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Mechanism of pyrolysis of 3,3,4,5-tetrasubstituted 1-pyrazolines. McKinley, James William 1969

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MECHANISM OF PYROLYSIS OF 3,3,4,5-TETRASUBSTITUTED  1-PYRAZOLINES  BY  J.W. B.Sc,  University  A THESIS SUBMITTED  McKINLEY of British  Columbia, 1967  IN PARTIAL FULFILMENT OF  THE REQUIREMENTS FOR THE DEGREE OF MASTER OF. SCIENCE  i n t h e Department o f CHEMISTRY  We a c c e p t t h i s T h e s i s as conforming required  t o the  standard  THE UNIVERSITY OF BRITISH COLUMBIA December, 1969  In presenting this thesis in partial fulfilment of the requirements for an advanced degree at the University of British Columbia, I agree that the Library shall make it freely available for reference and study. I further agree tha  permission for extensive copying of this thesis  for scholarly purposes may be granted by the Head of my Department or by his representatives.  It is understood that copying or publication  of this thesis for financial gain shall not be allowed without my written permission.  Depa rtment The University of British Columbia Vancouver 8, Canada  Date  r  ABSTRACT  A s e r i e s of t e t r a s u b s t i t u t e d 1-pyrazolines all  t h r e e carbon c e n t e r s has  The  1-pyrazolines  s u b s t i t u t e d at  decomposed  thermally.  i n which t h r e e o f the s u b s t i t u e n t s occupy a pseudo  e q u a t o r i a l p o s i t i o n and a x i a l p o s i t i o n give  the r e m a i n i n g s u b s t i t u e n t o c c u p i e s  a pseudo  as the major product the c y c l o p r o p a n e w i t h  t i o n of configuration. two  been p r e p a r e d and  uniquely  On  the o t h e r hand,the 1 - p y r a z o l i n e s  s u b s t i t u e n t s are pseudo e q u a t o r i a l and  a random d i s t r i b u t i o n o f c y c l o p r o p a n e s .  two  reten-  i n which  are pseudo a x i a l  Evidence i s p r e s e n t e d  give that  former s e t o f p y r a z o l i n e s have a l a r g e r degree o f f o l d i n g between two  planes  d e f i n e d by  suggests t h a t the  C-3,  C-4,  C-5  and  C-5,  N-2,  l a r g e r the degree o f f o l d i n g i n the  m o l e c u l e the more s t e r e o s p e c i f i c i t y t h e r e proposed t o account  i s . Two  i n v o l v i n g a concerted  i n g an i n t e r m e d i a t e  resembling  case o f one  there  are two  products.  s u b s t i t u e n t s b o t h e q u a t o r i a l and  the o t h e r  one  involv-  pyrazoline  i s pseudo  isomer i n which  a x i a l gave 6 7 %  T h i s s u p p o r t s the mechanism i n v o l v i n g c o n c e r t e d t h a t i s t r a n s t o the  are  r e t e n t i o n of  i s o m e r i c p y r a z o l i n e s , the  c y c l o p r o p a n e p r o d u c t s whereas the C-5  the hydrogen at C-4  This  diradical.  i n which t h r e e s u b s t i t u e n t s are pseudo e q u a t o r i a l and a x i a l gave 99%  the  pyrazoline  mechanism and  a pyramidal  p a i r o f C-5  C-3.  mechanisms  f o r the c y c l o p r o p a n e formed w i t h  c o n f i g u r a t i o n - one  In the  N-1,  the  leaving nitrogen.  olefin  migration  of  - i i i TABLE OF CONTENTS Page I.  INTRODUCTION  .  .  1  P y r o l y s i s of 1-Pyrazolines  II.  1  a)  3 - A c e t y l and 3-Carbomethoxy-1-Pyrazolines  1  b)  3,5-Diaryl-l-Pyrazolines  13  c)  3-Cyano-3-Carbomethoxy-l-Pyrazolines  14  d)  A l k y l Substituted 1-Pyrazolines  19  RESULTS AND DISCUSSION  36  P r e p a r a t i o n and Product D i s t r i b u t i o n s  36  Identification  of Pyrazolines  45  Identification  o f Cyclopropanes  49  Identification  of Olefins  52  Discussion  55  a)  O l e f i n Formation  55  b)  C y c l o p r o p a n e Formation  60  I I I . EXPERIMENTAL  73  G e n e r a l Statement  73  N - N i t r o s o - N - e t h y l Urea  73  Diazoethane  74  Benzaldehyde Hydrazone  74  Phenyl Diazomethane  74  3-Methyl-3-pentene-2-one,  ( Z ) - (131)  3-Methyl-4-phenyl-3-butene-2-one,  ( E ) - (132)  75 76  - iv Page  3-Acetyl-3',4'-dimethyl-5-(and 5 ' ) - p h e n y l - l - p y r a z o l i n e s (118 and  119)  7  6  a)  P r e p a r a t i o n and Enrichment  76  b)  Pyrolysis  78  c)  Product D i s t r i b u t i o n  and Product  Identification  80"  3'-Acetyl-3,4'-dimethyl-5-(and 5 ' ) - p h e n y l - l - p y r a z o l i n e s (120 and  121)  8  1  a)  P r e p a r a t i o n and Enrichment  81  b)  Pyrolysis  8  c)  Product D i s t r i b u t i o n  and Product I d e n t i f i c a t i o n  2  ^  8  3-Acetyl-3',4-(and3*,5')-dimethyl-4 -phenyl-l-pyrazolines 1  (122 and  123)  a)  P r e p a r a t i o n and Enrichment  b)  Pyrolysis  c)  Product D i s t r i b u t i o n  E r y t h r o - and (134 and  135)  and Product I d e n t i f i c a t i o n  .  ( E ) - (128)  ^ 8  7  8  8  and .  ( E ) - (128)  90  Methyl-2-methyl-3-phenyl-2-pentenoate,  .(E)- (140)  (141)  3-Methyl-4-phenyl-3-hexene-2-one,  89  and  (129)  (Z)-. (158)  4  88  (129)  3-Methyl-4-benzyl-3-pentene-2-one,  (Z)-  8  threo-3-methyl-4-phenyl-5-hexene-2-one  M e t h y l 3-methyl-3-benzyl-2-butenoate,  (Z)-  4  8  T r i m e t h y l a-phosphonopropionate  (Z)-  8  and 91  ( E ) - (136)  and 92  - V Page BIBLIOGRAPHY  94  APPENDIX  97  Nomenclature  97  - vi LIST OF TABLES Table I  3,3,4,5-Tetrasubstituted-l-pyrazolines  II  P y r o l y s i s Products  f o r 1-Acetyl-l ,2 -dimethyl-3-(and 1  3')-phenyl-l-pyrazolines l,2-dimethyl-3-(and  III  P y r o l y s i s Products  1  (118 and 119) and l ' - A c e t y l -  3 )-phenyl-l-pyrazolines 1  f o r 1-Acetyl-l',3-(and  dimethyl-2 -phenyl-l-pyrazolines 1  1»,3')-  (122 and 123)  IV  N.m.r. Data f o r 3 , 3 , 4 , 5 - T e t r a s u b s t i t u t e d  1-Pyrazolines  V  N.m.r. Data f o r 1 , 1 , 2 , 3 - T e t r a s u b s t i t u t e d  Cyclopropanes  VI  N.m.r. Data f o r D e t e r m i n a t i o n Preferences  VII  o f Conformational  of 3-Methyl-3-acetyl-l-pyrazolines  C y c l o p r o p a n e Products  from  3,3,4,5-Tetrasubstituted-l-  pyrazolines  VIII  D i s t r i b u t i o n o f Cyclopropane Products  for Pyrazolines  w i t h E l e c t r o n Drawing Group a t C-3  IX  D i s t r i b u t i o n o f Cyclopropane Products 1-pyrazolines  X  and A l k y l S u b s t i t u t e d  D i s t r i b u t i o n o f Products  for 3,5-diaryl1-pyrazolines  f o r the P y r o l y s i s o f D i f f e r -  ent R a t i o s o f t h e P y r a z o l i n e s 118 and 119  XI  D i s t r i b u t i o n o f Products  f o r the Pyrolysis o f D i f f e r -  ent R a t i o s o f t h e P y r a z o l i n e s 120 and 121  - Vll -  Table  XII  Page  D i s t r i b u t i o n o f Products f o r the ent  R a t i o s o f the  Pyrazolines  122  Pyrolysis and  123  of D i f f e r 8 7  - viii  -  LIST OF FIGURES Figure 1"  Page I o n i c mechanism f o r t h e p y r o l y s i s o f  3,4-dimethyl-3-  carbomethoxy-1-pyrazolines  2  2  O l e f i n f o r m a t i o n from p r e f e r r e d  conformations  o f 3,5-  dimethyl-3-carbomethoxy-l-pyrazolines  3  Intermediate i n dihydrofuran formation  4  Preferred  conformations  of  5  7  3,5-dimethyl-3-acetyl-l-  pyrazolines  5  T r a n s i t i o n s t a t e s o f the o l e f i n forming r e a c t i o n f o r cis-  6  7  and t r a n s - 3 - m e t h y l - 4 - e t h y 1 - 1 - p y r a z o l i n e s  K i n e t i c scheme f o r t h e  9  3-methyl-3-carbomethoxy-l-  pyrazolines  H  7  R a d i c a l mechanism f o r 3 , 5 - d i a r y l - l - p y r a z o l i n e s  15  8  T r a n s i t i o n s t a t e f o r t h e p y r o l y s i s o f 3-cyano-3-carbomethoxy-4-alkyl-4-aryl-l-pyrazolines  9  K i n e t i c scheme f o r p y r o l y s i s o f a l k y l pyrazolines  10  substituted  1-  . ..  20  A l t e r n a t i v e k i n e t i c scheme f o r p y r o l y s i s o f a l k y l substituted  11  18  1-pyrazolines  21  Rate d e t e r m i n i n g t r a n s i t i o n s t a t e f o r 3 - v i n y l - l pyrazoline  ...  22  - ix Figure  Page  12  ir-Cyclopropane i n t e r m e d i a t e s  13  Concerted  23  t r a n s i t i o n s t a t e f o r o l e f i n forming  reaction  f o r c i s - and t r a n s - 4 - d e u t e r i o - 3 - m e t h y l - 1 - p y r a z o l i n e s . .  14  Two t r i m e t h y l e n e i n t e r m e d i a t e s from c i s - and t r a n s - 3 , 4 dimethyl-1-pyrazoline  15  25  26  T r a n s i t i o n s t a t e s and o l e f i n s expected  on b a s i s o f  c o n c e r t e d mechanism f o r p y r o l y s i s o f c i s - and  trans-3,4-  dimethyl-5,5-d2-l-pyrazolines  27  16  K i n e t i c scheme f o r Z,3-d^-  29  17  K i n e t i c scheme f o r 4-d^- and 4 , 4 - d 2 ~ l - p y r a z o l i n e s  18  Pyramidal exo-  and 3 , 3 , 5 , 5 - d ^ - l - p y r a z o l i n e s  d i r a d i c a l mechanism f o r d e c o m p o s i t i o n  ....  of  and endo-5-methoxy-2,3-diazabicyclo[2.2.1]-2-  heptene  19  30  33  T r a n s i t i o n state f o r concerted nitrogen e l i m i n a t i o n from e x o - 5 , 6 - d i d e u t e r i o - 2 , 3 - d i a z a b i c y c l o [ 2 . 2 . 1 ] - 2 heptene  20  Favourable  35  conformations  o f c i s - and t r a n s - 3 , 5 -  dimethyl-3-acetyl-l-pyrazolines  21  Conformational  46  p r e f e r e n c e s o f 5-(and 5 ' ) - p h e n y l - 3 , 4 1  1  dimethyl-3-acetyl-l-pyrazolines  22  P r e f e r r e d conformations  and C-5 chemical  o f some 3 - m e t h y l - 3 - a c e t y l - l - p y r a z o l i n e s  47  shift  values 48  -  X  -  Figure 23  Page Thermal rearrangement o f 1 - a c e t y l - l , 3 - d i m e t h y l - 2 1  1  phenyl-cyclopropane  24  51  R e a c t i o n sequence i n p r e p a r a t i o n o f 3-methyl-4-phenyl3- hexene-2-one, (E) and  (Z)  S3  ~>  25  3-Methyl-4-phenyl-3-hexene-2-one,  (E) and  (Z)  assignment by n.m.r  26  27  S3  R e a c t i o n sequence f o r p r e p a r a t i o n of 3-methyl-4benzyl-3-pentene-2-one,  (E) and  (Z)  55  P r e f e r r e d conformations  of 3 - a c e t y l - 3 ' , 5 - and  (3',5')-  4- p h e n y l - l - p y r a z o l i n e s  28  S6  C o n c e r t e d mechanism f o r f o r m a t i o n o f  cyclopropanes  with r e t e n t i o n of c o n f i g u r a t i o n  29  Pyramidal  67  d i r a d i c a l mechanism f o r f o r m a t i o n ~ o f  cyclo-  propanes w i t h r e t e n t i o n of c o n f i g u r a t i o n  30  Intermediate  resembling  in p y r o l y s i s of 2-heptene  a pyramidal  diradical  67  species  endo-5-methoxy-2,3-diazabicyclo[2.2.1]7  ^  - xi -  ACKNOWLEDGEMENT  I wish t o thank Dr. D.E. McGreer f o r h i s h e l p f u l and  constant  encouragement throughout t h i s  research.  discussions  I.  }  INTRODUCTION  P y r o l y s i s o f 1-Pyrazolines (a)  3-Acetyl  and  3-Carbomethoxy-l-Pyrazolines  von Auwers and Konig  (1,2) s t u d i e d t h e s t e r e o c h e m i s t r y  p r e p a r a t i o n o f cyclopropanes  by the a d d i t i o n o f diazomethane t o double  bonds a c t i v a t e d by e l e c t r o n - w i t h d r a w i n g decomposition  o f the  groups, f o l l o w e d by  of the r e s u l t i n g p y r a z o l i n e s .  They concluded  thermal t h a t when  t h e i n t e r m e d i a t e p y r a z o l i n e s are 1 - p y r a z o l i n e s , t h e c y c l o p r o p a n e s r e t a i n t h e geometry o f t h e i n i t i a l (3-5)  olefins.  Other s t u d i e s by Jones  on 2 - p y r a z o l i n e s were based on the assumption t h a t  decompose w i t h r e t e n t i o n o f geometry.  they conclude  (6,7).  1-pyrazolines  However, major e r r o r s i n the  a n a l y t i c a l r e s u l t s o f von Auwers and Konig McGreer and co-workers  formed  have been demonstrated by  In l a t e r work by Jones and T a i (8,9),  t h a t a t b e s t the r e a c t i o n i s p a r t i a l l y  stereospecific  w i t h r e s p e c t t o t h e t h r e e and f o u r p o s i t i o n s o f t h e p y r a z o l i n e . Rinehart thermal cis-  and Van Auken (10,11) p r e p a r e d  and p h o t o l y t i c decompositions  and s t u d i e d both t h e  o f t h e two i s o m e r i c p y r a z o l i n e s ,  and t r a n s -3,5-dimethy1-3-carbomethoxy-1-pyrazo1ines  (1_ and 2 ) .  P y r o l y s i s o f t h e s t e r e o c h e m i c a l ^ pure p y r a z o l i n e s 1_ and 2_ gave f o u r products  i n c l u d i n g two c y c l o p r o p a n e s ,  i n d i c a t i n g the r e a c t i o n gives  products  o f mixed s t e r e o c h e m i s t r y , a l t h o u g h  a s l i g h t degree o f s t e r e o -  - 2 -  C0 CH 2  rV N  C0 CH 2  C0 CH  3  2  \/ /\ C 0  3  2  C H  3 > ~  C  0  2  C  H  3  3  18  12  66  28  35  33  N  1  C0 CH 2  N =  3  N  2  selectivity  i s noted.  The r e s u l t s were e x p l a i n e d by t h e i o n i c mechanism  as shown i n F i g u r e 1.  I i  NI  C0 CH 2  rC  M N  1 or 2  S  T  E  C0 CH  3  2  P  Ja  CH„ 3  CH  ^  H  ?  — N  2  C0 CH 2  3  s t e p b CH_ 3, 3  3  CH.  +  step d  C0 CH 2  s t e p c CH cyclopropanes  ^  CH.  .3 and 4  F i g u r e 1 - I o n i c mechanism f o r t h e p y r o l y s i s o f 3,4-dimethyl-3carbomethoxy-l-pyrazolines.  3  3  - 3The C-3 N-2 bond i s f i r s t broken t o g i v e the i o n i c s p e c i e s which t h e r e is  i s competition  expected t h a t  7_ i n  between r o t a t i o n and l o s s o f n i t r o g e n .  loss of nitrogen  It  (step b) i s f a s t e r than r o t a t i o n , and  thus t h e resonance forms 8^ and 9 would c y c l i z e immediately upon formation  (step c) , r e s u l t i n g i n some s t e r e o s e l e c t i v i t y .  losing nitrogen  (step b ) , t h e  i o n i c species  1_ can a l s o p o s s i b l y  d i s p l a c e m e n t o f t h e diazonium group by b a c k s i d e carbanion  ( s t e p d) .  Besides give  a t t a c k o f t h e C-3  With l a r g e r groups p r e s e n t a n y o f t h e s e }  routes  would p r e d i c t an i n c r e a s e i n s t e r e o s e l e c t i v i t y as a r e s u l t o f more hindered  rotation.  S i m i l a r l y , s t e r e o s e l e c t i v i t y should  the p y r a z o l i n e i s m o d i f i e d and  i n such a way as t o i n c r e a s e t h e s t a b i l i t y ,  hence t h e l i f e - t i m e , o f t h e i n t e r m e d i a t e s  t h a t t h e p y r a z o l i n e s themselves i s o m e r i z e out  ( r e v e r s e o f step a) was r u l e d isomeric  (10) and t h e two i s o m e r i c  and t r a n s - 3 , 5 - d i m e t h y l - 3 - c a r b o m e t h o x y - 1 - p y r a z o l i n e s  P y r o l y s i s o f the three p y r a z o l i n e s  10  pyrazoline  (7,12,13) have i n v e s t i g a t e d t h e p y r o l y s i s o f  3-methyl-3-carbomethoxy-l-pyrazoline  product  The p o s s i b i l i t y  detected.  McGreer and co-workers  cis-  involved.  s i n c e a f t e r p a r t i a l p y r o l y s i s none o f t h e o t h e r  c o u l d be  be reduced when  pyrazolines,  (11 and 12).  10, 11, and L2 gave the f o l l o w i n g  distributions.  13  14  15  65  15  15  16 5  - 4 -  -rY. N==  3  4  17  18  19  18  48  0  32  2  60  15  22  0  3  N  11  12 There are two the a,B  and  i s , the o l e f i n  17_ from the p y r a z o l i n e  hydrogen m i g r a t i o n  t i o n s as shown i n F i g u r e  i n the  2.  The  m  formed e s s e n t i a l l y  An  explanation  with nitrogen  of a l l ,  stereo-  11 and  i s p o s s i b l e assuming  elimination,  and conforma-  r e s u l t s then suggest t h a t the to the  the  t  1_2 e x i s t e n t i r e l y i n the  leaving nitrogen,are  hydrogens  migrating  reaction.  second f e a t u r e from the d a t a i s the  r e a c t i o n i n which the  First  18_ from the p y r a z o l i n e  Y\_ and  as H ,which are t r a n s  olefin-forming  The  12_.  i s concerted  assuming t h a t the p y r a z o l i n e s  designated  from t h i s d a t a .  B,y-unsaturated e s t e r s are  s p e c i f i c a l l y ; that olefin  important f e a t u r e s  cyclopropane-forming  c i s - p y r a z o l i n e 11 g i v e s predominantly  c y c l o p r o p a n e £,and the  the  trans-  c y c l o p r o p a n e 5_ w i t h the methyls c i s i s the  predominant c y c l o p r o p a n e from the t r a n s - p y r a z o l i n e  12.  Thus  the  c y c l o p r o p a n e - f o r m i n g r e a c t i o n i s not  s t e r e o s e l e c t i v e and  requires  i n v e r s i o n e i t h e r at C-3  t r a n s i t i o n s t a t e may  involve  or C-5.  The  d i r a d i c a l 9 or a d i p o l a r s t r u c t u r e 7_ ( F i g u r e  1) but McGreer  and  a  - 5 -  H  12  l i  11  Figure 2 - O l e f i n formation  from p r e f e r r e d conformations  of  3,5-  dimethyl-3-carbomethoxy-1-pyrazolines.  ..co-workers f a v o u r a c o n c e r t e d p r o c e s s .  The  e f f e c t o f s o l v e n t has  t o r a i s e the p r o p o r t i o n o f the o l e f i n s i n the product c o n s t a n t o f the s o l v e n t i s r a i s e d and products  a r e formed through  t h i s suggests  One  two  product  cyclopropane  To o b t a i n i n v e r s i o n by a  extremes f o r n i t r o g e n e x p u l s i o n are  i s l o s s o f n i t r o g e n i n theC-3,C-4 and C-5  f o r m a t i o n o f two  t h a t the  dielectric  a s l i g h t l y d i f f e r e n t t r a n s i t i o n s t a t e and  presumably l e s s p o l a r than the o l e f i n s . concerted process  as the  been  considered.  plane,accompanied  by  p - o r b i t a l s a t C-3 and C-5 which would bond t o g i v e  of retained configuration.  The  other i s l o s s o f n i t r o g e n  p e r p e n d i c u l a r t o the C-3,C-4 and C-5 p l a n e g i v i n g two C-3 and C-5 p a r a l l e l  to each o t h e r .  p - o r b i t a l s at  However,the groups a t C-3  and C-5 would  -  be s u f f i c i e n t l y c l o s e t o C-N  bonds  6  -  each other  to  cause unequal  i n the t r a n s i t i o n s t a t e ? w h i c h would permit  t h e m o l e c u l e and e v e n t u a l l y McGreer  e_t a l _ .  (14)  lead to  i n v e r s i o n at  3,5-dimethyl-3-acetyl-l-pyrazoline  furan  20. g a v e f i v e  products  (27), and p y r o l y s i s o f  including  a twisting  (20)  (Zl_ a n d 2 2 ) .  including  the p y r a z o l i n e s  2,3,5-trimethyl-4,5-dihydrofuran  the  of  center.  have a l s o s t u d i e d the p y r o l y s i s o f  pyrazolines;3-methyl-3-acetyl-l-pyrazoline  pyrazoline  one  stretching of  the  and c i s - and Pyrolysis  three  trans-  of  the  2,3-dimethyl-4,5-dihydro21_ a n d 22^ g a v e s i x (33).  products  The  formation o f the dihydrofuran d e r i v a t i v e s  i s explained  assuming an i n t e r m e d i a t e 34 ( F i g u r e 3) i s formed with n e g a t i v e  3,  Figure 3 - Intermediate  i n dihydrofuran  b u i l t up o n C - 3 o f t h e p y r a z o l i n e .  charge  products  formation.  As t h i s n e g a t i v e charge i s d e l o c a l i z e d  i n t o t h e c a r b o n y l oxygen, t h e oxygen w i l l be a b l e t o p a r t i c i p a t e i n a ring closure reaction.  The f a c t t h a t the d i h y d r o f u r a n d e r i v a t i v e 33_  i s formed e x c l u s i v e l y from the p y r a z o l i n e 21_ shows t h a t s t e r i c p r e s e n t p l a y an important 22 e x i s t  roll.  factors  Assuming t h a t t h e p y r a z o l i n e s 21 and  e n t i r e l y i n t h e conformations  F i g u r e 4 - P r e f e r r e d conformations  as shown i n F i g u r e 4, then i t can  of 3,5-dimethyl-3-acetyl-l-pyrazolines.  