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The solution and solid state photochemistry of some substituted acetophenones Harkness, Brian Robert 1986

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THE SOLUTION AND SOLID STATE PHOTOCHEMISTRY OF SOME SUBSTITUTED ACETOPHENONES  by BRIAN ROBERT HARKNESS c.,  (Hons), University of British Columbia,  1984  A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE  in  THE FACULTY OF GRADUATE STUDIES DEPARTMENT OF CHEMISTRY  We accept this thesis as conforming to the requi red_standard  They'll ni versity of British Columbia August, 1986 © Brian Robert Harkness, 1986  In p r e s e n t i n g  this  thesis i n partial  fulfilment of the  r e q u i r e m e n t s f o r an a d v a n c e d d e g r e e a t t h e U n i v e r s i t y of B r i t i s h Columbia, I agree that it  freely  the Library shall  a v a i l a b l e f o r r e f e r e n c e and study.  agree t h a t p e r m i s s i o n f o r extensive for  thesis  s c h o l a r l y p u r p o s e s may be g r a n t e d by t h e h e a d o f my  understood that financial  copying o r p u b l i c a t i o n o f t h i s  gain  Department o f The U n i v e r s i t y o f B r i t i s h 1956 Main M a l l V a n c o u v e r , Canada V6T 1Y3 At/v^-frr  It is thesis  s h a l l n o t be a l l o w e d w i t h o u t my  permission.  Date  I further  copying of t h i s  d e p a r t m e n t o r by h i s o r h e r r e p r e s e n t a t i v e s . for  make  3)^,  Columbia  written  ii  ABSTRACT A series of a-methyl-a-cycloalkyl- and a-cycloalkyl-parasubstituted acetophenones have been synthesized.  These compounds were  found to react photochemically in the s o l i d state to give c y c l i z a t i o n and cleavage products as expected for a Norrish Type II reaction. It has been found that a-methyl substitution of a - c y c l o a l k y l para-carboxyacetophenones  (cyclohexyl and cyclooctyl) results in changing  the hydrogen abstraction t r a n s i t i o n state from boatlike to c h a i r l i k e . This result is based on the assumption that the abstraction geometry is similar to the geometry of the ground state ketone as determined by X-ray crystallography. The differences in the ratios of c y c l i z a t i o n to cleavage in the s o l i d state as compared to solution wer found to be no greater than 10% for most of the ketones studied.  This suggests that formation of  c y c l i z a t i o n and cleavage products are topochemically allowed in the s o l i d state.  Alternatively,  the reaction may not be under topochemical control,  however, the high melting points of the compounds studied tend to support the f i r s t  possibility.  a-Methylation of a-cyclopentyl-para-carboxyacetophenone the percent cleavage from 100% to 45%.  decreased  This result is l i k e l y due to a  change in the geometry of the starting ketone which occurs upon a-methylat ion. Solid state photolysis of acetophenones (cyclooctyl  a-cycloalkyl-para-substituted  and cycloheptyl) results in almost exclusive  formation of the trans-cyclobutanol.  This result has been attributed to a  r e s t r i c t i o n of the motions required for cis-cyclobutanol s o l i d state.  formation in the  iii  TABLE OF CONTENTS  Page ABSTRACT TABLE OF CONTENTS LIST OF FIGURES  ii iii iv-ix  LIST OF TABLES  x,ix  LIST OF ABBREVIATIONS  xii  ACKNOWLEDGEMENTS  xiii  INTRODUCTION  1  RESEARCH OBJECTIVES  35  DISCUSSION  41  Synthesis  41  Identification of Photoproducts  52  Geometry of Hydrogen Abstraction  74  Ratios of Cyclization to Cleavage  79  The Effect of Different Media on  99  the Cyclobutanol Ratios Quantum Yields and Rate Studies  106  EXPERIMENTAL  114  General  114  Synthesis of Starting Materials  116  Photochemical Studies  134  BIBLIOGRAPHY  161  APPENDIX  166  iv  LIST OF FIGURES Figure  Title  Page  1  I r r a d i a t i o n o f 2-hexanone  1  2  Type I e l i m i n a t i o n from simple ketones  2  3  P h o t o l y s i s of 2-pentanone  2  4  Formation of a 1,4 b i r a d i c a l  3  5  Formation of propene-2-ol from 2-pentanone  4  6  Photochemical  5  7  Physical  8  Energy diagram f o r s i n g l e t and t r i p l e t n,n excited states  7  9  T r a n s i t i o n s t a t e s f o r hydrogen a b s t r a c t i o n by an a l k o x y r a d i c a l and ketone t r i p l e t  9  e x c i t a t i o n of a c a r b o n y l  d e s c r i p t i o n of an n , n  group  excited state  6  10  Parameters d e f i n i n g s p a t i a l r e l a t i o n s h i p o f the " n " o r b i t a l to the a b s t r a c t a b l e hydrogen atom  11  11  McLafferty  rearrangement i n s t e r o i d s  12  12  McLafferty  rearrangements of ketones  13  13  P h o t o r e a c t i o n s of valerophenone  14  14  S o l v e n t e f f e c t s on the b e h a v i o r of the 1,4 b i r a d i c a l of valerophenone  15  15  Photochemical r a c e m i z a t i o n of ( 4 S ) ( + ) - 4 - m e t h y l - 1 - p h e n y l hexanone  17  16  p - O r b i t a l geometries c o n s i d e r e d i d e a l for cleavage  21  17  P h o t o l y s i s of 1-adamantyl  22  18  Suggested c o n f o r m a t i o n of the 1,4 b i r a d i c a l of a simple a l k y l phenyl ketone  acetone  23  V  Figure  Title  Page  19  Suggested geometry for cyclobutanol formation  24  20  S t e r e o s e l e c t i v i t y of cyclobutanol formation  25  21  Two d i f f e r e n t conformers of a molecule giving r i s e to d i f f e r e n t photoproducts  26  22  The photochemistry of a-methyl-cyclopentyl phenyl ketone  28  23  The photochemistry of a-methyl-cyclohexyl phenyl ketone  29  24  The photochemistry of ene-dione 1  32  25  p-hydrogen abstraction geometry for ene-diones  33  26  The photochemistry of a-cyclohexylp-chloroacetophenone  35  27  The photochemistry of 7-tridecanone  37  28  a - C y c l o a l k y l - p a r a - s u b s t i t u t e d acetophenones with a v a i l a b l e y-hydrogen  38  29  Design of the a-methyl ketones  39  30  Design of the ketones lacking an a-methyl substituent  39  31  Design of the ketones bearing v a r i a b l e para-substituents  40  32  Synthesis of cyclooctyl acetic acid  41  33  Synthesis of cycloheptyl acetic acid  42  34  Synthetic routes towards the synthesis of a-and para-substituted-a-cycloalkyl acetophenones  44  35  Products of F r i e d e l - C r a f t s a c y l a t i o n of substituted benzenes using c y c l o o c t y l acetyl chloride and aluminum t r i c h l o r i d e as c a t a l y s t  45  vi  Figure  Title  Page  36  McLafferty rearrangement of a-cyclooctyl-para-substituted acetophenones  46  37  The synthesis of a-cyclooctyl-paracyano and para-carboxyacetophenones  48  38  a-Cycloalkyl-para-cyanoacetophenone derivatives and their melting points  49  39  a-Cycloalkyl-para-carboxyacetophenone derivatives and their melting points  49  40  a-Cycloalkyl-para-carbomethoxyacetophenone derivatives and their melting points  51  41  Products from the photolysis of a-cycloalkyl-para-chloroacetophenones  53  42  I.U.P.A.C. numbering scheme for bicyclo [n.2.0] alkanols  54  43  The photolysis of some a - c y c l o o c t y l para-substituted acetophenones  55  44  Experimental and l i t e r a t u r e melting points of para-substituted acetophenones  56  45  Retro 2+2 fragmentation pattern observed for [6.2.0] cyclobutanols  57  46  400 MHz H nmr spectra of the c i s - and trans-cyclobutanols derived from a-cycloocty1-para-cyanoacetophenone  47  *H nmr spectrum of the cis-cyclobutanol decoupled at 0.38 ppm  61  48  Photolysis of a-methyl-a-cyclooctyl-paracarboxyacetophenone  64  H nmr of the major cyclobutanol isolated from photolysis of a-methyl-a-cyclooctylpara-carboxyacetophenone  66  49  X  l  59  vi i  Figure 50  L  51  L  Title  Page  H N.O.E. difference spectra of the cyclobutanol shown in f i g u r e 49  67  H nmr of the second cyclobutanol i s o l a t e d from photolysis of a-methyla-cycl ooctyl-para-carboxyacetophenone  68  H N.O.E. difference spectra of the second cyclobutanol derived from a-methyl-a-cyclooctyl-paracarboxyacetophenone  69  H nmr spectrum of the major cyclobutanol derived from photolysis of a-methyl-acycl ohexyl -para-carboxyacetophenone  71  H nmr spectrum of the major cyclobutanol derived from a-methy 1 - a - c y c l o p e n t y l para-carboxyacetophenone  73  52  1  53  l  54  1  55  Boatlike and c h a i r l i k e abstraction geometries  77  56  Stereodiagrams f o r boatlike and c h a i r l i k e abstraction geometries  79  57  Photoproducts derived from a-methyl-acycl oalkyl -para- carboxyacetophe nones  80  58  % Cleavage from the photolysis of a-methyl-a-cycloalkyl acetophenones in benzene, a c e t o n i t r i l e , and the s o l i d state  59  The photochemistry of ene-dione 1 in benzene and the s o l i d state  82  60  % Cleavage from the photolysis of a - c y c l oal kyl-pa ra-carboxy acetophenones i n polar solvent, benzene and the s o l i d state  83  61  % Cleavage vs para-substituent in various media f o r the a - c y c l o o c t y l acetophenones  84  62  % Cleavage in the s o l i d state as compared ' to the values of 9 and 0 f ° several a - c y c l oalkyl -para-chloroacetophenones  86  1  2  r  81  vi i i  Figure  Title  Page  63  Magnitude of the angle n as the c y c l o a l k y l ring size increases from 4 to 8 for the a-cycloalkyl-para-chloroacetophenones  88  64  Bond r o t a t i o n s required for the formation of the trans-cyclobutanol  89  65  Calculated s t r a i n energies for some b i c y c l o [n.2.0] alkanes  92  66  Photolysis of cyclobutyl phenyl ketone  93  67  % Cleavage recorded for non-methylated and a-methyl-a-cyclopentyl phenyl ketones  95  68  The b i r a d i c a l generated from a-methyla-cyclopentyl-para-carboxyacetophenone as viewed down the a-p carbon bond  96  69  Two conformers of the b i r a d i c a l generated from a-cyclopentyl-para-carboxyacetophenone  98  70  The r a t i o of trans- to c i s - c y c l o b u t a n o l s formed from the photolysis of a - c y c l o o c t y l para-chloroacetophehone in d i f f e r e n t media  100  71  Geometries of the c i s - and trans-cyclobutanols  101  72  Packing diagram of a - c y c l o o c t y l para-chloroacetophenone  102  73  Percentage of the major cyclobutanol as a function of the t o t a l cyclobutanol produced from photolysis of a - m e t h y l - a - c y c l o a l k y l para-carboxyacetophenones in various media  104  74  X-ray c r y s t a l structure of a-methyl-acyclooctyl-para-carboxyacetophenone  106  75  Total product quantum y i e l d s for several substituted acetophenones in benzene  107  76  Y-Hydrogen and P-hydrogen abstraction distances and angles for a-methyl-ac y c l o o c t y l and a-methyl-a-cyclohexylpara-carboxyacetophenones  109  ix  Figure  Title  Page  77  Stern-Volmer plots for a - c y c l o o c t y l - p a r a cyanoacetophenone and a - c y c l o h e p t y l - p a r a cyanoacetophenone  111  78  Hydrogen abstraction rate constants for valerophenone and a r i g i d b i c y c l i c ketone  113  X  LIST OF TABLES Table  Title  Page  I  The photochemistry of a - s u b s t i t u t e d valerophenones in benzene  18  II  The photochemistry of p-substituted butyrophenones in benzene  19  III  The photochemistry of y - s u b s t i t u t e d butyrophenones in benzene  20  IV  Hydrogen abstraction geometries for several substituted acetophenones  75  The s t r a i n energies for some cycloalkanes and the c a l c u l a t e d s t r a i n energies for some cycloalkenes  91  V  VI  Product r a t i o s from the photolysis of ketone (9)  138  VII  Product r a t i o s from the photolysis of ketone (20)  140  VIII  Product r a t i o s from the photolysis of ketone (21)  142  IX  Product r a t i o s from the photolysis of keto-acid (26)  145  X  Product r a t i o s from the photolysis of keto-acid (27)  146  XI  Product r a t i o s from the photolysis of keto-acid (28)  149  XII  Product r a t i o s from the photolysis of keto-acid (29)  151  XIII  Product r a t i o s from the photolysis of keto-acid (30)  153  XIV  Product r a t i o s from the photolysis of keto-acid (31)  155  XV  Product r a t i o s from the photolysis of keto-ester (32)  155  xi  Title Product r a t i o s from the photolysis of keto-ester (33) Product r a t i o s from the photolysis of keto-ester (34) Product r a t i o s from the photolysis of keto-ester (35) Product r a t i o s from the photolysis of keto-ester (36) Product r a t i o s from the photolysis of keto-ester (37) Quantum y i e l d s for ketones 20, 21, 33-37, in benzene Values of $ / $ and quencher concentrations for ketones 20 and 21 0  xi i  LIST OF ABBREVIATIONS  Anal.  micro analysis  °C  degrees celcius  cone.  concent r a t i on  gc  gas l i q u i d chromatography  1  nmr  H  proton nuclear magnetic resonance  i r  i n f r a r e d spectroscopy  lit.  literature  m  parent ion  max  maximum  m/e  mass/charge  mi n  mi nute(s)  mp  melting point  ms  mass spectroscopy  NOE  Nuclear Overhauser Effect  rt  retention time  s  seconds  uv  ultraviolet  +  0  ratio  spectroscopy  phenyl group  abbreviations f o r m u l t i p l i c i t i e s  of H nmr signals  s  singlet  d  doublet  t  triplet  q  quartet  dd  doublet of doublets  m  multiplet  1  xi i i  ACKNOWLEDGEMENTS  I wish to express my sincere thanks to Professor John Scheffer f o r his excellent guidance and helpful suggestions throughout the course of my research and the preparation of t h i s t h e s i s .  I also thank Stephen Evans  and Professor J . T r o t t e r , without whom t h i s work would not be possible.  I  thank Omkaram Nalamasu f o r allowing me to quote some of his experimental results.  I also wish to thank a l l of the members of Dr. Scheffer's and  Dr. T r o t t e r ' s research group, past and present, who have made the l a s t two years very enjoyable ones. F i n a l l y , the assistance of the elemental a n a l y s i s , nmr, and mass spectroscopy s t a f f is appreciated.  To rty Parents  1  INTRODUCTION  One of the more s i g n i f i c a n t events i n photochemical occurred during the early 1930's.  history  At t h i s time, a group headed by  R. Norrish i r r a d i a t e d a sample of 2-hexanone with u l t r a v i o l e t l i g h t and unexpectedly obtained propene and acetone as products (figure l ) . 1  Figure 1:  I r r a d i a t i o n of 2-hexanone  This p a r t i c u l a r photochemical transformation has become known as the Norrish Type II reaction.  P r i o r to the photolysis of 2-hexanone, by  N o r r i s h , i t was known that i r r a d i a t i o n of simpler ketones resulted in the extrusion of carbon monoxide and the formation of an alkane from the alkyl radicals (figure 2 ) .  The photochemical transformation r e s u l t i n g in  homolysis of the bond between the carbonyl-carbon and an a-carbon atom  2  0  hv  > C O + «CH, + RCH « 0  R  Figure 2:  Type I e l i m i n a t i o n from simple ketones  has become known as the Norrish Type I r e a c t i o n . Early studies of the Norrish Type II reaction found that simple a l i p h a t i c ketones bearing y-hydrogen atoms formed a ketone and an o l e f i n as the products of u l t r a v i o l e t i r r a d i a t i o n .  The l i s t of products grew in  1958 when N.C. Yang discovered that i r r a d i a t i o n of 2-pentanone r e s u l t s in the formation of three products, these being acetone, an o l e f i n and a cyclobutanol  (figure 3 ) . 2  As the r e s u l t of his studies of 2-pentanone,  CH  Figure 3:  Photolysis of 2-pentanone  3  Yang proposed that the Norrish Type II process involved an i n i t i a l  1,5  hydrogen atom transfer r e s u l t i n g in the formation of a 1,4 b i r a d i c a l ( f i g u r e 4). This b i r a d i c a l could close to form a cyclobutanol or cleave  OH  Hi  Figure 4:  Formation of a 1,4 b i r a d i c a l  to form an o l e f i n and an e n o l . the observed ketone.  The enol could rapidly tautomerize to form  To v e r i f y the hypothetical enol intermediate,  J . N . P i t t s monitored the i n f r a r e d spectra of concurrently photolyzed 2-pentanone g a s . 3  Infrared analysis was able to detect propene-2-ol which  slowly tautomerized to acetone ( f i g u r e 5 ) .  Evidence for the involvement  of a y-hydrogen was obtained when the photolysis of 2-hexanone-5-d resulted in the formation of a c e t o n e - d ^ .  2  Yang also noticed a large  isotope e f f e c t on the rate of y-hydrogen abstraction by the carbonyl  4  tautermerize + other  Figure 5:  0  products  Formation of propene-2-ol from 2-pentanone  oxygen atom . 5  With all of the prior data in mind, the definition of the Norrish Type II reaction was expanded to describe a process by which a ketone, containing an abstractable y-hydrogen atom, undergoes, upon electronic excitation, a 1,5 hydrogen transfer to yield both bond cleavage and cyclization products. The photochemical abstraction of a y-hydrogen atom is believed to occur from the n,n excited state of the carbonyl group (figure 6 ) . 6  This  transition involves the excitation of an electron from the doubly occupied  *  n-orbital to the n -orbital.  This transition can be achieved using  ultraviolet radiation with a wavelength of 270-350 nm.  It has been  5  fx  n  *y  2  (  Figure 6:  o  orbital  * )  Atomic orbital diagram for the excitation of a carbonyl group  * postulated that the n,n  excitation of carbonyl compounds produces an  alkoxy radical-like excited state in which an electron deficiency on the oxygen atom induces diradical character on the carbonyl group (figure 7 ) > . 7  8  6  to*  11  R  R  R  —  1  E  ±±  R  ** >  JL_  n  i£  dlradlcal  Figure 7:  Valence bond diagram for the n,n  excited state  * The n,n multiplicities.  excited state diradical can exist in either of two The radical  electrons can have the same spin to produce  the t r i p l e t excited state or can have opposite spins to produce the singlet excited state. * the n,n  When an electron i s excited from the n  excited state i t w i l l  configuration.  initially  2  orbital  to  exist in the singlet  The singlet excited state can then undergo one of several  possible transformations (figure 8 ) . 6  7  K C .r c JC -  "St C  !  4-  {  - i  So' I  c .£ i i «•  S  5  5 w  c  8  o  t I  5  "5c, "SI c  Figure 8:  c  u  o -9  T3  o w u  V  _5  I I  c M  E «J  - Singlet i  Singlet 01 configuri  M w  c  > c c  i i • i  £-  fc  w.  e  Z K  V  c *  i I  i i  .£ t c  £  J£ ~  S  5  ri l  r-  J  e t Mi C cc t S  t  E  w  c c c  c o  .£• *  c  I  -  C  Energy diagram for s i n g l e t and t r i p l e t n,n  excited s t a t e s  6  1.  The s i n g l e t can intersystem cross to the t r i p l e t  2.  The molecule can undergo a photochemical reaction from the s i n g l e t state.  state.  8  3.  The excited s i n g l e t can revert back to the ground state by e i t h e r a non-radiative decay t r a n s i t i o n or by emitting l i g h t in the form of fluorescence.  I f the s i n g l e t does intersystem cross to the t r i p l e t excited state i t can undergo one of two possible transformations. 1.  The molecule can undergo a photochemical reaction from the t r i p l e t state.  2.  The excited t r i p l e t can revert back to the ground state by e i t h e r a non-radiative decay t r a n s i t i o n or by emitting l i g h t in the form of phosphorescence. •  I t has been well established that both s i n g l e t and t r i p l e t n,n a l i p h a t i c ketones can undergo Type II e l i m i n t a i o n  9 _ 1 2  » . 1 3  states of  Cyclobutanol  formation from a l i p h a t i c ketones occurs mostly from the t r i p l e t  state . 1 4  Wagner studied the e f f e c t s of piperylene (1,3 pentadiene) on the type II photoreactions of a l i p h a t i c ketones in s o l u t i o n . 1 4  Piperylene i s an  e f f i c i e n t quencher which accepts energy from t r i p l e t excited k e t o n e s . 13  The excited t r i p l e t ketones transfer t h e i r excited state energy to the diene and revert back to the ground state without forming products. Wagner found that the Stern-Volmer p l o t (see appendix 1) of ® /$, where $ Q  Q  i s the quantum y i e l d in benzene and $ i s the quantum y i e l d in benzene at a p a r t i c u l a r quencher concentration, against the concentration of piperylene was non-linear for a l i p h a t i c ketones as even high concentrations of quencher f a i l e d to t o t a l l y quench the photoelimination r e a c t i o n .  The most  obvious explanation for t h i s r e s u l t i s that the elimination reaction proceeds from both the s i n g l e t and t r i p l e t excited s t a t e s .  9  The behavior of aromatic ketones i s s l i g h t l y d i f f e r e n t from that of a l i p h a t i c ketones i n that intersystem crossing from the s i n g l e t to the t r i p l e t state i s 100% e f f i c i e n t ,  and both e l i m i n a t i o n and c y c l i z a t i o n  occur only from the t r i p l e t state *. 11  Wagner found that at even high  concentrations of quencher the Stern-Volmer plot is s t i l l  linear .  rapid rate of intersystem crossing f o r a l k y l phenyl ketones i s i n the lack of any observable s i n g l e t state  The  1 5  reflected  reactivity.  * The geometry of hydrogen abstraction by the t r i p l e t n,n  excited  state i s of p a r t i c u l a r importance in deciding whether a y-hydrogen atom can be abstracted by the electron d e f i c i e n t n-orbital oxygen.  of the carbonyl  Wagner has suggested that 1,5 hydrogen transfers i n a c y c l i c  systems r e f l e c t a t o r s i o n f r e e , c h a i r l i k e , six-membered c y c l i c t r a n s i t i o n state (figure 9 )  1 7  .  alkoxy r a d i c a l  Figure 9:  ketone  triplet  T r a n s i t i o n states f o r hydrogen abstraction by an alkoxy and ketone t r i p l e t  radical  10  Hesse has shown t h a t t h e C-H-0 a n g l e must be c o n s i d e r a b l y than 180° f o r hydrogen t r a n s f e r s by a l k o x y r a d i c a l s  1 8  .  less  S t r a i n present  in  t h e c y c l o h e p t a n e - and c y c l o p e n t a n e - 1 i k e t r a n s i t i o n s t a t e s f o r 1,6 and 1,4 hydrogen t r a n s f e r s  has been used as an e x p l a n a t i o n f o r t h e r a r i t y of 6 and  0 hydrogen a b s t r a c t i o n by t h e e x c i t e d k e t o n e .  This result  accordance w i t h t h e w e l l known o r d e r 1,5 > 1,6 » i n t r a m o l e c u l a r hydrogen t r a n s f e r s  in acyclic  is  in  1,4 i n t h e r a t e s of  systems * . 1 8  The  1 9  involvement of a c h a i r l i k e a b s t r a c t i o n geometry i s however not an a b s o l u t e requirement f o r v-hydrogen a b s t r a c t i o n . recently  S c h e f f e r and T r o t t e r  shown t h a t 1,5 hydrogen t r a n s f e r s can a l s o o c c u r from a b o a t l i k e  reactant geometry . 20  F u r t h e r m o r e , S c h e f f e r and T r o t t e r have attempted to  c o r r e l a t e the a b s t r a c t a b i l i t y r e l a t i o n s h i p of t h e c a r b o n y l  of a v-hydrogen atom w i t h t h e "n" o r b i t a l  spatial  to the v - h y d r o g e n . 2 1  geometric parameters have been d e f i n e d and t h e s e d e s c r i b e t h e r e l a t i o n s h i p of the " n " o r b i t a l They a r e d e f i n e d as f o l l o w s •A ,  have  Three spatial  to t h e hydrogen atom being a b s t r a c t e d .  ( f i g u r e 10):  t h e d i s t a n c e between t h e a b s t r a c t i n g oxygen atom and t h e a b s t r a c t a b l e hydrogen atom;  T_ ,  t h e a n g l e d e f i n e d by t h e o x y g e n * h y d r o g e n v e c t o r and i t s  projection  on t h e mean p l a n e of the c a r b o n y l group which c o n t a i n s t h e oxygen n-orbital); A_ ,  t h e a n g l e between t h e c a r b o n y l c a r b o n , t h e c a r b o n y l oxygen and a b s t r a c t a b l e hydrogen atom.  11  Figure 10:  Parameters defining s p a t i a l r e l a t i o n s h i p of the "n" o r b i t a l the abstractable hydrogen atom  to  Scheffer and Trotter have suggested that the ideal geometry for hydrogen abstraction occurs when -c i s 0° and A i s 90-120°.  The l e a s t favourable  geometry occurs when T approaches 90° and A approaches 0° or 180°. Scheffer and T r o t t e r have also suggested that the distance for hydrogen abstraction by oxygen has an upper l i m i t of approximately 2.7 A, which i s the sum of the Van der Waals r a d i i of the oxygen and hydrogen atoms > . 2 1  2 2  The mass spectroscopy analogue of the Norrish type II r e a c t i o n , the McLafferty rearrangement, also involves a 1,5 hydrogen transfer to the r a d i c a l - c a t i o n of the carbonyl group.  Through the use of r i g i d s t e r o i d a l  ketones and molecular models, Djerassi has determined an upper l i m i t of 1.8 A for the distance between the abstracting oxygen and abstractable hydrogen atoms (figure l l )  2 3  .  