e l l o w powdery s o l i d further  The s o l v e n t was c a r e f u l l y  dimer  and was c o l l e c t e d The y i e l d  (85.9% o v e r a l l  96a c r y s t a l l i z e d by  filtration  of the a n a l y t i c a l l y  yield  from  94a).  A  pure  second  243 crop was not i s o l a t e d . In four separate 85.2%  syntheses,  y i e l d s of 83.3%, 85.0%,  and 92.6% were obtained.  MP : 168.0 - 170.0°C (dec)  Moi. Wt. .Calcd-  for 5 C  H 1  6  4  N  4  0 8  852.5051  :  high r e s o l u t i o n mass spectrometry:  Anal.  Calcd. f o r  C  Found  H 5  1  N 6  4  0 8  : 4  :  Found, by  852.5045  C, 71.80; H, 7.56; N, 13.13.  : C, 72.04; H, 7.55; N, 13.35.  "H NMR  (6, CDC1 )  :  3  1.03 ( t , 6H, J=7.5 Hz, 3'-CH CH ), 2  3  1.18-1.54, 1.34 (br, t , 24H, c h a i n - 2-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-CH ,-.-Q-CH CH ) , 2.15 (s, 6H, 4-CH_ ), 2.30 (s, 6H, 2  3  3  4'-CH ), 2.21-2.58, 2.43 (m, q, 8H, c h a i n 1-CH and 11-CH , 3  2  3 -CH CH ),  3.98 (s, 4H, b r i d g e C H ) , 4.29 (q, 4H, J=7 Hz,  ,  2  2  3  2  0-CH -CH ), 7.34 [ s , 2H, C(H)=C(CN) ] , 8.90 (br, 2H, l'-NH), 2  9.24  1 3  C  3  2  (br, 2H, 1NH).  NMR  140.57  (6, CDC1 ) 3  : 162.13  ( p y r r o l e 2-C), 136.25  (C=0), 140.78 [C(H)=C(CN) ] ,  ( p y r r o l e 4-C), 127.09, 126.02, 125.16  ( p y r r o l e 3-C, 2'-C, 3'-C, 4'-C), 124.15 ( p y r r o l e 5'-C), 116.84 59.96  (0-CH CH ), 30.30 2  3  (G=N), 115.96  (pyrrole 5-C), 118.91  (C=iJ) , 64 . 27 [CH=C(CN) ~, 2  (chain 2-C and 10-C) , 29.59  4-C, 5-C, 6-C, 7-C, 8-C, 9-C), 23.95  (chain 3-C,  (bridge CH , c h a i n 1-C and 2  244 (3'-CH CH ), 15.38 P ' - C ^ C H ^ , 14.46 (OCH CH ),  11-0,17.39 10.52  2  (4'-CH ),  IR — 1585  9.62  3  Mass spectrum  : (v max  3  :  2  (4-CH ). 3  m/e, 852 (M ), 806 (M-C H 0 H ) , 2 ->  KBr)  +  +  c  :  3  3100-3600  760 (M-2.C H_OH) n  2  o  (broad, N-H), 2210 (C=N), ' '  (C=C) cm" . 1  1,T0-Bis{5-(2,2-dicyanovinyl)-2-[(5-ethoxycarbonyl-3-ethyl4-methylpyrrol-2-yl)methyl]-4-methylpyrrol-3-yl>decane (n=10)  96b  Compound 94b (1.82 g. 3.79 mmol), i n methylene c h l o r i d e (100 mL) was c h l o r i n a t e d u s i n g a s o l u t i o n o f s u l f u r y l (1.03 g. 7.62 mmol) i n methylene c h l o r i d e f o r the undecane analogue  94a.  chloride  (50 mL) as d e s c r i b e d  The b i s a-chloromethyl  derivative  was then r e a c t e d w i t h 2 - e t h o x y c a r b o n y l - 4 - e t h y l - 3 - m e t h y l p y r r o l e 7 9 (1.50 g. 8.29 mmol) i n a c e t i c a c i d decane l i n k e d dipyrromethane  (200 mL) t o g i v e the  dimer 96b i n 88.9% o v e r a l l  yield.  The product, c r y s t a l l i z e d out o f the r e a c t i o n mixture, was found t o be a n a l y t i c a l l y  pure.  The r e p e t i t i o n o f t h i s s y n t h e s i s r e s u l t e d i n f i r s t crop y i e l d s of 86.7% and 87.4%.  245 MP  :  Moi.  198.0 - 200.5°C (dec)  Wt. C a l c d .  C  50 62 8°4 H  N  :  r e s o l u t i o n mass s p e c t r o m e t r y  Anal. Calcd. Found  1  H  for  c  o 62 8°4 H  5  N  8  (6, C D C 1 )  :  3  1.16-1.53, 1.36 2  4  8  9  F o u n d , by  4  high  :  C  '  7  -  1  5  7  ;  '  H  7  - '' > 4 5  13.35.  N  ( t , 6H, J=7 . 5 Hz,  3'-CH CH_ ), 2  3  ( b r , t , 22H, c h a i n .- 2-, 3-, 4-, 5-, 6-, 2  ( a , 6H, 4-CH_ ), 2.29  3  2.22-2.59, 2.41  (m, q, 8H, c h a i n  ( a , 4H, b r i d g e  CH_ ), 4.29  7.34  [ s , 2H, C ( H ) = C ( C N ) ] , 8.87  1~CH  ,  2  3  0-CH -CH ), 2  ( b r , 2H, 1'-NH),  2  3'-CH CH ),  2  (q, 4H, J=7 Hz,  2  3  and 1 0 - C H ,  2  7-,  (s , 6H, 4 - C H ) ,  3  3.98  C  •  : 838.4884  1.03  8- , 9-CH , Q-CH CH_ ), 2.15  1 3  8  : C, 71.51; H, 7.42; N, 13.47.  NMR  2H,  3  3  9.22 ( b r ,  1-NH).  NMR  (6, 10% TFA-CDC1 )  [C(H)=C(CN) ], 2  141.78  128.96, 126.57, 126.12 (pyrrole  5 - C ) , 118.11  ( p y r r o l e 3-C,  9- C ) ,  29.80  2  14.29  chain  3  Mass s p e c t r u m  3  :  m/e,  2'-C, 3'-C,  (4'-CH ) 3  838  6-C,  125.12  (C^I) , 116.11  (CsN) ,  7-C, 8 - C ) , 24.18  (bridge  ( 3 ' - C H C H ) , 15.29 ( 3 ' - C H C H ) , 2  /  9.71  (M ) , 792 +  4'-C),  ( c h a i n 2-C and  2  1-C and 1 0 - C ) , 17.43 2  ( p y r r o l e 4 - C ) , 129.81,  [ C H = C ( C N ) ] , 30.31  ( c h a i n 3-C, 4-C, 5-C,  (OCH CH- ), 10.86  (C=0), 142.75  ( p y r r o l e 5 ' - C ) , 116.88  ( 0 - C H - C H ) , 61.26 2  164.75  ( p y r r o l e 2 - C ) , 138.58  61.92  CH ,  :  3  3  2  3  (4-CH >. 3  (M-C H,-OH) , +  0  746  (M-2 C^H^OH)  246  1.9-Bis{5-(2,2-dicyanovinyl)-2-[ (5-ethoxycarbonyl-3-ethyl4-methylpyrrol-2-yl)methyl]-4-methylpyrrol-3-yl}nonane (n=9)  96c  T h i s compound was p r e p a r e d t h a t employed  i n t h e p r e p a r a t i o n o f compound  96a.  mmol) o f s t a r t i n g m a t e r i a l 9 4 c , an o v e r a l l  88.0%  o f t h e a n a l y t i c a l l y p u r e m a t e r i a l was o b t a i n e d .  88.1%  MP  :  t h e p r o d u c t was i s o l a t e d  and 88.6% y i e l d .  A second  -Calcd.  for C  4 g  H  N 0 Q  4  h i g h r e s o l u t i o n mass s p e c t r o m e t r y  In  i n 8 6.4%,  c r o p was n o t i s o l a t e d .  for  Found  : C, 71.12; H, 7.21; N, 13.38  4  H  N 6  0  ;  F o u n d , by  C, 71.33; H, 7.33; N, 13.58;  o 8  824.4737  : 824.4727  -Calcd.  c  9  :  Anal.  NMR  yield of  205-210 C (dec)  Mo 1.Wt  H  as  W i t h 2.01 g  (4.31  three other attempts,  X  by t h e same p r o c e d u r e  4  (6, CDC1 ) : 1.00 ( t , 6H, J=7.5 Hz, 3 ' - C H C H ) , 1.143  2  3  1.48, 1.35 ( b r , t , 20H, c h a i n 2-, 3-, 4-, 5-, 6-, 7-, 8-CH , 2  0-CH -CH_ ) , 2.15 (s , 6H, 4-CH_ ), 2.29 (s , 6H, 4 ' - C H ) , 2  3  3  2.56, 2.40 (m,q, 8H, c h a i n 1"CH  3  2  and 9-CH , 3 ' - C H C H ) , 2  2  (s , 4H, b r i d g e C H ) , 4.31 ( q , 4H, J=7 Hz, 0 - C H C H ) , 2  [s,  2  2H, C ( H ) = C ( C N ) J , 9.03 ( b r , 2H, l ' - N H ) , 2  3  3  2.22  7  3.99  7.34  9.23 ( b r , 2H, 1-NH)  247 1 3  C  NMR  3  141.85  (pyrrole  2 - C ) , 1.38 .78  126.64, 126.14 (pyrrole  (pyrrole  5 - C ) , 118.09  ( O s M ) , 62.00 2-C  2  (3'-CH CH ),  14.27  3  spectrum  :  3'-C,  824  4'-C),  125.17  (CsN),  115.84  [C (H) =C (CN) ] , 30.32  (chain  4-C,  5-C,  ( 0 - C H C H ) , 10.84  m/e,  2  116.79  and 9-C), 17.43 2  142.97[C(H)=C(CN) ],  4 - C ) , 129.85, 128.93,  5'-C),  ( c h a i n 3-C,  c h a i n 1-C  2  2'-C,  (pyrrole  (bridge CH , 2  3-C,  3  29.77  (C=0),  (pyrrole  ( 0 - C H C H ) , 60.90  and 8-CX,  Mass  164.80  ( 6 , 10%TFA-CDC1 ):  +  7 - C ) , 24.19  (3'-CH CH ), 2  3  (4'-CH ) , 9.70  3  (M -), 778  6-C,  (M-C H OH) , 732 +  2  5  15.27 (4-CH ). 3  (M-2.C H OH) 2  5  1,8-Bis{5-(2,2-dicyanovinyl)-2-[(5-ethoxycarbonyl-3-ethyl4-methylpyrrol-2-yl)methyl]-4-methylpyrrol-3-yl}octane (n=8)  96d  The and  chlorination  the subsequent  were c a r r i e d  pounds i n t h i s be u s e d  Due  series  94d  (2.01 g , 4.4 6 mmol)  to the dipyrromethane  to the procedure given  to the lower  solubility  ( 8 - c a r b o n c h a i n ) , more  For the c h l o r i n a t i o n  dimer  96d  f o r the  o f t h e com-  s o l v e n t had t o  t o g e t t h e s t a r t i n g m a t e r i a l s and p r o d u c t s  solution. compound  conversion  out according  undecane analogue.  o f compound  into  step, the b i s a-methyl  94d was d i s s o l v e d i n 180 mL m e t h y l e n e  chloride  248 (cf. of  80 mL u s e d  to d i s s o l v e  t h e undecane analogue  250 mL o f a c e t i c (cf.  94a) and f o r t h e c o u p l i n g  was u s e d  150 mL o f a c e t i c  Further, the  acid  a p p r o x i m a t e l y t h e same amount  acid  dimer  to concentration  solid  was removed and a s e c o n d  overall  MP  :  Calcdv  Found  :  "H NMR  for C  H 4  8  N 5  8  0 8  (6, C D C 1 ) 3  : 1.01  2.15  ( s , 6H, 4 - C H ) , 2.30  (m, q, 8H, c h a i n 1-CH b r i d g e C H ) , 4.29 2  (H)=C(CN) 1, 2  141.76  4  and a d d i n g m e t h a n o l .  The  : C, 71.08; H, 7.21; N. 13.82;  2  2-, 3-, 4-, 5-, 6-,  8.93  2  2  3  (q, 4H, J=7 Hz, 0 C H C H ) , 2  ( b r , 2H, l ' - N H ) ,  2 - C ) , 138.51 (pyrrole  ( p y r r o l e 5 - C ) , 118.09  2  :  3  9.23  164.73  (pyrrole  3  3.99  7.34  2.40  5'-C),  (s" , 4H, :  1-NH).  (C=0) , 142.71 [ C (H) =C (CN) ] , 2  4 - C ) , 129.78, 128.87,  3-C, 2'-C, 3'-C, 4 ' - C ) ,  (pyrrole  3  [ s , 2H,  ( b r , 2H,  116.87  ( 0 - C H - C H ) , 61.29 [ C ( H ) = C ( C N ) J , 30.28 2  2  3  3  (pyrrole  6-CH , 0-CH CH_ ),  and 8-CH , 3'-CH_ CH ),  2  1.14-1.46,  3  ( s , 6H, 4 ' - C H ) , 2.22-2.54,  (6, 10% TFA-CDC1 )  126.48, 126.08  61.93  c r o p was i s o l a t e d by c o n -  ( t , 6H, J=7.5 Hz, 3 ' - C H C H ) ,  3  NMR  The  C, 7 0.75; H, 7.09; N, 13.57.  ( b r , t , 18H, c h a i n  C  o f methanol.  (dec.)  1.36  1 3  temperature,  f o r t h i s c o v e r s i o n was 90.9%.  202.5 - 206.5  Anal.  t o room  and t h e a d d i t i o n  the mother l i q u o r s  yield  96d, c r y s t a l l i z e d o u t when  s o l u t i o n was c o o l e d  prior  centrating  to g e t the product i n s o l u t i o n .  a c i d w i t h the undecane a n a l o g u e ) .  the dipyrromethane  acetic  step,  125.06  (G=N), 115.89 (chain  (G=N),  2-C and  249  7-C), "29.69  ( c h a i n , 3-C, 4-C, 5-C, 6-C) , 24.12  chain  1-C and 8 - C ) , 17.40  14.28  ( O C H - C H ) , 10.85 2  3  O ' - C I ^ C B ^ ) , 15.27  (4'-CH ), 3  9.67  (bridge CH , 2  O'-CI^CH^,  (4-CH >. 3  l,ll-Bis{2-[(5-carboxy-3-ethyl-4-methylpyrrol-2-yl)methyl]5-formyl-4-methylpyrrol-3-yl}undecane  (n=ll)  107a  250  In adapter,  a 1 liter  erlenmeyer  a nitrogen inlet  and  flask  a reflux  f i t t e d with condenser,  a  Claisen  placed  1,11-  bis{5-(2,2-dicyanovinyl)-2-[(5-ethoxycarbonyl-3-ethyl-4methylpyrrol-2-yl)methyl]-4-methylpyrrol-3-yl}undecane (1.88  g.  (23 g) was  2.21  i n water  heated  added. into  was  starting  solid  nm. the  lower  magnetically stirred and  n-propanol  suspension  (7 0 mL)  was  s t a r t i n g m a t e r i a l immediately i n a p a l e brown s o l u t i o n .  continued  and  every  half  w i t h w a t e r and was  an  h o u r an  compared w i t h  aliquot  that of  diluted  went  The  i t s uv-visible  m a t e r i a l i n methylene c h l o r i d e ,  i n t e n s e a b s o r p t i o n a t 27 5 n m a n d  During  the r e a c t i o n ,  simultaneous  wavelengths.  appeared  spectrum the  with  ethanol.  i n c r e a s e i n the  In 1.5  completely,  h,  a t 269  nm  The the  and  nm)  c o n d e n s e r was  s o l v e n t was  allowed  nm,  intensity  t h e peak a t 4 07  indicating  320  a shoulder  t h e peak a t 407  d i c y a n o v i n y l p r o t e c t i n g groups.  and  hydroxide  s t a r t i n g m a t e r i a l showed a s t r o n g a b s o r p t i o n a t 4 07  with  (now  of potassium  resulting  T h i s spectrum  moderately 315  The  temperature  removed, d i l u t e d  recorded;.  The  yellow  solution  a solution  (200 mL).  to r e f l u x  The  refluxing was  mmol) and  96a  nm,  around  diminished  o f peaks a t  nm  had  dis-  the complete removal of The  were v e r y  lower  wavelength  the  bands  intense.  removed, added more w a t e r to b o i l  a  off until  the  (3 00  reflux  mL)  temperature to  reached  100°C.  room t e m p e r a t u r e ,  partially  while  filtered  under s u c t i o n  to f a c i l i t a t e  final  acidified by  clear  filtration),  with g l a c i a l  filtration,  dessicator  over potassium solid  was q u a n t i t a t i v e .  MP  acetic  hydroxide  was  :  .for  C  H 4  1  5  N 6  0 4  :  c  6  : C, 70.45; H, 8.16; N,  "H NMR  (6, DMSO-d ) : 0.84  water.  c o o l e d i n i c e and  The s o l i d  was  collected  i n a vacuum  f o r s e v e r a l days. pure.  The  the y i e l d  The  yield  was g r e a t e r  2  18H, c h a i n 2-, 3-, 4-,  5-, 6-,  ( s , s, m,  chain.  2  2  and 1 1 - C H ) , 3.82  2H, HC=0),  Mass S p e c t r u m  11.00  : m/e,  (M-2 =C0 ) . 2  70.26; H, 8.05; N,  7-, 8-,  3  2  3  , 3'-CH .CH  ( s , 4H, b r i d g e C H ^ ) , ( b r , 2H,  (M-H) , 698 +  1.21  10-CH ),  1  3  (M , weak), 699 +  9-,  20H, 4-CH_ , 4 - C H  ( b r , 2H, 1-NH), 11.45  700  7.99;  ( t , 6H, J=7 Hz, 3 ' - C H C H ) ,  6  1-CH_  /  8.20.  2.15, 2.18, 2.16-2.46  612  material  by a d d i n g more was  paper  139.0 - 142.5°C (dec)  Found  (s,  541 f i l t e r  and t h e brown  analytically  In every attempt,  The  95%.  Anal. ,Calcd.  (br,  acid.  (Whatman  washed w i t h w a t e r and d r i e d  p a l e brown f l u f f y  than  paper  ( 14 00 mL)  solution  to cool  u n d e r n i t r o g e n , when t h e p r o d u c t  d i s s o l v e d , w h i l e on t h e f i l t e r The  allowed  s e p a r a t e d o u t as a brown s l i m y m a t e r i a l -  s o l u t i o n was was u s e d  The s o l u t i o n was  2  9.49 l'-NH).  (M-2H)  3  252  I, 10-Bis{2-[(5-carboxy-3-ethyl-4-methylpyrrol-2-yl)methyl15-formyl-4-methylpyrroi-3-y1)decane  The deprotected (21 g  dipyrromethane  and  i n 200  dimer  mL  taken  f o r the r e a c t i o n  spectral  changes o b s e r v e d , t o be  i n 96.3%  159.0  H  1  : C,  NMR  (br,  69.84; H,  6  c h a i n - 2-,  2.20,  2.18-2.44  1-CH  and  2  I I . 05  (darkened  H  5 4  analogue  time  were s i m i l a r . pure  progressively  3-,  ( s , s , m,  : m/e, +  686  : C,  6  N,  69.94; H,  The  and  was  above 14 8°C  and  4-,  5-,  20H,  J=7  6-,  4-CH  ( s , 4H,  3  +  Hz,  N,  8.16;  7-,  3'-CH CH ), 2  8-,  3  9-CH ), 2  4'-CH , 3'-CH 3  b r i d g e CH ) , 9.54  ( b r , 2H,  (M ,  7.92;  8.29.  ( t , 6H,  1-NH), 11.49  (M-2.C0 ) . 2  4  : 0.84  2  ( b r , 2H,  N 0  7.81;  1 0 - C H ) , 3.85  Mass s p e c t r u m 598  4 Q  (6, DMSO-d )  16H,  hydroxide  as t h e  analytically  was  mp).  Anal. .Calcd: for C Found  1.8 0 mmol)  yield.  - 162.0°C  decomposed a t  g,  as w e l l  complete,  p r o d u c t , a p a l e brown s o l i d , was  :  (1.51  w a t e r ) as d e s c r i b e d f o r t h e undecane  The  MP  96b  107b  s a p o n i f i e d w i t h aqueous p o t a s s i u m  96a.  obtained  (n=10)  2  CH  1.22  2.18, , chain-  ( s , 2H,  HC=0),  l'-NH).  weak), 685  (M-H) , 684 +  (M-2H) , +  253 1,9-Bis{2-f ( 5 - c a r b o x y - 3 - e t h y l - 4 - m e t h y l p y r r o l - 2 - y l ) m e t h y l ] formyl-4-methylpyrrol-3-yl}nonane  T h i s compound was that  employed  I n one  prepared  i n the p r e p a r a t i o n o f  attempt,  2.51  were r e a c t e d w i t h g  g  (3.05  107c  by  the  the  mmol) o f  aqueous p o t a s s i u m  same p r o c e d u r e  undecane a n a l o g u e  starting  hydroxide  (96.7%) o f t h e p r o d u c t  (26.5  give  of  w a t e r were r e q u i r e d t o d i s s o l v e t h e p o t a s s i u m acidification.  T h i s was  the  undecane  analogue.  MP  :  - 153.5°C  Anal.  152.0  Caled.for  F o u n d , C,  1  H  NMR  I . 22  C  39  H  N 5 2  68.94; H,  4 6 0  7.82;  chain  2-,  2.20,  2.16-2.46 ,(s, s, m,  1-CH  and  2  I I . 02  9 - C H ) , 3.84 2  ( b r , 2H,  1NH),  Mass s p e c t r u m :  m/e,  than  as 107a.  96c  g i n 250  O n l y 14 00 salt  mL)  mL of  107c,  that required for  (dec)  :  C  '  N,  (6, DMSO-dg) : 0.86 ( b r , 14H,  less  107c.  material  to  before  2.04  (n=9)  -5-  -  6 2  '*  ( t , 6H,  3-, 20H,  11.47  4-,  +  7.79;  J=7  Hz,  5-,  N,  8.33;  6-,  3'-CH CH_ ), 2  7-,  3  8-CH ),  2.18,  2  4-CH , 4'-CH , 3 ' - C H C H ,  chain  bridge  HC=0),  3  ( b r , 2H,  (M ,  '  H  8.51.  ( s , 4H,  67 2  6 9  3  CH ), 2  2  9.52  3  ( s , 2H,  l'-NH).  w e a k ) , 67 0  (M-2H) , 58 4 +  (M-2.C0 ) o  +  254 1,8-Bis{2-[(5-carboxy-3-ethyl-4-methylpyrrol-2-yl)methyl]5-formyl-4-methylpyrrol-3-yl}octane  The  dipyrromethane dimer  reacted with potassium n-propanol  pure product  :  10 7 d  96d (1.03 g, 1.27 mmol) (12.5 g) i n w a t e r  (50 mL) a s d e s c r i b e d f o r t h e s y n t h e s e s  cane a n a l o g u e 1 0 7 a .  MP  hydroxide  (n=8)  The y i e l d  107d was 764 mg  232.5°C  (darkened  was  (150 mL) and o f t h e unde-  o f t h e p a l e brown  analytically  (91.4%).  p r o g r e s s i v e l y above 187°C and  decomposed a t mp).  Anal.  Calcd.  Found  : C, 69.27; H, 7.67; N, 8.59.  1  H NMR  for  c  H 3  8  5  (6, DMSO-d ) 6  N 0  4 6 O  :  : 0.86  C  '  6  9  -  2  8  f  H  ' 7.65; N, 8.50.  ( t , 6H, J=7 Hz, 3'-CH CH_ ), 1.23 2  3  (br,  12H, c h a i n 2-, 3-, 4-, 5-, 6-, 7 - C H ) , 2.18, 2.21, 2.16-  2.48  ( s , s, m, 20H, 4-CH , 4'-CH , 3'-CH_ CH , c h a i n 1-CH  2  3  9 - C H ) , 3.85 2  (br,  3  ( s , 4H, b r i d g e C H ) , 9.54 2  2  3  2  and  ( s , 2H, HC=0), 11.03  2H, 1-NH), 11.48 ( b r , 2H, l ' - N H ) .  Mass s p e c t r u m  : m/e,  658 ( M , weak), 656 (M-2H) , 570 +  +  (M-2.C0 ) o  +  255 1 , l l - B i s {2-[ ( 5 - b e n z y l o x y c a r b o n y l - 3 - e t h y l - 4 - m e t h y l p y r r o l - 2 - y l ) methyl]  -5-(2-cyano-2-methoxycarbonylvinyl)-4-methylpyrrol-3-yl}  undecane  117  Q  117  l,ll-Bis[  5-(2-cyano-2-methoxycarbonylvinyl)-  2,4-dimethylpyrrol-3-yl]undecane methylene c h l o r i d e  (80 mL) was t r e a t e d ,  solution :of'sulfuryl chloride mixture orated  under reduced  derivative addition used  c h l o r i d e (1.45 g  (40 mL) o v e r was a l l o w e d  115 (2.80 g, 5 mmol) i n  a period  to s t i r  o f 30 min.  The r e a c t i o n 10 m i n  and e v a p -  The b i s a - c h l o r o m e t h y l  o u t o f t h e s o l u t i o n on t h e  o f hexane and was f i l t e r e d ,  i n the next r e a c t i o n  10.7 mmol) i n m e t h y l e n e  f o r a further  pressure.  116 c r y s t a l l i z e d  f  dropwise, with a  without  washed w i t h hexane and  further  purification.  256 The in  glacial  b i s g-chloromethylpyrrole•116  acetic  acid  ( 1 5 0 mL)  -4-ethyl-3-methylpyrrole under 70°  the starting  clear  dark  indicated  a single  solution  solution  and water was t h e n  excess  methylene  chloride  chloride with  heated reached  producing  50 mL  and  a  mixture  The s o l u t i o n  was  crystallization This  caused  product  : 91.0 -  ( 1 0 0 mL)  The d r i e d  the  starting  chloride.  methylene  acid  bicarbonate  chloride  g e l (90 g , a c t i v i t y I ) .  