be seen t h a t i n 21_ t h e oxygen i s i n a more f a v o u r a b l e p o s i t i o n f o r ring closure.  The amount o f d i h y d r o f u r a n i s a l s o i n f l u e n c e d by the  r e a c t i o n medium. i n a non-polar  The p e r c e n t a g e  o f the d i h y d r o f u r a n isomer i s h i g h e s t  solvent.  There i s a l s o an i n t e r e s t i n g c o r r e l a t i o n between the c i s - and  - 8 -  trans-3,5-dimethy1-3-acetyl-1-pyrazolines  (21 and 22) and t h e c i s - and  trans-3,5-dimethyl-3-carbomethoxy-1-pyrazolines  (11 and 12).  t r a n s - p y r a z o l i n e s 22 and 1__ g i v e almost i d e n t i c a l product ratios  (cis-cyclopropane:trans-cyclopropane:olefin)  61:17:22 r e s p e c t i v e l y . ratios  3-carbomethoxy p y r a z o l i n e H ^ a n d 3 - a c e t y l p y r a z o l i n e 21. trans-cyclopropane,the  distribution  o f 60:15:25 and  For the c i s - p y r a z o l i n e s , t h e product  (cis-cyclopropane:trans-cyclopropane:olefin) 16:24:37 p l u s  I f the dihydrofuran  distribution  a r e 18:48:34 f o r t h e  23% d i h y d r o f u r a n  f o r the  p o r t i o n i s added onto t h e  r a t i o becomes 16:47:37 f o r the p y r a z o l i n e ___ .  which i s c l o s e t o t h e r a t i o observed f o r the c o r r e s p o n d i n g c a r b o m e t h o x y - p y r a z o l i n e 12_. i s being  The two  trans-3-  T h i s suggests t h a t the d i h y d r o f u r a n  formed a t t h e expense o f t h e t r a n s - c y c l o p r o p a n e  product  during the  p y r o l y s i s o f the c j _ _ - p y r a z o l i n e 21. McGreer and Wu by p r e p a r i n g  (15) demonstrated s t e r e o s p e c i f i c o l e f i n  formation  and p y r o l y z i n g t h e two i s o m e r i c p y r a z o l i n e s . c i s - and t r a n s -  3-methyl-4-ethyl-3-carbomethoxy-l-pyrazolines  (35 and 36).  Each  p y r a z o l i n e gave s t e r e o s p e c i f i c a l l y a d i f f e r e n t a , g - u n s a t u r a t e d e s t e r . This s t e r e o s p e c i f i c i t y  can be r e l a t e d t o t h e s t r u c t u r e o f the p y r a z o l i n e  through t h e requirement t h a t l o s s o f n i t r o g e n must be from the s i d e o f the p y r a z o l i n e t h a t i s t r a n s t o t h e m i g r a t i n g The  product  corresponding  hydrogen a t C-4.  d i s t r i b u t i o n shows t h e same g e n e r a l  4-methyl p y r a z o l i n e s 1_ and 2_.  t r e n d s as t h e  P y r a z o l i n e s 3_5 and 36_ do  however show a g r e a t e r p r o p o r t i o n o f c y c l o p r o p a n e  product,and a t t h e  same time a g r e a t e r tendency towards s t e r e o s p e c i f i c f o r m a t i o n cyclopropanes.  The mechanism based on c o n c e r t e d  o f the  m i g r a t i o n o f hydrogen  - 9 -  C0 CH  CO„CH  J  \  2  *  .  2  A  <  / C0 CH 2  37  N =  J  C0 CH  3  2  \  \  C 3  /  ,2  3  38  39  40  41_  9  0  56  4  72  13  N  35 C0 CH 2  3  11  N =  N  36  from C-4 t o C-5 t r a n s t o t h e l e a v i n g n i t r o g e n can be a p p l i e d i n t h i s case.  The t r a n s i t i o n s t a t e s 4_2 and 4_3 may be a n t i c i p a t e d f o r t h e  p y r a z o l i n e s 35_ and 36 as i n F i g u r e 5.  C0 CH 2  H  43  42  F i g u r e 5 - T r a n s i t i o n s t a t e s o f the o l e f i n forming and  reaction for c i s -  trans-3-methyl-4-ethyl-l-pyrazolines.  Another example t h a t i l l u s t r a t e s formation  3  N  H  the c o n c e r t e d  type  olefin  i s the c i s , t r a n s - and c i s , c i s - 3 , 4 , 5 - t r i m e t h y 1 - 3 - c a r b o m e t h o x y -  1-pyrazolines  (44 and 4 5 ) .  On the b a s i s o f the proposed o l e f i n  3  _ _ / ~  forming  - 10 -  r e a c t i o n , t h e a , 8 - u n s a t u r a t e d e s t e r s expected from the p y r o l y s i s o f t h e p y r a z o l i n e s 44 and 4_5 w i l l be t h e same i n b o t h c a s e s .  N =  N  45  McGreer and M a s t e r s  (16) have determined t h e k i n e t i c s and p r o d u c t  d i s t r i b u t i o n f o r the p y r o l y s i s o f 3 - m e t h y l - 3 - c a r b o m e t h o x y - l - p y r a z o l i n e (10) and i t s 4,4-d^ and 5,S-d^  analogues  p h t h a l a t e , n i t r o b e n z e n e and foramide. k^/k  D  50_ and _51_ i n t e t r a l i n ,  The k i n e t i c  isotope  n-butyl  effects  f o r t h e 5,5-d2 p y r a z o l i n e 51_ o f 1.22 and f o r t h e 4,4-d2 p y r a z o l i n e  50 o f 1.36 a r e c o n s i s t e n t w i t h a mechanism i n v o l v i n g m i g r a t i o n o f t h e C-4 hydrogen c o n c e r t e d w i t h l o s s o f n i t r o g e n .  13 C0 CH 2  14  15  68.9  14.7  12.3  4.1  78.2  9.6  10.2  2.0  77.8  8.9  10.5  2.8  63.8  14.6  16.2  5.4  16  3  n-butylphthalate 10  D  N  2  C0 CH 2  3  n-butylphthalate neat  = N 50  C0 CH 2  3  neat N—N 51  U s i n g t h e scheme i n F i g u r e 6 t h e k i n e t i c ;  i s o t o p e e f f e c t can be  d i v i d e d i n t o a c o n t r i b u t i o n from t h e o l e f i n forming r e a c t i o n and a  olefins V  C0 CH  (I  . N =  2  N  3  cyclopropane  F i g u r e 6 - K i n e t i c scheme f o r the 3 - m e t h y l - 3 - c a r b o m e t h o x y - l - p y r a z o l i n e s .  - 12 -  contribution  from t h e c y c l o p r o p a n e f o r m i n g r e a c t i o n by making use o f  the p r o d u c t d i s t r i b u t i o n s . analogue  For the p y r a z o l i n e  10 and i t s 4,4-d2  50:  H k D  k  oH k cH  31.1 68.9  , oD and k _ cD  1.94  and  k  n  oH cH k + k oD cD +  n  k  u  .  k  n  21.1 78.2  k  Thus  K  For  the p y r a z o l i n e  =1.20 cD  ___ and i t s 5 , 5 - ^  analogue 5_1_:  __H  k  oH  D  K  oD  K  ^  oD  oH k „ cH k  =  +  k  cH K  _ •  „  cD  33.2 66.8  _____ k _ cD  36.2 63.8  Thus  r^oD  =1.12  and  ^  = cD  1.28  - 13 -  A primary isotope e f f e c t a magnitude o f 1.41 (17a) and B l a c k s The  f o r the hydrogen on C-4  i s expected  with  t o 2.36,based on s t u d i e s by S e s t e r and R a b i n o v i t c h  (17b)  isotope effect  f o r the c y c l o p r o p a n e t o o l e f i n i s o m e r i z a t i o n .  i n the c y c l o p r o p a n e t o p r o p y l e n e r e a c t i o n has been  a t t r i b u t e d to. a p r i m a r y e f f e c t a s s o c i a t e d w i t h the b r e a k i n g o f the m i g r a t i n g C-D  bond.  e f f e c t o f 1.20  may  For the c y c l o p r o p a n e forming r e a c t i o n the i s o t o p e be a t t r i b u t e d t o a secondary  isotope effect  3 r e l a t e d t o the change o f h y b r i d i z a t i o n from sp  2 towards sp  found i n  cyclopropane. The 51_ was  k i n e t i c isotope effect  d i v i d e d i n t o 1.12  and  o f 1.22  1.28  forming r e a c t i o n r e s p e c t i v e l y .  found f o r the 5 , 5 - ^  f o r the o l e f i n and  pyrazoline  cyclopropane  T h i s p r o v i d e s evidence t h a t the C-5  bond i s b r e a k i n g i n the t r a n s i t i o n s t a t e i n the o l e f i n forming  N-1  reaction.  T h i s a l s o p r o v i d e s e v i d e n c e t h a t t h e r e i s a change o f h y b r i d i z a t i o n at C-5  and  the C-5  N-1  bond i s b r e a k i n g i n the t r a n s i t i o n s t a t e o f the  c y c l o p r o p a n e forming r e a c t i o n .  T h i s secondary  l i n e w i t h t h a t found by S e l t z e r and co-workers F u r t h e r mention w i l l be made o f deuterium  isotope effect  is in  (17a-c) f o r a z o a l k a n e s .  isotope effects  i n the  d i s c u s s i o n o f d e u t e r a t e d a l k y l p y r a z o l i n e s (19-23). (b)  3,5-Diary1-1-Pyrazolines  Overberger  and co-workers  (25-28) have p r e p a r e d a s e r i e s o f  d i a r y l - l - p y r a z o l i n e s and determined thermal  the p r o d u c t r a t i o s and r a t e s o f  decomposition.  The k i n e t i c s t u d i e s on the 3 , 5 - d i a r y l - l - p y r a z o l i n e s i n d i c a t e d e l e c t r o n i c c o n t r i b u t i o n s had  i  3,5-  little  •  •  effect  s i n c e the r a t e s and  that  - 14 -  trans-cyclopropane  6 5 ""I^V  C  H  C  6 5  cis-cyclopropane  89  H  11  52  £-0Me-C H ....|^Y6  4  N =  C H -p_6  OMe  4  93.3  6.7  57.0  43.0  N  53  £  - O M e - C H _ _ ^ N p C H -p_- OMe 6  4  6  N=  4  N  54  E-; - 6 4 | lr C1  C  H  ,,,,  XV  N =  C  6 4-^ H  N  C  1 100  55  a c t i v a t i o n energies  f o r the t r a n s - p y r a z o l i n e s  52, 53 and 55 were  e s s e n t i a l l y t h e same. E l e c t r o n s p i n resonance s t u d i e s o f t h e p h o t o l y t i c d e c o m p o s i t i o n o f p y r a z o l i n e _52_ i n d i c a t e d t h e p r e s e n c e o f a f r e e r a d i c a l .  T h i s suggested  a mechanism i n v o l v i n g a f r e e r a d i c a l as i l l u s t r a t e d i n t h e scheme i n F i g u r e 7.  (c)  3-Cyano-3-Carbomethoxy-1-Pyrazolines  A s t r u c t u r e such as t h e i o n i c s p e c i e s  1_ i n F i g u r e  p o s i t i v e charge i s b u i l t up a t C-5 o f t h e p y r a z o l i n e transition state.  1 suggests t h a t  system i n t h e  I f t h i s i s t h e case, rearrangements c h a r a c t e r i s t i c  -  15  -  N=N Ar  /  \  H  H  H  Ar  Ar  1  1 Ar  Ar Figure  of  7 -  R a d i c a l mechanism f o r  et_ al_  (29)  H  Ar  H  3,5-diaryl-l-pyrazolines,  carbonium i o n s s h o u l d be p o s s i b l e f o r  McGreer  v  the p y r a z o l i n e  h a v e p r e p a r e d a number  of  system.  4,4-dialkyl-3-cyano-  carbomethoxy-l-pyrazolines.  C0 CH  ^ 2 ^ 3  2  C0 CH 2  59  2  \  •  60  /  S 61  C N  C N  3  22  39  39  CN  N=  _/  CN  C0 CH  N  56 C0„CH.  CN  y C0 CH 2  C0 CH 2  N—  57  N  CN  3  62  63  15  85  3  ( c i s and  trans)  3  - 16 -  CO_CH 3  2  C 0  y  C H  3  C 0  \ s-S  N  C02CH3 N — N  64  C N  CN ( c i s and trans)  65_  CN  25  35  / -\  '  2  C H  CN and trans)  __6 ( c i s 40  The r e s u l t s o b t a i n e d f r o m t h e p y r o l y s i s o f t h e p y r a z o l i n e s 57 a n d 58_ a r e c o n s i s t e n t w i t h t h e d e v e l o p m e n t at C-5 o f  the p y r a z o l i n e  system.  of  a positive  56,  charge  I n a d d i t i o n , p r e l i m i n a r y s t u d i e s on  the r a t e o f p y r o l y s i s w e r e c a r r i e d o u t results  3  i n a variety of  solvents.  s u g g e s t a t r a n s i t i o n s t a t e w h i c h i s more p o l a r t h a n  The  the  starting material. H a m e l i n and C a r r i e p r e p a r e d a number o f  (30 a - e )  3-cyano-3-carboethoxy  alkyl-4-aryl-l-pyrazolines product d i s t r i b u t i o n s at  C02CH3  N  (or  (31)  have  3-carbomethoxy)-4-  and s t u d i e d t h e p y r o l y s i s r e a c t i o n .  70°  Ar  6 5 N —  and McGreer and W i g f i e l d  i n nitrobenzene  CN •  N  /  Ar  S  C02CH3  (cis  and t r a n s )  Typical  a r e shown.  CN  N  /  Ar  C  \  ___/  ( c i s and  33  53  14  36  52  12  • • 67_  _58(5,5-d2)  C H  3  CN  C02CH3  ( c i s and t r a n s )  °2  trans)  - 17 -  N — N  *CN  1 0 0  69  C0 CH 2  p-OMe-C,H/**1I  3  '''CN '  3 8  5 2  1 0  70  C0 CH 2  E  -NO -C H;2  3  34  - - CN  6  49  17  21 E-N0 -C H 2  C0 CH  6  2  3  »*| T"' %  N=N  92  C N  72  The c i s - p y r a z o l i n e s 69 and 72_ (carbomethoxy  and a r y l c i s ) gave  p r e d o m i n a t e l y t h e o l e f i n from a r y l migration,whereas t h e t r a n s - p y r a z o l i n e s 67, 70 and 71_ gave p r e d o m i n a t e l y the o l e f i n from methyl m i g r a t i o n . kinetic  study was a l s o c a r r i e d  out f o r t h e p y r o l y s i s r e a c t i o n and t h e  v a l u e o f t h e secondary deuterium k i n e t i c suggests that at the t r a n s i t i o n  i s o t o p e e f f e c t o f k^/k^ = 1.03  state there i s l i t t l e progress i n the  bond b r e a k i n g o f the C-5 N-1 bond. T h i s r e s u l t d i f f e r s c o n s i d e r a b l y the  result  o b t a i n e d by McGreer and Masters  isotope effect  o f k^/k^ = 1.22 f o r n  D  A  from  (16) who o b t a i n e d an  3-methyl-3-carbomethoxy-5,5-d.-l-  2  -  18  -  pyrazoline. It  was a l s o f o u n d t h a t  there  is negligible effect  g o i n g from p_-methoxyphenyl  to phenyl  that  group  migration of  the  also progressed to again d i f f e r s that  the  C-4  transition  aryl  hydrogen  i s the  i n the t r a n s i t i o n s t a t e .  4,4-d2-l-pyrazoline was i n v o l v e d  50_ i n w h i c h i t  was  This found  i n considerable participation i n  entropy  of  those  information  activation values.  found by McGreer  transition state  compared t o t h e  observed i n reactions occurring v i a  obtained  The  from the  negative  and M a s t e r s  are c o n s i s t e n t w i t h a d d i t i o n a l c o n s t r a i n t the  suggests  the  state.  consistent with  of  This  on  and any r e s u l t i n g p a r t i c i p a t i o n has  Another i n t e r e s t i n g piece of study  to p_-nitrophenyl.  a n e g l i g i b l e degree  from the  on t h e r a t e  i n the  (16)  same  values  are  although  degrees of  they  freedom  s t a r t i n g material which  ionic transition states  not  in  is polar  media. Another fact rate  drawn out  by  solvent  i n t e t r a l i n to nitrobenzene  to  effects  formamide  i s that  t h e change  of  was f o u n d t o b e 1 : 3 4 : 3 . 4  x  3 10  .  Such a change o f  rate  can be a t t r i b u t e d  more p o l a r t h a n t h e s t a r t i n g m a t e r i a l . together  (the  activation,  5,5-d2  solvent  isotope effect, effect  r e p r e s e n t e d as i n F i g u r e  on r a t e s )  to  Considering a l l the  a r y l groups the  a transition  on r a t e s ,  transition state  state  results entropy  73_ may  of  be  8. A r . ^ ^ t ^ ^ ^ .CN CO  CH_  21 Figure  8 - Transition  state  for  the p y r o l y s i s  alkyl-4-aryl-l-pyrazolines.  of  3-cyano-3-carbomethoxy-4-  -  (d)  Alkyl  19  -  Substituted-l-Pyrazolines  C r a w f o r d and c o - w o r k e r s  (19a-c)  of a l k y l  have p r e p a r e d and s t u d i e d  substituted 1-pyrazolines.  the  kinetics  of a series  kinetics  w e r e o b s e r v e d t o g r e a t e r t h a n 95% c o m p l e t i o n a n d t h e r a t e  found t o be independent o f p r e s s u r e . a r e i n c r e a s e d on t h e p y r a z o l i n e , t h e continuous decrease from 42.4 pyrazoline  82_.  First  As t h e number o f m e t h y l  order was  groups  a c t i v a t i o n e n e r g i e s show a  Kcal/mole for  74_ t o 3 7 . 7  The d e c r e a s e p e r m e t h y l g r o u p o f  Kcal/mole  approximately  for  one  K c a l / m o l e may b e d u e t o a n i n c r e a s e i n g r o u n d s t a t e e n e r g i e s .  The  entropy  pyrazoline  of  a c t i v a t i o n v a r i e s from 11.2  82_,as i s e x p e c t e d i f  eu f o r  74_ t o 4 . 6  t h e t r a n s i t i o n s t a t e more c l o s e l y r e s e m b l e s  s t a r t i n g m a t e r i a l s on p r o c e e d i n g from p y r a z o l i n e  l ^ ^ l  cyclopropane  olefin  89.2  10.8  N^=N  N j X V ^ N  93.3  6.7  N  N  ' ' { ^ Y  N  75  82.  33.2 c i s 66.1  trans  72.6  cis  25.4  trans  olefin  0.7  N  =  2.0  80  52.3 N— N 76  to  the  79  j^Y' =  74  cyclopropane  74  N  eu f o r  99.36  47.7 N  __N 81  0.64  -  PS N—  98.6  20  -  1.4  0.25  99.75  N  N  N 82  77  3.3  96.7  ( ^ f \  N= 7__  trace  83 I n t h e same w o r k . t h e  A k i n e t i c isotope  effect  C-4 of  deuterated pyrazoline  k^/k^  = 1.07  84 was  was o b s e r v e d .  the proposed r e a c t i o n sequence i n F i g u r e the  100  N  N  9 the  prepared.  Following  isotope effect  for  o l e f i n f o r m i n g r e a c t i o n may b e c a l c u l a t e d .  x • I  —  CD) >  J  Figure  9 -  intermediate  K i n e t i c scheme f o r p y r o l y s i s  Assuming k  c H  From p r o d u c t  /k  c D  k  Then  __H c  oD  =  1.80  W  A of  alkyl substituted  =1.0  distributions k y k ^  2  = 47.7/52.3  n / k _ = oD cD  34.0/66.0  1-pyrazolines.  21 olefin cyclopropane 47.7  Nr=N 52.3  74  L  66.0  34.0  N —N 84  The v a l u e o f 1.80 i s c l o s e t o t h e v a l u e observed i z a t i o n o f deuterated cyclopropanes  (17a,b).  f o r t h e isomer-  The a l t e r n a t i v e  approach  o f assuming t h a t t h e o l e f i n and c y c l o p r o p a n e come from d i f f e r e n t g i v e s r i s e t o t h e k i n e t i c scheme o u t l i n e d i n F i g u r e 10  CD)  t  H(D)  jS~  -  CH,  A y  N=N 74 o r 84  H(D)  F i g u r e 10 - A l t e r n a t i v e k i n e t i c scheme f o r p y r o l y s i s o f a l k y l substituted 1-pyrazolines.  H  k . + k .. oH cH k  n  +  oD  ^oH k „ cH  47.7 52.3  k  1.07  n  cD  oD  and :  cD  34.0 66.0  paths  -  oK  Then  =  The v a l u e o f increases scheme that  0.84  the rate  (Figure  1.50  10)  of  implies  is highly  that  10.2  s u b s t i t u t i o n of deuterium at 19%,thus  improbable.  It  i n d i c a t i n g such  was t h e r e f o r e  i n t e r m e d i a t e i s formed a f t e r  and Cameron  (21)  kcal/mole less  i n the rate  a nitrogen-free  intermediate  by the p y r o l y s i s o f (86).  than the parent  Because the  concluded  the  rate  The  agreement  expected value  with the  energy of  complete  secondary isotope e f f e c t (18a-c).  The  i n advance o f  as r e p r e s e n t e d i n F i g u r e the  C - 5 N-1  by (85)  activation  suggested  derealization  t h e C - 3 N-2 o f k^/k^  bond i s = 1.21  is  almost in  conclusion i s that  b o t h c a r b o n - n i t r o g e n bonds a r e b r e a k i n g i n t h e r a t e state  i s furnished  1-pyrazoline, this  i s a t t a i n e d and t h u s  completely broken.  far  a  3-vinyl-l-pyrazoline  determining t r a n s i t i o n s t a t e ,  i n v o l v i n g the v i n y l group  transition  C-4  step.  and 3 - v i n y l - 5 , 5 - d 2 " l - p y r a z o l i n e was  that  0.84  c y c l o p r o p a n e by  Further evidence for Crawford  cH  and  a common n i t r o g e n - f r e e  determining  22 -  determining  11, w i t h t h e C - 3 N - 2  bond  rupture  bond.  —N  ....  N  N  N  ///  //  85 Figure  11  -  Rate determining t r a n s i t i o n s t a t e  for  3-vinyl-l-pyrazoline.  -  On  23  -  the b a s i s o f the r e s u l t s o b t a i n e d from deuterium  e f f e c t s , the n i t r o g e n - f r e e i n t e r m e d i a t e was propane. c i s - and the two other may  thought  isotope  o f as a i r - c y c l o -  Comparison o f the r e s u l t s from p y r a z o l i n e s 79_ and trans-3,5-dimethyl-1-pyrazolines  80,  respectively, indicates that  t e r m i n a l carbons o f the i n t e r m e d i a t e are not f r e e o f each  (or t h e l i f e t i m e o f the i n t e r m e d i a t e i s s h o r t ) so t h a t e q u i l i b r i u m  be r e a c h e d .  I f an e q u i l i b r i u m c o u l d be reached,then  from both p y r a z o l i n e s 79_ and e x p l a i n why  t h e two  80_ would be  i d e n t i c a l . One  products  possibility,  to  t e r m i n a l carbons a r e not f r e e , i s i n terms o f  pir-pir bonding as i n s p e c i e s 87.  