The magnitude of the angle t has also been  12  m/e  F i g u r e 11:  259  M c L a f f e r t y rearrangement i n s t e r o i d s  i m p l i c a t e d i n the a b i l i t y of the c a r b o n y l oxygen ,to a b s t r a c t a y-hydrogen i n t h e M c L a f f e r t y rearrangement.  Ketone (1)  M c L a f f e r t y rearrangement whereas k e t o n e (2)  ( f i g u r e 12)  d i d not undergo  was o b s e r v e d t o r e a r r a n g e .  T h i s r e s u l t was e x p l a i n e d on t h e b a s i s of an u n f a v o u r a b l e t a n g l e of 80° i n k e t o n e (1) ketone (2). and (2)  as opposed t o the more f a v o u r e d T a n g l e of 50° i n From m o l e c u l a r models, the d i s t a n c e d f o r both k e t o n e s  was e s t i m a t e d t o be 1.6  A . 21+  (1)  The a n g l e x was a l s o o b t a i n e d from  m o l e c u l a r models of the a c t u a l systems.  13  Ketone 1  Figure 12:  Ketone (1) does not undergo McLafferty rearrangement whereas ketone (2) does  Following the abstraction of a y-hydrogen atom, the 1,4 b i r a d i c a l intermediate can undergo three d i f f e r e n t chemical (figure 1.  transformations  13) . 2 5  The y-carbon radical can reabstract the hydrogen on the hydroxy radical and revert back to the ground state ketone.  2.  The a-p carbon bond can cleave to form an alkene and an e n o l . enol can tautomerize to form the observed ketone.  3.  The 1,4 b i r a d i c a l can undergo a ring closure reaction to form a cyclobutanol.  The  14  0  Figure 13:  Photoreactions of valerophenone  Wagner has studied the effects of polar and non-polar solvents on the behavior of the 1,4 b i r a d i c a l generated by photolysis of valerophenone.  It was found that the quantum y i e l d f o r t o t a l  photoreacti on rose from 0.45 i n non-polar solvents to unity in alcohols and a c e t o n i t r i l e . 1 6  The polar solvent effect is not due to a change i n  the excited state of the ketone since the n,n  t r i p l e t has a sharply  decreased dipole moment and only weak dipole interactions are expected  26  *  2 7  .  Rather, the increased quantum y i e l d observed in polar  solvent has been a t t r i b u t e d to strong hydrogen bonding between the solvent and the hydroxyl group of the 1,4 b i r a d i c a l .  The hydrogen bonding  15  s t a b i l i z e s the hydroxy r a d i c a l impeding reverse hydrogen abstraction by the y-carbon r a d i c a l .  The net r e s u l t i s that a l l of the 1,4 b i r a d i c a l s  polar solvent y i e l d photoproducts.  This i s in contrast to the r e s u l t s  obtained from photolysis in non-polar solvents where the majority of the b i r a d i c a l s revert back to the ground state ketone ( f i g u r e 14). Photolysis in polar solvents also has an e f f e c t on the r a t i o s of cis-  and trans-l-phenyl-2-methylcyclobutanol.  In a non-polar solvent,  such as hexane, a 5:1 t r a n s : c i s r a t i o of cyclobutanols i s observed.  Non-Polar Solvent  Figure 14:  Polar  Solvent  Solvent e f f e c t s on the behavior of the 1,4 b i r a d i c a l of valerophenone  In  in  16  a p o l a r solvent, such as t e r t - b u t a n o l , the t r a n s : c i s r a t i o f a l l s t o 2 : 1 . 1 6  This e f f e c t has been explained i n terms of an increase i n the s t e r i c bulk of the hydroxy group due to hydrogen bonded solvent molecules.  The s t e r i c  interference between the hydrogen bonded hydroxyl group and the 2-methyl group in the t r a n s i t i o n state f o r the formation of the trans-isomer results in an increase i n the cis-isomer product. Further evidence f o r the involvement of a reverse hydrogen a b s t r a c t i o n step was obtained from the study of a l k y l phenyl ketones containing a c h i r a l y-carbon atom.  Wagner found that i r r a d i a t i o n of  (4s)-(+)-4-methyl-l-phenyl-l-hexanone, of o p t i c a l a c t i v i t y .  in benzene, results in a rapid loss  The sample was i r r a d i a t e d to a conversion of 16% and  the i s o l a t e d unreacted ketone was found t o have undergone 31% racemization . 28  A s i m i l a r photochemical racemization of  (4s)-(+)-5-methyl-2-heptanone was also observed by Y a n g . 11  The  racemization of the y-carbon was postulated to occur in the f o l l o w i n g sequence of events (figure 15). 1.  Formation of a 1,4 b i r a d i c a l .  2.  Racemization of the y-carbon.  3.  Reverse hydrogen abstraction by the y-carbon forming the ground state ketone.  17  ]. Rotation  *0  2. Rever»e Abstraction  F i g u r e 15:  Photochemical hexanone  r a c e m i z a t i o n of  (4s)-(+)-4-methyl-l-phenyl  In a d d i t i o n t o r e v e r s e hydrogen a b s t r a c t i o n , the 1,4  biradical  i n t e r m e d i a t e can a l s o g i v e r i s e t o e l i m i n a t i o n and c y c l i z a t i o n To d a t e , l i t t l e  i s known about the n a t u r e of the 1,4  products.  biradical  i n t e r m e d i a t e and the f a c t o r s c o n t r o l l i n g the r a t i o of c y c l i z a t i o n cleavage.  Stephenson and Brauman have suggested t h a t the  to  stereochemistry  o f p r o d u c t f o r m a t i o n i s determined by how w e l l c y c l i z a t i o n and cleavage compete w i t h bond r o t a t i o n s  2 9  made e x t e n s i v e i n v e s t i g a t i o n s  .  Wagner » » 2 5  3 0  3 1  and L e w i s  3 2  *  3 3  have  i n t o the e f f e c t s o f a, p and y s u b s t i t u e n t s  on the p h o t o c h e m i s t r y of s i m p l e a l k y l  phenyl k e t o n e s .  I t was hoped t h a t  the study o f these systems would b r i n g t o l i g h t the p r i n c i p l e s  which  govern the r a t i o of c y c l i z a t i o n to c l e a v a g e , the r a t e s of hydrogen a b s t r a c t i o n and the s t e r e o c h e m i s t r y  of the p r o d u c t s .  Lewis has shown t h a t a-methyl s u b s t i t u e n t s can g r e a t l y the percentage o f c y c l i z a t i o n valerophenone . 3 3  p r o d u c t s from the p h o t o l y s i s  increase  of  For example, a-methyl and a,a-dimethyl s u b s t i t u t i o n  of  valerophenone i n c r e a s e s the percentage of c y c l i z a t i o n from 22 t o 43 and  18  71% respectively (table I ) .  P-Substituents have been observed to have a  variable e f f e c t on the photochemistry of butyrophenone (table I I ) .  For  example, photolysis of buty rophenone results i n 10% c y c l i z a t i o n which  Ketone  Table I:  (J> Total  7. Cyclization  lc^ X 10  8  22 (18)  0.42  1.4  43  0.29  1.3  71  0.074  I.I  sec"  1  The photochemistry of a-substituted valerophenones in benzene (brackets indicate results obtained by Wagner )  3  25  increases t o 15% f o r P-methyl butyrophenone but decreases t o 3% f o r P,p-dimethyl buty rophenone.  The e f f e c t s of y-substituents on the  percentage of c y c l i z a t i o n f o r y - s u b s t i t u t e d butyrophenones can also be v a r i a b l e , with the changes being less dramatic than those observed f o r a and p s u b s t i t u t i o n (table  III)  2 5  .  3 5  .  19  %  Ketone  0^C Table I I :  Cj> T o t a l .  X 10  10  0.40  0.076  15  0.31  0.20  3  0.18  0.54  Cyclization  8  sec"  The photochemistry of p-substituted butyrophenones in benzene 33  1  20  Ketone  %  0  0 0 0 Table I I I :  Cyclization  Total  kjj X 1 0  8  sec"  12 (10)  0.38  0.076  18 (22)  0.40  1.25  0.28  5.0  1  The photochemistry of y - s u b s t i t u t e d butyrophenones i n benzene (brackets indicate results obtained by L e w i s ) 25  Wagner has suggested that cleavage of a 1,4 bi radical  33  intermediate  can occur most e f f i c i e n t l y when the molecule is in a conformation i n which the two "p" o r b i t a l s are p a r a l l e l to the C-C o-bond being broken (figure 1 6 ) » . 2 5  3 1  21  0 Transoid  Figure 16:  Gauche  Cisoid  p-Orbital geometries considered ideal for cleavage  For example, i t has been suggested that the lack of type II cleavage from 1-adamantyl  acetone may be the r e s u l t of an unfavourable o r i e n t a t i o n of  the radical "p" o r b i t a l s with the a-p carbon bond being cleaved (figure 1 7 ) . 3 6  A l t e r n a t i v e l y , the lack of cleavage products may also  r e f l e c t the high s t r a i n energy involved in the formation of adamantene i f cleavage were to occur.  22  Figure 17:  Photolysis of 1-adamantyl  acetone  Wagner has postulated that the bi radical intermediate, formed from the photolysis of alkyl phenyl ketones, e x i s t s in the conformation shown in f i g u r e 18.  In t h i s model the "p" o r b i t a l on the y-carbon is p a r a l l e l  t o , and the benzylic "p" o r b i t a l perpendicular to the a,p C-C b o n d . 25  In  order f o r cleavage to occur there must be a 90° rotation of the bond between the carbonyl carbon and the a-carbon.  If such a rotation was to  23  OH  H  90° r o t a t i o n for cleavage  R -  H. H,  a  F i g u r e 18:  CH,  Suggested c o n f o r m a t i o n of the 1,4 b i r a d i c a l phenyl ketone  of a s i m p l e  o c c u r , a-methyl s u b s t i t u e n t s would c r e a t e a s t e r i c b a r r i e r t o r o t a t i o n and thus impede the a b i l i t y cleavage geometry. f o r cleavage  this  of the molecule t o a t t a i n the  The s t e r i c h i n d e r a n c e would lower the rate  constant  (kcA) i n r e l a t i o n t o the rate constant f o r c y c l i z a t i o n  The t r a n s i t i o n s t a t e f o r c y c l i z a t i o n orbitals  alkyl  r e q u i r e s the o v e r l a p of the "p"  on the Y-carbon and the h y d r o x y - c a r b o n .  o r b i t a l s w i t h the a,P  (key).  S i n c e o v e r l a p of the "p"  bond i s not r e q u i r e d , Lewis has p o s t u l a t e d t h a t  t r a n s i t i o n state f o r c y c l i z a t i o n is  n o n - p l a n a r so as t o minimize  eclipsing interactions  >  (figure 1 9 )  3 2  3 3  .  1,2  Lewis has suggested t h a t  the  the  24  Figure 19:  Suggested geometry f o r cyclobutanol formation  decrease in the amount of c y c l i z a t i o n f o r p,P-dimethyl  substituted  butyrophenone is due to the introduction of a 1,3 d i a x i a l  interaction  which d e s t a b i l i z e s the t r a n s i t i o n state f o r c y c l i z a t i o n . 3 3  The importance of s t e r i c i n t e r a c t i o n s on the behavior of 1,4 b i r a d i c a l s is also evident in the stereochemistry of the c y c l i z a t i o n products.  As shown in figure 20, photolysis of a-methyl buty rophenone  gives e x c l u s i v e l y the trans-isomer of the c y c l i z a t i o n p r o d u c t . 33  This  25  0  Figure 20:  S t e r e o s e l e c t i v i t y of the cyclobutanol formed upon p h o t o l y s i s of a-methyl buty rophenone  high degree of s t e r e o s e l e c t i v i t y has been a t t r i b u t e d t o a repulsive i n t e r a c t i o n between the aromatic ortho-hydrogens and the a-methyl group of the 1,4 bi radical f o r c i n g the bi radical to form the more favoured trans cycl obutanol. Although y - s u b s t i t u t i o n has only a small effect on the competition between c y c l i z a t i o n and cleavage, i t does have a tremendous impact on the rates of hydrogen abstraction by the e l e c t r o n - d e f i c i e n t  oxygen atom.  The  r e a c t i v i t i e s are of the order 200:25:1 f o r the formation of a tertiary-secondary-primary y-carbon r a d i c a l , which r e f l e c t s the dependance of  on the y C-H bond d i s s o c i a t i o n energy  1 4  »  3 5  »  3 7  .  The addition of a , p and y substituents has been observed to lower the quantum y i e l d f o r the formation of products from a l k y l phenyl ketones.  26  Lewis has suggested that t h i s decrease i s due to s t e r i c i n t e r a c t i o n s which increase the energy of the t r a n s i t i o n states for c y c l i z a t i o n and cleavage and make return of the b i r a d i c a l to the ground s t a t e , by reverse hydrogen a b s t r a c t i o n , more favourable. The substituent e f f e c t s on the behavior of 1,4 b i r a d i c a l intermediates c l e a r l y show that the ground state geometry of the s t a r t i n g ketone may be very important in determining the product s e l e c t i v i t y . Lewis has stated that ground state molecular conformations can influence photochemical behaviour when the excited state reactions are more rapid than conformational i s o m e r i s m ' . 3 7  3 8  This i s p a r t i c u l a r l y evident when  the two conformers can give r i s e to d i f f e r e n t photoproducts ( f i g u r e 2 1 ) .  AB  hv  hv AB  Figure 21:  B  ± B  Two d i f f e r e n t conformers of a molecule giving r i s e to d i f f e r e n t photoproducts  Lewis has proposed two l i m i t i n g cases which may influence the r a t i o s of the products f o r m e d . 40  Case I:  The energy b a r r i e r for conformational isomerism is lower than  27  the a c t i v a t i o n energies f o r the formation of X or Y * (k^  B  » k^.kg)  and the product ratios w i l l depend on the  a c t i v a t i o n energies of  the t r a n s i t i o n states leading t o products  A and B Case I I : The energy b a r r i e r f o r excited state conformational isomerism i s higher than the a c t i v a t i o n energy f o r the formation of X or Y * (k « k kg) and the product r a t i o depends on the r e l a t i v e * * A B  A>  population of A  and B , which are in turn dependent on the  r e l a t i v e populations of A and B. The photochemical behavior of a-methyl cycl opentyl phenyl ketone has been observed t o e x h i b i t case I behavior. The pseudorotation of the cyclopentane ring is more rapid than a-cleavage or y-hydrogen abstraction * (k^g > k , a  ky), and is a t t r i b u t e d t o a low energy b a r r i e r f o r alkane bond  rotations in cyclopentane.  Although y-hydrogen abstraction can only occur  from the a x i a l conformation A (figure 2 2 ) » , the l i f e t i m e s of the two 5 1  5 2  conformers must be the same since i t was found that the rates of formation of benzaldehyde and the cyclobutanol were i d e n t i c a l , thus implying a rapidly e q u i l i b r a t i n g cyclopentane r i n g .  The photochemistry of a-methyl  cycl ohexyl phenyl ketone (figure 23) has been shown to be an example of case II behavior.  The formation of benzaldehyde and the cyclobutanol  28  Figure 22:  The photochemistry of a-methylcyclopentyl  phenyl ketone  product has been observed to occur at d i f f e r e n t rates which are dependent on the conformer l i f e t i m e s t * k  AB  << k , a  A  and - C g  3 8  '  4 0  .  If the rate constant  k^, then the product quantum y i e l d s should depend on the ground  state populations for the d i f f e r e n t conformers as well as the e f f i c i e n c y of product formation from the radical pair and b i r a d i c a l  intermediates.  The quantum y i e l d s for the formation of benzaldehyde and the cyclobutanol  29  were found to agree well with the conformational populations of the s t a r t i n g ketone in s o l u t i o n .  Figure 23:  This result is in agreement with the  The photochemistry of a-methylcyclohexyl phenyl ketone  existence of a large rotational energy b a r r i e r preventing rapid i nterconversion of the cyclohexane ring of the s t a r t i n g ketone. Many organic molecules have been observed to exist as rapidly e q u i l i b r a t i n g conformational isomers of s i m i l a r energy in s o l u t i o n .  This  30  fact makes i t d i f f i c u l t to obtain single products from a reactant which may give several products from more than one conformational isomer. Attempts have been made to control the geometry of the reactant species so as to obtain a more selective conversion  to products.  These attempts have  involved the use of organized media which may l i m i t the available geometries of the reactant species and thus a l t e r the ratios and number of products formed.  These organized media often consist of:  1.  Micellar systems  2.  Monolayer assemblies  3.  Inclusion complexes  4.  Liquid c r y s t a l s  5.  Glassy matrixes  6.  C r y s t a l l i n e state The  use of highly structured media, such as the c r y s t a l l i n e state,  to control photochemical reactions, has received considerable recent years * > 1  the reactants  1  42  >  1+3  > . 44  attention in  In contrast to solution state reactions,  in the s o l i d state are usually locked in a fixed orientation  with this orientation being the minimum energy state of the molecule. 1918,  Kohlschutter  In  proposed that reactions in crystals proceed with a  minimum of atomic and molecular movement * . 1  5  The topochemical  postulate  originating at this time suggests that the nature and properties of the products from a s o l i d state reaction are governed by the c r y s t a l l i n e influence of the three dimensionally  periodic environment.  Schmidt  refined the d e f i n i t i o n of the topochemical postulate by suggesting that solid-state reactions are controlled by the r e l a t i v e l y fixed distances and  31  orientations of the molecule, as determined by the crystal between p o t e n t i a l l y reactive centers.  lattice,  What is implied is that f o r a  p a r t i c u l a r reaction type, there should e x i s t geometries and distances beyond which a reaction cannot occur.  Furthermore, the molecular  structure of the products may be a function of the geometry of the reactant in the c r y s t a l . 4 6  What is p a r t i c u l a r l y advantageous about studying chemical reactions in the c r y s t a l l i n e state is that the geometry and atomic distances of the reactant species may be obtained from X-ray crystallography.  S o l i d state magic angle spinning N.M.R. spectroscopy  also lends i t s e l f quite well to the study of organic s o l i d s .  These two  techniques may be used to draw s t r u c t u r e - r e a c t i v i t y c o r r e l a t i o n s  for  photochemical transformations i n the s o l i d state. Scheffer and T r o t t e r have used the techniques of X-ray crystallography and s o l i d state magic angle spinning N.M.R. spectroscopy to determine the s o l i d state geometry of ene-dione 1 (figure 24). s o l u t i o n , t h i s ene-dione can e x i s t in conformations A or B.  In  Conformation  32  1 (R.'CHfrRfCtH,)  Figure 24:  The photochemistry of ene-dione 1  A gives photoproducts 2 and 3, whereas conformation B gives photoproducts 2'and 3 ' .  Solution state photolysis of ene-dione 1 produces a mixture of  2, 2 ' , 3 and 3 ' , the r a t i o of which is dependent on the extent of conversion.  In the s o l i d state ene-dione 1 has been shown to exist  in conformation A and gave only the enone-alcohol 2 as the product. cyclobutanone 3 was not formed in the s o l i d state.  solely The  Scheffer and T r o t t e r  a t t r i b u t e t h i s result to an unfavourable s o l i d state s t e r i c e f f e c t  33  accompanying cyclobutanone formation but not enone-alcohol formation. formation of products 2 and 2' has been found to occur via a H abstraction by 0  4  followed by C  2  - C  8  bonding.  is brought about by a t r a n s f e r of H to C 8  3  The  5  The formation of 3 and 3'  followed by C  2  - C  8  bonding.  Scheffer and T r o t t e r have studied the geometric requirements f o r P- hydrogen abstraction by the carbonyl oxygen of ene-diones (figure 25). It was found that the abstraction distances varied between 2.26 and 2.58 A and that t and A were close to ideal (0° to 8° f o r t and 81° to 86° f o r A)  4 8  .  Scheffer and T r o t t e r have extended the study of hydrogen  abstraction distances and angles to the Norrish Type II reaction.  Figure 25:  The  p-Hydrogen abstraction geometry f o r ene-diones  study involved the photolysis of a series of a-cycl o a l k y l - p - c h l oroacetophenone derivatives ( c y c l o b u t y l , cycl opentyl, cycl ohexyl, c y c l o h e p t y l , exo-2-norbornyl and 1-adamantyl).  All  six  ketones were reported to undergo the Norrish Type II process in the s o l i d state . 2 1  It was found that the distance f o r y-hydrogen abstraction by the  34  carbonyl oxygen could be much l a r g e r than 1.8 A and s t i l l  occur.  An  abstraction distance of 3.1 A f o r the abstraction of a y-hydrogen from a-cyclobutyl-p-chloroacetophenone was reported.  The angles A and T were  also observed to deviate considerably from the t h e o r e t i c a l l y ideal values of 90°-120° and 0° r e s p e c t i v e l y .  In an extreme case the value of x was  found to be 62° f o r the abstraction of a y-hydrogen from a-1-adamantyl-p-chloroacetophenone. The s o l i d state geometry of the six-membered t r a n s i t i o n state f o r y-hydrogen abstraction was found to vary from boat to twist boat to c h a i r l i k e depending on the a - c y c l o a l k y l  moiety.  Scheffer and T r o t t e r have also studied the effect of l a t t i c e control on the p a r t i t i o n i n g of the 1,4 bi radical intermediate.  Most of  the ketones studied show very s i m i l a r ratios of c y c l i z a t i o n to cleavage i n s o l u t i o n and the s o l i d state.  Only the cyclohexyl compound (figure 26)  was observed to show a s i g n i f i c a n t l y d i f f e r e n t c y c l i z a t i o n to cleavage r a t i o in the s o l i d state compared to the s o l u t i o n state.  For t h i s  compound, a s l i g h t increase in the amount of cleavage was observed in the s o l i d s t a t e , and t h i s was explained in terms of a topochemical of the motions required f o r c y c l i z a t i o n .  restriction  35  0  T  /  CI  Figure 26:  The photochemistry of a-cycl ohexyl-p-chloroacetophenone  Research Objectives The objective of t h i s research is to study the effects of a - c y c l oal kyl ring size ( c y c l o o c t y l , c y c l o h e p t y l , cycl ohexyl and cyclopentyl) as well as the effect of a-methyl substituents on the photochemistry of para-substituted acetophenones.  It is hoped that f o u r  important questions may be answered from t h i s work. 1.  The e f f e c t of a-methyl substituents and c y c l o a l k y l  ring size on the  geometry f o r hydrogen abstraction by the oxygen "n" o r b i t a l . 2.  The e f f e c t of a-methyl substituents and c y c l o a l k y l competition between c y c l i z a t i o n and cleavage.  ring size on the  It is known that  a-methyl substituents increase the amount of c y c l i z a t i o n product upon photolysis of simple alkyl phenyl ketones i n s o l u t i o n . 3 3  Perhaps  36  t h i s trend may also be true f o r a - m e t h y l - a - c y c l o a l k y l - p a r a substituted acetophenones.  I f t h i s i s the case, i t may be possible  to c o r r e l a t e the geometry of the s t a r t i n g ketone, as determined by X-ray c r y s t a l l o g r a p h y , to the observed r a t i o s of c y c l i z a t i o n to cleavage.  Likewise, s i m i l a r c o r r e l a t i o n s may be made for the e f f e c t s  of c y c l o a l k y l ring size on the r a t i o of c y c l i z a t i o n to cleavage. 3.  The e f f e c t of a-methyl substituents and c y c l o a l k y l ring size on the stereochemistry of the photoproducts and how the stereochemistry may be related to the geometry of the s t a r t i n g ketone.  4.  The e f f e c t of a-methyl substituents and c y c l o a l k y l ring size on the quantum y i e l d s for product formation can be observed. The design of the ketones involved in t h i s study i s of p a r t i c u l a r  importance. 1.  The two most important design features are the f o l l o w i n g :  The molecules must be c r y s t a l l i n e such that X-ray a n a l y s i s i s possible.  I t would be b e n e f i c i a l to study a molecule which has a  high melting point in order to minimize melting during p h o t o l y s i s . 2.  The molecule must have an a v a i l a b l e y-hydrogen atom when photolyzed i n the s o l i d s t a t e .  I t has been shown that 7-tridecanone does not  react in the s o l i d state but does react in the melt ( f i g u r e 27).  37  hv  10*  No Reaction  33,*  >  HH  Figure 27:  (melt)  T y  p  e  II  , y  The photochemistry of 7-tridecanone  This behavior i s believed to be the r e s u l t of the molecule e x i s t i n g in an extended conformation in the s o l i d , thus making the y-hydrogen i n a c c e s s i b l e to the abstracting k e t o n e . 49  shown that the y-hydrogens of  Scheffer and Trotter have  a-cycloalkyl-para-substituted  acetophenones can be within the abstracting distance of the carbonyl oxygen(figure  28)  2 0  .  2 1  .  8 0  .  38  Figure 28:  <x-Cycloalkyl-para-substituted acetophenones with a v a i l a b l e Y-hydrogen  The molecules involved in t h i s study w i l l be very s i m i l a r to those already studied by Scheffer and T r o t t e r ' . 