m a t e r i a l 8_0„ e l u t e d o u t w i t h was r e m o v e d  using different  using  was e v e n t u a l l y i s o l a t e d  5%  ethyl  of the  s o l v e n t systems;  chloride-methanol,  ether, but i n every  93.0°C  sodium  The c r y s t a l l i z a t i o n  acetate, methylene  the residue  and t h e r e m a i n i n g  on s i l i c a  and t h e product  by e v a p o r a t i n g  to dryness,  s a t u r a t e d aqueous  (40 m L ) .  was a t t e m p t e d  chloride-diethyl  MP  and  of the reaction  product.  was e v a p o r a t e d  a-free pyrrole  chloride-ethyl  glass,  Tic analysis  chromatographed  acetate-methylene  The  solution,  as b e f o r e , u s i n g methanol.  by e x t r a c t i o n  ( 2 x 4 0 mL)  product  , 1 1 . 1 mmol)  into  dipyrromethane  up i n m e t h y l e n e  removed  The  2-benzyloxycarbonyl  to o i l out. The  taken  suspended  When t h e t e m p e r a t u r e  down t o a p p r o x i m a t e l y  was a t t e m p t e d , product  bath.  m a t e r i a l went  red solution.  evaporated  together with  8_0 ( 2 . 7 g  n i t r o g e n , on a water  was  methylene  methylene  i n s t a n c e , i to i l e d o u t . as a  the solvent, yield  non-crystallizable 5.22  g  (81.6%).  Anal,. .Calcd.. Found  1  H  f o r C^H^NgOg  (6, CDC1 )' : 1.03  18H, c h a i n ,  2.14  (s , 6H, 4-CH ) , 2.31  2-, 3-, 4-,  chain,  ,  2  3  /  isomers),  3  0-CH C H ), 2  6  5  1-CH  3.94  7.90  i s o m e r ] , 7.37  C  9-, 1 0 - C H ) , 2  (s , 6H, 4 ' - C H ) , 2.28-2.60  and 1 1 - C H ) , 3.76, 3.8 5  2  (m, 8H,  3  (s , s , 6H,  2  (s , 4H, b r i d g e CH^) , 5.29  (s , 4H, ;  [ s , 2H, C ( H ) = C ( C N ) C 0 C H , hook a t 7.252  (m, 10H, C g H ^ ) , 8.84  NMR  (6, C D C 1 ) 3  : 165.16  3  ( b r , 2H, l ' - N H ) ,  9.40  —  Z  (pyrrole  4 - C ) , 128.42  (pyrrole  (benzene r i n g - t h r e e (pyrrole 123.60  (pyrrole  [ C (H) =C (CN) C 0 „ C H , hook a t 138.94 —  Z  2 - C ) , 136.44  carbons),  127.71  (pyrrole  5 - C ) , 119.48  (chain 8-C,  ( 3 ' - C H C H ) , 15.39 2  3  Mass s p e c t r u m  :  1043  +  6  5  2  2'-C),  126.98  ( p y r r o l e 3-C), 5V-C),  (pyrrole c  — Z  (bridge  ( M - C H C H O H ) , 108  (pyrrole  127.94  ( - 0 - C H „ - C H ) , . 52.45  5  CH , 2  P'-CH^CH^),  m/e,  o  (benzene 1 - C ) , 135.65  (C=N), 118.31  2-C and 1 0 - C ) , 29.59  9-C), 23.84  6  3 ' - C ) , 124.39  [ C ( H ) = C ( C N ) C O „ C H _ ] , 65.56 Z  3  (benzene r i n g - t w o c a r b o n s ) ,  4 ' - C ) , 125.23  —  30.37  2  Z o o  137.71  86.00  ( C 0 C H , hook a t 1 6 6 . 7 8 - i s o m e r ) ,  (CO-CH^C^H,.) , 138.45  isomer],  934  5-, 6-, 7-, 8-,  3  2H, 1-NH).  161.54  7^C,  2  3  3 -CH_ CH '  1 3  ( t , 6H, J= 7.5, 3 '-CH CH_ ) , 1.25  3  (br,  (br,  8.06;  : C, 72.53; H, 7.05; N, 7.99.  NMR  0-CH  : C, 72.53; H, 7.15; N,  (chain, chain  10.60  b  o  :  .  i-  3-C, 4-C,  5-C,  (4 ' -CH ) , 9 . 36  \i  6 C, 7  (4-CH ).  3  (C H ?  3  (M-C H CH ) ,  +  ( C g H ^ C t ^ O H ) , 91  >  1-C and 8 - C ) , 17.33  (M , v . weak), 952 +  (-Q-CH-)  c  +  6  + 7  ) .  5  2  258  1,ll-Bis{2-[(5-carboxy-3-ethyl-4-methylpyrrol-2-yl)methyl]5-(2-cyano-2-methoxycarbonylvinyl)-4-methylpyrrol-3-yl} undecane  118  118  l,ll-Bis{2-[(5-benzyloxycarbonyl-3-ethyl-4-methylpyrrol -2-yl)methyl]-5-(2-cyano-2-methoxycarbonylvinyl)-4-methylpyrrol - 3 - y l } u n d e c a n e 117  (2.11 g, 2.02  charcoal  i n tetrahydrofuran  (182 mg),  a t room t e m p e r a t u r e o f h y d r o g e n was  u n d e r 1 atm  with  expected  volume i n a p p r o x i m a t e l y  1 h.  filtered  and t h e s o l u t i o n The p r o d u c t  and  the s o l u t i o n  for  complete  was  was a l l o w e d  precipitation.  time  stirred  The u p t a k e  and r e a c h e d  The c a t a l y s t  concentrated  crystallized  palladized  (50 mL), were  of hydrogen.  and l i n e a r  of methanol.  rapid  mmol) and 10%  after  the  was  the a d d i t i o n  o u t as a y e l l o w  powder  to stand o v e r n i g h t i n the f r e e z e r  The  s o l i d was  f i l t e r e d and washed w i t h m e t h a n o l t o g i v e  (65.5%) o f a n a l y t i c a l l y were c o n c e n t r a t e d  MP  :  Calcd;. f o r  Found  H  f o r a second crop  C  H 4  6  •  2  0  :  6  C  8  (6, DMSO-dg) : 0.87  1.23  ( b r , 18H, c h a i n ,  2.16  ( s , 6H, 4 - C H ) , 2  1-CH  3  ( s , 4H, b r i d g e  o f 0.34  665[M-(2 C 0  2  : m/e, + C H 7  i ; L  6 8  2  -  1 9  '' '  g  liquors  (19.5%).  ( t , 6H, J=7 Hz, 5-, 6-, 3  2  CH_ ), 7.91 2  N)].  9.74.  9.66.  and 11-CH >, 3.83  774  "7.24; N,  H  ( s , 6H, 4 ' - C H )  ( b r , 2H, 1-NH), 11.12  Mass s p e c t r u m  '  2-, 3-, 4-, 2.21  3  3'-CH CH , c h a i n  10.55  N  9  : C, 68.18; H, 7.44; N,  NMR  4.07  The m o t h e r  180.0 - 1 8 1 . 0 ° C  Anal.  1  pure m a t e r i a l .  1.14  S'-CH^H^),  7-, 8-, /  9-,  2.26-2.49  ( s , 6H,  10-CH ) 2  (m, 8H,  0-CH ), 3  [ s , 2H, C (H) =C (CN) C 0 C H ] , 2  3  (br, l'-NH).  (M-2 C 0 ) , 742 2  [M-(2 C 0  2  + CH OH)], 3  1,11-Bis{ 5-  ( 2 - c y a n o - 2 - m e t h o x y c a r b o n y l v i n y l ) -2-[- ( 3 - e t h y l -  4-methyloyrrol-2-yl)methyl] -4-methylpyrrol-3-yl}undecane  119  119  l , l l - B i s { 2-[ ( 5 - c a r b o x y - 3 - e t h y l - 4 - m e t h y l p y r r o l - 2 yl)methyl]  -5-(2-cyano-2-methoxycarbonylvinyl)-4-methylpyrrol-  3 - y l } u n d e c a n e 118  (1.39 g  fluorbacetic  (15 mL)  5 min.  acid  Removal  1.61  mmol) and r e d i s t i l l e d t r i -  were s t i r r e d  o f an a l i q u o t  under n i t r o g e n f o r  i n t o methylene c h l o r i d e  checking  by t i c ( i n 2% m e t h a n o l - m e t h y l e n e c h l o r i d e )  a single  yellow  yellow  removed  revealed  r e d by b r o m i n e v a p o u r .  spot remained a t the o r i g i n , i n d i c a t i n g  disappearance was  spot, colored  and  o f the s t a r t i n g m a t e r i a l .  by e v a p o r a t i n g u n d e r r e d u c e d  No  the complete  Most o f the  acid  p r e s s u r e , the  261  residue  t a k e n up i n m e t h y l e n e c h l o r i d e  saturated (30 mL)  aqueous s o d i u m b i c a r b o n a t e  and d r i e d  by c o n c e n t r a t i n g  the presence o f methanol.  The y i e l d  crystalline  g  solid  was  were c o n c e n t r a t e d  MP  (2x30 mL)  1.02  and c o o l e d  The m o t h e r  i n ice,  to obtain  micro-  liquors  an  additional  : 132.0 - 1 3 4 . 0 ° C  Found  for 47 C  H  N 6 2  6 4 0  :  C  '  7 2  -  8 4  "  H  '  8.06; N, 10.84.  : C, 73.00; H, 7.90; N, 10.73.  "''H NMR  (6, C D C 1 ) ;  1.07  3  1.28  ( b r , 18H, c h a i n ,  2.06  ( , 6H, 4 ' - C H ) , 2.17 s  2  ( t , 6H, J=7 .5 Hz,  2-, 3-, 4-,  3  3'-CH CH , c h a i n 3  1-CH  and 11-CH ) , 3.84  2  2  (br,  2H, l ' - N H ) ,  2  2  3  9-,  2.24-2.62  ( s , 6H,  (m, 8H,  G-CH_ ), 3  [ s , 2H, C ( H ) = C ( C N ) C 0 C H ] , 9.41 ( b r , 2  3  3  : 165.22  (C=0), 140.43  ( p y r r o l e 2-C),  137.80  [ C ( H ) = C ( C N ) ] , 135.68  (pyrrole  4 - C ) , 124.15  123.45  (pyrrole  (pyrrole  2 ' - C ) , 120.70  88.62  2  •:)  (<5, C D C 1 ) 2  3 ' - C ) , 119.71  10-CH )  ( d , 2H, J=2 Hz, 5"-H), 7.56  2H, 1-NH) .  NMR  3'-CH CH_ ),  7-, 8-,  3  ( s , 4H, b r i d g e C H ) , 6.51 7.91  5-, 6-,  ( s , 6H, 4 - C H ) ,  3.94  C  solution i n  (10.4%)' .  Anal. Calcd.  1 3  this  The  of the orange,  (81.8%).  with  and w a t e r  w i t h a n h y d r o u s magnesium s u l f a t e .  p r o d u c t was c r y s t a l l i z e d  0.13 g  (75 mL), washed  5 - C ) , 122.44  (C^N), 118.49  [C(H)=C(CN) ], 2  52.44  (pyrrole (0-CH ), 3  4 ' - C ) , 115.11 30.44  (chain,  ( p y r r o l e 3-C), (pyrrole (pyrrole  5'-C),  2-C and 1 0 - C ) ,  29.59  (chain,  (bridge CH , 2  3-C, 4-C, c h a i n 1-C  ( 3 ' - C H C H ) , 10.33 2  3  Mass s p e c t r u m  5-C,  1-C,  8-C,  3  9.56  7 7 4 ( M ) , 742 +  9-C), 23.84  P'-CB^CR^),  and 11-C) , 17.59  (4'-CH ),  : m/e,  6-C,  15.65  (4-CH ). 3  (M-CH" OH) , 665 +  (M-C_ H N ) . +  7  1n  l,ll-Bis{2-[(3-ethyl-4-methylpyrrol-2-yl)methyl]-5-formyl4-methylpyrrol-3-yl}undecane  108a  l,ll-Bis{5-(2-cyano-2-methoxycarbonylvinyl)-2[  (3-ethyl-4-methylpyrrol-2-yl)methyl]-4-methylpyrrol-3-yl}  undecane 119  (903 mg,  1.17 mmol) and p o t a s s i u m h y d r o x i d e  (4 g)  in  water  (75 mL)  of  reflux,  were h e a t e d  n-propanol  under n i t r o g e n .  (35 mL)  was added  s t a r t i n g m a t e r i a l and t h e r e a c t i o n was spectroscopy. of  i n intensity.  indicating was  and by  MP  as a f i n e  filtration,  dessicator  over  : C, 75.61; H,  NMR  (br,  a t A=320  and nm  The  reaction  When t h e a l c o h o l  separated out, p a r t l y  crystalline solid.  3 9  H  hydroxide,  5 6  N 0 4  2  T h i s was  yield  was  as brown lumps isolated  i n a vacuum682 mg  (95.6%).  :  3  1.08  18H, c h a i n 2-, 3-, 4-, 6H, 4 ' - C H ) , 3  2  3  2  2.27  9.47  ( t , 6H, J=7.5 Hz, 3 ' - C H C H ) , 2  5-, 6-,  and 1 1 - C H ) , 3.87  Cs, 2H,  7-, 8-,  3  2  HC=0).  9.14;  9.35.  ( s , 6H, 4 - C H ) ,  2H, J=2 Hz, 5'-H), 8.07  1-NH),  : C, 76.43; H, 9.21; N,  9.06; N,  (6,CDC1 )  3 ' - C H C H , 1-CH (d,  characteristic  : 157.0 - 1 5 8 . 5 ° C  Found  (s,  2.5 h.  uv-visible  wavelength  A new band a p p e a r e d  potassium  Calcd. for C  H  to lower  washed w i t h w a t e r and d r i e d  Anal.  1  shifted  f  i n approximately  o f f , the product  partly  followed by  the d e p r o t e c t i o n o f the formyl group.  complete  boiled  to s o l u b i l i z e the  The a b s o r p t i o n band a t 4 07 nm,  the c y a n o a c r y l a t e group  decreased  At the onset  3  9-, 10-CH ) , 2.05 2  2.27-2.63  (m, 8H,  ( , 4H, b r i d g e C H ) , s  ( b r , 2H, l ' - N H ) ,  1.29  2  9.41  6.44  ( b r , 2H,  264 1 3  C  NMR  (6, CDC1 ) 3  : 175.93  (C=0), 138.10  133.20  (pyrrole  4 - C ) , 128.27  (pyrrole  123.35  (pyrrole  2 ' - C ) , 121.39  (pyrrole  4 ' - C ) , 114.78  (pyrrole  29.63  (chain,  3-C, 4-C,  23.81  (chain,  1-C and 1 1 - C ) , 22.97  ( 3 ' - C H C H ) , 15.82 2  3  Mass s p e c t r u m 121  (C H 8  N ) , 94 +  1;L  :  5 ' - C ) , 30.77 5-C, 6-C,  612  (C H N) . +  6  g  ( p y r r o l e 3-C),  3 ' - C ) , 117.76  (pyrrole  2-C and 1 0 - C ) ,  7-C, 8-C,  ( M ) , 583 +  5 - C ) , 123.34  (chain,  9-C,  10-C),  ( b r i d g e C H ) , 17.68 2  P ' - C I ^ C H ^ , 10.35  m/e,  ( p y r r o l e 2-C),  ( 4 ' - C H ) , 8.92 3  ( M - C H ) , 122 +  2  5  (4-CH >. 3  (CgH^N)" " 1  265  3.8  SYNTHESES OF STRAPPED  3.8.1  PORPHYRINS  7 17-Diethyl-2,8,12,18-tetramethyl-3,13/  undecamethyleneporphyrin  109a  109a  n  =11  Method A  (i)  Decarboxylation:  l , l l - B i s { 2- [ ( 5 - c a r b o x y - 3 - e t h y l - 4 - m e t h y l p y r r o l - 2 y l ) m e t h y l ] - 5 - f o r m y l - 4 - m e t h y l p y r r o l - 3 - y l } u n d e c a n e 107a (715 mg,  1.02 mmol) was d i s s o l v e d  (160 mL)  i n a 500 mL e r l e n m e y e r  adapter  and a n i t r o g e n  inlet.  i n dimethylformamide  flask,  fitted  with a Claisen  The uv s p e c t r u m o f a d r o p o f  266 this  solution,  diluted  w i t h methylene c h l o r i d e ,  b a n d s , one a t 280 nm, a n d t h e o t h e r stirred  showed two  a t 320 nm.  The m a g n e t i c a l l y  d i m e t h y l f o r m a m i d e s o l u t i o n was h e a t e d a t i t s r e f l u x  temperature  (153°C) f o r 2 h .  was  i n t o methylene c h l o r i d e  removed  recorded.  The i n t e n s i t y  decrease r e l a t i v e  At regular  intervals,  an a l i q u o t  and i t s uv s p e c t r u m  o f t h e 28 0 nm band was o b s e r v e d t o  t o t h a t o f t h e 320 nm band, w h i c h was t a k e n  as an i n d i c a t i o n o f t h e e x t e n t o f d e c a r b o x y l a t i o n .  In 2 h,  t h e 28 0 nm band was r e d u c e d t o a s h o u l d e r . The nitrogen,  s o l u t i o n was c o o l e d  t o room t e m p e r a t u r e u n d e r  e v a p o r a t e d under reduced p r e s s u r e  50 mL and added  t o methylene c h l o r i d e  then e x t r a c t e d w i t h water  filtered,  diluted  and u s e d i n t h e c y c l i z a t i o n  (ii)  Intramolecular  flasks,  toluene-p-sulfonic and d i l u t e d  w i t h anhydrous  chloride  step.  covered with acid  o u t i n two 2 - l i t e r  aluminum  foil,  (4.0 g ) , d i s s o l v e d  with methylene c h l o r i d e  slowly  sodium-  t o 500 mL w i t h m e t h y l e n e  was c a r r i e d  methane d i m e r 108a p r e p a r e d added v e r y  T h i s was  2+2 c o u p l i n g :  The c y c l i z a t i o n erlenmeyer  (200 m L ) .  (3x6 0 mL) t o remove most o f t h e  remaining dimethylformamide, d r i e d sulphate,  to approximately  above  each  containing  i n methanol  (6 00 mL).  (25 mL)  The d i p y r r o -  ( i n m e t h y l e n e c h l o r i d e ) was  to the magnetically  s o l u t i o n by means o f a s y r i n g e pump.  stirred  acid  catalyst  The s y r i n g e pump, o p e r a t -  267 ing  a t i t s slowest speed,  20 mL  syringe. The  to  t o o k a p p r o x i m a t e l y 7 h. t o empty one  The e n t i r e  a d d i t i o n was c o m p l e t e d  reddish v i o l e t  s o l u t i o n was c o n c e n t r a t e d down  a p p r o x i m a t e l y 150 mL and e x t r a c t e d  bicarbonate With  solution  the removal  i n 6 days.  (3x50 mL)  of the a c i d  with saturated  t o remove t h e a c i d  the s o l u t i o n  catalyst.  turned dark  b u t was f l u o r e s c e n t  under  to  (an o i l pump had t o be c o n n e c t e d  dryness  rotary  i n vacuo  e v a p o r a t o r t o remove t h e l a s t  formamide), and  The  The  as d e s c r i b e d  Chromatographic  a methylene  eluted  slurry  out.  of a c t i v i t y  throughout  band c o u l d  t h e brown i m p u r i t i e s ) .  show any f l u o r e s c e n c e u n d e r  chromatographed I silica  was a l m o s t c o l o r l e s s . chloride  be o b s e r v e d  chloride  column; t h e on t h e c o l u m n ,  out d i dnot  The e l u t i o n  until  was  the eluate  The s o l v e n t was c h a n g e d  and t h e p o r p h y r i n e l u t e d  g e l (8 0 g •.) .  (due t o t h e m a s k i n g  eluting  365 nm l i g h t .  using  non-porphyrin  the e n t i r e  The s o l u t i o n  c o n t i n u e d w i t h pure methylene  chloride  of the porphyrin.  The p o r p h y r i n was a d s o r b e d  a l t h o u g h no s p e c i f i c  methylene  to the  traces of dimethyl-  c r u d e p o r p h y r i n was f i r s t  chloride  taken  below.  purification  i m p u r i t i e s were a d s o r b e d  by  T h i s was t h e n  column was o v e r l o a d e d and t h e d a r k brown  excess  brown  t h e r e s i d u e t a k e n up i n minimum m e t h y l e n e  chromatographed  (iii)  365 nm l i g h t .  sodium  t o 2%  methanol-  o u t as a d a r k  268  purple  solution,  together  with  some brown i m p u r i t i e s  (observed  on t i c ) . The on  activity  as  the  partially  IV  silica  solvent.  The  adsorbed a t the and  gel  origin.  and  also discarded.  The  exhibiting  A  was  collected  sacrificing  basic the  alumina  eluting  the o r i g i n  by  type  then  final  purification  and  the p o r p h y r i n  cyclization appeared  only  A l l the  the  the p o r p h y r i n  was  crystallized 232  overall  mg..  yields  product  o u t was  porphyrin without  out  using  20  g.  first  The  concentrated  (39.6%) o f of  this  clean and  the p o r p h y r i n  crops  rechromatographed  on  only; and  109a.  and  39.6%  the  particular  A l l the  t h e mother  s t o r e d i n the  obtained.  and  yields  (some d e c o m p o s i t i o n  second c r o p  the  decarboxylation-  (108a).  were combined  a combined  moved.  at  f r o m n i t r o m e t h a n e , d r i e d on  starting material  were f o r t h e  i n ) and  the  column.  porphyrin.  carried  to depend, to a l a r g e e x t e n t ,  later  the  was  methanol-  i m p u r i t i e s were a d s o r b e d  solution eluting  a l l preparations  T h i s was  t o 1%  separated  r e a c t i o n v a r i e d between 22.0%  sample o f t h e recorded  was  brown  spectrum) which  m o v i n g on  be  o u t was  (3% w a t e r added) w i t h m e t h y l e n e c h l o r i d e as  vacuum-line, to give The  i m p u r i t i e s were  a f l u o r e s c e n t band  changed  the product  since i t could not  solvent.  reddish v i o l e t  set  etio  a c o n s i d e r a b l e amount o f  The  of  the  t r a c e o f brown i m p u r i t y moved a l m o s t b e h i n d  and  rechromatographed  band e l u t i n g  followed  s o l v e n t was  methylene c h l o r i d e to get  some o f  first  an  was  ) u s i n g methylene c h l o r i d e and  T h i s was  The  porphyrin  (40 g  porphyrin  non-fluorescent.  (very d i l u t e  purified  liquors refrigerator. had  269 MP  :  297.0  Mol.Wt.  - 298.0°C  Calcd.  for C  3 Q  H  5 ( )  N  : .574.4036;  4  r e s o l u t i o n mass s p e c t r o m e t r y  Anal.  Calcd.  for C^H^Nj  F o u n d : C, 81.22; H,  1  H  NMR  3.72  2  3.64 3  and one p r o t o n  0.12  (m, 2H, c h a i n p r o t o n s ,  -2.82  (m, 4H, c h a i n p r o t o n s ) ,  1 3  C  NMR  2  3  Visible  16.61  termini) ,  CH CH ), 2  3  protons),  (m, 4H, c h a i n  -3.46  (4C, meso c a r b o n s  protons),  ( b r , 2H, NH),  2  - (nm) , e,  3  (CH C1 ) 2  2  (16C, a - a n d  -4.03  p-pyrrolic  5-, 10-, 15-, 2 0 - C ) ,  (11C, c h a i n  (2C,CH CH ),  spectrum  log  and 15-H),  : 146.73, 145.12, 143.67,  3  28.67, 27.00, 25.98, 25.38 CH CH ),  ( t , 6H,  protons  protons).  (6, 10% TFA-CDC1 )  99.94  9.75.  termini,  (m, 2H, c h a i n  -2.58  140.56, 140.24, 140.05, 139.20 100.89,  each a t c h a i n  3  -0.12  5-H  each a t c h a i n  ( s , 6H, two CH_ ) , 1.84  (m, 4H, c h a i n p r o t o n s ) ,  (m, 2H, c h a i n  N,  ( s , 2H, m e t h i n e  ( s , 2H, m e t h i n e p r o t o n s  (m, s , 8H, one p r o t o n  two CH_ ) , 3.37 1.43  3  8.77;  9.77.  : 9.97  3  (m, 6H, CH_ CH  3.65,  N,  (400 MHz,6, C D C 1 )  10-H and 20-H), 9.80  high  : 574.4040  : C, 81.49; H,  8.73;  F o u n d , by  carbons),  12.21, 11.75  141.41, carbons),  28.86,  20.21  (2C,  (4C, C H ) . 3  :  400.7  503.1  539.8  571.9  625.8  5.24  4.05  4.05  3.80  3.59  270 Method B :  The  starting  material for this  a-formyl-a'-unsubstituted via  dipyrromethane dimer  the cyanoacrylate-benzyl  (317  mg,  ester route.  