The  conversion of a 1-pyrazoline  a n i t r o g e n - f r e e i n t e r m e d i a t e w i t h an a n t i s y m m e t r i c  F i g u r e 12_  the  singlet  into  trimethylene  - ir-Cyclopropane i n t e r m e d i a t e s .  s t r u c t u r e 88_ may  a l s o be c o n s i d e r e d .  Such a s t r u c t u r e as 88_ i s  e s p e c i a l l y d e s i r a b l e s i n c e the immediate consequence o f t h i s  species  i s t h a t c o n r o t a t i o n would be p r e f e r r e d t o g i v e the i n v e r t e d s t e r e o chemistry,which  i s i n agreement w i t h e x p e r i m e n t a l  results  obtained  from the p y r o l y s i s o f s e v e r a l 3 , 5 - d i s u b s t i t u t e d - l - p y r a z o l i n e s (11,13,14). Crawford and  and E r i k s o n (22) have s t u d i e d the t h e r m o l y s i s o f c i s -  trans-4-deuterio-5-methyl-1-pyrazolines  (89 and  90) r e s u l t i n g i n T  - 24 further  evidence  for  metric trimethylene is  that  the  pyrazolines of  the  a nitrogen-free singlet  same t r i m e t h y l e n e and thus  initial  mediate  cis-2-butene  the  that  olefins is  results  a l s o do n o t  of  the hydrogen  only  intermediate  allow for  from  ratios  antisym__9 a n d 90_  both  independent  an  inter-  d i s t r i b u t i o n s are  nearly  hydrogen:deuterium  equal for both p y r a z o l i n e s .  the p o s s i b i l i t y of  a concerted  The  migration  t h e d e p a r t i n g n i t r o g e n a s shown b y  i n Figure  trans-2-butene  1-butene  the proposal of  the product  nearly  transoid to  9 1 a a n d 91b  operating, only  result  trans-1-butene  consistent with  of n i t r o g e n , i n  for  of p y r a z o l i n e  i d e n t i c a l product  t h e same f o r b o t h _39 a n d 90_ a n d t h e r a t i o o f migration  such as the  stereochemistry.  r e s u l t s are quite free  advantage  structure j _ l w i l l  should give  cyclopropane  The  88_. The  intermediate  13.  If  a t r a n s o i d mechanism  92_ i n w h i c h t h e h y d r o g e n  the  were  migratedjwould  -  25  -  \ /  /  92  89  Figure  13  - Concerted t r a n s i t i o n state cis-  result would  .  and  olefin.forming reaction  for  trans-4-deuterio-3-methyl-l-pyrazolines.  S i m i l a r l y , o n l y c i s - 2 - b u t e n e 93 i n w h i c h d e u t e r i u m  migrated  result. F u r t h e r s t u d i e s by Crawford  and A l i  consistent with the n i t r o g e n - f r e e an a n t i s y m m e t r i c t r i m e t h y l e n e the p y r o l y s i s of 95)  for  results  i n t e r m e d i a t e proposed as s p e c i e s  singlet.  They p r e p a r e d and  were f o u n d  a n a l o g u e s 96 a n d 97_.  f o r the  A 45.4  94  have g i v e n  c i s - and t r a n s - 3 , 4 - d i m e t h y l - 1 - p y r a z o l i n e s  and t h e i r 5 , 5 - d 2  and 1.21  (23)  Isotope e f f e c t s  c i s and t r a n s - p y r a z o l i n e s  studied (94  and  of  1.19  94 a n d 95  A 33.0  14.3  7.2  88,  46.0  21.8  16.3  15.8  N=N  95 respectively,implying that the C-5 N-1 bond is breaking in the rate determining transition state. That the product distributions from 94 and 95_ are different can be explained by use of two discrete intermediates 98 and 99_ (Figure 14) both being produced from each pyrazoline but in }  Figure 14 - Two trimethylene intermediates from c i s - and trans-3,4-dimethy11-pyrazolines.  different ratios^depending on the relative populations of the two conformations.  The results are also indicative of non-stereospecific  olefin formation as already shown by use of c i s - and trans-4-deuterio3-methyl-l-pyrazoline (23).  For a transoid elimination of nitrogen,the  olefins 100 and 101 in Figure 15 would be the expected products. Howeverjit was found that only 4% of 100 was formed from 96 and only  -  27  W- N  _, l—  D  2  -  ,W....  M  96 •' 1  _____  // 15  \  :  N  CD H 2  N = <  states  6%  101  2  - Transition  2  v  ...\ I ///  CD H 0  100  H  iZ  ,  v  N  2  N  Figure  ;  D  N  and o l e f i n s e x p e c t e d on t h e b a s i s  c o n c e r t e d mechanism f o r p y r o l y s i s o f c i s - and  of  trans-3,4-  dimethyl-5,5-d2-l-pyrazolines. 6% o f in  101  from p y r a z o l i n e  Figure  14.assuming  97.  that  This  the major  pyrazoline  94_ i s 9 9 , a n d t h e m a j o r  95  i s 98.  It  to  steric  crowding  Al-Sader rates  of  b o t h C-4 forming  i s suggested that i n the  rate  and C r a w f o r d  a series  hyperconjugative 3-deuterium  (24)  have  group at  Isotope  f o r both the  o l e f i n and  l a r g e r than  i n the r a t e  to  determining  propylene  11.57  cis-  C-4  leads  state.  1-pyrazolines.  is  scheme  trans-pyrazoline  studied the product  i n t e r a c t i o n s may b e g i v i n g r i s e  cyclopropane  74  from the  second methyl  The.C-4 i s o t o p e e f f e c t  88.43  from the  determining t r a n s i t i o n  of deuterated  isotope effects  N—N  intermediate  intermediate  the  and C-5 were d e t e r m i n e d reaction.  can be e x p l a i n e d by t h e  the  ratios effects  and at  cyclopropane expected,but enhanced  step.  kt,Ar> n V  1.00  -  28 -  cyclopropane  J>2  n  propylene  87.99  ^H^D  12.01  1.19  N = N 102  D  2 ^  D  ;  87.43  12.57  1.40  89.21  10.79  1.05  90.27  9.73  1.12  103  H  D  104  D  2  N =  N  105  I t was f o u n d t h a t pyrolysis  of pyrazoline  isotope effect  of k° n  with  sp  2  o f C D 2 H - C H = C H 2 a n d CD=CH-CH 3 f r o m t h e  102 was 5 2 : 4 8 , g i v i n g /k°  1 0 3  = 0.92.  an i n v e r s e  The v a l u e  effect 3  to sp,.  intramolecular  of 0.92 i s consistent  D  t h e i n c r e a s e i n o l e f i n o n g o i n g f r o m 102 t o 1 0 3 .  isotope r  1 0 2  the r a t i o  The  i s e x p l a i n e d by t h e change i n h y b r i d i z a t i o n •  '  '  inverse on g o i n g  from  -  29  -  2k  N—  ->  N  074  y  H  intermediate c97  74  s  0102 0102  / :D H  intermediate  2  NIZ N 102  C102  2k  0103  D  ,CD H 2  intermediate  N~ N  C103  103  Figure  16  -  K i n e t i c scheme f o r  3,3-d2~  and  074' Assuming  (  H  0102  From t h e p r o d u c t  2k,  =  1.0  distributions  074 11.57 88.43  H C77  ,0102  H  0102  *  K  D  ,C102  Then  -  C74 c C102  =  _ "  1.00  12.01 87.99  3,3,5,5-d^-l-pyrazolines.  -  Similarly,by  assuming  .0102 k D 'Q_Q3 k D  1.00  C102 c C103  Then  ^,  .  . .C74..C102  The v a l u e s that  30 -  there  of k  /k  is little  .  1.01  , .C102..C103  n n  =1.00  and k  /k  . =1.01  o r n o c h a n g e i n t h e C - H o r C-D f o r c e  o f the t e r m i n a l methylene  groups  A scheme may a l s o b e d r a w n a s shown i n F i g u r e  =  t o c y c l o p r o p a n e and  constants  propylene.  o u t f o r t h e C-4 d e u t e r a t e d  pyrazolines  0104  17.  intermediate  N—N  suggest  y CH_D  —Q1Q4—^  104  D  D  0105  CH_D  y intermediate N ~  D„  N  D  105  Figure  17  - K i n e t i c scheme f o r 4 - d ^ - a n d  From t h e p r o p y l e n e CD-CH3 t o CH2=CH-CH2D  arrived  from p y r a z o l i n e  was 2 : 1 , g i v i n g  an i s o t o p e  1.50. 074 Assuming  4,4-d2-l-pyrazolines.  0104  =  1.01  104 >the r a t i o effect  of  o f CH^=  kjj104/kp104  -  From t h e p r o d u c t  31  -  distributions  074  Ji  _  11.57 88.43  ,C74  ,0104 H  0104 +  K  K  D  10.79 89.21  ,C104 k  Then  k  C 7 4  =  , C104 k k  1.13  0104  S i m i l a r l y , b y assuming  =  0105 k  1.01  D  , C104 ™  e  7105 k  n  Thus d e u t e r i u m  "  1  s u b s t i t u t i o n at  m o l e c u l e s l o w s down t h e r a t e  A  5  the  C-4  at which the  p o s i t i o n of  intermediate  the  pyrazoline  cyclizes 3  cyclopropane.  This  i s what i s e x p e c t e d on g o i n g f r o m sp  hybridization,keeping  i n mind t h a t  t h e C-H bonds  to 2  to  sp  i n cyclopropane  closely  2 r e s e m b l e sp  hybridization.  In summary,the derivatives For  isotope effects  for  the  deuterated  are:  3-d_ deuterium Z  substitution  k^/k^ ML)  =0.92  1-pyrazoline  -  For  4-cL  32  -  deuterium s u b s t i t u t i o n  i  k[!/k!? n u  =  S u  = 1  K  Recently,Crawford  and M i s h r a (32)  3,5-dimethyl-l-pyrazoline 25.6% o f purity of  (106).  trans-1,2-dimethyl  having the  the intermediate,then  If  (108a  (108b),  the trimethylene  a racemic mixture  of  <  diradical  the  heptene  (109  and 1 1 0 ) ,  of  gave  23% o p t i c a l  (Figure  19)  were  108 s h o u l d r e s u l t .  In  order  . .' <  f  108b  25  23% o p t i c a l p u r i t y , u s e  and  106  i n d i c a t i n g an e x c e s s  purity  i s made o f a p y r a m i d a l  i n t e r m e d i a t e p r o p o s e d by A l l r e d and S m i t h  u s i n g exo-  The  thus  23% o p t i c a l o f 108b  system,  of  a n d 108b)  t  73  to account f o r  (3R:5R)-(+)-trans-  s p e c i e s 107  108a  106  1 3  have p r e p a r e d  cyclopropane  <U  -  On t h e r m o l y s i s . p y r a z o l i n e  S:S c o n f i g u r a t i o n  double i n v e r s i o n .  /k  1.50  (33).  In  their  endo-5-methoxy-2,3-diazobicyclo[2.2.1]-2they have  attributed  inversion to  s t r u c t u r a l l y i n v e r t e d p y r a m i d a l d i r a d i c a l s 113  the  a n d 114  i n v e r s i o n was c o n s i d e r e d t o b e a c o n s e q u e n c e o f  recoil  formation (Figure  from  18)  energy  01ef  -  CH,0  ^5 N  109  33  -  .  111  C H  3°  112  37-i  63  N  (endo)  6-r  N  CH_0 3  11«  110  /' <•  ->  (exo)  r e l e a s e d b y C-N accounts  for  94  bond b r e a k i n g .  the  excess of  Ring closure before  the product  of  inverted  complete e q u i l i b r a t i o n structure.  CH30 N 109  (exo)  //  N // CH 0 3  CH,0  Figure  18  -  N  (endo)  t  113  CH30  114  111  CH^O  112  P y r a m i d a l d i r a d i c a l mechanism f o r  I10  decomposition of  endo-5-methoxy-2,3-diazabicyclo[2.2.1]-2-heptene.  exo-  and  -  Thus C r a w f o r d  34  -  and M i s h r a s u g g e s t t h a t  the  data u t i l i z e s the pyramidal d i r a d i c a l .  the  excess of double  i n v e r s i o n found  racemic trans-cyclopropane,  for  cannot d i s t i n g u i s h i f  the  pyrazoline  Neither The is  example of  t h e one t h a t  and M a r t i n  This  best  scheme w i l l  the  fits  rationalize  the t r a n s - c y c l o p r o p a n e .  intermediate.  trimethylene  are  The d a t a  intermediate  The  thus  i s formed  from  or from the pyramidal d i r a d i c a l s t r u c t u r e or from  can the data t e l l first  scheme t h a t  t h e c i s _ - c y c l o p r o p a n e and o l e f i n s  b e l i e v e d to a r i s e from a t r i m e t h y l e n e far  the  if  the pyramidal d i r a d i c a l i s e q u i l i b r a t i n g .  a bicyclic  system i n which the major  r e s u l t s f r o m d o u b l e i n v e r s i o n was r e p o r t e d b y  (34).  The p y r a z o l i n e  D  both.  product Roth  exo-5,6-dideuterio-2,3-diazobicyclo-  116  117  25  [2.2.1]-2-heptene  (115)  gave a 3:1  dideuterio-bicyclo[2.1.0]pentane was a t t r i b u t e d  mixture (116  of  a n d 117)  trans.  and  The p r e d o m i n a n t  to concerted e l i m i n a t i o n of nitrogen with  ing back-side p - o r b i t a l  overlap  i n the  cis-2,3-  transition state  product  accompany(Figure  19).  -  35  -  N Figure  19  - Transition state  for  concerted nitrogen elimination  from  exo-5,6-dideuterio-2,3-diazabicycloT2.2.1]-2-heptene.  This of  i n t r o d u c t i o n h a s t r e a t e d two m a i n a s p e c t s i n t h e  1-pyrazolines  - one t h e o l e f i n f o r m i n g r e a c t i o n , and t h e o t h e r  cyclopropane forming r e a c t i o n . 1-pyrazolines evidence for propane (pa.rt at  C-4  (part  of  of  (d)  formation of  for  o l e f i n and  cyclo-  substituent  formation  However, of  there  i s very  little  cyclopropane derivatives  of nitrogen  has  known a b o u t  the  from 3 - a c e t y l  or  pyrazolines. t h i s research to  further  investigate  the  c y c l o p r o p a n e d e r i v a t i v e s by t h e p r e p a r a t i o n and p y r o l y s i s 3-methyl-3-acetyl-l-pyrazolines  carbon centers.  of pyrazolines  It  uniquely  was a l s o a n t i c i p a t e d t h a t  would g i v e r e s u l t s t h a t would emphasize  conformation  reaction.  intermediate,both  i s considerable  " i n t r o d u c t i o n " ) } a t r a n s o i d mechanism i n w h i c h t h e  a series of  of the  "introduction"),there  substituted  pyrazolines  i s the purpose of  three  alkyl  the  3 - a c e t y l and 3-carbomethoxy  3-carbomethoxy  all  case of  the p y r a z o l i n e migrates with concerted loss  mechanism o f  of  In the  In the case of  been w e l l e s t a b l i s h e d .  It  of  a trimethylene  formation.  (a)  pyrolysis  of the  starting  substituted the the  at  same s e r i e s importance  1 - p y r a z o l i n e i n the o l e f i n  forming  - 56 -  II.  P r e p a r a t i o n and P r o d u c t The Table  I.  1-pyrazolines  RESULTS AND DISCUSSION  Distributions p r e p a r e d f o r t h e p r e s e n t work a r e l i s t e d  The p y r a z o l i n e s w e r e p r e p a r e d b y t h e a d d i t i o n o f  diazoethane  or phenyldiazomethane to the appropriate  in  either  a,8-unsaturated  ketone. TABLE  I  3,3,4,5-Tetrasubstituted-1-Pyrazolines COCH 3  1-Pyrazoline  R„ 2  R, 3  118  H  CH, o  119  H  CH, o  H  120  CH,  H  C£HC  121  CH, 5  H  H  122  H  C,HC o b  123  H  C,HC o b  o  .  R. 4 C H r o b  o b  -  R. 5 H C,HC o b H C H r o b  CH, 3  H  H  CH, 3  - 37  -  A d d i t i o n o f phenyldiazomethane t o 3-methyl-3-pentene-2-one, ( E ) (24)  gave the p y r a z o l i n e s  P u r i f i c a t i o n by  118  and  119  i n about a 2:1  column chromatography gave a m i x t u r e o f the two  i s o m e r i c p y r a z o l i n e s as a c l e a r c o l o u r l e s s l i q u i d . c o u l d not be  The  pyrazolines  118  I t was  not p o s s i b l e to s e p a r a t e  the  However,the p y r a z o l i n e t o 62%  of separating  by  successive  118  An  t.l.c.  or by  enriched  i n order  column chromato-  to 85%  column chromatography.  the p y r a z o l i n e s was  from the p y r o l y s i s o f each.  was  119  isomeric pyrazolines  t o o b t a i n pure samples o f each, e i t h e r by  z o l i n e 119  and  the  The  purpose  was  pyra-  t o e s t a b l i s h the product d i s t r i b u t i o n s  i n d i r e c t second method became a v a i l a b l e  t o determine the p r o d u c t s o f p y r o l y s i s from p y r a z o l i n e 118,as i t discovered  C-5  crystallized.  24  graphy.  ratio respectively.  t h a t when a m i x t u r e o f the two  pyrazolines  kept a t room temperature over s e v e r a l weeks o n l y  was  i n ether s o l u t i o n 118  pyrolyzed.  I n v e s t i g a t i o n o f the d e c o m p o s i t i o n p r o d u c t s by column chromatography r e v e a l e d t h a t none o f the c y c l o p r o p a n e 127 propane 127  must o c c u r  was  present.  e x c l u s i v e l y from p y r a z o l i n e  119  Thus c y c l o and  the  d e c o m p o s i t i o n p r o d u c t s must t h e r e f o r e be r e p r e s e n t a t i v e o f p y r a z o l i n e 118.  E v i d e n c e t h a t the p y r a z o l i n e  118  was  decomposing e x c l u s i v e l y a t  room temperature i n e t h e r s o l u t i o n i s the f a c t t h a t the s t a r t i n g  ratio  -  of  1 1 8 : 1 1 9 was a b o u t  2:1 r e s p e c t i v e l y and a f t e r  approached 1:3 r e s p e c t i v e l y . product  38 -  It  i s assumed t h a t  s e v e r a l weeks t h e r a t i o the difference  distributions i s negligible for pyrazoline  s o l u t i o n compared t o n e a t The p r o d u c t  118 i n e t h e r  pyrolysis.  d i s t r i b u t i o n f o r 118 i s t h a t  a t room t e m p e r a t u r e .  The p r o d u c t  f o r the ether  solution.  118:119  F i v e p r o d u c t s were i d e n t i f i e d ,  c y c l o p r o p a n e s a n d two a , 6 - u n s a t u r a t e d  distributions  of  a n d t h e n c o r r e c t i n g t o 100% 119 u s i n g t h e r e s u l t s f o r t h e  d e c o m p o s i t i o n o f 118 i n e t h e r three  solution  d i s t r i b u t i o n f o r 100% 119 i s  c a l c u l a t e d u s i n g t h e neat p y r o l y s i s o f a 25:75 r a t i o respectively  of  are given i n Table  II.  ketones,and the product  T h e r e were two m i n o r p r o d u c t s  that  +  126  129  remained u n i d e n t i f i e d . were t h e d i h y d r o f u r a n Formation  ring  127  i s possible that  the unidentified  derivatives  of dihydrofuran  3-acetyl-l-pyrazolines pyrazoline  It  .128  130 e x p e c t e d f r o m p y r a z o l i n e  119.  p r o d u c t s was shown t o b e c h a r a c t e r i s t i c o f  (14).  I n one o f t h e c o n f o r m a t i o n s  119 , t h e a c e t y l g r o u p w o u l d b e i n a f a v o u r a b l e  closure to occur.  products  possible for position for  - 39 -  The peaks a t t r i b u t e d t o t h e a , 8 - u n s a t u r a t e d ketones had t h e same r e t e n t i o n times as 128 and 129 o b t a i n e d by t h e independent and were i s o l a t e d i n about propane  127.  two o l e f i n s hydrogen  synthesis  10% p u r i t y a l o n g w i t h 90% o f t h e c y c l o -  The 10% p o r t i o n was determined t o be a m i x t u r e o f t h e  128 and 129 on t h e b a s i s o f t h e c h a r a c t e r i s t i c  a b s o r p t i o n s i n t h e n.m.r. spectrum.  benzylic  Only 129 i s expected  from t h e p y r o l y s i s o f 118 o r 119 (15) and t h e low y i e l d o f 128 and 129 makes the s i g n i f i c a n c e o f t h i s r e s u l t u n c e r t a i n .  I t may be t h a t  t h e r m a l i s o m e r i z a t i o n on t h e v.p.c. column has t a k e n p l a c e as c o n s i d e r a b l e o v e r l a p o f t h e two peaks o c c u r r e d , c h a r a c t e r i s t i c o f such isomerization. A d d i t i o n o f p h e n y l diazomethane (25)  gave t h e p y r a z o l i n e s  t o 3-methyl-3-pentene-2-one, (Z) -  120 and 121 i n about a 2:1 r a t i o  . P u r i f i c a t i o n by column chromatography i s o m e r i c p y r a z o l i n e s as a w h i t e  respectively.  gave a m i x t u r e o f t h e two C-5  solid.  120  121  - 40 As i n t h e c a s e o f t h e possible to t.l.c. 120  two p y r a z o l i n e s  118  separate the isomeric pyrazolines  o r column chromatography.  t o 80% a n d 121  to  However,  a n d 1 1 9 , i t was completely,  p o s s i b l e t o s e p a r a t e p a r t i a l l y t h e two p y r a z o l i n e s l i z a t i o n from ether-petroleum crystals were thus  according to obtained.  size.  ether,  Samples e n r i c h e d t o  i n Table  II.  ketone,and  three  formation  also  separation of  95% 120 a n d 75% 120 a n d 121  derivative 120  150  r e s u l t i n g from r i n g c l o s u r e of the p y r a z o l i n e  olefin  128 was i d e n t i f i e d s o l e l y o n t h e b a s i s o f c o m p a r i s o n o f  121  (14).  125  +  126  and  128  given  i d e n t i f i e d although i t  COCH, 5  121  are  the c a l c u l a t e d d i s t r i b u t i o n s are  of the dihydrofuran  the  enriched samples.  