2 0  2 1  In t h i s case an a-methyl  group w i l l be attached to the s t a r t i n g ketone.  The para-substituent  will  be a carboxylic acid functional group to ensure that the molecules w i l l be high melting s o l i d s .  The size of the c y c l o a l k y l  cyclopentyl to cyclooctyl  (figure 29).  ring w i l l be varied from  39  y  n -  Figure 29:  5,6,7,8  Design of the a-methyl ketones  To better understand the e f f e c t s of a-methyl s u b s t i t u t i o n , another series of compounds analogous to those in f i g u r e 29 but lacking an a-methyl substituent w i l l also be studied (figure 3 0 )  n  Figure 30:  5 0  -  .  5 3  .  5,6,7,8  Design of the ketones lacking an a-methyl substituent  F i n a l l y , the e f f e c t s of larger ring ketones with varying para-substituents w i l l also be studied.  In t h i s case the packing of the  40  molecules in the c r y s t a l l a t t i c e may influence the behavior of these ketones when photolyzed in the s o l i d state (figure 31).  X - C I , CN, COOH  n -  Figure 31:  7,8  Design of the ketones bearing variable para-substituents  41  RESULTS AND DISCUSSION Synthesis  The synthesis of the a-cycloalkyl-para-substituted-acetophenones required for t h i s study has centered on the a v a i l a b i l i t y of c y c l o a l k y l a c e t i c acids as s t a r t i n g m a t e r i a l s .  Cyclohexyl and cyclopentyl  acetic  acids are both commercially a v a i l a b l e , however, cycloheptyl and c y c l o o c t y l a c e t i c acids are not.  Fortunately, synthetic routes for c y c l o o c t y l and  cycloheptyl acetic acids have been reported in the l i t e r a t u r e . The synthesis of cyclooctyl acetic acid has been accomplished by B l i c k e and Johnson  55  using the sequence of reactions outlined in  figure 32.  The f i r s t step involves the conversion of cyclooctene (la) to  Figure 32:  Synthesis of cyclooctyl acetic acid  42  c y c l o o c t y l bromide (1), using hydrobromic acid dissolved in g l a c i a l acid as the brominating reagent.  acetic  Reaction of cyclooctyl bromide with the  sodium enolate of diethyl malonate r e s u l t s in a n u c l e o p h i l i c  displacement  of the bromine atom by the carbanion r e s u l t i n g in the formation of the d i e s t e r (2a).  Hydrolysis in a s o l u t i o n of potassium hydroxide, followed  by decarboxylation y i e l d s cyclooctyl acetic acid (2). The synthesis of cycloheptenyl acetic acid (3) has been accomplished by McCarthy and Brown o u t l i n e d in f i g u r e 33.  56  using the sequence of reactions  C a t a l y t i c hydrogenation of cycloheptenyl  acid using a method developed by J . F . Sauvage et a l . cycloheptyl acetic acid (5).  Figure 33:  Synthesis of cycloheptyl acetic acid  5 7  generates  acetic  43  The f i r s t step of t h i s reaction sequence involves the reaction of cycloheptanone with cyanoacetic acid in the presence of a small amount of ammonium acetate.  Under these c o n d i t i o n s , small q u a n t i t i e s of the enolate  of cyanoacetic acid are generated and t h i s attacks the carbonyl carbon of cycloheptanone.  Removal of water from the r e f l u x i n g reaction as an  azeotrope with benzene drives the reaction to completion. of the resultant product y i e l d s cycloheptenyl a c e t o n i t r i l e .  Decarboxylation This compound  was converted to cycloheptenyl acetic acid upon r e f l u x i n g in a s o l u t i o n of potassium hydroxide dissolved in water and ethanol.  Catalytic  hydrogenation of cycloheptenyl acetic acid using hydrogen gas at a pressure of 500 l b s / i n  2  and 10% palladium on charcoal as c a t a l y s t y i e l d s  cycloheptyl acetic acid (5). With the a v a i l a b i l i t y of the four c y c l o a l k y l acetic acids ( c y c l o o c t y l , c y c l o h e p t y l , c y c l o h e x y l , and cyclopentyl) as s t a r t i n g m a t e r i a l s , i t was possible to develop a synthetic strategy towards the synthesis of the a and para-substituted a - c y c l o a l k y l required for t h i s study. outlined in figure 34.  acetophenones  The strategy follows the sequence of steps  44  X • OMe,  Figure 34:  Me,  CI  Synthetic routes towards the synthesis of a and p a r a - s u b s t i t u t e d - a - c y c l o a l k y l acetophenones  The f i r s t step in the synthesis involves the conversion of the cycl oalkyl acetic acid to the corresponding acetyl chloride using a modified version of a procedure u t i l i z e d by B l i c k e et a l .  5 5  .  The  c y c l o a l k y l acetyl chloride was reacted with a mono-substituted benzene d e r i v a t i v e , in a F r i e d e l - C r a f t s a c y l a t i o n reaction catalyzed by aluminum  45  t r i c h l o r i d e , to form an a - c y c l o a l k y l - p a r a - s u b s t i t u t e d acetophenone. same procedure was used by Wagner  58  to synthesize several  The  different  para-substi tuted valerophenones. The reaction of cyclooctyl acetyl chloride with e i t h e r chlorobenzene, toluene, anisole or fluorobenzene in the presence of aluminum t r i c h l o r i d e y i e l d s the compounds shown in figure 35.  X=CA X=0Me X=Me X=F Figure 35:  : : : :  m.p. = o i l at o i l at o i l at  48-49°C 22°C 22°C 22°C  Products of F r i e d e l - C r a f t s a c y l a t i o n of substituted benzenes using cyclooctyl acetyl chloride and aluminum t r i c h l o r i d e as a catalyst  The following spectroscopic data supports the proposed s t r u c t u r e s . 1.  The i n f r a r e d spectra of these compounds show a strong carbonyl absorption at 1675-1685 c m  -1  which i s i n d i c a t i v e of an alkyl  phenyl  ketone. 2.  The 400 MHz H nmr spectra show two d i s t i n c t signals in the aromatic X  region, each of which integrates for two protons.  This evidence  46  suggests that p a r a - s u b s t i t u t i o n had occurred.  In a d d i t i o n , the two  a-hydrogen atoms appear as doublets at 2.8-3.0 ppm; the a-hydrogen to 6-hydrogen coupling constant measures 8 Hz. 3.  The mass spectra of these compounds e x h i b i t the correct parent ion mass.  In a d d i t i o n , the base peaks in the spectra correspond to a  McLafferty rearrangement of the parent ion (figure 36). 4.  The structure of a-cyclooctyl-para-chloroacetophenone was v e r i f i e d by X-ray c r y s t a l l o g r a p h y . 62  The R f a c t o r f o r t h i s determination was  calculated to be 4.4%.  Figure 36:  McLafferty rearrangement of acetophenones  a-cyclooctyl-para-substituted  47  The para-methoxy and para-methyl-a-cyclooctyl-acetophenones were found to be l i q u i d s at room temperature and as a result were of l i t t l e use to t h i s study.  The para-fluoro d e r i v a t i v e is also a l i q u i d , but as shown  i n f i g u r e 34 i t can serve as a valuable synthetic intermediate f o r the synthesis of other para-substituted-a-cycloalkyl acetophenones. The remaining cycl oal kyl acetyl chlorides  (cycloheptyl,  cycl ohexyl, and cycl opentyl) were reacted with f luorobenzene i n the presence of aluminum t r i c h l o r i d e , producing the corresponding a - c y c l oal k y l - p a r a - f luoroacetophenones . 60  X  Two aromatic signals in the  H nmr spectra at approximately 7.1 and 8.0 ppm, i n t e g r a t i n g f o r two  protons each, are observed f o r a l l the para-fluoro d e r i v a t i v e s .  This  pattern suggests that p a r a - s u b s t i t u t i o n of fluorobenzene had occurred. The mass spectra of each compound e x h i b i t s the correct parent ion mass and the base peak corresponds to a McLafferty rearrangement of the parent ion. Infrared analysis shows a strong alkyl phenyl ketone stretching band at 1684 c m . - 1  A l l of the compounds in t h i s series are o i l s at room  temperature. At t h i s stage of the synthesis the a - c y c l oal k y l - p a r a fluoroacetophenones could be methylated in the a - p o s i t i o n leading to the formation of the a-methyl ketone s e r i e s .  Omitting the methylating step  would lead to the synthesis of a number of d i f f e r e n t a - c y c l oal k y l - p a r a substituted acetophenones (figure 37).  The a-methylation was accomplished  by reaction of the a-cycloalkyl-para-fluoroacetophenone with l i t h i u m diisopropyl amide at 0°C to generate the corresponding enolate.  48  n -  7,8  Figure 37:  The synthesis of a-cyclooctyl-para-cyano and para-carboxy acetophenones  The enolate was then allowed to react with methyl iodide generating the a-methyl analogue of the s t a r t i n g ketone.  This a l k y l a t i o n step was  conducted using a modified version of an a l k y l a t i o n procedure developed by P.L. C r e g e r . 59  The H nmr of the a-methyl-a-cycl oalkyl-pa ra1  fluoroacetophenones e x h i b i t a methyl doublet at approximately 1.1 ppm. The coupling constant between the a-methyl group and the a-hydrogen measures 7 Hz. The next step in the synthesis involved the reaction of the p a r a - f l u o r o alkyl phenyl ketones with sodium cyanide i n dimethyl sulphoxide at 110-120°C f o r two days.  The cyanide ion displaces the  p a r a - f l u o r o substituent to form the a-cycloalkyl-para-cyanoacetophenone compounds.  The same method was used by Wagner  58  to synthesize  para-cyanovalerophenone from para-fluorovalerophenone. spectroscopic data supports the proposed s t r u c t u r e s .  The f o l l o w i n g  49  1.  The H nmr spectra e x h i b i t two signals in the aromatic region, each X  of which integrates for two protons.  This suggests that s u b s t i t u t i o n  had occurred in the p a r a - p o s i t i o n . 2.  The mass spectra of these compounds e x h i b i t the correct parent ion mass.  In a d d i t i o n , the base peak in the spectra corresponds to a  McLafferty rearrangement of the parent i o n . 3.  The i n f r a r e d spectra of these compounds e x h i b i t a strong n i t r i l e stretching band in the 2225 c m  -1  region.  In a d d i t i o n , the alkyl  phenyl ketone band i s observed at 1687 c m . - 1  These compounds and t h e i r respective melting points are shown in f i g u r e 38.  In t h i s series only the a - c y c l o o c t y l - and a - c y c l o h e p t y l - p a r a -  cyanoacetophenones are s o l i d s at room temperature.  CN  Figure 38:  n  R  melting point (°C)  8 7 8 7 6 5  H H CH CH CH CH  62-63°C 41-42°C o i l at 22°C o i l at 22°C o i l at 22°C o i l at 22°C  3 3  3 3  a-Cycloalkyl-para-cyanoacetophenone d e r i v a t i v e s and t h e i r melting points  To obtain s o l i d s of the a-methyl analogues, i t was necessary to convert the para-cyano functional group to the carboxylic a c i d .  The  para-cyano compounds were added to a r e f l u x i n g mixture of water, potassium  50  hydroxide and ethanol. Wagner  58  These hydrolysis conditions were employed by  to hydrolyze para-cyanovalerophenone t o  para-carboxyvalerophenone.  The resultant a-methyl-a-cycloalkyl-  para-carboxyacetophenones are a l l s o l i d s at room temperature. methylated a - c y c l oalkyl-para-carboxyacetophenones  The n o n -  are also s o l i d s .  AIT of  the para-carboxy compounds have been found to have melting points greater than 100°C (figure 3 9 . ) .  COOH  0^ Figure 39:  n  R  8 7 8 7 6 5  H H CH CH CH CH  melting point (°C) 188-189°C 183-184°C 137-138°C 152-153°C 157-158°C 140-141°C  3 3 3 3  a-Cycloalkyl-para-carboxyacetophenone derivatives and t h e i r melting points  The f o l l o w i n g spectroscopic data supports the proposed s t r u c t u r e s . 1.  The mass spectra of these compounds e x h i b i t the correct parent ion mass.  In a d d i t i o n , the base peak in the spectra corresponds to a  McLafferty rearrangement of the parent ion. 2.  A low f i e l d acid proton is observed i n the H nmr.  3.  Infrared analysis reveals a broad 0-H stretching band around  l  2900 c m . - 1  In a d d i t i o n , two carbonyl peaks are observed in the  regions 1683 c m  -1  and 1700 c m , these correspond to the keto and  acid carbonyl s t r e t c h i n g bands  - 1  respectively.  51  4.  X-ray crystallography has v e r i f i e d the structures of a-cyclooctyl-para-carboxyacetophenone , a-methyl-a-cyclooctyl-para62  carboxyacetophenone , a-methyl-a-cyclohexyl -para62  carboxyacetophenone » , and a-methyl-a-cyclopentyl-para60  carboxyacetophenone . 63  6 1  The calculated R factors have been found t o  be 4 . 2 , 4.6, 5.8% and 6.5% r e s p e c t i v e l y . The f i n a l step in the synthesis involved the conversion of the para-carboxy compounds to the corresponding carbomethoxy d e r i v a t i v e s . This conversion was accomplished by reacting diazomethane with the a - c y c l oal kyl-para-carboxyacetophenone precurser, dissolved in ether. Diazomethane was prepared using a method developed by Th. J . DeBoer and H.J. B e c k e r . 64  The carbomethoxy derivatives are s o l i d s with the majority  of these having low melting points (figure 40).  COOCH.  Figure 40:  n  R  melting point (°C)  8 7 8 7 6 5  H H CH CH CH CH  40-41°C 54-55°C 39-40°C 59-60°C 82-83°C 38-39°C  3 3 3 3  a-Cycloalkyl-para-carbomethoxyacetophenone thei r melti ng poi nts  derivatives and  The f o l l o w i n g spectroscopic data supports the proposed structures.  52  1.  The mass spectra of these compounds e x h i b i t the correct parent ion mass.  In a d d i t i o n , the base peak in the spectra corresponds to a  McLafferty rearrangement of the parent i o n . 2.  The  l  H nmr spectra e x h i b i t s a sharp s i n g l e t at approximately 4.0 ppm  which integrates for the three protons of the methyl e s t e r . 3.  Infrared analysis reveals two carbonyl stretching bands at approximately 1680 c m  -1  and 1720 c m  -1  which correspond to the keto  and ester carbonyl stretching bands r e s p e c t i v e l y . 4.  A l l of the keto-esters showed acceptable elemental  analysis.  I d e n t i f i c a t i o n of the Photoproducts  Scheffer and T r o t t e r have shown that a - c y c l o a l k y l - p a r a chloroacetophenones ( c y c l o h e p t y l , c y c l o h e x y l , cyclopentyl and c y c l o b u t y l ) undergo the Norrish Type II reaction when photolyzed in the s o l i d and solution s t a t e s * . 2 0  2 1  Photolysis of these compounds was found to give  r i s e to four products, these being an alkene, para-chloroacetophenone and two isomeric cyclobutanols (figure 41).  The two cyclobutanols have been  53  0  trans-cyclobutanol  Figure 41:  cis-cyclobutanol  Products from the photolysis of a - c y c l o a l k y l - p a r a chl oroacetophenones  designated c i s and trans.  In the case of the c i s - isomer, the hydroxyl  group i s cis to the nearest bridgehead hydrogen atom and in the transisomer the hydroxyl group is trans to the nearest bridgehead hydrogen. I d e n t i f i c a t i o n of the c i s - and trans-isomers has been made possible through the use of H nmr spectroscopy. X  The cis-cyclobutanols have been  observed to show a low f i e l d doublet of doublets at 2.8 ppm (J=6.5 and 4 Hz).  This signal integrates f o r one proton and has been assigned to H  (figure 4 1 ) .  The assignment has been based on H^ l y i n g w i t h i n the  deshielding region of the r o t a t i o n a l l y hindered aryl group.  54  Scheffer and T r o t t e r have also found that trans-cyclobutanols have shorter g.c. retention times than the corresponding c i s isomers.  A  s i m i l a r observation was also noted by Wagner f o r the retention times of the c i s - and trans-cyclobutanols derived from substituted valerophenones . 25  To aid in the assignment of the structure and stereochemistry of these b i c y c l i c [ n . 2 . 0 ] alkanols the f o l l o w i n g I.U.P.A.C. numbering scheme has been used (figure 42).  Figure 42:  I.U.P.A.C.  numbering scheme f o r b i c y c l o [ n . 2 . 0 ] alkanols  Photolysis of a series of a - c y c l o o c t y l - p a r a - s u b s t i t u t e d acetophenones (para-chl oro, para-cyano and para-carboxy) in a c e t o n i t r i l e results in the conversion of the s t a r t i n g ketones into four photoproducts (figure 43).  55  0  Figure 43:  The photolysis of some a - c y c l o o c t y l - p a r a - s u b s t i t u t e d acetophenones  G.C. analysis of the resultant product mixtures showed three major product peaks.  The retention time of cyclooctene was too short to be detected  under normal g.c. conditions.  The second cleavage product, a  para-substituted acetophenone, was observed to have a short g.c.  retention  time as compared to the retention times recorded f o r the cyclobutanols. The cleavage product and the isomeric cycl obutanol s were i s o l a t e d using column chromatography.  The photoproducts derived from the para-carboxy  ketone were e s t e r i f i e d , using diazomethane, p r i o r to column chromatography and g.c.  analysis.  56  The i s o l a t e d cleavage products were i d e n t i f i e d by the f o l l o w i n g spectral and physical 1.  characteristics.  The mass spectra of the para-substituted acetophenones e x h i b i t the correct parent ion mass.  2.  1  H nmr shows a sharp s i n g l e t peak at 2.7 ppm which integrates f o r the three protons of the a-methyl group.  Two signals in the aromatic  region of the spectra account f o r the four aromatic protons.  An  additional signal is observed f o r para-carbomethoxyacetophenone at 4.0 ppm.  This peak integrates f o r three protons and accounts f o r the  methyl e s t e r hydrogens. 3.  The i n f r a r e d spectra of these compounds show a strong a l k y l phenyl ketone s t r e t c h i n g band at approximately 1675 c m . - 1  Para-  cyanoacetophenone shows a strong n i t r i l e stretching band at 2230 c m  -1  and para-carbomethoxyacetophenone shows a strong e s t e r carbonyl s t r e t c h i n g band at 1723 c m . - 1  4.  The melting points of the para-substituted acetophenones also agree quite well with the recorded l i t e r a t u r e values shown in figure 44.  X -CA -CN -COOMe  Figure 44:  Obs. m.p. (°C) o i l (a 22° 60-61° 93-94°  l i t . m.p. (°C) 20° 60-61° 6 5  66  0,2 ° 66  Experimental and l i t e r a t u r e melting points of para-substituted acetophenones  57  The two isomeric cycl obutanol s, from each s t a r t i n g ketone, were i s o l a t e d and i d e n t i f i e d from the following spectroscopic data. 1.  Infrared spectra of these compounds show a strong, broad, hydroxyl stretching band around 3440 c m . - 1  region 1600-1800 c m products.  -1  The absence of any bands in the  v e r i f i e s the lack of a carbonyl group i n the  The para-carbomethoxy cycl obutanol s do show an e s t e r  carbonyl stetching band at 1724 c m . - 1  2.  The mass spectra of the cycl obutanols e x h i b i t the correct parent ion masses.  In a d d i t i o n , these compounds were also found to undergo a  mass spectral  retro 2+2 fragmentation producing the observed base  peak (figure 45).  Herzschuh and Epsch have also observed that  X - C l , COOMe, CN  Figure 45:  Retro 2+2 fragmentation pattern observed f o r [ 6 . 2 . 0 ] cycl obutanol s  58  b i c y c l i c [ n . 2 . 0 ] alkanes undergo an e f f i c i e n t  retro 2+2 mass spectral  fragmentation as the major fragmentation pattern o b s e r v e d . 78  3.  The d i s t i n c t i o n between c i s - and trans-cyclobutanols has been made using  l  H nrnr spectroscopy.  The 400 MHz H nmr spectra f o r the c i s l  and the trans-para-cyano [ 6 . 2 . 0 ] cyclobutanols are shown in f i g u r e 46.  46a:  The t i nmr spectrum of the trans-cyclobutanol l  Trans-cyclobutanol  is very  59  it  5 ppm  46b:  3 ppm  ppm  2 ppm  1 ppm  C i s - c y c l obutanol  Figure 46:  400 MHz H nmr spectra of the c i s - and trans-cyclobutanols derived from a-cycl ooctyl-para-cyanoacetophenone X  complicated, making i t d i f f i c u l t to draw any s t r u c t u r a l  correlations.  Only the four aromatic protons resonating at 8.0 and 8.1 ppm are distinguishable.  The  l  H nmr of the cis-isomer on the other hand is  more revealing, showing the following c h a r a c t e r i s t i c s : i)  a doublet of doublets is observed at 2.8 ppm (J=8 and 4 Hz) which is in the exact region of the spectrum in which H^ was observed i n the cis-cyclobutanols i d e n t i f i e d by Scheffer and Trotter . ; 2 0  2 1  60  i i ) a signal i s observed at 0.38 ppm.  The fact that t h i s s i g n a l ,  which integrates for one proton, i s located at such a high f i e l d suggests that i t must be located in the s h i e l d i n g region of n electron density above and below the plane of the aryl group. I t was thought that the shielded hydrogen atom would most l i k e l y be one of the hydrogen atoms bonded to C . 7  To provide more  conclusive proof, a series of decoupling experiments was c a r r i e d out.  I t was found that decoupling the signal at 0.38 ppm  s i m p l i f i e s the signal at 2.29 from a m u l t i p l e t to a doublet (J=8 Hz), as shown in f i g u r e 47.  Such a simple s p l i t t i n g  61  Figure 47:  1  H nmr spectrum of the cis-cyclobutanol decoupled at 0.38 ppm  pattern can only be accounted f o r by e i t h e r of the two ring j u n c t i o n hydrogen atoms or Hg of the cyclobutanol ring. atoms H^ and H  can be eliminated as p o s s i b i l i t i e s  x  Hydrogen  since  decoupling of the signal at 2.80 ppm (H^) has no effect on the signal at 2.29 ppm.  Thus, the signal at 2.29 can be assigned t o  bridgehead hydrogen H . 8  coupling with H . x  The coupling constant of 8 Hz is due to  A small coupling of H with the second H may 8  7  also be present but is so small that i t cannot be detected, and results in the signal at 2.29 appearing as a doublet.  62  The assignment of a c i s or trans ring junction cannot be deduced from the H nmr spectra.  It has been shown  X  67  that the differences between  the cis and trans proton coupling constants f o r substituted cyclobutanes is often s m a l l , however, the c i s coupling constant was always found to be greater than the trans coupling constant.  The ranges of magnitude f o r the  coupling constants were found to be 8-12 Hz and 8-10 Hz f o r the c i s and trans geometries r e s p e c t i v e l y . 67  constant between H  :  and H  or trans arrangement.  8  For the c i s - c y c l o b u t a n o l , the coupling  (J=8 Hz) is w i t h i n the range expected f o r a c i s  Scheffer and T r o t t e r have suggested that the  cyclobutanols formed upon photolysis of a - c y c l oal k y l - p a r a chl oroacetophe nones (cycloheptyl, cycl ohexyl, cycl opentyl and cyclobutyl) contain cis fused r i n g s . . 2 0  2 1  Since only two major cyclobutanol  products are observed in the photolysis of a - c y c l ooctyl-para-substituted acetophenones, i t is u n l i k e l y that the b i c y c l i c rings are trans fused.  If  i n fact the crossover point from c i s to trans fused rings has been reached, then we would expect to observe more than two cyclobutanols.  In  a d d i t i o n , the proton H^ appears in a p o s i t i o n expected f o r the c i s product as determined by Scheffer and T r o t t e r f o r the c i s - c y c l obutanol derived from photolysis of a - c y c l ohexyl-para-substituted acetophenones.  If in the  case of the a - c y c l ooctyl ketones the ring junction was to become t r a n s , then the chemical s h i f t of t h i s signal would be expected to change due t o a change in the p o s i t i o n of the aryl group.  In spite of t h i s evidence,  the assignment of a c i s ring j u n c t i o n must remain t e n t a t i v e since the bridgehead geometry cannot be absolutely determined.  63  Photolysis of the a - c y c l o h e p t y l - p a r a - s u b s t i t u t e d acetophenones also gave rise to the formation of cleavage and c y c l i z a t i o n products.  The  para-cyano and para-carboxyacetophenone cleavage products, derived from the photolysis of the corresponding a - c y c l o h e p t y l - p a r a - s u b s t i t u t e d acetophenones were i d e n t i f i e d by comparing t h e i r physical and spectral properties with samples i s o l a t e d from the photolysis of the cyclooctyl d e r i v a t i v e s and with the l i t e r a t u r e values. trans) were also i s o l a t e d as products.  Two cyclobutanols (cis and  These e x h i b i t the spectroscopic  c h a r a c t e r i s t i c s expected f o r cycl obutanols. strong 0-H s t r e t c h i n g band around 3440 c m . - 1  Infrared analysis shows a Mass spectroscopy e x h i b i t s  the correct parent ion mass and also records a base peak molcular ion which corresponds to a retro 2+2 fragmentation of the parent ion.  H nmr  i  of the cis-isomer shows a doublet of doublets at approximately 2.85 ppm (J =7.75 and 4.5 Hz) accounting f o r H^.  The cis-isomer also produces a  high f i e l d signal at approximately 0.44 ppm accounting f o r proton H .  