using a solution  methanol  (25 mL) and m e t h y l e n e c h l o r i d e  experimental  details  108a  (200 mL): was  of toluene-p-sulfonic acid  f o r the c y c l i z a t i o n  chromatographic p u r i f i c a t i o n  described  i n Method A a b o v e .  porphyrin  109a was 153 mg  (600 mL).  (4 g) i n  The  r e a c t i o n , work-up  were t h e same a s  those  The y i e l d o f t h e p u r i f i e d  (51.5%).  of  t h i s m a t e r i a l were i d e n t i c a l  of  10 9a p r e p a r e d  by Method A.  prepared  Compound 108a  0.52 mmol) i n m e t h y l e n e c h l o r i d e  cyclized  and  s y n t h e s i s was t h e  The s p e c t r a l  to those Further,  p o i n t d i d n o t show any d e p r e s s i o n .  observed t h e mixed  properties i n t h e samples melting  271 7,17-Diethyl-2,8,12,18-tetramethyl-3,13-decamethylene  3.8.2  porphyrin  109b  109  T h i s compound was for  the  and  product  :  37.3%  was  chloride  MP  n=10  prepared  by  t h e Method A  s y n t h e s i s of the undecamethylene p o r p h y r i n  five preparations, overall 34.7%  b  of  the p o r p h y r i n  crystallized  solutions using  269.0 -  MoT.Wt. C a l c d .  yields  (from 109b  107b)  of  109a.  The  methylene  nitromethane.  270.5°C  for C^H^IS^  r e s o l u t i o n mass s p e c t r o m e t r y  :  560.3879  : 560.3873.  ;  In  29.1%, 31.3%,33.2%,  were o b t a i n e d .  from the chromatographed  described  F o u n d , by  high  Anal.  Calcd. f o r C  3 g  H gN 4  : C,  4  81.38; H, 8.63; N, 9.99;  Found:  C, 81.04; H, 8.62; N, 9.93.  '''H NMR  (400 MHz,  6, CDC1 )  10-H and 20-H), 9.67 (m, 4H, C H C H ) ,  3.60  (s, 6H, C H ) , 3.46  2  2  8'-H), -1.17  (m, 2H, c h a i n 4'-H,  3  1.51  7'-H), -2.23  9'-H), 0.03  (m, 2H,  8'-H), -1.79  (m, 2H, c h a i n 5'-H,  (m, 2H, c h a i n 4'-H,  6'-H),  7'-H), -5.87  6'-H).  ( 6 : , 10% TFA- CDC1 )  NMR  3.27  (m, 2H, c h a i n  (m, 2H, c h a i n 3'-H,  (br, 2H, NH), -5.13  (m, 2H, c h a i n 5'-H,  C  ( t , 6H, C H C H ) ,  9'-H) , "fd . 4 6 (m, 2H, c h a i n 2'-H,  t  c h a i n 3'-H,  -3.27  (m, 2H, c h a i n l ' - H , lO'-H),  (m, 2H, c h a i n l ' - H , lO'-H),  3  3  I 3  3.67  3  (s, 6H, C H ) , 1.81  (s, 2H, methine protons  (s, 2H, methine protons 5-H and 15-H),  4.06  2'-H,  : 9.89  3  3  \ 146 . 87/, 145 . 61 > 143.'61, •  141.22, 140.44, 140.29, 138.95, 138.23 p y r r o l i c carbons), 100.24, 100.05  (16C, a - and 6-  (4C, meso carbons 5-, 10-,  15--, 20-C) , 28.47, 27.94, 26.96, 26.46, 25. 96 (10C, c h a i n c a r b o n s ) , 20.20  (2C, CH CH ), 2  3  16.62  (2C, C H C H ) , 2  3  11.77 (4C,  CH ). 3  V i s i b l e spectrum  (CH„C1 ) : 2 2  max  A  ( n m )  '  log e ,  4  0  2  -0  507.5  544.4  572.7  626.2  5.21  3.96  4.03  3.78  3.37  273 3.8.3  7,17-DiethyT-2,8,12,18-tetramethyl-3,13-nonamethylene  porphyrin  109c  109  n= 9  C  The p r o c e d u r e u s e d i n t h e p r e p a r a t i o n o f t h i s p o r p h y r i n was t h e same a s t h a t employed of  i n the preparation  t h e u n d e c a m e t h y l e n e p o r p h y r i n 109a (Method A ) . T h i s p o r p h y r i n was f o u n d t o be a d s o r b e d o n t o  gel,  more t h a n t h e u n d e c a m e t h y l e n e  analogues.  On a c t i v i t y  I silica  silica  and t h e d e c a m e t h y l e n e  g e l , 5% m e t h a n o l - m e t h y l e n e  c h l o r i d e was n e c e s s a r y t o make t h e p r o d u c t t o move, b u t i t eluted  out with  some i m p u r i t i e s .  2% m e t h a n o l - m e t h y l e n e  chloride  eluted  o n c e a g a i n , was c o n t a m i n a t e d w i t h undecamethylene  IV s i l i c a g e l ,  out the porphyrin but  impurities.  Unlike the  and d e c a m e t h y l e n e a n a l o g u e s , t h i s d i d n o t  move w i t h m e t h y l e n e c h l o r i d e water).  On a c t i v i t y  I n 10% e t h y l  a l o n e , on b a s i c  a l u m i n a (3%  acetate-methylene c h l o r i d e , the  274 porphyrin the  e l u t e d out  pure, l e a v i n g a l l the  impurities at  origin.  porphyrin  The  maximum y i e l d  was  26.8%.  20.0%, 21.8%, 25.1% t h e p o r p h y r i n was observed,  In f o u r o t h e r and  later,  that this  MoT.  Wt.  Calcd.  Calcd. : C,  NMR  (m,  yields  out  of  In a l l i n s t a n c e s  from n i t r o m e t h a n e . (109c), was  less  the  r e v e r s e was  undecamethylene  analogues.  It  was  soluble  true for  330°C  Anal.  for C  3 ?  H  4 6  N  20-H) 4H,  for C ^ H ^ N j  81.33; H,  (400  10-H,  purified  syntheses,  porphyrin  MHz,  6,  , 9.36  CH CH ), 2  l ' - H , . 9 ' - H ) , 3.03, ringCH_ ), 3  1.79  8 ' - C H ) , -1.14 2  chain  3'-H,  5'-CH  ) , -4.15  4'-H,  6'-H).  3  3.00  2H,  7'-H), -3.06 (m,  2H,  ;  Found by  high  81.27; H,  : 9.71  ( s , 2H,  methine protons CH_ ) , 3.29 3  (m, s ,  8H,  chain  CH CH_ ) , 0.56 2  chain  8.48;  N,  10.25.  10.24.  (s , 6H,  ( t , 6H, (m,  N,  CDC1 )  3.57  3  54 6.37 23  : 546.3737.  : C,  8.57;  (s., 2H,  :  4  r e s o l u t i o n mass s p e c t r o m e t r y  Found  f o r the  were o b t a i n e d .  i n nitromethane;  t h e d e c a m e t h y l e n e and  >  25.0%  crystallized  i n methanol than  MP-:  obtained  3  3'-H,  ( b r , 2H, c h a i n 4 -H, 1  (m,  methine  5-H, (m,  15-H) 2H,  9'-H  4H,  chain  NH) , --3.33  (m,  6'-H), -4.35  ,  3.97  chain  1*-H,  7'-H), -1.56  protons  (m, 2H, (m,  and 2'-CH , 2  2H, chain 2H,  chain  NMR  ( 6 , 10% TFA-CDCT )  : 146.60, 144.65, 141.21,  3  139.59, 139.07, 134.27 101.48,  99.72  (16C, a-and g - p y r r o l i c  (4C, meso c a r b o n s  (9C, c h a i n c a r b o n s ) ,  16.47  11.66  (2C, C H C H ) ,  Visible  2  3  Spectrum (CH C1 ) 2  A  (nm), max log - , e  2  carbons),  5-, 10-, 15-, 2 0 - C ) ,  28.22, 25.84, 24.97  140.42,  20.12  (2C,  28.72, CH CH ), 2  3  (4C, C H ) . 3  :  405.3  513.5  551.7  579.1  633.0  5.23  3.91  4.08  3.82  3.43  3.9 i SYNTHESES OF DURENE-BIS-PENTANOIC ACID AND  ITS PRECURSORS  1,4-Bis C 2 , 2 - d i c a r b o x y e t h y l ) - 2 , 3 , 5 , 6 - t e t r a m e t h y l b e n z e n e  121 Freshly was d i s s o l v e d  cut metallic  sodium  i n anhydrous e t h a n o l  (12.85 g,  (600 mL)  in a  0.56  moi)  2-liter  121  276 erlenmeyer 160.4  flask,  1.0  g  moi)  under n i t r o g e n . was  stirred  (152  D i e t h y l malonate  1,4-bis(chloromethyl)  i n , f o l l o w e d by  -2,3,5,6-tetramethylbenzene[bis(chloromethyl)durene] 0.25  moi)  ethanol. was  w h i c h was The  refluxed  remained mixture moving  s t a r t i n g m a t e r i a l d i d not d i s s o l v e . on  a stirrer-hot  throughout d i d not  starting material  anhydrous  The  mixture  (4 00  was  mL)  continued  added.  until  added u n t i l  hydroxide The  mL)  and  next (250  solution  a l l of the s o l i d  reaction  but a s i n g l e  was  distilled  fast  the s o l u t i o n The  A white  solid  became a c i d i c .  filtration,  analytically  g,  100°C.  Water  (approximately  precipitated  The  150 solid  (94.9%).  pure without  In a n o t h e r  was  boiling  mL  aqueous  was 1-liter  erlenmeyer solution  hydrochloric  o u t when t h e o f a c i d were added  was  collected  dried The  by  in air for  p r o d u c t was  found  recrystallization.  preparation starting  a  i n water  into a 3-liter  washed w e l l w i t h w a t e r and  s e v e r a l d a y s t o g i v e 86.8  moi)  concentrated  A further  cooled.  3.04  off and  of ethanol  reached  treated, dropwise,'with mL).  g,  dissolved  reheated to b o i l i n g .  t h e s o l u t i o n was  t o be  (200  distillation  the temperature  of water), transferred  acid  solid  of the  t h e r e a c t i o n m i x t u r e , c o o l e d t o room t e m p e r a t u r e  flask  g  of  a white  A t i c analysis  ( a p p r o x i m a t e l y 200  of potassium  and  h;  (57.8  spot.  solution  was  f o r 0.5  plate>  this period.  show any  Ethanol from  5 0 mL  washed down w i t h a n o t h e r  mL,  with  64.7  g  bis  277 (chloromethyl)durene,  the product  121 was i s o l a t e d  i n 98.2%  yield.  MP  :  278.0 - 280.0°C (dec)  Anal. Calcd. f o r  C  C,  X  H 1  8  2  2°8  :  C  '  5  9  -  0  1  ;  H  ' 6.05.  Found  :  58.95; H, 5.92.  H NMR  (270 MHz, 6, DMSO-d,) : 2.13 b  3.13-3.22  (m, 4H, s i d e  ( s , 12H, d u r e n e - C H j , j  c h a i n 1 - C H ) , 3.22-3.33 2  (m, 2H,-CH  (C0 H) ). 2  2  Mass s p e c t r u m  :  m/e  278  (M-2.C0 ) , 219 [ M- (2 . CG" +CH C0 H) ] , +  205 [ M - ( 2 . C 0 + C H C H C 0 H ) ] , +  2  2  2  +  2  2  44  2  2  2  (CC> ) . +  2  1,4-Bis(2-carboxyethyl)-2,3,5,6-tetramethylbenzene  122  COjH  122 Quinoline flask  fitted  (140 mL) was p l a c e d i n a 2 - l i t e r  with a Claisen  adapter  erlenmeyer  and a n i t r o g e n i n l e t and  278 heated  a t t h e maximum  the onset  of reflux,  small portions. observed  refluxed  the a d d i t i o n .  adhering  and c o n t i n u e d  for  a further  and  poured  10 m i n . t o e n s u r e  into  crystallized  to the g l a s s .  to recover  d i o x i d e was glass  apparatus  heating;  adapter,  quinoline  w a s h i n g down a l l  The s o l u t i o n was  heated  complete d e c a r b o x y l a t i o n  6M h y d r o c h l o r i c a c i d  o u t was c o l l e c t e d  At  121 was added i n  The e n t i r e  a t the top of the C l a i s e n  solid  acid  e v o l u t i o n o f carbon  i n aluminum f o i l  the  saved  of a stirrer-hotplate.  the b i s malonic  Vigorous  throughout  was wrapped  setting  (400 mL).  by f i l t r a t i o n  the q u i n o l i n e .  The s o l i d  The p r o d u c t  and t h e f i l t r a t e  was washed w e l l  w i t h water under s u c t i o n . The solution bath. of  crude  More s o l i d  The  i n water  a saturated  (500 mL) on a steam  to dissolve  (total  the product.  plug.  The f i l t r a t i o n  filtrate  collected give  by f i l t r a t i o n ,  62.15 g  :  Anal.  with concentrated  was e x t r e m e l y  hydrochloric acid  volume  The s o l u t i o n  h o t , u s i n g a steam-heated Buchner  b i s ( c a r b o x y e t h y l ) d u r e n e was r e p r e c i p i t a t e d  the  C,  a celite  with  s o d i u m b i c a r b o n a t e and w a t e r  1500 mL) were added  carrying  was h e a t e d  o f sodium b i c a r b o n a t e  was f i l t e r e d w h i l e  MP  solid  funnel slow.  by a c i d i f y i n g and was  washed w i t h w a t e r and d r i e d  i n a i r to  (96.3%).  284.0 - 2 8 6 . 0 ° C  C a l c d . f o r C, .-H__0. l b zz 4  68.48; H, 7.93.  : C, 69.04; H, 7.97;  Found :  1  H  NMR  2.39  (<5 , DMSO-d,) :  2.13  (m, 4H, s i d e chain  (S, 12H, durene CH_),  2.06-  2-CH ), 2.72-3.02 (m, 4H, side 2  chain  1-CH ). 2  A 1 g- sample of 122 was converted to i t s d i m e t h y l e s t e r f o r the purpose of c h a r a c t e r i z a t i o n . r e f l u x e d with four e q u i v a l e n t s e v o l u t i o n of gases ceased.  The s o l i d  was  of t h i o n y l c h l o r i d e u n t i l the  The excess reagent was d r i v e n o f f  by e v a p o r a t i n g , i n vacuo, with carbon t e t r a c h l o r i d e and the b i s a c i d c h l o r i d e was refluxed- with methanol f o r 1 h. was evaporated o f f , the r e s i d u e  taken up i n methylene c h l o r i d e  and the a c i d i c i m p u r i t i e s removed sodium b i c a r b o n a t e and water.  Methanol  by e x t r a c t i o n with  The d i e s t e r was  saturated  crystallized  out by r e p l a c i n g methylene c h l o r i d e with aqueous methanol and p u r i f i e d by chromatography  (silica gel, activity I).  C0 CH 2  MP  :  Anal.  3  108.5 - 110.0°C  Calcd.  C, 7 0.35;  H,  for 8.53.  C  H 1  8  0 2  6  : 4  c  /  70.56; H, 8.55;  Found :  280 L  H  NMR  (6, C D C 1 )  ; 2.19  3  ( s , 12H, d u r e n e CH ) , 2.30 3  (m, 4H, s i d e  c h a i n 2 - C H ) , 2.90  1-CH ),  ( s , 6H,  2  1 3  C  3.66  NMR  - 3.14  2  (6,CDC1 )  2.54  chain  -Q-CE^).'  : 173.46  3  (m, 4H, s i d e  -  (durene  2-C,  (C=0), 135.19  4-C),  132.42  3-C,  5-C,  33.93  ( s i d e c h a i n 2 - C H ) , 26.13  (durene  6-C), 51.59  (0-CH ), 3  (side c h a i n 1-CH ),  2  1-C and  2  16.28  (durene-CH ) • 3  Mass s p e c t r u m 219  : .m/e  306  ( M ) , 275 +  (M-OCH ) , +  3  233  (M-CH C0 CH ) , +  2  2  (M-CH CH C0 CH ) . +  2  2  2  3  1,4-Bis(2-ethoxycarbonylethyl)-2,3,5,6-tetramethylbenzene  C 0  123  2 2 S C  H  123  1 , 4 - B i s ( 2 - c a r b o x y e t h y l ) - 2 ,3 ,'5 , 6 - t e t r a m e t h y l b e n z e n e 12 2  (158.94 g,- 0.57 moi) . e t h a n o l  and  concentrated s u l f u r i c  erlenmeyer toluene) was  flask  fitted  acid  (27 mL)  on a s t i r r e r - h o t  condenser.  plate  (200 mL)  were p l a c e d i n a  with a Dean-Stark t r a p  surmounted by a r e f l u x  refluxed  (400 mL) , t o l u e n e  The  (filled  2-liter with  solution  f o r approximately  4 h.  3  During in  this  p e r i o d , no w a t e r was  the t r a p .  the r e a c t i o n  The c o n t e n t s flask,  and t h e a z e o t r o p e imately  observed  t o g e t h e r w i t h more e t h a n o l  was  allowed  to c o l l e c t  out but the s o l u t i o n  More t o l u e n e  (4 00 mL)  on a steam b a t h  was  added  to dissolve  washed  c o o l over  ice.  The  solid  ether  give  (79.6%).  151.80 g,  was  The  into  product  two p h a s e s .  and t h e s o l u t i o n was Water  reheated  (500 mL)  removed.  collected  (boiling  c o o l e d , the  The  was  organic to  by f i l t r a t i o n ,  r a n g e 3 0 - 6 0 ° C ) and d r i e d filtrates g  were  washed to  concentrated  ( 9 . 8 % ) , f o r an  overall  o f 89.4%.  :  118.5  -  120.0°C  Anal. Calcd. for C 72.10; H,  -"-H NMR  2.90  (approx-  w i t h w a t e r and a l l o w e d  t o g i v e a s e c o n d c r o p o f 18.66  (s,  mL)  i n the t r a p  separated  the s o l i d .  s e v e r a l times  with petroleum  C,  was  and t h e c l o u d y w a t e r p h a s e was  p h a s e was  MP  (100  into  3 00 mL) .  crystallized  yield  out  i n t h e t r a p were i n t r o d u c e d  When t h e r e a c t i o n m i x t u r e  added  to separate  2 0  durene C H ) , 3  -0-CH -CH ) . 2  3  O  4  : 1.25  3  - 3.12  3 Q  : C,  71.82; H,  9.04;  Found  :  9.11.  (6, C D C 1 )  12H,  H  (m, 4H,  2.28  ( t , 6H, - 2.50  J=7  Hz,  -OCH CH_ ),  2.18  (m, 4H,  side chain  2-CH ),  2  s i d e c h a i n 1 - C H ) , 4.14 2  3  (q, 4H,  2  J=7  Hz,  282 1 3  C  NMR  ( , .CDC1 )  :  3  173.10 (C=0) , 135.25 (durene 1-C  4-C), 132.39 (durene 2-C,  3-C,  34.21  26.15  (side c h a i n 2-C)  (durene CHg),  Mass spectrum C 0  2 2 5 C  H  ) +  '  2  3  3  14.28  : ( M  C H  6-C),  60.41  (-0-CH CH ), 2  (side c h a i n 1-C),  3  16.30  (0-CH -CH ). 2  m/e "  5-C,  and  2  334 C H  2  3  (M ), 289 +  C 0  2 2 5 C  H  ) +  ( M - O C „ H ) , 247  (M-CH„  +  c  '  1, 4-Bis (3-hydroxypropyl) -2,3,5, 6-tetramethylbenzene  •-  124  CHjOH  124 1,4-Bis(2-ethoxycarbonylethyl)-2,3,5,6-tetramethylbenzene (16.7 g, 0.05  moi)  was  i n a 1 - l i t e r erlenmeyer  d i s s o l v e d i n dry t e t r a h y d r o f u r a n (200 f l a s k f i t t e d with a C l a i s e n adapter,  n i t r o g e n i n l e t , a dropping f u n n e l (pressure e q u a l i z i n g surmounted by a c a l c i u m c h l o r i d e d r y i n g tube. magnetically s t i r r e d 0.22  moi)  was  (8.5 g>  added, f o l l o w e d by the r a p i d dropwise  the r e a c t i o n mixture  0.36  type)  To the  s o l u t i o n , sodium borohydride  of boron t r i f l u o r i d e e t h e r a t e (45 mL, of  mL)  moi).  addition  Tic analysis  ( i n C H C l ) showed a s i n g l e spot, with 2  2  a lower r ^ v a l u e than t h a t of the s t a r t i n g m a t e r i a l .  283 The (50 mL) under  and  e x c e s s d i b o r a n e was  water  reduced  as a w h i t e solid  was  (100 mL)  and  destroyed with acetic  t h e s o l v e n t was  solid.  More w a t e r  collected  by  (3 00 mL)  filtration.  by d i s s o l v i n g  reprecipitating  was  The  MP  :  i n warm e t h a n o l  w i t h water.  Two  C,  1  H  77.02; H,  side  C  C  H 1  2 - C H ) , 2.26  (<S,  3  2-C,  3-C,  C  /  7  : m/e, +  2  6  -  ( s , 2H,  7  5  ;  '  H  1°-  136.16 6-C),  250  recrystallized  , an  4 7  ;  overall  Found  :  4H,  (m,  side  4H,  -CH_ OH) . 2  1-C  and  4-C),  (CH OH), 32.82 2  16.38  (durene  205 +  (side chain  3  +  2  132.23  CH ).  (M-CH CH OH) ,  ( C H ) ^\ . 3  (m,  2.66-2.90  3  63.14  +  1.58-1.94  CH ),  (durene  (M ),  [C . ^  -OH),  durene  ( t , 4H,  :  5-C,  ( M - C H C H C H O H ) , 147 2  :  ( s i d e c h a i n 2-C),  Mass s p e c t r u m 2  6°2  3.78  CDC1 )  26.96  2  ( s , 12H,  2  NMR  6  : 1.50  chain l - C H ^ ,  1-C),  and  10.64.  3  (durene  (350 mL)  c r o p s of the g  was  159.5°C  (6, C D C 1 )  chain  1 3  -  Calcd. for  NMR  the  89.6%.  158.0  Anal.  added and  crude product  b i s ( h y d r o x y p r o p y l ) d u r e n e amounted t o 11.2 of  evaporated  p r e s s u r e c a u s i n g the product to separate out  recrystallized  yield  acid  2  191  284  1,4-Bis(3-bromopropyl)-2,3,5,6-tetramethylbenzene  127  CH Br 2  127 1,4-Bis 12 6  (7.5 g  , 0.03  were h e a t e d did in  the  moi)  at reflux  not d i s s o l v e , an o v e r a l l  mixture  (3-hydroxypropyl)-2,3,5,6-tetramethylbenzene  but  A t i c analysis  was  (20 mL)  and  The  pressure after  (83.3%).  The  o u t as  added and  was  reaction  s p o t , moving  faster  another  obtained.  g  r  temperature,  the a c i d e x t r a c t e d  methylene c h l o r i d e and  adding methanol.  s i l v e r y white  mL)  material  s a t u r a t e d sodium b i c a r b o n a t e  mother l i q u o r s  c r o p o f 0.90 In  starting  o f the  c o o l e d t o room  (100 mL)  (2x30 mL).  crystallized  The  (24  a pale yellow o i l , r e s u l t i n g  w i t h anhydrous sodium s u l f a t e  reduced  90.9%  into  showed a s i n g l e  solution  out w i t h water  second  aqueous hydrobromic-. a c i d  material.  methylene c h l o r i d e  dried  turned  30 min  The  solution  48%  under n i t r o g e n .  emulsion.  after  starting  and  solution  evaporated The  was  under  product  needles, y i e l d  9.4  g  were c o n c e n t r a t e d t o g i v e a  (7.9%).  p r e p a r a t i o n , an o v e r a l l  yield  of  than  MP  :  113.0 -  114.0°C  Anal.  