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A study of the Norrish type II reaction in the solid state : structure-reactivity correlations based… Nalamasu, Omkaram 1986

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A STUDY OF THE NORRISH TYPE I I REACTION IN THE SOLID STATE: STRUCTURE-REACTIVITY CORRELATIONS BASED ON X-RAY CRYSTALLOGRAPHY By OMKARAM NALAMASU B.Sc., Osmania U n i v e r s i t y , I n d i a , 1978 M . S c , The U n i v e r s i t y o f Hyderabad, I n d i a , 1980 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY IN THE FACULTY OF GRADUATE STUDIES (DEPARTMENT OF CHEMISTRY) We a c c e p t t h i s t h e s i s as c o n f o r m i n g t o the r e q u i r e d s t a n d a r d THE UNIVERSITY OF BRITISH COLUMBIA AUGUST 1986 © OMKARAM NALAMASU, 1986 In presenting t h i s thesis i n p a r t i a l f u l f i l m e n t of the requirements for an advanced degree at the University of B r i t i s h Columbia, I agree that the Library s h a l l make i t f r e e l y available for reference and study. I further agree that permission for extensive copying of t h i s thesis for scholarly purposes may be granted by the head of my department or by his or her representatives. I t i s understood that copying or publication of t h i s thesis for f i n a n c i a l gain s h a l l not be allowed without my written permission. Department of CWA/VAA^ The University of B r i t i s h Columbia 1956 Main Mall Vancouver, Canada V6T 1Y3 D E - 6 n/sn To Awa, Bapu, and Annayya - i i i -ABSTRACT The Norrish type II rea c t i o n of 31 substrates with the general a-cycloalkyl-p-substituted acetophenone structure was investigated i n s o l i d and s o l u t i o n media. The difference i n p h o t o r e a c t i v i t y between the s o l i d and s o l u t i o n states and the requirements f o r photochemical hydrogen ab s t r a c t i o n have been derived from X-ray c r y s t a l structure data obtained f o r 17 de r i v a t i v e s . The differe n c e i n st e r e o e l e c t r o n i c requirements for hydrogen transf e r among Norrish type I I , McLafferty and Barton reactions are discussed. Six-atom abstra c t i o n geometries other than chair, namely boat and h a l f - c h a i r , and smooth hydrogen abstractions at 0-•-H distances greater than the previously supposed upper l i m i t of 2.7A were observed. Abstractions also occurred at abstraction angles that are as unfavorable as 62° f o r r (the degree to which the hydrogen i n question l i e s outside the mean plane of the carbonyl group) and 77° f o r A (the C-0-•-H angle). The i d e a l values of r and A are 0° and 90-120°, r e s p e c t i v e l y . The e f f e c t of the s o l i d state on ph o t o r e a c t i v i t y was found to range from very small to s i g n i f i c a n t . The photochemistry of a-adamantyl-p-methoxyacetophenone delineates the importance of packing e f f e c t s i n st e e r i n g the course of a unimolecular r e a c t i o n i n the s o l i d state. The diff e r e n c e i n the s o l i d state r e a c t i v i t y between the two c r y s t a l modifi-cations of a-adamantyl-p-chloroacetophenone has been found to be a r e s u l t of conformational factors rather than packing e f f e c t s . No c o r r e l a t i o n was evident i n comparing the s o l u t i o n state hydrogen -iv-a b s t r a c t i o n r a t e c o n s t a n t s w i t h t h e h y d r o g e n a b s t r a c t i o n g e o m e t r i e s o b t a i n e d from X - r a y c r y s t a l l o g r a p h y f o r the c y c l o b u t y l , c y c l o p e n t y l , c y c l o h e x y l , c y c l o h e p t y l and c y c l o o c t y l d e r i v a t i v e s o f a - c y c l o a l k y l - p -c h l o r o a c e t o p h e n o n e . T h i s was i n t e r p r e t e d as i n d i c a t i n g a s i g n i f i c a n t c o n t r i b u t i o n t o t h e h y d r o g e n a b s t r a c t i o n r a t e c o n s t a n t i n s o l u t i o n from non-minimum e n e r g y c o n f o r m a t i o n s w i t h b e t t e r h y d r o g e n a b s t r a c t i o n g e o m e t r i e s t h a n t h a t o f the minimum energy c o n f o r m a t i o n s p r e s e n t i n t h e c r y s t a l . An a b s o l u t e asymmetric s y n t h e s i s w i t h >80% o p t i c a l y i e l d was a c h i e v e d by p e r f o r m i n g p h o t o l y s e s on t h e c h i r a l c r y s t a l s o f t h e a c h i r a l s t a r t i n g m a t e r i a l , a - 3 - m e t h y l - l - a d a m a n t y l - p - c h l o r o a c e t o p h e n o n e . F i n a l l y , p h o t o l y s e s o f a - c y c l o h e x y l and c t - c y c l o p e n t y l a c e t o p h e n o n e as g u e s t : h o s t complexes w i t h D i a n i n ' s compound ( 4 - p - h y d r o x y p h e n y l - 2 , 2 , 4 - t r i m e t h y l -chroman) r e v e a l e d t h a t the s e l e c t i v i t y a c h i e v e d i n t h i s c o n s t r a i n e d medium i s s i m i l a r t o t h a t o b t a i n e d i n t h e s o l i d s t a t e . -v-TABLE OF CONTENTS Page ABSTRACT i i i LIST OF FIGURES v i i i LIST OF SCHEMES x i LIST OF TABLES x i i i ACKNOWLEDGEMENTS x v i INTRODUCTION 1 1. G e n e r a l 1 The t o p o c h e m i c a l p o s t u l a t e 3 Cinnamic a c i d s 4 Coumarins 6 2 - B e n z y l - 5 - b e n z y l i d e n e c y c l o p e n t a n o n e s 8 P o l y m e r i z a t i o n r e a c t i o n s 10 a) P o l y d i a c e t y l e n e s 10 b) F o u r - c e n t e r p o l y m e r i z a t i o n s 12 C r y s t a l e n g i n e e r i n g 14 2. U n i m o l e c u l a r r e a c t i o n s 15 3. Hydrogen a b s t r a c t i o n 26 7-Hydrogen a b s t r a c t i o n 31 N o r r i s h type I I r e a c t i o n 32 4. O b j e c t i v e s o f p r e s e n t r e s e a r c h 37 - v i -5. Outline of t h i s thesis 40 RESULTS AND DISCUSSION 44 Preparation of substrates 44 1. a-Cyclohexyl-p-substituted acetophenones: 49 Conformation i n the s o l i d state 50 Hydrogen abstraction geometry 52 Photochemistry 54 2. Substrates that undergo cleavage 70 (A) Q-Cyclopentyl-p-substituted acetophenones: . . . . 70 Conformation i n the s o l i d state 70 Geometric parameters 71 Photochemistry 74 (B) Q-Cyclobutyl-p-chloroacetophenone, 45: 77 Conformation i n the s o l i d state 77 Hydrogen abstraction geometry 78 Photochemistry 79 (C) Q-Exo-2-bicyclo[2.2.l]heptyl-p-substituted acetophenones 84 Hydrogen abstraction geometry 84 Photochemistry 84 3. Compounds that undergo cleavage as well as closure: 89 Conformation i n the s o l i d state 89 Hydrogen abstraction geometry 90 Photochemistry 91 - v i i -4 . A c o r r e l a t i o n between molecular conformation and b i r a d i c a l p a r t i t i o n i n g to photoproducts i n the Norrish type II rea c t i o n 94 5. The importance of non-minimum energy conformations i n the Norrish type II rea c t i o n . . . . 101 6. The photochemistry of a-adamantyl acetophenones: . . . 1 1 8 (A) A rever s a l of s t e r e o s e l e c t i v i t y of cyclobutanol formation i n the s o l i d state . . . 126 (B) R e a c t i v i t y differences between dimorphs . . . . 135 7 . S o l i d state asymmetric synthesis i n unimolecular reactions 142 8. Photochemical studies i n Dianin's compound 155 9. Geometric requirements f o r hydrogen abstraction: . . . 161 McLafferty rearrangement 161 Barton re a c t i o n 164 Angular r e l a t i o n s h i p s i n hydrogen atom abstraction 169 Norrish type II rea c t i o n 171 Norrish type II vs McLafferty reaction 173 EXPERIMENTAL 182 BIBLIOGRAPHY 250 - v i i i -LIST OF FIGURES Figure Caption Page 1 2-Benzyl-5-benzylidenecyclopentanone 9 2 I l l u s t r a t i o n of geometric parameters involved i n the abstraction of hydrogen by oxygen (A) and carbon (B) 27 3 Representation of d (0-•-H distances), r (angle between 0 -• -H vector and i t s p r o j e c t i o n on plane of carbonyl group), and A (C-0---H angle) . . . 34 4 a-Cyclohexylacetophenone conformational isomers . . . 42 5 Newman pr o j e c t i o n down Cg-Cg carbon-carbon bond . . . 51 6 Stereodiagram of a-cyclohexyl-p-chloro-acetophenone, 28 51 7 P i c t o r i a l representation of bo a t l i k e hydrogen abstrac t i o n geometry i n compound 28 52 8 Motions involved i n the formation of trans-cyclobutanol from 1 , 4-hydroxybiradical 62 9 Conversion vs percentage of c y c l i z a t i o n f o r the s o l i d state i r r a d i a t i o n of ketone 28 66 10 Boatlike abstraction geometry seen i n a-cyclopentyl-p-chloroacetophenone, 38 73 11 Stereodiagram depicting two conformers of a-cyclopentyl-p-carboxyacetophenone (43) present i n the c r y s t a l 73 12 H a l f - c h a i r l i k e abstraction geometry i n a-cyclobutyl-p-chloroacetophenone, 45 78 13 P i c t o r i a l diagram of the hydrogen abstraction geometry i n 46 85 14 P i c t o r i a l presentation of boatlike hydrogen abstraction seen i n a-cycloheptyl-p-chloro-acetophenone, 50 90 - i x -1 5 Stern-Volmer p l o t s 1 1 0 1 6 V a r i a t i o n i n d, T , A w i t h r o t a t i o n about the a, {5 (Cg-Cg) bond. The 0° r o t a t i o n c o r r e s p o n d s to the c r y s t a l c o n f o r m a t i o n shown 1 1 3 1 7 Cg-C Q Bond r o t a t i o n vs energy 1 1 5 1 8 Rates o f hydrogen a b s t r a c t i o n i n a - c y c l o -alkoxyacetophenones 1 1 7 1 9 P r o t o n NMR spectrum o f d e h y d r a t i o n p r o d u c t 56d . . . . 1 2 1 2 0 1 3 C NMR spectrum o f d e h y d r a t i o n p r o d u c t 56d 1 2 2 2 1 P r o t o n NMR spectrum o f T r a n s - e y e l o b u t a n o l 56t . . . . 1 2 4 2 2 P a r a l l e l p a c k i n g o f a r o m a t i c groups i n 56 1 3 1 2 3 Photograph o f p l a t e and n e e d l e m o d i f i c a t i o n o f a-adamantyl-p-chloroacetophenone c r y s t a l s . . . . 1 3 8 2 4 P e r c e n t a g e o f c o n v e r s i o n vs r a t i o o f c i s - c y c l o -b u t a n o l i n the s o l i d s t a t e i r r a d i a t i o n o f 54p . . . . 1 3 9 2 5 M o l e c u l a r c o n f o r m a t i o n i n n e e d l e (54n) and p l a t e (54p) m o d i f i c a t i o n s o f a - a d a m a n t y l - p - c h l o r o -acetophenone 1 4 1 2 6 J--'C NMR spectrum o f a-3-methyl- 1-adamantyl-p-c h l o r o a c e t o p h e n o n e , 58 1 4 6 2 7 Photograph o f c r y s t a l s o f a - 3 - m e t h y l - l -adamantyl-p-chloroacetophenone, 58. 1 4 8 2 8 C r y s t a l s o f a-3-methyl-l-adamantyl-p-c h l o r o a c e t o p h e n o n e , 58 a f t e r i r r a d i a t i o n 1 5 3 2 9 The D i a n i n ' s Compound and i t s cage 1 5 6 3 0 P a r t i a l 1 3 C CPMAS s o l i d s t a t e NMR spectrum o f D i a n i n ' s compound w i t h a - c y c l o h e x y l -acetophenone, 37 1 5 9 3 1 F u n c t i o n a l i z a t i o n o f C^g and C^g carbons w i t h a l k o x y r a d i c a l s 1 6 7 3 2 S t e r e o s e l e c t i v i t y i n the B a r t o n r e a c t i o n 1 6 8 3 3 Arrangement o f atomic o r b i t a l s i n c a r b o n y l groups. (a) Kasha model, (b) R a b b i t e a r model . . . . 