The  6  signal f o r the bridgehead hydrogen H  7  is found at 2.3 ppm.  Photolysis of a-methyl-a-cyclooctyl-para-carboxyacetophenone  in  a c e t o n i t r i l e resulted in the formation of several products as shown i n f i g u r e 48.  P r i o r to analysis and i s o l a t i o n , the products were converted  to t h e i r methyl esters using diazomethane.  The product with the  64  0  t h r e e  Figure 48:  Photolysis of  isomers  a-methyl-a-cyclooctyl-para-carboxyacetophenone  shortest g . c . retention time was i s o l a t e d and found to be para-carbomethoxypropiophenone.  The structure of t h i s compound was  v e r i f i e d by the following spectroscopic c h a r a c t e r i s t i c s : 1.  The mass spectrum shows the correct parent ion mass.  2.  The presence of the a- and e-hydrogens i s v e r i f i e d by a t r i p l e t at 1.2 ppm (3H, J=8 Hz) and a quartet at 3.0 ppm (2H, J=8 Hz).  A sharp  s i n g l e t at 3.9 ppm integrates for the three protons of the methyl ester and a m u l t i p l e t at 8.1 ppm accounts for the four remaining aromatic hydrogens.  65  3.  The infrared spectrum reveals two carbonyl stretching bands at 1680 crn  -1  and 1723 c m , accounting f o r the presence of the ketone - 1  and e s t e r functional  groups.  Three other photolysis products were also observed having retention times in the region expected f o r cycl obutanols. were i s o l a t e d using column chromatography. shortest cyclobutanol  Two of these  The f i r s t of these had the  retention time and was found to comprise 70% of the  t o t a l cyclobutanol product in a c e t o n i t r i l e .  The second cyclobutanol had a  retention time close to that observed f o r the para-carbomethoxy-trans [ 6 . 2 . 0 ] cyclobutanol and was found to comprise 19% of the t o t a l cyclobutanol product i n a c e t o n i t r i l e . f o l l o w i n g spectroscopic 1.  These two cycl obutanols showed the  characteristics.  The infrared spectra of these compounds show a strong 0-H stretch at approximately 3400 c m . - 1  2.  Mass spectroscopy e x h i b i t s the correct parent ion mass as well as a base peak ion which corresponds to a retro 2+2 fragmentation of the parent ion.  3.  The H nmr of the cycl obutanols gives some clues as to t h e i r 1  stereochemistry.  The H nmr of the major cyclobutanol formed in X  a c e t o n i t r i l e is shown i n f i g u r e 49.  The methyl group on C  1 0  is  66  Figure 49:  ti nmr of the major cyclobutanol i s o l a t e d from photolysis of a-methyl-a-cyclooctyl-para-carboxyacetophenone  l  c l e a r l y v i s i b l e , appearing as a doublet at 1.08 ppm (J=7.5 Hz). Decoupling the signal at 1.08 ppm r e s u l t s in the m u l t i p l e t observed at 2.11 s i m p l i f y i n g to a doublet (J=9 Hz). has no e f f e c t on the m u l t i p l e t at 2.24 ppm.  Decoupling at 2.11 ppm Based on these r e s u l t s ,  the signal at 2.11 can be assigned to proton H . 1 0  The signal at 2.24  can not be assigned to proton H , since i t does not couple to proton x  H . 1 0  The s p l i t t i n g pattern of the signal at 2.24 does resemble the  s p l i t t i n g pattern of H for the cis-cyclobutanol shown in figure 46, 8  67  thus the signal at 2.24 was t e n t a t i v e l y assigned to proton H .  This  8  assignment was v e r i f i e d by an N.O.E. difference experiment. I r r a d i a t i o n of the aromatic protons Hm r e s u l t s in the enhancements shown in figure 50.  The endo assignment of the C  methyl group  1 0  *H nmr s p e c t r u m  •  9 *_  T-  j  -T  7  6  5  1 4  1 3  . i . Jl "IT  " 1  H N.O.E.  J  •  /  W  " H  1  1  r1  \  H 8  d i f f e r e n c e spectrum  1  1 2  1  , 0  I.  0  •  .  Figure 50: H N.O.E. difference spectra of the cyclobutanol shown in f i g u r e 49 1  i s based on the observation that no enhancement of the C i s observed, whereas proton H  1 0  1 0  methyl group  does e x h i b i t a strong enhancement.  Lewis  has observed that the cyclobutanol derived from the photolysis of a-methylbutyrophenone strongly prefers the geometry in which the methyl group and the aryl group are in a trans o r i e n t a t i o n * . 3 7  3 8  Irradiation  of Hm also r e s u l t s in the enhancement of H i n d i c a t i n g that the 8  cyclobutanol i s in fact t r a n s .  68  The second cyclobutanol i s o l a t e d produces the H nmr shown i n X  f i g u r e 51.  The methyl group on C  ~<  ~—•  5  Figure 51:  ppm  4  1 0  is c l e a r l y v i s i b l e in the *H nmr,  —i  p  3  pm  -i  ppm  2  -i  ppm  1  -i—  ppm  0  —  H nmr of the second cyclobutanol i s o l a t e d from photolysis of a-methyl-a-cyclooctyl-para-carboxyacetophenone  l  appearing as a doublet at 1.07 ppm (J=6.5 Hz).  Decoupling the signal at  1.07 ppm results in the m u l t i p l e t observed at 2.51 s i m p l i f y i n g to a doublet (J=9.5 Hz).  Hence, the signal at 2.51 ppm can be assigned to H . 1 0  Decoupling the signal at 2.19 ppm results in the s i m p l i f i c a t i o n of the m u l t i p l e t at 2.51 ppm to a quartet (J=6.5 Hz) and s i m p l i f i c a t i o n of the m u l t i p l e t at 2.37 ppm to a doublet (J =11 Hz). 2.19 ppm can be assigned to H  L  Hence, the signal at  since i t couples to H . 1 0  The signal at  69  2.37 ppm also couples to  and thus, t h i s signal can be assigned to H . 8  The doublet s p l i t t i n g of H the C  7  hydrogens.  8  i s due to a strong coupling of H t o one of 8  It is worth noting that decoupling of the H high f i e l d 7  proton of the para-cyano-cis [ 6 . 2 . 0 ] cyclobutanol also results in the collapse of H from a m u l t i p l e t to a doublet.  Again the observation of a  8  doublet s p l i t t i n g pattern is most l i k e l y due to the fact that coupling of H  8  to the second C  7  hydrogen is too weak to be detected.  In an N.O.E. difference experiment (figure 52), i r r a d i a t i o n of  *H nmr spectrum  1  •  —1  i  8  i -  i  -i  T  7 6 5 4 N . O . E . d i f f e r e n c e spectrum  n  Figure 52:  l  '  i  •  *  -  —i•  3  2 Hg  1/  r—  1  |  0  *.  -T  H N.O.E. difference spectra of the second cyclobutanol derived from a-methyl-a-cyclooctyl-para-carboxyacetophenone  the aromatic protons Hm results i n a strong enhancement of the signal due to H . 1 0  C l e a r l y the methyl group at C  1 0  is trans to the aryl group.  A  70  weak enhancement of the signal f o r H suggests that H  is also observed.  is cis to the aryl group.  8  enhancement of H  8  8  r e l a t i v e to H  1 0  This observation  The rationale f o r the weak  is not known.  In t h i s case the  assignment of the ring junction stereochemistry r e l a t i v e to the aryl group cannot be p o s i t i v e l y determined. The t h i r d cyclobutanol could not be i s o l a t e d from the product mixture.  It accounted f o r 11% of the t o t a l cyclobutanol products formed  in acetonitrile.  I d e n t i f i c a t i o n was made using combined gas  chromatography-mass spectroscopy ( g . c . m . s . ) . parent ion f o r the cyclobutanol.  The g.c.m.s. does not show a  This can be accounted f o r by the lowered  s e n s i t i v i t y of the g.c.m.s. system used f o r t h i s a n a l y s i s .  The mass  spectrum does e x h i b i t a base peak ion corresponding to a retro 2+2 fragmentation of the parent i o n . Photolysis of a-methyl-a-cycloheptyl-para-carboxyacetophenone resulted in the formation of cycl oheptene, para-carboxypropiophenone and three isomeric cyclobutanols.  It was found that cleavage of the  1,4 b i r a d i c a l generated from the a-cycl oheptyl ketone is the predominant process in a c e t o n i t r i l e . photolysis mixture.  Cyclobutanols were found to comprise 30% of the  These were i d e n t i f i e d as t h e i r methyl esters and have  been observed to e x h i b i t base peaks which correspond to a retro 2+2 fragmentation of the parent ions in t h e i r g.c.m.s. Photolysis of a-methyl-a-cycl ohexyl-para-carboxyacetophenone  in  a c e t o n i t r i l e resulted i n the formation of cyclohexene, para-carboxypropi ophenone and four isomeric cyclobutanols.  The major cyclobutanol  product, i s o l a t e d as i t s methyl e s t e r , was found to comprise 56% of the t o t a l cyclobutanol product formed in a c e t o n i t r i l e .  It was isolated using  71  column chromatography and analyzed s p e c t r o s c o p i c a l l y .  The i n f r a r e d  spectrum of the cyclobutanol e x h i b i t s a broad 0-H stretching band at 3497 c m .  Mass spectroscopy e x h i b i t s the correct parent ion mass and a  - 1  base peak corresponding to a retro 2+2 fragmentation of the parent ion is The 400 MHz H nmr spectrum of the major cyclobutanol i s shown  observed.  l  in f i g u r e 53.  The methyl group on C  5 ppm  Figure 53:  l  at 1.11 ppm.  k  ppm  8  i s c l e a r l y v i s i b l e as a doublet  3 ppm  2 ppm  l pp  m  H nmr spectrum of the major cyclobutanol derived from photolysis of a-methyl-a-cyclohexyl-para-carboxyacetophenone  Decoupling of the signal at 1.11 ppm r e s u l t s in the  m u l t i p l e t observed at 2.31 ppm s i m p l i f y i n g to a doublet (J=10 Hz). signal at 2.31 can therefore be assigned to proton H . 8  The  In an N.O.E.  difference experiment, i r r a d i a t i o n of Hm r e s u l t s in the enhancement of H and in a d d i t i o n , the bridgehead hydrogen H  6  i s resolved from the  8  72  m u l t i p l e t signal at 1.7 ppm.  The f a c t that the signal due to the C  1 0  methyl group i s not enhanced c l e a r l y indicates that the methyl group i s s i t u a t e d trans to the aryl group.  Enhancement of the bridgehead proton H  6  i n d i c a t e s that the system i s a trans-cyclobutanol. The three minor cyclobutanol isomers observed from the photolysis of a-methyl-a-cyclohexyl-para-carboxyacetophenone were i d e n t i f i e d by the presence of a base peak in t h e i r g.c.m.s. which corresponds to a retro 2+2 fragmentation of the parent i o n . Photolysis of a-methyl-a-cyclopentyl-para-carboxyacetophenone,  in  a c e t o n i t r i l e , resulted in the formation of cyclopentene, para-carboxypropiophenone and two isomeric cyclobutanols.  The major  cyclobutanol was found to comprise 11% of the t o t a l cyclobutanol formed. This cyclobutanol was i s o l a t e d , as i t s methyl e s t e r , using column chromatography and studied s p e c t r o s c o p i c a l l y .  The i n f r a r e d spectrum of  the cyclobutanol shows a broad 0-H stretching band at 3466 c m . - 1  Mass  spectroscopy e x h i b i t s the correct parent ion mass and in addition a base peak corresponding to a retro 2+2 fragmentation of the parent ion is observed.  The 400 MHz W nmr spectrum of the major cyclobutanol i s shown  i n figure 54.  l  The methyl group on C  7  i s c l e a r l y v i s i b l e as a doublet  73  5 ppm  Figure 54:  1  A ppm  3 ppm  2  PP  m  1  PP  m  0  H nmr spectrum of the major cyclobutanol derived from photolysis of a-methyl-a-cyclopentyl-para-carboxyacetophenone  at 1.15 ppm (J=7 Hz).  The m u l t i p l e t observed at 2.53 ppm integrates for  two protons and the m u l t i p l e t at 2.79 ppm integrates for one proton. Decoupling the signal at 2.53 ppm r e s u l t s in the collapse of the methyl signal at 1.15 ppm (J=7 Hz) from a doublet to a s i n g l e t . the protons resonating at 2.53 ppm must be proton H . 7  C l e a r l y one of  Decoupling the  signal at 2.53 ppm also s i m p l i f i e s the m u l t i p l e t at 2.79 ppm from a m u l t i p l e t to a doublet (J=2.1 Hz). assigned to e i t h e r H or H . x  5  Hence, the signal at 2.79 ppm may be  In an N.O.E. difference experiment,  i r r a d i a t i o n of Hm r e s u l t s in a strong enhancement of the signal at 2.53 ppm and a weak enhancement of the signal at 2.79 ppm.  Since both of  74  the proton signals at 2.53 ppm are enhanced and the methyl group on C  7  not  enhanced suggests that the C methyl group i s trans to the aryl group. 7  The two remaining protons on the cyclobutane ring are also enhanced i n d i c a t i n g that the aryl group i s c i s to the bridgehead hydrogen H  5  in the  trans-cyclobutanol. The minor cyclobutanol isomer observed from the photolysis of a-methyl-a-cyclopentyl-para-carboxyacetophenone was i d e n t i f i e d by the presence of a base peak in i t s g.c.m.s. which corresponds to a retro 2+2 fragmentation of the parent i o n .  Geometry o f Hydrogen a b s t r a c t i o n  Of the f i f t e e n substituted acetophenones photolyzed in t h i s study, f i v e have had t h e i r structure determined by X-ray c r y s t a l l o g r a p h y . these f i v e cases, the geometry of the i n i t i a l can be observed.  For  hydrogen abstraction step  The geometry of hydrogen abstraction by the carbonyl  oxygen has been analyzed with respect to the previously defined parameters d, x and A (figure 10).  In a d d i t i o n , the overall geometry of the  six-membered t r a n s i t i o n states for abstraction have also been observed. These r e s u l t s are shown in table IV.  As seen in table IV, the distance  75  ketone  Table IV:  d(A)  Abstraction geometry  *(°)  M°)  2.7  46  77  2.7  49  77  boat  2.6  50  79  chai r  2.6  44  90  boat .  2.7  61  73  chai r  3.1* 3.5  50 56  58 73  boat  boat  62  62  6 2  5 0  5 3  6 1  63  Hydrogen abstraction geometries f o r several substituted acetophenones; (*) conformations in the s o l i d state t w 0  between the carbonyl oxygen atom and the y-hydrogen atom can be as great as 3.1 A and s t i l l  react photochemically in the s o l i d s t a t e .  Clearly,  most of the abstracting distances shown i n table IV f a l l w i t h i n the  76  hydrogen a b s t r a c t i o n l i m i t of approximately 2.7 A , as suggested by Scheffer and T r o t t e r * . 2 0  2 1  The a - m e t h y l - a - c y c l o p e n t y l ketone was  observed to have an abstracting distance of 3.1 A .  Scheffer and T r o t t e r  have also observed an abstaction distance of 3.1 A f o r a - c y c l o b u t y l - p a rachloroacetophenone . 21  This result suggests that 2.7 A may not be the  upper l i m i t f o r hydrogen abstaction.  Alternatively,  i t is possible that  bond rotations i n the c r y s t a l may lead t o a more favorable abstraction geometry.  The value of t has been observed to range from 44° t o a maximum  of 61°, yet hydrogen abstraction is s t i l l  observed.  This data suggests  that abstraction may occur from geometries in which the angle T has deviated s u b s t a n t i a l l y from the ideal value of 0°.  The observed values of  A are quite close to the ideal value of 90-120° as suggested by Scheffer and T r o t t e r * . 2 0  2 1  The geometry of the six-membered t r a n s i t i o n state f o r  hydrogen abstraction has been observed to vary from a c h a i r to a boat configuration.  It can be seen that f o r the a - c y c l o a l k y l - p a r a -  carboxyacetophenones (cyclohexyl and c y c l o o c t y l ) , the s i x membered t r a n s i t i o n state adopts a boatlike geometry.  This result is in agreement  with the boatlike abstraction geometries observed f o r the series of a - c y c l o a l k y l - p a r a - c h l oroacetophenones reported by Scheffer and Trotter * . 2 0  2 1  The introduction of an a-methyl substituent i n t o these  compounds changes the geometry f o r hydrogen abstraction such that a b s t r a c t i o n of a Y-hydrogen atom by the carbonyl oxygen of an a - m e t h y l - a cycloalkyl-para-carboxyacetophenone  (cyclohexyl and c y c l o o c t y l )  occurs  77  X  b o a t - l i k e t r a n s i t i o n state  Figure 55:  chair-like transition  state  B o a t l i k e and c h a i r l i k e abstraction geometries  through a c h a i r l i k e t r a n s i t i o n s t a t e .  This change i n the a b s t r a c t i o n  geometry of the six-membered t r a n s i t i o n state i s the result of a rotation about the a-carbon-carbonyl carbon bond which occurs with the addition of an a-methyl substituent.  For example, the addition of an a-methyl group  onto a - c y c l ooctyl-para-carboxyacetophenone  results i n a 91° rotation about  the a-carbon-carbonyl carbon bond as shown i n f i g u r e 55. The geometric change i s induced by a s t e r i c repulsion between the a-methyl group and the aromatic r i n g .  Stereodiagrams f o r the boat and chair abstraction  geometries are shown i n f i g u r e 56. Unlike the a-methyl-a-cycl ooctyl and a-methyl-a-cyclohexyl-para-carboxyacetophenones, a-methyl-a-cyclopentylpara-carboxyacetophenone assumes a boatlike hydrogen abstraction geometry.  78  C(U)  Figure 56a:  C(li)  a-Cyclooctyl-para-carboxyacetophenone, with a b o a t l i k e a b s t r a c t i o n geometry  79  Figure 56b:  a-Methyl-a-cyclooctyl-para-carboxyacetophenone, with a c h a i r l i k e abstraction geometry  Ratios of c y c l i z a t i o n to cleavage The 1,4 biradical generated from photolysis of a-methyl-acycloalkyl-para-carboxyacetophenones can undergo three possible transformations.  The biradical can fragment to form cleavage products,  close to form cyclobutanol products or revert to the ground state ketone by reverse hydrogen  abstraction (figure 57).  The percentage of cleavage  80  Figure 57:  Photoproducts derived from a - m e t h y l - a - c y c l o a l k y l - p a r a carboxyacetophenones  products from the b i r a d i c a l generated in benzene, a c e t o n i t r i l e and the s o l i d state are shown in f i g u r e 58.  As shown in the diagram, the r a t i o of  c y c l i z a t i o n to cleavage in the s o l i d state i s not s u b s t a n t i a l l y from that observed in s o l u t i o n .  different  This r e s u l t suggests that the motions  required for the formation of cleavage and c y c l i z a t i o n products  81  R i n g Size (n)  Figure 58:  % cleavage from the photolysis of a-methyl-a-cycloalkyl acetophenones in benzene, a c e t o n i t r i l e and the s o l i d state  are topochemically permitted in the s o l i d s t a t e .  Scheffer has shown that  p h o t o l y s i s of ene-dione 1 (figure 59) also gives the same photoproduct r a t i o s in the s o l i d state and b e n z e n e . 48  This r e s u l t i s due to the f a c t  82  Benzene S o l u t i o n Solid state  Figure 59:  l 1  The photochemistry of ene-dione 1 in benzene and the s o l i d state  that the molecular motions leading to the two photoproducts are topochemically allowed in the s o l i d s t a t e . It i s also possible that the s i m i l a r i t y between the s o l u t i o n and s o l i d state r e s u l t s may be due to c r y s t a l melting during p h o t o l y s i s . The percentage of cleavage products from the photolysis of a s e r i e s of a-cycloalkyl-para-carboxyacetophenones  (cyclooctyl, cycloheptyl,  cyclohexyl and cyclopentyl) in polar solvents ( a c e t o n i t r i l e and t - B u O H ) , 50  benzene and the s o l i d state are shown in figure 6 0 . 5 0  From t h i s p l o t ,  can be seen that the r a t i o of c y c l i z a t i o n to cleavage i s  slightly  it  83  8.  8-  *>  c  8  es  R-  A Benzene • l Acetonitrile •t-BuOH O Solid State  O  2  5.0  e.o  —i— 7.0  R i n g Size (n) Figure 60:  -1—  e.o  % cleavage from the photolysis of a - c y c l o a l k y l - p a r a carboxyacetophenones in polar solvent, benzene and the solid state 5 5  d i f f e r e n t in the s o l i d state as compared to s o l u t i o n .  The most dramatic  e f f e c t is an increase in the amount of c y c l i z a t i o n observed when a-cyclooctyl-para-carboxyacetophenone  i s photolyzed in the s o l i d s t a t e .  I t has been observed that a l l of the cyclooctyl d e r i v a t i v e s e x h i b i t higher  84  ratios of c y c l i z a t i o n i n the s o l i d than i n s o l u t i o n .  The percent cleavage  from the photolysis of several a - c y c l o o c t y l - p a r a - s u b s t i t u t e d acetophenones i s shown in f i g u r e 61.  In the case of the a - c y c l o o c t y l - p a r a - s u b s t i t u t e d  O Benzene ^ Acetonitrile • Solid State  co • CD CP  C  o  X - CI  X - CN  — i  X - COOH  r  para-substituent  Figure 61:  % cleavage vs para-substituent a - c y c l o o c t y l acetophenones  in various media f o r the  85  acetophenones i t appears that the c r y s t a l l a t t i c e s l i g h t l y impedes the r o t a t i o n s required for cleavage, thus favouring c y c l i z a t i o n .  The nature  of these motions w i l l be discussed l a t e r . Referring back to figures 58 and 60, i t i s apparent that there is no c o r r e l a t i o n between the cycloalkane ring size and the c y c l i z a t i o n to cleavage r a t i o .  I t i s also evident that the cyclohexyl and the cyclooctyl  d e r i v a t i v e s give the highest amount of c y c l i z a t i o n , whereas the cyclopentyl and cycloheptyl d e r i v a t i v e s tend to favour cleavage.  This  trend was also observed by Scheffer and Trotter for the photolysis of a series of a - c y c l o a l k y l - p a r a - c h l o r o a c e t o p h e n o n e s » . 20  21  I t was o r i g i n a l l y  thought that the s e l e c t i v i t y between c y c l i z a t i o n and cleavage i s due to whether the "p" o r b i t a l s of the b i r a d i c a l were in a favourable geometry for cleavage, keeping in mind that cleavage i s considered to be most favourable when the two "p" o r b i t a l s are coplanar with the a-p a-bond being cleaved.  The c a l c u l a t e d geometry of the "p" o r b i t a l s for the  b i r a d i c a l s generated from the a-cycloalkyl-para-chloroacetophenones ( c y c l o o c t y l , c y c l o h e p t y l , cyclohexyl,. cyclopentyl and cyclobutyl) are shown in figure 62 along with the r a t i o of c y c l i z a t i o n to cleavage in the solid state.  The geometry of the r a d i c a l "p" o r b i t a l on the carbonyl  carbon i s assumed to be orthoganol to the plane c o n s i s t i n g of the carbonyl carbon atom, the oxygen atom and the two carbon atoms alpha to the carbonyl carbon.  The geometry of the radical "p" o r b i t a l on the y-carbon  i s assumed to be orthoganol to the plane of the p, y and 6 carbon atoms. I t i s clear from figure 62 that the calculated b i r a d i c a l  "p" o r b i t a l  86  Ring Size  Figure 62:  0!  (°)  0  2  (°)  % cleavage  4  90  129  9 2  21  5  90  112  9 2  21  6  95  88  45  7  94  99  69  8  96  132  4  2 1  2 1  % cleavage in the s o l i d state as compared to the values of 0 and 0 f ° several a-cycloalkyl-para-chloroacetophenones X  2  r  geometries do not c o r r e l a t e with the observed r a t i o of c y c l i z a t i o n to cleavage.  If t h i s was the case then these b i r a d i c a l s would be expected to  give mostly c y c l i z a t i o n products, since the b i r a d i c a l "p" o r b i t a l s are e s s e n t i a l l y orthoganol to the o-bond being cleaved.  87  In l i g h t of t h i s r e s u l t we must look at other factors which may govern the r a t i o of c y c l i z a t i o n to cleavage. 1.  These may be the f o l l o w i n g :  the nature of the molecular motions required for product formation and;  2.  the thermodynamic s t a b i l i t i e s of the products formed. Referring to f i g u r e 60, there appears to be a trend toward an  increase in the r a t i o of c y c l i z a t i o n to cleavage as the c y c l o a l k y l s i z e increases.  ring  The most obvious geometric change observed i s an increase  i n the magnitude of the intraannular t o r s i o n angle n , accompanying an increase i n r i n g s i z e ( f i g u r e 63).  The values of n recorded in f i g u r e 63  88  I  Ring Size 4 5 6 7 8 Figure 63:  n  (°)  14 30 55 67 104  Magnitude of the angle n as the c y c l o a l k y l ring size increases from 4 to 8 for the a-cycloalkyl-para-chloroacetophenones  have been obtained from c r y s t a l ! o g r a p h i c studies of a - c y c l o a l k y l - p a r a chl oroacetophenones. If cleavage of the a - c y c l o a l k y l ketones is to occur, then the intraannular t o r s i o n angle fl must approach a value of 0° to a t t a i n the syn-pariplanar geometry required for alkene formation.  Significant  deviations of n away from t h i s geometry should favour c y c l i z a t i o n , since c y c l i z a t i o n does not require a planar t r a n s i t i o n geometry.  In a d d i t i o n ,  89  when the value of n becomes much greater than 0°, a large motion i s required to a t t a i n the planar geometry required for cleavage.  Thus, the  rate of motion of the ring towards the cleavage geometry may be slow compared to the rotations that bring the molecule into the geometry for c y c l i z a t i o n ( f i g u r e 64).  For example, photolysis of a - c y c l o p e n t y l - p a r a -  carboxyacetophenone resulted in 100% cleavage.  