place,  120  enrich  isomeric cyclopropanes  Two m i n o r p r o d u c t s w e r e n o t  p o s s i b l e that the  was  by  by slow r e c r y s t a l -  d i s t r i b u t i o n s from t h e i r  Four p r o d u c t s were o b t a i n e d , one a , 6 - u n s a t u r a t e d  It  w i t h subsequent  The p r o d u c t d i s t r i b u t i o n s f o r  c a l c u l a t e d u s i n g the product  either  i t was p o s s i b l e t o  50% b y c o l u m n c h r o m a t o g r a p h y .  not  (VHr o b 127  is  took The retention  - 41 -  times w i t h a u t h e n t i c samples o f 128 and 129.  Only 128 i s expected i f  a t r a n s o i d c o n c e r t e d e l i m i n a t i o n o f n i t r o g e n (15) takes p l a c e . u n i d e n t i f i e d p r o d u c t was p r e s e n t i n l e s s than one p e r c e n t . possibility  The o t h e r  The  t h a t t h i s u n i d e n t i f i e d p r o d u c t was the c y c l o p r o p a n e 133  was e x c l u d e d on t h e grounds t h a t when a sample c o n t a i n i n g t h i s p r o d u c t was h e a t e d a t 220° f o r 2 hours t h i s same p r o d u c t d i d n o t r e a r r a n g e t o the Y*6-isomers a c e t y l group  134 and 135 a s would be expected i n the case o f an t  c i s t o a methyl  group  i n a cyclopropane d e r i v a t i v e (35).  The peak i n t h e v.p.c. a s s i g n e d as t h e a,g-unsaturated remained  ketone  128 a l s o  unchanged on h e a t i n g t o 220° f o r 2 h o u r s .  133  134 and 135 ( e r y t h r o and t h r e o )  To f u r t h e r e x c l u d e c y c l o p r o p a n e 135 as a p r o d u c t , a sample c o n t a i n i n g b o t h p y r a z o l i n e s 120 and 121 was decomposed a t 120-30° and the n.m.r. o f t h e r e s u l t i n g p r o d u c t s was r u n . e x p e c t e d f o r t h e C-3 methyl ( T a b l e V) were n o t o b s e r v e d . the Y > ^ - i  s o m e r  s  C h a r a c t e r i s t i c peaks i n t h e n.m.r.  and a c e t y l methyl  o f c y c l o p r o p a n e 133  A l s o absent were any peaks a t t r i b u t e d t o  p o s s i b l e from t h e p y r o l y s i s o f 133.  A d d i t i o n o f d i a z o e t h a n e t o 3-methyl-4-phenyl-3-butene-2-one, ( E ) (132) gave t h e p y r a z o l i n e s 122 and 123 i n a r a t i o o f 90:10 r e s p e c t i v e l y . A f t e r t h r e e treatments o f t h e o l e f i n w i t h the d i a z o compound,the crude p r o d u c t was t r i t u r a t e d w i t h p e t r o l e u m  e t h e r t o y i e l d white  crystals.  - 42 TABLE I I Pyrolysis  Products f o r 3-Acetyl-3',4'-dimethyl-5-(and 5 ' ) - p h e n y l - l -  pyrazolines  (118 and 119) and 3 ' - A c e t y l - 3 ' , 4 - d i m e t h y l - 5 - ( a n d 5')-phenyl-  1-pyrazolines  (120 and 121).  -  *  A 126  A 125  1-Pyrazoline  ct,B-E a,6-Z* 128 and 129  A 127  1  0  118  1  98  119  13  25  120  91  6  0  3  121  26  22  7  45  G e o m e t r i c a l assignment  21(7:14)  was not made.  R e c r y s t a l l i z a t i o n from e t h e r - p e t r o l e u m e t h e r y i e l d e d 122.  41  The mother l i q u o r , now c o n s i s t i n g  t h e pure  o f about a 50:50 m i x t u r e o f COCH- 6 5 C  COCH C  X  +  *  CH„CHN  pyrazoline  6"5^,  - 1  f  +  COCH,  H  /'"j  f  6 5 H  132  122  122 and 123, was seeded w i t h pure c r y s t a l s o f 122 and l e f t On removing  the a d d i t i o n a l  f o r one week.  c r y s t a l s o f 122, t h e mother l i q u o r was  f r a c t i o n a t e d by column chromatography. of f r a c t i o n s containing  123  Product d a t a f o r t h e p y r o l y s i s  122 and 123 i n t h e r a t i o s o f 28:72, 32:68 and  - 43 36:64 the  r e s p e c t i v e l y  d a t a  from  123  from  were  p u r e  g i v e n  i n  122  d e t e r m i n e d .  p e r m i t t e d  T a b l e  C.H, b 5/,„.  c a l c u l a t i o n s  C  COCH, ^ "3  136  ^A^fJOCH / \ ™ 3  \ „ V-COCH^ n n n  /  S 137  125  6 C  TABLE  P r o d u c t s  (122  f o r  6 5 H  3-Acetyl-3',5-(and  a n d  127  I I I  3*,5')-dimethyl-4'-phenyl -  123)  a,8-E  8.Y-Z 139  A  A  125  126  un.  t r a c e  1  20  1  6  1 - P y r a z o l i n e  136  137  138  122  0  0  0  • 0  79  123  28  37  2  0  21  G e o m e t r i c a l  S  5  126  *  c o m p o s i t i o n  C_H /  +  138  1 - p y r a z o l i n e s  w i t h  COCH.  /  \  C  p r o d u c t  123  '  P y r o l y s i s  t h e  sample  5  N  A  122  •  o f  28:72  t h e  COCH _/  H  A N /  C, H_ 6"5v  from  I I I .  C° 3 6 5 / /,,. C H  T h e d a t a  assignment  1  based  o n  t r a n s o i d a l  A  5  e l i m i n a t i o n  (15)  127  -  44 -  TABLE  IV  N.m.r. Data^for 3,3,4,5-Tetrasubstituted-l-pyrazolines Pyrazoline  ,...  N  2  COCH  C-3 methyl  7.58  3" C-4 or J „ C-5 methyl 4 5  H-4  H-5  8.82  8.08  5.32  8.97  10.4  7.76  8.52  . 7.29  4.63  9.65  8.5  7.96  8.31  8.4  5.10  9.03  9.8  7.58  8.68  7.7  4.69  9.82  7.5  7.52  8.93  6.78  5.18  8.48  8.4  COCH,  118  C0CH  //  3  C  6 5  N  H  z.  119  C0CH  //  3  C  6 5 H  120  L C  N  COCH, N  6 5"  N  H  121 C H ...'j ^ 6  5  s  C0CH  3  N  //  N  122  -  45 -  TABLE I V Pyrazoline  COCH 3  (Continued)  C-3 methyl  H-4  H-5  8.50  6.27  5.91  C-4 o r C-5 methyl  J.  7.0  8.56  123  1 2  Chemical  s h i f t values  Drawn i n p r e f e r r e d 3  in T units.  conformation.  u  Hz  units. S i x p r o d u c t s were i d e n t i f i e d and o n e , c o n s i s t i n g o f about  total  was n o t .  Three o f t h e p r o d u c t s were  isomeric cyclopropanes,  and t h e r e m a i n i n g p r o d u c t s were c t , B - and B , y - u n s a t u r a t e d No e v i d e n c e f o r t h e B , y - u n s a t u r a t e d hexene-2-one,  (Z)-(139)  Identification of  olefin  Table the  IV.  -N=N-  unequally.  3-methyl-4-phenyl-4-  Pyrazolines  on t h e b a s i s o f n . m . r .  i s o m e r i c a t C - 5 was made  and t h e p e r t i n e n t  I n t h e f i v e membered p y r a z o l i n e d o u b l e bond a f f e c t s  data i s given i n  ring the anisotropy  When t h e p y r a z o l i n e  of substituents  of  t h e s u b s t i t u e n t s a t C - 3 , C - 4 , and C-5 i s i n one o f i t s c o n f o r m a t i o n s ,  pseudo a x i a l p o s i t i o n s a r e i n a s h i e l d i n g zone and t h u s shifts  ketones.  was f o u n d .  The a s s i g n m e n t t o t h e 1 - p y r a z o l i n e s primarily  1% o f t h e  the  the chemical  i n these positions are s h i f t e d u p f i e l d ;  whereas  the pseudo equatorial positions are i n a deshielding zone and thus the chemical shifts are lowered in value. For example, consider the two isomeric pyrazolines, c i s - and trans-3,5-dimethyl-3-acetyl-l-pyrazolines (21 and 22) which are drawn i n their preferred conformation in Figure 20. trans-pyrazoline 22 is expected  The C-3 methyl of the  to be at higher f i e l d than the C-3  8.40 x 7.78  trans-22  T  cis-21  Figure 20 - Favourable conformations of cis- and trans-3,5-dimethyl-lpyrazolines and chemical shifts of C-3 substituents.  methyl of the cis-pyrazoline 21.  In other words, the C-3 methyl of the  trans-pyrazoline i s expected to spend more time in the shielding zone of the -N=N-  group than the C-3 methyl of the cis-pyrazoline.  A  similar argument holds for the acetyl groups at C-3 (14). For the series of pyrazolines prepared in this work i t i s necessary to differentiate between pairs of compounds isomeric at C-5,for example, pyrazolines 118 and 119.  The conformation for pyrazoline 118  in which three groups are in the pseudo equatorial position is expected to be the preferred conformation; whereas pyrazoline 119 will have i t s two conformations more equally populated, since each isomer has two substituents in both the pseudo equatorial and pseudo axial positions (13-15).  Hence the C-3 methyl, C-4 hydrogen and C-5 hydrogen  of 118 are expected to be at higher f i e l d than the same three groups i n  -47  Figure  21  -  Conformational  -  preferences  of  5-(and  dimethyl-3-acetyl-l-pyrazolines  pyrazoline  119.  Likewise,the  e x p e c t e d t o be a t holds  for  the  pyrazolines The methyl,  chemical s h i f t s  a n d 121  (Table  C-5 m e t h y l ,  which are c o n s i s t e n t w i t h the C-5 hydrogens  of pyrazolines  C-4  above 122  for  of  i s at  shift  the  123  i s e x p e c t e d t o be a t  than the is  C-5 hydrogen  C-5 hydrogen  of  d e s h i e l d e d by about  by about  1.2  T or of  122,  1.2  0.73  122  least  substituents  pyrazolines  at  are  argument in  The  a n d 123  chemical  chemical s h i f t  ppm h i g h e r t h a n t h e 5.18  T.  the  relative of  the  C-5  chemical  0.73  ppm  then e i t h e r the C-5 hydrogen  the  acetyl  S i n c e the C-5 hydrogen  0 . 3 ppm l o w e r a n d n o t  due t o  -  shifts  However,  the opposite  ppm o r t h e C - 5 h y d r o g e n  ppm - p r e s u m a b l y  122  - have  a n d 123 h a v e  hydrogen of  the  methyl  A similar  rationalization.  f r o m what i s e x p e c t e d . 3.91  118.  hydrogen  chemical s h i f t s 123  119).  IV).  corresponding substituents C-3 m e t h y l ,  of  and  and t h e C-4  lower f i e l d i n p y r a z o l i n e  relative  120  a c e t y l group  (118  5')-phenyl-3',4'-  effect  of  of  123  of is  the phenyl  of  higher 122 shielded group  at  C-4. An e x p l a n a t i o n shifts  i s not  for  evident.  the p o s i t i o n of  the  It  to determine  is difficult  C-5 hydrogen  chemical  which of  the  two  C-5 hydrogens  has the normal  3-acetyl-l-pyrazolines hydrogen  of  48 chemical s h i f t , s i n c e comparisons with  (Figure  122 i s much l o w e r  22) t e n d t o s u g g e s t  that  the C-5  than expected and t h e C-5 hydrogen  123 i s s l i g h t l y h i g h e r t h a n e x p e c t e d .  COCH3  other  On t h i s b a s i s , i t  appears  of that  the  COCH3  II  H.  N H  5.53  H  5.67  20 C,H  Figure  /  22 - P r e f e r r e d some  phenyl  group  3  conformations  and H-5 c h e m i c a l s h i f t  122.  Other valuable  information  '• .  i s the magnitude  on t h e d i h e d r a l a n g l e  ethane  (36).  Overberger  of the v i c i n a l (13),  e t al_  vicinal  trans-(a,a)-coupling  c i s coupling for the trans-pyrazoline  coupling  constant,  similar to  (27)  and t r a n s - 3 , 5 - b i s ( p - m e t h o x y p h e n y l ) - 1 - p y r a z o l i n e s has a v i c i n a l  ,  which a i d s i n the assignments to t h e C-5  which i s dependent  pyrazoline  of  which i s c i s at C-5 i n  .  1-pyrazolines  derivatives  values  3-methyl-3-acetyl-l-pyrazolines.  a t C-4 i s d e s h i e l d i n g t h e hydrogen  the pyrazoline  isomeric  C 0 C H  have prepared c i s (54 a n d 5 3 ) .  of  11.5  o f about  Hz  The c i s -  compared t o t h e  8 . 0 Hz.  Similar  - 49 coupling constants (Table  a r e observed f o r t h e C-5 i s o m e r i c  IV) i n which t h e p y r a z o l i n e s  couplings  118, 120 and 122 d i s p l a y l a r g e r  than t h e r e s p e c t i v e p y r a z o l i n e s  119, 121 and 123.  P h y s i c a l data t h a t a r e c o n s i s t e n t w i t h 1-pyrazolines 118, 121  are the  values.  the assignments t o t h e  The R^ v a l u e s  o f the three  120 and 122 a r e l e s s than t h e i r C-5 i s o m e r i c and 123 r e s p e c t i v e l y .  1-pyrazolines  pyrazolines  counterparts  119,  The p r o d u c t d i s t r i b u t i o n s a l s o support the  s t r u c t u r a l assignments i n t h a t the p y r a z o l i n e s  118, 120 and 122 g i v e  as t h e major p r o d u c t from p y r o l y s i s t h e c y c l o p r o p a n e r e s u l t i n g from r e t e n t i o n o f c o n f i g u r a t i o n , whereas t h e p y r a z o l i n e s  119, 121 and 123  g i v e a more random d i s t r i b u t i o n o f p r o d u c t s .  I d e n t i f i c a t i o n o f Cyclopropanes There a r e f o u r p o s s i b l e c y c l o p r o p a n e p r o d u c t s and these a r e presented  i n Table  V.- I d e n t i f i c a t i o n i s based on t h r e e  r e l a t i v e p o s i t i o n s o f t h e chemical and  the thermal rearrangement o f  d e r i v a t i v e s t o y,6-unsaturated The  chemistry in this  s h i f t s , t h e H-2 H-3 c o u p l i n g  constants,  ketones. s h i f t s o f t h e 1-methyl and  important i n f o r m a t i o n  between C - l and C-2.*  the  cis-l-acetyl-3-methyl-cyclopropane  r e l a t i v e p o s i t i o n s o f the c h e m i c a l  1 - a c e t y l groups p r o v i d e  aspects:  i n determining  the stereo-  I t i s expected t h a t the s u b s t i t u e n t ,  case e i t h e r a c e t y l o r m e t h y l , c i s t o t h e p h e n y l group w i l l  be more s h i e l d e d , r e l a t i v e t o t h e group when i t i s t r a n s .  It i s  found t h a t i n c y c l o p r o p a n e s 125 and 127 the a c e t y l resonances a r e a t 7.81 and 7.79 T r e s p e c t i v e l y , w e l l w i t h i n t h e normal range o f 7.4-7.9 T.  *  C-2 i s always taken as t h e carbon b e a r i n g  t h e p h e n y l group.  -  50 -  TABLE V N.m.r.  Data^or  1,1,2,3-Tetrasubstituted  Cyclopropane  C  6VA/° C H 3  Cyclopropanes  C0CH3  C^CH^  C2-H  C3-H  C3~CH3  J  8.20  8.51  7.99  7.66  8.76  7.0  7.79  8.88  7.19  8.2  8.95  9.8  7.81  8.92  7.15  8.6  8.88  6.4  8.2  8.5  H  _H  (Hz)  126  COCH  C L  3  H  6 5  127  AcOCH3 C  6 5*  c  125  H  6\AJ OCH  133  * 2  Chemical s h i f t values Approximate  The  expected  in x units. values.  respective C - l methyls  o f 125 a n d 127  a p p e a r a t 8 . 9 2 a n d 8 . 8 7 T.  However , i n t h e c a s e o f c y c l o p r o p a n e 1 2 6 , t h e a c e t y l r e s o n a n c e i s by about  0 . 4 ppm t o h i g h e r f i e l d a t 8 . 2 0 x a n d t h e C - l m e t h y l  0 . 4 ppm l o w e r a t 8 . 5 1 x . the a c e t y l group Roberts n.m.r.  Thus t h e p h e n y l  group  and must be c i s i n c y c l o p r o p a n e  e_t al_. ( 3 7 )  have  is  shifted about  significantly shields 126.  s t u d i e d the a b s o l u t e magnitudes  of the  c o u p l i n g c o n s t a n t s f o r s e v e r a l c y c l o p r o p a n e d e r i v a t i v e s and  - 51 have found that in general J . > J. > J . I n particular, values cis trans gem of J . were found to be in the range of 8.0 - 11.2 Hz and J. in cis trans &  r  b  the range of 5.2 - 7.0 Hz.  For the cyclopropanes 125 and 126 the ?  ^ - H j coupling constants of 6.4 and 7.0 Hz respectively are consistent with trans coupling. For the remaining cyclopropane 127 ,the coupling of 9.8 Hz is attributed to cis coupling. The H-2 H-3 coupling constant establishes the stereochemistry between C-2 and C-3. The third check used in the identification of the cyclopropanes was the expectation that the cyclopropanes, in which the acetyl and C-3 methyl are cis, would rearrange thermally to the y>6"-unsaturated ketones (35). Thus on heating cyclopropane 123 at 227° for 3.5 hours, complete rearrangement took place to the erythro- and threo-y,5-unsaturated ketones 134 and 135 in a ratio of 2:1 respectively.  Identification  of the erythro- and threo-isomers was based on the fact that the substituent - methyl or acetyl - which is cis to the phenyl group in the most stable conformation will be shielded (38). Neither cyclopropane  126 or 127 rearranged under similar reaction conditions. H, ^'H  C,H 6 5  125  COMe H H  C=C  6 5 erythro-134 C  H  Figure 23 - Thermal rearrangement cyclopropane.  v  H  COCH,  H  C=C 6 5 threo-135 C  H  of 1-acetyl-l',3-dimethyl-2'-phenyl-  - 52 -  Thus t h e r e a r e t h r e e p i e c e s o f e v i d e n c e , a l l o f which a r e i n t e r n a l l y c o n s i s t e n t and p r o v i d i n g an unambiguous assignment t o t h e t h r e e i s o m e r i c c y c l o p r o p a n e s 125, 126 and 127.  Identification of Olefins The t h e r m a l d e c o m p o s i t i o n o f p y r a z o l i n e phenyl-3-hexene-2-one, one,  ( E ) - (136) and  125 gave  3-methyl-4-  3-methyl-4-phenyl-4-hexene-2-  (E)- (137) i n 28 and 37% r e s p e c t i v e l y .  The c o r r e s p o n d i n g Z_  isomer o f 136, t h a t i s , 3-methyl-4-phenyl-3-hexene-2-one, was d e t e c t e d i n about 2%.  (Z)-  (138)  The c o r r e s p o n d i n g Z_- 139 isomer o f 157  was not d e t e c t e d a t a l l (Table I I I ) . According t o the t r a n s o i d n i t r o g e n e l i m i n a t i o n and 8,Y-unsaturated ketones  (15),the exp-  136 and 137 a r e expected t o be t h e major  o l e f i n s from t h e p y r o l y s i s o f p y r a z o l i n e 123.  S i n c e the v.p.c.  r e t e n t i o n times o f the o l e f i n s from t h e p y r o l y s i s o f 123 a r e almost i d e n t i c a l , i t was n e c e s s a r y t o i s o l a t e them t o g e t h e r . n.m.r. a r e c l e a r l y r e s o l v e d f o r 136 and 137. peaks, p o s s i b l y due t o t h e o l e f i n p r e s e n t i n t h e n.m.r.  Peaks i n the  However, s e v e r a l  smaller  138 and o t h e r i m p u r i t i e s were a l s o  In o r d e r t o c o n f i r m t h e s t r u c t u r e o f the a,B-  u n s a t u r a t e d ketone 136 and t h e p r e s e n c e o f 138, a m i x t u r e o f the a,gunsaturated o l e f i n s  136 and 138 were s y n t h e s i z e d f o r comparison.  A modified Wittig  (39), u s i n g propiophenone  and t r i m e t h y l a-  phosphonopropionate gave methyl-2-methyl-3-phenyl-2-pentenoate, ( E ) (140) and ( Z ) - (141) i n a 1:2 r a t i o r e s p e c t i v e l y .  Hydrolysis of the  e s t e r s gave t h e c o r r e s p o n d i n g a c i d s 142 and 143 i n about a 1:2 r a t i o respectively.  Subsequent  r e a c t i o n o f t h e a c i d s w i t h methyl  (40) y i e l d e d a m i x t u r e o f t h e o l e f i n s  lithium  136 and 138 i n a r a t i o o f 1:9  - 53 -  respectively. 0 CO-,CH„ C , H r y 'Z ~6^5  II  CO„CH ;"2~"3  x  ^  C  6"5  CQ2CH3  i4£  141 (1:2)  C02H  /  •  \  iii Figure  C6H5  C02H  \  +  /\  (1:2)  made b y  t h e Z-  /\  "~\/ 6  5  E-  136  (E)-  (136)  and,  138  (Z)-  a c e t y l and p h e n y l  due t o t h e p h e n y l  0 . 5 ppm t o group  4  \  8.34  6 5 H  8.51  3-methyl-4-phenyl-3(138).  (Figure  138  the  T whereas  acetyl of  the  25).  8.51 x COCH,  —  \  8.10  x  138  3-Methyl-4-phenyl-3-hexene-2-one, a s s i g n m e n t s by  7.95  A similar shift  C,H o  x  136 a n d  resonances i n  c i s , has the x.  i s observed  136 25 -  /\  isomer g i v e s a normal a c e t y l peak a t  7.95 x COCH,  Figure  \  t h e a c e t y l and C - 3 m e t h y l  isomer, w i t h the  C  C 0 C H  (1:9)  peak s h i f t e d u p f i e l d by about C-3 methyl  H  s t r u c t u r e s to the ct,3-unsaturated ketones  comparison of  The 138  of  c  136  24 - R e a c t i o n s e q u e n c e i n p r e p a r a t i o n o f  Assignment  n.m.r.  >  HI  hexene-2-one,  is  COCHj  n.m.r.  (E)-  (136)  and  (Z)-  (138)  Authentic and t h e r e f o r e  s a m p l e s o f 157 a n d 139 w e r e n o t a v a i l a b l e f o r c o m p a r i s o n assignment  transoid nitrogen predict  that  137  the C-5 methyl  and p h e n y l  123.  i s based e n t i r e l y on t h e  (15).  