Calcd.for C  Found  : C, 50.95; H, 6.49; B r , 4 2.28.  1  H  NMR  2.17  1 6  (6,CDC1 )  H  :  3  ( s , 12H, d u r e n e  Br  2 4  2  : C, 51.09; H, 6.43; B r , 42.48:  1.84-2.10  (m, 4H, s i d e c h a i n  C H ) , 2.68-2.92  (m, 4H, s i d e  3  2-CH" ) , 2  chain  1-CH ) , 3.45 ( t , 4H, J=6.5, CH_ Br) . 2  1 3  C  2  NMR  ( 6 , C D C 1 ) : 135.39 3  (durene 1-C and 4 - C ) , 132.33.  (durene 2-C, 3-C, 5-C, 6-C) , 33.92 chain  1-CH" ) , 29.37 2  Mass s p e c t r u m  :  (side chain  ( C H B r ) , 32.69 :(side 2  2-CH" ), 16.44 (durene-CH" ) .  m/e, 374-376-378  2  3  ( M ) , 267-269 +  (M-CH.,CH Br)  1 , 4 - B i s (4 , 4 - d i c a r b o x y ' b u t y l ) -2 ,3 , 5 , 6 - t e t r a m e t h y l b e n z e n e  12 9  129 To a s t i r r e d in  anhydrous  ethanol  s o l u t i o n o f sodium  (2.4 g , 104 mmol)  (200 mL), d i e t h y l m a l o n a t e  +  0  (25 mL, 26.4  165  mmol) and t h e b i s ( b r o m o p r o p y l ) d u r e n e  127 (15g . , 40 mmol)  were added and t h e r e s u l t i n g ' m i x t u r e . w a s h e a t e d on a h o t p l a t e under n i t r o g e n .  As t h e s o l u t i o n  material dissolved,  giving  a single imately  t h e complete product.  reached  f o r 3 0 min  separated  and a t i c a n a l y s i s  The s o l v e n t was d i s t i l l e d  o f f (approx-  hydroxide  (45 g ) i n w a t e r  the r e f l u x  hydrochloric solid,  acid.  yield  (200 mL).  temperature  The p r o d u c t  15.9 g  with  with  crystallized  (94.9%).  193.5 - 195°C (dec)  Anal.  1  bromide)  100°C and t h e h o t s o l u t i o n was a c i d i f i e d  out as a w h i t e  :  Within  conversion o f the s t a r t i n g m a t e r i a l to  of potassium  concentrated  C,  (sodium  h e a t i n g was c o n t i n u e d u n t i l  MP  the s t a r t i n g  120 mL) and t h e r e a c t i o n m i x t u r e was t r e a t e d  a solution The  solid  The s o l u t i o n was r e f l u x e d  indicated  reflux,  a pale yellow solution.  10 m i n . o f h e a t i n g a w h i t e out.  reached  Calcd. f o r 2 3 0 ° 8 C  H  :  C  /  6  2  >  5  5  ;  2  H  ' - '" 7  1 6  Found :  62.32; H, 7.20.  H NMR  2-CH  2  (6, DMSO-d,,) 3-CH ),  :  1.14-1.98  (m, 8H, s i d e  chain  2.07 ( s , 12H, b e n z e n e C H ) , 2.38-2.74  2  3  (m, 4H,  s i d e c h a i n 1 - C H ) , 3.25 ( t , 2H, J=7 Hz, C H(CC> H) ). 2  [C H y  +  2  ( C H ) ] , 44 +  3  2  : m/e, 334 (M-2.C0 ) , 247 [ M - ( 2 . C 0 + C H C H C H C 0 H ) 1  Mass s p e c t r u m 147  2  3  4  (CC> ) . +  2  2  2  2  2  2  287 1,4-Bis(4-carboxybutyl)-2,3,5,6-tetramethylbenzene -bis-pentanoic  acid)  (Durene  130  HOjC^ CO^  130 1,4-Bis(4,4-dicarboxybutyl)-2,3,5,6 12 9  (15.5 g  quinoline  , 36.7 mmol) was d e c a r b o x y l a t e d  (50 mL)  tetramethylbenzene  i n refluxing  i n t h e manner d e s c r i b e d f o r 1 , 4 - b i s  (2 , 2 - d i c a i r boxy e t h y l ) -2 ,3 ,5 , 6 - t e t r a m e t h y l b e n z e n e crude  p r o d u c t was r e d i s s o l v e d  filtered  through  concentrated  MP  :  • H NMR 1  and  a celite  i n h o t aqueous s o d i u m  p l u g and r e p r e c i p i t a t e d  hydrochloric acid  t o g i v e 11.6 g  (6, DMSO-d^) :  1.10-1.82  carbonate,  with  (94.6%).  2  4 - C H ) , 2.42-2.76 2  ( s , m,  (m, 8H, s i d e c h a i n 2-CH 16H, d u r e n e C H ,  characterization,  3  n  side  (m, 4H, s i d e c h a i n 1 - C H ) .  One gram o f t h i s m a t e r i a l was c o n v e r t e d for  The  210.0 - 2 1 1 . 0 ° C  3 - C H ) , 2.13, 2.06-2.38  chain  121.  2  to i t s dimethyl  ester,  i n t h e manner d e s c r i b e d f o r compound 122.  288  CH  MP  :  3  74.5 - 75.0 C U  Anal.  Calcd. f o r C 2 3 4 ° 4 H  C, 72.89; H, 9.45;  :  2  Found :  C, 72.70; H, 9.34.  1  H NMR  (6, CDC1 )  :  3  3- C H ) ,  2.21  2  1.24-1.98  (m, 8H, s i d e c h a i n 2-CH , 2  (s, 12H, durene C H ) , 2.24-2.50  (m, 4H, s i d e  3  c h a i n 4-CH ), 2.54-2.80 2  (m, 4H, s i d e c h a i n 1-CH ) , 3.66 (s'', 2  6H, 0-CH ). 3  1 3  (S , CDC1 )  € NMR  3  4- C), 131.99 33.95  :  174.01  (durene 1-C and  (durene 2-C, 3-C, 5-C, 6-C), 51.41  ( C H C 0 C H ) , 30.38, 29.40 2  (C=0), 136.45  2  3  (0-CH ), 3  (side c h a i n 1-C, 2-C), 25.50  (side c h a i n 3-CH ), 16.35 '(durene C H ) . 2  Mass Spectrum 247  : m/e,  362  (M ), 261  (M-CH CH CH C0 CH ) ,  +  +  2  2  2  2  3  (M-CH CH CH CH C0 CH ) , 147 [ C H (CH ) ] , 115 [ ( C H ) . +  2  C0 CH ] . +  2  3  3  2  2  2  2  3  +  ?  3  3  2  4  3.10  SYNTHESES OF DURENE-BIS-PENTANE BRIDGED DIMERS THE  AND  PORPHYRIN  1,4-Bis[5-(5-ethoxycarbonyl-2,4-dimethylpyrrol-3-yl)-5oxopentyl]-2,3,5,6-tetramethylbenzene  132  132 Durene-bis-pentanoic was c o n v e r t e d  to i t sb i s acid  used t o a c y l a t e  acid  130  chloride  two e q u i v a l e n t s  (16.7 g , 0.05 moi) and t h i s i n t u r n  of the B-free p y r r o l e  The e x p e r i m e n t a l d e t a i l s f o r t h i s a c y l a t i o n r e a c t i o n as  given  f o r the synthesis  chain  analogues.  was a d d e d w i t h i n  tained three  15 m i n  a t room t e m p e r a t u r e . crops,  to give  were  unlike the  O n l y one mole o f s t a n n i c  was u s e d p e r atom o f c h l o r i n e and  6_6 .  o f t h e undecane a n a l o g u e 88a.  The b i s a c i d c h l o r i d e was a s o l i d straight  was  i n the a c y l a t i o n  chloride  reaction,  t o t h e r e a c t i o n mixture mainThe p r o d u c t was i s o l a t e d i n  an o v e r a l l y i e l d  o f 21.2 g  (67.1%).  An a n a l y t i c a l  sample was r e c r y s t a l l i z e d  a concentrated minimum  MP  :  H  trifluoroacetic  Calcd.  Found  1  s o l u t i o n o f 132 i n m e t h y l e n e c h l o r i d e and  207.5 -  Anal.  209.0°C  for 3 C  H 8  5  N 2  2°6  :  ( f i , 10% TFA-CDC1 )  2  Hz,  4-, 4 ' - , C H ) , 4.47  (6, 10% TFA-CDC1 )  ;  H  '  8  - '" 2 8  N  /  4.43.  ( t , b r , 14H,  ( s , 12H, d u r e n e  (s., 6H, p y r r o l e 2.96  ( t , 4H,  ( q , 4H, J=7 Hz,  :  3  6-C), 123.03  (pyrrole  (-0-CH CH ), 2  (chain,  204.11  ( e s t e r C=0), 142.50  (durene 1-C and 4 - C ) , 132.37  3  2-CH ), 3  J=7.5  0-CH_ -CH ), 2  42.27  3  (pyrrole  (pyrrole  3  (chain  5-C and  2 - C ) , 136.59 3-C,  ( p y r r o l e 5-C),  CO-CH "), 2  (chain,  2 - C H ) , 14.26 3  C=0,  4-C, d u r e n e 2-C,  3 - C ) , 118.61  (pyrrole  4-CH,).  (chain  (pyrrole  1-, 1'-, 2-, 2 ' - C ) , 26.12  (durene C H ) , 15.44 13.03  2  1.46, 1.38-2.10  1-, l ' - C H ^ ) ,  2  5 ' - C ) , 164.25  62.57  1  ( b s , 2H, NH).  NMR  5-C,  *  4.63-  3  (m, 4H, c h a i n  C  2  4 - C H ) , 2.42  2.58-2.85  1 3  7  2  (s , 6H, p y r r o l e  10.20  '  2-, 2'-, 3-, 3 * - C H ) , 2.24  3  chain  C  :  3  0-CH CH , c h a i n 2.39  acid.  : C, 72.10; H, 8.08; N,  NMR  by a d d i n g e t h a n o l t o  30.62, 29.88 3-, 3 ' - C ) , 16.41 (-0-CH -CH ), 2  3  CH  3  Mass s p e c t r u m  : Relative Intensity  m/e 632  19  209  100  (%)  Assignment M  +  OH  H3C  ®  AVN  194  148  IR —  (v  max  KBr):  3280  (NH), 1645-1665  (C=0)  cm  292  1,4-Bis[5-(5-ethoxycarbonyl-2,4-dimethylpyrrol-3-yl)pentyl] 2/3,5,6-tetramethylbenzene  133  133 The diketone 132 (17 g , 26.9 mmol) was suspended i n tetrahydrofuran  (150 mL) and t r e a t e d with sodium  (3 g , 79.4 mmol) and boron t r i f l u o r i d e 111 mmol) i n the u s u a l manner. analogues,  (14 mL ,  U n l i k e the s t r a i g h t c h a i n  the s o l i d d i d not appear to d i s s o l v e and a t i c  a n a l y s i s of the r e a c t i o n mixture unreacted  etherate  borohydride  starting material.  and boron t r i f l u o r i d e  etherate  showed more than 8 0% o f  More sodium borohydride  (5 mL) were added and allowed  to s t i r f o r 30 min. but no change was observed More t e t r a h y d r o f u r a n r e a c t i o n mixture  (1 g)  on t i c .  (300 mL) was added to the  and with 5 min. o f s t i r r i n g , a l l the s o l i d  went i n t o s o l u t i o n and no s t a r t i n g m a t e r i a l c o u l d be d e t e c t e d on t i c . The excess diborane was destroyed and the r e a c t i o n mixture worked up i n the u s u a l manner.  The crude  s o l i d was  d i s s o l v e d i n hot t e t r a h y d r o f u r a n (300 mL), f i l t e r e d to  remove brown i m p u r i t i e s and r e c r y s t a l l i z e d to  give  14.3 g  overall  MP  :  Calcd.  Found  H  :  NMR  an  o f 88.3%.  for C  H 3  8  C, 75.18; H,  ( S, C D C 1 ) 3  chain,  2-, 2'-,  2.24-2.50  m  3  N 5  6  0 2  4  9.32;  : C, 75.46; H, N,  4'-CH ), 2  ( t , b r , 18H, 2.20, 2.22, 3  5-, 5 ' - C H ) ,  2.50-2.80  2  2  2  Mass s p e c t r u m : Relative Intensity 62  558  29  180  100  134  90  (%)  ( b s , 2H,  3  2.28, 3  (m, 4H, c h a i n  3  604  4.63:  0-CH ~CH  28H, p y r r o l e 2-CH , d u r e n e C H ,  (q, 4H, J=7 Hz, 0 - C H ~ C H ) , 8.73  m/e  9.33; N,  4.72.  : 1.35, 1.32-1.62  3-, 3'-, 4-,  (s,s,s, ,  4-CH , c h a i n 4.32  o f w h i t e powdery s o l i d , i n two c r o p s ;  198.0 - 199.0 °C  :  Anal.  1  yield  from methanol  pyrrole  1-,  NH).  1'-CH  2  294 I  ( ™.  R  v  v  KBr):.  3310 (N-H),  1670 (C=0)  cm . 1  1,4-Bis\5-(5-benzyloxycarbonyl-2,4-dimethylpyrrol-3-yl)pentyl]2/3/5,6-tetramethylbenzene  134  134  The  diethyl  transesterified described dibenzyl  i n 125 mL o f r e d i s t i l l e d  f o r t h e undecane analogue e s t e r 134 was 15.5 g  was  recrystallized  MP  :  Anal. Found  e s t e r 133 (13.1 g , 21.5 mmol) was  from  89a.  (98.1%).  benzyl  a l c o h o l as  The y i e l d o f t h e An a n a l y t i c a l  sample  tetrahydrofuran-methanol.  171.0 - 172. 0° C  Calcd.  f o rC  4 g  H  6 ( )  N 0 2  4  : C, 79.08; H, 8.30; N, 3.84.  : C, 78.91; H, 8.47; N, 3.83.  1  H  NMR  4-,  (<5 , C D C 1 )  :  3  4'-CH ), 2  1.46  2.19, 2.22, 2.30, 2.22-2.50  2-CH , d u r e n e CH" , p y r r o l e 3  3  2.78  (m, 4H, c h a i n  7.30-7.52  1 3  C  1-C  NMR  (m, 10H, C H ) , 8.60 g  (durene 2-C, 3-C,  (pyrrole  5-C,  4 -C), ,  24.20  ( s , 4H,  164.53  (chain,  6-C), 131.03  (pyrrole  (chain  pyrrole  (durene C H ^ ) , 11.69, 11.34  pyrrole  2.50-  0-CH_ C H ), 2  6  (C=0) , 137.17  (benzene 2-C, 3-C,  3 - C ) , 115.57  28H,  2  (benzene 1 - C ) , 134.25  30.96, 30.82, 30.24, 30.07 4-,  :  3  ( s , s , s , m,  3'-,  5  ( b s , 2H, NH).  5  (<5, 10% TFA-CDC1 )  2-, 2'-, 3-,  5-, 5 ' - C H ) ,  3  2  128.91, 128.69, 128.39 123.96  4-CH , c h a i n ,  1-, 1 ' - C H ) , 5.31  and 4 - C ) , 135.81  132.35  ( b r , 12H, c h a i n  termini,  (pyrrole  ( p y r r o l e 2-C), ( p y r r o l e 4-C), 4-C,  5-C, 6-C),  5 - C ) , 67.37  1-, 1'-,  (durene  (-0-CH C H ), 2  2-, 2'-, 3-, 5-C,  5'-C),  3'-,  16.49  2-CH^, 4-CH-,).  Mass—spectrum m/e  Relative Intensity  728  88  620  36  24 2  3?  (%)  Assignment M  H  100  91  68  cL  c  ^N—i^ " 0  Hf  108  +  (M-C H CH.OH) 6 5~"2' :  H  3  ^  0  (C H CH OH) 6  5  C H 7  2  + 7  6  +  +  5  296 IR —  (v  max  KBr)::  3330  (NH),  1670  (C=0)  cm  1,4-Bis[5-(5-formyl-2,4-dimethylpyrrol-3-yl)pentyl]-2,3,5,6tetramethylbenzene  This as The  compound  t h a t employed crude-bis  yield before  137  i n the preparation  formylpyrrole  and was c o n v e r t e d purification. An a n a l y t i c a l  the  purified  hydroxide  MP  :  was p r e p a r e d  by t h e same p r o c e d u r e of the dialdehyde  was-obtained  i n quantitative  t o t h e d i c y a n o v i n y l d e r i v a t i v e 138, , sample was p r e p a r e d  by  d i c y a n o v i n y l d e r i v a t i v e 138 w i t h  i n n-propanol.  233.0 - 234. 0° C  93c.  deprotecting aqueous  potassium  Anal.  Calcd.  Found  : C, 78.87; H, 9.47; N,  1  H  NMR  for  C  4 4 H  3  (6, 270 MHz,  N 8  2°2  CDC1 ) 3  2'-, 3-, 3'-, 4-, 4'-CH 2.26  C  '  7 9  -  0 2  '"  H  '  9.36; N, 5.42;  5.43.  :  ) , 2.20  1.46  ( b r , 12H, c h a i n  ( s , 12H, d u r e n e  3  5-, 5 ' - C H ) , 2.56-2.69 2  3  ( b s , 2H, NH), 9.44  Mass s p e c t r u m  :  m/e,  3  (m, 4H, c h a i n  1-,  2-,  C H ) , 2.22,  ( s , s, 12H, p y r r o l e 2-CH , 4 - C H ) , 2.30-2.43  chain 8.99  :  (m, 4H,  l'-CH^,  ( s , 2H, HCO) .  516  (M ) , +  488  (M-CO) , 473 +  [M-(CO+CH )] . +  3  IR  (v  KBr).:  3260  (NH) , 1640  (C=0)  cm" . 1  1,4-Bis{5-[5-(2,2-dicyanovinyl)-2,4-dimethylpyrrol-3-yl]pentyll2,3,5,6-tetramethylbenzene  The  138  c r u d e d i a l d e h y d e 137_ (6.51 g :) and m a l o n o n i t r i l e  (2.0 g , 30.3 mmol) were r e f l u x e d the presence  of cyclohexylamine  the r e a c t i o n mixture to  i n toluene  (2 mL).  As u s u a l , t i c o f  showed two y e l l o w s p o t s i n a d d i t i o n  t h e slow moving s t a r t i n g m a t e r i a l .  material  (300 mL) i n  I n 1.5 h  no s t a r t i n g  c o u l d be s e e n o n t i c and t h e s l o w e r m o v i n g  yellow  spot  ( c o r r e s p o n d i n g t o t h e mono p r o t e c t e d d e r i v a t i v e ) was  very  faint.  another  No c h a n g e i n t i c c o u l d be o b s e r v e d  after  3 0 min. Toluene  The  even  solid  was e v a p o r a t e d  was c o l l e c t e d  i n v a c u o and m e t h a n o l  by f i l t r a t i o n  The m o t h e r l i q u o r s were e v a p o r a t e d  and washed w i t h  added. methanol.  to dryness, the residue  t a k e n up i n m e t h y l e n e c h l o r i d e , m e t h a n o l added and c o n centrated  t o g i v e a second The  first  and s e c o n d  c h r o m a t o g r a p h e d on s i l i c a c h l o r i d e was u s e d to  0.2% e t h y l  eluted  0.5%,  I , 120 g , ) .  initially, chloride  but very slowly.  Methylene  b u t was c h a n g e d  later.  The p r o d u c t  The amount o f e t h y l  i n t h e s o l v e n t was i n c r e a s e d g r a d u a l l y  t o 0.3%,  t o 0.8%, a t w h i c h s t a g e t h e i m p u r i t i e s  eluting out. The  and  as t h e s o l v e n t  0.7% a n d f i n a l l y  started  c r o p s were c o m b i n e d and  gel (activity  acetate-methylene  out cleanly  acetate  crop.  s o l v e n t was e v a p o r a t e d ,  the b i sd i c y a n o v i n y l  derivative  as a lemon y e l l o w powder, y i e l d the b i s . b e n z y l analytically  ester  pure.  134).  i n vacuo,  methanol  added  138 was c r y s t a l l i z e d o u t  4.82 g  The s o l i d  (62.6%  overall  t h u s o b t a i n e d was  from  299 MP  :  228.5 - 229.5°C  Anal.  Calcd.  Found  1  for C  : C, 7 8.49;  H NMR  4 Q  H gN 4  :  6  C, 78.39; H, 7.89; N, 13.71  H, 7.77; N, 13.63.  (6, 270 MHz, CDC1 )  :  3  1.44  (br, 12H, c h a i n  2-, 2'-,  3- , 3'-, 4-, 4'-CH  ), 2.13 (s, 6H, p y r r o l e 4-CH-), 2.20 ( , 2 12H, durene C H ) , 2.31 (s, 6H, p y r r o l e 2-CH ), 2.34-2.45 s  J  3  (m, 4H, c h a i n  C  5-, 5'-CH ), 2.56-2.69 2  [ s , 2H, C(H)=C(CN) 1,  7.28  1 3  3  2  NMR  9.29  (6, 10% TFA-CDC1 ) 3  (m, 4H, c h a i n  1-, l ' - C H ) , 2  (bs, 2H, NH).  : 145.09 ( p y r r o l e 2-C), 140.97  [C (H)=C(CN) ], 138.80 ( p y r r o l e 4-C), 136.85 (durene 1-C and 2  4- C), 132.19  (durene 2-C, 3-C, 5-C, 6-C), 126.94  3-C), 125.04  ( p y r r o l e 5-C)., 117.24  (pyrrole  (C=N) , 116.29 (C=N) ,  58.77 [C(H)=C(CN) ], 30.83 (chain, durene t e r m i n i i 1-C, 2  1*-C), 30.11 (chain, 2-, 2'-,  3-, 3'-, 4-, 4'-C), 24.04  (chain, p y r r o l e t e r m i n i i 5-, 5'-C), 16.45 (durene C H ) , 3  12.59 ( p y r r o l e 2-CH ), 9.81 3  Mass spectrum  I  R  (  v  (C=C)  m  a  v  : m/e,  ( p y r r o l e 4-CH ). 3  612 (M ), 597 (M-CH ) , 184 +  +  3  (  C  H 1 1  N 1 0  KBr ) :. 3300-3460 (broad, NH) , 2200 (C=N) , 1590 ;  cm" . 1  3 )• +  300 l , 4 - B i s { 5 - [ 2-1 ( 5 - e t h o x y c a r b o n y l - 3 - e t h y l - 4 - m e t h y l p y r r o l - 2 y l ) methyl] -5-(2 , 2 - d i c y a n o v i n y l ) - 4 - m e t h y l p y r r o l - 3 - y l ] p e n t y l } 14 0  -2,3,5,6-tetramethylbenzene  NC  140  T h i s compound was as t h a t 96a.  employed  Starting  vinylpyrrole  t h e same p r o c e d u r e  i n the p r e p a r a t i o n o f the undecane  from  138,  p r e p a r e d by  1.23  1.74  g  g  analogue  (2.01 mmol) o f t h e b i s d i c y a n o (89.2%) o f t h e  dipyrromethane  14 0 were o b t a i n e d as a d a r k y e l l o w powder. It  s h o u l d be  emphasized  t h a t u n l i k e w i t h the  straight  c h a i n analogues, the lower  required  the a d d i t i o n  reaction  to completion  o f more a c e t i c (In t h i s  solubility acid  of the p r o d u c t  to d r i v e  c a s e , 600 mL  of  the  solvent  301  were r e q u i r e d  as compared w i t h a p p r o x i m a t e l y  undecane a n a l o g u e ) . from methylene  MP  :  Calcd.  Found  H  sample was  chloride-methanol.  for C„H^,N 0, bu /4 o 4  :  o  C, 74.20; H, 7.68; N,  (6, 270 MHz,  CH ) , 1.32 3  CDC1 ):  1.02  3  ( t , 6H, J=7.5 Hz, 3'-CH  ( t , 6H, J=7 Hz, -OCH CH_ ) , 1.44 2  3  2-, 2'-, 3-, 3'-, 4-, 4 ' - C H ) , 2.13 ( s , 12H, d u r e n e C H ) , 2.26  (m, 8H, 4 '-CH_ CH , c h a i n 2  (m, 4H, c h a i n  1-, 1'-CH  3  ) , 3.94  (q, 4H, J=7 H, 0 - C H C H ) , 2  l'-NH),  C  (s , 6H, p y r r o l e  3  2.33-2.48  9.17  NMR  ( b r , 2H,  (durene 1-C,  (pyrrole  (pyrrole  ( C s N ) , 61.97  1-C,  2.56-2.69  2  2  [C(H)=C(CN) ] , 8.75  (pyrrole  (-0-CH -CH ),  durene t e r m i n i  3  3  164.74  ( b r , 2H,  3  l'-C),  (C=0), 142.93 (pyrrole  3-C,  (pyrrole  2'-C,  [C(H)=  4 - C ) , 136.89  (durene 2-C, 3-C, 5-C,  5 - C ) , 118.09 2  4-CH ),  4'-CH ),  5-, 5 ' - C H ) ,  2 - C ) , 138.78  4 - C ) , 132.21  128 .98, 126.51, 126.11 125.19  chain  ( s , 4H, b r i d g e C H ) , 4.23  :  3  141.89  2  1-NH).  (6, 10% TFA-CDC1 )  C(CN) 1, 2  7.28  3  ( b r , 12H,  ( s , 6H, p y r r o l e  2  I 3  11.54  : C, 73.99; H, 7.51; N, 11.60.  NMR  2.20  recrystallized  186.0 - 190.0°C  Anal.  1  An a n a l y t i c a l  8 0 mL o f t h e  6-C), 129.82,  3'-C , 4 ' - C ) ,  5 ' - C ) , 116.75  60.99  [C(H)=C(CN) ],  30.19  ( 4 C ) , 29.97  2  (C=N), 115.67  30.82  (chain,  (chain, 2-,  2'-,  302  3-, 3'-, 4-, 4'-C), 24.20 ( c h a i n , p y r r o l e (pyrrole  17.44  3 ' - C H C H ) , 16.42 2  3 ' - C H C H ) , 14.24 2  (pyrrole  —  (  Vax  3  2  5-, 5'-C),  (durene C H ) , 15.29  (pyrrole  3  (pyrrole  ( - 0 - C H C H ) , 10.85  3  termini  3  4'-CH ) 3  9.76  f  4-CH ). 3  K  (C=0), 1580  B  r  )  :  3  4  1  0  ( N H )  '  3  3  2  0  ( N H )  '  2  2  1  0  ( C  -  N )  '  1  7  1  0  (C=C).  