In t h i s case, the  intraannular t o r s i o n angle n i s approximately 30° and thus only a small amount of motion i s required for cleavage.  On the other hand, the value  of n f o r a-cyclooctyl-para-carboxyacetophenone i s 99° and as a r e s u l t , a large motion i s required to a t t a i n the geometry required for cycloalkene formation.  Perhaps the increase in the amount of c y c l i z a t i o n in the  Figure 64:  Bond rotations required for the formation of the trans-cyclobutanol  90  s o l i d state photolysis of a - c y c l o o c t y l - p a r a - s u b s t i t u t e d acetophenones (figure 60) may be due to a l a t t i c e  r e s t r i c t i o n which impedes n rotation  to the extent that the rotations required f o r c y c l i z a t i o n are favoured. If we assume that the r a t i o of c y c l i z a t i o n to cleavage f o r the a-cycloalkyl-para-carboxyacetophenones  is s o l e l y a function of the  cycl oalkyl intraannular t o r s i o n angle n , then we would expect the amount of c y c l i z a t i o n to increase as the intraannular t o r s i o n angle increases. This is not the case and i t is obvious that there are other factors  in  addition to the intraannular t o r s i o n angle which are i n f l u e n c i n g the r a t i o of c y c l i z a t i o n to cleavage.  One of these factors may be the thermodynamic  s t a b i l i t i e s of the photolysis products. cycl oalkanes  69  The s t r a i n energies of the  ( c y c l o o c t y l , c y c l o h e p t y l , cycl ohexyl and cycl opentyl) as  well as the calculated s t r a i n energies f o r the c y c l o a l k e n e s » > 7 0  7 1  7 2  (cis-cyclooctene, cis-cycloheptene, cyclohexene and cyclopentene) are shown in table V.  It can be seen that the s t r a i n energy of  91  Ring Size (n)  5 6 7 8 Table V:  Strain Energies  (kcal/mole)  cycloalkane  cycloalkene  6.5 0.0 6.3 9.6  6.8 2.5 6.7 7.4  7 0 7 0 7 0 7 0  ;6.9 ;2.6 ;7.25 ;8.8  7 1  7 2 7 2  7 2  The s t r a i n energies for some cycloalkanes and the c a l c u l a t e d s t r a i n energies for some cycloalkenes  cyclopentane i s very close to that for cylopentene, whereas the s t r a i n energy of cyclohexene i s approximately 2.5 kcal/mole higher than cyclohexane.  This may be a factor in the large amount of c y c l i z a t i o n  observed from oc-cyclohexyl-para-carboxyacetophenone as compared to a-cyclopentyl-para-carboxyacetophenone.  Likewise, the s t r a i n energy  difference between cycloheptane and cycloheptene i s also very small which may be a factor in the increase in the amount of cleavage observed in going from the cyclohexyl to the cycloheptyl ketone.  According to  table V, cyclooctene should be more stable than cyclooctane.  This r e s u l t  does not c o r r e l a t e with the photochemical data which shows a large decrease in the amount of cleavage for the a - c y c l o o c t y l - p a r a - s u b s t i t u t e d acetophenones. The thermodynamic s t a b i l i t y of the cyclobutanol products may also influence the r a t i o s of c y c l i z a t i o n to cleavage.  It i s very d i f f i c u l t  make any c o r r e l a t i o n between the s t a b i l i t i e s of the bicyclo  [n.2.0]  to  92  alkanols and the observed r a t i o of c y c l i z a t i o n to cleavage simply because the thermodynamic data a v a ila b le f o r these systems is quite l i m i t e d .  Some  data is a v a i l a b l e f o r the b i c y c l o [ n . 2 . 0 ] alkanes (n=3,4,5,6), but these have been found to vary in the l i t e r a t u r e .  The calculated s t r a i n energies  of some b i c y c l o [ n . 2 . 0 ] alkanes are shown in f i g u r e 65.  n (C  Figure 65:  Vn  3 4 5 6  The s t r a i n  ring s t r a i n (kcal/mole) 30.5 ;34.4 28.2 ;32.0 -32.0 -36.8 1 7  7 4  75  714  7 8  7 8  Calculated s t r a i n energies f o r some b i c y c l o [ n . 2 . 0 ] alkanes  energies reported f o r the b i c y c l i c [ 5 . 2 . 0 ] and [ 6 . 2 . 0 ] systems have not been calculated d i r e c t l y but are reported in the l i t e r a t u r e as approximations based on b i c y c l o [ n . 1 . 0 ] alkane s t a b i l i t e s .  It is  clear  that the ratios of c y c l i z a t i o n to cleavage do not correlate well with the reported s t r a i n energies f o r b i c y c l i c [n.2.0] alkanes.  This is evident  when we observe that the b i c y c l i c [ 6 . 2 . 0 ] alkane system has been reported to have the highest s t r a i n energy, yet the b i c y c l o [ 6 . 2 . 0 ] alkanols are the major products from photolysis of a - c y c l o o c t y l - p a r a - s u b s t i t u t e d acetophenones.  There are two problems associated with comparing the  s t r a i n energies encountered in the formation of the b i c y c l i c alkanols with the corresponding b i c y c l i c [ n . 2 . 0 ] alkanes.  [n.2.0]  Firstly,  in  93  forming the b i c y c l o [ n . 2 . 0 ] alkanols we are only interested i n the s t r a i n energy of forming the cyclobutane ring. formed.  The second ring has al ready been  Secondly, the e c l i p s i n g i n t e r a c t i o n s i n v o l v i n g the ring  substituents has not been taken i n t o account.  In l i g h t of t h i s  reasoning,  e c l i p s i n g and ring s t r a i n cannot be ruled out as factors i n f l u e n c i n g the r a t i o of c y c l i z a t i o n to cleavage.  It is possible that the reduced y i e l d s  of c y c l i z a t i o n products from the a - c y c l oheptyl and a-cycl opentyl ketones may be due to s t e r i c and s t r a i n factors involved i n cyclobutanol formati on. It is also worth noting that the s t r a i n energies of the photoproducts often do not c o r r e l a t e with the photoproduct  ratio.  Photolysis of cyclobutyl phenyl ketone results in a preference f o r the ring closure product over B e l i m i n a t i o n  7 6  (figure 66).  This result has  minor  Figure 66:  Photolysis of cyclobutyl phenyl ketone  product  94  been explained in terms of the r a d i c a l "p" o r b i t a l s being unable to overlap with the a - p carbon bond as i s required for cleavage to occur. The percent cleavage observed in the photolysis of the a-methyl-a-cycloalkyl-para-carboxyacetophenone series ( f i g u r e 58) shows some s i m i l a r i t i e s with the percent cleavage observed for the a - c y c l o a l k y l para-carboxyacetophenone series ( f i g u r e 60).  In both cases the c y c l o o c t y l  and cyclohexyl phenyl ketones have been shown to e x h i b i t the highest r a t i o s of c y c l i z a t i o n to cleavage with respect to the cyclopentyl and cycloheptyl phenyl ketones.  The most dramatic difference between the  non-methylated and a-methyl ketones was observed for the a-cyclopentyl ketone d e r i v a t i v e s .  a-Cyclopentyl-para-carboxyacetophenone produces only  cleavage products upon p h o t o l y s i s , whereas, for the a-methyl analogue, a-methyl-a-cyclopentyl-para-carboxyacetophenone, c y c l i z a t i o n accounts for 55% of the t o t a l products ( f i g u r e 67).  The difference observed in the  95  ketone  % cleavage  45%  100%  Figure 67:  50  % cleavage recorded f o r non methylated and a-methyl-a-cyclopentyl phenyl ketones  r a t i o of c y c l i z a t i o n to cleavage is not due to a change in the intraannular t o r s i o n angle n since a-methyl s u b s t i t u t i o n does not s i g n i f i c a n t l y change the c y c l o a l k y l  ring geometry.  s u b s t i t u t i o n does change the geometry of the ketone.  However, a-methyl The X-ray crystal  structure has indicated that the conformation of the b i r a d i c a l from a-methyl-a-cyclopentyl-para-carboxyacetophenone figure 68.  e x i s t s as shown i n  The conformation of the a-methyl-a-cyclopentyl  ketone as  96  Figure 68:  The b i r a d i c a l generated from a-methyl-a-cyclopentyl-paracarboxyacetophenone as viewed down the a-6 carbon bond  viewed down the a-B carbon bond (figure 68) appears to be in a geometry which very c l o s e l y resembles the geometry required f o r c y c l i z a t i o n .  Thus,  only a minimum amount of motion is required f o r c y c l i z a t i o n allowing c y c l i z a t i o n to compete with cleavage.  The motion required f o r c y c l i z a t i o n  of a - c y c l opentyl - para-chl oroacet ophenone is shown in f i g u r e 69.  In t h i s  case, the rate of cleavage is greater than the rate of the bond rotations  97  Figure 69: The b i r a d i c a l generated from a-cycl opentyl-parachloroacetophenone as viewed down the a-p carbon bond  required f o r c y c l i z a t i o n , hence, cleavage is the predominant process. There i s , however, a problem with t h i s explanation.  This problem l i e s  in  the fact that a - c y c l opentyl-para-carboxyacetophenone e x i s t s in two lowest energy conformations i n the c r y s t a l .  One of these conformations resembles  the conformation of a - c y c l opentyl-para-chl oroacetophenone as shown in figure 69, whereas the second resembles the geometry observed f o r a-methyl-a-cycl opentyl-para-carboxyacetophenone as shown i n f i g u r e 68. According to the theory just presented, both c y c l i z a t i o n and cleavage should be observed from the photolysis of a-cycl opentyl-paracarboxyacetophenone.  Since only cleavage is observed, t h i s suggests that  98  e i t h e r the theory is incorrect or only one of the conformations of a-cycl opentyl- para-carboxyacetophenone is reacting.  The hydrogen  a b s t r a c t i o n distances (d) and the angles x and A f o r these two conformers are given in f i g u r e 70.  Conformer I, which is expected to give mostly  Conformer I  Conformer II  d=2.9A T=48°  A=77°  Figure 70:  Two conformers of the b i r a d i c a l generated from a-cycl opentylpara-carboxyacetophenone  cleavage products, has a favourable hydrogen abstraction distance which i s w i t h i n the abstraction distance of approximately 2.7 A suggested by Scheffer and T r o t t e r .  The values of x and A, 17° and 80°, do not deviate  much from t h e i r ideal values of 0° and 90-120° r e s p e c t i v e l y .  The second  conformer, which is expected to produce more c y c l i z a t i o n products, has a l a r g e r hydrogen abstraction distance of 2.9 A.  In addition the angle x of  48° deviates considerably from the ideal value of 0°.  These angles and  distances suggest that conformer I may be reacting more rapidly i f not e x c l u s i v e l y with respect to conformer I I .  This may explain why only  99  cleavage is observed f o r the photolysis of a-cycl opentyl-paraca rboxyacet ophe none. The effect of a-methyl substituents on the r a t i o of c y c l i z a t i o n t o cleavage f o r the l a r g e r ring a - c y c l o a l k y l phenyl ketones  (cyclooctyl,  cycloheptyl and cyclohexyl) appears to be less dramatic than the e f f e c t produced upon a-methylation of a-cyclopentyl-para-carboxyacetophenone. The r a t i o of c y c l i z a t i o n to cleavage f o r a-methy 1-a-cyclohexyl-paracarboxyacetophenone is e s s e n t i a l l y the same as observed f o r the nonmethylated analogue.  For the a-methy1-a-cyclooctyl and a-methyl-a-  cycloheptyl acetophenones the amount of c y c l i z a t i o n is decreased by approximately 15% with respect to the non-a-methylated analogues (see figures 58 and 60).  The reason f o r t h i s decrease is not obvious looking  at the geometry of the s t a r t i n g ketone.  It may be possible that the  a-methyl group may d e s t a b i l i z e the t r a n s i t i o n state required f o r c y c l i z a t i o n via e c l i p s i n g i n t e r a c t i o n s with other ring substituents in the formation of the b i c y c l o [ n . 2 . 0 ] alkanols (n=5,6).  The E f f e c t of D i f f e r e n t Media on t h e C y c l o b u t a n o l R a t i o s  The ratios of the cycl obutanols formed from the photolysis of a - c y c l o a l k y l - p a r a - s u b s t i t u t e d acetophenones was observed to d i f f e r in d i f f e r e n t media.  For example, the ratios of trans- t o c i s - c y c l o b u t a n o l s  formed from the photolysis of a-cyclooctyl-para-chloroacetophenone benzene, a c e t o n i t r i l e and the s o l i d state are shown in figure 71.  in  100  6 CI  OH  HO-h-V~~\ hv  u  '  I  J  H  CI  H cis  trans  Sol vent  trans: cis  Benzene A c e t o n i t r i le S o l i d State Figure 71:  77:23 56:44 96:4  CI  The r a t i o of trans- to cis-cyclobutanols formed from the photolysis of a-cycl ooctyl-para-chl oroacetophenone in d i f f e r e n t media  In benzene and the s o l i d s t a t e , formation of the trans-cyclobutanol  is  favoured.  is  formed.  Thus, in these two media, the less hindered cyclobutanol Photolysis of a-cyclooctyl-para-chloroacetophenone  acetonitrile  in  resulted in more of the c i s - c y c l obutanol being formed.  This  result can be explained in terms of hydrogen bonding which increases the s t e r i c bulk of the hydroxy radical to the extent that i t becomes able to  101  compete with the aryl group f o r the more stable c i s p o s i t i o n with respect t o the nearest bridgehead hydrogen atom i n the cyclobutanol. The almost e x c l u s i v e formation of the trans-cyclobutanol from the s o l i d state photolysis of a - c y c l o o c t y l and a-cycloheptyl-para-substituted acetophenones can be a t t r i b u t e d to a topochemical r e s t r i c t i o n preventing the formation of the cis-isomer.  The predicted geometry of the b i r a d i c a l  generated from a-cyclooctyl-para-chloroacetophenone i s shown i n f i g u r e 72. It should be noted that only one of the two possible d i s r o t a t o r y or conrotatory motions lead t o the formation of cyclobutanols with c i s - f u s e d rings.  trans-cyclobutanol  Figure 72:  cis-cyclobutanol  Geometries of the c i s - and trans-cyclobutanols  102  Formation of the c i s - c y c l obutanol requires a 90° r o t a t i o n of the aryl group.  This r o t a t i o n i s topochemically disallowed since i t would r e s u l t  in the aromatic system bumping into the adjacent aryl group.  The packing  arrangement of the ketone molecules in the c r y s t a l l a t t i c e r e s u l t s in a 3.5 A i n t e r p l a n a r distance between the aryl groups.  This separation i s  not large enough to accommodate the motions required for the formation of the c i s - c y c l o b u t a n o l .  The packing diagram f o r a - c y c l o o c t y l - p a r a -  chl oroacetophenone i s shown in figure 73.  Figure 73:  Packing diagram of  trans-cyclobutanol  Formation of the  a-cyclooctyl-para-chloroacetophenone  i s topochemically allowed since the 90° aryl group  r o t a t i o n is not necessary for i t s formation.  Model studies also suggest  that the trans-cyclobutanol may be much better suited to f i t into the initial  reactant cavity than the c i s - c y c l o b u t a n o l .  To further v e r i f y  this  103  p o s s i b i l i t y i t would be b e n e f i c i a l to know the exact product geometries; however, X-ray c r y s t a l structures of the cyclobutanol products are unavailable. Experimentally, i t was also found that a small amount of the topochemically disfavoured cis-cyclobutanol was formed.  This r e s u l t may  be due to a p a r t i a l melting of the sample during p h o t o l y s i s . The product mixtures obtained from the photolysis of the a-methyl-a-cycloalkyl-para-carboxyacetophenones  r e s u l t s in the formation  of one major cyclobutanol and one, two or three additional minor cyclobutanol products.  The major cyclobutanol has the stereochemistry as  shown in figure 74. The methyl group in t h i s case i s trans to the aryl  104  " major  "  + other cyclobutanols  ring size (n) 5 6 7 8 Figure 74:  benzene {%)  A c e t o n i t r i l e {%)  S o l i d State (%)  77 56 54 70  76 48 60 76  100 49 63 31  Percentage of the major cyclobutanol as a function of the t o t a l cyclobutanol produced from photolysis of a-methyl - a cycloalkyl-para-carboxyacetophenones in various media  group which i s also the case for the major cyclobutanol derived from a-methylvalerophenone in b e n z e n e * . 32  33  The aryl group i s in the more  stable p o s i t i o n c i s to the nearest bridgehead hydrogen. For most of the a-methyl-a-cycloalkyl-para-carboxyacetophenones, the cyclobutanol r a t i o changes very l i t t l e in going from benzene to a c e t o n i t r i l e to the s o l i d s t a t e .  A possible explanation for t h i s r e s u l t  could be that these compounds are conformational^ r i g i d e x i s t i n g in the same conformations in the s o l i d state and s o l u t i o n .  Photolysis of  105  a-methyl-a-cyclooctyl-para-carboxyacetophenone in the s o l i d s t a t e , however, r e s u l t s in a very d i f f e r e n t cyclobutanol r a t i o than that observed in s o l u t i o n .  In t h i s case the minor cyclobutanol in s o l u t i o n has become  the major cyclobutanol in the s o l i d s t a t e .  The stereochemistry of t h i s  cyclobutanol i s not known since i t was formed in only 6% t o t a l y i e l d in a c e t o n i t r i l e and i s o l a t i o n was not p o s s i b l e . of the s t a r t i n g ketone i s shown in f i g u r e 75.  The X-ray c r y s t a l  Looking at the geometry of  the s t a r t i n g ketone, i t appears that the 1,4 b i r a d i c a l close to form a c i s - c y c l o b u t a n o l .  structure  "p" o r b i t a l s could  Further evidence for t h i s was obtained  when i t was found that the cyclobutanol has a s i m i l a r retention time to the cis-cyclobutanol derived from a-cyclooctyl-para-carboxyacetophenone.  106  Figure 75: X-ray c r y s t a l structure of a - m e t h y l - a - c y c l o o c t y l - p a r a carboxyacetophenone  Unfortunately, without any other s t r u c t u r a l evidence i t i s impossible to draw any s t r u c t u r e , r e a c t i v i t y  correlations.  Quantum Yields and Rate Studies  The quantum y i e l d s for product formation from the photolysis of several a - c y c l o a l k y l - p a r a - s u b s t i t u t e d acetophenones is shown in figure 76. The quantum y i e l d s for these ketones, as determined in benzene s o l u t i o n ,  107  n »  6  Ring Size (n) Figure 76:  Total product quantum y i e l d s f o r several acetophenones in benzene  are considerably less than u n i t y .  substituted  This i n e f f i c i e n c y , as suggested by  Wagner, can be accounted f o r by reverse hydrogen abstraction from t h e hydroxy-radical to the y-carbon r a d i c a l . The quantum y i e l d s f o r product formation from a-cyclooctyl and a-cycl oheptyl-para-cyanoacetophenones as well as a-cycl oheptyl-para-  108  carbomethoxyacetophenone was observed to be approximately 0.17.  Wagner  has determined that the quantum y i e l d s for type II e l i m i n a t i o n from para-cyano and para-carbomethoxyvalerophenones are both 0.19 in benzene solvent . 5 8  The quantum y i e l d s for t o t a l product formation from a series  of a-methyl-a-cycloalkyl-para-carbomethoxyacetophenones has been observed to be quite low in benzene solvent.  I t has been found that the t o t a l  quantum y i e l d for product formation from a-cycloheptyl-para-carboxyacetophenone i s almost three times as large as i t s corresponding a-methyl analogue.  Lewis has suggested that the lowering of quantum y i e l d s upon  a-methyl s u b s t i t u t i o n may be due to s t e r i c i n t e r a c t i o n s i n v o l v i n g the a-methyl group which increase the energy of the t r a n s i t i o n states required for c y c l i z a t i o n and cleavage, making return of the b i r a d i c a l to the ground s t a t e , by reverse hydrogen a b s t r a c t i o n , more f a v o u r a b l e * . 3 2  3 3  I t has been determined by X-ray crystallography that the B-hydrogen atoms on the a-methyl group may be in a better hydrogen abstraction geometry than the y-hydrogen atoms on a-methyl-a-cyclooctyl and a-methyl-cyclohexyl-para-carboxyacetophenone, as shown in f i g u r e 77.  109  Y--hydrogen  n  6 8 Figure 77:  p-hydrogen  d(A)  *(°)  M°)  2.7 2.6  61 50  73 79  d(A)  M°) 6 32  2.6 2.5  84 83  y-Hydrogen and P-hydrogen abstraction distances and angles f o r a-methyl-a-cyclooctyl and a-methyl-a-cyclohexyl-paraca rboxyacet ophe nones  The data c l e a r l y indicate that f o r these ketones, the p hydrogen atoms are more favourably oriented f o r abstaction than the y-hydrogen atoms.  If we  assume that the para-carbomethoxy ketones have a s i m i l a r geometry to the para-carboxy ketones in benzene, then the low quantum y i e l d s observed f o r the a-methyl ketones may also be due to a reversible p a b s t r a c t i o n . However, i t should be pointed out that the P-hydrogen is primary whereas the y-hydrogen i s secondary, thus, the rate of y-hydrogen abstraction may be much l a r g e r than the rate of P-hydrogen a b s t r a c t i o n .  For example, i t  is known that the rate of y-hydrogen abstraction i s 25x f a s t e r f o r valerophenone as compared toibutyrophenone . 25  The t e r t i a r y p-met pyre hydrogen has also been observed to be close to the abstracting carbonyl oxygen.  The distance between the P-methine  hydrogen has been observed to range from 2.5 A f o r a - c y c l o o c t y l - p a r a chloroacetophenone, to 3.5 A f o r a-methyl-a-cyclooctyl-para-  no  carboxyacetophenone.  This data suggests that the low quantum y i e l d s ,  benzene, may also be the result of a reversible B-methine hydrogen abst racton. The Stern-Volmer plots f o r the quenching of a-cycl ooctyl and a - c y c l oheptyl-para-cyanoacetophenone t r i p l e t s i n benzene are shown i n f i g u r e 78.  In both cases, the plots of * /* against quencher  in eg  in d-t-  0.0  |  |  0.04  1  1  0.08  1  0.12  Quencher Concentration (M) Figure 78a  in  Ill  Figure 78b  Figure 78: Stern-Volmer plots f o r a - c y c l ooctyl-para-cyanoacetophenone (a) and a - c y c l oheptyl-para-cyanoacetophenone (b)  concentration (2,5-dimethyl-2,4-hexadiene) are l i n e a r with slopes of 9.11 M"  1  and 6.78 M  respectively.  -1  f o r the a - c y c l o o c t y l and a-cycl oheptyl ketones  According to the Stern-Volmer r elationship (appendix I ) ,  112  the slope of the plot a> /* against quencher concentration 0  i s equal to k q x  where x i s the t r i p l e t l i f e t i m e and kq i s the rate of quenching by 2,5dimethyl-2,4-hexadiene. 5 x 10 M" 9  s"  1  The value of kq has been determined to be  in benzene, i f i t i s assumed that the rate of quenching i s  1  d i f f u s i o n controlled *, the values of % can be calculated to be 11  1.82 x 10" s and 1.36 x 1 0 9  s f o r the a-cyclooctyl and  -9  a-cycloheptyl-para-cyanoacetophenone t r i p l e t s respectively.  The l i f e t i m e  T i s equal to the inverse of the sum of the rate constants which deactivate the ketone t r i p l e t .  If i t i s assumed that hydrogen abstraction  is the major pathway f o r deactivation of the ketone t r i p l e t , then x i s equal to the inverse of the hydrogen rate constant k^. abstraction rate constants k 7.4 x 10  8  s"  1  Thus, the hydrogen  can be calculated to be 5.5 x 10  H  f o r the a-cyclooctyl and a-cycloheptyl  8  s  - 1  and  ketones respectively.  These rates are similar in magnitude to the rate of hydrogen abstraction of 5.7 x 10  s  8  _ 1  and 6.7 x 10  8  s"  1  for a-cycloheptyl and  a-cyclooctyl-para-chloroacetophenones r e s p e c t i v e l y * . 2 1  7 9  Wagner has  found the rates of y-hydrogen abstraction f o r para-cyanovalerophenone to be 6.89 x 10  7  s  - 1  as compared to 3.7 x 10  7  s  _ 1  for  para-chlorovalerophenone . 58  It i s interesting to note that the rate of hydrogen abstraction by the a-cyclooctyl and a-cycloheptyl-para-substituted (para-chloro  acetophenones  and para-cyano) are approximately lOx faster than the  corresponding para-substituted  valerophenones.  This result i s l i k e l y due  to the fact that the v-hydrogen in the a-cycloalkyl acetophenones i s in a  113  better geometry for abstraction than the corresponding para-substituted valerophenones. Another example of t h i s i s shown in figure 79.  The b i c y c l i c  ketone undergoes hydrogen abstraction nearly lOOx f a s t e r than  Figure 79:  Hydrogen abstraction rate constants for valerophenone and a r i g i d b i c y c l i c ketone  valerophenone.  This r e s u l t has been a t t r i b u t e d to the fact that the  Y-hydrogen atom and the carbonyl oxygen of the b i c y c l i c ketone are locked in a conformation p a r t i c u l a r l y favourable for hydrogen abstraction whereas valerophenone must form a six-membered t r a n s i t i o n state for abstraction to occur . 7 7  114  EXPERIMENTAL  General Melting points (mp_) were determined on a Fisher-Johns hot stage apparatus and are uncorrected.  Infrared spectra (i_r) were recorded on a  Perkin-Elmer model 710 B spectrometer or a Perkin-Elmer model 1710 F o u r i e r transform spectrometer.  