thermal  a,8-unsaturated (Z)-  groups  a r e c i s , as t h e y  The m a j o r a , B - u n s a t u r a t e d  decomposition of pyrazolines ketones  (129).  Identification  ketone  The e x p e c t e d  8,y-unsaturated  o f t h e two k e t o n e s  would are i n product  retention  those obtained  A modified Wittig phosphonopropionate (144)  and (Z)-  acids  146 a n d 147  lithium Fifty  percent  ketone  (128) detected  and by c o m p a r i s o n  from an a u t h e n t i c  phenyl  of  mixture.  acetone and t r i m e t h y l  a(E)-  Conversion of the esters to the corresponding  t h e two k e t o n e s  reaction of the acids with 128 a n d 129 i n a 1 : 2  of the r e a c t i o n product  was o n e o f t h e  methyl  ratio  respective  B,y-unsaturated  isomers.  It  was n o t p o s s i b l e t o d e t e r m i n e  the stereochemistry o f the  isomeric 3-methyl-4-benzyl-3-pentene-2-ones by u s i n g t h e c h e m i c a l s h i f t s C-5 hydrogens group  the  (E)-  3-methyl-3-benzyl-2-butenoate,  and subsequent  (40) gave  gave  k e t o n e s were n o t  i n the n . m . r .  (39),using  gave m e t h y l  (145).  a n d 119  128 a n d 129 was b a s e d o n t h e p r e s e n c e  absorptions  times with  121  3-methyl-4-benzyl-3-pentene-2-one,  of b e n z y l i c h y d r o g e n  two  Such a mechanism  c o n s i s t e n t w i t h t h e t r a n s o i d e l i m i n a t i o n mechanism. The  and  of structure  e l i m i n a t i o n mechanism  the s t a r t i n g p y r a z o l i n e is  54 -  are at  exceptions.  field  (136)  of the b e n z y l i c hydrogens.  o f an a , 8 - u n s a t u r a t e d lower  (E)-  ketone  i n the n . m . r . ;  One i s t h e k e t o n e s  that  however,  and (Z)-  (138)  Normally  the  are c i s to the acetyl there  are at  3-methyl-3-pentene-2-one  least, (E)-  (24)  - 55 -  CO  CH . * c-V c  •CO.  H  C H C0 CH 2  + g,Y-isomer  >  ^  '  (Z_)-  (25)  respectively  (E)-  i n which the C-5 (14).  The  y  3  C  6 5H  (128)  147  +  ^  ^  /  3,Y  _ a c i  d  + g,Y-isomer C  0  C  H  3  and (Z)-  (129).  hydrogens r e s o n a t e at 8.18  o t h e r i s two  4-phenyl-3-pentene-2-one (E)and C-6  and  145  R e a c t i o n sequence f o r p r e p a r a t i o n o f 3 - m e t h y l - 4 - b e n z y l - 3 -  pentene-2-one,  and  +  C>CH  /  -  144  5  c o r r e s p o n d i n g a c i d s 146  6 5  F i g u r e 26  6 3  (136)  ketones and  (Z)-  and  8.19  from t h i s work, 3-methyl(138), w i t h both the  hydrogens o f the E_ isomer appearing at h i g h e r f i e l d than  C-5 the  c o r r e s p o n d i n g peaks o f the !_ isomer.  Discussion (a)  Olefin  Formation  Part  (a) o f the d i s c u s s i o n w i l l be concerned  from the p y r o l y s i s o f 1 - p y r a z o l i n e s . o l e f i n forming r e a c t i o n from  a,8-  and  B,y-unsaturated  (Table I I I ) .  formation  The main f e a t u r e c o n c e r n i n g  the  the p y r o l y s i s o f the t e t r a s u b s t i t u t e d  p y r a z o l i n e s i n t h i s work i s t h a t p y r a z o l i n e 122 p r o d u c t s , whereas the C-5  with o l e f i n  gives only  i s o m e r i c p y r a z o l i n e 123 ketones  g i v e s 67  1-  cyclopropane percent  and 33 p e r c e n t c y c l o p r o p a n e  T h i s r e s u l t demonstrates the dependence o f t h e  products olefin  CH_  - 56 -  f o r m i n g r e a c t i o n s on the c o n f o r m a t i o n o f t h e s t a r t i n g  1 - p y r a z o l i n e and  s u p p o r t s t h e mechanism i n v o l v i n g c o n c e r t e d l o s s o f n i t r o g e n from t h e s i d e o f t h e p y r a z o l i n e t h a t i s t r a n s t o t h e m i g r a t i n g hydrogen a t C-4 (13-15)".  That o l e f i n f o r m a t i o n r e s u l t e d from p y r a z o l i n e 123 and  not from p y r a z o l i n e 122 depends on t h e f a c t t h a t p y r a z o l i n e 122 must p o p u l a t e e n t i r e l y t h e c o n f o r m a t i o n i n which t h r e e groups m e t h y l , phenyl) group  ( a c e t y l , C-5  occupy pseudo e q u a t o r i a l p o s i t i o n s and t h e r e m a i n i n g  (C-3 methyl) o c c u p i e s a pseudo a x i a l p o s i t i o n ; whereas p y r a z o l i n e  123 p o p u l a t e s b o t h conformations  (Figure 27).  COCH  C  6 5 H  123  <?6 5 H  H N  s  I  COCH  3  / / /  and  COCH,///  N_/« s H  COCH. 137  136 F i g u r e 27 - P r e f e r r e d conformations 1-pyrazolines  o f 3-acetyl-3',5-(and  (122 and 123).  COCH,  3',5')-4-phenyl-  - 57 -  That p y r a z o l i n e 122 o c c u p i e s o n l y one c o n f o r m a t i o n p y r a z o l i n e 123 o c c u p i e s b o t h c o n f o r m a t i o n s  and t h a t  i s d e r i v e d from n.m.r. s t u d i e s .  I t has been e s t a b l i s h e d by McGreer and co-workers  (13-15) t h a t a  s u b s t i t u e n t a t C-4 o r C-5 p r e f e r s t o occupy a pseudo e q u a t o r i a l I t i s t h e r e f o r e expected  position.  t h a t p y r a z o l i n e 122 p r e f e r s the c o n f o r m a t i o n  w i t h t h r e e o f i t s s u b s t i t u e n t s pseudo e q u a t o r i a l and one pseudo a x i a l . P y r a z o l i n e 123 i s expected with the conformation  t o occupy more e q u a l l y b o t h  conformations,  a v o i d i n g t h e 3 , 5 - d i a x i a l (methyl and methyl)  i n t e r a c t i o n b e i n g t h e major c o n t r i b u t o r ( F i g u r e 27). p y r a z o l i n e 123 s h o u l d more r e a d i l y y i e l d A d d i t i o n a l evidence  olefin  Thus t h e  products.  f o r c o n f o r m a t i o n a l p r e f e r e n c e based  on n.m.r.  i s o b t a i n e d from c h e m i c a l s h i f t v a l u e s , i n p a r t i c u l a r , the C-3 and a c e t y l methyl resonances  (Table V I ) .  Representative values f o r a  p y r a z o l i n e t h a t o c c u p i e s both conformations 3-methyl-3-acetyl-l-pyrazoline  equally are obtained  ( 2 0 ) . That both c o n f o r m a t i o n s  p y r a z o l i n e 20_ a r e e q u a l l y p o p u l a t e d i s based  on two f a c t o r s .  from  of One i s  t h a t t h e C-5 hydrogens have i d e n t i c a l c h e m i c a l  s h i f t v a l u e s and t h e  o t h e r i s t h a t t h e two i s o m e r i c a , 6 - u n s a t u r a t e d  ketones  a r e formed  e q u a l l y (14) Chemical  s h i f t v a l u e s o f p y r a z o l i n e s t h a t occupy o n l y one  c o n f o r m a t i o n may be o b t a i n e d from c i s - and t r a n s - 3 , 5 - d i m e t h y l - 3 - a c e t y l 1-pyrazolines  (21 and 22).  I t appears  that the conformational preference  o f a 3 - m e t h y l - 3 - a c e t y l - l - p y r a z o l i n e may be d e c i d e d upon e i t h e r by t h e p o s i t i o n o f the C-3 and a c e t y l methyl resonances between t h e two v a l u e s  (Table.VI).  o r by t h e d i f f e r e n c e  Thus t h e C-3 and a c e t y l methyl  chemical  s h i f t s o f 21_ and 22_ s h o u l d g i v e an i n d i c a t i o n o f v a l u e s  expected  f o r o t h e r C-3 methyl and C-3 a c e t y l  1 - p y r a z o l i n e s t h a t have  -  58  -  TABLE VI N.m.r.  Data  for  Determination of  Conformational  Preferences  of  3-Methyl-3-acetyl-1-pyrazolines Pyrazoline1  3-methyl(x)  acetyl methyl(x)  A(ppm)  1.41  1.10  0.98  0.84  - 59 -  TABLE VI  Pyrazoline  (Continued)  3-methyl(x)  a c e t y l methyl(x) A(ppm)  0.76  0.75  0.62  0.35  120  Drawn i n p r e f e r r e d c o n f o r m a t i o n . I n f l u e n c e d by C-4  p h e n y l group.  - 60 a p r e f e r e n c e f o r one c o n f o r m a t i o n over t h e o t h e r ( T a b l e V I ) . p y r a z o l i n e s 21_ and 22_ occupy stereospecific  c o n f o r m a t i o n i s based on the  f o r m a t i o n o f an a , g - u n s a t u r a t e d  v a l u e s o f the C-3 methyl a t 7.75  o n l y one  resonance  That  a t 8.49  ketone  from each.  T and the C-3  acetyl  The methyl  x f o r p y r a z o l i n e 123 f a l l between the r e s p e c t i v e v a l u e s f o r  p y r a z o l i n e s 20 and 21, i n d i c a t i n g p o p u l a t i o n o f both c o n f o r m a t i o n s , w i t h the one  i n which the two methyls  a r e pseudo e q u a t o r i a l b e i n g p r e f e r r e d .  On t h e o t h e r hand t h e v a l u e s o f the C-3  and a c e t y l methyl  f o r p y r a z o l i n e 122 a r e more extreme than expected on t o p y r a z o l i n e 22_.  resonances  comparison  T h i s not o n l y i n d i c a t e s a s t r o n g p r e f e r e n c e f o r one  c o n f o r m a t i o n but a l s o may  i n d i c a t e a l a r g e r degree o f f o l d i n g i n  p y r a z o l i n e 122  compared t o _22_.  i n more d e t a i l  i n part  T h i s l a t t e r p o i n t w i l l be d e a l t w i t h  (b) o f the d i s c u s s i o n , c o n c e r n i n g the f o r m a t i o n  o f c y c l o p r o p a n e s from 1 - p y r a z o l i n e s . The p o i n t b e i n g made from the comparison C-5  i s o m e r i c p y r a z o l i n e s 122 and  125  o f the p r o d u c t s from  i s t h a t the C-4  hydrogen  pseudo e q u a t o r i a l b e f o r e i t can m i g r a t e e i t h e r t o C-5 p y r a z o l i n e 122 hydrogen  e x i s t s i n o n l y one c o n f o r m a t i o n  i s always  o r C-5.  ( F i g u r e 27),the  the  must be Since C-4  pseudo a x i a l and thus i s never i n a f a v o u r a b l e  p o s i t i o n t o m i g r a t e t r a n s t o the l e a v i n g n i t r o g e n . 125, o c c u p y i n g b o t h c o n f o r m a t i o n s , now e q u a t o r i a l i n one o f the c o n f o r m a t i o n s .  has a C-4  However, p y r a z o l i n e  hydrogen  pseudo  I t i s through t h i s  conformation  t h a t the f o r m a t i o n o f 6 7 p e r c e n t o l e f i n takes p l a c e .  (b)  Cyclopropane  Formation  Part  (b) o f the d i s c u s s i o n w i l l be concerned w i t h c y c l o p r o p a n e  f o r m a t i o n from the p y r o l y s i s o f 1 - p y r a z o l i n e s .  Stereochemical aspects  - 61  -  of cyclopropane formation  have been s t u d i e d by McGreer and  (12-15) f o r b o t h 3,4-  3,5-dialkyl-3-acetyl-(and  pyrazolines  and  (Table V I I I ) .  1-pyrazolines  by Overberger and  co-workers  (25-28),and on 3,4-  understanding of cyclopropane formation  The  by  studying  - i n which t h r e e o f the  o t h e r pseudo a x i a l  - give  at b o t h C-3  and  121  and  - i n which two  and  the o t h e r two  123  propanes.  C-5  In the  and  s u b s t i t u e n t s are pseudo e q u a t o r i a l and  the  the c y c l o p r o p a n e r e s u l t i n g from r e t e n t i o n  as the major p r o d u c t ; whereas the p y r a z o l i n e s  l a t t e r case,  sets of pyrazolines  the major p r o d u c t may  121  and  - on one 123.  hand 118,  V I I I and  pyrazolines  22) .  The  and  and  not be  the  C-5.  120  and  122  - and  on  I t i s the former s e t o f p y r a z o l i n e s  abnormal s i n c e o t h e r  examples from T a b l e  or may  i s a d i s t i n c t d i f f e r e n c e between  3,5-disubstituted  c i s - and  1-pyrazolines  g i v e as the major c y c l o p r o p a n e  r e s u l t i n g from i n v e r s i o n at e i t h e r C-3  (____  119,  o f the s u b s t i t u e n t s are pseudo e q u a t o r i a l  an e l e c t r o n withdrawing group at C-3  the one  118,  pseudo a x i a l - g i v e a random d i s t r i b u t i o n o f c y c l o -  the o t h e r hand 119,  with  1-pyrazolines 120  T h i s r e s u l t suggests t h a t t h e r e  t h a t appear t o be  the  centers.  f a c t t h a t the p y r a z o l i n e s  c y c l o p r o p a n e r e s u l t i n g from r e t e n t i o n at both C-3  the two  3,5-  the p y r o l y s i s o f  most s i g n i f i c a n t f e a t u r e i n the p y r o l y s i s o f the i s the  and  (19a-c,22,23,32)  study t o extend  s u b s t i t u t e d at a l l t h r e e carbon  i n t h i s work (Table VII) 122  co-workers  I t i s the purpose o f the p r e s e n t  pyrazolines uniquely  3-carbomethoxy)-1-  Other s t u d i e s have been made on 3 , 5 - d i a r y l -  d i s u b s t i t u t e d - 1 - p y r a z o l i n e s by Crawford and (Table I X ) .  co-workers  o r C-5  (13,14).  Typical  trans-3,5-dimethyl-3-acetyl-l-  most obvious d i f f e r e n c e s - u s i n g p y r a z o l i n e s  122  and  123  as  an  -  62 -  TABLE Cyclopropane Products1  from  VII  3,3,4,5-Tetrasubstituted-l-pyrazolines  J_?l  1-Pyrazoline  126  127  133  C6H  / COCH. C . H / o o o  COCH_  i C  6 5^  L  COCH, C^H* 3 6 5  0  "'tOCH, 3  N  i' »  H  COCH,  l  °i5  9 8  °i3,5  118  T  1  C H  • N  K ( /  fi  6  91  N  6  120  \ T  6 5  0  3  ^13,5  °i5  N  122  z_ ,  . ,  i3  -N  —  7  N //  COCH,  C6H 4_^L;  / l 3  5  °i3  7 9  i3,5  »  i  •  2  °  i 5  5  i3  119  .COCH  JL !  C  6  C  H  5  ^ _ _ 121~~  N  // N  i5  2 6  2 2  i3,5  4 5  i3  6H5\  I  COCH, 123 3  N // 91 " 21. N 1  5  _ 5., _ i3,5  6  u  0. i3  Inversion requirements follow cyclopropane percentages: i3 - inversion a t C - 3 ; i 5 - i n v e r s i o n a t C - 5 ; i 3 , 5 - i n v e r s i o n a t C - 3 and C - 5 .  -  63 -  TABLE  VIII  D i s t r i b u t i o n of Cyclopropane Products  f o r Pyrazolines with  Electron  Withdrawing Groups a t C - 3 Pyrazoline  cis-A  trans-A  other  ref.  C02CH3  I  '  w  C 0 2  CH  18  12i3  70  (11)  28i3  35  27  (11)  3  60 16  ^ 24. 1 3  CO C H 3 22  61i3 N  =  o  r  5  17  or  s  60 (14} 22  (14)  60  (15)  17  (15)  N  C02CH3 35  31 •N N — ~  9  i 3  N  ;C02CH3 36  H  C  146  ,6H5  °2 3 f^C'^Z-"^ C  N  ~  72  i 3  N  C H  2 9  -  6  »  7 i  3  0  -  4  (31)  -  64 -  TABLE  IX  D i s t r i b u t i o n of Cyclopropane Products Alkyl  Substituted  Pyrazoline  C  H  C  "  H  53  ,|  .  Other  Ref.  i 3 or 5  n  8 9  C28)  0  p_-anisyl J,  =  £-anisyl —  trans-A  5  N' — 'N p_-anisy}(  and  1-Pyrazolines  cis-A  6 S^. 6  for 3,5-Diaryl-l-pyrazolines  6.7i3  o  r  5  93.0  0  (28)  0  (28)  0  (28)  £-anisyl 1  43.0  1  C 1 - C , H „ ,/ C-H.-CI 6 4 '#,/\^» 6 4 •55 N — N  79 N  =  N  80 N  ZZ N  rV  0  3 3  7 2  i3  -  57.0.^  or 5  n T  . _  1 0 0  ^ i S o r S  2  • ^ 3 or 5  7  ("J  -0  (19)  50.  4.9  (22)  50  5.3  (22)  2  5  '  ° '  4  2  D  89  1 _ N =  D  1  N  50  1 3  P T  50  94  [  45.4  ~  N —- N  21  I ' N =: N  2°_  — N N ~  I  1 3  46.0._  13  3 3 , 0  i3  21.8  2 1  -  6  22.2  .  ( ) 23  (23)  -  example  -  65  is that pyrazoline  pyrazoline  125  122  occupies both  118, is  (a)  of  the  The  e x p l a n a t i o n chosen to  120  a n d 122  d i f f e r e n c e between  between N-2,  N-1,  e x p l a i n the  C-3 and C - 5 , w h e r e a s  fact  c y c l o p r o p a n e s does not  where the degree of  the plane of  atoms  pyrazolines  C-3,  C-4,  C-5  retention  121,  and  123  depend on t h e  Instead,  it  is  obvious proposed  f o l d i n g i n the  pyrazoline  angle  and t h e p l a n e o f  atoms  C-3,  have e s t i m a t e d t h e c i s - d i h e d r a l a n g l e and  a n g l e t o be about  25° and 1 4 5 ° r e s p e c t i v e l y (11  and 1 2 ) .  was b a s e d o n t h e o b s e r v e d c o u p l i n g c o n s t a n t s o f c i s - and t r a n s - ( a , a ) - c o u p l i n g .  25° and 1 4 5 ° g i v e s a f o l d i n g o f the pyrazolines  1_1 a n d 1_2.  The  about  about  This  118,  than u s u a l .  H-3  The H-4  a n d 122  for  8 . 0 Hz  for  both  c a l c u l a t e d dihedral angles  25° b e t w e e n t h e two p l a n e s  Assuming t h a t  120  the  estimation  of  in  the t r a n s - ( a , a ) - c o u p l i n g ,  i n c r e a s e s as t h e a x i a l - a x i a l d i h e d r a l a n g l e i n c r e a s e s  then the p y r a z o l i n e s  Hz  119,  f o l d i n g i s d e f i n e d as t h e  and t r a n s - 3 , 5 - d i m e t h y l - 1 - p y r a z o l i n e s  constant  from  C-5.  trans-(a,a)-dihedral  the  that  pyrazoline  conformational populations.  M c G r e e r _3_t al_ (13)  cis-  concerning  a n d 123 h a s b e e n d i s c u s s e d p r e v i o u s l y  i s the d i f f e r e n c e between the degree of  molecule,  point  t h e m a j o r c y c l o p r o p a n e i s t h e one i n w h i c h  g i v e a random s e l e c t i o n o f  it  122  This  conformation}whereas  discussion.  observed at both  that  e x i s t s i n o n l y one  conformations.  conformational preferences of i n part  -  have a l a r g e r degree o f  t r a n s - c o u p l i n g observed are  10.4,  (36), folding  9 . 8 and  8.4  respectively. It  i s possible that  r i n g system accounts f o r  this  l a r g e r degree of  the major product  f o l d i n g i n the  from p y r a z o l i n e s  pyrazoline  118,  120  and  122  being  t h e c y c l o p r o p a n e formed w i t h r e t e n t i o n a t b o t h C-3 and C-5.  If the a x i a l - a x i a l  coupling  constant  i s proportional  t o t h e degree o f  f o l d i n g t h e n i t i s e x p e c t e d t h a t t h e f o l d i n g d e c r e a s e s from 118  t o 120 t o 122 w i t h t r a n s - c o u p l i n g s  respectively.  This order  specificity 122  o f 10.4, 9.8, and 8.4 Hz  a l s o c o r r e l a t e s w i t h t h e degree o f s t e r e o -  o f 98 t o 91 t o 79 p e r c e n t  respectively.  pyrazolines  The s t e r e o s p e c i f i c i t y  f o rpyrazolines  118, 120 and  r e f e r s t o the percentage  o f t h e c y c l o p r o p a n e formed w i t h t h e same c o n f i g u r a t i o n as t h e s t a r t i n g pyrazoline. A n o t h e r i n d i c a t i o n o f t h e degree o f f o l d i n g i s o b t a i n e d chemical s h i f t values  o f t h e C-3 and a c e t y l methyl r e s o n a n c e s , o r t h e i r  d i f f e r e n c e , i n t h e n.m.r. (Table V I ) . r e s p e c t i v e groups f o r p y r a z o l i n e s values  from t h e  However, t h e resonances o f the  118, 120 and 122 have more extreme  t h a n e x p e c t e d on comparison t o c i s - and t r a n s - 3 , 5 - d i m e t h y l - 3 -  acetyl-l-pyrazolines  (21 and 22) which occupy o n l y one c o n f o r m a t i o n (14)  ( F i g u r e 4 ) . The more extreme v a l u e s a t t r i b u t e d to increased f o l d i n g places shielding  i n t h e n.m.r. spectrum c a n be  f o l d i n g o f the p y r a z o l i n e molecule.  the substituents  a t C-3 ( o r C-5) i n a more  (equatorial) or deshielding  Increased  intense  ( a x i a l ) zone o f t h e -N=N-  double  bond. On t h e b a s i s o f t h e p r e c e d i n g  explanation  o f t h e r e s u l t s , two  mechanisms a r e p r o p o s e d t o account f o r t h e l a r g e degree o f r e t e n t i o n i n the formation  o f c y c l o p r o p a n e s from p y r a z o l i n e s  One mechanism i s t h a t as t h e p y r a z o l i n e at  t h e same time some o v e r l a p  118, 120 and 122.  i s expelling nitrogen,  there i s  o f t h e p o t e n t i a l bonding o r b i t a l s between  67 C-3 is  and C-5 and thus a c y c l o p r o p a n e w i t h r e t e n t i o n o f c o n f i g u r a t i o n formed  i n a concerted process  ( F i g u r e 28).  How much bonding  there  i s between t h e C-3 and C-5 p o s i t i o n s o f t h e p y r a z o l i n e i n t h e t r a n s i t i o n s t a t e i s dependent on t h e degree o f f o l d i n g i n the s t a r t i n g  pyrazoline  molecule. COCH.  