1,4-Bis(5-[2-[(5-carboxy-3-ethyl-4-methylpyrrol-2-yl)methyl] -5-formyl-4-methylpyrrol-3-yl]pentyl}-2,3,5,6-tetramethylbenzene 141  The p r o c e d u r e u s e d  f o r the synthesis  o f t h i s compound  was  t h e same a s t h a t employed  dipyrromethane s o l v e n t s used material  dimer  107.  f o r 1.21 g  i n the preparation of the  The q u a n t i t i e s  o f r e a g e n t and  (1.25 mmol) o f t h e s t a r t i n g  140 were, 7.5 g  potassium  h y d r o x i d e , 100 mL o f  w a t e r and 6 0 mL o f n - p r o p a n o l . When p r o p a n o l was d r i v e n o f f a f t e r of  the reaction  to  300 mL. t h e p r o d u c t d i d n o t o i l o u t b u t r e m a i n e d  emulsion  and w a t e r added  (with t h e s t r a i g h t  than double  into  acid  solution).  with  acetic  give  1.01 g, ( 9 9 . 0 % ) . varied  powdery s o l i d analytically  MP  ;  Anal.  1  H  chain analogues,  isolated  isolated  more  to g e t the  and d r i e d t o  other preparations,  to quantitative.  from  a s an  the  The p a l e brown  t h e r e a c t i o n m i x t u r e was  pure.  158.0 - 1 6 0 . 0 ° C (dec)  5 Q  H  6 6  N 0 4  6  : C, 73.32; H, 8.12; N, 6.84;  : C, 73.28; H, 8.22; N, 6.80.  NMR  (br,  In s e v e r a l  between 9 0%  volume  The s o l u t i o n was a c i d i f i e d  and t h e p r o d u c t  Calcd. for C  Found  carbon  the t o t a l  t h i s volume o f w a t e r was r e q u i r e d  gummy p r o d u c t  yield  to bring  the completion  (6 , D M S O - d J o  :  0.84 ( t , 6H, 3'-CH CH_), 1.32 z — j 0  12H c h a i n 2-, 2'-, 3-, 3'-, 4-, 4 - C H ) , 1.96 - 2.44 ,  2  (m,  b r , 36H, d u r e n e CH" , p y r r o l e  5-,  5'-CH , 3 ' - C H C H ) , 3.78 ( b r , 4H, b r i d g e CH_ ), 9.48  3  2  2  3  2-, 4-CH" ', c h a i n 1-, 1'-, 3  2  304  ( s , 2H, HCO) , 10.94  Mass  spectrum  : . 818  ( b s , 2H, 1-NH), 11.48  ( b s , 2H,  l'-NH).  ( M , v e r y w e a k ) , 816  (M-2H) ,  730  +  +  (M-2C0 ) . +  2  7 ,17-Di-ethyl-2 , 8 ,12 , 1 8 - t e t r a m e t h y l - 3 ,13—[-2 ,3 ,5 , 6 - t e t - r a m e t - h y l — p h e n y l erie-1, 4 - b i s (pen tame t h y lene)"] p o r p h y r i n  143  U3 The  synthesis  of this  p o r p h y r i n and i t s c h r o m a t o -  g r a p h i c p u r i f i c a t i o n were c a r r i e d for  the undecamethyleneporphyrin  starting  from the dipyrromethane  o u t i n t h e manner 109a.  The o v e r a l l  141 v a r i e d  described yield,  between 22% and 31%. The  p o r p h y r i n was c r y s t a l l i z e d  from the methylene c h l o r i d e s o l u t i o n  u s i n g methanol r a t h e r than nitromethane s i n c e i t was more s o l u b l e i n the l a t t e r  MP  :  Moi.  solvent.  273.0 - 274.5°C  Wt. C a l c d . f o r C. H, N. 0  :  n  692.4818 ;  Found, by high  r e s o l u t i o n mass spectrometry : 692.4866.  Anal.  Calcd. for  Found C  C  H 4 8  N 6 0  4  :  C  '  8 3  - '" 1 9  : C, 81.50; H, 8.90; N, 7.72;  48 60 4* H  N  NMR  C  H  3  0  H  :  C  '  8 1  -  2 2  ;  H  H  ' 8.7 3; N, 8.08;  Anal. Calcd. f o r  ' 8.84; N, 7.73.  (270 MHz, 6, CDCl ) 3  : 9.94 (s, 2H, methine protons  10-H and 20-H), 9.86 (s, 2H, methine protons 5-H and 15-H), 4.09  (m, 6H, CH_ CH and one proton each a t c h a i n t e r m i n i ) ,  3.84  (m, 2H, one proton each a t c h a i n t e r m i n i ) , 3.64  2  3  (s,  6H, two C H ) , 3.48 (s, 6H, two C H ) , 1.90, 1.87 ( t , m, 3  3  10H, CH CH_ and four c h a i n p r o t o n s ) , 1.40 ( t , 4H, c h a i n 2  3  durene t e r m i n i ) , 0.91 (m, 2H, c h a i n p r o t o n s ) , 0.69 (m, 2H, c h a i n p r o t o n s ) , -1.06 (m, 4H, c h a i n p r o t o n s ) , 3.81 (bs, 2H, N-H)  1 3  C  NMR  (6, 10% TFA-CDC1 ) 3  :  146.07, 143.08, 142.90, 142.71,  141.25, 140.31, 139.17 (16C, a - and 3 - p y r r o l i c carbons),  134.79  (2C, durene 1-C, 4-C), 130.25 (4C, durene 2-, 3-, 5-, 6-C),  99.87 , 98.91 27.20  (10C, c h a i n  CH CH ), 2  12-,  (4C,meso c a r b o n s 5-, 10-, 15-, 20-C)., 30.80, 29.  3  14.65  carbons),  (4C, d u r e n e  20.16  (2C, C H C H ) , 2  3  C H ) , 12.28, 11.68 3  16.67 (2C,  (4C, 2-,  8-,  18-CH ).  Visible  3  spectrum  (CH C1 )  max  (nm),  log  e,  2  2  :  400.7  500.8  537.0  569.8  623.9  5.16  4.04  3.98  3.76  3.64  CHAPTER 4  SPECTRAL ASSIGNMENTS AND COMPARISON  TABLES  308 4.1  1  H-NMR SPECTRA AND PORPHYRIN  The shifts  COMPARISON TABLES QF  INTERMEDIATES  tables  I to VII l i s t  of chain linked  t h e p r o t o n nmr  by t h e s p e c t r u m  w h i c h has been s e l e c t e d These t a b l e s why  for  similar  tables.  s p e c t r a both  demonstrate analytical  The m a g n i t u d e o f t h e c h e m i c a l  a s c a n be r e a d i l y  compounds  shifts  tend  t o be  s e e n by i n s p e c t i n g  these  s p e c t r a were u s e f u l  the homogeneity o f samples b u t a l s o impurities  derivative  as t h e r e p r e s e n t a t i v e compound.  functions i n similar  The nmr  not only i n v e r i f y i n g in identifying  major  p r e s e n t by r e a s o n o f s i d e - r e a c t i o n s , e t c . Some f e a t u r e s o f t h e p r o t o n nmr  intermediates  s h o u l d be n o t e d  dipyrromethane  dimer  here.  spectra o f these  In every  bis-pyrrole  with a simple alkane chain  (except  t h e d i k e t o n e s 88a - 8 8 c ) t h e c h a i n m e t h y l e n e r e s o n a n c e s observed pyrrole rest  i n two d i s t i n c t termini,  as a b r o a d  groups;  as a m u l t i p l e t rise  near  6 1.3.  for  I) a p p e a r  i n three groups;  the protons next  were  the four protons a t the (6 2.18 - 2.50) and t h e As expected,  m e t h y l e n e p r o t o n s o f t h e d i k e t o n e s , 88a - 88c, Table  dimers  table i s  o f the undecane l i n k e d  and t h e i l l u s t r a t e d  i n t h i s work.  analogous  very  and  Each  p r o t o n nmr was one o f t h e most i m p o r t a n t  tools  chemical  b i s p y r r o l e s and d i p y r r o m e t h a n e  s y n t h e s i z e d d u r i n g t h e c o u r s e o f t h i s work. accompanied  STRAPPED  a triplet  to the c a r b o n y l group,  the chain (Figure  around  22;  6 2.8  a multiplet  for  the next  rest.  a d j a c e n t CH^  groups,  In the d u r e n e - b i s - p e n t a n e  the c h a i n methylene p r o t o n s for  two  differences.  t e r m i n i produce  the broad  protons  is shifted  (Figure  25;  facilitate  used  termini  are  the  4-CH^  and n-C  and  6-C.  nucleus  a t 6 2.14  protons  pattern a t the  a t 6 2.5  of  except  durene  - 2.8,  and  i n t e r m e d i a t e methylene 0.2  ppm  that  i n order  to  the c h a i n carbon  atoms o f  durene  i n a manner s i m i l a r T h e r e f o r e the  T h i s numbering data  shifts exhibit  system i s due  here  (n=10) whereas t h e  t h e nmr  chemical  5-ethoxycarbonyl  resonance  emphasized  1-C  throughout  the p y r r o l e  the resonances  approximately  simple alkane c h a i n s .  5-C  f o r the  24).  have been numbered  The of  2  to the  the comparison,  remain  maintained  due  rise  a similar  t h e CH"  d o w n f i e l d by  s h o u l d be  f o r the  termini,  rise  cf Figure  bis-pentane  exhibit  First,  a broad  series,  a separate m u l t i p l e t  second,  It  and  g r o u p o c c u r s a t 6 2.20.  pyrrole  durene  system  and  has  been  4- m e t h y l  interesting  ( F i g u r e 23; to the  that  tables.  o f t h e 2an  to  2-CH^  Table  pattern.  protons For  I I ) , the  group whereas  Comparisons of v a r i o u s  the  310  methyl/ethyl  s u b s t i t u t e d p y r r o l e s have a l l o w e d  ment o f s p e c i f i c shown  changed  Table  shift  benzyl  esters  are also  I V , t h e undecane decane exhibit  only  Table  A s shown i n F i g u r e and nonane  a single  methyl  group  appear  linked b i s resonance  i s one.of once more  26  2 Hz  while apart.  the cyanovinyl ( F i g u r e 27;  V ) , b u t i t c a n be shown c o n c l u s i v e l y t h a t t h e o r d e r  reversed;  while  singlets  g r o u p was  resonances  t h e o c t a n e a n a l o g u e , t h e two s i g n a l s a r e o n l y  w e l l separated  observed  (Figure 24, 25; Table I I I ) .  (HC=0), t h e two m e t h y l  When t h e e l e c t r o n - w i t h d r a w i n g  is  patterns  t o move c l o s e r t o g e t h e r .  formylpyrroles  two  f o ra simple t r i m e t h y l p y r r o l e  e n o u g h , when t h e e l e c t r o n w i t h d r a w i n g  t o an aldehyde  appeared  in  chemical  the corresponding  Interestingly  and  shifts  the assign- -  below.  Similar for  chemical  4 3  the upfield  t h e one d o w n f i e l d  signal  i s now d u e t o t h e 4 - m e t h y l ,  i s due t o t h e 2-methyl group.  compound  94a was r e a c t e d  with  chloride  (known t o s u b s t i t u t e o n e p r o t o n  When  2 equivalents of sulfuryl each o f t h e two  type,  311 a-methyl field  groups),  signal  shifted  the product  o f t h e above p a i r ,  (115 It  no  and t h e one u p f i e l d  was  results  n=11  have been o b t a i n e d  116) a s w e l l a s w i t h  f o r the reversal  attempt  of the order  i s made h e r e Another  with dimeric  simple monopyrrolic  i s possible that a theoretical  oped  t h e down-  slightly.  94a  Similar  95a d i d n o t e x h i b i t  cyanoacrylates derivatives.  e x p l a n a t i o n c o u l d be d e v e l o f methyl resonances, but  t o do s o .  interesting  feature,observed  i n the proton  nmr s p e c t r a o f d i m e r i c p y r r o l e s p o s s e s s i n g an a - f o r m y l g r o u p or  an a - d i c y a n o v i n y l g r o u p , was t h e e x i s t e n c e o f a  near  1.7 d e l t a .  The i n t e n s i t y  of this  resonance  peak was f o u n d  to vary  312 from  less  t h a n 1 p r o t o n up  t o 2 o r 3 p r o t o n s and  c o n s t a n t even f o r d i f f e r e n t For  the simple alkane  was  well  protons (137,  (6 ^ 1 . 3 ) ,  but  ;  138  and  14 0)  latter (6  series,  ~-1.5)  (6 - — 1 . 3 ) .  d i m e r i c systems,  peak  the b r o a d - r i s e of the c h a i n methylene  e x t r a peak i n t e r f e r e d  T h i s was  as e x p e c t e d ,  series  w i t h the c h a i n  since  the c h a i n methylene p r o t o n s appear  i n the downfield  of the c o r r e s p o n d i n g p r o t o n s of the alkane  analogues  When t h e s p e c t r a were r e c o r d e d a t 27 0 MHz,  two  resonances  one  at higher f i e l d  were r e s o l v e d  as  (6 = 1.44  attributed  was  broad  singlets  accounted  As  the  and  f o r the  expected,  this  of  1.7  hydrogen  peak was  r e c o r d e d i n the presence  the  expected  T h i s e x t r a peak n e a r  to p r o t o n s of water m o l e c u l e s ,  bonded t o t h e compound. when t h e s p e c t r u m  two  ppm)  number o f p r o t o n s o f t h e c h a i n . d e l t a was  this  i n t h e compounds o f t h e d u r e n e  this  methylene resonance.  not  s a m p l e s o f t h e same compound.  linked  s e p a r a t e d from  was  removed D 0. o  FIGURE 22  :  H NMR  S p e c t r u m ( 1 0 0 MHz)  o f 88a i n 10% TFA-CDC1  i— LO 1  TABLE I  :  H NMR  DATA OF C H A I N L I N K E D B I S P Y R R O L E  DIKETONES  ( i n 10%  TFA-CDC1,)  88 X =  -<CH ) 2  GROUP  Chain  4  88c  to  1  (n-3)  1  CH -CH -0 3  Chain  2  3' a n d  Durene -  CH  (n-2)'  3  (n=9)  "<CH ) 2  88b  4  (n=ll)  -(CH ) 2  88a  5  (n=ll)  -CH .CH .C (CH ) .CH 2  2  132  6  1.36  1.33  1.33  1.38-2.10 (3',4',7',8')  1.43  1.43  1.43  1.46  1.69  1. 66  1.69 2 ,24  3  4-CH  3  2.57  2.57  2.57  2.39  Pyrrole  2-CH  3  2.59  2.59  2.59  2.42  Chain, durene t e r m i n i 5 , 6'  2.58-2.85  1  2' a n d  CH -CH -0 3  N-H  2  (n-l)'  4  (n=10)  Pyrrole  Chain,  3  2.87  2.86  2.86  2.96  4.46  4.45  4.46  4.47  10.15  10.15  10.15  10.20  2  TABLE  II :  H-NMR DATA OF C H A I N L I N K E D B I S P Y R R O L E a - E T H Y L E S T E R S  ( i n CDC1 ) 3  89  X =  -(CH ) 2  GROUP  Chain  89c  2' t o  (n-1)'  CH ~CH -0 3  (n=9)  1.12-1.60 1.29  2  Durene  7  -(CH )g2  89b  (n=10)  1.12-1.60 1.30  -(CH )g2  89a  (n=ll)  - ( C H ) . C ( C H ) . (CH ) 2  4  g  133  3  1.08-1.58  1.32-1.62 (2',3',4',7',8',9')  1.31  1.35  CH,  4  2. 22  2-CH  3  2 .14  2.14  2.14  2.20  Pyrrole  4-CH  3  2.22  2.20  2.22  2.28  Chain, pyrrole termini l and n 1  1  2.18-2.48  2.20-2.48  2.18-2.44  Chain, durene t e r m i n i 5',6  2.24-2.50 2.50-2.80  1  CH -CH_ -0  4.25  4.26  4.26  4.32  N-H  8 .77  8.81  8.73  8.73  2  2  (n=10)  Pyrrole  3  4  i—  1  TABLE  I I I : H 1  NMR  DATA OF C H A I N L I N K E D B I S - P Y R R O L E g - B E N Z Y L E S T E R S  ( i n CDC1 )  90 X =  -<CH ) 2  GROUP  Chain  2  1  Pyrrole Durene  to  2-CH CH  Pyrrole  90d  (n-l)  3  1  6  (n=8)  "(CH ) 2  7  9 0 c (n=9)  -(CH ) -  -(CH ) -  9 0 b (n=10)  90a  2  8  2  9  (n=ll)  1.29  1.28  1.27  1 . 27  2.15  2.18  2 .17  2 .18  4-CH  2.22-2.44  2.29 2.24-2.50  2.29 2.18-2.55  2.26 2.20-2.52  C H -CH -0 6*5  N-H  3  4  2  4  (n=10)  1.46  2.19  2.30 2.22-2.50  2.50-2.78  1  C  134  6  ( 2 ' , 3 ' , 4 ' , 7 ' , 8 ' ,9')  Chain, durene termini, 5' ,6 , 2  4  2.22 2.29  3  1  5  2  3  Chain, pyrrole t e r m i n i , 1',n ,  6  -(CH ), .C (CH ) .(CH ) -  5.20 7.30-7.52 8 .83  5.31 7.28-7.52 8 .62  5.31  5.31  7.25-7.55  7.22-7.56  8.63  8.67  5.31 7.30-7.52 8 .60 VD  TABLE  IV  "H NMR  DATA OF C H A I N L I N K E D B I S - F O R M Y L P Y R R O L E S  ( i n CDC1 ) 3  93  X  =  -<CH )g2  GROUP  93d  Chain,  2'to (n-l) •  Durene  CH  Pyrrole  (n=8)  1.30  "(CH ) 2  93c  7  (n=9)  1.26  "(CH 93b  )  (n=10)  1. 27  "(CH ) 2  93a  (n=ll)  1.26  ( C H ) . C ( C H ) . (CH ) 2  4  6  137  3  2  4  (n=10)  1.46 ( 2 ' , 3 ' ,4' ,7' ,8',9')  3  CH  2.22,2,24  3  Chain, pyrrole t e r m i n i , 1', n  1  2.22-2.44  2.21 2.22-2.42  2.20 2.20 2.26-2.48  2.27 2.27-2.49  Chain, durene t e r m i n i , 5 , 6'  2.22,2.26 2.3 0 - 2 . 4 3 2.56-2.69  1  H-C=0  9.48  9.38  9.44  9.50  9.44  N-H  9. 90  9.96  9.98  9.84  8.99  Data  4  from  27 0 MHz  spectrum U)  TABLE V  :  H-NMR DATA OF CHAIN LINKED BIS-ct-DICYANOVINYLPYRROLE  NC  X =  "(CH ) 2  GROUP  Chain,  2'  94d  to(n-1)'  6  (n=8)  CN  NC  CN  94  -(CH ) 2  94c  ( i n CDC1-)  7  (n=9)  "(CH ) 2  94b  8  (n=10)  "(CH ) 2  94a  9  (n=ll)  1.30  1.29  1. 28  1.24  2.15  2.15  2.15  2.12  2.33  2.33  2 . 27  (CH ) .C (CH ) . 2  4  6  138  3  4  (CH ) 2  4  (n=10)  1.44 (2',3',4',7',8' ,9')  Pyrrole Durene  4-CH  3  2.13  CH^ 2.20  Pyrrole  2-CH  2.33  3  Chain, p y r r o l e t e r m i n i 1',n 1  2.30-2.50  2.26-2.52  2.26-2.50  2.27-2.47  C h a i n , durene t e r m i n i , 5',6' C(H)=C(CN)  n  N-H *  Data  from  27 0 MHz  2 .31 2.34-2.45  2.56-2.69 7.36  7.35  7.34  7 .28  7.28  9.36  9.36  9.56  9.35  9.29  spectrum  CO LO  TABLE V I  "H NMR DATA OF CHAIN LINKED ct-DICYANOVINYL-a ' -ETHOXYCARBONYL DIPYRROMETHANE DIMERS  ( i n CDC1 ) 3  NC  /  CN  96 X = GROUP  3'-CH CH 2  3  -0-CH -CH 2  Chain,  3  2"to(n-l)  -<CH ) -  -<CH > -  "(CH ) -  -(CH ) -  96d  96c (n=9)  96b (n=10)  96a ( n = l l )  1.01  1.00  1.03  1.03  1.02  1.36  1.35  1.36  1.34  1.32  2  g  (n=8)  1.14-1.46  2  7  1.14-1.48  2  8  1.16-1.53  2  q  1.18-1.54  (CH ) .C (CH ) . 2  4  6  *140  3  4  (CH ) 2  4  (n=10)  1.44 (2",3",4",7",8",9")  LO K>  TABLE V I - C o n t i n u e d  GROUP  Pyrrole  4-CH  96d  96c  2.15  3  2.15  96b  2.15  96a  2.15  Durene CH^ Pyrrole  2.30  3  Chain,pyrrole t e r m i n i : 1 ,n 2  2.13 2.20  4'-CH  3'-CH CH  140  2.22-2.54 2.4 0  3  2.29  2.29  2.22-2.56  .22-2.59  2.4 0  2.41  2.30 2.21-2.58 2.43  C h a i n , durene termini,5",6" Methane b r i d g e CH„  2.26 2.33-2.48 2.33-2.48 2.56-2.69  3 .99  3 .98  3.98  3.94  4.29  4.31  4.29  4.29  4.23  7.34  7.34  7.34  7.31  7.28  l'-NH  8.93  9.03  8.87  8.90  8.75  1- NH  9.23  9.23  9.22  9.24  9.17  0- C H - C H 2  3  C(H)=C(CN)  2  J  '  q  q  y  y  * Data  f r o m 27 0 MHz  spectrum  TABLE-VII.:  H-NMR DATA OF C H A I N  X=  -(CH )g-  GROUP  3'-CH CH 2  Chain, Pyrrole  3  2"to(n-1)" 4-CH  Durene CH Pyrrole  3  3  4 -CH., 1  L I N K E D a-FORMYL-a'-CARBOXY DIPYRROMETHANE DIMERS  2  -(CH ) -  1 0 7 d (n=8)  1 0 7 c (n=9)  2  7  -(CH )  8  -  -(CH ) 2  9  1 0 7 b (n=10) 1 0 7 a ( n = l l )  - (CH ) .C 2  4  141  6  ( i n DMSO-d  (CH ) . (CH ) 3  (n=10)  0.86  0.86  0.84  0.84  0.84  1.23  1.22  1.22  1.21  1.32  2.18  2.18  2.18  2.15  2.21  2.20  2.20  2.18  4  2.13  2  4  TABLE V I I -  Continued  GROUP  107d  107c  107b  107a  141  Chain,pyrrole termini,  l",n"  3'-CH CH Chain, durene t e r m i n i , 5",6" 2  2.16-2.48  2.16-2.46  2.18-2.44  2.16-2.46 1.94-2.44  3  Methane b r i d g e CH  _ oc  o oA  3.85  3.82  3.78  9. 54  9.49  9.48  2  H-C=0  9.54  9.52  1-N-H  11.03  11.02  11.05  11. 00  10. 94  l'-N-H  11.48  11.47  11.49  11.45  11.48  330 Figures the  30-34  intermediates  ester  route  synthesized  isolation  immediate p r e c u r s o r  ct' - b e n z y l  be  This  route  1 0 8 w h i c h was  i n both  solution  and  and  T h i s was  order  isomers  of the  routes,  intended  the  stage  route,  the and  crystallized t o be  for.  t h a t the  from the  isolated  suggested  t o be  as  due  been c o n f i r m e d  steric  i n one  nonthe  groups.  c o n s i d e r i n g the uses  They a r e  these  g e n e r a l l y assumed  crowding.  simple  a  i s n o t known f o r  c a r b o n y l group t r a n s to the p y r r o l e  to minimize  chromato-  to  a t the c y a n o a c r y l a t e  here,  first  a-cyanoacrylate-  the  cyanoacrylates  hardly matters  compounds a r e exist with  in this  t h e r e f o r e had  glass.  stereochemistry  certain,  at this  c o u l d n o t be  e x i s t e n c e of geometric  has  porphyrin.  o f compound  recalled  synthesized  e s t e r 117  crystallizable  in  spectra of  cyanoacrylate-benzyl  to the p o r p h y r i n  should  dipyrromethane  The  i n the  nmr  obtain i t s spectral properties. It  graphed  the p r o t o n  t o t h e undecane s t r a p p e d  made p o s s i b l e t h e  thereby  illustrate  This  to  nucleus  stereochemistry  monopyrrolic  cyanoacrylate,  70  by  X-ray c r y s t a l l o g r a p h y The  exhibited of  proton  isomerism  at  the expected  one  fifth  6 3.76.  a t the  the  cyanoacrylate <5 3 . 