Infrared spectra recorded on the Perkin-Elmer  model 710 B spectrometer were c a l i b r a t e d using the 1601 c m polystyrene.  -1  band of  The p o s i t i o n of absorption maxima are given in c m .  Neat  - 1  i n f r a r e d spectra were obtained f o r a l l o i l s and the spectra of s o l i d s were obtained i n KBr p e l l e t s .  U l t r a v i o l e t spectra (uv) were obtained in  a c e t o n i t r i l e or MeOH and recorded on a Pye Unicam Ph 880 UV/Vis spectrophotometer.  The proton nuclear magnetic resonance spectra ( H nmr) X  were observed in deuterochloroform and recorded at 80 MHz on a BrCfker WP-80 spectrometer, at 270 MHz using an Oxford instrument with a 63.4 KG superconducting magnet, a Nickolet 32 K computer and Broker TT-23 console, at 300 MHz on a Varian XL-300 spectrometer or at 400 MHz on a BrUker WH-400 spectrometer.  Signal positions are given in ppm with  tetramethylsi 1 ane as the reference. constants are l i s t e d in brackets.  Signal m u l t i p l i c i t i e s and coupling  Low and high resolution mass spectra  (ms) were recorded on a Kratos model MS 50 mass spectrometer.  Combined  gas chromatography-mass spectroscopy was performed on a Kratos MS 80 mass spectrometer coupled to a Karlo-Erba gas chromatograph.  Gas  chromatography f o r the product r a t i o studies was performed on a Hewlett-Packard 5890 A gas chromatograph coupled to a Hewlett-Packard  115  3392 A i n t e g r a t o r .  The c a r r i e r gas was helium and the mode of detection  was flame i o n i z a t i o n .  The column head pressure was 20 p s i .  Retention  times ( r t ) are recorded in minutes and the following column and programs were used:  .210° Program 1: Column A:  i^L . 1 min  ' 20°C/min  Carbowax 12m (0.25n) .200° Program 2:  All  I1°L.-" 1 min  20  ° / C  min  reactions i n v o l v i n g water-sensitive reagents were c a r r i e d out under  dry nitrogen using oven-dried glassware. p u r i f i e d as f o l l o w s :  The solvents and reagents were  tetrahydrofuran was d i s t i l l e d from l i t h i u m aluminum  hydride; benzene, di i s op ropy 1 amine, dimethyl sulphoxide and ethanol were d i s t i l l e d from calcium hydride.  Benzene used in photochemical quenching  and rate studies was washed with sulphuric a c i d , water, d i l u t e sodium hydroxide and water. distilled.  It was then dried over phosphorous pentoxide and  Spectral grade benzene and a c e t o n i t r i l e were used f o r product  r a t i o determinations.  Photolysis was performed using a 450 W medium  pressure Hanovia lamp placed in a water-cooled Pyrex immersion well (X > 290 nm) or a Molectron UV 22 pulsed nitrogen l a s e r (A. = 337 nm). Microanalysis was performed by Peter Borda of the U.B.C. Department.  Chemistry  The X-ray c r y s t a l structure of compound 30 was determined by  116  Dr. Sara A r i e l , and a l l the remaining X-ray structures were determined by Stephen Evans.  Synthesis of S t a r t i n g  C y c l o o c t y l Bromide  Materials  (1)  Following the procedure of W i l l s t a t t e r and Waser , 274 g 54  (2.5 moles) of cyclooctene was added to 400 mi of g l a c i a l acetic a c i d . This s o l u t i o n was s t i r r e d at room temperature while hydrobromic acid was slowly bubbled through i t .  The hydrobromic acid addition was maintained  f o r 5 hours, a f t e r which time the addition was stopped and the s o l u t i o n s t i r r e d for twelve additional hours.  The mixture was taken up in 500 mi  of water and the organic layer was extracted three times with 200 ml of d i e t h y l ether.  The combined ether extracts were washed twice with 100 mil  of water followed by 100 ml of aqueous sodium bicarbonate s o l u t i o n and f i n a l l y with a further 100 ma of water.  The organic layer was dried over  anhydrous sodium sulphate and f i l t e r e d .  The product was concentrated by  rotary evaporation followed by vacuum pumping.  D i s t i l l a t i o n at 83°C  (0.5 mm Hg) y i e l d e d 337 g (1.8 moles, 71% y i e l d ) of the c l e a r o i l (lit  5 4  :  b.p. 90.5-91.5°C (10 mm Hg); y i e l d , 93%):  l  H nmr (CDCA , 80 MHz)  1.1-1.9 (10H, m), 2.0-2.5 (4H, m), 4.4 (IH, m); m/e ( r e l a t i v e 111 (52.6), 69 (100).  product 3  intensity)  117  Cyclooctyl Acetic Acid (2) Following the procedure of B l i c k e and J o h n s o n , 19.8 g 55  (0.79 moles) of sodium metal was slowly added to 460 mSL of dry ethanol which was s t i r r i n g under a nitrogen atmosphere.  When a l l of the sodium  metal had d i s s o l v e d , 160 g (0.86 moles) of diethyl malonate was added dropwise, over 10 minutes, to the s t i r r i n g solution of sodium ethoxide. The reaction was s t i r r e d at room temperature for two hours.  Next, 150 g  (0.79 moles) of c y c l o o c t y l bromide (1) was added to the reaction mixture, dropwise over a period of 15 minutes. and s t i r r e d f o r 3.5 days.  The reaction was brought to r e f l u x  I t was then cooled to 0°C and the p r e c i p i t a t e d  sodium bromide s a l t was removed by suction f i l t r a t i o n .  The ethanol  solvent was removed by rotary evaporation to y i e l d a dark o i l .  The o i l  was added to a r a p i d l y s t i r r i n g s o l u t i o n of 300 mJl water, 89 g of potassium hydroxide and 40 ml of ethanol. r e f l u x for a period of 3.5 hours.  The reaction was heated to  The solution was cooled to room  temperature, a c i d i f i e d with 160 ml of concentrated hydrochloric a c i d , and s t i r r e d for 24 hours.  The resultant o i l y layer was removed and the  remaining aqueous phase was extracted twice with 100 ml of diethyl  ether.  The o i l y layer and organic extracts were combined, washed with 100m£ of water and dried over anhydrous magnesium sulphate. f i l t e r e d and concentrated by rotary evaporation.  The s o l u t i o n was The resultant o i l was  transferred to a round bottom flask containing 1 g of copper-bronze and heated to approximately 100°C under vacuum (35 mm Hg) for 4 days.  The  resultant product d i s t i l l e d at 168-172°C (0.5 mm Hg) to y i e l d 61.7 g (0.36 moles, 46% y i e l d ) of the product ( l i t  5 5  :  y i e l d 42.5%):  ir  (neat)  118  1708 cm-  1  (broad, O O ) , 3000 cm"  1  (broad, OH); H nmr (CDCi , 80 MHz) X  3  1.0-1.9 (15H, m), 2.3 (2H, s ) , 10.84 (IH, s ) ; m/e ( r e l a t i v e i n t e n s i t y ) 170 (m+, 1.7), 152 (0.82), 111 (100), 69 (91.3).  Cycloheptenyl Acetic Acid  (3)  Following the procedure of McCarthy et a l .  5 6  ,  of cycloheptanone was added to 150 ml of dry benzene.  100 g (0.89 moles) Cyanoacetic acid  (76 g, 0.89 moles) and 3.0g (50 mmoles) of ammonium acetate were added to the f l a s k , and the reaction was brought to r e f l u x .  The reaction was  maintained at r e f l u x f o r 2.5 days while water was continuously being removed from the r e a c t i o n .  When no more water was being evolved the  reaction was stopped and the benzene solvent was removed by rotary evaporation to y i e l d an o i l .  The o i l was decarboxylated by heating i t at  approximately 100°C at reduced pressure (30 mm Hg) for a period of 1 day. The o i l was cooled and taken up in 100 ml of diethyl ether.  The organic  phase was washed with 50 ml of water, 50 ml of a saturated sodium bicarbonate s o l u t i o n and 50 ml of water. anhydrous sodium sulphate and f i l t e r e d .  The ether layer was dried over The ether was removed by rotary  evaporation and the o i l d i s t i l l e d at 128-134°C (26-30 mm Hg): 2280 c m  -1  (C^N).  ir_ (neat)  The resultant o i l was added to a s t i r r i n g solution of  250 ml water, 80 g of sodium hydroxide and 30 mi of water. was brought to r e f l u x and allowed to react f o r 3 days.  The mixture  The reaction was  cooled to room temperature and a c i d i f i e d with 170 ml of concentrated hydrochloric a c i d . 1 day.  The reaction was s t i r r e d at room temperature for  The o i l y layer was separated from the aqueous layer and the  aqueous layer extracted twice with 150 ml of diethyl ether.  The ether  119  extracts and the o i l y layer were combined, dried over anhydrous sodium sulphate, and f i l t e r e d .  The ether solvent was removed by rotary  evaporation to y i e l d a yellow o i l .  The o i l was d i s t i l l e d at 150-160°C  (15 mm Hg) to y i e l d 72.1 g (0.47 moles, 53% y i e l d ) of a c l e a r o i l b.p. 155-160 (15 mm Hg); y i e l d 75%): (broad, C=0), 2900 cm"  1  l r (neat) 1635 cm-  1  (lit  5 6  :  (C=C), 1704 cm"  (broad, OH); ^ nmr (CDCi , 400 MHz) 1.45-1.6 3  (4H, m), 1.6-1.8 (4H, m), 2.11 (2H, m), 2.20 (2H, m), 5.71 (IH, m), 10.4 (IH, s, broad); m/e ( r e l a t i v e i n t e n s i t y ) 154 (m , 42.6) 136 (14.7), +  94 (100).  Cycloheptyl Acetic Acid  (4)  Following a modified procedure of Sauvage et a l .  5 7  , 27.2 g  (0.177 moles) of cycloheptenyl acetic acid (3) was dissolved in 75 ml of dry methanol and placed in a bomb hydrogenation apparatus. added 2 g of 10% palladium on charcoal. temperature for two days under 500 l b s / i n  To t h i s was  The reaction was s t i r r e d at room 2  of hydrogen gas.  The mixture  was f i l t e r e d and the methanol removed by rotary evaporation to y i e l d an o i l as product: L  j_r (neat) 1708 cm"  1  (broad, C=0), 2930 cm-  1  (broad, OH);  H nmr (CDC* , 80 MHz) 0.7-2.0 (13H, m), 2.3 (2H, d, J=7 Hz), 10.7 3  (IH, s, broad); m/e ( r e l a t i v e i n t e n s i t y ) 156 (m , 2.1), 138 ( 2 . 3 ) , +  97 (100).  C y c l o o c t y l A c e t y l C h l o r i d e (5)  Following a modified procedure of Blicke and J o h n s o n , 3.4 g 55  1  120  (0.020 moles) of c y c l o o c t y l acetic acid (2) was placed in a dry round bottom f l a s k .  To t h i s was added 3 mi (0.042 moles) of thionyl  chloride,  and the reaction was s t i r r e d at room temperature f o r 45 minutes.  The  excess thionyl chloride was removed by vacuum pumping and the resultant o i l was d i s t i l l e d at 122°C (0.6 mm Hg) to y i e l d 3.43 g (0.018 moles, 91% y i e l d ) of the product.  The cyclooctyl acetyl chloride was immediately  u t i l i z e d in F r i e d e l - C r a f t s a c y l a t i o n reactions and no spectroscopic data was obtained.  Cycloheptyl Acetyl Chloride  (6)  Acid chloride (6) was prepared from cycloheptyl acetic acid (4) i n the same sequence of steps as in the synthesis of cyclooctyl chloride ( 5 ) .  acetyl  The product was d i s t i l l e d at 102°C (0.5 mm Hg) to y i e l d an  o i l in 93% y i e l d .  The cycloheptyl acetyl chloride was immediately used in  F r i e d e l - C r a f t s a c y l a t i o n reactions and no spectroscopic data was obtained.  Cyclohexyl Acetyl Chloride  (7)  Acid c h l o r i d e (7) was prepared from cyclohexyl acetic acid (Aldrich) in the same sequence of steps as in the synthesis of (5). product was d i s t i l l e d at 62°C (0.5 mm Hg) to y i e l d a clear l i q u i d in 94% y i e l d .  The cyclohexyl acetyl chloride was immediately used in  F r i e d e l - C r a f t s a c y l a t i o n reactions and no spectroscopic data was obtained.  The  121  Cyclopentyl Acetyl Chloride  (8)  Acid Chloride (8) was prepared from cyclopentyl a c e t i c acid ( A l d r i c h ) in the same sequence of steps as in the synthesis of (5).  The  product was d i s t i l l e d at 36°C (0.5 mm Hg) to y i e l d a c l e a r l i q u i d in 95% y i e l d .  The cyclopentyl acetyl chloride was immediately used in  F r i e d e l - C r a f t s a c y l a t i o n reactions and no spectroscopic data was obtained.  2 - c y c l o o c t y l - l - ( 4 - c h 1 o r o p h e n y 1 )-ethanone  (9)  a-Cyclooctyl-para-chloroacetophenone modified procedure of Wagner et a l .  5 8  6 2  (9) was prepared following a  ; 3.43 g (18 mmoles) of c y c l o o c t y l  acetyl c h l o r i d e (5) was added to 2.4 g (18 mmoles) of aluminum trichloride.  To t h i s mixture was added 5.5 mi (54 mmoles) of  chlorobenzene and the reaction was s t i r r e d under dry c o n d i t i o n s . of hydrochloric acid were observed to be evolved. to s t i r at room temperature f o r 24 hours. and quenched with ice cold water. with 100 ml of diethyl ether.  Bubbles  The mixture was allowed  The reaction was cooled to 0°C  The organic phase was extracted twice  The combined organic extracts were washed  with 50 mi of an aqueous sodium bicarbonate solution and twice with 50 mi of water.  The organic phase was dried over anhydrous sodium sulphate and  filtered.  The diethyl ether was removed by rotary evaporation and vacuum  pumping to y i e l d a yellow o i l .  The o i l was d i s t i l l e d and the higher  b o i l i n g f r a c t i o n was c o l l e c t e d at 219°C (0.3 mm Hg) to y i e l d a c l e a r o i l which immediately c r y s t a l l i z e d to y i e l d 3.55 g (13 mmoles, 75% y i e l d ) of the product.  R e c r y s t a l l i z a t i o n from ethanol y i e l d e d white c r y s t a l s , mp_  122  48-49°C:  vr (KBr) 1681 cm" (C=0); H nmr (CDCA , 400 MHz) 1.38 (2H, m), 1  X  3  1.45-1.80 (12H, m), 2.26 (IH, m), 2.84 (2H, d, J=8 Hz), 7.42 (2H, d, J=8.8 Hz), 7.88 (2H, d, J=8.8Hz); m/e ( r e l a t i v e i n t e n s i t y ) 264/266 (m+, 0.45/0.13), 154/156 (100/35.9), 139/141 (56.4/19.3); mass, C H 0 C i / C H 0 C X : 3 5  1 6  2 1  264.1269/266.1255; Found:  C, 72.69;  264.1281/266.1281, Found:  3 7  1 6  calculated  2 1  A n a l . , c a l c u l a t e d for C H i 0 C A : 16  2  C, 72.56; H, 8.00,  H, 8.00; uv Umax, n , n * , MeOH) 316 nm,  emax=40 l i t r e s • m o l e s  -1  • cm . - 1  2-cyclooctyl-l-(4-methoxypheny1)-ethanone  (10)  a-Cyclooctyl-para-methoxyacetophenone (10) was prepared from anisole and c y c l o o c t y l acetyl chloride in the same sequence of steps as in the synthesis of ( 9 ) .  The o i l recovered was d i s t i l l e d at 195-200°C  (0.5 mm Hg) to y i e l d a c l e a r o i l .  The o i l was r e c r y s t a l 1 i z e d 4 times from  petroleum ether at approximately -70° to y i e l d an o i l at room temperature as the f i n a l product in 47% y i e l d :  j_r (neat) 1676 c m  - 1  (C=0); H nmr l  (CDCJI3, 400 MHz) 0.85 (IH, m), 1.2-1.8 (13H, m), 2.24 (IH, m), 2.98  (2H, d, J=8Hz), 3.82 (3H, s ) , 6.89 (2H, d, J=8.8 Hz), 7.90 (2H, d, J=8.8 Hz);  m/e ( r e l a t i v e i n t e n s i t y ) 260 (m+, 0.10), 150 (100), 135  (65.7).  2-cyclooctyl-l-(4-methy!phenyl)-ethanone  (11)  a-Cyclooctyl-para-methylacetophenone (11) was prepared from toluene and c y c l o o c t y l acetyl c h lor id e in the same sequence of steps as i n the synthesis of ( 9 ) .  The o i l recovered was d i s t i l l e d at 190-200°C  (0.5 mm Hg) to y i e l d a c l e a r o i l as product i n 66% y i e l d :  ir^ (neat)  123  1685 cm-  1  (C=0); H nmr (CDCi , 400 MHz) 1.3-1.7 (14H, m), 2.27 (1H, m), 1  3  2.39 (3H, s ) , 2.82 (2H, d, J=7.6 Hz), 7.23 (2H, d, J=8.4 Hz), 7.84 (2H, d, J=8.4 Hz); m/e ( r e l a t i v e i n t e n s i t y ) 244 (m+, 0.10), 134 (100), 119 (30.7); c a l c u l a t e d mass, C H 0 : 1 7  2 4  244.1827, Found:  244.1831.  2-cyclooctyl-l-(4-f1uoropheny1)-ethanone (12) a-Cyclooctyl-para-fluoroacetophenone  (12) was prepared from  fluorobenzene and c y c l o o c t y l acetyl c h l o r i d e in the same sequence of steps as in the synthesis of (9).  The o i l recovered was d i s t i l l e d at 196-198°C  (0.5 mm Hg) to y i e l d a c l e a r o i l as product i n 83% y i e l d : 1682 cm"  1  ir_ (neat)  (C=0); H nmr (CDCi , 400 MHz) 1.3-1.8 (14H, m), 2.27 (IH, m), l  3  2.84 (2H, d, J=7.6 Hz), 7.1 (2H, m), 7.9 (2H, m); m/e ( r e l a t i v e  intensity)  248 (m , 2.20), 138 (100), 123 (40.7). +  2-cycloheptyl-l-(4-f1uoropheny1)-ethanone (13) (13) was prepared from  a-Cycloheptyl-para-fluoroacetophenone  fluorobenzene and cycloheptyl acetyl chloride (6) in the same sequence of steps as in the synthesis of (9).  The o i l recovered was d i s t i l l e d at  159°C (0.5 mm Hg) to y i e l d a c l e a r o i l as product i n 80% y i e l d : 1686 cm"  1  ir^ (neat)  (C=0); H nmr (CDCi , 400 MHz) 1.26 (2H, m), 1.38-1.85 (10H, m), X  3  2.22 (IH, m), 2.85 (2H, d, J=7.6 Hz), 7.10 (2H, m), 7.98 (2H, m); m/e ( r e l a t i v e i n t e n s i t y ) 234 (m+, 1.9), 138 (100), 123 (70.0), 95 (35.8).  2-cyclohexyl-l-(4-fluorophenyl)-ethanone ( 1 4 ) a-Cyclohexyl-para-fluoroacetophenone  60  (14) was prepared from  124  fluorobenzene and cyclohexyl acetyl chloride (7) in the same sequence of steps as in the synthesis of (9).  The o i l  recovered was d i s t i l l e d at  138°C (0.5 mm Hg) to y i e l d a c l e a r o i l i n 87% y i e l d : (OO):  l  j_r (neat) 1686 cm"  1  H nmr (CDCi , 300 MHz) 0.85-1.4 (5H, m), 1.5-1.85 (5H, m), 2.09 3  (IH, m), 2.79 (2H, d, J=7.5 Hz), 7.11 (2H, m), 7.97 (2H, m); m/e ( r e l a t i v e i n t e n s i t y ) 220 (m , 3 . 0 ) , 138 (100), 123 (58.9), 95 (20.3); +  mass, C H 0 F : 1 H  1 7  220.1263, Found:  calculated  220.1264.  2-cyc1opentyl-l-(4-fluorophenyl)-ethanone  (15)  a-Cyclopentyl-para-fluoroacetophenone  6 0  (15) was prepared from  fluorobenzene and cycl opentyl acetyl chloride (8) i n the same sequence of steps as in the synthesis of (9).  The o i l  recovered was d i s t i l l e d at  129°C (0.7 mm Hg) to y i e l d a c l e a r o i l product i n 88% y i e l d : 1687 cm"  1  j!  (neat)  ( 0 0 ) , H nmr (CDCi , 300 MHz) 1.13 (2H, m), 1.56 (4H, m), 1.85 X  3  (2H, m), 2.33 (IH, m), 3.92 (2H, d, J=7.5 Hz), 7.09 (2H, m), 7.95 (2H, m), m/e ( r e l a t i v e i n t e n s i t y ) 206 (m , 3.5), 138 (45.0), 123 (54.3), 95 (100). +  2-cyclooctyl-2-methyl-l-(4-f1uorophenyl)-ethanone  (16)  a-Methyl-a-cyclooctyl-para-fluoroacetophenone f o l l o w i n g a modified procedure of Creger et a l .  5 9  ,  (16) was prepared  i n which 100 mi of dry  tetrahydrofuran was added to 5.1 mi (36 mmoles) of diisopropylamine.  This  mixture was s t i r r e d under a nitrogen atmosphere and cooled t o 0°C f o r a period of 5 minutes.  A s o l u t i o n of 23.4 mi of 1.55 M n-butyl l i t h i u m in  hexanes was slowly added to the flask and the resultant s o l u t i o n was  125  s t i r r e d at 0°C f o r 20 minutes.  Ketone (12) (7.5 g, 30 mmoles) was  dissolved in 20 ml of dry tetrahydrofuran and t h i s solution was added dropwise over 10 minutes to the s t i r r i n g solution of l i t h i u m diisopropyl amide.  The reaction was s t i r r e d at 0°C for 2 hours.  The generation of  the enolate could be monitored by the formation of a deep red colored s o l u t i o n in the reaction f l a s k .  Methyl iodide (2.3 ml, 36 mmoles) was  added to the reaction and the solution was allowed to slowly warm to room temperature.  The reaction was s t i r r e d at room temperature for two days.  The reaction of the enolate with the methyl iodide could be monitored by observing the loss of the deep red c o l o r in the s o l u t i o n . was quenched with 50 ml of water. with 100 ml of diethyl ether.  The reaction  The organic phase was extracted twice  The combined extracts were washed with  50 ml of an aqueous brine s o l u t i o n and then twice with 50 ml of water. The organic phase was dried over anhydrous sodium sulphate and f i l t e r e d . The diethyl ether solvent was removed by rotary evaporation and vacuum pumping to leave 7.5 g (28 mmoles, 93% y i e l d ) of an o i l .  The o i l was  analyzed by gas chromatography and found to contain 10% s t a r t i n g material and 90% product:  rr (neat) 1682 c n r  1  (C=0);  H nmr (CDCi , 300 MHz) 1.13  l  3  (3H, d, J=7.0 Hz), 1.20-1.80 (14H, m), 2.03 (IH, m), 3.33 (IH, m), 7.31 (2H, m), 7.96 (2H, m); m/e ( r e l a t i v e i n t e n s i t y ) 262 (m+, 0 . 8 ) , 152 (100), 123 (74.0), 95 (38.0).  2-cycloheptyl-2-methyl-l-(4-f1uoropheny1)-ethanone (17)  a-Methyl-a-cycloheptyl-para-fluoroacetophenone (17) was prepared  126  from (13) in the same sequence of steps as in the synthesis of (17). o i l was i s o l a t e d in 93% y i e l d .  An  The o i l was analyzed by g.c. and found to  contain 13% s t a r t i n g material and 87% product:  ir_ (neat) 1682 c m  - 1  (C=0);  H nmr (CDCA , 300 MHz) 1.10 (3H, d, J=7.0 Hz), 1.1-1.8 (12H, m), 1.9  X  3  (IH, m), 3.32 (IH, m), 7.09 (2H, m), 7.93 (2H, m);  m/e ( r e l a t i v e  i n t e n s i t y ) 248 (m , 0.7), 152 (100), 123 (77.1), 95 (25.8). +  2-cyclohexyl-2-methy1-l-(4-fluorophenyl)-ethanone (18) a-Methyl-a-cyclohexyl-para-fluoroacetophenone  (18) was prepared  from (14) in the same sequence of steps as in the synthesis of (17). o i l was i s o l a t e d in 85% y i e l d .  An  The o i l was analyzed by g.c. and found to  contain 10% s t a r t i n g material and 90% product:  jjr (neat) 1681 c n r  1  (C=0);  H nmr (CDCA , 300 MHz) 0.8-1.3 (4H, m), 1.1 (3H, d, J=7 Hz), 1.5-1.8  l  3  (7H, m), 3.24 (IH, m), 7.09 (2H, m), 7.95 (2H, m); m/e ( r e l a t i v e i n t e n s i t y ) 234 (m+, 0.5), 152 (100), 123 (54.3), 95 (15.2); c a l c u l a t e d mass, C H 0 F : 1 5  234.1420, Found:  1 9  234.1428.  2-cyclopentyl-2-methy1-l-(4-fluorophenyl)-ethanone (19) a-Methyl-a-cyclopentyl-para-fluoroacetophenone  (19) was prepared  from (15) in the same sequence of steps as in the synthesis of (17). yellow o i l was i s o l a t e d in 90% y i e l d .  The o i l was analyzed by g.c. and  found to contain 8% s t a r t i n g material and 92% product: 1681 cm"  1  A  ir. (neat)  (C=0); H nmr (CDW , 300 MHz) 0.90-1.90 (10H, m), 1.18 (3H, d, l  3  J=7 Hz), 3.22 (IH, m), 7.05 (2H, m), 7.95 (2H, m); m/e ( r e l a t i v e i n t e n s i t y ) 220 (m+, 0.5), 152 (48.9), 123 (100), 95 (35.2).  127  2-cyclooctyl-l-(4-cyanopheny1)-ethanone  (20)  a-Cycl ooctyl-para-cyanoacetophenone a modified procedure of Wagner and S i e b e r t  (20) was prepared following 5 8  in which 6.67 g (27 mmoles)  of (12) was dissolved in 50 mi of dry dimethyl sulphoxide to which was added 4.3 g (89 mmoles) of sodium cyanide.  The reaction was heated to  110-120°C and s t i r r e d f o r 2 days under anhydrous conditions.  The reaction  was cooled to room temperature and quenched with 50 mi of water. organic phase was extracted twice with 75 mi of diethyl ether.  The The ether  extracts were combined, washed twice with 50 mi of water and dried over anhydrous sodium sulphate.  The s o l u t i o n was f i l t e r e d and the diethyl  ether removed by rotary evaporation and vacuum pumping to y i e l d a reddish colored s o l i d .  The s o l i d was chromatographed on a column (2.5 cm x 20 cm)  of s i l i c a gel 60 (230-400 mesh) using a step gradient of 0-5% ethyl acetate in petroleum ether as the eluent.  The combined f r a c t i o n s  containing the product were concentrated giving 5.5 g (22 mmoles, 76% y i e l d ) of a white s o l i d product. white c r y s t a l s , mp_ 62-63°C:  R e c r y s t a l 1 i z a t i o n from ethanol gave  j_r (KBr) 1687 cm"  1  (C=0), 2230 cm- (C=N), 1  nmr (CDCi , 300 MHz) 1.2-1.8 (14H, m), 2.28 (IH, m), 2.87 (IH, d, 3  J=7.5 Hz), 7.77 (2H, d, J=8.5 Hz), 8.03 (2H, d, J=8.5 Hz);  m/e ( r e l a t i v e  i n t e n s i t y ) 255 (m , 2.7), 145 (100), 130 (29.2); calculated mass, +  C H 0N:  255.1623, Found:  C, 79.96,  H, 8.29, Found:  1 7  2 1  255.1623; A n a l . , calculated f o r C H 0 N : 1 7  2 1  C, 79.89; H, 8.49; uv (\ max, n , n * , MeOH)  324 nm, emax=123 l i t r e s • m o l e s  -1  • cm . - 1  128  2-cycloheptyl-l-(4-cyanopheny1)-ethanone (21) (21) was prepared from (13)  a-Cycloheptyl-para-cyanoacetophenone  in the same sequence of steps as in the synthesis of (20).  Following  column chromatography, a white s o l i d was i s o l a t e d in 71% y i e l d .  The s o l i d  was r e c r y s t a l l i z e d from ethanol to y i e l d white c r y s t a l s , mp_ 41-42°C: vr_ (KBr) 1692 cm-  1  (C=0), 2224 cm-  1  (C=N); U nmr (CDCi , 400 MHz) 1.26 l  3  (2H, m), 1.4-1.8 (10H, m), 2.19 (IH, m), 2.89 (2H, d, J=7.5 Hz), 7.76 (2H, d, J=8.5 Hz), 8.03 (2H, d, J=8.5 Hz); m/e ( r e l a t i v e i n t e n s i t y ) 241 (m , 6.9), 145 (100), 130 (67.8); c a l c u l a t e d mass, C H 0 N : +  16  19  Found:  241.1466; A n a l . , c a l c u a l t e d for C H 0 N :  Found:  C, 79.46, H, 7.96; uv Umax, n , n * , MeOH) 324 nm,  1 6  emax=101 l i t e r s • m o l e s  -1  1 9  241.1466,  C, 79.63; H, 7.94,  • cm . - 1  2-cyclooctyl-2-methy1-l-(4-cyanophenyl)-ethanone (22) a-Methyl-a-cyclooctyl-para-cyanoacetophenone (22) was prepared from (16) using the same sequence of steps as in the synthesis of (20). Following column chromatography, a c l e a r o i l was i s o l a t e d in 83% y i e l d : vr_ (neat) 1687 c m  -1  (C=0), 2230 c m  -1  (C=N); H nmr (CDCi , 300 MHz) 1.15 X  3  (3H, d, J=7 Hz), 1.2-1.85 (14H, m), 2.03 (IH, m), 3.35 (IH, m), 7.79 (2H, d, J=8.5 Hz), 8.00 (2H, d, J=8.5 Hz); m/e ( r e l a t i v e i n t e n s i t y ) 260 (m , 0.3), 159 (100), 130 (23.0). +  2-cycloheptyl-2-methyl-l-(4-cyanophenyl)-ethanone (23) a-Methyl-a-cycloheptyl-para-cyanoacetophenone (23) was prepared  129  from (17) using the same sequence of steps as i n the synthesis of (20). Following column chromatography, a c l e a r o i l was i s o l a t e d i n 80% y i e l d : (neat) 1692 cm" ( O O ) , 2224 cm" (C=N); *H nmr (CDC* , 300 MHz) 1.13  ir  1  1  3  (3H, d, J=7 Hz), 1.2-1.8 (12H, m), 1.95 (IH, m), 3.38 (IH, m), 7.75 (2H, d, J=8.5 Hz), 8.00 (2H, d, J=8.5 Hz); m/e ( r e l a t i v e  intensity)  255 (m , 0.23), 159 (100), 130 (29.3). +  2-cyclohexyl-2-methy1-l-(4-cyanophenyl)-ethanone ( 2 4 ) a-Methyl-a-cyclohexyl-para-cyanoacetophenone  6 0  (24) was prepared  from (18) using the same sequence of steps as i n the synthesis of (20). Following column chromatography, a c l e a r o i l was i s o l a t e d i n 60% y i e l d : (neat) 1687 cm" ( 0 0 ) , 2232 cm" (C=N)i  ir  1  1  X  H nmr (CDCA , 300 MHz) 3  0.8-1.3 (4H, m), 1.17 (3H, d, J=7 Hz), 1.5-1.9 (7H, m), 3.30 (IH, m) 7.77 (2H, d, J=8.5 Hz), 8.01 (2H, d, J=8.5 Hz);  m/e ( r e l a t i v e i n t e n s i t y ) 241  (m , 1.1), 159 (100), 130 (30.9); c a l c u l a t e d mass f o r C H 0 N : +  1A  Found:  1Q  241.1467,  241.1473.  