COCH, 3 — N 7  /  I C  COCH.  /// N  6 5 H  118  126  F i g u r e 28 - C o n c e r t e d mechanism f o r f o r m a t i o n o f c y c l o p r o p a n e s w i t h retention of configuration. An a l t e r n a t i v e e x p l a n a t i o n , which a l l o w s f o r an i n t e r m e d i a t e , utilizes  the formation o f a pyramidal d i r a d i c a l  d e s c r i b e d by A l l r e d and Smith diradical  ( F i g u r e 29) as  (33) ( F i g u r e 18).  However, t h e p y r a m i d a l  i s n o t " i n v e r t e d " a t C-3 and C-5, where i n v e r s i o n was a  consequence o f r e c o i l  from t h e energy r e l e a s e d by the C-N bond b r e a k i n g  (33), b u t i s formed merely from t h e e x p u l s i o n o f n i t r o g e n without ( F i g u r e 29).  Upon the f o r m a t i o n o f t h i s p y r a m i d a l d i r a d i c a l ,  recoil  immediate  r i n g c l o s u r e r e s u l t s i n a c y c l o p r o p a n e w i t h r e t e n t i o n a t C-3 and C-5. I t may be t h a t a t r u e p y r a m i d a l d i r a d i c a l  i s n o t produced  but that the  H ,. ^ u  COCH  3  COCH. N COCH.  C,H 6"5  C  118  6 5 H  126  F i g u r e 29 - Pyramidal d i r a d i c a l mechanism for;, f o r m a t i o n o f c y c l o p r o p a n e s with r e t e n t i o n o f c o n f i g u r a t i o n .  - 68 -  back l o b e s have some development. between the p y r a m i d a l d i r a d i c a l p - o r b i t a l s are f u l l y  T h i s would g i v e an i n t e r m e d i a t e  and a t r i m e t h y l e n e s p e c i e s where the  developed.  The more the i n t e r m e d i a t e  resembles  a p y r a m i d a l d i r a d i c a l , t h e more c y c l o p r o p a n e w i t h r e t e n t i o n o f c o n f i g u r a tion.  Thus the l a r g e r the degree  the more the i n t e r m e d i a t e w i l l E x a c t l y why for  o f f o l d i n g i n the p y r a z o l i n e m o l e c u l e  resemble  the p y r a m i d a l  diradical.  a g r e a t e r f o l d i n g i n the p y r a z o l i n e m o l e c u l e  g r e a t e r o v e r l a p o f the d e v e l o p i n g bond between C-3  ism 1) o r s h o u l d make the i n t e r m e d i a t e resemble pyramidal d i r a d i c a l  (mechanism 2) i s not  should allow  and C-5  (mechan-  more s t r o n g l y a  understood.  Thus a mechanism i n v o l v i n g e i t h e r a c o n c e r t e d p r o c e s s or an i n t e r m e d i a t e r e s e m b l i n g a p y r a m i d a l d i r a d i c a l i s proposed important p a r t i n the f o r m a t i o n o f c y c l o p r o p a n e s c o n f i g u r a t i o n i s observed.  The  degree  i n which r e t e n t i o n o f  t o which a p y r a z o l i n e g i v e s a  c y c l o p r o p a n e w i t h r e t e n t i o n o f c o n f i g u r a t i o n appears degree  of folding  118,the degree  i n the p y r a z o l i n e m o l e c u l e .  of folding  the c y c l o p r o p a n e  126  dependent on  the  In a p y r a z o l i n e such  as  i s l a r g e and p y r o l y s i s g i v e s 98 p e r c e n t o f  r e s u l t i n g from r e t e n t i o n a t C-3  p y r a z o l i n e s such as c i s - and (21 and 22)  t o p l a y an  and the analogous  and C-5.  In  trans-3,5-dimethyl-3-acetyl-l-pyrazoline 3-carbomethoxy-l-pyrazolines  10_ and  11,  the c y c l o p r o p a n e w i t h the same s t e r e o c h e m i s t r y as the s t a r t i n g p y r a z o l i n e v a r i e s from 15 t o 18 p e r c e n t l e s s e r degree by n.m.r. degree  (Table V I I I ) .  o f f o l d i n g i n p y r a z o l i n e s 10,  However,the degree  i n p y r a z o l i n e s 10,  o f f o l d i n g may  11, 21 and  t h a t the c y c l o p r o p a n e s w i t h r e t e n t i o n  T h i s i s c o n s i s t e n t w i t h the 11, 21 and  22 as  indicated  be t o such a l e s s e r  2_2 compared t o 118,  120  o f s t e r e o c h e m i s t r y may  and  122  not be  formed  - 69 at a l l through e i t h e r o f t h e above two mechanisms but r a t h e r  through  some a l t e r n a t i v e r o u t e . Another  f e a t u r e o f t h e r e s u l t s i s t h a t c y c l o p r o p a n e 133 was never  observed as a p r o d u c t o f p y r o l y s i s from any o f the s i x p y r a z o l i n e s i n t h i s study  (Table V I I ) .  I t was a n t i c i p a t e d t h a t p y r a z o l i n e  g i v e t o some e x t e n t c y c l o p r o p a n e 133, s i n c e the p y r a z o l i n e  121 would and c y c l o -  propane have t h e same s t e r e o c h e m i s t r y about  the carbon atoms.  was t h e case w i t h t h e analogous  119 and 123 as c y c l o p r o p a n e s  pyrazolines  w i t h r e t e n t i o n o f c o n f i g u r a t i o n were formed The  from b o t h  pyrazolines.  chemical s h i f t v a l u e s (Table VI) o f the a c e t y l and C-3 methyls  of pyrazoline  121 i n d i c a t e t h a t t h e m o l e c u l e o c c u p i e s e n t i r e l y the  c o n f o r m a t i o n i n which t h e C-3 a c e t y l group  and t h e C-5 p h e n y l group a r e  pseudo e q u a t o r i a l ; whereas t h e n.m.r. o f t h e analogous and  Such  pyrazolines  119  123 i n d i c a t e s t h a t b o t h c o n f o r m a t i o n s a r e o c c u p i e d , w i t h t h e conforma-  t i o n most h i g h l y p o p u l a t e d b e i n g the one i n which t h e 3 , 5 - d i a x i a l i n t e r a c t i o n i s avoided.  T h i s suggests t h a t f o r 3 , 5 - d i a x i a l i n t e r a c t i o n s ,  p h e n y l and a c e t y l ( p y r a z o l i n e 121) i s much g r e a t e r and methyl  (pyrazoline  119) o r methyl and methyl  than e i t h e r phenyl  ( p y r a z o l i n e 123).  Such  a s e v e r e i n t e r a c t i o n o f a p h e n y l and a c e t y l may a l s o be i n d i c a t i v e o f an equally severe i n t e r a c t i o n i n the t r a n s i t i o n s t a t e . i n t e r a c t i o n between an a c e t y l and p h e n y l group which e x p l a i n s  However, such an  cannot be the main f a c t o r  the l a c k o f f o r m a t i o n o f c y c l o p r o p a n e 133 s i n c e c y c l o -  propane 126, w i t h a p h e n y l and a c e t y l c i s , i s formed each o f the p y r a z o l i n e s  119, 121, and 123.  The a d d i t i o n a l f a c t o r must  t h e r e f o r e be due t o t h e p r e s e n c e o f t h e C-4 methyl t o both t h e a c e t y l group  s u b s t a n t i a l l y from  group which i s c i s  a t C-3 and t h e methyl group  a t C-5 i n t h e  - 70 -  starting  p y r a z o l i n e 121, and which g i v e s r i s e t o s t e r i c crowding i n  the t r a n s i t i o n  state.  B e f o r e c o n t i n u i n g on t o the next p o i n t c o n c e r n i n g double i n v e r s i o n a t C-3  and C - 5 , i t  i s f i r s t n e c e s s a r y t o comment b r i e f l y  on  the f o r m a t i o n o f b i c y c l o [ 2 . 1 . 0 ] p e n t a n e d e r i v a t i v e s from the c o r r e s p o n d ing 2,3-diazobicyclo[2.2.1]-2-heptene have proposed of r e c o i l complete structure  (33,34).  an i n v e r t e d p y r a m i d a l d i r a d i c a l  from energy r e l e a s e d by C-N  A l l r e d and Smith formed  bond b r e a k i n g .  from the  (33)  consequences  Ring c l o s u r e b e f o r e  e q u i l i b r a t i o n accounts f o r the excess o f the p r o d u c t o f i n v e r t e d ( F i g u r e 18).  However, the p r o d u c t o f i n v e r t e d s t r u c t u r e  a l s o be r a t i o n a l i z e d u s i n g the second mechanism  ( F i g u r e 29) from  may  this  work i n v o l v i n g an i n t e r m e d i a t e r e s e m b l i n g a p y r a m i d a l d i r a d i c a l , w h i c h accounted f o r the l a r g e degree  o f r e t e n t i o n i n the f o r m a t i o n o f  c y c l o p r o p a n e p r o d u c t s from p y r a z o l i n e s 118,  120 and  122  (Table V I I ) .  E x p u l s i o n o f n i t r o g e n from the b i c y c l i c p y r a z o l i n e without r e c o i l double i n v e r s i o n would r e s u l t  i n an i n t e r m e d i a t e ( F i g u r e 30)  and  resembling  a p y r a m i d a l d i r a d i c a l i n which the back lobes are p a r t i a l l y  developed.  The d i s t i n c t  120 and  d i f f e r e n c e between the i n t e r m e d i a t e s from 118,  F i g u r e 30 - I n t e r m e d i a t e r e s e m b l i n g a p y r a m i d a l d i r a d i c a l p y r o l y s i s of  122  species i n  endo-5-methoxy-2,3-diazabicyclo[2.2.1]-2-heptene.  - 71 and the intermediate from 109 and 110 is that in the former case the larger front lobes are pointing towards each other; however, in the latter case the strain of the five membered ring results in the back lobes pointing towards each other.  Taking into consideration the bonding  in bicyclo[2.1.0]pentane (46),the back lobes are in a favourable geometric position to bond as opposed to the front lobes.  Allred and Smith  (33) have suggested that the pyramidal diradical in their case can equilibrate, although not entirely, before ring closure occurs. However,in the second mechanism in this work the intermediate resembling a pyramidal diradical ring closes immediately upon formation. Similar work by Roth and Martin (34) has indicated predominance of double inversion in the pyrolysis of exo-5,6-dideuterio-2,3-diazobicyclo[2.2.1]-2-heptene (115) (Figure 19).  Their proposed mechanism  involving concerted elimination of nitrogen with accompanying backside p-orbital overlap in the transition state seems equally improbable from a geometrical point of view since the developing backside p-orbitals are directed away from each other. The feature in the present study concerning double inversion is the substantial contribution of the cyclopropane in which inversion has taken place at both C-3 and C-5 of the starting pyrazolines 119, 121 and 12 3 (Table VII). There are several mechanisms which can explain double inversion, two of which have been mentioned in the preceding two paragraphs.  As pointed out, the use of an "inverted"  pyramidal diradical by Allred and Smith (33) is not necessary from the point of view that an intermediate resembling a pyramidal diradical can equally explain the predominance of the double inverted product. The other mechanism by Roth and Martin (34) seemed unlikely from a  - 72 -  g e o m e t r i c a l p o i n t o f view. Thus a t h i r d mechanism may be r e q u i r e d t o e x p l a i n t h e c o n s i d e r a b l e amount o f double  i n v e r t e d cyclopropane  product  o f t h e 1 - p y r a z o l i n e s 119, 121 and 123.  formed from the p y r o l y s i s  One such mechanism would  i n v o l v e a t r i m e t h y l e n e i n t e r m e d i a t e , i n which a symmetrical on d i s r o t a t i o n , would g i v e c y c l o p r o p a n e s b o t h C-3 and C-5.  trimethylene  with r e t e n t i o n or i n v e r s i o n at  However ,to t h i s date t h e r e i s no c o n c l u s i v e  evidence  that a trimethylene intermediate p a r t i c i p a t e s i n the p y r o l y s i s o f 1 - p y r a z o l i n e s w i t h an e l e c t r o n withdrawing group a t C-3, a l t h o u g h t h e existence o f a trimethylene intermediate i s quite well established i n the p y r o l y s i s o f a l k y l  s u b s t i t u t e d 1-pyrazolines  As p o i n t e d out i n p a r t  (19-24,32).  (a) o f the I n t r o d u c t i o n , v e r y l i t t l e i s  known about t h e f o r m a t i o n o f c y c l o p r o p a n e  d e r i v a t i v e s from t h e p y r o l y s i s  o f 1 - p y r a z o l i n e s t h a t have an e l e c t r o n - w i t h d r a w i n g o r carbomethoxy, a t t h e C-3 p o s i t i o n . 28)  group, such as a c e t y l  A c o n c e r t e d mechanism ( F i g u r e  o r a mechanism i n v o l v i n g an i n t e r m e d i a t e r e s e m b l i n g  diradical  ( F i g u r e 29) has been proposed t o account  cyclopropanes zoline.  a pyramidal  f o r the formation o f  t h a t have t h e same s t e r e o c h e m i s t r y as t h e s t a r t i n g  However,additional  f u r t h e r the understanding  experimental  data are r e q u i r e d i n order t o  o f cyclopropanes  e i t h e r C-3 o r C-5 o r by a double  pyra-  formed by an i n v e r s i o n a t  i n v e r s i o n a t C-3 and C-5.  III. General  Statement  Melting points Infrared  (m.p.) and b o i l i n g p o i n t s  (b.p.) are u n c o r r e c t e d .  ( i . r . ) - s p e c t r a were r e c o r d e d on a P e r k i n - E l m e r model  spectrophotometer. sodium  EXPERIMENTAL  chloride  The 60 MHz  A l l s p e c t r a were measured as a l i q u i d  film using  plates. n u c l e a r magnetic  resonance  (n.m.r.) s p e c t r a were  r e c o r d e d on e i t h e r a V a r i a n A s s o c i a t e s Model A-60  s p e c t r o m e t e r or a  J e l c o Model C-60  The  magnetic  137  s p e c t r o m e t e r by M i s s P. Watson.  100 MHz  nuclear  resonance s p e c t r a were r e c o r d e d on a V a r i a n A s s o c i a t e s Model  HR-100 s p e c t r o m e t e r by Mr.  R.  Burton.  The  s p e c t r a were run as  e i t h e r i n carbon t e t r a c h l o r i d e o r d e u t e r i o c h l o r o f o r m (Merck, and Dohm) w i t h T e t r a m e t h y l s i l a n e as the i n t e r n a l The vapour-phase  chromatography  Sharp  reference.  (v.p.c.) u n i t s used were an  Aerograph Model A-90-P and an Aerograph Model A-90-P3. used were 10' x 1/4"  solutions  A l l columns  unless otherwise i n d i c a t e d .  The e l e m e n t a l m i c r o a n a l y s e s were performed by Mr.  P.  Borda.  Petroleum e t h e r r e f e r s t o the f r a c t i o n b o i l i n g between 30-60°.  N-Nitroso-N-ethyl  Urea  N - N i t r o s o - N - e t h y l u r e a was g i v e n by C h i u ( 4 1 ) .  p r e p a r e d a c c o r d i n g t o the procedure  - 74 -  Diazoethane Diazoethane was prepared from N-nitroso-N-ethyl urea according to the procedure given by Chiu (41). Benzaldehyde Hydrazone A procedure similar to that of Curtius (42) was used in the preparation of benzaldehyde hydrazone.  Into a 250 ml round bottom flask  equipped with a mechanical stirrer was placed 1.5 g of barium oxide and 50 g (1.0 mole) of hydrazine hydrate.  Over a period of one hr  95 g (0.90 mole) of freshly d i s t i l l e d benzaldehyde (Analar) was added.  The reaction mixture was stirred vigourously at 100° for 6 hr.  Before completion of the reaction a considerable amount of solid was formed,but during the course of the reaction the solution again became clear.  The reaction mixture was cooled, diluted with ether, and filtered.  The ether layer was dried with sodium sulphate and concentrated with a rotatory evaporator.  The crude reaction product was d i s t i l l e d under  vacuum to yield 90 g (0.74 mole) of a clear pale yellow liquid: 82%; b.p. 138-40° (14 mm);  yield  n.m.r. 4.08 T (broad singlet) nitrogen  protons, 2.43 x (singlet) benzylic hydrogen, 2.40 and 2.74 x (multiplets' with areas of 2 and 3 respectively) ^2^5 system of aromatic hydrogens. Phenyl Diazomethane A procedure similar to Standinger (43),with yellow mercuric oxide (AC) as the oxidant,was used in the preparation of phenyl diazomethane. Into a 250 ml Erlenmeyer was placed 12 g (0.1 mole) of benzaldehyde hydrazone, 70 ml of petroleum ether and 1 ml of saturated potassium hydroxide alcoholic (ethanol) solution.  The flask was placed in an  - 75 i c e - w a t e r b a t h and over a p e r i o d o f 20 min m e r c u r i c o x i d e was m i x t u r e was  a l l o w e d t o s t i r f o r an a d d i t i o n a l filtered.  made up t o 100 ml w i t h p e t r o l e u m p r e p a r a t i o n was  g (0.1 mole) o f  added t o the m a g n e t i c a l l y s t i r r e d  p e t r o l e u m e t h e r l a y e r was  w i t h 0.1  21.6  solution.  The  10 min and the decanted  The r e s u l t i n g r e d s o l u t i o n  e t h e r and used immediately.  c a r r i e d out i n a fume hood.  molar q u a n t i t i e s o f methyl  was  The  Based on the r e a c t i o n  i s o p r o p e n y l ketone,  methylmethacrylate,  and m e t h a c r y l o n i t r i l e , the y i e l d o f p h e n y l diazomethane v a r i e d between 50 and  65%.  3-Methyl-3-pentene-2-one,  ( Z ) - (25)  I r r a d i a t i o n o f 12 g (0.12 mole) o f 3-methyl-3-pentene-2-one, ( E ) (24)  ( A l d r i c h ) i n 100 ml o f e t h e r f o r 16 h r i n a s i l i c a tube u s i n g a o  Hanovia 450 W lamp (2537 A) r e s u l t e d i n a p p r o x i m a t e l y 25% c o n v e r s i o n t o the d e s i r e d _Z isomer 25_ as determined by v.p.c. 138°, 120 ml p e r m i n ) . were 8.6  and  11.0  respectively).  The  r e t e n t i o n .times f o r the Z_ and E  min r e s p e c t i v e l y  The  (didecyl phthalate,  e t h e r was  (lit.  (14): b.p.  isomers  124° and  147°  removed and a simple d i s t i l l a t i o n gave a  f r a c t i o n b o i l i n g between 131-136° which c o n s i s t e d o f a 50:50 m i x t u r e o f the Z_ and E_ i s o m e r s .  The  50:50 m i x t u r e was  u s i n g a N e s t e r and Faust s t a i n l e s s f r a c t i o n between 124-30° was  then f r a c t i o n a l l y  s t e e l spinning-band apparatus.  c o l l e c t e d and c o n s i s t e d o f a 90:10  o f t h e Z_ and E_ isomers r e s p e c t i v e l y .  S i n c e the s p i n n i n g - b a n d  l a t i o n f a i l e d t o p u r i f y the Z_ isomer s u f f i c i e n t l y , was  distilled  c o l l e c t e d u s i n g the v . p . c . r e s u l t i n g  1.8  The  ratio distil-  g (0.18 mole)  i n g r e a t e r than 95%  purity.  - 76 -  3-Methyl-4-phenyl-3-butene-2-one, The o l e f i n (44). of  (E)-  (132)  132 was p r e p a r e d a c c o r d i n g t o t h e p r o c e d u r e o f Noyce  I n t o a 500 ml round bottom f l a s k was p l a c e d 106 g (1.0 mole)  benzaldehyde and 72 g (1.0 mole) o f methyl e t h y l ketone t o g e t h e r  w i t h 3 ml o f c o n c e n t r a t e d s u l p h u r i c a c i d and 100 ml o f a c e t i c The m i x t u r e was s t i r r e d a t 75-85° f o r 3 h r .  acid.  The r e a c t i o n was m o n i t o r e d  by v.p.c. (SE 30, 2 1 0 ° , 120 ml p e r m i n ) . The r e a c t i o n m i x t u r e was poured onto 650 g o f i c e and water and extracted with ether. chloride solution, sodium c h l o r i d e .  The e t h e r was e x t r a c t e d w i t h s a t u r a t e d  10% sodium c a r b o n a t e , and a g a i n w i t h s a t u r a t e d The s o l u t i o n was d r i e d over sodium s u l p h a t e , concen-  t r a t e d u s i n g a r o t a t o r y e v a p o r a t o r , and vacuum d i s t i l l e d the  sodium  f r a c t i o n between 100-105°  from e t h e r - p e t r o l e u m e t h e r  a t 0.5 mm.  to c o l l e c t  The p r o d u c t was r e c r y s t a l l i z e d  (1:1) t o g i v e white c r y s t a l s :  y i e l d 23%;  m.p. 37-40°; n.m.r. 7.97 x (doublet J = 1.5 Hz) C-3 m e t h y l , 7.60 x ( s i n g l e t ) a c e t y l m e t h y l , 2.54 x ( m u l t i p l e t ) v i n y l hydrogen,  2.65 x  ( s i n g l e t ) a r o m a t i c hydrogens.  