1 7 0 Ground and excited state geometries of butanal c a l c u l a t e d by Dewar - x i -LIST OF SCHEMES Scheme Page - X l l -2 3 47 2 4 48 2 5 48 2 6 48 2 7 55 2 8 56 29 68 3 0 80 3 1 81 82 3 3 93 3 4 100 3 5 103 106 3 7 119 38 130 39 145 4 0 147 162 4 2 163 4 3 163 4 4 165 4 5 165 4 6 167 47 180 - x i i i -LIST OF TABLES T a b l e C a p t i o n Page I The hydrogen a b s t r a c t i o n by oxygen t h r o u g h a five-membered t r a n s i t i o n s t a t e 28 I l a The hydrogen a b s t r a c t i o n by carbon through a six-membered t r a n s i t i o n s t a t e 29 l i b The hydrogen a b s t r a c t i o n by ca r b o n t h r o u g h a f i v e - o r six-membered t r a n s i t i o n s t a t e 30 I I I Hydrogen a b s t r a c t i o n parameters f o r a - c y c l o h e x y l - p - s u b s t i t u t e d acetophenones 53 IV NMR parameters o f c y c l o b u t a n o l s 57 V C y c l i z a t i o n : c l e a v a g e r a t i o s f o r the p h o t o l y s i s o f a - c y c l o h e x y l - p - s u b s t i t u t e d acetophenones, 28-37 59 VI B i r a d i c a l parameters f o r k e t o n e s , 28-33 61 VII D e n s i t i e s and i n t e r p l a n a r d i s t a n c e s c a l c u l a t e d f o r k etones 28-33 from c r y s t a l d a t a 64 V I I I C i s - and t r a n s - c y c l o b u t a n o l r a t i o s f o r the p h o t o l y s i s o f a - c y c l o h e x y l - p - s u b s t i t u t e d acetophenones, 28-37 . . . 67 IX Hydrogen a b s t r a c t i o n parameters f o r a - c y c l o -p e n t y l - p - s u b s t i t u t e d acetophenones 72 X C y c l i z a t i o n : c l e a v a g e r a t i o s f o r the p h o t o l y s i s o f a - c y c l o p e n t y l - p - s u b s t i t u t e d acetophenones, 38-44 . . 75 XI P h o t o c h e m i s t r y o f a - c y c l o b u t y l - p - c h l o r o -acetophenone, 45 79 XI I Hydrogen a b s t r a c t i o n parameters f o r a-exo-2 - b i c y c l o - [ 2 . 2 . l ] h e p t y l - p - s u b s t i t u t e d acetophenones 85 X I I I P h o t o c h e m i s t r y o f n o r b o r n y l d e r i v a t i v e s o f acetophenone, 46-49 86 XIV Hydrogen a b s t r a c t i o n parameters f o r a - c y c l o h e p t y l - p - s u b s t i t u t e d acetophenones, 50 and 51 . . . 91 - x i v -XV P h o t o c h e m i s t r y o f a - c y c l o h e p t y l - p -s u b s t i t u t e d acetophenones 92 XVI C i s - and t r a n s - e y e l o b u t a n o l r a t i o s f o r the i r r a d i a t i o n o f a - c y c l o h e p t y l - p - s u b s t i t u t e d acetophenones 92 XVII S o l i d s t a t e i r r a d i a t i o n o f c h l o r o s u b s t r a t e s . . . 97 X V I I I B i r a d i c a l parameters f o r a - c y c l o a l k y l - p -c h l o r o acetophenones 96 XIX C r y s t a l d e n s i t i e s ( d ) , i n t e r p l a n a r d i s t a n c e s (h) and C n " ^ 9 " c 1 0 " ^ l l d i h e d r a l a n g l e s 97 XX MMP2 c a l c u l a t i o n s p e rformed on a - c y c l o h e x y l - p -c h l o r o a c e t o p h e n o n e , 28 109 XXI Quantum y i e l d , k i n e t i c and s t r u c t u r a l d a t a f o r p - c h l o r o s u b s t r a t e s I l l XXII R e l a t i v e hydrogen a b s t r a c t i o n r a t e c o n s t a n t s from c y c l o a l k a n e s by f r e e r a d i c a l s 116 X X I I I NMR parameters f o r c i s - and t r a n s - c y c l o b u t a n o l s . . . 125 XXIV P h o t o c h e m i s t r y o f a - a d a m a n t y l - p - s u b s t i t u t e d acetophenones 127 XXV Hydrogen a b s t r a c t i o n parameters f o r a - a d a m a n t y l - p - s u b s t i t u t e d acetophenones 129 XXVI P a c k i n g parameters f o r a - a d a m a n t y l - p - s u b s t i t u t e d acetophenones 132 XXVII M u l t i p l i c i t y dependent p h o t o c h e m i s t r y o f a-adamantylacetone (72) 133 XXVIII P h o t o p r o d u c t r a t i o s as a f u n c t i o n o f r e a c t i o n medium 137 XXIX G e n e r a t i o n o f o p t i c a l a c t i v i t y i n s o l i d s t a t e i r r a d i a t i o n s 150 XXX E n a n t i o m e r i c s h i f t d i f f e r e n c e s (AA5) 151 XXXI A b s t r a c t i o n parameters f o r a - 3 - m e t h y l - l -adamantyl-p-chloroacetophenone, 58 154 XXXII H o s t / g u e s t r a t i o s and p h o t o c h e m i s t r y o f i n c l u s i o n complexes 158 - X V -XXXIII 6 Values (C-H...0 angle) for a-cycloalkyl-p-substituted acetophenones 173 XXXIV McLafferty fragmentation of a - c y c l o a l k y l -p-chloro acetophenones 178 XXXV V a r i a t i o n of 0- - -H7 distances and abstrac t i o n angles by r o t a t i o n around Ca-Cp bond 179 - x v i -ACKNOWLEDGEMENT I g r a t e f u l l y acknowledge the encouragement, guidance, patience and friendship of my supervisor, Dr. John R. Scheffer. I am deeply indebted to him for arousing and sustaining my i n t e r e s t i n t h i s area of research through many invaluable discussions. A debt of gratitude i s owed to Mr. Stephen Evans, Dr. Sara A r i e l and Dr. James Trotter who performed a l l the X-ray crystallography and t h e o r e t i c a l c a l c u l a t i o n s reported i n t h i s t h e s i s . I t was a pleasure c o l l a b o r a t i n g with such an enthusiastic team. I would l i k e to thank my friends at UBC and the Chemistry Department, whose friendship made my stay at UBC most enjoyable. Special thanks are due to Mr. Pokkuluri Phaniraj f o r proof reading and to Mrs Rani Theeparajah f o r typing t h i s t h e s i s . I express my gratitude to the Chemistry Department f o r f i n a n c i a l support i n the form of a Teaching Ass i s t a n t s h i p . Thanks are also due to the s t a f f of the departmental NMR, MS and elemental analysis laborator-ies f o r courteous and r e l i a b l e assistance. 1 INTRODUCTION 1. GENERAL M a t t e r can be c l a s s i f i e d i n t o t h r e e b r o a d c l a s s e s - gases, l i q u i d s and s o l i d s . While m o l e c u l e s a r e a r r a n g e d randomly i n gas and l i q u i d media (which can be termed f l u i d o r d i s p e r s e d media), m o l e c u l e s are o r d e r e d i n the s o l i d phase. S t u d i e s o f m o l e c u l a r s t r u c t u r e have been c a r r i e d o ut i n a l l t h r e e media, b u t c h e m i c a l r e a c t i o n s have been con-d u c t e d p r i m a r i l y i n gas and l i q u i d media because o f the n o t i o n t h a t the m o l e c u l a r motions r e q u i r e d f o r r e a c t i o n a r e n o t f e a s i b l e i n s o l i d s . O r g a n i c c h e m i s t s have, t o a l a r g e e x t e n t , i g n o r e d the c h e m i s t r y o f o r g a n i c s o l i d s because o r g a n i c s o l i d s a r e g e n e r a l l y low m e l t i n g and h i g h l y v o l a t i l e compared t o i n o r g a n i c s o l i d s . I n a d d i t i o n , i t i s d i f f i c u l t t o s u p p l y the h i g h a c t i v a t i o n e n e r g i e s r e q u i r e d f o r many r e a c t i o n s below the m e l t i n g p o i n t o f the c r y s t a l . However, the problem o f s u p p l y i n g a c t i v a t i o n energy a t ambient o r even v e r y low temp e r a t u r e s can be s o l v e d by u s i n g p h o t o c h e m i c a l a c t i v a t i o n . The b r a n c h o f o r g a n i c c h e m i s t r y t h a t d e a l s w i t h the r e a c t i o n s o f o r g a n i c c r y s t a l s u s i n g p h o t o c h e m i c a l a c t i v a t i o n i s c a l l e d " O r g a n i c S o l i d S t a t e P h o t o c h e m i s t r y " . While the stu d y o f the r m a l r e a c t i o n s i n o r g a n i c s o l i d s can be t r a c e d back to the o r i g i n s o f o r g a n i c c h e m i s t r y i t s e l f , the study o f p h o t o c h e m i c a l r e a c t i o n s i n v o l v i n g o r g a n i c c r y s t a l s i s r e l a t i v e l y r e c e n t . ^ Wohler i s now c r e d i t e d w i t h d i s c o v e r i n g i n 1828 the thermal t r a n s f o r m a t i o n o f ammonium c y a n a t e to u r e a i n the s o l i d s t a t e . Photo-- 2 -c h e m i c a l phenomena i n the s o l i d s t a t e were s t u d i e d f i r s t i n the l a t e 19th and e a r l y 20th c e n t u r i e s . P h o t o c h e m i c a l r e a c t i o n s i n the s o l i d s t a t e , such as the d i m e r i z a t i o n o f the c i n n a m i c a c i d s , the photochromism o f the s a l i c y l a l d e h y d e a n i l s , f u l g i d e s and t e t r a c h l o r o n a p h t h o q u i n o n e , were s t u d i e d by Markwald,^ C i a m i c i a n , ^ Stobbe,^ de Jong-* and S e n i e r . ^ U n f o r t u n a t e l y , t h i s adventurous e r a o f s o l i d s t a t e p h o t o c h e m i s t r y came to an end i n the e a r l y 1920s, m a i n l y because o f the l a c k o f methods c a p a b l e o f g i v i n g an i n s i g h t i n t o the m o l e c u l a r arrangement i n c r y s -t a l s . ^ Many s o l i d s t a t e c h e m i s t s o f t h a t e r a were c o r r e c t i n t h e i r p r e d i c t i o n t h a t the p u z z l i n g p h o t o c h e m i c a l b e h a v i o r o f the s u b s t r a t e s i n the s o l i d s t a t e c o u l d be answered i n the f u t u r e by the t h e n n o v e l t e c h n i q u e o f X - r a y c r y s t a l l o g r a p h y . The r e c e n t surge i n o r g a n i c s o l i d s t a t e c h e m i s t r y , ^ ' ^ e s p e c i a l l y s o l i d s t a t e p hotochemistry,10-21 ^as been the r e s u l t o f s e v e r a l developments: 1. The advent o f advanced d i f f r a c t o m e t e r s and d i g i t a l computers has g r e a t l y f a c i l i t a t e d the c r y s t a l s t r u c t u r e d e t e r m i n a t i o n o f s m a l l o r g a n i c m o l e c u l e s . I t i s a p p r o p r i a t e to mention i n t h i s c o n t e x t the c o n t r i b u t i o n s o f Nobel P r i z e w i n n e rs, Jerome K a r l e and H e r b e r t Hauptmann who by d e v e l o p i n g d i r e c t methods o f c r y s t a l s t r u c t u r e d e t e r m i -n a t i o n , have r e v o l u t i o n i z e d the f i e l d o f X - r a y c r y s t a l l o g r a p h y . 2. The p r oblem o f s u p p l y i n g the h i g h a c t i v a t i o n e n e r g i e s r e q u i r e d f o r the r e a c t i o n s i n the s o l i d s t a t e has been overcome by the development o f a r t i f i c i a l l i g h t s o u r c e s l i k e mercury lamps and l a s e r s . The s i t u a t i o n today i s g r e a t l y d i f f e r e n t from the time when p h o t o c h e m i s t s had to depend on s u n l i g h t f o r p h o t o c h e m i c a l r e a c t i o n s . One a u t h o r o f t h a t time n o t e d t h a t " w i t h the sun as the c h i e f s o u r c e o f r a d i a t i o n , p r o g r e s s i n - 3 -the f i e l d o f t e n depended on the weather".^2 3_ Techn i q u e s such as -LJCPMAS NMR (carbon-13 c r o s s p o l a r i z e d magic a n g l e s p i n n i n g n u c l e a r magnetic resonance s p e c t r o s c o p y ) and HREM ( h i g h r e s o l u t i o n e l e c t r o n m i c r o s c o p y ) have opened up new v i s t a s o f r e s e a r c h i n the s o l i d s t a t e , s u p p l y i n g v a l u a b l e i n f o r m a t i o n about s o l i d s t a t e p r o c e s s e s . 