8 5 ,  intensity  Together,  s i x protons  117  (Figure  f e a t u r e s that suggested  t o t h e methoxy peak a t  approximately observed  s p e c t r u m o f compound  some s t r i k i n g  cis-trans  addition  nmr  they  of  an  the  group.  anomalous  the  former,  31)  existence In hook, was  integrated perfectly  (2 methoxy g r o u p s ) .  It i s clear  for  331 t h a t t h e s e two isomerism  resonances  since  the environment  w o u l d be d i f f e r e n t , to the p y r r o l e  two  vinyl  protons;  aryl  p r o t o n s and Both  (Figure but  33)  115  to the presence  The  ( F i g u r e 30)  also exhibited  than  the  and  well  spectra  of c r y s t a l l i z a t i o n  a t 6 3.76  the minor isomer  extremely  expected  f o r the  of  the dipyrromethane  very minor v i n y l  large quantities,  cyano-  be due  could not  existed  t h e r e b y making t h e difficult.  to  the  the  119  peaks a t 6  Thus i t seems r e a s o n a b l e t o assume t h a t  c a s e o f t h e compound 117, relatively  f o r the  i n t h e same r e g i o n .  p r o t o n nmr  t h e i s o m e r i c methoxy s i g n a l  observed.  The  o f the m u l t i p l e t  the s o l v e n t resonance  isomers.  7.25,  o f t h e m i n o r peak c o u l d n o t  t h e above o b s e r v a t i o n s may  e x i s t e n c e o f two bis-pyrrole  to l e s s  the  peak a t 6  a t the u s u a l p o s i t i o n  proton, integrated  due  to  o f t h e m a j o r peak a t 6 7.90.  the i n t e g r a t i o n  be d e t e r m i n e d  protons  observation related  the e x i s t e n c e o f a minor v i n y l  which appeared  acrylate  o f t h e methoxy  on w h e t h e r i t i s c i s o r t r a n s  interesting  considerably upfield latter,  depending  cis-trans  ring.  Another a b o v e , was  are the r e s u l t of  7.25,  be i n the in  process  4 .2  •"''C-NMR SPECTRA AND PORPHYRIN  13 for  C nmr  COMPARISON TABLES OF  STRAPPED  INTERMEDIATES  s p e c t r o s c o p y was u s e d  the purpose o f supplementing  characterization  . . i n t h i s work  . . primarily  p r o t o n nmr d a t a  of intermediates.  i n the  However, i n c e r t a i n  13 instances the  C nmr a l o n e was  s u c c e s s f u l l y used  s t r u c t u r e s of unexpected  possible minor  by-products.  to p o s t u l a t e the presence  impurities i n certain  of  section  and t h e s t r u c t u r e o f  each  provide a comparison of the chemical  chain lengths.  table  caused  The t a b l e s g i v e n i n  t h e b i s p y r r o l e s and t h e d i p y r r o m e t h a n e  different  F u r t h e r , i t was  i n t e r m e d i a t e s which  problems i n subsequent r e a c t i o n s . this  to p r e d i c t  dimers of  As i n t h e p r e v i o u s  i s accompanied  by t h e s p e c t r u m  a n a l o g u e w h i c h h a s been s e l e c t e d  shifts  section,  o f t h e undecane  as the r e p r e s e n t a t i v e  compound. 13 The noise decoupled this  C nmr d a t a spectra.  have been o b t a i n e d The s o l v e n t u s e d  work was d e u t e r o c h l o r o f o r m .  the assignments, atoms, were b a s e d  especially  this  compound 10%  solvent.  w h i c h had b e e n  Whenever s u f f i c i e n t  trifluoroacetic  acid  because  o f the p y r r o l e carbon  on t h e a l r e a d y a v a i l a b l e d a t a  c o u l d n o t be d i s s o l v e d  proton  throughout  T h i s was m a i n l y  those  m o n o p y r r o l e s and d i p y r r o m e t h a n e s , in  from  on  simple  obtained  quantities of a  i n deuterochloroform  i n deuterochloroform  (w/w)  alone,  338 was  used,  provided  The  changes i n c h e m i c a l  the presence  of a c i d  assignments. s o l v e n t was maintain  prepared  shift  into  account  emphasized  a c c u r a t e l y , no  values  compounds c o u l d be The  were b a s e d  Therefore,  for a particular  p a r t l y due  on  carbons  and  was  electrostatic  already available dipyrromethanes  the p y r r o l e r i n g  carbons  n o t p o s s i b l e due  A number o f  carbon  /  CN  variations of  analogous  those  of  shift  comparison  monopyrroles  Paine  78  and  v a l u e s compared  in well.  the peaks c o r r e s p o n d i n g  to  (shown below)  t o anomalous v a l u e s o f t h e  NC  constant  electron-withdrawing  of dipyrromethanes  CHAIN  this  substituents attached,  with d i f f e r e n t  unambiguous a s s i g n m e n t o f  the  made t o  the  c o n s i d e r a t i o n s and  data.  to  to c o n c e n t r a t i o n e f f e c t s .  the  most i n s t a n c e s , t h e c h e m i c a l  was  that although  attempt  g r o u p s have been s t u d i e d p r e v i o u s l y by  The  due  during  assignments of the peaks, p a r t i c u l a r l y  the p y r r o l e r i n g  and  were t a k e n  I t s h o u l d be  in acid.  values anticipated  these determinations.  chemical  with  shift  stable  t h e m o l a r c o n c e n t r a t i o n o f t h e compounds  throughout in  t h a t t h e compound was  observed  chemical  shifts.  monopyrrolic group,  When compared w i t h t h e s h i f t s  systems  the carbons  carrying  2-,4-,5- and  icant variation.  On  had  and  in  moved u p f i e l d  value  that  undecane d e r i v a t i v e  or  t h a t due 6 126  and  to  t o 3'-C  to l o w f i e l d  6 130  (Table X I I I ) .  series  2 -C 1  resulting I t would comparable the  ( t h e o n l y sample whose s p e c t r u m  was  these resonances  to r a t i o n a l i z e  signif-  except i n the case of  i n deuterochloform alone).  made t o a s s i g n  d i d n o t show any  each of these resonances o c c u r s a t a  i n the d i f f e r e n t  recorded  5'-  individual  withdrawing  t h e o t h e r hand, t h e peak due  f o u r p e a k s between  be n o t i c e d  t h e same e l e c t r o n  of  No  attempt  to i n d i v i d u a l  has  carbon  t h e anomalous c h e m i c a l s h i f t s  been atoms  observed.  II.  • I • I • I  40pOHz 20 10  X/  i i i i '  i i  1  88 a  Hr  J—i—i—I  I . I . I  n=  11  fit** /W»vnf fr»  1  250  I  1  200  I  1  I E  I  1  T—l—i—I—r—i—i  I  150  100  50  1  I  1  I  1  EjZ  0  5  FIGURE 35  :  C NMR  S p e c t r u m o f 88a i n 10% TFA-CDC1  CO o  TABLE V I I I  : C-NMR DATA OF CHAIN  LINKED BIS-PYRROLE  13  DIKETONES [ i n 10% T F A - C D C l ^ (w/w)]  88  x  ~(CH ) 2  88c  7  (n=9)  -(CH ) 2  88b  8  (n=10)  -(CH ) 2  88a  Q  (n=ll)  GROUP  (CH ) .C (CH ) .(CH ) 2  4  6  132  3  l ' - C , n'-C(C=0)  203.79  203.68  204.07  204.11  Ester  C=0  163.95  163 .76  164.00  164.25  142.25  141.94  142.31  142.50  2-C  Durene 1-C, Durene  4-C  4  136.56  2-C,3-C,5-C,6-C 132.37  Pyrrole  4-C  132.19  131.96  132.26  Pyrrole  3-C  122.78  122.79  122 .80  123.03  Pyrrole  5-C  118 .49  118.42  118.49  118.61  62.32  62 .16  62.34  62.57  Ester  2  (n=10)  Chain  Pyrrole  4  -0-CH ~CH 2  3  u>  TABLE V I I I - Continued  88c  8 8b  88a  132  Chain 2'-C, (n-1)'-C (-CH -CO-)  42.23  42.27  42.27  42.27  Chain, 4'-C t o (n-3)'-C  29.32  29.41 29.24  29.37  30.62 29.88  Chain, 3'-C, (n-2)'-C  25.57  25.58  25.74  26.12  GROUP  2  Durene CEU  16.41  P y r r o l e 2-CH"  3  Ester-Q-CH -CH 2  P y r r o l e 4-CH  3  3  15.44  15.39  15.43  15.44  14.23  14 .23  14.23  14.26  12.94  12.89  12.94  13.03  FIGURE 3 6 :  C NMR S p e c t r u m o f  89a i n  CDC1  TABLE IX :  13  C-NMR DATA OF CHAIN LINKED BIS PYRROLE g-ETHYL ESTERS  ( i n CDC1.  89  "(CH ) -  X  2  89c  7  (n=9)  -<CH ) 2  8  89b (n=10)  -(CH ) 2  89a  9  (n=ll)  GROUP Ester  C=0  162.04  161.84  162.24  Pyrrole  2-C  129.75  129.49  130.04  Pyrrole  4-C  127.00  127.05  126.99  Pyrrole  3-C  122.37  122.42  122.36  Pyrrole  5-C  116.78  116.79  116.76  59.55  59.52  59.56  30.90  30.88  30.95  29. 61  29.62  29.69  Ester  -0-CH -CH  Chain  [2'-C,  Chain  [3 '-C t o (n-2) »C ]  2  3  (n-l)'-C]  TABLE IX -  Continued  GROUP  8 9c  8 9b  8 9a  Chain, pyrrole termini ( l ' - C , n'-C)  „. . ^4.Ub  24.06  24.10  Ester  14.59  14.62  14; 6 4  -0-CH -CR" 2  3  n (  Pyrrole  2-CH  3  11.4 3  11.47  11.41  Pyrrole  4-CH  3  10.66  10.62  10.73  • I I I I I •  I I I I I  I l l l l l l l l . i l  4*0 Hi HMO 10DO  90Q  n=11  LXJL i  200  FIGURE 37  • i  150  :  C NMR  • i  '  i  i  i  i  i  i  i  i  i  100  S p e c t r u m o f 90a i n  i  i  i  i  i  1—i—i—i—i—i—i—r~r  50  CDC1  0  TABLE X : C-NMR DATA OF CHAIN LINKED BIS PYRROLE a-BENZYL ESTERS (90a,90b 90c: i n CDC1 ; 13  3  90d, 134 i n 10% TFA-CDC1 ) 3  90  -(CH ) -  X =  2  90d  GROUP  E s t e r C=o Durene 1 - C ,  g  (n=8)  163.21  -(CH ) 2  7  -(CH )g2  -(CH ) 2  q  90c ( n = 9 ) 90b (n=10)  90a (n-11)  161.57  161.68  161.53  4-C  Benzene 1-C  2-C  2  4  6  134  3  136.25  136.85  136.83  136.77  164.53  135.81 132.35  132.30  130.16  130.05  130.37  4  (n=10)  137.17  Durene 2-C, 3-C, 5-C, 6-C Pyrrole  - (CH ) .C (CH ) . (CH )  134.25  2  4  TABLE X - C o n t i n u e d  GROUP  90d  90c  90b  90a  134  Benzene 2-C, 3-C, 4-C, 5-C, 6-C.  128.66 128.18  128.49 127.93  128.49 128.01  128.46 127.91  128.91 128.69 128.39  Pyrrole  4-C  129.25  127.61  127.64  127.52  131.03  Pyrrole  3-C  123.24  122.52  122.57  122.50  123.96  Pyrrole  5-C  115.96  116.39  116.41  116.37  115.57  66.34  65.33  65. 37  65.30  67 .37  30.90  30.84  30.88  30.85  30.96 30.82  Chain[3'-C t o (n-2) «-C] 29.53 Chain, p y r r o l e 24.03 t e r m i n i (l'-C,n'-C)  29.53 24.03  29.61  29.61  24.04  24 . 02  30.24 30. 07 24 .20  Ester-0-CH„-C,H — 2 6 5 c  Chain[2 -C, 1  (n-1)'±C]  16.49  Durene CH"  3  Pyrrole  2-CH  3  Pyrrole  4-CH  3  11.11  11.44  11.48  11.37  10.77  10.78  10.84  11.69 11. 34  •  I  •  I  •  I  .  I  .  I  .  I  •  I  i  I  •  i  •  i  •  [  •  i  i  i  i  I  •  I  I  I  i  I  i  I  i  I  i"T~T  ^ - 2>n ICH  H  C H  V  3  „  N  93a  I  200  FIGURE 38  I  :  I  I  I  I  I  I  I  I  I  150  I  I  I  I  C NMR S p e c t r u m o f  I  '  I  I  I '  100  n=  I  !1  •  93a i n CDC1  I.  '  I  I  I '  50  I  '  I  •  I  1  I  R  0  13  TABLE XI  C-NMR DATA OF CHAIN LINKED BIS g-FORMYLPYRROLES  ( i n CDC1 ) 3  93 -(CH ) 2  GROUP  93d  6  (n=8)  -(CH ) 2  7  93c (n=9)  -(CH ) 2  8  93b (n=10)  "(CH ) 2  93a  9  (n=ll)  Aldehyde C=0  175.56  175.52  175.53  175.52  Pyrrole  2-C  136.55  136.61  136.51  136.74  Pyrrole  4-C  132.58  132.60  132.63  132.71  Pyrrole  5-C  127.96  127.89  127.88  127.87  Pyrrole  3-C  123.38  123.43  123.46  123.44  Chain[ 2 '-C, (n-l) '-C]  30.57  30.58  30.60  30.61  Chain[3'C t o (n-2)'-C]  29.51 29.35  29.51  29.58  29.59  Chain, p y r r o l e t e r m i n i ( l ' - C , n'-C)  23.76  23.74  23.77  23.76  Pyrrole  2-CH^  11.61  11. 60  11. 63  11. 61  Pyrrole  4-CH  8.89  8.86  8.87  8 .87  , i i i i i i i i i i i i i i i~r  .I.I.I.I.I 40\N Hi 10DO 1000  Wain  •io H NC'  3  H  "CN  NC  9*Q  1  I  1  1  I  I I 1  1  I  150  200  CN  n»11  1  I  100  13 FIGURE 3 9 :  C NMR  S p e c t r u m o f 94a i n CDC1.  I  1  I  50  '~1  r  0  TABLE X i i ' :  13  C^NMR DATA OF CHAIN LINKED BISa-DICYANOVTNYLPYRROLES  (94a, 94b, 94c i n CDC1  94d, 138 i n 10% TFA-CDC1 )' 3  NC  CN  NC  CN  94  X =  -<CH )g2  94d  GROUP  (n=8)  (CH ) 2  7  94c (n=9)  -(CH ) 2  8  94b (n=10)  "(CH ) 2  9  94a (n=ll)  - ( C H ) . C ( C H ) . (CH ) 2  4  6  3  138 ,(n=10)  P y r r o l e 2-C  145.85  141.31  141.25  141.37  145.09  C(H)=C'(CN)  140.49  140.49  140.48  140.48  140.97  139.19  136.36  136.38  136.44  138.80  2  P y r r o l e 4-C Durene 1-C,4-C  136.85  Durene 2-C,3-C, 5-C, 6-C  132.19  P y r r o l e 3-C  127.29  125.82  125.79  125.82  4  126.94  2  4  3  TABLE X I I - C o n t i n u e d  94d  94c  94b  94a  GROUP  138  125.22  124.14  124.11  124.14  125.04  C =N  117 .12  117.54  117.61  117.64  117.24  C ;=.N  116.21  116.18  116.18  116.26  116.29  2  57 .97  62.55  62.62  62.51  58.77  Chain[2 -C, (n-1)'-C]  30.26  30.24  30.27  30.25  30.83  C h a i n [3'-C t o (n-2)'-C]  29.61  29.47  29.61 29.49  29.59  Chain,pyrrole termini(1 -C, n'-C)  24.03  23.93  23.93  23.92  Pyrrole  5-C  C (H)=C(CN) 1  1  Durene  CH  30.11  24.04  16.45  3  Pyrrole  2-CH"  Pyrrole  4-CH  3  12.57  12.51  12.56  12.56  12.59  9.80  9.64  9.64  9.64  9.81  I  I  I  I  200  I  I  I  I  I  I  I  I  I  I  150  '  I  I  I  I  I  I  100  13 C NMR S p e c t r u m o f  96a i n  '  I  '  I  I  50 8  FIGURE 4 0 :  I  CDC1  3  I  I  I  '  I  '  I  1  0  I  1  I  1  "  TABLE X I I I  :  13  C-NMR DATA OF CHAIN LINKED a-DICYANOVINYL-a'-ETHOXYCARBONYL  DIPYRROMETHANE DIMERS  (96a i n C D C l ^  ;  gjjb,  96d and 1 4 0 i n 10% TFA-CDC1 ) 3  96 X=  C=0  C(H)=C(CN)  -(CH ) -  "(CH ) -  "(CH ) -  96d  9_6c (n=9)  96b  96a  2  GROUP  Ester  "(CH ) -  2  6  (n=8)  2  7  2  8  (n=10)  2  9  (n=ll)  -(CH ) .C (CH ) . 2  4  6  140  3  164.73  164.80  164.75  162.13  164.74  142.71  142.97  142.75  140.78  142.93  2-C  141.76  141.85  141.78  140.57  141.89  Pyrrole  4-C  138.51  138 .78  138.58  136.25  138 .78  4-C  (CH ) 2  4  (n=10)  Pyrrole  Durene 1-C,  4  136.89 tn  TABLE X I I I - C o n t i n u e d  GROUP  96d  96c  96b  96a  Durene 2-C,3-C, 5-C,6-C  140  132.21  P y r r o l e 3-C  129.78  129.85  129.81  127.09  129.82  Pyrrole  2 -C  128.87  128.93  128.96  126.02  128.98  P y r r o l e 3'-C  126.48  126.64  126.57  125.16  126.51  Pyrrole  126.08  126.14  126.12  (125.16)  126.11  P y r r o l e 5-C  125.06  125.17  125.12  124.15  125.19  P y r r o l e 5'-C  118.09  11.8 . 09  118.11  118.91  118.09  C=N  116.87  116.79  116.88  116.84  116.75  115.8:9  115.84  116.11  115.96  115.67  61.29  60.90  61.26  64. 27  60.99  61. 93  62.00  61. 92  59.96  61. 97  30.28  30.32  30.31  30.30  30.82  1  4'-C J  ' '  cm C(H)=C(CN)  n  Ester  0-CH -CH 2  Chain[2"-C, (n-l)"-C] Chain[3"-C t o (n-2) -C] M  3  30.19 29.69  29.77  29.80  29.59  29. 97  TABLE X I I I  - Continued  GROUP  96d  9 6c  96b  9 6a  14 0  Chain,pyrrole t e r m i n i (1-C,n"-C) and methane b r i d g e CH„  24.12  24.19  24 .18  23.95  24.20  Pyrrole  17.40  17.43  17.43  17 .39  17.44  3'-CH -CH 2  3  Durene CH^ Pyrrole Ester  16.42  3'-CH -CH 2  0-CH ~CH 2  Pyrrole  4'-CH  Pyrrole  4-CH  3  3  3  3  15.27  15.27  15.29  15.38  15.29  14.28  14.27  14 .29  14 .46  14 . 24  10.85  10.84  10.86  10.52  10.85  9.67  9.70  9.71  9.62  9.76  358 4.3  NMR  DATA OF STRAPPED PORPHYRINS  F i g u r e s 41 - 44 the four strapped of t h i s work.  i l l u s t r a t e the proton nmr  porphyrins  In order  s p e c t r a of  s y n t h e s i z e d d u r i n g the  course  to conserve space, the f o l l o w i n g  a b b r e v i a t i o n s w i l l be used f o r the f r e e base  porphyrins,  throughout the d i s c u s s i o n : Compound Number  The  T r i v i a l Name  Abbreviation  106  Etioporphyrin II  H  2 E  109a  Undecamethyleneporphyrin  H  2 11  109b  Decamethyleneporphyrin  H  2 10  109c  Nonamethyleneporphyrin  H  2 ,9  143  Dureneporphyrin  H  2 D  nmr  spectrum of each p o r p h y r i n was  c h l o r o f orm  P  P  P  P  P  recorded  s o l u t i o n using tetramethylsilane  in  (TMS)  deuteroas  the  r e f e r e n c e standard.  Except i n the case of e t i o p o r p h y r i n I I ,  where s o l u b i l i t y was  a l i m i t i n g f a c t o r , i n every  instance  the c o n c e n t r a t i o n of the sample s o l u t i o n was  approximately  at 0 0 5  M.  the v a r i a t i o n of chemical and  other  thereby  T h i s was  important  s h i f t s due  maintained  i n order to minimize  to the c o n c e n t r a t i o n  effects  a f f o r d a d i r e c t comparison of peak p o s i t i o n s .  Concentration  dependence of f r e e base p o r p y r i n s p e c t r a  has  7 9  been i n v e s t i g a t e d by Abraham e t a l .  8  and  Janson and  Not only d i d i t become apparent t h a t c o n c e n t r a t i o n r e s u l t i n c o n s i d e r a b l e changes i n chemical could become nonequivalent.  0  Katz  could  s h i f t s , but  protons  These c o n c e n t r a t i o n e f f e c t s have  109C  i 10  6  8  FIGURE 4 2 : • H NMR S p e c t r u m 1  -1  2  5  (400; MHz) o f  109c i n  CDC1  n= 9  1  1  -2  -3  . -U  1 '  -5  3  co (Ti O  109b  A  A r 0  j j ~T~  10  8  9  FIGURE 43  :  7  i  6  H NMR S p e c t r u m  T  JU-j  AJ  r  CDC1.  il  -2  /V_j\ 0  2  A_J\ 1  -1  1  -r  (400 MHz) o f 109b i n  A  A r  -1  A_A  FIGURE 44  :  1  H NMR S p e c t r u m  (400 MHz) o f 109a i n  CDC1-  j  u>  363  been a t t r i b u t e d molecules  by Abraham t o t h e  in solution The  n  those The  A  o f H P^ 2D n  and  s t r a i g h t chain strapped  H„P,' ) were r e c o r d e d z i i H^P^, 2 E  a t 270  MHz  t h r e e p o r p h y r i n s H2Pg, **2 10 P  been r e c o r d e d observed  a t 270  a t 4 00 MHz.  MHz  chemical  and  no  a t 400  and a n c  ^  100 H  2 11  WH-4  shifts  P  MHz  porphyrins  whereas  MHz,-respectively. ' ^ ^ a<  P  r e v  i°  u s  ly  improvement i n r e s o l u t i o n  T h i s c o u l d be due  l i m i t a t i o n s , of the Bruker The  porphyrin  79 '.  s p e c t r a o f the  ( H „ P , H_P, and z y z i u  s e l f - a g g r e g a t i o n of  to the  00 m a c h i n e a t t h e  was  computer time  of  use.  o f e t i o p o r p h y r i n I I compared  well  81  with  The  the d a t a p u b l i s h e d p r e v i o u s l y .  four methine  as a s i n g l e t  (meso) p r o t o n s  a t 6 10.12, t h e  8,12,18) as a s i n g l e t protons  of e t h y l  (5,10,15,20) were  observed  four r i n g methyl protons  a t 6 3.64  and  g r o u p s as a t r i p l e t  t h e m e t h y l and and  (2,  methylene  a quartet at  6  1.89  364 and  4.12  respectively.  approximately  The  i n n e r N-H  protons expected  6 -4 were n o t o b s e r v e d ,  p r o b a b l y due  at  t o exchange  broadening. Several  interesting  c h a n g e s were o b s e r v e d  i n the  s p e c t r a o f t h e s t r a p p e d p o r p h y r i n s when compared w i t h of  etioporphyrin  etioporphyrin as  linking  o v e r one into  II.  structural  the  3,  1 3 - e t h y l groups  f a c e o f the m a c r o c y c l e .  illustrated  change i n g o i n g  by  by  the  this  i n the form The  structural  splitting  change was  and  introduced clearly  resonances.  