3-Acetyl-3',4'-dimethyl-5-phenyl-l-pyrazoline*  (118) and 3 - A c e t y l - 3 , 4 1  d i m e t h y l - 5 - p h e n y l - l - p y r a z o l i n e (119) 1  (a)  P r e p a r a t i o n and Enrichment  To an e t h e r s o l u t i o n o f 9.8 g (0.1 mole) o f , one,  ( E ) - (124) was added p h e n y l diazomethane  benzaldehyde h y d r a z o n e ) .  The s o l u t i o n was l e f t  3-methyl-3-pentene-2-  (from 12 g (0.1 mole) o f a t -5° f o r 10 days.  P y r a z o l i n e f o r m a t i o n was i n d i c a t e d by use o f n.m.r. *  See Appendix  f o r nomenclature  The r a t i o o f t h e  1  - 77  two as  pyrazolines 1:2  119  and  respectively.  118  The  was  -  estimated  pyrazolines  s o l u t i o n i n ether-petroleum  e t h e r at  Column chromatography  i n the crude r e a c t i o n m i x t u r e  118  and  119  ( s i l i c a g e l , ether-petroleum  liquids.  successive  f r a c t i o n s , i t was  l a r g e r R^-  By d e t e r m i n i n g  and  found t h a t the p y r a z o l i n e  118:  n.m.r. 8.82  x (doublet J = 10.4  hydrogen, 2.7  Hz)  and  7.58  x ( d o u b l e t J = 8.5  hydrogen, 2.7  7.46;  „ I t was  118  x (doublet J = 7.0 C-5  hydrogen, 8.08  119:  n.m.r. 8.52  and  7.76  Hz)  C-5  hydrogen, 7.29  12.95.  Found:  C,  Hz)  C-4  (multiplet)  Hz)  C-4  and  methyl,  x (multiplet)  72.29; H,  or by  column chromatography.  and  7.36;  N,  C-4  t o 85%  and  the p y r a z o l i n e  A second method was  119  unsuccessful  at 55°,  119):  or  to 62% by  successive 118.  p y r a z o l i n e over  discovered  100%  pyrazoline  used t o e n r i c h the p y r a z o l i n e  i t was  C,  13.11. 118  However, the  A l t h o u g h the p r e f e r e n t i a l d e c o m p o s i t i o n o f one o t h e r was  the  x ( s i n g l e t s ) C-3  f o r C.,H.,0N„ (as a m i x t u r e o f 118 13 16 2.  N,  enriched  columns.  had  x  not p o s s i b l e t o o b t a i n pure samples o f 100%  t.l.c.  was  119  in  x ( m u l t i p l e t ) a r o m a t i c hydrogens.  Anal. Calcd.  119 by  as c l e a r  x ( s i n g l e t s ) C-3  a c e t y l methyl r e s p e c t i v e l y , 9.65.x (doublet J = 7.5  72.19; H,  second  x ( m u l t i p l e t ) aromatic hydrogens.  For the p y r a z o l i n e  4.63  119  the r a t i o o f the p y r a z o l i n e s  a c e t y l methyls r e s p e c t i v e l y , 8.97  m e t h y l , 5.32 C-4  118  to  value.  For the p y r a z o l i n e and  e t h e r , 5:95  main f r a c t i o n s , the  the pure p y r a z o l i n e s  colourless  a  -5°.  10:90) on the crude r e a c t i o n m i x t u r e gave two o f which y i e l d e d t o g e t h e r  were s t o r e d as  the  t h a t over a p e r i o d  s e v e r a l weeks slow d e c o m p o s i t i o n o f the p y r a z o l i n e 118  took p l a c e  of  - 78 -  at room temperature,  thus e n r i c h i n g  described previously  i t was  p r o d u c t s from 100%  possible  from the second f r a c t i o n . a t room temperature  (b)  decomposition  f r a c t i o n , and the  119  decomposition  i n the r a t i o 25:75 r e s p e c t i v e l y  Evidence that  118 decomposed  exclusively  i n ether-petroleum ether s o l u t i o n r e s u l t e d  the f i r s t  Thus the c y c l o p r o p a n e 127 must o c c u r  from the d e c o m p o s i t i o n o f the o t h e r p y r a z o l i n e  Pyrolysis  from  f r a c t i o n from column chromatography c o n t a i n e d  none o f the c y c l o p r o p a n e 127. exclusively  and  Using column chromatography as  t o determine the  118 from the f i r s t  p r o d u c t s from a m i x t u r e o f 118  the f a c t t h a t  119.  119.  and Product I d e n t i f i c a t i o n  The p y r o l y s i s o f the p y r a z o l i n e s 118 and 119 was  c a r r i e d out  e i t h e r as a neat sample at 100-120° o r as a neat sample p y r o l y z e d i n the i n j e c t o r o f the v.p.c.  The v.p.c.  (FFAP, 218°, 120 ml p e r  showed 6 peaks A, B, C, D, E, and F w i t h r e t e n t i o n 16.4,  17.6,  and  Peak A was trace  20.0  min  12.2,  13.6,  respectively.  not i s o l a t e d o r i d e n t i f i e d as i t was  present i n only  amounts. Peak B was  125 and  i s o l a t e d and i d e n t i f i e d as a m i x t u r e o f the c y c l o p r o p a n e  the r e a r r a n g e d y,6-isomers  Peak C was  stretching methyls  f r e q u e n c y ) ; n.m.r respectively,  ( d o u b l e t J = 7.0  134 and  135 on the b a s i s  i s o l a t e d and i d e n t i f i e d as the compound  dimethyl-2-phenyl cyclopropane  C-l  times 8.6,  min)  Hz)  C-2  5 l i n e s ) C-3 hydrogen,  (126):  8.20  8.76  and 8.51  7.66  x (broadened  cm  1-acetyl-l',3'-  * (carbonyl  x (singlets) acetyl  x ( d o u b l e t J = 6.2  hydrogen,  2.8  i . r . 1695  o f n.m.r.  and  Hz) C-3 m e t h y l , 7.99  x (multiplet  o f approximately  s i n g l e t ) aromatic  hydrogens.  x  Anal.  Calcd.  for  C,_H..,0:  79  C,  -  8 2 . 9 3 ; H,  8.57.  Found:  C,  83.06;  io io H,  8.55• Peaks  present that toF  D and E were not  i n l a r g e amounts  o f t h e major peak ratio of  10:90  i n the n . m . r .  and,  F.  from the p y r a z o l i n e s  olefins  readily  olefins  of  isomerize  broad s i n g l e t s for  times  Peak  the benzylic  authentic  stretching  methyl,  and C - l m e t h y l s 7.19  for  i s possible that  it  on t h e v . p . c .  fact  that  hydrogens  samples that  were  x  (doublet 2.9  C,,H  x 0:  n.m.r.  (100  MHz)  respectively, J  = 9 . 8 Hz)  (broadened C,  (127):  Evidence  the n . m . r .  singlet)  8 2 . 9 3 ; H,  8.57.  (E)-  expected the  Considerable for  displays  i n the appropriate similar  both two  region. retention  synthesized. compound  i.r.  1690  7.79  and 8 . 8 8  8.95 x C-2  is  column.  t h e peaks D and E have  cyclopropane  frequency);  C-3 hydrogen, Calcd.  and 119,  F was i s o l a t e d a n d i d e n t i f i e d a s t h e  dimethyl-2'-phenyl  acetyl  these o l e f i n s  i n the  evidence i s that  as t h e  118  o n l y one o f  thermally  lies  hydrogens  s a m p l e s , peaks D and  t h e t w o p e a k s D a n d E was o b s e r v e d .  being present  Additional  the b e n z y l i c  to  D and E  3-methyl-4-benzyl-3-pentene-2-one,  Although  (13,15)  overlapping  not  t i m e s were c l o s e  By c o m p a r i s o n o f  times with authentic  structures  (129).  were  P a r t i a l s e p a r a t i o n gave an a p p r o x i m a t e  and r e t e n t i o n  (Z)-  form s i n c e they  and s i n c e t h e i r r e t e n t i o n  respectively.  E were a s s i g n e d the (128)  i s o l a t e d i n pure  cm  hydrogen,  (carbonyl  1  (doublet  x J  8.2  1-acetyl-l',3'-  (singlets) = 6.4  x  C,  C-3  (multiplet)  aromatic hydrogens. Found:  Hz)  82.89;  Anal. H,  8.75.  - 80 -  (c)  Product  Distribution  TABLE X Distribution  1  o f Products f o r the P y r o l y s i s  2  of Different  R a t i o s o f the  P y r a z o l i n e s 118 and 119 R a t i o of 118:119 3  100:0  4  126  129  127  1  98  1  0  85:15  5  2  91  1  6  74:26  5  2  86  3  9  51:49  5  6  66  7  21  38:62  5  8  54  13  25  10  43  16  31  13  25  21  41  25:75  4  0:100  Average  125  6  o f t h r e e runs by v.p.c.  D i s t r i b u t i o n o f p r o d u c t s from neat and v.p.c. Average  of three integrations  o f C-5  Correction results.  are i d e n t i c a l .  hydrogens.  P r e f e r e n t i a l decomposition o f p y r a z o l i n e s S u c c e s s i v e f r a c t i o n a t i n g by column  Pyrolysis  118 and 119 a t r . t .  chromatography.  t o 100% u s i n g r e s u l t s o f p r e f e r e n t i a l  decomposition  - 81 -  3'-Acetyl-3,4'-dimethyl-5-phenyl-l-pyrazoline  (120) and  3'-Acetyl-3,4'-  d i m e t h y l - 5 - p h e n y l - l - p y r a z o l i n e (121) 1  (a)  P r e p a r a t i o n and Enrichment  To an e t h e r s o l u t i o n o f 1.8 g (0.18 mole) o f 3-methyl-3-pentene-2one,  ( Z ) - (25) was added p h e n y l  o f benzaldehyde h y d r a z o n e ) .  diazomethane (from 3.2 g (0.27 mole)  The s o l u t i o n was l e f t  P y r a z o l i n e f o r m a t i o n was i n d i c a t e d by use o f n.m.r. two as  p y r a z o l i n e s 121 and 120 was e s t i m a t e d 1:2 r e s p e c t i v e l y .  a t -5° f o r 2 weeks. The r a t i o o f the  i n t h e crude r e a c t i o n m i x t u r e  The p y r a z o l i n e s 120 and 121 were s t o r e d as a  s o l u t i o n i n ether-petroleum Column chromatography  ether a t -5°. ( s i l i c a g e l , ether-petroleum  10:90) on the crude r e a c t i o n m i x t u r e  e t h e r , 5:95 t o  gave two main f r a c t i o n s , t h e  second o f which y i e l d e d t o g e t h e r t h e pure p y r a z o l i n e s 120 and 121 as w h i t e s o l i d s .  By d e t e r m i n i n g  the r a t i o o f t h e p y r a z o l i n e s i n  s u c c e s s i v e f r a c t i o n , i t was determined t h a t the p y r a z o l i n e 121 had t h e larger  value.  For t h e p y r a z o l i n e 120: and  n.m.r. 8.31 and 7.96 T ( s i n g l e t s ) C-3  a c e t y l methyl r e s p e c t i v e l y , 9.03 T (doublet J = 6.8 Hz) C-4 m e t h y l ,  5.10 T ( d o u b l e t J = 9.8 Hz) C-5 hydrogen, 8.4 x ( m u l t i p l e t C-4 hydrogen, 2.7 x ( s i n g l e t ) a r o m a t i c F o r t h e p y r a z o l i n e 121: and  n.m.r. 8.68 and 7.58 x ( s i n g l e t s ) C-3  a c e t y l methyl r e s p e c t i v e l y , 9.82 x (doublet J = 7.4 Hz) C-4 m e t h y l ,  4.69  x ( d o u b l e t J = 7.5 Hz) C-5 hydrogen, 7.7 x ( m u l t i p l e t C-4  hydrogen, 2.7 x ( s i n g l e t ) a r o m a t i c C  1 3  hydrogens.  H  1 6  0N  Found:  2  (as a m i x t u r e  hydrogens.  o f 120 and 121) :  C, 72.40; H, 7.40; N, 12.70.  Anal. Calcd. f o r  C, 72.19; H, 7.46; N, 12.95.  - 82 -  As to  i n t h e case o f t h e p y r a z o l i n e s 118 and 119, i t was n o t p o s s i b l e  o b t a i n pure samples o f t h e p y r a z o l i n e s 120 and 121 by t . l . c .  column chromatography. 80%  H o w e v e r , p y r a z o l i n e 120 c o u l d be e n r i c h e d t o  and p y r a z o l i n e 121 t o 50% by one r u n u s i n g column chromatography.  As a r e s u l t  o f combining s e v e r a l f r a c t i o n s o b t a i n e d  chromatography and r e c r y s t a l l i z i n g t h a t two d i f f e r e n t types were r e c r y s t a l l i z e d for  o r by  two weeks.  from column  f o r m i c r o a n a l y s i s i t was d i s c o v e r e d  of crystals  slowly developed.  from e t h e r - p e t r o l e u m  ether  (10:90) and l e f t  By s e p a r a t i n g t h e c r y s t a l s a c c o r d i n g  to size,  e n r i c h e d t o 95% and 75% i n 120 and 121 r e s p e c t i v e l y were  (b) The 130-140°.  P y r o l y s i s and Product pyrolysis  The p y r a z o l i n e s a t -5°  samples  obtained.  Identification  o f p y r a z o l i n e s 120 and 121 was c a r r i e d out neat a t  The p r o d u c t s  o f p y r o l y s i s were a n a l y z e d  u s i n g the v.p.c.  (FFAP, 2 1 8 ° , 120 ml p e r min) which showed 6 peaks, A, B, C, D, E, and F w i t h r e t e n t i o n times 8.4, 12.2, 13.6, 16.4, 18.6 and 20.0 min respectively. Peak A was n o t i s o l a t e d and i d e n t i f i e d as i t was p r e s e n t  i n only  t r a c e amounts. Peak B was i s o l a t e d and i d e n t i f i e d 125  and t h e r e a r r a n g e d  Y> 5<  l s o m e r  s  as a m i x t u r e o f the c y c l o p r o p a n e  134 and 135 on t h e b a s i s o f n.m.r.  Peak C was i s o l a t e d as a m i x t u r e w i t h peak B and i d e n t i f i e d as the c y c l o p r o p a n e  126 on the b a s i s o f n.m.r. and comparison o f r e t e n t i o n  times. Peak D was p r e s e n t be  isolated.  i n o n l y s m a l l amounts and t h e r e f o r e c o u l d not  I t s r e t e n t i o n time does h o w e v e r , f a l l  i n t o the same  - 83 -  r e g i o n as one o f t h e two a , 6 - u n s a t u r a t e d ketones  128 and 129.  o f t h e s m a l l amount o f peak D p r e s e n t i t was d i f f i c u l t  Because  to t e l l i f  i s o m e r i z a t i o n , as suggested i n the s e c t i o n d e a l i n g w i t h t h e two ketones 128  and 129 from t h e p y r o l y s i s o f t h e p y r a z o l i n e s 118 and 119, was  occurring.  More important i s t h e f a c t t h a t on h e a t i n g t h e p r o d u c t s o f  p y r o l y s i s a t 220° f o r 2 hours, the peak D d i d n o t decrease i n s i z e . Thus peak D c o u l d n o t be t h e c y c l o p r o p a n e 133 which under t h e s e c o n d i t i o n s would r e a r r a n g e t o t h e Y j ^ - o l e f i n s  134 and 135.  Peak E was a l s o p r e s e n t i n v e r y s m a l l amounts and t h e r e f o r e was not i s o l a t e d o r i d e n t i f i e d . Peak F was i s o l a t e d and i d e n t i f i e d as the c y c l o p r o p a n e 127 on t h e b a s i s o f n.m.r. and r e t e n t i o n  (c)  Product  times.  Distribution TABLE XI  D i s t r i b u t i o n * o f Products f o r t h e P y r o l y s i s o f D i f f e r e n t R a t i o s o f the P y r a z o l i n e s 120 and 121 2 Ratio o f 120:121  125  126  128  25:75  42  18  5  35  58:42  65  12  1  22  95:5  88  7  91  6  0  3  22  7  45  100:0  3  0:100  3  . 26  trace  127  5  Average o f t h r e e runs by v . p . c . I n t e g r a t i o n o f n.m.r. s p e c t r a . C o r r e c t i o n t o 100% u s i n g 25:75 and 95:5 r a t i o s o f 120 and 121 respectively.  - 84 3-Acetyl-3',5-dimethyl-4'-phenyl-l-pyrazoline dimethyl-4'-phenyl-l-pyrazoline ' (a)  P r e p a r a t i o n and  was  and became c l e a r and  colourless.  estimated first 35%  (0.07  The  formation  of the o l e f i n  second and  ether-ether  white s o l i d : and  m.p.  x  hydrogen, 2.8 C^H^ON.: i o 16 I N,  and  132 was  and  123  -5°.  was  removed w i t h  triturated  Recrystallization  107°; n.m.r. 8.93  (doublet J = 8.4  Hz)  x ( m u l t i p l e t ) aromatic  C, 72.19; H-, 7.46;  N,  The  then t r e a t e d  C-4  7.52  x  hydrogen, 5.18  Found:  as a (singlets)  x (doublet J = 7.0  hydrogens.  12.95.  and  with  from  (95:5) y i e l d e d the pure p y r a z o l i n e 122  65-68° dec  was  123 were s t o r e d  the s o l v e n t was  a c e t y l methyls r e s p e c t i v e l y , 8.48  m e t h y l , 6.78  indicated  r e s u l t e d i n about  crude r e a c t i o n product  petroleum  -5°  week i n t e r v a l between the  e t h e r at  e t h e r t o g i v e white c r y s t a l s .  mole)  week at  respectively.  olefin  The p y r a z o l i n e s 122  petroleum  C-3  as 90:10  weeks a f t e r t h e t h i r d treatment The  g (0.20  f o r one  p y r a z o l i n e s 122  The  w i t h a one  as a s o l u t i o n i n e t h e r - p e t r o l e u m  a r o t a t o r y evaporator.  left  132 w i t h diazoethane  of pyrazoline products.  t h i r d treatment.  (from 23.4  P y r a z o l i n e f o r m a t i o n was  r a t i o o f the two  t w i c e more w i t h d i a z o e t h a n e  mole) o f 3-methyl-4-phenyl-3-  s o l u t i o n was  i n the crude r e a c t i o n m i x t u r e  treatment  Two  g  added d i a z o e t h a n e  urea).  The  3-Acetyl-3',5'-  Enrichment  of N-nitroso-N-ethyl  by use o f n.m.r.  and  (123)  To an e t h e r s o l u t i o n o f 11.2 butene-2-one, ( E ) - (132)  (122)  Hz)  C-5  x ( m u l t i p l e t ) C-5  Anal. Calcd. f o r C,  71.96; H,  7.61;  12.95. The mother l i q u o r from the above r e c r y s t a l l i z a t i o n was  by n.m.r. as a 50:50 m i x t u r e  o f the two  pyrazolines.  The  approximated  solvent  was  - 85 -  removed from t h e mother l i q u o r and then d i l u t e d w i t h 10 ml o f petroleum ether-ether  (95:5) and seeded w i t h pure c r y s t a l s o f t h e p y r a z o l i n e  122. . The s o l u t i o n was l e f t  f o r one week a t -5°, a f t e r which  observed t h a t n o t o n l y a d d i t i o n a l a l s o a l i q u i d , presumably  i t was  c r y s t a l s o f 122 were p r e s e n t b u t  the pyrazoline  123.  A f t e r t h e removal  o f the  s o l i d w h i t e c r y s t a l s , t h e mother l i q u o r was then f r a c t i o n a t e d by column chromatography  ( s i l i c a g e l , p e t r o l e u m e t h e r - e t h e r , 95:5 t o 90:10).  Three f r a c t i o n s were used f o r t h e p r o d u c t d i s t r i b u t i o n s t u d y . r a t i o o f t h e two p y r a z o l i n e s  The  123 and 122 i n t h e t h r e e f r a c t i o n s , as  determined by t h e i n t e g r a t i o n o f t h e two a c e t y l peaks, was 72:28, 68:32, and 64:36 r e s p e c t i v e l y . i t was found t h a t not  possible  By c o n s i d e r i n g  the pyrazoline  successive f r a c t i o n s ,  123 had t h e l a r g e r  value.  I t was  t o c r y s t a l l i z e any o f t h e f r a c t i o n s and thus t h e p y r a z o l i n e  123 must be a l i q u i d . For  the pyrazoline  123:  n.m.r. 8.50 and 7.75 T ( s i n g l e t s ) C-3  and a c e t y l methyls r e s p e c t i v e l y ,  8.56 T (doublet J = 7.0 Hz) C-5 m e t h y l ,  6.27 T (doublet J = 7.0 Hz) C-4 hydrogen, hydrogen,  2.8 T ( m u l t i p l e t )  5.9 T ( m u l t i p l e t )  a r o m a t i c hydrogens;  performed on t h e m i x t u r e o f t h e two p y r a z o l i n e s  (b)  Pyrolysis  The p y r a z o l i n e s  12.2,  no m i c r o a n a l y s i s was 122 and 123.  and Product I d e n t i f i c a t i o n 122 and 123 were decomposed neat a t 140-145°.  p r o d u c t d i s t r i b u t i o n was determined by v.p.c. min)  C-5  The  (FFAP, 208°, 120 ml p e r  which showed f i v e peaks A, B, C, D, and E w i t h r e t e n t i o n  times  13.4, 14.0, 21.0, and 23.5 min r e s p e c t i v e l y . Peak A was i s o l a t e d and found t o c o n s i s t  (>95%).  The f i r s t  compound i d e n t i f i e d was  o f two major p r o d u c t s 3-methyl-4-phenyl-3-hexene-  - 86 2-one, ( E ) - (136):  i.r.  1685 cm"  1  (carbonyl s t r e t c h i n g  frequency);  n.m.r. (100 MHz) 7.93 T ( s i n g l e t ) a c e t y l m e t h y l , 8.35 T ( m u l t i p l e t showing l o n g range c o u p l i n g ) a l p h a m e t h y l , 9.11 T ( t r i p l e t J = 7.3 Hz) C-6 hydrogens, 7.60 T ( q u a r t e t showing  long range c o u p l i n g J = 7.3 Hz)  C-5 hydrogens, 2.8 T ( m u l t i p l e t ) a r o m a t i c hydrogens.  The second  compound was i d e n t i f i e d as 3-methyl-4-phenyl-4-hexene-2-one, i.r.  (__)-  (137)  1715 cm" ; n.m.r. (100 MHz) 7.78 T ( s i n g l e t ) a c e t y l m e t h y l , 8.88 T 1  and 8.45 x ( d o u b l e t s J = 7.0 Hz) C-3 and C-5 methyl r e s p e c t i v e l y , 6.65 ( q u a r t e t J = 7.0 Hz) C-5 hydrogen, 4.43 T ( q u a r t e t J = 7.0 Hz) v i n y l hydrogen, 4.43 T ( q u a r t e t J = 7.0 Hz) v i n y l hydrogen, 2.8 T ( m u l t i p l e t ) a r o m a t i c hydrogens.  The n.m.r. o f peak A a l s o i n d i c a t e d t h e p r e s e n c e  o f t h e o t h e r a,3-unsaturated (Z)-  (138).  ketone  3-methyl-4-phenyl-3-hexene-2-one,  Peaks i n the n.m.r. (100 MHz) a s s i g n e d t o t h e o l e f i n 138  by comparison w i t h an a u t h e n t i c sample were:  8.10 T ( s i n g l e t )  acetyl  m e t h y l , 8.50 T ( s i n g l e t ) a l p h a m e t h y l , 9.07 T ( t r i p l e t J = 7.5 H z ) . I t was n o t p o s s i b l e t o c o n c l u d e i f any o f t h e r e m a i n i n g extraneous peaks i n t h e n.m.r. were due t o the o t h e r B,y-isomer phenyl-4-hexene-2-one,  ( Z ) - (159) s i n c e an a u t h e n t i c sample was not  a v a i l a b l e f o r comparison. 