4. The s u c c e s s f u l a p p l i c a t i o n o f s o l i d s t a t e p h o t o c h e m i s t r y i n i n f o r m a t i o n s t o r a g e / r e t r i e v a l , p h o t o b i o l o g y and o r g a n i c s y n t h e s i s has made i t an a p p l i e d s c i e n c e . A l l the above f a c t o r s t o g e t h e r make t h i s f i e l d an e x c i t i n g and r a p i d l y d e v e l o p i n g one. The Topochemical Postulate A b r o a d d e f i n i t i o n o f a t o p o c h e m i c a l l y c o n t r o l l e d r e a c t i o n was f i r s t i n t r o d u c e d by K o h l s c h u t t e r i n 1918.^3 H e d e f i n e d a t o p o c h e m i c a l l y c o n t r o l l e d r e a c t i o n as one i n which the s t r u c t u r e o f the p h o t o p r o d u c t ( s ) i s governed by the t h r e e - d i m e n s i o n a l ( b u l k ) or tw o - d i m e n s i o n a l ( s u r f a c e ) arrangement o f the m o l e c u l e s i n the s o l i d , w i t h the c l e a r i m p l i c a t i o n t h a t the m o l e c u l a r p a c k i n g and the mutual o r i e n t a t i o n o f the m o l e c u l e s are the key f a c t o r s i n d i r e c t i n g the c o u r s e o f a r e a c t i o n i n s o l i d s . I n the f o l l o w i n g pages, the development o f the t o p o c h e m i c a l p r i n c i p l e i s d e s c r i b e d by examining the s o l i d s t a t e p h o t o c h e m i s t r y o f v a r i o u s systems. - 4 -Cinnamic Acids Liebermann i n 1890 d i s c o v e r e d t h a t upon e x c i t a t i o n by u l t r a v i o l e t l i g h t , t r a n s - c i n n a m i c a c i d s undergo [2+2] d i m e r i z a t i o n s i n the s o l i d s t a t e , b u t i s o m e r i z e to the c o r r e s p o n d i n g c i s - i s o m e r s i n the s o l u t i o n s t a t e . ^ T h i s r e a c t i o n was i n t e r p r e t e d l a t e r as a l a t t i c e c o n t r o l l e d r e a c t i o n by B e r n s t e i n and Quimby.^^ However, the b a s i c i d e a s o f t o p o c h e m i s t r y have been the r e s u l t o f the p i o n e e r i n g s t u d i e s by G e r h a r d Schmidt and h i s co-workers on the c i n n a m i c a c i d s and o t h e r systems. Schmidt was the f i r s t t o r e c o g n i z e t h a t t h e r e e x i s t s a c o r r e l a t i o n between the p h o t o r e a c t i v i t y i n the s o l i d s t a t e and the m o l e c u l a r a r r a n g e m e n t . ^ The arrangement o f the t r a n s - c i n n a m i c a c i d s i n the c r y s t a l l i n e s t a t e conforms t o t h r e e p a t t e r n s : the a - type, c h a r a c t e r i z e d by an i n t e r m o l e c u l a r c e n t r e - t o - c e n t r e d i s t a n c e o f 3.6-4.1 A between the o l e f i n i c d ouble bonds, and by an a n t i - p a r a l l e l , c e n t r o s y m m e t r i c a r r a n g e -ment o f the monomers. In the ft-type, the n e i g h b o r i n g o l e f i n i c double bonds a r e t r a n s l a t i o n a l l y e q u i v a l e n t w i t h c o n s i d e r a b l e f a c e - t o - f a c e o v e r l a p . The c e n t r e - t o - c e n t r e d i s t a n c e between the r e a c t i v e double bonds i s 3.9- 4.1 A. The 7 -type i s i d e n t i f i e d by an i n t e r m o l e c u l a r mean pl a n e d i s t a n c e o f 4.7-5.1 A between the o l e f i n i c double bonds. The monomers are a g a i n r e l a t e d by a t r a n s l a t i o n b u t the a d j a c e n t double bonds o f the monomers are o f f s e t i n such a way t h a t t h e y do n o t o v e r l a p v e r y much. The i r r a d i a t i o n o f the t r a n s - c i n n a m i c a c i d s (Scheme 1) i n the s o l i d - 5 -state yields a centre-symmetric t r u x i l l i c acid (head-to-tail) dimer from the a-polymorph, and a mirror symmetric truxinic acid (head-to-head) dimer from the ^ -polymorph. The 7-type is photostable because of a larger distance and poorer overlap between the adjacent double bonds of the monomers compared to the arrangement in the a and ^-polymorphs.^ Scheme 1: The solid state photochemistry of trans-cinnamic acids. - 6 -Based on the c l e a r c o r r e l a t i o n observed between the molecular alignment i n the c r y s t a l and the s t e r i c configuration of the photopro-ducts (cyclobutanes, i n t h i s case), Schmidt proposed the "topochemical postulate", which states that reactions i n the c r y s t a l l i n e state tend to occur with a minimum of atomic and molecular motion.26,28 For [2+2] photocycloadditions, Schmidt proposed a maximum i n t e r -molecular distance of 4.2 A between the rea c t i v e double bonds above which no photochemical dimerization takes place. Schmidt also pointed out that i t i s not only necessary that the neighboring cinnamic acid double bonds are within 4.2 A, but that they should also be p a r a l l e l for a successful dimerization. The study of m-bromo-trans-cinnamic acid exemplifies the l a t t e r c r i t e r i o n . The c r y s t a l structure of t h i s compound unambiguously shows that the adjacent double bonds are separated by a distance of 3.9 A, but the c r y s t a l i s photostable because the poten-t i a l l y r eactive double bonds are r e l a t e d by a g l i d e plane and are non- p a r a l l e l r e s u l t i n g i n a poor overlap between them.^9 Coumarins Photodimerization of substituted coumarins i n the s o l i d as well as the s o l u t i o n states has been known since 1 9 0 2 , a n d i n t e r e s t i n g l y , coumarin i t s e l f i s l i g h t - i n a c t i v e i n the s o l i d state. Ramamurthy and hi s co-workers have recently investigated the s o l i d state photochemistry of 28 d e r i v a t i v e s of coumarin to determine the role played by the substituents i n bringing about a favorable molecular arrangement for - 7 -[2+2] photocycloaddition i n the photostable coumarin molecule. 3^ Of the 28 d e r i v a t i v e s they studied, only 12 underwent photo-dimerization. The important findings of the i n v e s t i g a t i o n include the i d e n t i f i c a t i o n of the acetoxy and chloro groups as u s e f u l steering groups i n a l i g n i n g the coumarin molecules for photodimerizations, and the anomalous photochemical behavior of 7-methoxy (1) and 7-chlorocou-marins (2). 1 2 7-methoxycoumarin 7-chlorocoumarin 7-Methoxycoumarin (1) undergoes a topochemical photodimerization i n s p i t e of a n o n - p a r a l l e l arrangement of the r e a c t i v e double bonds. X-ray crystallography reveals that the centre-to-centre distance between the o l e f i n i c bonds i s 3.83 A, but the p o t e n t i a l l y reactive double bonds of the monomers i n the asymmetric u n i t are rotated by 65° with respect to each other r e s u l t i n g i n a poor overlap between them. Since the dimerization proceeds i n a topochemical fashion, i t appears l i k e l y that p a r a l l e l i s m between reacting double bonds i s not a s t r i c t requirement as previously supposed. Topochemical dimerizations have also been reported i n the l i t e r a t u r e f o r other systems possessing n o n - p a r a l l e l double b o n d s . 3 2 " 3 6 - 8 -The o b s e r v e d t o p o c h e m i c a l d i m e r i z a t i o n o f n o n - p a r a l l e l double bonds i n v a r i o u s m o l e c u l e s makes i t n e c e s s a r y to a l l o w f o r a c e r t a i n degree o f i n h e r e n t o r i e n t a t i o n a l freedom i n the c r y s t a l l a t t i c e . The energy c a l c u l a t i o n s p e rformed i n the case o f 7-methoxycoumarin (1) r e v e a l t h a t a r o t a t i o n o f 20° i n the r e q u i r e d d i r e c t i o n c o u l d be a c h i e v e d w i t h o u t s i g n i f i c a n t e x p e n d i t u r e o f energy. In a d d i t i o n , the e l e c t r o n i c e x c i t a -t i o n i s supposed to i n c r e a s e the a t t r a c t i v e f o r c e s between the n e i g h b o r -i n g m o l e c u l e s . ^ I t appears l i k e l y t h a t an extended c o o p e r a t i v e motion o f the monomers i n the c r y s t a l l a t t i c e as a r e s u l t o f e l e c t r o n i c e x c i t a -t i o n might w e l l a c c o u n t f o r the o b s e r v e d p h o t o d i m e r i z a t i o n s i n v o l v i n g the n o n - p a r a l l e l double bonds. The o t h e r i n t e r e s t i n g r e s u l t p r o v i d e d by t h e s e workers i s the p h o t o c h e m i c a l d i m e r i z a t i o n o f 7 - c h l o r o c o u m a r i n (2). T h i s compound undergoes a t o p o c h e m i c a l d i m e r i z a t i o n even though the c e n t r e - t o - c e n t r e d i s t a n c e between the n e i g h b o r i n g o l e f i n s i s 4.45 A ( s i g n i f i c a n t l y h i g h e r t h a n Schmidt's upper l i m i t o f 4.2 A f o r p h o t o d i m e r i z a t i o n s ) . I t appears l i k e l y from t h i s i n v e s t i g a t i o n t h a t the upper l i m i t o f 4.2 A f o r the p h o t o d i m e r i z a t i o n s might not be a v e r y r i g i d one o r might v a r y depending on the system. 2 - B e n z y l - 5 - b e n z y l i d e n e Cyclopentanones (BBCP) An i n - d e p t h s t u d y o f the 2 - b e n z y l - 5 - b e n z y l i d e n e c y c l o p e n t a n o n e s was t a k e n up i n the s o l i d s t a t e by J.M. Thomas and h i s c o l l a b o r a t o r s a t Cambridge, England. ^ '21.38-40 xhey i n v e s t i g a t e d many d e r i v a t i v e s o f the b a s i c s k e l e t o n 2 - b e n z y l - 5 - b e n z y l i d e n e c y c l o p e n t a n o n e (BBCP, F i g . 1) - 9 -to analyze the e f f e c t of substituents on the packing and various other topochemical phenomena. Some of the v a r i a t i o n s introduced to the BBCP basic skeleton include substituents at the ortho, meta and para posi-tions of the benzyl and benzylidene moieties, s u b s t i t u t i o n on the cyclopentanone r i n g , and the replacement of cyclopentanone by cyclohexa-none. F i g . 1: 2-Benzyl-5-benzylidenecyclopentanone (BBCP). The following features of the s o l i d state photochemistry of the BBCP der i v a t i v e s are of i n t e r e s t : 1) The isomorphic behavior of BBCP derivatives containing chloro, methyl or bromo groups at the para p o s i t i o n of the benzylidene r i n g . This i s s u r p r i s i n g i n the l i g h t of the large differences i n volume between bromo and chloro (or methyl) groups. 