s i g n i f i c a n c e were t h e c h a n g e s o b s e r v e d  methine proton resonances  envisaged  of a c h a i n ,  asymmetry  of c e r t a i n  the r i n g methyl  that from  I I t o t h e s t r a p p e d p o r p h y r i n s c o u l d be  the molecule  special  The  nmr  Of  i n the proton  resonances. It in  was  c h e m i c a l s h i f t s were n o t  established based it  interesting  was  on  large,  that  although the  a definite  i n the case of the resonances  the v a r i a t i o n of the c h a i n l e n g t h .  H  2 D P  a  S  c  t h e d u r e n e cap was t o two  o  n  s  i ' i s  t  n  <  ?  °f  a  simple  purpose  durene-capped  12 c a r b o n  i n length.  be  groups,  For t h i s  chain; i . e . ,  c o n s i d e r e d as b e i n g a p p r o x i m a t e l y  methylene groups  changes  trend could  o f common  necessary to c o n s i d e r the s t r a p of the  porphyrin  alent  to note  T a b l e XIV  equivshows  365  U 3  some i n t e r e s t i n g duction  v a r i a t i o n s i n chemical  o f the s t r a p caused  methine proton  the s p l i t t i n g  i n going  from H P 2  the  two s i g n a l s was o b s e r v e d  ly,  t h e r e was an u p f i e l d  2  g  to increase.  shift  being  greater  than t h a t o f the other.  This u p f i e l d  later),  two  should  and i t was r e a s o n a b l e  these  to  the chain  two p o s i t i o n s more t h a n t h e o t h e r  (10-, 20-) . Similar  the  affect  resonance  a t 5- and 15-  s u g g e s t t h a t t h e d i s t o r t i o n s c a u s e d by r e d u c i n g length  significant-  one o f t h e p a i r  shown t o be due t o t h e m e t h i n e p r o t o n s (discussed  More  o f b o t h p e a k s on l o w e r i n g t h e  t h e change o f t h e u p f i e l d  positions  l e n g t h was  to H P , the separation of  D  length,  ring  o f the s i n g l e  As t h e c h a i n  chain  was  The i n t r o -  r e s o n a n c e o f e t i o p o r p h y r i n I I i n t o two s i n g l e t s ,  e a c h i n t e g r a t i n g t o two p r o t o n s . decreased,  shifts.  c h a n g e s were o b s e r v e d  r i n g methyl protons.  f o r t h e r e s o n a n c e s due t o  The i n t r o d u c t i o n o f t h e s t r a p  TABLE XIV :  COMPARISON OF CHEMICAL SHIFTS FOR SELECTED RESONANCES OF PORPHYRINS  H  METHINE  RING C H  2 E P  H  2 D P  H  2 11 P  2 10 P  H P 2  9  9.94  9.97  9.89  9.71  9.86  9.80  9. 67  9.36  3.64  3.64  3.60  3.57  3.48  3.37  3.27  3.00  •3.81  •3.46  •3.27  -3. 06  10.12  C - H  3.64  3  -3.78  N-H  Reference  H  81  (Tl  367 caused chain  a splitting l e n g t h was  of  the  reduced,  increased  and  effect  of  the v a r i a t i o n  on  peak  one  should  ponding values upfield o f ^2^9  n  d  a  be  c  n  a  n  change was  porphyrin  from a reduced  g  of  e  of  resonance the  progressively  As  noted  increased  a reduced r i n g was  shift  current the  methyl protons,  i n going  expected  the  reason.  T h i s was  strapped  porphyrins,  6 -3.46  ppm  N-H  (H„P  two  peaks  seems t o be  P^  the  corres-  same d i r e c t i o n  of  the  ring  ring  current  could  for  the  chain  to g r e a t e r was  upfield  from H P 2  f o r the  N-H  shift  w h i c h moves down t o  6 -3.27  of  would  f o r the  observed. N-H  Of  resonance  f o r H^P  n n  If the  o f methine  2  the  the  protons.  t o H P g , one  what was  exhibits  was  decreased,  distortion  upfield E  the  distortion.  from the  f o r the  arise  movement  l e n g t h was  the  planar  c o n s i s t e n t with  observed  i s that  from  f r o m i t s most s t a b l e  earlier, this  protons  current of  stabilization resulting  essentially 2  greater  f o r the methine  r e s o n a n c e t o move d o w n f i e l d  H  the  ) , a maximum  i n the  smaller  arising  reason  of  the  the  other.  observed  above . i n t e r p r e t a t i o n  change i n c h e m i c a l  as  most o b v i o u s i n t e r p r e t a t i o n  as  lead  and  t h a t compared w i t h  porphyrin  a change t h a t w o u l d  porphyrin  length  to a lowering A  6 3.64  Once a g a i n ,  than the  was  0.64  The  due  configuration.  The  one)  ppm  macrocycle.  distortion  of chain  noted  o f 0.76  the m e t h y l p r o t o n s . this  separation  of e t i o p o r p h y r i n I I  shift a  the  peak a t  b o t h p e a k s moved u p f i e l d .  (the u p f i e l d  It  single  and  6  have same the at -3.06  and  for  H^Pg  The  position  H2P  D  ( t h e N-H  o f t h e N-H  appeared  noted  that  t o be  ring  o f t h e N-H  most i n t e r e s t i n g  by  observed  e f f e c t due shifts.  resonances  t o -6  As  peak. nmr  the l a r g e u p f i e l d  shifts  B e i n g above  the  these protons experience a  t o the r i n g  c u r r e n t which l e a d  illustrated  i n F i g u r e s 41-44,  to  the  the  from  a p p r o x i m a t e l y +4  ppm  ppm.  current effects  shifts  similar  observed  that  systems.  in their  porphyrin  (discussed  moved 1.6  and  53_ and 1.2  of protons a r i s i n g  2.7  in section  ppm  The m u l t i p l e t s  5.5 due  B a t t e r s b y and  by o t h e r w o r k e r s  Hamilton  doubly b r i d g e d "anthracene  upfield  the aromatic and  from d i a m a g n e t i c r i  have p r e v i o u s l y b e e n o b s e r v e d  studying  shifted  This should  f e a t u r e of the p r o t o n  of chemical s h i f t s ;  Upfield  strap  be  of the c h a i n methylene p r o t o n s are d i s p e r s e d over  a wide range up  i t should  e x p e r i e n c i n g the  the c h a i n methylene p r o t o n s .  p l a n e of the p o r p h y r i n r i n g , shielding  but  c u r r e n t of the durene m o i e t y . shift  -3.78).  dureneporphyrin  6 -3.81  s p e c t r a o f s t r a p p e d p o r p h y r i n s was exhibited  II i s at 6  of the  p r o t o n s would be  i n an u p f i e l d The  resonance  anomalous a t  t h e s e two  diamagnetic result  peak o f e t i o p o r p h y r i n  ppm  1.4),  relative  signals  upfield  from  had  3 3  capped"  the anthracene  protons  t o those o f the  free  the p y r i d i n e r e s i d u e  relative  to the  to the c h a i n methylenes  free d i o l  have been  52.  observed  31  up  to 6 -1.  upfield  Traylor  shifts  and  co-workers  have a l s o r e p o r t e d  f o r t h e c h a i n p r o t o n s and  large  imidazole protons  of  369 t h e i r " t a i l - b a s e " p o r p h y r i n s ( s e c t i o n 1.4), upon c o o r d i n a t i o n of the base t o a metal c e n t r e . at 6 2.34  and 6 -0.17  same methylene  group.  In t h i s system, two  resonances  have been assigned to two protons of the T h i s i l l u s t r a t e s the v a r i a t i o n o f the  r i n g c u r r e n t e f f e c t experienced by protons depending on the d i r e c t i o n i n which they are p o i n t i n g .  F u r t h e r , the 2 and 4  p o s i t i o n s of the i m i d a z o l e l i g a n d were s t r o n g l y s h i f t e d by the r i n g c u r r e n t of the macrocycle;  upfield  an e f f e c t which i s known  to i n c r e a s e i n s t r e n g t h both approaching the p o r p h y r i n plane and the l i g a n d a x i s through the metal. The unambiguous assignment by s e v e r a l f a c t o r s .  82  of the peaks was complicated  The r o t a t i o n about the i n d i v i d u a l carbon-  carbon bonds produce d i f f e r e n t r o t a t i o n a l conformations i n which the chemical environment  of a proton would be d i f f e r e n t .  T h i s i s p a r t i c u l a r l y important s i n c e the r i n g c u r r e n t experienced at the d i f f e r e n t conformations would not be the same. rigid  In a  s t r a p as encountered here, one can expect the r o t a t i o n  at the carbon-carbon bonds to be r e l a t i v e l y slow room temperature)  (at l e a s t a t  and t h e r e f o r e the protons on the same carbon  would not produce a time-averaged resonance. the s p e c t r a of these p o r p h y r i n s was  The a n a l y s i s of  f u r t h e r complicated by the  f a c t t h a t i n c e r t a i n i n s t a n c e s , more than one nucleus i s b u r i e d i n a complex a b s o r p t i o n m u l t i p l e t , where s e v e r a l of the c o u p l i n g constants are of s i m i l a r s i z e .  In a d d i t i o n to v i c i n a l  and  geminal c o u p l i n g s , long-range c o u p l i n g through more than three s a t u r a t e d bonds could e x i s t here.  Since the v i c i n a l  coupling  370 constant varies individual at  as a f u n c t i o n o f t h e d i h e d r a l  J v a l u e would  depend on  the e q u i l i b r i u m c o n f o r m a t i o n  each carbon i n these presumably  be d i f f i c u l t  to determine  Keeping  strained  of  H  2 10  t h e above f a c t o r s  """  P  the peaks  n o  r  d  arising  e  r  t  obtain  o  from  i n mind, a s e r i e s  that  1  (Figure  t h e 20 c h a i n m e t h y l e n e  multiplets,  each m u l t i p l e t least  50 Hz,  simpler  43).  o f two  of  protons.  The  several  I t would  be  as 10  features  noticed  distinct  protons, a feature  (cf. Figures  41,42,44).  that  In  addition,  i s s e p a r a t e d from i t s n e a r e s t neighbour  w h i c h made i t p o s s i b l e  without having a s i g n i f i c a n t  to i r r a d i a t e  i n f l u e n c e on  double  assignment  b a s e d on  p r o t o n s appear  each c o n s i s t i n g  made t h e a n a l y s i s  would  decamethylene-  a first-order  s t u d y was  n  i n i t s spectrum  the  the c h a i n methylene  s e l e c t i o n o f H P, for this 2 10 observed  s t r a p s , which  accurately.  r e s o n a n c e e x p e r i m e n t s were c a r r i e d o u t o n porphyrin  a n g l e , the  t h e one  by  at  a peak next to  it. Figures a series  45-49 i l l u s t r a t e  of double resonance  c h a i n methylene  protons.  ten  i n t h e same r a n g e  r e s o n a n c e s due  labelled  two  termini  and  on  by  ( C - l and  o b t a i n e d by  carried  o u t on  a direct  these spectra  the  comp-  were  t h e same e x p a n s i o n .  f r o m t h e one  lowest f i e l d  p r o t o n s can e a s i l y chain  spectrum,  to the c h a i n methylene  A to J , s t a r t i n g The  experiments  In o r d e r t o a f f o r d  a r i s o n w i t h the undecoupled recorded  the s p e c t r a  The  p r o t o n s have been  a t the lowest  r e s o n a n c e s A and  B,  field.  each of  two  a s s i g n e d to the f o u r p r o t o n s a t the C-10).  Being a t t a c h e d to the p e r i p h e r y  371 of  the p o r p h y r i n r i n g ,  deshielding of  effect  due  the m a c r o c y c l e .  f r o m C - l and  C-10  A  T h a t b o t h A and  readily (Figure  change i n t h e f i n e this  irradiation  seen  that  p r o t o n each further  from  C-2  c o n f i r m e d by  and  46b  loss  B and  D but  Although  from  irradiation  C-2  and  B.  C.  C and  indicating  at D  addition, also  that  I t can  due  the  also this of  B  one  (Figure  As  the r e s u l t  was 45c)  expected,  of decoupling of c h a n g e s were  the resonance  t h a t E was  significant  due  to  atoms C-3  from  and  C-8.  was  p r o t o n s o f C-3  and  C-3  and  C-8.  protons  As  the  one  change, t h i s  ( a s s i g n e d t o t h e o t h e r two  to protons  observed  at E exhibited  p r o v i d e d the c o n f i r m a t i o n f o r the e a r l i e r  ment t h a t F was  a  T h i s assignment  at resonance  adjacent carbon  show any  In  D.  T h i s suggested  the next  of  significant  D should c o n s i s t  a s s i g n e d t o t h e o t h e r two  The  C-9)  D,  of the c h a i n .  in addition,  F d i d not  tentatively  in a  E t o J a r e u n a f f e c t e d by  illustrates  of a c o u p l i n g .  p r o t o n each  C-9  C and  the p r o t o n s a t resonance a t A,  the i r r a d i a t i o n  resulted  the i r r a d i a t i o n  o n l y A,  Figure  by  protons of  D a r e c o u p l e d t o t h o s e a t A.  T h e r e f o r e , b o t h C and  which a f f e c t e d  the  a t resonance  the resonances  irradiation.  n o t two  a change a t r e s o n a n c e  sharpening of the l i n e s  be  each  s t r u c t u r e o f the resonance  caused  p r o t o n s a t C and  this  system  B contain 1 proton  demonstrated 45b);  largest  n-electron  to the d e l o c a l i z e d  o f t h e c h a i n , and  same c a r b o n , was the resonance  these p r o t o n s e x p e r i e n c e the  C-8. of  assign-  illustrated  372  T  1  1  0  1  -  X=grease  FIGURE 4 5  :  1  :—r  1  -  2  -3  8  Partial  1  H  NMR  Spectra of  109b;  Ca)  Normal  Spectrum  Cb).  Simultaneous  Irradiation  at 6  (c)  Simultaneous  Irradiation  a t 6 3.4 6  3.67  I 3  i .  2  1  I  —1  1  0  -1  X=grease  FIGURE 46  :  1 -  1 2  -  3  1 -  4  0  Partial  H NMR  S p e c t r a o f 109b;  (a)  Normal  Spectrum  (b)  Simultaneous  Irradiation  a t 6 1.51  (c)  Simultaneous  Irradiation  a t 6 0.46  1  r  -5  -6  374 i n F i g u r e 4 6c, together  with  interesting peak due  the those  As  t o C-2 C-3  and  C-8  C-7.  resulted  protons)  protons).  at G i n d i c a t i n g and  strongly  suggesting f r o m C-4  assigned of  the  t o one  correct.  decoupling a situation were due by  the  protons  irradiations  significant assigned  Thus, the  not  first  t o C-3  results  H contained  e a c h f r o m C-5  at F  on  and  C-8  (Figure D  (both  47b). due two  a t C-5  and  proved  C-6.  this  D and  I but  a t these  not  o f C-3  C-6  two  J to  C-4  The  results  E, r e s u l t e d  be  in in  (Figure  That  47c),  H and  J  were f u r t h e r s u b s t a n t i a t e d  peaks;  C-8  J  two  be  assignment to  a t H and  F w h i c h had and  from  i t s coupling,  ( p r o t o n s o f C-3,and C - 8 ) ,  and  lost  the o t h e r  p e a k s H and  the above assignment.  change a t E and  to protons  (E).  to l o s e p a r t of  This l e f t  a t G and  to protons  C-8  the  u n a f f e c t e d but f u r t h e r  c h a n g e s a t C,  expected  affect  (assigned to the o t h e r  observed  C-7.  proton  to causing  was  resonance contains protons  t h a t I and  Irradiation  i t  I n a d d i t i o n , a l a r g e c o u p l i n g was  I was  and  and  at.E(assigned  at F  changed  d i d not  i n c h a n g e s a t C and  subsequent d e c o u p l i n g s  addition  a t C-3  However, t h e peak H was resonance  Once a g a i n ,  interesting  and  that this  upfield,  protons  protons  some v e r y  this  C-9  two  C.  irradiation  o f the protons  produced  and  B and  that this  t o the o t h e r  expected,  s t r u c t u r e of resonance F  o f A,  to note  Decoupling protons)  fine  n e i t h e r caused  a  p r e v i o u s l y been  ( F i g u r e s 48c  and  order, a s s i g n m e n t .of t h e p r o t o n s  49c). at  375  FIGURE 47  :  Partial  H NMR  Spectra  of  109b;  (a)  Normal  Spectrum  (b)  Simultaneous  Irradiation  a t 6 +0.03 >  (c)  Simultaneous  Irradiation  a t <S  -1.17  376  FIGURE 4 8  :  Partial.  H NMR  Spectra of  109b;  (a)  Normal  Spectrum  (b)  Simultaneous  Irradiation  a t 6 -1.7 9  (c)  Simultaneous  Irradiation  at 6  -2.23  ® D  F  E  G  H  I  -1  -6  X =grease  FIGURE 4 9  :  Partial  H NMR  Spectra of  J  109b;  (a)  Normal  Spectrum  Cb)  Simultaneous  (c)  Simultaneous I r r a d i a t i o n  Irradiation  at 6  -5.13  a t <5 -5.87  378  the d i f f e r e n t  c h a i n carbon  atoms c o u l d  be made as  shown  below:  1 4  1  1 2  3  1 1  1  0  -  1  1 -  1  2  -  1  3  -  4  1 -  the c h a i n ,  that,  a s one g e t s t o w a r d s  i s was  carbon  surprising  atom c o u l d  carbon  results  4  a t each carbon ring on  effect,  systems.  two p r o t o n s on t h e same  ppm  a p a r t which  7) a p p e a r  illustrate  3.34  ppm  the s i g n i f i c a n c e  especially with respect  could  ring  c u r r e n t s depending  from  the macrocycle. A similar  as  The two p r o t o n s apart.  These  o f the conformation  to the diamagnetic  c u r r e n t of the p o r p h y r i n macrocycle.  t h e same c a r b o n  5 (as w e l l  i s the h i g h e s t sep-  f o r any n e u t r a l m o l e c u l e .  (and c a r b o n  clearly  that  studying similar  The two p r o t o n s on c a r b o n  6) r e s o n a t e 3.64  a r a t i o n observed on  to note  current  be s e p a r a t e d a s much as t h a t o b s e r v e d i n  p e a k s G/I and H/J. carbon  the c e n t r e o f  the protons experience a higher r i n g  a f e a t u r e o b s e r v e d by o t h e r w o r k e r s But  -6  ..  5  I t would be n o t i c e d  r  1 5  'CThe two  protons  experience substantially, d i f f e r e n t on whether they p o i n t towards  series  of decoupling experiments  o r away  were  379  carried based two  out with nonamethyleneporphyrin  on  the a n a l y s i s  p r o t o n s on  of the  the c e n t r a l  i  i  1  1  4  3  2  1  H^Pg  and  the  assignments  s p e c t r a a r e shown b e l o w .  carbon  1  (C-5)  1 0  appeared  1  -  1  -  1 2  -  in  one  r  1 3  -  The  4  -  5  S  multiplet in  two  a t 5 -3.33  multiplets  p r o t o n s on C-5 since  w h i l e t h e p r o t o n s a t C-4  a t 6 -4.15  and  r e s o n a t e as one  -4.35.  multiplet  t h e c h a i n c o n s i s t s o f an odd  The  and fact  i s not  C-6  appeared  that  surprising  number o f c a r b o n  atoms  t h e e q u i l i b r i u m c o n f o r m a t i o n o f t h e c h a i n p r o t o n s may i n both  the p r o t o n s o f the c e n t r e carbon  direction.  The  information available  s u g g e s t w h e t h e r t h e two  protons  pointing  i s not  are p o i n t i n g  both  result  in  one  sufficient towards  and  to  the  p o r p h y r i n o r away f r o m i t . The resonances  fact  t h a t none o f t h e c h a i n m e t h y l e n e  o v e r l a p s w i t h any  other resonance  the o b s e r v a t i o n o f o t h e r i n t e r e s t i n g double  resonance  multiplet resulted  experiments  a t 6 4.06  of  H  P 2  i o *  a l s o made p o s s i b l e  f e a t u r e s d u r i n g the I r r a d i a t i o n of  (the m e t h y l e n e p r o t o n s o f e t h y l  i n an a p p r o x i m a t e l y  12%  proton  the  groups)  increase i n intensity  of  380 the methine  r e s o n a n c e a t 6 9.67,  T h i s change, enabled  attributed  relative  to the n u c l e a r  the assignment o f the u p f i e l d  t h e 5- and  15- m e t h i n e  protons.  