82.93; H, 8.57.  3-methyl-4-  Found:  Anal. Calcd. f o r C ^ H ^ O  (peak A ) :  C,  C, 83.10; H, 8.71.  Peaks B and C were i s o l a t e d and i d e n t i f i e d t o g e t h e r .  Peak B was  a s s i g n e d as h a v i n g c o n s i s t e d o f t h e c y c l o p r o p a n e 125 and t h e r e a r r a n g e d Y,6-olefins  134 and 155.  Peak C was a s s i g n e d as h a v i n g c o n s i s t e d o f  the c y c l o p r o p a n e 125 on the b a s i s o f r e t e n t i o n times and c h a r a c t e r i s t i c peaks i n t h e n.m.r.: methyls r e s p e c t i v e l y .  8.32 and 8.55 T ( s i n g l e t s ) C - l and a c e t y l The peak B was c o l l e c t e d by v.p.c. f o r i . r . ,  - 87 -  n.m.r. and m i c r o a n a l y s i s . phenyl  cyclopropane  F o r t h e compound  125:  1-acetyl-l',3-dimethyl-2 1  i . r . 1690 cm * ( c a r b o n y l s t r e t c h i n g f r e q u e n c y ) ;  n.m.r. (100 MHz) 8.92 and 7.81 T ( s i n g l e t s ) C - l and a c e t y l methyls r e s p e c t i v e l y , 8.88 T (doublet J = 6.4 Hz) C-3 m e t h y l , 7.15 T (doublet J  = 6.4 Hz) C-2 hydrogen, 8.6 x ( m u l t i p l e t ) C-3 hydrogen, 2.9 x  aromatic 135):  hydrogens.  Anal. Calcd. f o r C ^ H ^ O  C, 82.93; H, 8.57.  Found:  o f 125, 134 and  C, 82.83; H, 8.78.  Peak D was not i s o l a t e d as i t was p r e s e n t I t was i d e n t i f i e d as c y c l o p r o p a n e  (mixture  (singlet)  i n only a small quantity.  126 o n l y on t h e b a s i s o f i t s r e t e n t i o n  time. Peak E was i s o l a t e d and i d e n t i f i e d as t h e cyclopropane r e t e n t i o n time and n.m.r. were i d e n t i c a l i s o l a t e d from t h e d e c o m p o s i t i o n  (c)  Product  t o t h e same  127. I t s  cyclopropane  o f the p y r a z o l i n e s 119, 120 and 121.  Distribution TABLE XII  D i s t r i b u t i o n * o f Products  f o r the P y r o l y s i s o f D i f f e r e n t Ratios o f  t h e P y r a z o l i n e s 122 and 123 2 Ratio o f 122:123  125  126  0  79  trace  36:64  45  41  32:68  46  100:0  olefins  3  28:72 0:100  4  unid.  127  1  20  2  1  11  39  3  1  11  48  37  4  1  10  67  21  5  1  6  Average o f t h r e e runs by v.p.c. Average o f t h r e e i n t e g r a t i o n s o f a c e t y l  hydrogens.  From p u r e P y r a z o l i n e 122. C o r r e c t e d t o 100% u s i n g 100:0 and 28:72 r a t i o s o f 122 and 123 r e s p e c t i v  - 88 Rearrangement o f 1 - a c e t y l - l , 3 - d i m e t h y l - 2 ' - p h e n y l t o e r y t h r o - and 1  threo-3-methyl-4-phenyl-5-hexene-2-one  (134 and 135)  Four 50 mg samples o f t h e c y c l o p r o p a n e 125 a l r e a d y c o n t a i n i n g some o f t h e  Y > 5 - o l e f i n s were s e a l e d i n pyrex tubes  (2 mm diam) and  p l a c e d i n a f u r n a c e m a i n t a i n e d a t 227° f o r 3.5 h o u r s . 550,  The v.p.c. (DC  2 1 0 ° , 120 ml p e r min) i n d i c a t e d t h a t t h e c y c l o p r o p a n e 125 had  c o m p l e t e l y r e a r r a n g e d t o t h e y,6-olefins  134 and 135.  The r a t i o o f t h e  t h r e o 135 t o e r y t h r o 134 isomer was e s t i m a t e d by n.m.r. a t 2:1. I t was n o t p o s s i b l e t o s e p a r a t e t h e two Y>6-isomers by v.p.c.  The  r e a r r a n g e d p r o d u c t s c o u l d however be c o l l e c t e d as a m i x t u r e on t h e v.p.c. as a c l e a r c o l o u r l e s s  liquid:  i.r.  1723 cm * ( c a r b o n y l s t r e t c h i n g  f r e q u e n c y ) ; n.m.r. (100 MHz) 7.95 and 8.25 x ( s i n g l e t s ) a c e t y l o f 135 and 134 r e s p e c t i v e l y , 9.16 and 8.92 x C-3 methyls  7.17 x ( m u l t i p l e t o f 8 l i n e s ) C-3 hydrogens,  multiplet  C, 82.93; H, 8.57.  Found:  and t h e C-3 methyls  i n t h i s case methyl be s h i e l d e d  Trimethyl  Anal. Calcd. f o r C^H^O:  C, 8.71; H, 8.75.  Assignment  of acetyl  was made on t h e b a s i s t h a t the f u n c t i o n ,  o r a c e t y l , t h a t i s c i s t o t h e p h e n y l group  (38) i n the most s t a b l e  will  conformation.  q-phosphonopropionate  T r i m e t h y l a-phosphonopropionate procedure g i v e n by K i n s t l e distilled  4.12 x  40 Hz wide o f a r e a one) and 5.03x(complex m u l t i p l e t  32 Hz wide o f a r e a two) v i n y l hydrogens.  methyls  ( d o u b l e t s J = 6.9 Hz)  o f 135 and 134 r e s p e c t i v e l y , 6.60 x ( t r i p l e t J = 9.0 Hz)  C-5 hydrogens, (complex  methyls  (39).  was p r e p a r e d a c c o r d i n g t o the  The r e s u l t i n g r e a c t i o n m i x t u r e was '  t o g i v e a 31% y i e l d o f p r o d u c t b o i l i n g between 93-100° a t 0.3  mm.  "I  - 89 Methyl 3-methyl-3-benzyl-2-butenoate,  (E)- (144) and Methyl 3-methyl-  3-benzyl-2-butenoate, (Z)- (145) The procedure according to Kinstle (39) was used.  To a slurry of  4.32 g (0.18 mole) of sodium hydride (Ventron) in 200 ml of dry 1,2dimethoxyethane maintained at 15° was added dropwise in one hour 35.3 g (0.18 mole) of trimethyl a-phosphonopropionate.  After the  addition,the grey solution was stirred for one hr at room temperature and for 5 min at 35°.  The solution was cooled to 15° and 24.1 g (0.18  mole) of freshly d i s t i l l e d phenyl acetone (Eastman) was added dropwise in 20 min with rapid stirring.  The mixture was warmed to room tempera-  ture and stirred vigorously for 15 min and then 20 min at 65°. (300 g) was added with stirring.  Ice  The mixture was extracted with five  100 ml portions of ether. The combined ether extracts were washed with two 100 ml portions of water to remove the glyme.  The ether layer  was dried over sodium sulphate and the ether was removed to give 20.8 g (54%) of crude product.  The v.p.c. (Ap J , 222°, 120 ml per min)  showed at least three products A, B, and C with retention times 18.6, 19.6 and 21.1 min with A and B overlapping considerably. •indicated the presence of both a 70:30 ratio respectively. unsaturated esters:  The n.m.r.  a,g- and B,Y-isomers in approximately  For the a,8- 144 and 145 and 3 , Y  i . r . 1715-1740 cm  1  -  (overlapping carbonyl stretch-  ing frequencies); n.m.r. 8.68 T (doublet J = 7.2 Hz) C-2 8,y-methyl, 8.0-8.4T(multiplets) vinyl methyls, 6.80 x (quartet J = 7.2 Hz) C-2 B,y-hydrogen, 6.54 T (broad singlet) a,8-benzylic hydrogens, 6.3-6.4 T  carbomethoxy methyls, 3.65 x (broad singlet) 3 , Y i n y l  hydrogen, 2.8-2.9 x aromatic hydrogens.  -V  Anal. Calcd. for C-.-H-.-O^  - 90 (mixture o f peaks A, B, and C ) :  C, 76.43; H, 7.90.  C, 76.20;  Found:  H , 8.10.  3-Methyl-4-benzyl-3-pentene-2-one, (E)- (128) and 3-Methyl-4-benzyl-3pentene-2-one, (Z) - (129) The g e n e r a l p r o c e d u r e a c c o r d i n g t o Vogel  (45) was used i n t h e  c o n v e r s i o n o f t h e e s t e r s 144 and 145 t o t h e i r c o r r e s p o n d i n g a c i d s and 147.  In a 100 ml f l a s k was r e f l u x e d 6 g o f t h e crude e s t e r s  and 145 i n 50 ml o f 20% sodium h y d r o x i d e f o r 2.2 h o u r s .  146 144  The crude  r e a c t i o n m i x t u r e was c o o l e d and e x t r a c t e d t w i c e w i t h e t h e r and then a c i d i f i e d w i t h hydrogen  chloride.  The r e s u l t i n g s o l u t i o n was e x t r a c t e d  t w i c e w i t h e t h e r which was d r i e d w i t h magnesium s u l p h a t e .  Removing t h e  e t h e r gave 2.1 g o f a white s o l i d c o n t a i n i n g the crude a c i d s 146 and  147. The c o n v e r s i o n o f t h e a c i d s t o t h e c o r r e s p o n d i n g methyl was done a c c o r d i n g t o t h e procedure o f DePuy (40) . necked round bottom  ketones  Into a 50 ml 3  f l a s k equipped w i t h a condenser, m e c h a n i c a l s t i r r e r ,  and n i t r o g e n was p l a c e d 2.1 g (0.011 mole) o f the crude a c i d s 146 and  147 and 25 ml o f anhydrous e t h e r . was added dropwise.  M e t h y l l i t h i u m i n e t h e r (0.022 mole)  A f t e r t h e a d d i t i o n , s a t u r a t e d ammonium  was added dropwise t o d e s t r o y t h e excess methyl  lithium.  chloride Two c l e a r  l a y e r s r e s u l t e d and t h e e t h e r l a y e r was s e p a r a t e d and washed w i t h a s a t u r a t e d ammonium c h l o r i d e s o l u t i o n , t w i c e w i t h water, and d r i e d magnesium s u l p h a t e . ketone. yield  The e t h e r was removed t o y i e l d  over  1.0 g o f crude  Bulb t o b u l b d i s t i l l a t i o n y i e l d e d 0.8 g (0.004 mole).  from t h e a c i d s was 38% and from phenyl acetone was 8%.  The The y i e l d  -  of  the acids The  A,  from phenyl  v.p.c.  (FFAP,  ketone  218°,  B,. a n d C w i t h r e t e n t i o n  m i n and w i t h overlapped mixture the  considerably,  8,y-isomer  and 129.  of  methyls,  6.54  benzylic  hydrogens.  (doublet hydrogen,  J  Anal. 8.57.  n.m.r.  x  (100  = 6 . 9 Hz)  ketones  (broad  x  MHz)  i n the crude  C-3 m e t h y l ,  (broad at  8.08,  8.14  a,0-isomers  Calcd.  for  C^H^O 82.51;  x  vinyl  and 8.41 and t o  the  The p r o c e d u r e  (Z)-  areas  x  1:2  cm  t i m e s as  1680  peaks  (100  a n d 1685  MHz)  cm"  7.81  (singlets)  C-3  respectively)  (carbonyl  1  acetyl methyl,  (quartet J  = 6 . 9 Hz)  stretching  8.80  x  C-3  hydrogen. x were  assigned to  a-methyl  (mixture of peaks A, H,  i.r.  n.m.r.  1710  128  119.  and 8 . 2 6  (singlet)  B,  of  the  the  two  8,Y-isomers.  a n d C) :  C,  82.93;  H,  8.66.  Methyl-2-methyl-3-phenyl-2-pentenoate, phenyl-2-pentenoate,  and  and 129:  8.25  6.77  singlet)  the  C,  118  i.r.  x  17.6  reaction  ketones  same r e t e n t i o n  singlets of  7.91  and  T h u s p e a k A was a s s i g n e d a s  128  ketone:  of  described for  ratio  of pyrazolines  8,Y-unsaturated  Found:  8,y  acetyl methyls,  and 6 . 5 9  Multiplets B-methyls  to  stretching frequencies);  (singlets)  3.58  a,8  16.3,  peaks  Peaks A and B  B and C have the  peaks  x  frequency);  respectively.  The  carbonyl  the  3:1:2  15.8,  B and C as t h e a , 0 - u n s a t u r a t e d  and 7 . 8 2  For  showed t h r e e m a i n  and peaks  the a,B-unsaturated  (overlapping  20%.  5 0 : 5 0 by n . m . r .  D and E from t h e p y r o l y s i s For  was  120 m l p e r m i n )  The  at  -  times of approximately  an a r e a r a t i o  was e s t i m a t e d  91  (E)-  (140)  and  Methyl-2-methyl-3-  (141)  according to  the preparation  Kinstle  of the  (39)  esters  was u s e d a s 144  and 145.  previously A bulb  to  bulb  - 92 -  d i s t i l l a t i o n o f t h e crude r e a c t i o n p r o d u c t gave a c l e a r c o l o u r l e s s l i q u i d whose v . p . c .  (FFAP 212°,  r e t e n t i o n time 10.7 minutes.  120 ml p e r min) showed one peak w i t h  The n.m.r. i n d i c a t e d t h a t t h e peak  c o n s i s t e d o f t h e two expected a , 8 - u n s a t u r a t e d e s t e r s  140 and 141 i n a  2:1 r a t i o r e s p e c t i v e l y . For t h e e s t e r s  140 and 141:  i . r . 1725 and 1735 cm"  1  (overlapping  s t r e t c h i n g f r e q u e n c i e s ) ; n.m.r. 6.29 and 6.77 T ( s i n g l e t s )  carbonyl  carbomethoxy methyls r e s p e c t i v e l y , 8.32 and 8.00 T ( s i n g l e t s ) a l p h a methyls r e s p e c t i v e l y , 9.05 T ( t r i p l e t J = 3.8 Hz) C-5 hydrogens, 6.56.6 T ( o v e r l a p p i n g Anal.  Calcd.  quartets)  f o r C^H-,0 •  C-4 hydrogens, 2.9 x a r o m a t i c hydrogens. C, 76.43; H, 7.90.  Found:  C, 76.02; H, 7.91.  3-Methyl-4-phenyl-3-hexene-2-one, ( E ) - (136) and 3-Methyl-4-phenyl-3hexene-2-one, ( Z ) -  (138)  A procedure, s i m i l a r t o the conversion and  145 t o t h e i r c o r r e s p o n d i n g a c i d s  o f t h e methyl e s t e r s 144  146 and 147, was used except  i t was n e c e s s a r y t o r e f l u x t h e r e a c t i o n m i x t u r e f o r 24 h o u r s .  that  The  n.m.r. i n d i c a t e d a 72:28 m i x t u r e o f t h e a c i d s w i t h the E_ isomer predominating.  For the acids  142 and 143:  n.m.r. 7.96 and 8.30 x  ( s i n g l e t s ) a l p h a m e t h y l s , 9.06 x ( t r i p l e t J = 3.8 Hz) C-5 hydrogens, 7.26  and 7.52 x ( q u a r t e t s )  C-4 hydrogens, -0.95 x (broad  singlet) acid  proton. The esters  conversion  o f the acids  142 and 143, d e r i v e d  140 and 141, was c a r r i e d out a c c o r d i n g  DePuy (40) and i s s i m i l a r t o t h a t d e s c r i b e d ketones 128 and 129.  The y i e l d  from t h e methyl  t o the procedure o f  f o r the preparation  o f 136 and 138 from t h e i r  a c i d s was 8.0%, and from propiophenone 0.6%.  o f the  corresponding  The y i e l d o f t h e a c i d s  - 93 from propiophencme was 7.5%. The  v.p.c.  (FFAP 215°,  two  overlapping  The  n.m.r. i n d i c a t e d t h a t  120 ml p e r min) showed as the major p r o d u c t  peaks A and B w i t h r e t e n t i o n  t h e two ketones 138 and 136 were p r e s e n t i n  a r a t i o o f 90:10 a l t h o u g h t h e i n i t i a l ratio  times 9.0 and 9.4 minutes.  c o r r e s p o n d i n g a c i d s were i n a  o f 72:28 r e s p e c t i v e l y . For  t h e ketones 136 and 138:  carbonyl stretching  frequencies);  i . r . 1680-90 cm  1  (overlapping  n.m.r. (100 MHz) 7.95 and 8.51 T  ( s i n g l e t s ) a c e t y l methyls r e s p e c t i v e l y , 8.34 and 8.10 T  (multiplets  a l p h a methyls r e s p e c t i v e l y , 9.00 and 9. 1 0 T ( t r i p l e t s J = 7.4 Hz) C-6 hydrogens, 7.53 x ( q u a r t e t Calcd.  for C  H 0: io ib 1 T  1 £  J = 7.4 Hz) C-5 hydrogens o f 138.  C, 82.93; H, 8.57.  Found:  Anal.  C, 83.05; H, 8.58.  - 94 BIBLIOGRAPHY  1.  K. von Auwers and F. Konig.  Ann. 496, 27 (1932).  2. . K. von Auwers and F. Konig.  Ann. 496, 252 (1932).  3. W.M. J o n e s .  J . Am. Chem. Soc.  8_0, 6687 (1958).  4.  W.M. J o n e s .  J . Am. Chem. Soc. 81_, 5153 (1959).  5.  W.M. Jones.  J . Am. Chem. Soc. 82_, 3136 (1960).  6.  D.E. McGreer.  7.  D.E. McGreer, W. Wai and G. C a r m i c h a e l .  J . Org. Chem. 25, 852 (1960). Can. J . Chem. _5_8, 2410  (1960). 8.  W.M. Jones and W.T. T a i . J . Org. Chem. 27_, 1030 (1962).  9.  W.M. Jones and W.T. T a i . J . Org. Chem. Z7, 1324 (1962).  10.  K.L. R i n e h a r t and T.V. Van Auken.  J . Am. Chem. Soc.  8_2, 5251 (1960)  11.  T.V. Van Auken and K.L. R i n e h a r t .  J . Am. Chem. Soc. 84_,  12.  D.E. McGreer, P. M o r r i s and G. C a r m i c h a e l .  3736 (1962)  Can. J . Chem. 41, 726  (1963). 13.  D.E. McGreer, N.W.K. C h i u , M.G. V i n j e and K.C.K. Wong.  Can. J .  Chem. 43, 1407 (1965). 14.  D.E. McGreer, N.W.K. C h i u and M.G. V i n j e .  Can. J . Chem. 43, 1398  (1965). 15.  D.E. McGreer and W.S. Wu. Can. J . Chem. 4J5, 461 (1967).  16.  I.M. M a s t e r s , Ph.D. T h e s i s , U n i v e r s i t y o f B r i t i s h Columbia, 1968.  17.  a) D.W. S e t s e r and B.S. R a b i n o v i t c h .  J . Am. Chem. Soc. 86,  565 (1964). b) A.T. Blades Can. J . Chem. 39, 1401 (1961).  18.  a) S. S e l t z e r and F.T. Dunne.  J . Am. Chem. Soc.  _b) S. S e l t z e r . J . Am. Chem. Soc. 85_, 14 (1963). J . Am. Chem. Soc.  83, 2625 (1961).  >  87_, 2628 (1965) . c) S. S e l t z e r .  - 95 -  19.  a) R.J. Crawford, R.J. Dummel and A. M i s h r a . J . Am. Chem. Soc. 87_, 3023 (1965).  b) R.J. Crawford, A. M i s h r a and R.J. Dummel.  •Chem. Soc. 88, 3959 (1966).  J . Am.  c) R.J. Crawford and A. M i s h r a .  J.  Am. Chem. Soc. 88, 3963 (1966). 20.  R.J. Crawford and D.M. Cameron.  J . Am. Chem. Soc. 88, 2589 (1966).  21.  R.J. Crawford and D.M. Cameron.  Can. J . Chem. 45_, 691 (1967).  22.  R.J. Crawford and G.L. E r i k s o n .  J . Am. Chem. Soc. 89, 3907 (1967).  23.  R.J. Crawford and L.H. A l i . J . Am. Chem. Soc. 89_, 3908  24.  B.H. A l - S a d e r and R.J. Crawford.  25.  C.G. Overberger and J.P. Anselme.  26.  C.G. O v e r b e r g e r , J.P. Anselme and N. Weinshenker. Soc. 86, 5364  27.  (1967).  Can. J . Chem. 46, 3301 (1968). J . Am. Chem. Soc. 86_, 658 (1964) J . Am. Chem.  (1964).  C.G. O v e r b e r g e r , N. Weinshenker and J.P. Anselme.  J . Am. Chem.  Soc. 87, 4119 (1965) . 28.  C.G. O v e r b e r g e r , R.E. Zangaro  and J.P. Anselme.  J . O r g . Chem. 31_,  2046 (1966). 29.  D.E. McGreer, R.S. McDaniel and M.G. V i n j e . 1389  30.  Can. J . Chem. 43_,  (1965).  a) J . Hamelin and R. C a r r i e .  Compte. Rend. 261, 5345  b) J . Hamelin and R. C a r r i e .  Compte. Rend.260, 3102 (1965).  c) J . Hamelin  and R. C a r r i e .  B u l l . Soc. Chim. F r . 2162 (1968).  d) J . Hamelin  and R. C a r r i e .  B u l l . Soc. Chim. F r . 2513 (1968).  e) J . Hamelin  and R. C a r r i e .  C u l l . Soc. Chim. F r . 2521 (1968).  31.  Y.Y. W i g f i e l d ,  Ph.D. T h e s i s ,  32.  A. M i s h r a and R.J. Crawford.  33.  E.L. A l l r e d  and R.L. Smith.  University  (1965).  o f B r i t i s h Columbia, 1969.  Can. J . Chem. 47, 1515 (1969). J . Am. Chem. Soc. 89, 7133 (1967).  - 96 -  34.  W.R. Roth and M. M a r t i n .  35.  D.E. McGreer and N.W.K. C h i u .  36. "37.  .M. K a r p l u s .  Ann. 702, 1 (1967). Can. J . Chem. 46, 2217 (1968).  J . Chem. Phys. 30, 11 (1959).  D.J. P a t e l , M.E.H. Howden and J.D. R o b e r t s . 3218  J . Am. Chem. Soc. 85_,  (1963).  38.  G.H. Schmid.  Can. J . Chem. 46, 3415 (1968).  39.  T.H. K i n s t l e , Ph.D. T h e s i s , U n i v e r s i t y o f I l l i n o i s , 1963.  40.  C H . DePuy, G.M. Dappen, K.L. E i l e r s  and R.A. K l e i n .  J . Org. Chem.  29, 2813 (1964). 41.  N.W.K. C h i u , M.Sc. T h e s i s , U n i v e r s i t y o f B r i t i s h Columbia, 1964.  42.  T. C u r t i u s and L. P f l u g .  J . p r . Chem. 44_, 535 (1892); Chem. Soc.  A b s t . 456 (1892). 43.  H. S t a u d i n g e r and A. Gaule.  Ber. 4 £ , 1906 (1916).  44.  D.S. Noyce and W.L. Reed.  45.  A . I . V o g e l , " P r a c t i c a l O r g a n i c C h e m i s t r y " , Longmans Green and  J . Am. Chem. Soc. 81_, 624 (1959).  Co. L t d . , New York, N.Y., 1943, page 921. 46.  M. Pomerantz and E.W. Abrahamson. (1966).  J . Am. Chem. Soc. 88, 3970  - 97 -  APPENDIX  Nomenclature  The  main purpose o f the f o l l o w i n g system o f nomenclature i s t o  unambiguously a s s i g n t h e s t e r e o c h e m i s t r y skeleton  about t h e t h r e e  o f c y c l o p r o p a n e s and 1 - p y r a z o l i n e s  at a l l t h r e e  carbon c e n t e r s .  carbon  that are uniquely  substituted  A "prime" used as a s u p e r s c r i p t on t h e  carbon number i n d i c a t e s s u b s t i t u e n t s on one s i d e o f t h e r i n g  system  whereas t h e l a c k o f a s u p e r s c r i p t i n d i c a t e s s u b s t i t u e n t s on t h e o t h e r side. For example, p y r a z o l i n e  118 becomes  3-acetyl-3 ,4'-dimethyl-5-  p h e n y l - l - p y r a z o l i n e and t h e C-5 isomer 119 becomes dimethyl-5'-phenyl-l-pyrazoline. dimethyl-2-phenyl  cyclopropane.  1  3-acetyl-3',4'-  Cyclopropane 126 i s c a l l e d  1-acetyl-l ,3' 1  

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