2 ) The establishment of the chloro/methyl i n t e r c h a n g e a b i l i t y rule i n - 10 -f o r m i n g s o l i d s o l u t i o n s by v i r t u e o f t h e i r s i m i l a r volumes.41-43 3) The s u r p r i s i n g t o p o t a c t i c p h o t o d i m e r i z a t i o n [a t o p o t a c t i c r e a c t i o n i s one which proceeds i n a s i n g l e c r y s t a l ( s t a r t i n g m a t e r i a l ) - s i n g l e c r y s t a l ( p r o d u c t ) manner w i t h o u t phase s e p a r a t i o n . Such r e a c t i o n s r e s u l t i n a p r o d u c t m a t r i x t h a t can be c r y s t a l l o g r a p h i -c a l l y r e l a t e d t o the r e a c t a n t m a t r i x ] o f BBCP m o l e c u l e s w i t h s u b s t i -t u e n t s a t the p a r a p o s i t i o n o f the b e n z y l moiety, even though the d i m e r i z a t i o n r e s u l t s i n l a r g e v a r i a t i o n s o f the c e l l parameters a, b and c. 4) The s o l i d s t a t e p h o t o c h e m i s t r y i s i n g e n e r a l a c c o r d w i t h the topo-c h e m i c a l arguments. Polymerization Reactions a) Polydiacetylenes The s o l i d s t a t e p h o t o p o l y m e r i z a t i o n o f d i a c e t y l e n e s and c o n j u g a t e d d i o l e f i n s has added a new d i m e n s i o n to t o p o c h e m i c a l l y c o n t r o l l e d p r o -c e s s e s . The p h o t o p o l y m e r i z a t i o n o f d i a c e t y l e n e s has grown i n t o an i n t e r e s t i n g and v e r y u s e f u l r e s e a r c h a r e a l a r g e l y because o f i t s a b i l i t y t o p r o v i d e n e a r l y d e f e c t - f r e e s i n g l e c r y s t a l s w i t h a p o l y c o n j u g a t e d backbone. P r e s e n t l y i n polymer c h e m i s t r y , t o p o t a c t i c and t o p o c h e m i c a l p o l y m e r i z a t i o n i s one o f the e a s i e s t and most r e l i a b l e ways o f p r e p a r i n g p o l y m e r i c s i n g l e c r y s t a l s o f m a c r o s c o p i c s i z e . - ^ Wegner has d e f i n e d t o p o c h e m i c a l p o l y m e r i z a t i o n as a n o n - d i f f u s i o n a l c o n v e r s i o n o f monomer s i n g l e c r y s t a l s t o polymer s i n g l e c r y s t a l s w i t h - 11 -the r e t e n t i o n of symmetry (Scheme 2).^>^^ The polymerization of diacetylenes proceeds through a 1,4-trans-addition pathway. The polymer-i z a t i o n of diacetylenes i s highly s t e r e o s p e c i f i c , devoid of any side products, and can be induced not only by l i g h t but also by heat and 7-rays. I Scheme 2: Schematic i l l u s t r a t i o n of the topochemical polymerization of diacetylene chains i n s o l i d state. Reaction takes place only i f 0<45° and d~3.4-4.0 A. - 12 -b ) F o u r - c e n t r e p o l y m e r i z a t i o n s F o u r - c e n t r e p o l y m e r i z a t i o n i s a g e n e r a l term u s e d f o r the photo-p o l y m e r i z a t i o n o f c o n j u g a t e d d i o l e f i n s t o y i e l d a c y c l o b u t a n e u n i t b a s e d polymer i n b o t h the s o l i d and s o l u t i o n s t a t e s . On the b a s i s o f c r y s t a l -l o g r a p h i c and m e c h a n i s t i c i n v e s t i g a t i o n , i t has been d e t e r m i n e d t h a t f o u r - c e n t r e p o l y m e r i z a t i o n i s n o t o n l y a t o p o c h e m i c a l b u t o f t e n a t o p o t a c t i c r e a c t i o n , g e n e r a t i n g polymer c r y s t a l s from monomer c r y s t a l s i n q u a n t i t a t i v e y i e l d s . ^ H i r s h f e l d and Schmidt had s u g g e s t e d the p o s s i b i l i t y o f topochemi-c a l p o l y m e r i z a t i o n , p r o v i d e d s u i t a b l e c o n t a c t s a r e m a i n t a i n e d between the r e a c t i v e c e n t r e s d u r i n g the c o u r s e o f the p o l y m e r i z a t i o n . ^ A l o n g w i t h the p o s t u l a t e they were a l s o s u c c e s s f u l i n d e m o n s t r a t i n g polymer f o r m a t i o n from a l l t r a n s - 1 , 3 , 5 - h e x a t r i e n e - l , 5 - d i c a r b o x y l i c a c i d . ^ F o u r - c e n t r e p o l y m e r i z a t i o n i s unique, as i t p r o c e e d s i n a s t e p w i s e mechanism, n o t o n l y i n s o l u t i o n but a l s o i n the s o l i d s t a t e . I t i s r a t h e r s u r p r i s i n g to n o t e t h a t the p h o t o p o l y m e r i z a t i o n o f 2 , 5 - d i s t y r y l p y r a z i n e (3, Scheme 3) i s the f i r s t example o f a p o l y m e r i z a -t i o n r e a c t i o n to p r o c e e d v i a a s t e p w i s e p a t h w a y . ^ The e s s e n c e o f the t o p o c h e m i c a l p r i n c i p l e as a r e s u l t o f the p i o n e e r i n g s t u d i e s o f Schmidt on the c i n n a m i c a c i d s and by o t h e r groups on v a r i o u s b i m o l e c u l a r or p o l y m e r i z a t i o n r e a c t i o n s can be summarized i n the f o l l o w i n g i m p o r t a n t p o s t u l a t e s : 1) The n a t u r e o f the m o l e c u l a r p a c k i n g i n the c r y s t a l i s f a r more im p o r t a n t than the i n t r i n s i c r e a c t i v i t y o f the m o l e c u l e i t s e l f . 2) The symmetry, s e p a r a t i o n d i s t a n c e and the r e l a t i v e o r i e n t a t i o n o f - 13 -Scheme 3: Four-centre photo polymerization of 2,5-distyrylpyrazine neighboring reactive centres, play a dominant r o l e i n deciding the course of the reaction. 3 ) Molecules which e x i s t i n many conformations i n dispersed media adopt one or very few low energy conformations i n the s o l i d state. In addition, molecules which are randomly oriented i n the f l u i d state are hig h l y organized i n the s o l i d state. Such conformational s e l e c t i v i t y and immobility caused by the c r y s t a l l a t t i c e often r e s u l t i n very high s e l e c t i v i t i e s i n the s o l i d state reactions. 4) The phenomenon of molecules c r y s t a l l i z i n g i n more than one confor-mation i n the s o l i d state i s r e f e r r e d to as conformational polymor-phism.^ These d i f f e r e n t c r y s t a l forms often display d i f f e r e n t r e a c t i v i t i e s , giving valuable i n s i g h t s i n understanding the r e l a t i o n s h i p between structure and r e a c t i v i t y . 5 ) The rea c t i o n pathways are well defined and are very l i m i t e d i n the 1 4 s o l i d state. 6) For every r e a c t i o n i n the s o l i d state, there e x i s t s an i d e a l arrangement of molecules and a maximum distance, deviations from which render the reaction unfavorable. C r y s t a l Engineering Although several remarkable, highly s t e r e o s p e c i f i c reactions proceed smoothly i n the s o l i d state, the s p e c i a l packing arrangements required f o r such high s e l e c t i v i t y are not those of deliberate design, but are a r e s u l t of fortunate circumstances. Unless i t i s possible to design and engineer organic c r y s t a l s to display the desired photoreacti-v i t y , there i s a danger that t h i s f i e l d could become an academic c u r i o s i t y . The process of steering molecules to c r y s t a l l i z e into c e r t a i n space groups that possess the required packing c h a r a c t e r i s t i c s , symmetries and intermolecular distances and other topochemical factors i s c a l l e d c r y s t a l e n g i n e e r i n g . ^ I t has been the usual p r a c t i c e i n the organic s o l i d state to study several c l o s e l y r e l a t e d compounds to understand the underlying struc-t u r a l features of a system. The information derived from such studies i s then used to design a new molecule that c r y s t a l l i z e s i n a c r y s t a l form possessing the required topochemical properties. Several ways of performing c r y s t a l engineering have been reported i n the l i t e r a t u r e , and some of the most common and successful ways are the following: - 15 -1) C o - c r y s t a l l i z a t i o n w i t h m e r c u r i c c h l o r i d e t o a t t a i n a double bond s e p a r a t i o n d i s t a n c e o f l e s s than 4.2 A . - ^ 2) D i c h l o r o s u b s t i t u t i o n on an a r o m a t i c r i n g t o i n d u c e c r y s t a l l i z a t i o n i n a yS-modif i c a t i o n . 2 <^ 3) C h l o r o / m e t h y l i n t e r c h a n g e a b i l i t y f o r a t t a i n i n g a p h o t o r e a c t i v e arrangement f o r a p h o t o s t a b l e m o l e c u l e by i n c o r p o r a t i n g s m a l l amounts o f the p h o t o s t a b l e compound i n t o the l a t t i c e o f the photo-a c t i v e s u b s t r a t e . ^ 2 Scope u n d o u b t e d l y e x i s t s f o r c r y s t a l e n g i n e e r i n g o f many o t h e r t y p e s o f c r y s t a l s . T h i s i s e s p e c i a l l y p r o m i s i n g i n the l i g h t o f the modest s u c c e s s e s a l r e a d y a c h i e v e d i n e n g i n e e r i n g c r y s t a l s f o r s e v e r a l b i m o l e c u l a r and p o l y m e r i z a t i o n r e a c t i o n s . 2. UNIMOLECULAR REACTIONS While the s o l i d s t a t e p h o t o s y n t h e s i s o f i n d i g o ( 5 ) from 2 ' - n i t r o -c h a l c o n e (4) was r e p o r t e d by E n g l e r and Dorant i n 1895 (Scheme 4, page 16), the e x a c t mechanism o f t h i s rearrangement i s s t i l l unknown.^ The same i s t r u e o f the photochromism o f the N - s a l i c y l i d e n e a n i l s . The r e a c t i o n has been known f o r more than 100 y e a r s , and r e c e n t l y the d i f f e r e n t i a l p h o t o b e h a v i o r o f these a n i l s i n the s o l i d s t a t e has been a t t r i b u t e d m a i n l y to the p a c k i n g d i f f e r e n c e s among them. N e i t h e r the n a t u r e o f the p h o t o c h e m i c a l l y i n d u c e d c o l o r - t r a n s i e n t nor the pronounced r e a c t i v i t y d i f f e r e n c e s between the t h e r m a l and p h o t o c h e m i c a l s o l i d s t a t e - 16 -reactions has been understood. The story of these two s o l i d state unimolecular photorearrangements i s t y p i c a l and serves as a clear example to i l l u s t r a t e the chemist's lack of i n t e r e s t i n these problems. Such lack of a c t i v i t y i n unimolecular reactions i s d i f f i c u l t to r a t i o n a l i z e considering the unique advantages they o f f e r over bimolecu-Scheme 4: The s o l i d state photosynthesis of indigo. 17 l a r or polymerization reactions. The c r u c i a l packing arrangement required f o r a successful bimolecular reaction i s not a p r e r e q u i s i t e for a unimolecular reaction to proceed. Unimolecular reactions also o f f e r the unique opportunity of examining the ph o t o r e a c t i v i t y exhibited by a singl e conformer present i n the c r y s t a l l i n e state. Such examination i s only possible f o r unimolecular reactions and not for bimolecular reac-tions, as the packing mode of the monomers rather than the i n t r i n s i c r e a c t i v i t y of the monomer i s the decisive force i n d i r e c t i n g the path of the r e a c t i o n i n a bimolecular reaction. Unimolecular reactions often display higher s e l e c t i v i t y and follow an e n t i r e l y d i f f e r e n t reaction pathway to give novel products i n the s o l i d state. A dramatic example which i l l u s t r a t e s how the l a t t i c e constraints are responsible for alternate, less motion topochemical pathways i n unimolecular photoreac-tions i s provided by Matsuura (Scheme 5 ) . - ^ Dimers «*- 0 * Solid State hi/ 0 6 benzene hi/ 7 Scheme 5: The s o l i d and so l u t i o n state photochemistry of santonin. 