2 - c y c l o p e n t y l - 2 - m e t h y l - l - ( 4 - c y a n o p h e n y l ) - e t h a n o n e (25) a-Methyl-a-cyclopentyl-para-cyanoacetophenone  (25) was prepared  from (19) using the same sequence of steps as i n the synthesis of (20). Following column chromatography, a c l e a r o i l was i s o l a t e d i n 84% y i e l d : ir  (neat) 1686 cm" ( 0 0 ) , 2232 cm" (C=N); H nmr (CDW , 300 MHz) 1.0 1  1  l  3  (2H, m), 1.20 (3H, d, J=7 Hz), 1.2-2.0 (6H, m), 2.15 (IH, m), 3.28 (IH, m), 7.74 (2H, d, J=8 Hz), 8.00 (2H, d, J=8.5 Hz),  m/e ( r e l a t i v e  i n t e n s i t y ) 227 (m , 0.90), 212 ( 3 . 1 ) , 159 (100), 130 (67.7). +  130  2-cyclooctyl-l-(4-carboxypheny1)-ethanone  (26)  62  ' a-Cyclooctyl-para-carboxyacetophenone (26) was prepared f o l l o w i n g a modified procedure of Wagner and S i e b e r t  58  in which 5.5 g (22 mmoles)  of (20) was added to a s t i r r i n g s o l u t i o n of 10 ml ethanol and 40 ml of a 30% s o l u t i o n of potassium hydroxide in water. r e f l u x and s t i r r e d at r e f l u x for 1 day.  The reaction was brought to  The reaction was cooled to room  temperature and a c i d i f i e d with concentrated hydrochloric a c i d .  The  organic layer was extracted twice with 100 ml of diethyl ether.  The  combined extracts were washed twice with 50 ml of water and dried over anhydrous sodium sulphate.  The s o l u t i o n was f i l t e r e d and the ether  solvent removed by rotary evaporation to y i e l d 4.24 g (15 mmoles, 71% y i e l d ) of a white s o l i d .  The s o l i d was r e c r y s t a l 1 i z e d from ethanol to ir_ (KBr) 1688 cm"  y i e l d clear c r y s t a l s , mp_ 188-192°C: 2900 cm"  1  1  (broad, C=0),  (broad, OH); H nmr (CDCA , 400 MHz) 1.4 (2H, m), 1.45-1.8 l  3  (12H, m), 2.29 (IH, m), 2.91 (2H, d, J=7 Hz), 8.02 (2H, d, J=8.4 Hz), 8.20 (2H, d, J=8.4 Hz), 9.9 (IH, s, broad); m/e ( r e l a t i v e i n t e n s i t y ) 274 (m , 1.7), 164 (100), 149 (48.8); +  274.1569, Found: H, 8.08, Found:  c a l c u l a t e d mass for C H 0 : 1 7  2 2  274.1574; A n a l . , c a l c u l a t e d for C H 0 : 1 7  2 2  3  3  C, 74.42;  C, 74.60; H, 7.98.  2-cycloheptyl-l-(4-carboxypheny1)-ethanone  (27)  a-Cycloheptyl-para-carboxyacetophenone  (27) was prepared from (21)  using the same sequence of steps as in the synthesis of (26). s o l i d product was i s o l a t e d i n 80% y i e l d .  A white  The s o l i d was r e c r y s t a l 1 i z e d  from ethanol to y i e l d clear c r y s t a l s , mp_ 183-184°C:  vr. ( ) KBr  1 6 8 7  c m _ 1  131  (C=0), 2900 cm" (broad, OH); H nmr (CDCJc , 400 MHz) 1.25 (2H, m) 1.4-1.8 1  l  3  (10H, m), 2.2 (IH, m), 2.92 (2H, d, J=7 Hz), 8.04 (2H, d, J=8.4 Hz), 8.20 (2H, d, J=8.4 Hz), 10.0 (IH, s, broad); m/e ( r e l a t i v e i n t e n s i t y ) 260 (m , 3 . 5 ) , 164 (100), 149 (45.9), calculated mass f o r C| H, 0^: +  ft  Found:  260.1412; A n a l . , calculated f o r C H 0 : 1 6  2 0  n  C, 73.82;  3  260.1412,  H, 7.74;  •  Found: C, 73.65, H, 7.85; uv (kmax, n,n , a c e t o n i t r i l e ) 325 nm.  2-cyclooctyl-2-methyl-l-(4-carboxyphenyl)-ethanone  (28)  a-Methyl-a-cyclooctyl-para-carboxyacetophenone  62  (28) was prepared  from (22) using the same sequence of steps as i n the synthesis of (26). white s o l i d product was i s o l a t e d in 71% y i e l d .  A  The s o l i d was  r e c r y s t a l l i z e d i n g l a c i a l a c e t i c acid and y i e l d e d c l e a r c r y s t a l s of a 1:1 mixed dimer of a c e t i c acid and (28), as determined by nmr and and X-ray crystallography, mp_ 137-138°C: 2900 cm"  1  ir  (KBr) 1683 cm" ( O O ) , 1700 cm" ( 0 0 ) , 1  1  (broad, OH); H nmr (CDCi , 400 MHz) 1.16 (3H, d, J=7 Hz), l  3  1.2-1.7 (14H, m), 2.05 (IH, m), 3.38 (IH, m), 8.00 (2H, d, J=8.4 Hz), 8.21 (2H, d, J=8.4 Hz), 9.9 (IH, s, broad); m/e ( r e l a t i v e i n t e n s i t y ) 288 (m , 0 . 8 ) , 178 (100), 149 (36.0); calculated mass f o r CmH^O,: +  288.1725,  Found: 288.1730.  2-cycloheptyl-2-methyl-l-(4-carboxyphenyl)-ethanone  (29)  a-Methyl-a-cycloheptyl-para-carboxyacetophenone  68  (29) was  prepared from (23) using the same sequence of steps as in the synthesis of (26).  A white s o l i d product was i s o l a t e d i n 82% y i e l d .  The s o l i d was  r e c r y s t a l l ized i n g l a c i a l a c e t i c acid to y i e l d c l e a r c r y s t a l s , mp_  132  152-153°C:  j_r (KBr) 1679 cm'  (C=0), 1694 cm'  1  1  (C=0), 2900 cm"  1  (broad,  OH); H nmr (CDC* , 400 MHz) 1.17 (3H, d, J=7 Hz), 1.2-1.8 (12H, m), 1.95 X  3  (IH, m), 3.44 (IH, m), 8.01 (2H, d, J=8.4 Hz), 8.22 (2H, d, J=8.4 Hz), 10.0 (IH, s, broad); m/e ( r e l a t i v e i n t e n s i t y ) 274 (m , 0 . 3 ) , 178 (100), +  149 (54.5), calculated mass f o r C HooQ,: 17  A n a l . , calculated f o r C H 2 0 : 1 7  2  274.1569, Found:  274.1571,  C, 74.42; H, 8.10, Found:  3  C, 74.20; H,  8.10.  2-cyclohexy1-2-methyl-l-(4-carboxypheny1)-ethanone  (30)  a-Methyl-a-cyclohexyl-para-carboxyacetophenone  6 Q  »  6 1  (30) was prepared  from (24) using the same sequence of steps as in the synthesis of (26). white s o l i d product was i s o l a t e d in 72% y i e l d .  The s o l i d was  recrystal 1 ized from a c e t i c acid to y i e l d c l e a r c r y s t a l s , mp_ 157-158°C: (KBr) 1678 cm"  1  (C=0), 1693 a n "  1  A  (C=0), 2900 cm"  j_r  (broad, OH), H nmr  1  l  (CDCi , 400 MHz) 0.9-1.3 (4H, m), 1.17 (3H, d, J=7 Hz), 1.6-1.8 (7H, m), 3  3.35 (IH, m), 8.02 (2H, d, J=8.4 Hz), 8.22 (2H, d, J=8.4 Hz), 9.8 (IH, s, broad); m/e ( r e l a t i v e i n t e n s i t y ) 260 (m , 0.9), 178 (100), 149 (54.2); +  calculated mass f o r C H 0 : 1 5  2 0  3  260.1412, Found:  260.1407.  2-cycl opentyl-2-methyl-l-(4-carboxypheny1)-ethanone  (31 )  a-Methyl-a-cycl opentyl-para-carboxyacetophenone  6 3  (31) was prepared  from (25) using the same sequence of steps as in the synthesis of (26). white s o l i d product was i s o l a t e d in 75% y i e l d .  The s o l i d was  r e c r y s t a l 1 ized in g l a c i a l a c e t i c acid to y i e l d c l e a r c r y s t a l s , mp_ 140-141°C:  21 (  K B r  )  1 6 8 0  c m _ 1  ( °)> c=  1 6 9 1  c m _ 1  ( °)> c=  2 9 0 0  c m _ 1  (broad,  A  133  OH); H nmr (CDCi , 400 MHz) 1.06 (IH, m), 1.23 (3H, d, J=7 Hz), 1.45-1.65 X  3  (5H, m), 1.72 (IH, m), 1.84 (IH, m), 2.20 (IH, m), 3.35 (IH, m), 8.02 (2H, d, J=8.4 Hz), 8.21 (2H, m, J=8.4 Hz), 10.0 (IH, s, broad); m/e ( r e l a t i v e i n t e n s i t y ) 246 (m , 1.2), 178 (84.9), 149 (100); +  mass for C H 0 : 1 5  C H 0 : 1 5  1 8  1 8  3  246.1256, Found:  C, 73.15; H, 7.37, Found:  3  calculated  246.1253; A n a l . , c a l c u l a t e d f o r C, 73.08; H, 7.40.  2-cyc1ooctyl-l-(4-carbomethoxyphenyl)-ethanone  (32)  Following the procedure of DeBoer and Backer *, a 100 ml 61  long-necked d i s t i l l a t i o n f l a s k was equipped with a condenser and dropping funnel, and f i l l e d with a s o l u t i o n of 3 g of potassium hydroxide, 10 mi of water and 40 mi of 2-ethoxyethanol. to 70-75°C.  The mixture was heated in an o i l  bath  A s o l u t i o n c o n s i s t i n g of 3 g (15 mmoles) of  N-methyl-N-nitrosotoluene-4-sulphonamide  dissolved i n 50 mi of d i e t h y l  ether was added to the d i s t i l l a t i o n flask dropwise over 5 minutes.  During  the d i s t i l l a t i o n the s o l u t i o n was s t i r r e d vigorously.  The d i s t i l l i n g  diazomethane s o l u t i o n was immediately added to a flask  containing  keto-acid (26).  The addition of diazomethane was allowed to proceed u n t i l  the s o l u t i o n retained the yellow color of diazomethane and the evolution of nitrogen gas ceased.  The excess diazomethane and diethyl ether were  allowed to evaporate y i e l d i n g a white s o l i d , mp_ 40-41 °C: 1677 cm-  1  (C=0), 1723 cm"  1  jjr (KBr)  (C=0); H nmr (CDCi , 300 MHz) 1.2-1.7 l  3  (14H, m), 2.28 (IH, m), 2.89 (2H, d, J=7 Hz), 3.95 (3H, s ) , 7.99 (2H, d, J=8.3 Hz), 8.12 (2H, d, J=8.3 Hz); m/e ( r e l a t i v e i n t e n s i t y ) 288 (m+, 5.3), 257 (10.7), 178 (100), 163 (48.7), 135 (19.6); A n a l . , c a l c u l a t e d for  134  C H 1 8  2 1 t  0 : 3  C, 74.97, H, 8.38, Found:  MeOH) 327, emax = 92 l i t r e s • moles"  C, 75.12; H, 8.48;  (\max,  uv  • cm" .  1  1  2-cycl oheptyl-l-(4-cartomethoxypheny1)-ethanone  (33)  a-Cycl oheptyl-para-carbomethoxyacetophenone  (33) was prepared from  (27) using the same sequence of steps as in the synthesis of (32). white s o l i d was i s o l a t e d as product, mp_ 54-55°C: (OO),  1723 cm"  1  n,n*,  A  j j r (KBr) 1676 c m  -1  (C=0); H nmr (CDCX , 300 MHz) 1.25 (2H, m), 1.4-1.8 l  3  (10H, m), 2.21 (IH, m), 2.90 (2H, d, J=7 Hz), 3.96 (3H, s ) , 7.99 (2H, d, J=8.3 Hz), 8.12 (2H, d, J=8.3 Hz), m/e ( r e l a t i v e i n t e n s i t y ) 274 (m , 1.8), +  243 (4.9), 178 (100), 163 (55.7), 147 (35.8); A n a l . , calculated f o r C H 0 : 1 7  2 2  3  C, 74.68, H, 8.08; uv (\max, n , n * .  C, 74.42, H, 8.08, Found:  MeOH) 327, emax = 158 l i t r e s • moles"  1  • cm" . 1  2-cyclooctyl-2-methy1-l-(4-carbomethoxypheny1)-ethanone  (34)  a-Methyl-a-cyclooctyl-para-carbomethoxyacetophenone  3 3  (34) was  prepared from (28) using the same sequence of steps as in the synthesis of (32).  A white s o l i d was i s o l a t e d as the product, mp_ 39-40°C:  1677 cm-  1  (C=0), 1725 cm"  1  (C=0);  l  v r (KBr)  H nmr (CDW , 270 MHz) 1.14 (2H, d, 3  J=7 Hz), 1.2-1.7 (14H, m), 2.1 (IH, m), 3.7 (IH, m), 3.95 (3H, s ) , 7.96 (2H, d, J=8.4 Hz), 8.13 (2H, d, J=8.4 Hz), m/e ( r e l a t i v e i n t e n s i t y ) 302 (m , 0 . 4 ) , 192 (100), 163 (46.9), 133 (28.0), A n a l . , calculated f o r +  C H 0 : 1 9  2 6  3  C, 75.66, H, 8.76; uv (Xmax, n . n * .  C, 75.46, H, 8.67, Found:  MeOH) 327, emax = 176 l i t r e s • m o l e s  -1  • cm . - 1  135  2-cycloheptyl-2-methyl-l-(4-carbomethoxyphenyl)-ethanone (35) a-Methyl-a-cycloheptyl-para-carbomethoxyacetophenone (35) was prepared from (29) using the same sequence of steps as in the synthesis of (32).  A white s o l i d was i s o l a t e d as the product, mp_ 59-60°C:  1672 cm-  1  (C=0), 1722 cm-  1  i £ (KBr)  ( O O ) ; H nmr (CDCi , 270 MHz) 1.15 (3H, d, X  3  J=7 Hz), 1.2-1.7 (12H, m), 1.91 (IH, m), 3.40 (IH, ra), 3.96 (3H, s ) , 7.97 (2H, d, J=8.4 Hz), 8.12 (2H, d, J=8.4 Hz); m/e ( r e l a t i v e i n t e n s i t y ) 288 (m , 0 . 1 ) , 192 (100), 163 (59.0), 133 (31.8); A n a l . , c a l c u l a t e d for +  c  i8  H  2t°3  c  :  C, 74.76; H, 8.41; uv (Xmax, n , n * ,  » 74.97; H, 8.39, Found:  MeOH) 372, emax = 100 l i t r e s • m o l e s  -1  • cm . - 1  2-cyclohexyl-2-methyl-l-(4-carbomethoxyphenyl)-ethanone (36) a-Methyl-a-cyclohexyl-para-carbomethoxyacetophenone (36) was prepared from (30) using the same sequence of steps as in the synthesis of (32).  A white s o l i d was i s o l a t e d as product, mp_ 82-83°C:  1672 cm-  1  ( 0 0 ) , 1724 cm"  1  ir_ (KBr)  (C=0); H nmr ( C D U , 300 MHz) 0.9-1.3 1  3  (4H, m), 1.15 (3H, d, J=7 Hz), 1.5-1.8 (7H, m), 3.33 (IH, m), 3.95 (3H, s ) , 7.97 (2H, d, J=8.3 Hz), 8.12 (2H, d, J=8.3 Hz); m/e ( r e l a t i v e i n t e n s i t y ) 274 (m , 0 . 8 ) , 243 ( 1 . 1 ) , 215 (6.8), 192 (100), 163 (73.7), 133 +  (31.0); A n a l . , c a l c u l a t e d for C H 0 : 1 7  2 2  3  C, 74.42; H, 8.08, Found:  C, 74.40; H, 8.06; uv (A.max, n,n*, MeOH) 327 nm, emax = 157 l i t r e s • m o l e s  -1  • cm . - 1  2-cyclopentyl-2-methyl-l-(4-carbomethoxyphenyl)-ethanone (37) a-Methyl-a-cyclopentyl-para-carbomethoxyacetophenone  (37) was  136  prepared from (31) using the same sequence of steps as in the synthesis of (32).  A white s o l i d was i s o l a t e d as product, mp_ 38-39°C:  1674 cm-  1  ( O O ) , 1724 cm-  1  jjr (KBr)  ( O O ) ; H nmr (CDC* , 270 MHz) 1.05 (IH, m), X  3  1.20 (3H, d, J=7 Hz), 1.4-1.9 (9H, m), 2.19 (IH, m), 3.33 (IH, m), 3.95 (3H, s ) , 7.98 (2H, d, J=8.4 Hz), 8.01 (2H, d, J=8.4 Hz); m/e ( r e l a t i v e i n t e n s i t y ) 260 (m , 0.9), 192 (71.0), 163 (100); A n a l . , c a l c u l a t e d for +  C  16 20°3 H  :  c  » 3 . 8 2 ; H, 7.47, Found: 7  C, 73.75; H, 7.61; uv  MeOH) 327 nm, emax = 124 l i t r e s • m o l e s  -1  (Xmax,  n,n*,  • cm . - 1  Photochemical Studies  Photolysis of 2-cyclooctyl-1-(4-chlorophenyl)-ethanone  (9)  a-Cyclooctyl-para-chloroacetophenone (800 mg) was dissolved in 250 ml of a c e t o n i t r i l e and placed in a 250 ml Pyrex immersion well (x > 290 nm).  The sample was deoxygenated for 45 minutes p r i o r to  i r r a d i a t i o n using a steady flow of nitrogen gas through the s t i r r i n g solution.  The nitrogen flow was continued while the sample was being  i r r a d i a t e d , at room temperature, using a 450 watt medium pressure Hanovia lamp.  Following a 3 hour i r r a d i a t i o n time, the a c e t o n i t r i l e solvent was  removed by rotary evaporation to y i e l d a yellow o i l .  This o i l was  analyzed by g.c. (column A, program 1) and found to contain 3 major products:  9a ( r t 1.59), 9b ( r t 7.51) and 9c ( r t 8 . 9 ) .  The products were  separated using a column (2.0 cm x 30 cm) of s i l i c a gel 60 (230-400 mesh) and a 0-4% ethyl acetate in petroleum ether solvent as the step gradient  137  eluent.  The products were separated and only the purest f r a c t i o n s (>90%)  were i s o l a t e d and characterized.  l - ( 4 - C h l o r o p h e n y l ) - e t h a n o n e (9a) Para-chloroacetophenone oil:  j r (neat) 1687 cm"  (9a) was i s o l a t e d as a s l i g h t l y yellow  (C=0); H nmr (CDCA , 80 MHz) 2.8 (3H, s ) , 7.45  1  X  3  (2H, d, J=8.4 Hz), 7.95 (2H, d, J=8.4 Hz); m/e ( r e l a t i v e i n t e n s i t y ) 154 (m , 56.5), 139 (100); ( l i t +  9-(la  t  8a,  1  :  mp 20°C).  9B)-(4-chlorophenyl)-bicyclo [ 6 . 2 . 0 ] decan-9-ol  Trans-cyclobutanol 3440 cm-  6 5  (9b)  (9b) was i s o l a t e d as a yellow o i l :  j_r (neat)  (broad, OH); » nmr (CDW , 400 MHz) 1.15-1.4 (5H, m), 1.52-1.63 l  3  (2H, m), 1.65-1.95 (6H, m), 2.2-2.4  (4H, m), 7.95 (4H, m);  m/e  (relative  i n t e n s i t y ) 264/266 (m , 0 . 7 / 0 . 2 ) , 154/156 (100/38.4), 139/141 (55.6/21.8), +  calculated mass f o r C , ^ H 0 C X / C , ^ H i O C A : 35  9  91  37  264.1281/266.1281, Found:  264.1272/266.1260.  9 - ( l a , 8a,  9 a ) - ( 4 - c h l o r o p h e n y l ) - b i c y c l o [ 6 . 2 . 0 ] decan-9-ol (9c)  Cis-cyclobutanol 3440 cm-  1  (9c) was i s o l a t e d as a yellow o i l :  j_r (neat)  (broad, OH); H nmr (CDC* , 400 MHz) 0.47 (IH, m), 1.02 L  3  (IH, rn), 1.1-1.45 (6H, m), 1.56 (IH, m), 1.65-2.0 (5H, m), 2.26 (IH, m), 2.48 (IH, s, broad, exchanges with D 0 ) , 2.80 (IH, dd, J=7.5 and 4 Hz), 2  7.32 (2H, d, J=8.3 Hz), 7.40 (2H, d, J=8.3 Hz), proton decoupling of the signal at 0.47 results in the s i m p l i f i c a t i o n of the m u l t i p l e t at 1.56 and causes the m u l t i p l e t at 2.26 t o collapse to a doublet of doublets (J =9.5  138  and 3 Hz); m/e ( r e l a t i v e i n t e n s i t y ) 264/266 (m , 0.6/0.1), 154/156 +  (100/37.4), 139/141 (46.1/19.1); c a l c u l a t e d mass for C  1 6  H  2 1  0a  3 5  /C  Product Ratio  1 6  H  2 1  0a  3 7  :  263.1281/266.1281, Found:  264.1285/266.1257.  Study  Three 0.4 mi Pyrex tubes were f i l l e d with a 0.10 M solution of (9) in benzene.  Three tubes were f i l l e d with a 0.10 M solution of (9) in  acetonitrile.  Three tubes were f i l l e d with a 0.01 M solution of (9) i n  a c e t o n i t r i l e and a further three tubes f i l l e d with 2 mg of crushed c r y s t a l s of ( 9 ) .  The solution samples were deoxygenated by subjecting  the tubes to three freeze-pump-thaw cycles under a nitrogen atmosphere. The s o l i d samples were pumped and placed under a nitrogen atmosphere.  The  s o l i d samples and the 0.01 M solution of (9) in a c e t o n i t r i l e were cooled to -32°C and photolyzed at 337 nm. The 0.1 M solutions were photolyzed at room temperature at 337 nm.  Solution state conversions were l i m i t e d to  10%, whereas the s o l i d state conversions were l i m i t e d to 2%. A l l of the samples were analyzed by g.c. and the r a t i o s of (9b + 9c):9a and 9b:9c are shown in table VI: SOLVENT  cone. (M)  Acetonitrile Acetonitrile Benzene S o l i d State  0.01 M 0.10 M 0.10 M  Table VI:  temp.°C -32 22 22 -32  ±2 ±2 ±2 ±2  (9b+9c):9a 85:15 73:27 70:30 96:4  ±3 ±1 ±2 ±1  9b :9c 51:49 56.44 77:23 96:4  Product r a t i o s from the photolysis of ketone (9)  ± 1 ± 1 ±1 ± 1  139  P h o t o l y s i s of 2 - c y c l o o c t y l - 1 - ( 4 cyanophenyl)-ethanone (20) a-Cyclooctyl-para-cyanoacetophenone  (750 mg) was i r r a d i a t e d  f o l l o w i n g the same procedure used in the i r r a d i a t i o n of (9).  The  resultant o i l was analyzed by g.c. (column A, program 1) and found to contain three major products; 20a (rt 1.57), 20b ( r t 9.22) and 20c (rt 10.86).  The products were separated using a column (2.0 cm x 30 cm)  of s i l i c a gel 60 (230-400 mesh) and a 0-7% ethyl acetate i n petroleum ether solvent as the step gradient eluent. and only the purest f r a c t i o n s  The products were separated  (>90%) were i s o l a t e d and characterized:  l - ( 4 - c y a n o p h e n y l ) - e t h a n o n e (20a) Para-cyanoacetophenone (20a) was i s o l a t e d as a white s o l i d , mp_ 60-61°C ( l i t  6 6  :  mp 60-61°C):  j_r (KBr) 1689 cm"  1  (C=0), 2230 cm"  (C=N);  1  ti nmr (CDU , 80 MHz) 2.7 (3H, s ) , 7.8 (2H, d, J=8.5 Hz), 8.1 (2H, d,  1  3  J=8.5 Hz),  m/e ( r e l a t i v e i n t e n s i t y ) 145 (m , 12.4), 130 (100), 102 +  (44.0).  9 - ( l a , p a , 9 B ) - ( 4 - C y a n o p h e n y l ) - b i c y c l o [6.2.0] decan-9-ol (20b) Trans-cyclobutanol (neat) 2229 cm"  1  (20b) was i s o l a t e d as a y e l l o w i s h o i l :  (C=N), 3470 cm"  1  (broad, OH);  l  J_r  H nmr (CDC* , 400 MHz) 3  1.15-1.45 (5H, m), 1.5-1.6 (2H, m), 1.65-2.0 (6H, m), 2.2-2.5 (4H, m), 8.0 (2H, d, J=8.5 Hz), 8.10 (2H, d, J=8.5 Hz); m/e ( r e l a t i v e i n t e n s i t y ) 255 (m , 2 . 3 ) , 145 (100), 130 (83.2); c a l c u l a t e d mass f o r C H 0 N : +  1 7  Found 255.1626.  2 1  255.1623,  140  9 - ( l a , 8a,  9a)-(4-cyanopheny1 ) - b i c y c l o [ 6 . 2 . 0 ] d e c a n - 9 - o l  Cis-cyclobutanol j_r (neat) 2229 cm"  1  (20c)  (20c) was i s o l a t e d as a y e l l o w i s h o i l :  (C=N), 3428 cm"  (broad, OH); IH nmr (CDCA , 400 MHz)  1  3  0.38 (IH, m), 1.0 (IH, m), 1.05-1.45 (6H, m), 1.53 (IH, m), 1.63-1.82 (3H, m), 1.84-1.95 (2H, m), 2.24 (IH, s, broad, exchanges with D 0 ) , 2.29 2  (IH, m), 2.80 (IH, dd, J=8 Hz and 4 Hz), 8.07 (4H, m), proton decoupling of the signal at 0.38 results in the signal at 2.29 c o l l a p s i n g to a doublet (J=8.0 Hz), proton decoupling of the signal at 2.29 r e s u l t s in the collapse of the m u l t i p l e t at 0.38 to a t r i p l e t of doublets (J=2.5 and 0.9 Hz), proton decoupling of the signal at 2.80 results in no observable change in the spectrum; m/e ( r e l a t i v e i n t e n s i t y ) 255 (m , 0 . 4 ) , 145 (100), +  130 (68.4);  calculated mass f o r CwH^ON:  Product R a t i o  255.1623, Found:  255.1627.  Study  The product r a t i o study f o r ketone (20) was conducted i n the same fashion as the product study f o r (9).  A l l of the samples were analyzed  by g.c. and the ratios of (20b+20c):20a and 20b:20c are shown in table V I I . SOLVENT  cone. (M)  Acetonitrile Acetonitrile Benzene S o l i d State  0.01 M 0.10 M 0.10 M  Table V I I :  temp.°C -32 22 22 -32  ±2 ±2 ±2 ±2  (20b+20c):20a 82:18 72:28 72:28 87:13  ±2 ±3 ±1 ±2  20b:20c 51:49 56.44 75:25 83:17  Product ratios from the photolysis of ketone (20)  ±1 ±1 ±1 ±1  141  Photolysis of 2-cycloheptyl-l-(4-cyanopheny1)-ethanone (21) a-Cycloheptyl-para-cyanoacetophenone (800 mg) was i r r a d i a t e d following the same procedure used in the i r r a d i a t i o n of ( 9 ) . The r e s u l t a n t o i l was analyzed by g.c. (column A, program 1) and found to contain three major products; 20a ( r t 1.59), 21b ( r t 7.10), and 21c ( r t 8.11).  The products were separated using a column (2.0 cm x 30 cm) of  s i l i c a gel 60 (230-400 mesh) and a 0-7% ethyl acetate i n petroleum ether solvent as the step gradient eluent.  The products were separated and only  the purest f r a c t i o n s (>90%) were i s o l a t e d and c h a r a c t e r i z e d :  l-(4-cyanopheny1)-ethanone (20a) Para-cyanoacetophenone was i d e n t i f i e d by i t s g.c. retention time, physical and spectral c h a r a c t e r i s t i c s as compared to an authentic sample. 8 - ( l a , 7a, 86)-(4-cyanophenyl)-bicyclo [5.2.0] nonan-8-ol (21b) Trans-cyclobutanol  (21b) was i s o l a t e d as a s l i g h t l y yellow o i l :  ijr (neat) 2229 cm" (C=N), 3402 c n r 1  1  (broad, OH); H nmr (CDCi , 400 MHz) X  3  1.24 (IH, m), 1.32-1.50 (2H, m), 1.53-1.82 (5H, m), 1.89-2.10 (3H, m), 2.23-2.50 (4H, m), 7.48 (2H, m), 7.61 (2H, m); m/e ( r e l a t i v e  intensity)  241 (m+, 3 . 3 ) , 145 (100), 130 (69.4); c a l c u l a t e d mass for C H 0 N : 1 6  241.1467, Found:  1 9  241.1466.  8 - ( l a , 7a, 8a)-(4-cyanophenyl)-bicyclo [5.2.0] nonan-8-ol (21c) Cis-cyclobutanol  (21c) was i s o l a t e d as a s l i g h t l y yellow o i l : _ir  (neat) 2229 cm" (C=N), 3402 (broad, OH); H nmr (CDCA , 400 MHz) 0.43 1  X  3  142  (IH, m), 0.89 (IH, m), 1.05 (1H, m), 1.15-1.55 (5H, m), 1.68-1.8 (2H, m), 1.9-2.0 (2H, m), 2.37 (1H, m), 2.66 (1H, s, broad, exchanges with D 0 ) , 2  2.84 (IH, dd, J=7.5 and 4 . 5 ) , 7.57 (2H, m), 7.64 (2H, m),  (relative  m/e  i n t e n s i t y ) 241 (m , 3.9), 145 (100), 130 (62.1); calculated mass f o r +  C H 0N: 1 6  1 9  241.1467, Found:  241.1467.  P r o d u c t R a t i o Study  The product r a t i o study f o r ketone (21) was conducted in the same fashion as the product study f o r (9).  A l l of the samples were analyzed  by g.c. and the ratios of (21b+21c):20a and 21b:21c are shown i n table V I I I . SOLVENT  cone. (M)  A c e t o n i t r i le A c e t o n i t r i le Benzene S o l i d State S o l i d State  0.01 M 0.10 M 0.10 M  Table V I I I :  temp.°C -32 22 22 0 -32  ±2 ±2 ±2 +2 ±2  (21b+21c):20a 75:25 65:35 47:53 37:63 36.64  ±4 ±5 ±3 ±1 ±1  21b:21c 65:35 66.34 85:15 72:28 76:24  ±1 ±1 ±1 ±2 ±1  Product ratios from the photolysis of ketone (21)  P h o t o l y s i s of 2 - c y c l o o c t y l - 1 - ( 4 - c a r b o x y p h e n y l ) - e t h a n o n e  a-Cycl ooctyl-para-carboxyacetophenone  (26)  (800 mg) was i r r a d i a t e d  f o l l o w i n g the same procedure used in the i r r a d i a t i o n of (9).  A yellowish  s o l i d remained following the removal of the a c e t o n i t r i l e solvent.  To this  was added diazomethane, using the same e s t e r i f i c a t i o n procedure used in the synthesis of (32).  The diethyl ether and excess diazomethane was  allowed to evaporate to y i e l d a yellowish o i l . g.c.  The o i l was analyzed by  143  (column A, program 1) and found to contain three major products; 26a (rt 1.67), 26b (rt 9.20) and 26c (rt 10.71).  The products were separated  using a column (2.0 cm x 30 cm) of s i l i c a gel 60 (230-400 mesh) with a 0- 9% ethyl acetate in petroleum ether solvent as the step gradient eluent. The products were separated and only the purest f r a c t i o n s  (>90%) were  i s o l a t e d and characterized:  1- (4-carbomethoxyphenyl)-ethanone (26a) Para-carbomethoxyacetophenone (26a) was i s o l a t e d as a white s o l i d , mp_ 93-94°C ( l i t (00);  6 6  :  mp 92°C):  j_r (KBr) 1678 cm"  1  ( O O ) , 1722 cm"  1  H nmr (CDC* , 80 MHz) 2.7 (3H, s ) , 4.0 (3H, s ) , 8.1 (4H, m); m/e  l  3  ( r e l a t i v e i n t e n s i t y ) 178 (m , 21.3), 163 (100). +  9 - ( l a , 8a, 9 B ) - ( 4 - c a r b o m e t h o x y p h e n y l ) - b i c y c l o [ 6 . 