A  of  H  2 io P  ethyl  w  a  s  t  *  i e  e x  resonance  similar  s t e n c e  °f  (expanded) q u a r t e t e x p e c t e d f o r the CH  2  spin  ob-  spectrum  p r o t o n s o f the  rather  than a simple  p r o t o n s o f an e t h y l  D e c o u p l i n g of the methyl p r o t o n s quartet  r e s u l t was  to  Simultaneous Irradiation a t 6 1.81  Undecoupled  t y p i c a l AB  (6 9.67)  n  the methylene  g r o u p s as a complex m u l t i p l e t  9.89.  effect,  H„P . z y f e a t u r e o b s e r v e d i n the  interesting l  at 6  Overhauser  t a i n e d w i t h the nonamethyleneporphyrin Another  to t h a t  (triplet  f o r the methylene  s y s t e m c a n be d e s c r i b e d  as ABR^  group.  a t 6 1.81)  gave a  p r o t o n s such t h a t f o r the e t h y l  the  side  ,9 3  chains.  Abraham and  Smith ' 7  were t h e f i r s t  the n o n - e q u i v a l e n c e o f the a-methylene  to  demonstrate  p r o t o n s u s i n g aquo-3  381  octaethylporphinatothallium Two  interpretations  either  the i n v e r s i o n  o f the methyl  the C ^ - C g ' , s i n g l e  in  intrinsic  the  asymmetry  metal the  observed  groups.  rically  ligands  a u t h o r s who  be  of  arise  both  protons.  the observed  result or  by  the  of  the  and  an a c t i v a t i o n I t was  was  methyl  from a s y m m e t r i c a l l y  c o o r d i n a t e geometry around from The  an  the  asymmet-  former  f a v o u r e d by  energy  concluded  o f t h i s magnitude would produce  give  would  inversion  "hindered r o t a t i o n "  calculated  rotation  s u f f i c i e n t to account f o r  d i f f e r e n t a x i a l ligands)  ^ for this rotation.  energy  which  the p o r p h y r i n r i n g  with rapid  could  (five  i s slow,  (i.e.,  coordinated (out-of-plane) metal.  interpretation  to  even  groups  o f the p o r p h y r i n m o l e c u l e  i t s l i g a n d s may  spectra,  m e t a l , o r two  mole  asymmetry  Such asymmetry  coordinated  bond  introduced into  atom and  shown b e l o w .  f o r t h e phenomenon wer,e s u g g e s t e d ;  about an  (III) hydroxide  o f c a . 20 t h a t an  a slow  enough  anisochronous behaviour of the  these kcal  activation rotation methylene  382 Dolphin energy for  for rotation  the  to r o t a t i o n  been o b s e r v e d .  octaethylporphyrin  "outside" of these  Busby  the  84  argued  c o u l d n o t be  above s y s t e m and  barrier has  and  as h i g h  that i n similar  should  be  With the  as  activation 20  no  y-oxo d i m e r o f  workers observed  the  this  Although  these  relief the that  of hindered  reversible the  r o t a t i o n of  breakdown o f  former e x p l a n a t i o n  r o t a t i o n be  exceedingly,  be the  explained  (III)  at  the  was 180°G.  either  by  e t h y l side chains  the dimer, the  authors  impossibly,  high.  the  or  by  argued  r e q u i r e s t h a t the b a r r i e r  i f not  and  environments,  complex p a t t e r n  to c o l l a p s e to a P a s c a l q u a r t e t o n l y  rotation  "inside"  different  observed  can  the  hindered  same complex p a t t e r n f o r  Further,  observations  where  scandium  (shown below) i n w h i c h t h e  two  k c a l mole  cases  even h i g h e r ,  sandwich p r e s e n t  methylene protons.  t h a t the  to  They  383 conclude that  the observed  protons r e s u l t s  a n i s o c h r o n i c i t y o f the methylene  from t h e i n h e r e n t  asymmetry o f t h e m o l e c u l e .  8 5 '8 6  Other workers of  '  these protons  4 .4  X  ' C NMR J  have a l s o o b s e r v e d i n metalloporphyrin  DATA OF STRAPPED  the non-equivalence systems.  PORPHYRINS  13 Figures strapped The  porphyrins  most s t r i k i n g  of only for  50-53 i l l u s t r a t e synthesized  feature  two r e s o n a n c e s  during  o f these  as any  relative  intensities  cyclization.  i n this  periphery  region  as w e l l  as e v i d e n c e f o r  change i n t h e  s h i f t s o f t h e meso c a r b o n s and t h e r e f o r e  7  been c l e a r l y  sensitive  the a c i d - c a t a l y z e d  t o c a u s e an o b s e r v a b l e  a change i n t h e peak p a t t e r n °  four  i n the molecules  The s u b s t i t u t i o n o f a m e t h y l g r o u p by an e t h y l  group i s s u f f i c i e n t  in  t h e same i n t e n s i t y )  c a n be u s e d during  work.  i s the existence  a t the porphyrin  t h e number o f r e s o n a n c e s  rearrangements taking place  chemical  spectra  The meso c a r b o n atoms a r e p a r t i c u l a r l y  therefore their  the course o f t h i s  (5-,10-,15- and 2 O 7 )  to the nature o f the s u b s t i t u e n t s and  C nmr s p e c t r a o f t h e  (of a p p r o x i m a t e l y  t h e f o u r meso c a r b o n s  (6--V-100).  the  illustrated  i n this 13  i n the  region.  result T h i s has  C nmr s p e c t r a o f t h e  "type isomers" of e t i o p o r p h y r i n .  Etioporphyrin  I  FIGURE 51  :  1 3  C  NMR  S p e c t r u m o f 109a i n 10% TFA-CDC1  FIGURE 52  :  C NMR  S p e c t r u m o f T09b i n 10% TFA-CDC1  FIGURE 53  :  C NMR  S p e c t r u m o f 109c i n 10% TFA-CDC1  388  Et  Me  \  \  y  Me Et  Et  /  Me  TYPE  exhibits  Et  Me  Me  Me  I  TYPE  etioporphyrin type  IV  \ Et  single II  isomers  Et  \  Et  a  Et  /  Me  Me  Me  Me  y  resonance  e x h i b i t s two three  Me  Me  Et  as  resonances  Me  Et  /  Me  Me  TYPE  expected,  98.94, 98.54).  (6  \  \  III  <5 98 . 16  at  Et  Et  TYPE  Et  /  y  Et  II  Et  \  \  Et  show  Me  /  each,  in  whereas  Type the  IV  III  and  ratio  of  synthesized  by  1:1:2. The two  two  different  exhibited  two  rearrangement and  samples  routes  its dipyrrolic  system.  I t can  the  strapped  of  four this  work.  catalysed  be  As  taken  seen  each, place  cyclization.  This  of  was  under  indicating during  were  (Figures  discussed  rearrangement  strapped  cyclized  porphyrins  drawback  the  etioporphyrin  presursor  significant  of  (both  resonances has  of  50-53)  earlier  most  to  that  to  little the  the  that  conditions)  acid  this  during  isomeric  particularly the  in  is  the  used the  cyclization  no  catalyst true  was  for  course the  acid  porphyrins  systems  crucial  or  porphyrin  ( s e c t i o n 2.6),  catalyst  since  identical  time  exposed  synthesized  leading  porphyrins  the  II  is  a  for synthesis carried  389 out over  a p e r i o d o f a p p r o x i m a t e l y one  week.  13 The divided  into  carbons, the  C resonances  f o u r major groups;  ( i i ) t h e meso c a r b o n s ,  substituents  Etioporphyrin region  and  and  t h e o t h e r two  For  the  two  would e x p e c t  o n l y seven  twice  the i n t e n s i t y The  ethyl  2 10 P  o f the t h i s was  resonances  ^  i n the  aromatic  3-carbons a-carbons. one  observed.  nonamethylene p o r p h y r i n  b u t one  a t 6 -20 ppm  CH^  side chains.  The  carbons  a  carbons.  types of  a n <  was  of  approximately  carbons  and  6-16  respectively  ppm of  of the r i n g methyl  can  be  the groups  are  between 11 and 12 ppm. The m e t h y l g r o u p s o f H^P-^ p r o d u c e d two s i g n a l s whereas t h o s e o f H „ P and z y n  v  e  r  i  s  e  t  o  o n l y one.  Although  g r e a t c a r e was  taken  to m a i n t a i n a c o n s t a n t molar  c o n c e n t r a t i o n of the p o r p h y r i n  in  to a s c r i b e  any  solution,  i t is difficult  structural  changes i n the m o l e c u l e s .  mentioned  here  CDCT^ and  therefore, The  that  of  rest.  and  9  carbons  i n d e e d what was  p e a k s were o b s e r v e d  two  the a l i p h a t i c  strapped porphyrins,  p o r p h y r i n H^Prj  as t h e  be  g-pyrrolic  to the c o r r e s p o n d i n g  t o t h e CH^  observed and H_P_ zu H  t o t h e two  carbons  "durene capped"  assigned  due  8 resonances;  H^Pg,  (iii)  only 4 resonances  b e i n g due  16 p y r r o l i c  ( i ) t h e a- and  (iv) the c h a i n methylene  II exhibits  (Table XV),  In the  o f the p o r p h y r i n s c o u l d  this difference I t should  t h e s p e c t r a were r e c o r d e d i n 10%  to  be TFA-  are o f the p o r p h y r i n d i c a t i o n s .  c h a i n methylene carbons  appear  i n the r e g i o n  TABLE XV  : COMPARISON OF  Assignment  C CHEMICAL SHIFTS OF PORPHYRINS  H  2 E P  143 . 54 a- and  B-pyrrolic  carbons  142.29 141.53 136.92  Durene r i n g Meso  98.39 97.95  Chain methylene carbons  20.11 16.42  CH -CH CH^-CH^ Durene  CH^  Porphyrin  2 D P  146.07 143.08 142.90 142.71 141.25 140.31 (140.31) 139.17  H  2 11 P  10% TFA-CDC1 ) 3  H  2 10 P  H  2 9 P  146.73 145.12 143.67 141.41 140.56 140.24 140.05 139.20  146.87 145.61 143.61 141.22 140.44 140.22 138.95 138.23  146.60 (146.60) 144.65 141.21 140.42 139.59 139.07 134.27  100.89 99. 94  101.24 100.05  101.48 99.72  134.79 130.25  carbons  carbons  H  n  99.87 98.91 30.80 29.46 (29.46) (29.46) 27 .20  28.86 28.67 (28.67) 27.00 25. 98 25.38  28.47 27.94 26.96 26.46 25.96  28.72 (28.72) 28.22 25.84 24.97  20.16 16.67  20.21 16.61  20.20 16.62  20.12 16.47  12 . 21 11.75  11.77  11.66  14 .65 CH^  11.67  12.28 11.68  391 between H  2 10' P  w;  25 ppm "- tn  a  and  3 0 ppm  The  group  (Figure  b r o a d e r and  6 c a r b o n s , t h e o t h e r two s p e c t r u m o f ^2 ±i P  which  two  single  this  field  b e i n g due  (Figure  ( 6 28.86 and  51)  could  and  spectrum  The  peaks  exhibited  28.67) a p p e a r e d  the broad resonance  of H„P  n  (Figure  a t 6 25.84 and  e a c h w h i l e t h e one  For  five E^l?^,  53)  a t <5 28 .72 would  the  The  as one  broad  also  from  two  be due be due  peak.  resonate at be due  to  carbons  a similar  each. pattern-  to 2 carbons to 4 carbons.  t o t h e odd  carbon  atom  chain. c a n be  seen t h a t  the resonances of the  atoms o f t h e c h a i n do n o t u n d e r g o as t h e p r o t o n r e s o n a n c e s do, Since  to  5 resonances, of  exhibited  24.97 would  27.20.  attributed  h e r e would  "hook" a t 6 28.22 s h o u l d be due  It  of  52).  be  c e n t r e c a r b o n o f t h e c h a i n may  The  of  For  to 2 carbons each.  5 carbons, the o t h e r t h r e e r e s u l t i n g  The  spectrum.  t h r e e s i g n a l s were o b s e r v e d , a t <$ 30.80, 29.46 and peak a t 6 29.46 was  The  C nmr  c h a i n o f an even number o f c a r b o n atoms,  s i g n a l s were o b s e r v e d i n one only  13  o f the  some c o m p l i c a t i n g  the s o l v e n t  acid  made h e r e t o a s s i g n  by  factors  as l a r g e  the e f f e c t  carbon  an u p f i e l d of r i n g  current.  s u c h as t h e p o s s i b l e  concentration  could  exist,  the resonances  to i n d i v i d u a l  shift  variation  no a t t e m p t i s carbon  atoms.  392 4.5  ELECTRONIC ABSORPTION SPECTRA OF  Porphyrins absorption  exhibit  PORPHYRINS  a characteristic  spectrum c o n s i s t i n g  o f one v e r y  electronic  i n t e n s e band  •  5 (e ^-10 ) a r o u n d four  less  i n t e n s e bands i n t h e r e g i o n f r o m  The S o r e t band the  400 nm, known as t h e " S o r e t " band and  nucleus  i s observed  i s fully  as a c h a r a c t e r i s t i c relative sensitive giving  of the four v i s i b l e  regarded  1  The  bands a r e  of the p e r i p h e r a l s u b s t i t u e n t s ,  t o f o u r main  500  and i s g e n e r a l l y  o f the m a c r o c y c l i c conjugation.  to the nature  -I—  i n a l l t e t r a p y r r o l e s i n which  conjugated  intensities  rise  500 t o 7 00 nm.  spectral  1  600  •  classifications.  1  500  •  1  600  nm  varying group  a's I V > I I I > I I > I .  of  i n a rhodo-type absorption  spectrum.  bands t o longer  each others  effect  producing  porphyrins itions  o r more u n s u b s t i t u t e d  work  exhibited very  absorption  spectra  as i l l u s t r a t e d  o f band  t h a t became more p r o n o u n c e d Furthermore,  a shift  was a l s o n o t e d increased In  fact,  i n going  al  contain  spectrum  this  the longest  (Figure  to this  resulting  from  repalthough  peripheral  pos-  The  t o IV, a change  l e n g t h was  bands t o longer  decreased. wavelengths  progressively  to the shortest H„P  n  2.  y  strap.  exhibited a the molecule  group.  a distortion  the short  55-58.  s p e c t r u m was t h e  58) a l t h o u g h  i s that  during  interesting electronic  too being  an e l e c t r o n - w i t h d r a w i n g  explanation  moiety,  from  whereas  synthesized  as the chain  the nonamethyleneporphyrin  rhodo-type not  XVI),  cancel out  i n the oxo-rhodo  I I Ir e l a t i v e  of absorption  (Table  Two e l e c t r o n -  i n Figures  o f t h e f r e e base  i n the intensity  shifts  spectra.  of this  feature  a l s o cause  i s particularly  strapped/capped, porphyrins  most s t r i k i n g  result-  substituted porphyrins  course  increase  result  spectrum  also exhibit similar The  the  four  IV  an e t i o - t y p e s p e c t r u m  o f mono m e s o a l k y l with  band  "pyrrole" moieties  such groups, d i a g o n a l l y placed,  resentative  than  wavelengths.  on a d j a c e n t  The p h y l l o - t y p e  at a 3 position  These groups  groups  spectrum.  electron-withdrawing  etc.)  I I I t o become more i n t e n s e  withdrawing  two  strongly  (formyl, carboxylic acid, ester  causes band ing  One  The o n l y  typical does logic-  i n the porphyrin  strap, causes  effectively  1-0-1  30 0  350  1  I  I  400  450  500  I 550  1—"^"T 600  650  700  nm.  WAVELENGTH  FIGURE  54  Electronic  Absorption  Spectra of  106  LO  WAVELENGTH  FIGURE 55  :  Electronic Absorption  Spectra of  143 CO Cn  FIGURE  56  Electronic Absorption  Spectra of  109a OJ  0>  WAVELENGTH  FIGURE  57  Electronic Absorption  Spectra of  109b U) —3  FIGURE 58  :  Electronic Absorption  Spectra of  109c CO CO  TABLE XVI : COMPARISON  OF ELECTRONIC ABSORPTION SPECTRAL DATA OF PORPHYRINS  (Free base i n C H C 1 ) 2  2  A.  nm  (log  e)  Porphyrin  H  H  H  H  H  2 E P  2 D P  2 11 P  2 10 P  2 9 P  Soret  Band IV  Band I I I  Band I I  Band I  396.5  497.0  530.0  565.7  619.7  (5.23)  (4.16)  (4.02)  (3.84)  (3.72)  400.7  500.8  537 .0  569.8  623 .9  (5.16)  (4.04)  (3.98)  (3.76)  (3.64)  400.7  503.1  539 .8  571. 9  625.8  (5.24)  (4.05)  (4.05)  (3.80)  (3.59)  402.0  507.5  544 .4  572.7  626.2  (5.21)  (3.96)  (4.03)  (3.78)  (3.37)  405.3  513.5  551.7  579.1  633 . 0  (5.23)  (3.92)  (4.08)  (3.82)  (3.43)  LO VO VO  400  the  same c h a n g e s i n t h e  as d o e s a s i n g l e It  should  observed no  be  of the m o l e c u l a r  electron-withdrawing  possible to provide  changes i n the  a theoretical  electronic  spectra  visible  exhibit  shoulders  ication square  absorption  ( ^ )  symmetry  D  n  i n the  relative  of  intensities  s t r a p t o one  s t r u c t u r e of  with  the  but  Although  band  of  appearing  simplif-  approach  towards the  spectrum i n  the  two  bands  strapped acid  appeared  from a p o r p h y r i n  a shorter strap.  two  the  absorption  weaker bands  dication. two  for  spectra,  dication  the  changed p r o g r e s s i v e l y i n g o i n g  a long  basis  This spectral  a result  also exhibited this  medium, t h e  fine  major bands, with  t o be  periphery.  so.  region of porphyrin  t o t h e main p e a k s .  i s thought  porphyrins  t o be  two  orbitals  group a t the  a t t e m p t w o u l d be made h e r e t o do The  as  energies  with  In a d d i t i o n , t h e  bands a l s o showed  significant  change. An of  the  interesting  strapped  decomposition new  especially  w h i c h c o u l d be are  peripheral  porphyrin  under the  was  absorption  d o u b l e bonds r e d u c e d . could  t o be H_P , Q  t h e r e f o r e be  and  The a way  case  i f exposed  ease  of  handling of  light.  A  s p e c t r u m a r o u n d 650 of a one  by  of  the  to l i g h t  which the  This  n  m  chlorin. the  change f r o m a  system i s reduced.  r a p i d i n the  the  the  i n f l u e n c e of  a t t r i b u t e d to the p r o d u c t i o n  the m a c r o c y c l i c  appeared  i n the  in solution  during  p o r p h y r i n - l i k e materials with  to a c h l o r i n in  porphyrins  band d e v e l o p e d  Chlorins  f e a t u r e observed  porphyrin strain  decomposition  nonamethylenef o r long periods  of  TABLE X V I I  : COMPARISON OF ELECTRONIC ABSORPTION SPECTRAL DATA OF PORPHYRINS (Dication  i n CH C1 ) 2  2  X  max  Porphyrin  H„P^ 2 E  H P 2  D  H ii P  2  H P 2  H P 2  1 Q  g  nm  (log ^  e)  Soret  Band A  Band  B  399.5  549.1  590.7  (5.58)  (4.25)  (3.90)  405.0  549.2  594.4  (5.57)  (4.16)  (3.76)  402.7  550.9  597.3  (5.58)  (4.12)  (3.79)  405.5  553.4  601.5  (5.55)  (4.08)  (3.75)  409.2  559.3  609.5  (5.53)  (4.03)  (3.95)  402 time, the  " f o u r band" s p e c t r u m was  observed  to  disappear  completely. The r e a c t i o n of  blue-black the  material  from  that of a  In a d d i t i o n t o e x h i b i t i n g o n l y  as  the  400  nm  a  i n the  t o be  visible not  band a r o u n d 385  t h e more i n t e n s e v i s i b l e  jugation  porphyrin  at least  band, i t c o u l d  porphyrin.  from the  8 - c a r b o n s e r i e s e x h i b i t e d an  spectrum q u i t e d i f f e r e n t  region,  isolated  10 be  nm  two  absorption  porphyrin.  b r o a d bands i n t h e  was  band.  1.5  t i m e s as  intense  Since  the  extended  con-  intense  concluded  visible  only  m a c r o c y c l e causes the t i m e s as  cyclization  as  band  around  t h e most  that this material  intense is  403  REFERENCES  1.  R. B o n n e t t i n "The P o r p h y r i n s " , (D. D o l p h i n , 1, p. 1, A c a d e m i c P r e s s , New Y o r k , (1978).  2.  A r e p o r t by t h e C o m m i s s i o n on t h e N o m e n c l a t u r e o f B i o l o g i c a l C h e m i s t r y , J . Am. Chem. 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