18 Santonin ( 6 ) , upon i r r a d i a t i o n , rearranges to lumisantonin ( 7 ) i n the s o l u t i o n state but gives no such product i n the s o l i d state i r r a d i a t i o n , instead, i t leads to products assumed to r e s u l t from the formation and subsequent dimerization of the cyclopentadienone ( 8 ) . The mechanism of t h i s transformation i s s t i l l unclear and warrants further study. Less motion pathways occurring under the influence of l a t t i c e constraints on atomic and molecular motions become v i a b l e a l t e r n a t i v e s even i n cases where these less motion pathways require higher a c t i v a t i o n energies compared to greater motion pathways to d i s s i p a t e the excess energy associated with the photoexcited state. Below and on the follow-ing pages are shown some of the diverse unimolecular photorearrangements studied. The s e l e c t i o n of the reactions i s random and not intended to be complete or even representative. SOLID 83% ( R e f . 60) 21 -One u n d e r l y i n g f e a t u r e among the above t r a n s f o r m a t i o n s , i n a d d i t i o n to t h e i r i n t e r e s t i n g phase dependent p h o t o c h e m i s t r y , i s the absence o f any s t r u c t u r a l e v i d e n c e (from X - r a y c r y s t a l l o g r a p h y ) to e x p l a i n t h e i r medium dependent p h o t o r e a c t i v i t y . U n t i l r e c e n t l y , a d e t a i l e d 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 t a k i n g advantage o f the s e v e r e l y r e s t r i c t e d environment p r o v i d e d by the c r y s -t a l l i n e s t a t e and u s i n g the d e t a i l e d i n f o r m a t i o n s u p p l i e d by X-ray c r y s t a l l o g r a p h y about the shape and s u r r o u n d i n g s o f the r e a c t a n t immedi-a t e l y p r i o r to the r e a c t i o n was not attempted f o r any u n i m o l e c u l a r r e a c t i o n . Such l a c k o f s y s t e m a t i c i n v e s t i g a t i o n s was p r o b a b l y the main impediment to any improvement i n u n d e r s t a n d i n g the r e a c t i v i t y p a t t e r n s f o r u n i m o l e c u l a r r e a c t i o n s , such as the n a t u r e o f the c r y s t a l l a t t i c e , the range and the n a t u r e o f the motions p e r m i t t e d and d e t a i l s about v a r i o u s p r o c e s s e s i n the s o l i d s t a t e . An e x t e n s i v e and s y s t e m a t i c i n v e s t i g a t i o n i n t o the s o l i d s t a t e p h o t o c h e m i s t r y o f u n i m o l e c u l a r r e a c t i o n s was t a k e n up by S c h e f f e r and h i s c o l l a b o r a t o r s i n the 1970s, and the photorearrangements o f d i v e r s e systems such as c y c l o h e x e n o n e s , 6 ^ e n e - d i o n e s , 6 ^ /?,7-unsaturated k e t o n e s , 6 6 1 , 4 - d i e n e s 6 ^ and k e t o n e s 6 ^ were examined i n the s o l i d as w e l l as i n the s o l u t i o n s t a t e s over the l a s t 15 y e a r s . S c h e f f e r had c l a s s i -f i e d s o l i d s t a t e u n i m o l e c u l a r photorearrangements i n t o t h r e e b r o a d c l a s s e s on the b a s i s o f the d i s t i n c t i o n s between t h e i r s o l i d and s o l u -t i o n s t a t e p h o t o r e a c t i v i t i e s . ^ 1) Systems which undergo i d e n t i c a l p r i m a r y p h o t o p r o c e s s e s i n both s o l i d and s o l u t i o n media to r e s u l t i n a common i n t e r m e d i a t e t h a t p a r t i t i o n s i t s e l f i n t o two or more p r o d u c t s : the r a t i o o f the 22 -p r o d u c t s i s medium-dependent because the p r o d u c t r e q u i r i n g exten-s i v e m o l e c u l a r and atomic motions o f the common i n t e r m e d i a t e does not form o r i s d i s f a v o r e d by the c r y s t a l l a t t i c e i n the s o l i d s t a t e . The s i t u a t i o n i s o u t l i n e d i n case I, Scheme 6. Compounds which undergo competing p h o t o p r o c e s s e s i n b o t h media and produce d i f f e r e n t i n t e r m e d i a t e s (case I I ) : the r e s u l t s o b t a i n e d i n the s o l i d s t a t e d i f f e r from those o b t a i n e d i n the s o l u t i o n s t a t e because the subsequent c o n v e r s i o n o f t h e s e i n t e r m e d i a t e s to p r o d u c t s i s t o p o c h e m i c a l l y a l l o w e d i n one case and f o r b i d d e n i n the o t h e r ( c a s e I I I , Scheme 7). The s i t u a t i o n e n c o u n t e r e d i n systems where two r e a c t i v e conformers e x i s t f o r the s t a r t i n g m a t e r i a l and the c r y s t a l l a t t i c e c o n t r o l s the p h o t o p r o d u c t s by c o n t r o l l i n g the e q u i l i b r i u m r a t i o o f t h e s e two r e a c t i v e conformers i s p r e s e n t e d i n case I I I . I n o r d e r to o b t a i n c o m p l e t e l y d i f f e r e n t r e s u l t s i n the s o l i d s t a t e from the r e s u l t s i n s o l u t i o n , the r e q u i r e m e n t i s k 2 » k ^ • As k^ approaches k2, more o f p h o t o p r o d u c t C would be formed i n s o l u t i o n , and C would be the s o l e p h o t o p r o d u c t i n b o t h media when k ^ » k 2 (Scheme 8) . I n the f o l l o w i n g pages, examples o f cases I - I I I a r e g i v e n . Cose I. Both C and D are produced insolation; only C is fo rmed in solid state. hi/ solution or solid state T i topochemically k, B forbidden -1 r D in solution k i ~ k2 k 3 ~ M hi/ hi/ Solid State C ONLY - 2 4 -Cose III. Only D is formed in solution; only C is formed in the solid state AT hi/ k, • C t topochemically forbidden k 2 » k II A 2 hi/ k 2 • D - 2 5 -Case II. Only D is formed in solution i only C is formed in the solid state hv K topochemically ^ B , — . » C • hv allowed topochemical ly k_o 2 forbidden k 3 ^ D O h i / solid A , 1 9 0 ° hi / solution I hi/ solution \ Scheme 7 26 3 . HYDROGEN ABSTRACTION The use o f the s o l i d s t a t e method f o r the i n v e s t i g a t i o n o f unimo-l e c u l a r p r o c e s s e s r e v e a l e d t h r e e g e n e r a l t y p e s o f hydrogen a b s t r a c t i o n p r o c e s s e s . The f i r s t i s an i n t r a m o l e c u l a r , f i v e membered t r a n s i t i o n s t a t e , /3-hydrogen a b s t r a c t i o n by an e x c i t e d c a r b o n y l oxygen o f an enone or ene-dione m o i e t y , 6 ^ the second and t h i r d comprise a 7-hydrogen a b s t r a c t i o n through a six-membered t r a n s i t i o n s t a t e , and a ^-hydrogen a b s t r a c t i o n t h r o u g h a five-membered r e a c t a n t geometry by one o f the c e n t r a l c a r b o n atoms o f an ene-dione o r enone chromophore.65d,e s ^ n c e t h e s e a b s t r a c t i o n s o c c u r i n the s o l i d s t a t e , where atomic and m o l e c u l a r motions a r e s e v e r e l y r e s t r i c t e d r e l a t i v e t o motions p e r m i t t e d i n the l i q u i d o r gas media, and s i n c e X-ray c r y s t a l l o g r a p h y p r o v i d e s d e f i n i t i v e i n f o r m a t i o n about the shape o f the m o l e c u l e i m m e d i a t e l y p r i o r t o the r e a c t i o n , i t was p o s s i b l e t o o b t a i n v a l u a b l e i n s i g h t s i n t o the geomet-r i e s i n v o l v e d i n the hydrogen a b s t r a c t i o n s . The 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 were d i s c u s s e d i n terms o f t h r e e parameters t h a t d e s c r i b e the ge o m e t r i c r e l a t i o n s h i p between the a b s t r a c t i n g c a r b o n o r oxygen atom and the hydrogen atom b e i n g a b s t r a c t e d . These a r e d, the d i s t a n c e between the a b s t r a c t i n g atom and the a b s t r a c t e d atom, i . e . , the oxygen...hydrogen and carbon...hydrogen d i s t a n c e s , T, the an g l e formed between the 0-•-H o r C---H v e c t o r and i t s p r o j e c t i o n on the mean p l a n e o f the c a r b o n y l group o r the ene-dione double bond, and A, the C=0---H o r C=C---H an g l e ( F i g . 2 ) . The v a l u e s o f d, r , and A are c o m p i l e d i n T a b l e s I and II f o r the compounds t h a t undergo i n t r a m o l e c u l a r hydrogen atom a b s t r a c t i o n i n the 27 -s o l i d s t a t e by oxygen and c a r b o n atoms. E x a m i n a t i o n o f the carbon-•-hydrogen and oxygen-•-hydrogen d i s t a n c e s from T a b l e s I and I I makes i t c l e a r t h a t the d i s t a n c e over which hydrogen a b s t r a c t i o n o c c u r s i s i n v a r i a b l y l e s s t h a n o r e q u a l to 2.9 A and 2.7 A f o r the a b s t r a c t i o n s i n v o l v i n g c a r b o n and oxygen atoms, r e s p e c t i v e l y . These d i s t a n c e s are a l s o the sum o f the v a n der Waals r a d i i o f the atoms i n v o l v e d . (van der Waals r a d i i c a l c u l a t e d by Bondi are r w ( 0 ) , 1.52 A; r w ( C ) , 1.70 A; r w ( H ) , 1.20 A ) . 6 9 Based on these d a t a , S c h e f f e r s u g g e s t e d t h a t i n t r a m o l e c u l a r p h o t o c h e m i c a l hydrogen a b s t r a c -t i o n o c c u r s when the a b s t r a c t i o n d i s t a n c e s i n the ground s t a t e o f the r e a c t a n t a r e l e s s than o r e q u a l t o the sum o f the van der Waals r a d i i o f the atoms i n v o l v e d i n the a b s t r a c t i o n . - 28 -Table I. The Hydrogen Abstraction by Oxygen Through a Five-membered T r a n s i t i o n State. Dione R i R 2 ^3 R 4 d (A) ' 0 ( ° ) *o (' a Ph H H H 2.5 3 81 b Me H Me Me 2.5 0 85 c H Me Me Me 2.3 1 86 d Me H CN H 2.6 8 84 e Me H H benzo 2.6 5 81 f h Me H H Me/H 1 2.5 6 85 g Me H Et/Me Me/EtJ 2.4 5 83 n Average f o r two m o l e c u l e s i n the asymmetric u n i t . 1 H a t C ( 2 ) , Me a t C ( 3 ) . j Me a t C ( 2 ) , E t a t C ( 3 ) , Me a t C ( 4 a ) , E t a t C ( 8 a ) . - 29 -T a b l e I l a : The Hydrogen A b s t r a c t i o n by Carbon Through a Six-membered T r a n s i t i o n S t a t e . f Dione R i R 2 R3 R 4 d (A) 'c (°) A c (' a Me H Me Me 2.9 52 73 b H Me Me Me 2.7 50 74 c benzo H Me Me 2.8 51 74 d benzo H Me/H f H/Me f 2.9 47 75 e benzo H Me/HS Me 2.9 50 74 •Ie a t C(2) and C(4a) , H a t C(3) and C(8a). § Me a t C(4a), H a t C(8a). 