2 . 0 ] decan-9-ol (26b) Trans-cyclobutanol j_r (neat) 1724 cm"  1  (26b) was i s o l a t e d as a s l i g h t l y yellow o i l :  ( 0 0 ) , 3490 cm"  1  (broad, OH);  l  H nmr  (CDCJt , 3  400 MHz)  0.86 (IH, m), 1.15-1.4 (5H, m), 1.55-1.65 (2H, m), 1.68-1.90 (4H, m), 1.97 (IH,  m), 2.11 (IH, s, broad, exchanges with D 0 ) , 2.25-2.45 (3H, m), 3.90  (3H,  s ) , 7.44 (2H, d, J=8 Hz), 7.98 (2H, d, J=8 Hz); m/e ( r e l a t i v e  2  i n t e n s i t y ) 288 (m , 0.9), 178 (100), 163 (48.3); +  c a l c u l a t e d mass f o r  C H 0 :  288.1726, Found:  9 - ( l a , 8a,  9 a ) - ( 4 - c a r b o m e t h o x y p h e n y l ) - b i c y c l o [ 6 . 2 . 0 ] decan-9-ol (26c)  1 8  2 4  3  Cis-cyclobutanol 1724 cm"  1  288.1723.  (26c) was i s o l a t e d as a y e l l o w i s h o i l :  ( 0 0 ) , 3469 cm"  1  (broad, OH);  X  _ir (neat)  H nmr (CDCA , 400 MHz) 0.45 3  144  (1H, m), 1.04 (IH, m), 1.1-1.49 (6H, m), 1.55 (IH, m), 1.65-2.0 (5H, m), 2.32 (IH, m), 2.50 (1H, s, broad, exchanges with D 0), 2.88 (IH, dd, J=7.5 2  and 4 Hz), 3.90  (3H, s ) , 7.53 (2H, d, J=8 Hz), 8.0 (2H, d, J=8 Hz);  ( r e l a t i v e i n t e n s i t y ) 288 (m , 0.8), 178 (100), 163 (40.3); +  mas£ for C H 0 : 1 8  2 4  3  288.1726, Found:  m/e  calculated  288.1729.  Product Ratio Study The product r a t i o study for keto-acid (26) was conducted in a modified version of the product study for (9).  Due to a lower  s o l u b i l i t y of keto-acid (26) in both benzene and a c e t o n i t r i l e , the concentration of a l l the solution samples was reduced to 0.01 M. s o l i d and s o l u t i o n samples were i r r a d i a t e d at room temperature.  The Following  i r r a d i a t i o n , the samples were transferred to 3 ml sample v i a l s where the photolysis solvents were allowed to evaporate.  To each sample v i a l was  added an excess of diazomethane in diethyl ether.  The v i a l s were sealed  for approximately 3 hours following which the excess diazomethane and ether were allowed to evaporate.  A l l of the resultant samples were  analyzed by g.c. and the r a t i o s of (26b+26c):26a and 26b:26c are shown i n table IX:  145  SOLVENT  cone. (M)  temp.°C  (26b+26c):26a  26b:26c  Acetonitrile Benzene S o l i d State  0.01 M 0.01 M  22 + 2 22 ± 2 22 ± 2  69:31 ± 5 64:36 ± 4 85:15 ± 5  53:47 ± 1 72:28 ± 4 92:8 ± 4  Table IX:  Product r a t i o s from the photolysis of keto-acid (26)  Photolysis of 2-cyc1ohepty1-l-(4-carboxypheny1)-ethanone (27) a-Cycloheptyl-para-carboxyacetophenone (800 mg) was i r r a d i a t e d following the same procedure used in the i r r a d i a t i o n of keto-acid (26). The resultant o i l was analyzed by g.c. (column A, program 1) and found to contain three major products; 26a ( r t 1.68), 27b ( r t 7.35), 27c ( r t 8.31). The products were separated in the same manner used in the i s o l a t i o n of products from keto-acid (26):  l-(4-carbomethoxypheny1)-ethanone (26a) Para-carbomethoxyacetophenone was i d e n t i f i e d by i t s g.c. retention time, physical and spectral c h a r a c t e r i s t i c s as compared to an authentic sample.  8 - ( l a , 7a, 8p)-(4-carbomethoxyphenyl)-bicyclo Trans-cyclobutanol 2 r (neat) 1724 cm"  1  (26b) was i s o l a t e d as a s l i g h t l y yellow o i l :  (C=0), 3423 cm"  1.23 (2H, m), 1.35-1.85  [5.2.0] nonan-8-ol (27b)  1  (broad, OH); H nmr (CDCJlg, 400 MHz)  (8H, m), 1.87-2.03  X  (2H, m), 2.1 (IH, s, broad,  exchanges with D 0 ) , 2.24-2.47 (2H, m), 3.94 (3H, s ) , 7.41 (2H, m), 7.98 2  (2H, m); m/e ( r e l a t i v e i n t e n s i t y ) 274 (m+, 1.1), 178 (100), 163 (51.8).  146  8 - ( l a , 7a, 8a)-(4-carbomethoxyphenyl)-bicyclo [ 5 . 2 . 0 ] nonan-8-ol (27c) Cis-cyclobutanol (neat) 1725 cm"  1  (27c) was i s o l a t e d as a s l i g h t l y yellow o i l : j_r  (C=0), 3424 cm"  1  (broad OH);  X  H nmr (CDCA , 400 MHz) 3  0.46 (1H, m), 0.87 (1H, m), 1.08 (IH, m), 1.17-1.85 (7H, m), 1.85-2.03 (2H, m), 2.16 (1H, s, broad, exchanges with D 0 ) , 2.37 (IH, m), 2.89 (IH, 2  dd, J=7.5 and 4.5 Hz), 3.91 (3H, s ) , 7.53 (2H, d, J=8 Hz), 8.03 (2H, d, J=8 Hz); m/e ( r e l a t i v e i n t e n s i t y ) 274 (m , 1.2), 178 (100), 163 (44.3), +  147 (43.2).  Product Ratio Study The product r a t i o study f o r keto-acid (27) was conducted in the same fashion as the product study f o r keto-acid (26).  A l l of the samples  were analyzed by g.c. and the ratios of 26a: (27b+27c) and 27b:27c are shown in table X:  SOLVENT  cone. (M)  A c e t o n i t r i le Benzene S o l i d State  0.01 M 0.01 M  Table X:  temp.°C 22 ± 2 22 ± 2 22 ± 2  26a:(27b+27c)  27b:27c  36:64 ± 3 50:50 ± 6 56:44 ± 5  69:31 ± 1 87:13 ± 1 96:4 ± 2  Product ratios from the photolysis of keto-acid (27)  Photolysis of 2-cyclooctyl-2-methyl-1-(4-carboxyphenyl)-ethanone a-Methyl-a-cyclooctyl-para-carboxyacetophenone  (28)  (1.2 g) was  i r r a d i a t e d following the same procedure used in the i r r a d i a t i o n of keto-acid (26).  The resultant o i l was analyzed by g.c. (column A,  program 1) and found to contain four major products,  28a (rt 1.92), 28b  147  (rt  7.74), 28c ( r t 8.76), 28d (rt 11.46).  Cleavage product 28a and  cyclobutanol 28b were i s o l a t e d using a column (2.0 cm x 30 cm) of s i l i c a gel 60 (230-400 mesh) with a 0-9% ethyl acetate i n petroleum ether solvent as the step gradient eluent.  The second cyclobutanol 28c was i s o l a t e d  using f i v e separate columns of the type used in the i s o l a t i o n of 28a and 28b.  The forth product 28d was i d e n t i f i e d by i t s g.c.-mass spectrum:  2-methyl-l-(4-carbomethoxyphenyl)-ethanone  Para-carbomethoxypropiophenone s o l i d , mp_ 77-78°C:  Ir  (KBr) 1680 cm"  1  (28a)  (28a) was i s o l a t e d as a white (C=0), 1723 cm"  1  (C=0); H nmr l  (CDC£ , 80 MHz) 1.2 (3H, t , J=8 Hz), 3.0 (2H, q, J=8 Hz), 3.9 (3H, s ) , 8.1 3  (4H, m); m/e ( r e l a t i v e i n t e n s i t y ) 192 (m , 3.3), 163 (100). +  9 - ( l a , 8a,  96,  10a)-(4-carbomethoxyphenyl)-10-methyl-bicyclo [6.2.0]  decan-9-ol  (28b)  Cyclobutanol 28b was i s o l a t e d as a c l e a r o i l : (C=0), 3495 cm"  1  jjr (neat) 1724 c m  -1  (broad, OH); H nmr (CDCi , 400 MHz) 1.08 (3H, d, X  3  J=7.5 Hz), 1.15-1.40 (5H, m), 1.50-1.60 (2H, m), 1.60-2.0 (7H, m), 2.11 (IH, m), 2.24 (IH, m), 3.92 (3H, s ) , 7.49 (2H, d, J=8 Hz), 8.00 (2H, d, J=8 Hz), proton decoupling of the signal at 2.11 results i n the doublet at 1.08 c o l l a p s i n g to a s i n g l e t ; proton decoupling the signal at 2.24 had no e f f e c t on the signals at 1.08 and 2.11, in an N.O.E.  difference  experiment, i r r a d i a t i o n of the doublet at 7.47 results in equal enhancement of the signals at 2.24 and 2.11; enhancement is also observed  148  for the signal at 8.00; m/e ( r e l a t i v e i n t e n s i t y ) 302 (m , 1.2), 192 (100), +  163 (78.4); c a l c u l a t e d mass for C H 0 :  302.1882, Found:  9-(4-carbomethoxyphenyl)-10-methyl-bicyc1o  [ 6 . 2 . 0 ] decan-9-ol  1 9  2 6  3  302.1890.  (28c)  - s t e r e o c h e m i s t r y unknown  Cyclobutanol 1725 cm-  1  (28c) was i s o l a t e d as a clear o i l :  (C=0), 3494 cm"  1  jl  (  n e a t  )  (broad, OH); H nmr (CDCl , 400 MHz) 0.90 X  3  (IH, m), 1.07 (3H, d, J=6.5 Hz), 1.1-1.8 (11H, m), 1.94 (IH, s, broad, exchanges with D 0 ) , 2.19 (IH, m), 2.37 (IH, m), 2.51 (IH, m), 3.91 2  (3H, s ) , 7.42 (2H, d, J=8 Hz), 8.01 (2H, d, J=8 Hz), proton decoupling of the signal at 1.07 r e s u l t s in the m u l t i p l e t at 2.51 c o l l a p s i n g to a doublet (J=9.5 Hz); proton decoupling of the signal at 2.51 r e s u l t s in the m u l t i p l e t at 2.37 c o l l a p s i n g to a doublet (J =11 Hz) and the m u l t i p l e t at 2.51 c o l l a p s i n g to a quartet (J=6.5 Hz);  proton decoupling of the signal  at 2.37 r e s u l t s in the s i m p l i f i c a t i o n of the signal at 2.19; in an N.O.E. difference experiment i r r a d i a t i o n of the doublet at 7.42 r e s u l t s in enhancement of the m u l t i p l e t at 2.51 and a weak enhancement of the m u l t i p l e t at 2.37, enhancement was also observed for the doublet at 8.01; m/e ( r e l a t i v e i n t e n s i t y ) 302 (m , 0 . 3 ) , 192 (100); c a l c u l a t e d mass for +  C H 0 : 1 9  2 6  3  302.1882, Found:  302.1886.  9-(4-carbomethoxypheny1)-10-methy1-bicyc1o  [ 6 . 2 . 0 ] decan-9-ol  (28d)  - s t e r e o c h e m i s t r y unknown  Cyclobutanol  (28d) was not i s o l a t e d .  I t was t e n t a t i v e l y  149  i d e n t i f i e d by i t s g.c.-mass spectrum. known:  Its absolute stereochemistry is not  m/e ( r e l a t i v e i n t e n s i t y ) 192 (100), 178 (8.8), 163 (16.8),  133 (18.4).  P r o d u c t R a t i o Study  The product r a t i o study f o r keto-acid (28) was conducted in the same fashion as the study f o r keto-acid (26).  A l l of the samples were  analyzed by g.c. and the ratios of (28b+28c+28d):28a and 28b:28c:28d are shown i n table XI.  Keto-acid (28) was photolyzed in the s o l i d state as a  1:1 mixed dimer with a c e t i c a c i d . SOLVENT  cone. (M)  A c e t o n i t r i le Benzene S o l i d State  0.01 M 0.01 M  temp.°C 22 ± 2 22 ± 2 22 ± 2  (28b+28c+28d):28a 28b:28c:28d 57:43 ± 5 66:34 ± 2 70:30 ± 2  70:19:11 ± 2 76:17:7 ± 2 31:14:55 ± 2  Table XI:  Product ratios from the photolysis of keto-acid (28)  Photolysis  of 2 - c y c l o h e p t y l - 2 - m e t h y l - 1 - ( 4 - c a r b o x y p h e n y l ) - e t h a n o n e  (29)  Preliminary photolysis of keto-acid (29) indicated that para-carboxypropiophenone  (28a) was the predominant product formed upon  photolysis of (29) in benzene and a c e t o n i t r i l e . i d e n t i f i e d as t h e i r methyl e s t e r s .  The photoproducts were  Para-carbomethoxypropiophenone was  i d e n t i f i e d by i t s g.c. retention time and mass spectra as compared to an authentic sample.  Three cycl obutanols were also formed as indicated by  g.c. analysis (column A, program 2): 29d ( r t 9.23).  29b (rt 6.85), 29c (rt 7.30), and  The cycl obutanols were not i s o l a t e d and have been  150  t e n t a t i v e l y i d e n t i f i e d by t h e i r g.c.-mass spectra.  The absolute  stereochemistry of the cycl obutanols is not known.  8-(4-carbomethoxyphenyl)-9-methyl-bicyclo [5.2.0] nonan-8-ol (29b) - stereochemistry unknown  m/e ( r e l a t i v e i n t e n s i t y ) 229 (23.9), 192 (100), 178 (18.2), 163 (40.9), 133 (25.0).  8-(4-carbomethoxyphenyl)-9-methyl-bicyclo [5.2.0] nonan-8-ol (29c) - stereochemistry unknown  m/e ( r e l a t i v e i n t e n s i t y ) 229 (4.23), 192 (100), 177 (12.7), 163 (23.9), 133 (25.4).  8-(4-carbomethoxyphenyl)9-methyl-bicyclo [5.2.0] nonane-8-ol (29d) - stereochemistry unknown  m/e ( r e l a t i v e i n t e n s i t y ) 192 (100), 177 (6.7), 163 (16.7), 133 (16.7).  Product Ratio Study  The product r a t i o study f o r keto-acid (29) was conducted i n the same fashion as the product study f o r keto-acid (26). A l l of the samples were analyzed by g.c. and the ratios of (29b+29c+29d):28a and 29b:29c:29d  151  are shown in table X I I : SOLVENT  cone. (M)  Acetonitrile Benzene S o l i d State  0.01 M 0.01 M  Table X I I :  temp.°C  (29b+29c+29d):28a 29b:29c:29d  22 + 2 22 + 2 22 ± 2  31:69 ± 2 32:68 ± 2 27:73 ± 1  54:32:14 ± 2 60:28:12 ± 1 63:13:24 ± 1  Product r a t i o s from the photolysis of keto-acid (29)  Photolysis of 2-cyclohexyl-2-methyl-l-(4-carboxypheny1)-ethanone (30) a-Methyl-a-cyclohexyl-para-carboxyacetophenone (1.0 g) was i r r a d i a t e d following the same procedure used in the i r r a d i a t i o n of keto-acid (26).  The r e s u l t a n t o i l was analyzed by g.c. (column A,  program 2) and found to contain f i v e products; para-carbomethoxypropiophenone 28a ( r t 2.34) and four cyclobutanols; ( r t 5.75), 30c ( r t 6.24), 30d ( r t 6.72), and 30e ( r t 7.05).  30b  The two major  components, 28a and 30b were i s o l a t e d using a column (2.0 cm x 30 cm) of s i l i c a gel 60 (230-400 mesh) with a 0-9% ethyl acetate in petroleum ether solvent as the step gradient eluent.  Para-carbomethoxypropiophenone  (28a)  was i d e n t i f i e d by i t s g . c . retention time and mass spectra as compared to an authentic sample.  The cyclobutanols which were not i s o l a t e d have been  t e n t a t i v e l y i d e n t i f i e d by t h e i r g.c.-mass spectra.  The stereochemistry of  these cyclobutanols i s not known.  7-(la, 6a,  76, 8a)-(4-carbomethoxyphenyl)-8-methyl-bicyclo [4.2.0]  octan-7-ol (30b) Cyclobutanol  (30b) was i s o l a t e d as a y e l l o w i s h o i l :  jhr (neat)  152 1724 cm"  1  (C=0), 3497 cm"  1  (broad, OH); H nmr (CDCI , 400 MHz) 1.11 l  3  (3H, d, J=7.5 Hz), 1.2-1.45 (3H, m), 1.57 (IH, m), 1.62-1.95 (6H, m), 2.31 (IH, m), 3.90 (3H, s ) , 7.43 (2H, d, J=9 Hz), 7.99 (2H, d, J=9 Hz), proton decoupling of the signal at 1.11 results in the multiplet at 2.31 c o l l a p s i n g to a doublet (J=10 Hz); in an N.O.E. difference experiment; i r r a d i a t i o n of the doublet at 7.43 results in the enhancement of the signal at 2.31 and in a d d i t i o n a signal is enhanced at 1.7 ppm; m/e ( r e l a t i v e i n t e n s i t y ) 274 (m , 0.1), 215 (60.4), 192 (100), 178 (43.6), 163 +  (93.4); c a l c u l a t e d mass f o r C H 1 7  9 O  0 : q  274.1569, Found:  7-(4-carbomethoxyphenyl)-8-methyl-bicyclo  274.1538.  [ 4 . 2 . 0 ] o c t a n - 7 - o l (30c)  - s t e r e o c h e m i s t r y unknown m/e ( r e l a t i v e i n t e n s i t y ) 215 (11.1), 192 (100), 177 (5.6), 163 (22.2), 133 (20.8).  7-(4-carbomethoxyphenyl)-8-methyl-bicyclo  [ 4 . 2 . 0 ] o c t a n - 7 - o l (30c)  - s t e r e o c h e m i s t r y unknown m/e ( r e l a t i v e i n t e n s i t y ) 215 (33.9), 192 (100), 163 (32.2), 133 (23.7).  7-(4-carbomethoxyphenyl)-8-methyl-bicyclo  [ 4 . 2 . 0 ] o c t a n - 7 - o l (30d)  - s t e r e o c h e m i s t r y unknown m/e ( r e l a t i v e i n t e n s i t y ) 215 (19.3), 192 (100), 177 (9.2), 163 (42.9), 133 (27.7).  153  Product Ratio Study The product r a t i o study f o r keto-acid (30) was conducted in the same fashion as the product study f o r keto-acid (26).  A l l of the samples  were analyzed by g.c. and the ratios of (30b+30c+30d+30e):28a and 30b:30c:30d:30e are shown in table X I I I : SOLVENT  cone. (M)  A c e t o n i t r i le Benzene S o l i d State  0.01 M 0.01 M  Table X I I I :  temp.°C 22 + 2 22 ± 2 22 ± 2  (30b+30c+30d+30e):28a 30b:30c:30d:30e 75:25 ± 3 61:39 ± 3 68:32 ± 2  56:11:11:22±1 48:17:15:20+1 49:3:6:42 ±2  Product ratios from the photolysis of keto-acid (30)  Photolysis of  2-cyclopentyl-2-methyl-1-(4-carboxyphenyl)-l-ethanone(31)  a-Methyl-a-cyclopentyl-para-carboxyacetophenone  (1.0 g) was  i r r a d i a t e d following the same procedure used in the i r r a d i a t i o n of keto-acid (26).  The resultant o i l was analyzed by g.c. (column A,  program 2) and found to contain 3 products, para-carbomethoxypropi ophenone 28a (rt 2.34), and two cyclobutanols, 31b ( r t 6.22) and 31c ( r t 6.54). The two major components 28a and 31b were i s o l a t e d using a column (2.0 cm x 30 crn) of s i l i c a gel 60 (230-400 mesh) with a 0-9% ethyl acetate i n petroleum ether solvent as the step gradient eluent.  The minor  cyclobutanol 31c was t e n t a t i v e l y i d e n t i f i e d by i t s g.c.-mass spectrum. The stereochemistry of cyclobutanol 31c is not known. Para-carbomethoxypropi ophenone was i d e n t i f i e d by comparison of i t s retention time and mass spectrum with an authentic sample.  g.c.  154  6 - ( l a , 5a, 66, 7a)-(4-carbomethoxypheny1)-7-methyl-bicyclo [ 3 . 2 . 0 ] heptan-6-ol  (31b)  Cyclobutanol (neat) 1726 cm"  1  (31b) was i s o l a t e d as a s l i g h t l y yellow o i l :  (C=0), 3466 cm"  1  _ir  (broad, OH); H nmr ( C D U , 400 MHz) X  3  1.15 (3H, d, J=7 Hz), 1.3-1.65 (6H, m), 1.92 (IH, s, broad, exchanges with D 0), 2.53 (2H, m), 2.79 (IH, m), 3.92 (3H, s ) , 7.33 (2H, d, J=8 Hz), 8.01 2  (2H, d, J=8 Hz), proton decoupling of the signal at 1.15 r e s u l t s in a s i m p l i f i c a t i o n of the s p l i t t i n g pattern f o r the m u l t i p l e t at 2.53;  proton  decoupling of the signal at 2.53 r e s u l t s in the doublet at 1.15 c o l l a p s i n g t o a s i n g l e t and the m u l t i p l e t at 2.79 t o c o l l a p s i n g t o a broad doublet (J=2.1 Hz); proton decoupling the signal at 2.79 results in a s i m p l i f i c a t i o n of the s p l i t t i n g pattern f o r the m u l t i p l e t at 2.53; in an N.O.E. difference experiment, i r r a d i a t i o n of the signal at 7.33 r e s u l t s  in  an enhancement of the signal at 2.53 and a weaker enhancement at 2.79, the signal at 8.01 i s also enhanced; m/e ( r e l a t i v e i n t e n s i t y ) 260 (m , 0 . 1 ) , +  192 (100), 163 (51.6); c a l c u l a t e d mass f o r C H 0 ^ : 1A  Found:  ?n  260.1412,  260.1409.  6-(4-carboroethoxyphenyl)-7-methyl-bicyclo [ 3 . 2 . 0 ] heptan-6-ol  (31c)  - stereochemistry unknown m/e ( r e l a t i v e i n t e n s i t y ) 192 (100), 177 (16.2), 163 (40.0), 133 (27.0).  Product R a t i o Study The product r a t i o study f o r keto-acid (31) was conducted in the  155  same fashion as the product r a t i o study f o r keto-acid (26). A l l of the samples were analyzed by g.c. and the ratios of (31b+31c):28a and 31b:31c are shown i n table XIV: SOLVENT  cone. (M)  Acetonitrile Benzene S o l i d State  0.01 M 0.01 M  Table XIV:  temp.°C  (31b+31c):28a  22 ± 2 22 ± 2 22 ± 2  68:32 ± 4 53:47 ± 2 55:45 ± 3  31b:31c 77:23 ± 2 76:24 ± 1 100:0  Product ratios from the photolysis of keto-acid (31)  In order to perform quantum y i e l d studies, the keto-acids were converted t o t h e i r corresponding methyl e s t e r s .  Photolysis of the keto-esters  y i e l d e d the same products as were obtained by e s t e r i f i c a t i o n of the photoproducts from the keto-acids.  The product ratios from the photolysis  of the keto-esters were obtained i n a c e t o n i t r i l e and benzene solvents in the same fashion as the product r a t i o study f o r ketone (9).  Photolysis of 2-cyclooctyl-l-(4-carbomethoxyphenyl)-ethanone  SOLVENT  cone. (M)  Acetonitrile Benzene  0.10 M 0.10 M  Table XV:  temp.°C 22 ± 2 22 + 2  (26b+26c):26a 68:32 ± 1 65:35 + 1  (32)  26b:26c 52:48 ± 1 75:25 ± 1  Product ratios from the photolysis of keto-ester (32)  156 P h o t o l y s i s of 2 - c y c l o h e p t y l - 1 - ( 4 - c a r b o m e t h o x y p h e n y l ) - e t h a n o n e  SOLVENT  cone. (M)  Acetonitrile Benzene  0.10 M 0.10 M  Table XVI:  temp.°C 22 ± 2 22 ± 2  (33)  (27b+27c):26a  27b:27c  38:62 ± 1 46:54 ± 1  65.35 ± 1 84:16 ± 1  Product ratios from the photolysis of keto-ester (33)  P h o t o l y s i s of  2-cyclooctyl-2-methyl-1-(4-carbomethoxyphenyl)-  ethanone (34)  SOLVENT  cone. (M)  Acetonitrile Benzene  0.10 M 0.10 M  Table XVII:  temp.°C 22 ± 2 22 ± 2  (28b+28c+28d):28a 28b:28c:28d 50:50 ± 3 57:43 ± 2  66:19:15 ± 1 75:19:6 ± 1  Product ratios from the photolysis of keto-ester (34)  P h o t o l y s i s of  2-cycloheptyl-2-methyl-1-(4-carbomethoxyphenyl)-  ethanone (35)  SOLVENT  cone. (M)  Acetonitrile Benzene  0.10 M 0.10 M  Table XVIII:  temp.°C 22 ± 2 22 ± 2  (29b+29c+29d):28a 29b:29c:29d 30:70 ± 2 29:71 ± 3  52:29:19 ± 1 59:27:14 ± 2  Product ratios from the photolysis of keto-ester (35)  157  Photolysis of  2-cyclohexyl-2-methyl-1-(4-carbomethoxyphenyl)-  ethanone (36)  SOLVENT  cone. (M)  A c e t o n i t r i le Benzene  0.10 M 0.10 M  Table XIX:  (30b+30c+30d+30e):28a 30b:30c:30d:30e  22 ± 2 22 + 2  48:52 ± 2 47:53 ± 2  58:7:9:26 ± 1 57:10:13:20± 2  Product ratios from the photolysis of keto-ester (36)  P h o t o l y s i s of ethanone  temp.°C  2-cyclopentyl-2-methyl-1-(4-carbomethoxypheny1)-  (37)  SOLVENT  cone. (M)  A c e t o n i t r i le Benzene  0.10 M 0.10 M  Table XX:  temp.°C 22 ± 2 22 ± 2  (31b+31c):28a  31b:31c  45:55 ± 2 61:39 ± 2  79:21 ± 2 72:28 ± 1  Product ratios from the photolysis of keto-ester (37)  Quantum Y i e l d s $  Quantum y i e l d s were determined following the procedure of Lewis  3  Three Pyrex tubes were f i l l e d with 3 ml of benzene containing the ketone (0.10 M) and an alkane internal standard.  Three d i s t i n c t standards were  used at a concentration of 1 mg/ml: 1. •2. 3.  Tetradecane (C Docosane  11+  ), Valerophenone standard  (C )  Tetracosane  22  (C ) 24  158  P r i o r to quantum y i e l d determinations, the accuracy of the g.c. detector response to the standard and photoproducts was accurately determined.  These were found not to deviate s u b s t a n t i a l l y from the  response f a c t o r of 1:1 f o r a 1:1 mass r a t i o of photoproduct to standard. The samples were degassed using three freeze-pump-thaw cycles and i r r a d i a t e d using a 450-W, medium pressure mercury lamp with a f i l t e r s o l u t i o n of potassium chromate to i s o l a t e the 313 nm l i n e .  The amount of  l i g h t absorbed was measured by simultaneous i r r a d i a t i o n of the tubes containing the ketone, with three tubes containing a 0.10 M s o l u t i o n of valerophenone and 1 mg/m! standard as the actinometer s o l u t i o n .  The  i r r a d i a t i o n was conducted on a merry-go-round apparatus, and product y i e l d s were determined by g . c , f o r conversions up to 4%. The y i e l d of acetophenone from valerophenone was calculated knowing the exact concentration of the internal standard, the detector response f a c t o r (1:1) and the r a t i o of acetophenone to internal standard, as determined by g.c. a n a l y s i s .  The quantum y i e l d of acetophenone from  valerophenone is known to be 0 . 3 3 by the samples was determined.  35  and thus, the amount of l i g h t absorbed  From the y i e l d s of the photoproducts and  knowledge of the amount of l i g h t absorbed by the samples, the quantum y i e l d s of the following ketones were determined. table XXI.  These are shown in  An accumulated e r r o r of ±15% in the quantum y i e l d s has been  calculated from the standard deviations observed following multiple g.c.  analysis. The ketone concentrations of 0.1 M ensured that the samples were  159  o p t i c a l l y opaque at 313 nm.  KETONE  STANDARD  20  C  22  $ CYCLIZATION  $ CLEAVAGE  $ TOTAL  0.11  0.06  0.17  21  C2 2  0.074  0.108  0.18  33  c  2H  0.11  0.064  0.174  34  C L>  0.0665  0.056  0.123  35  C L>  0.046  0.013  0.059  36  C  2 4  0.022  0.013  0.035  37  C  2 4  0.027  0.016  0.043  2  2  Table XXI:  Quantum y i e l d s f o r ketones 20, 21, 33-37, i n benzene  Rate Studies Rate studies were performed following the same i r r a d i a t i o n and degassing techniques u t i l i z e d i n the quantum y i e l d studies.  Several Pyrex  tubes containing 3 ml of a 0.1 M s o l u t i o n of ketone and 1 mg/ml of standard, i n benzene, were prepared with several concentrations of 2,5dimethyl-2,4-hexadiene.  The amount of l i g h t absorbed was calculated using  valerophenone as the actinometer.  The absolute y i e l d of the photoproducts  was determined and converted t o quantum y i e l d s f o r each quencher concentration. quencher  The quantum y i e l d f o r each ketone i n the absence of was divided by the quantum y i e l d s ($) determined at each  quencher concentration.  These values are shown i n table XXII.  For a  t r i p l e t state photoreacti on, a plot of § / § against quencher concentration Q  w i l l y i e l d a s t r a i g h t l i n e with a slope equal t o K i and an intercept  160  of 1.  The value T i s the t r i p l e t l i f e t i m e and  i s the rate of t r i p l e t  quenching by the quencher. KETONE  Cone. Quencher (M)  » /» 0  20  0.0 0.022 0.056 0.108 0.155 0.212  0.17 0.14 0.112 0.092 0.083 0.068  1.0 1.21 1.52 1.85 2.05 2.50  21  0.0 0.022 0.0564 0.108  0.18 0.154 0.123 0.091  1.0 1.17 1.46 1.98  Table XXII:  Values of $/<£> and quencher concentrations ketones 20 and 21 0  for  161  BIBLIOGRAPHY 1.  Norrish, R., and Appleyard, M., J . Chem. 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Omkaram: Omkaram, N., and Scheffer, J . R . , unpublished r e s u l t s .  166  APPENDIX  Quantum Y i e l d :  From the t r i p l e t  $ =§  CT  ——— sal H  §  n  state  d  LK  = quantum y i e l d of type II products  5>^y = quantum y i e l d f o r s i n g l e t to t r i p l e t intersystem crossing  k  H  = di radical formation from T.  k  H  +  Ik  d  0p  = e f f i c i e n c y of d i r a d i c a l to Type II products  k  H  = rate of hydrogen abstraction  k  n  = rate of t r i p l e t d e a c t i v a t i o n by radiative and non-radiative decay  Rate Study:  Stern-Volmer Analysis  — = 1 + k x [Q]  $  = quantum y i e l d in the presence of quencher  $°  = quantum y i e l d in the absence of quencher  kq  = bimolecular quenching rate constant  x  = triplet  lifetime  [Q] = quencher concentration  

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