30 -Table l i b : The Hydrogen Abstraction by Carbon Through Five- and Six-membered T r a n s i t i o n States. lone R i R 2 R 3 R 4 R5 d (A) 'c (°) Ac ( a Me H Me Me H ( c i s / R 3 ) 2.7 53 79 b Me H Me Me H ( t r a n s / R 3 ) 2.9 50 75 c Me H Me Me Me ( t r a n s / R 3 ) 2.8 50 78 d H H Me Me H ( c i s / R 3 ) 2.8 52 78 e H H Me Me H ( t r a n s / R 3 ) 2.9 51 72 f Me H H Me H ( c i s / R 3 ) 2.8 54 79 g H H H Me H ( c i s / R 3 ) 2.8 54 80 h Me H H H H ( c i s / R 3 ) 2.8 57 81 i H H H H H ( c i s / R 3 ) 2.8 56 82 - 31 -T u r n i n g to the a n g l e r 0 , i t i s e x p e c t e d t h a t the hydrogen a b s t r a c t i o n would be most f a c i l e i f r 0 i s c l o s e t o 0 ° . An a n g l e o f 0 ° f o r r Q would ensure an i d e a l arrangement f o r hydrogen a b s t r a c t i o n i n v o l v i n g the n , 7 r * e x c i t e d s t a t e o f the c a r b o n y l , as t h i s a n g l e would p l a c e t h e h ydrogen i n an i d e a l arrangement f o r a b s t r a c t i o n w i t h the a b s t r a c t i n g h a l f - o c c u p i e d n o r b i t a l on o x y g e n . ^ * ^ The a c t u a l v a l u e s o b s e r v e d f o r r 0 from T a b l e I are c l o s e to 0 ° . The o t h e r a n g l e A Q i s a l s o c r u c i a l f o r e f f i c i e n t hydrogen a b s t r a c t i o n i n v o l v i n g oxygen atoms. The a n g l e A Q i s the a n g l e formed between the c a r b o n y l c arbon, the c a r b o n y l oxygen and the hydrogen atom b e i n g a b s t r a c t e d . The optimum v a l u e f o r A Q i s 9 0 ° o r 1 2 0 ° depending on the n a t u r e o f the atomic o r b i t a l assumed to c o n t a i n the n - o r b i t a l e l e c t r o n s . ^ 2 The v a l u e s f o r A 0 from T a b l e I are a g a i n v e r y c l o s e to the i d e a l v a l u e o f 9 0 ° . I t was n o t p o s s i b l e from t h i s s t u d y to t e s t the l i m i t s f o r the a n g l e s A Q and r Q , as the o b s e r v e d a n g l e s a r e c l o s e t o the i d e a l v a l u e s f o r b o t h p a r a m e t e r s . 7-Hydrogen A b s t r a c t i o n The p r o c e s s whereby a hydrogen atom i s t r a n s f e r r e d from one atom to a n o t h e r i s termed hydrogen a b s t r a c t i o n and i s one o f the most u b i q u i -tous r e a c t i o n s i n a l l o f c h e m i s t r y . Most o f the i n f o r m a t i o n known about hydrogen a b s t r a c t i o n today i s d e r i v e d from the a b s t r a c t i o n s i n v o l v i n g a 7-hydrogen atom and an e l e c t r o n d e f i c i e n t oxygen atom. There a r e t h r e e main ways by which an oxygen atom can be a c t i v a t e d toward a b s t r a c t i o n o f a 7-hydrogen i n t r a m o l e c u l a r l y , and each o f t h e se ways i s a s s o c i a t e d w i t h a name r e a c t i o n . The a b s t r a c t i o n o f a 7-hy-drogen by an oxygen f r e e r a d i c a l i s termed the B a r t o n r e a c t i o n , / J and the a b s t r a c t i o n o f a 7 - h y d r o g e n by an oxygen r a d i c a l c a t i o n t h a t i s g e n e r a t e d by the removal o f an e l e c t r o n from the non-bonding o r b i t a l o f the c a r b o n y l oxygen i s named the M c L a f f e r t y r e a r r a n g e m e n t . ^ The 7 - h y d r o g e n a b s t r a c t i o n by an e l e c t r o n d e f i c i e n t oxygen o f the e x c i t e d s t a t e c a r b o n y l group i s termed the N o r r i s h type II r e a c t i o n ^ - 1 i n r e c o g n i t i o n o f the p i o n e e r i n g c o n t r i b u t i o n t o t h i s r e a c t i o n by N o r r i s h . N o r r i s h Type II R e a c t i o n The l i g h t - i n d u c e d c l e a v a g e and/or c y c l i z a t i o n o f ketones p o s s e s s i n g f a v o r a b l y d i s p o s e d 7 - h y d r o g e n atoms i s termed the N o r r i s h type II r e a c t i o n , and i s the most u b i q u i t o u s o f a l l o r g a n i c p h o t o r e a r r r a n g e -ments, and remains the o b j e c t o f much c u r r e n t m e c h a n i s t i c and s y n t h e t i c i n t e r e s t . ^ 5 • ^ 6 The i r r a d i a t i o n o f 7 - h y d r o g e n - c o n t a i n i n g c a r b o n y l compounds (9, Scheme 9 ) produces a 1 , 4 - b i r a d i c a l ( 10). The t h r e e most common r e a c t i o n s o f such b i r a d i c a l s a r e (1) c l e a v a g e t o a f f o r d an e n o l (11), i n v a r i a b l y i s o l a t e d as the c o r r e s p o n d i n g ketone (12) (but d e t e c t a b l e by s p e c t r o s c o p i c m e t h o d s ^ ) a n c i a n a l k e n e (13) , (2) c y c l i z a t i o n t o c y c l o b u t a n o l s (14), and ( 3 ) d i s p r o p o r t i o n a t i o n to r e g e n e r a t e the s t a r t i n g m a t e r i a l . The r e a c t i o n i s one o f g r e a t impor-ta n c e f o r i t s s y n t h e t i c p o t e n t i a l i n c o n s t r u c t i n g u n u s u a l and h i g h l y s t r a i n e d r i n g s y s t e m s , ^ ' ^ 9 and i s a l s o r e s p o n s i b l e f o r much o f the c u r r e n t knowledge o f the p r o p e r t i e s o f 1,4-biradicals^-*»^ a n d e n o l s . ^ In a d d i t i o n , the N o r r i s h type II r e a c t i o n has been i m p l i c a t e d as an i m p o r t a n t c o n t r i b u t o r t o polymer d e g r a d a t i o n . ^ - 3 3 -H R' •H R 0 V hi/ 0 / R ' ^ c y c l i z a t i o n R'" R 1 , 4 — b i r ad i ca l 10 O H R' 1 / 14 c l e a v a g e R 0 K 12 R 0 ' Eno l 11 H R' + 13 Scheme 9: The Norrish type II reaction. One of the major unresolved points of t h i s r e a c t i o n concerns the preferred geometry f or i n i t i a l hydrogen abstraction. For conformation-a l l y mobile systems, Wagner suggested a s t r a i n - f r e e , c h a i r l i k e , c y c l i c s i x atom reactant conformation f o r 7-hydrogen a b s t r a c t i o n . ^ The abs t r a c t i o n geometry can again be characterized by three parameters. These are d, the oxygen-•-hydrogen distance, r, the degree to which the hydrogen being abstracted l i e s outside the mean plane of the carbonyl group, and A, the angle between the carbonyl carbon, the carbonyl oxygen, and the 7-hydrogen (Fig. 3 ) . - 34 j V orbital F i g . 3 : R e p r e s e n t a t i o n o f d ( 0 - • - H d i s t a n c e ) , T ( a n g l e between 0---H v e c t o r and i t s p r o j e c t i o n on p l a n e o f c a r b o n y l g r o u p ) , and A ( C - 0 - • - H a n g l e ) . On t h e o r e t i c a l grounds, an i n t e r a t o m i c d i s t a n c e o f 1.8 A has been s u g g e s t e d to be the upper l i m i t ^ f o r the N o r r i s h type I I r e a c t i o n . The e x p e r i m e n t a l e v i d e n c e f o r t h i s o f t e n quoted upper l i m i t o f 1.8 A a r i s e s from s t u d i e s o f the M c L a f f e r t y rearrangement. D j e r a s s i and h i s co-workers, i n t h e i r s t u d i e s on s t e r o i d a l k e t o n e s , have e s t a b l i s h e d an upper l i m i t o f 1.8 A f o r the oxygen-•-hydrogen d i s t a n c e over which hydrogen t r a n s f e r does not take p l a c e . I n the 1 6 - k e t o s t e r o i d system (15, Scheme 10), the oxygen-•-hydrogen d i s t a n c e measured w i t h D r e i d i n g models was 1.5 A, and these k e t o s t e r o i d s undergo a smooth M c L a f f e r t y rearrangement. In the c o n f o r m a t i o n a l l y r i g i d 1 1 - k e t o s t e r o i d s (16) and 1 5 - k e t o s t e r o i d s (17), the i n t e r a t o m i c d i s t a n c e between the 7-hydrogen and the c a r b o n y l oxygen was measured to be 1.8 and 2.3 A, r e s p e c t i v e l y . S i g n i f i c a n t l y , n e i t h e r o f these m o l e c u l e s underwent any n o t i c e a b l e r e a c t i o n . Based on these r e s u l t s , D j e r a s s i c o n c l u d e d t h a t the upper - 35 -l i m i t f o r the a b s t r a c t i o n d i s t a n c e i n the M c L a f f e r t y rearrangement i s between 1.5 and 1.8 A. 8 5 T h i s maximum d i s t a n c e o f 1.8 A d e r i v e d from the M c L a f f e r t y rearrangement might n o t a p p l y f o r the N o r r i s h - t y p e I I r e a c t i o n , as shown by Lewis. Lewis and co-workers found t h a t b o t h endo- (18, Scheme 11) c6cr 0 15 1 6 1 7 Scheme 10: K e t o s t e r o i d s s t u d i e d by D j e r a s s i . and e x o - 2 - b e n z o y l norbornane (19) undergo the N o r r i s h type I I r e a c t i o n , b u t the oxygen-•-hydrogen d i s t a n c e measured u s i n g D r e i d i n g models r e v e a l e d t h a t t h i s d i s t a n c e i s 1.7 A i n 18, b u t a r e l a t i v e l y l o n g 2.2 A i n 19. A smooth N o r r i s h type I I r e a c t i o n was o b s e r v e d f o r b o t h k e t o n e s , b u t t h e g r e a t e r d i s t a n c e i n the case o f 19 was r e f l e c t e d i n an a p p r o x i -m a t e l y 600 f o l d s lower r a t e o f hydrogen a b s t r a c t i o n . 8 6 o T u r n i n g t o the an g l e r , Wagner has su g g e s t e d a c o s ^ r dependence f o r the r a t e o f a b s t r a c t i o n , ^ ^ as a l l the e v i d e n c e , b o t h t h e o r e t i c a l ^ and e x p e r i m e n t a l , ^ p o i n t s t o the f a c t t h a t the oxygen n - o r b i t a l i s the a b s t r a c t i n g o r b i t a l i n the a b s t r a c t i o n p r o c e s s . C o n s e q u e n t l y , a b s t r a c -36 Ph 19 Ph 18 Scheme 11: Endo-(18) and exo-2-benzoyl norbornane (19) investigated by Lewis. t i o n would be f a s t e s t when the hydrogen being abstracted i s coplanar with t h i s n - o r b i t a l . There i s some experimental evidence about the e f f e c t of the angle r from the studies of the McLafferty rearrangement. Henion and Kingston concluded that the lack of the r e a c t i o n f or ketone 20 was due to an unfavorable r of 80°. In comparison, ketone 21 does undergo the McLafferty rearrangement, the angle r was estimated to be 50° i n t h i s case. In both ketones 20 and 21 (Scheme 12), the estimated d from molecular models was 1.6 A . ^ Another example concerning the angle r i s from the work of Aoyama et a l . ^ These authors observed that keto-alcohol 22 (Scheme 12) does not undergo the Norrish type II re a c t i o n i n s p i t e of a close contact between keto oxygen and 7-hydrogen. This was interpreted as being due to the fa c t that the 7-hydrogen l i e s almost p r e c i s e l y i n the n - o r b i t a l nodal plane (r = 90°). I t appears from these studies that the upper l i m i t for the angle r i s between 50 and 80°. - 3 7 Scheme 12: Ketones studied by Henion and Kingston, and Aoyama et a l . 4 . OBJECTIVES OF PRESENT RESEARCH It i s c l e a r from the nature of the previous discussion that the study of organic reactions i n the s o l i d state has proved to be a very powerful t o o l i n e s t a b l i s h i n g s t r u c t u r e - r e a c t i v i t y r e l a t i o n s h i p s . The main aim of t h i s thesis was to study the Norrish type II rea c t i o n i n the s o l i d state with multiple objectives. One of the major objectives of the present research was to investigate the s t r u c t u r e - r e a c t i v i t y r e l a -tionships involved i n 7-hydrogen abstraction to e s t a b l i s h c e r t a i n empirical guidelines on hydrogen a b s t r a c t a b i l i t y . Such structure-r e a c t i v i t y patterns deduced from the s o l i d state studies are also of d i r e c t relevance to the s i t u a t i o n e x i s t i n g i n so l u t i o n , as organic molecules nearly always c r y s t a l l i z e i n t h e i r lowest energy s o l u t i o n conformations (consequently the major conformer i n s o l u t i o n ) . Such empirical guidelines on hydrogen a b s t r a c t a b i l i t y should f a c i l i t a t e the - 38 p r e d i c t a b i l i t y of the type II process i n both the s o l u t i o n and s o l i d states. A second important goal of the proposed research was to determine the e f f e c t of the immobilization caused by the c r y s t a l l a t t i c e on the p a r t i t i o n i n g of 1,4-hydroxybiradical (10, page 33). I t i s widely 7 S 7 fi recognized' J •'° that e f f i c i e n t cleavage requires a 1,4-hydroxybiradical conformation i n which both si n g l y occupied p - o r b i t a l s can overlap s i g n i f i c a n t l y with the c e n t r a l sigma bond being broken. The arrangement of t h i s b i r a d i c a l can be eit h e r transoid (23) or c i s o i d (24) i n nature. F a i l u r e to adopt one of these conformations leads to predominant c y c l i -z a tion (Scheme 13, page 39). I t could be a n t i c i p a t e d that the bond rotations and other motions necessary to achieve cleavage or c y c l i z a t i o n reactions w i l l be affe c t e d s i g n i f i c a n t l y by the c r y s t a l l i n e state. This i n turn r a i s e s the s y n t h e t i c a l l y a t t r a c t i v e prospect that i t might be possible to a l t e r the cleavage to c y c l i z a t i o n r a t i o by a l t e r i n g the reaction medium. Studies demonstrating such product control with phase change ( s o l u t i o n to s o l i d state) are known and have been interpreted i n terms of c r y s t a l l a t t i c e c o n t r o l . Unfortunately, these f a s c i n a t i n g studies always lacked the v i t a l X-ray s t r u c t u r a l data needed f or a complete understanding of such p r o c e s s e s , ' The information obtained from the s o l i d state r e a c t i v i t y could also be v e r i f i e d by studying some of the ketones i n the host c a v i t i e s of c r y s t a l l i n e host/guest complexes. The host system chosen for such a study was Dianin's compound.^0 The t h i r d major aim of th i s project was to determine i f a c o r r e l a -t i o n e x i s t s between the hydrogen abstraction rate constants measured i n s o l u t i o n by Stern-Volmer k i n e t i c s and the geometrical parameters 39 obtained from the X-ray s t r u c t u r a l data. I t i s expected that there should be a good c o r r e l a t i o n between the geometry from the s o l i d state Cleavage . , . Cyc l i z a t i on Scheme 13: The b i r a d i c a l conformations suitable f o r cleavage and c y c l i z a t i o n . and the r e a c t i v i t y i n the so l u t i o n state i f the minimum energy conformer present i n the s o l i d state i s also the major co n t r i b u t i n g conformer to the r e a c t i o n i n the s o l u t i o n state. The absence of such a c o r r e l a t i o n would then indicate a s i g n i f i c a n t contribution to the rate constant i n s o l u t i o n from non-minimum energy conformers having geometries that are more favorable f o r the type II process than that of the minimum energy - 40 -conformer. The fourth objective of i n v e s t i g a t i n g the p o s s i b i l i t y of two c r y s t a l polymorphs d i s p l a y i n g d i f f e r e n t r e a c t i v i t y i n the s o l i d state arose from the discovery that a-adamantyl-p-chloroacetophenone c r y s t a l l i z e s i n two c r y s t a l modifications. Several examples of poly-morphs d i s p l a y i n g d i f f e r e n t r e a c t i v i t i e s i n the s o l i d state are known fo r bimolecular reactions. However, only one study i n v o l v i n g the poly-morphs of the s a l i c y l i d e n e a n i l s was reported to e x h i b i t morphology dependent photochromic behavior, but t h i s study was not accompanied by a complete X-ray c r y s t a l l o g r a p h i c analysis, making i t d i f f i c u l t to r a t i o n -a l i z e f u l l y the d i f f e r e n t i a l photobehavior observed.^1 The f i f t h and f i n a l goal of t h i s research developed from the u t i l i z a t i o n of the c r y s t a l c h i r a l i t y of a c h i r a l s t a r t i n g materials to achieve absolute asymmetric syntheses. This aspect i s again very well investigated f o r bimolecular and polymolecular r e a c t i o n s , ^ but i s not reported f o r a unimolecular process. 5. Outline of t h i s thesis Key considerations i n deciding which systems to study involve the r e a l i z a t i o n that (1) most simple 7-hydrogen-containing carbonyl compounds whose s o l u t i o n state photochemistry have been well-studied are l i q u i d s at room temperature, and (2) of those that are c r y s t a l l i n e , many may be expected to adopt conformations i n the s o l i d state that are not s u i t a b l e f o r the Norrish type II reaction. This l a t t e r point i s exem-p l i f i e d by the case of 7-triacontanone ( 2 6 , Scheme 14). I r r a d i a t i o n of - 41 -7 - t r i d e c a n o n e ( 2 6 ) i n the s o l i d s t a t e r e s u l t e d i n no r e a c t i o n , whereas p h o t o l y s i s i n the m e l t gave normal type I I b e h a v i o r 92 The l a c k o f r e a c t i v i t y f o r 7 - t r i a c o n t a n o n e ( 2 6 ) i n the s o l i d s t a t e c a n be r a t i o n a l -i z e d c o n s i d e r i n g the f a c t t h a t a l i p h a t i c a l d e hydes and ketones p r e f e r c o n f o r m a t i o n s i n which the a,B c a r b o n - c a r b o n bond e c l i p s e s the c a r b o n y l group, J such c o n f o r m a t i o n p l a c e s the 7-hydrogen atoms too remote f o r a b s t r a c t i o n i n 7 - t r i d e c a n o n e . The r e a c t i o n p r o c e e d s i n the m e l t because bond r o t a t i o n s about the v a r i o u s c a r b o n - c a r b o n bonds p e r m i t a much c l o s e r approach o f to the c a r b o n y l oxygen. R l = 2 mp 26 n ~ C 6 H 1 3 n " C 1 8 H 3 7 33°C • hi/ NO REACTION N o r r i s h t y p e Scheme 14: The p h o t o c h e m i s t r y o f 7 - t r i a c o n t a n o n e The m o l e c u l e s chosen f o r t h i s i n v e s t i g a t i o n have the b a s i c a - c y c l o a l k y l a c e t o p h e n o n e s t r u c t u r e ( 2 7 ). The c h o i c e o f t h i s system was b a s e d on t h r e e main c r i t e r i a . (1) The p-methyl d e r i v a t i v e o f a - c y c l o -h e x y l a c e t o p h e n o n e i s a s o l i d and undergoes a smooth N o r r i s h type I I r e a c t i o n i n the s o l u t i o n s t a t e . ^ (2) Two most l i k e l y c o n f o r m a t i o n s t h a t might be adopted i n the s o l i d s t a t e , A and B, have a t a r g e t - 42 7-hydrogen atom i n a favorable p o s i t i o n for abstraction (Fig. 4), and (3) the basic skeleton can be modified very e a s i l y to synthesize a large number of molecules for a good 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 . The modifications performed on the basic skeleton include change of the substituent X on the phenyl group and v a r i a t i o n i n the cycloalkane r i n g s i z e . A t o t a l of 31 compounds was synthesized and t h e i r photochemistry was studied i n the s o l i d and s o l u t i o n states. The s o l u t i o n state studies were conducted i n benzene or aqueous (2% water) a c e t o n i t r i l e . A t o t a l of 17 c r y s t a l structures were determined by Mr. Stephen Evans, Dr. Sara A r i e l and Dr. James Tr o t t e r . Figure 4: a-Cyclohexylacetophenone conformational isomers. These 31 compounds can be divided into eight classes on the basis of the cycloalkane r i n g present (Scheme 15, page 43). For each class of compounds, the p-chloro d e r i v a t i v e was chosen as the representative example, and i t s c r y s t a l structure, quantum y i e l d , and hydrogen abstrac-t i o n rate constant (except for ketone 58) were determined. R e a c t i v i t y - 43 -differences among these d i f f e r e n t classes of compounds are discussed based on the representative p-chloro compound from each c l a s s . Scheme 15: - 4 4 -RESULTS AND DISCUSSION Preparation of Substrates Most o f the compounds t h a t were i n v e s t i g a t e d were s y n t h e s i z e d by a F r i e d e l - C r a f t s r e a c t i o n u s i n g c y c l o a l k y l a c e t y l c h l o r i d e s , aluminum c h l o r i d e and m o n o s u b s t i t u t e d b e n z e n e s . ^ C y c l o a l k y l a c e t y l c h l o r i d e s were p r e p a r e d from the c o r r e s p o n d i n g c y c l o a l k y l a c e t i c a c i d s by tre a t m e n t w i t h t h i o n y l c h l o r i d e . C y c l o p e n t y l , c y c l o h e x y l , 1-adamantyl, 3-methyl-1-adamantyl and e x o - 2 - n o r b o r n y l a c e t i c a c i d s a r e a v a i l a b l e c o m m e r c i a l l y and were u s e d as s u p p l i e d . C y c l o b u t y l and c y c l o h e p t y l a c e t i c a c i d s were p r e p a r e d a c c o r d i n g t o the p u b l i s h e d procedures.9 5 - 9 7 p-Cyano a n a l o g s o f a - c y c l o h e x y l (32) and a - c y c l o p e n t y l (42) acetophenones were made from the c o r r e s p o n d i n g a - c y c l o a l k y l - p - f l u o r o a c e t o p h e n o n e s (31 and 41) by a n u c l e o p h i l i c s u b s t i t u t i o n o f the f l u o r i d e i o n by the c y a n i d e i o n . ^ The c a r b o x y l i c a c i d s (33 and 43) were o b t a i n e d by a base c a t a l y z e d h y d r o l y -s i s o f the cyano compounds (32 and 42), and the methyl e s t e r (34) was p r e p a r e d e a s i l y by m e t h y l a t i o n o f the c a r b o x y l i c a c i d (33) w i t h methyl i o d i d e i n the p r e s e n c e o f sodium b i c a r b o n a t e . ^ Ketone 35 was s y n t h e s i z e d from c y c l o h e x y l m e t h y l magnesium bromide and p - t r i f l u o r o -m e thyl b e n z o n i t r i l e u s i n g a s t a n d a r d G r i g n a r d r e a c t i o n . ^ Below i s a summary o f the s y n t h e t i c schemes used to o b t a i n the s t a r t i n g m a t e r i a l s ( k e t o n e s ) . A l l k e tones were p u r i f i e d by two or more c r y s t a l l i z a t i o n s u n t i l c r y s t a l s from two s u c c e s s i v e r e c r y s t a l l i z a t i o n s had the same m e l t i n g p o i n t . 4 5 cnr- S O C l , C T f - A1C1, X COMPOUND C l 28 C H 3 29 OCH 30 F 31 C ( C H 3 ) 3 36 H 37 (Ref. 94) Scheme 16: P r e p a r a t i o n o f a - c y c l o h e x y l - p - s u b s t i t u t e d a c e t o p h e n o n e s . NaCN DMF C H 3 I NaHCO, COOCH3 a l e . KOH (Ref. 98) Scheme 17: P r e p a r a t i o n o f k e t o n e s , 3 2 , 33 a n d 34 0 C 6 H 5 C H MgBr Scheme 18: P r e p a r a t i o n o f k e t o n e 35 by G r i g n a r d r e a c t i o n . (Ref. 99) - 4 6 -Scheme 20: P r e p a r a t i o n of k e t o n e s , 42 and 43. a l e . KOH nr OH S0C1, r r Cl A1C1, C h l o r o Cl benzene Scheme 21: Preparation of a-cyclobutyl-p-chloroacetophenone. 47 A1C1 COMPOUND C l C H 3 OCH, H 4 6 4 7 4 8 4 9 Scheme 2 2 : P r e p a r a t i o n o f a - n o r b o r n y l - p - s u b s t i t u t e d a c e t o p h e n o n e s , CN C y a n o a c e t i c a c i d ammonium acetate COOH heat a l e . KOH (Ref. 97) H00<\ H H 2 / P d OH 0 S 0 C 1 , C l CH OCH, COMPOUND 50 51 52 Scheme 2 3 : P r e p a r a t i o n o f a - c y c l o h e p t y l - p - s u b s t i t u t e d a c e t o p h e n o n e s . - 48 -Scheme 24: Preparation of a-cyclooctyl-p-chloroacetophenone, 58. X Compound C l 5 4 n a n d 54p C H 3 55 OCH 3 56 H 57 Scheme 2 5 : P r e p a r a t i o n o f a - l - a d a m a n t y l - p - s u b s t i t u t e d a c e t o p h e n o n e s . Scheme 26: Preparation of a-3-methyl-l-adamantyl-p-chloroacetophenone. 49 1. a-Cyclohexyl-p-Substituted Acetophenones Wamser and Wagner have s y n t h e s i z e d and s t u d i e d the p h o t o c h e m i s t r y o f a-cyclohexyl-p-methylacetophenone (29) and a - c y c l o p e n t y l a c e t o p h e n o n e (44) i n the s o l u t i o n s t a t e , and the p h o t o c h e m i s t r y o f an analogue o f a - c y c l o h e x y l a c e t o p h e n o n e was a l s o s t u d i e d as bound t o i n s o l u b l e p o l y s t y r e n e beads. These s u b s t r a t e s undergo a smooth N o r r i s h type I I r e a c t i o n t o g i v e acetophenones and c y c l o a l k e n e s as the c l e a v a g e p r o d u c t s . I n t e r e s t i n g l y , no c y c l i z a t i o n p r o d u c t s were r e p o r t e d e i t h e r i n the s o l u t i o n s t a t e p h o t o l y s i s o r i n the polymer bound f o r m . ^ I n i t i a l e x periments performed by o t h e r workers i n our l a b o r a t o r y on p - C l ( 2 8 ) , p-CH 3 (29) and p-OCH 3 (30) d e r i v a t i v e s o f a - c y c l o h e x y l a c e t o -phenones, i n c o n t r a s t t o Wamser and Wagner's study, y i e l d e d c y c l o b u t a -n o l s ( c y c l i z a t i o n p r o d u c t s ) as the major p h o t o p r o d u c t s i n a l l s o l v e n t s t e s t e d i n c l u d i n g c y c l o h e x a n e , benzene, e t h a n o l , c h l o r o f o r m and a c e t o n i -t r i l e . However, the remarkable d i s c o v e r y o f t h i s s t u d y was t h a t i n the s o l i d s t a t e , a b o a t l i k e r a t h e r than a s t r a i n - f r e e c h a i r l i k e r e a c t a n t  c o n f o r m a t i o n was u t i l i z e d i n the hydrogen a b s t r a c t i o n . I t was a l s o r e p o r t e d t h a t the s o l i d s t a t e i r r a d i a t i o n s i n v a r i a b l y l e d to i n c r e a s e d amounts o f c l e a v a g e p r o d u c t s compared t o the amounts o b t a i n e d i n s o l u -t i o n i r r a d i a t i o n s . * ^ In o r d e r t o t e s t the g e n e r a l i t y o f t h i s b o a t l i k e a b s t r a c t i o n geometry and to i n v e s t i g a t e the e f f e c t o f the s u b s t i t u e n t s on 1,4-hydroxy b i r a d i c a l (10, page 33) p a r t i t i o n i n g to the p r o d u c t s , s e v e r a l p - s u b s t i t u t e d a - c y c l o h e x y l a c e t o p h e n o n e s were s y n t h e s i z e d and p h o t o l y z e d i n the s o l i d and s o l u t i o n s t a t e s . The c h o i c e o f the p-sub-- 50 -st i t u e n t s was based on the previously photolyzed p-substituted v a l e r -ophenones . • ^  » T h e p-substituents were selected f or study only i f they were compatible with a Norrish type II reac t i o n with a reasonable quantum y i e l d i n the valerophenone s e r i e s . The photochemistry of ten such substituted a-cyclohexylacetophenones was studied i n the s o l u t i o n and s o l i d states. Conformation i n the s o l i d state The X-ray c r y s t a l structures of f i v e d e r i v a t i v e s were d e t e r m i n e d ^ l to obtain information about reactant geometry and to understand s o l i d state photochemistry. A l l these ketones c r y s t a l l i z e i n a common conformation i n which the carbonyl-bearing side chain i s equatorial with respect to the chair-shaped cyclohexane r i n g . A Newman p r o j e c t i o n down the equ a t o r i a l carbon-carbon (Cg-Cq) bond (Fig. 5) and the stereodiagram for ketone 28 are provided below (Fig. 6). The Newman p r o j e c t i o n shows that i t i s the equatorial hydrogen that i s c l o s e r to the oxygen undergoes abstraction through a six-membered t r a n s i t i o n state. As mentioned e a r l i e r , the stereo view (Fig. 6) indic a t e s that t h i s six-atom arrangement i s a b o a t l i k e rather than a s t r a i n - f r e e c h a i r l i k e geometry. The boat-shaped hydrogen abstraction geometry i s p i c t o r i a l l y represented i n Figure 7 for c l a r i t y . - 51 Figure 6: Stereodiagram of a-cyclohexyl-p-chloroacetophenone , 2 8 - 52 -0 A r B o a t l i k e A b s t r a c t i o n Geometry d = 2.6 A r - 50° A = 90° Figure 7: P i c t o r i a l representation of boatlike hydrogen a b s t r a c t i o n geometry i n compound 28. Hydrogen Abstraction Geometry The hydrogen a b s t r a c t i o n d i s t a n c e s i n the ketones range from 2.6-2.7 A ( T a b l e I I I ) and a r e w i t h i n S c h e f f e r ' s upper l i m i t o f 2.7 A f o r hydr o g e n a b s t r a c t i o n by o x y g e n . ^ The a x i a l hydrogen (H a) i s q u i t e f a r away (3.8-3.9 A) from the oxygen atom compared t o the e q u a t o r i a l h ydrogen ( H e ) . The a n g l e r, the degree t o which the hydrogen i n q u e s t i o n l i e s o u t s i d e the p l a n e o f the c a r b o n y l group, ranges between 42-50° f o r the e q u a t o r i a l 7-hydrogen t h a t i s b e i n g a b s t r a c t e d . 5 3 R e g a r d l e s s o f t h e s e r e l a t i v e l y h i g h v a l u e s o f r , e f f i c i e n t N o r r i s h type I I r e a c t i o n was o b s e r v e d f o r a l l t e n ketones s t u d i e d i n the s o l i d s t a t e a s w e l l as i n s o l u t i o n . A c o s ^ r dependence f o r the r a t e o f hydrogen a b s t r a c t i o n was s u g g e s t e d by W a g n e r , a n d i n our k e t o n e s t h i s cos^r dependence reduces the hydrogen a b s t r a c t i o n r e a c t i v i t y from 1 . 8 (T = 4 2 ° ) to 2 . 4 ( r = 5 0 ° ) times r e l a t i v e t o the c o p l a n a r ( r = 0 ° ) hydrogen a b s t r a c t i o n . The T v a l u e s f o r H a range from 3 3 - 3 8 ° , b u t as p r e v i o u s l y d i s c u s s e d , t h e se hydrogens are q u i t e f a r away from the oxygen atom to be a b s t r a c t e d . T u r n i n g to the a n g l e A, the v a l u e s o b t a i n e d from s t r u c t u r a l d a t a f o r H e v a r y from 8 8 - 9 1 ° and a r e v e r y c l o s e to the i d e a l range o f 9 0 - 1 2 0 ° f o r an e f f i c i e n t r e a c t i o n . 1 0 2 ' 1 0 3 T a b l e I I I a l s o shows t h a t the 0-hydrogen i s s l i g h t l y c l o s e r ( 2 . 6 A ) t o the oxygen and i s l o c a t e d i n a b e t t e r p o s i t i o n f o r a b s t r a c t i o n (r = Table I I I . Hydrogen Abstraction Parameters f o r a-Cyclohexyl-p-substi-tuted Acetophenones p - S u b s t i t u e n t p - C l (28) p-CH 3 (29) p-0CH 3 (30) p-CN (32) p-COOH (33) He d ( A ) , r ( ° ) , A(°) 2 . 6 , 4 2 , 9 0 2 . 6 , 5 0 , 8 8 2 . 6 , 4 3 , 9 1 2 . 7 , 4 2 , 8 8 2 . 6 , 4 4 , 9 0 d ( A ) , T ( ° ) , A ( ° ) 3 . 8 , 3 6 , 6 7 3 . 8 , 3 8 , 6 5 3 . 8 , 3 7 , 6 8 3 . 9 , 3 3 , 6 7 3 . 8 , 3 8 , 6 7 »0 d ( A ) , r ( ° ) , A(°) 2 . 6 , 1 3 , 8 1 2 . 6 , 7 , 8 4 2 . 6 , 1 2 , 8 1 2 . 6 , 1 3 , 8 2 2 . 6 , 1 0 , 8 2 54 7-13°, A = 81-84°) r e l a t i v e t o the 7 hydrogens. Even though i t i s known t h a t 7-hydrogen a b s t r a c t i o n i s f a v o r e d by e n t r o p i c f a c t o r s ^ * ^ as w e l l as the absence o f r i n g s t r a i n . 1 ^ 5 A b s t r a c t i o n a t o t h e r p o s i t i o n s i s a l s o p o s s i b l e . S e v e r a l a-methylene compounds are known to undergo a b s t r a c -t i o n a t the / S - p o s i t i o n . - ^ 6 I n ketones 28-37, /3-hydrogen a b s t r a c t i o n s h o u l d a l s o be f a v o r e d because o f i t s t e r t i a r y n a t u r e . • ^ 7 Neverthe-l e s s , no p r o d u c t s c o r r e s p o n d i n g to /3-hydrogen a b s t r a c t i o n a r e o b s e r v e d i n any c a s e , e i t h e r i n s o l i d o r s o l u t i o n media. R e v e r s i b l e /3-hydrogen a b s t r a c t i o n i s a p o s s i b i l i t y and cannot be r u l e d out. The 1 , 3 - h y d r o x y b i r a d i c a l t h a t i s g e n e r a t e d as a r e s u l t o f /3-hydrogen a b s t r a c t i o n has no c l e a v a g e pathway open and c y c l i z a t i o n r e s u l t s i n a h i g h l y s t r a i n e d c y c l o p r o p a n o l . As a r e s u l t , r e v e r s e t r a n s f e r i s a l o g i c a l f a t e o f t h i s h y p o t h e t i c a l s p e c i e s . P h o t o c h e m i s t r y The i r r a d i a t i o n o f a - c y c l o h e x y l - p - s u b s t i t u t e d k etones was c o n d u c t e d i n the c r y s t a l l i n e phase as w e l l as i n 0.1 M benzene and aqueous (2% water) a c e t o n i t r i l e s o l u t i o n s . I n a l l media, the c y c l i z a t i o n p r o d u c t s , c i s - (59c) and t r a n s - c y c l o b u t a n o l s (59t) and c l e a v a g e p r o d u c t s , p-sub-s t i t u t e d acetophenones (59a) and c y c l o h e x e n e (59b) were d e t e c t e d (Scheme 27). No p r o d u c t s c o r r e s p o n d i n g to N o r r i s h type I r e a c t i o n were d e t e c t e d . The c y c l o b u t a n o l s and acetophenones were i s o l a t e d i n l a r g e s c a l e p h o t o l y s e s o f k etones, 28-30 and 32. The p - s u b s t i t u t e d acetophenones were i d e n t i f i e d by comparison o f t h e i r s p e c t r a w i t h those - 55 -59a 59b Scheme 2 7 : The N o r r i s h type I I r e a c t i o n o f a - c y c l o h e x y l a c e t o p h e n o n e s . o f a u t h e n t i c samples. The d e s i g n a t i o n c i s- e y e l o b u t a n o 1 i s g i v e n c u s t o m a r i l y t o the isomer i n which the h y d r o x y l group i s c i s to the a d j a c e n t r i n g j u n c t i o n hydrogen atom, and the d e s i g n a t i o n t r a n s -c y c l o b u t a n o l i s g i v e n t o the isomer where the h y d r o x y l group and the a d j a c e n t r i n g hydrogen a r e t r a n s t o one a n o t h e r . 1 1 0 The s t e r e o c h e m i c a l assignments were ba s e d on a c h a r a c t e r i s t i c l o w - f i e l d (6 -2.8) d o u b l e t o f d o u b l e t s ( J = 6.5 and 4 Hz) i n the c i s isomer a t t r i b u t a b l e to H^ (Scheme 28), which l i e s w i t h i n the d e s h i e l d i n g r e g i o n o f the a d j a c e n t a r y l group as a r e s u l t o f the l a t t e r ' s r e s t r i c t e d motion ( c i s to c y c l o h e x a n e ) . Any m o t i o n o f the a r y l group r e s u l t s i n s e v e r e non-bonded i n t e r a c t i o n s - 56 -c i s - c y c l o b u t a n o l t r a n s - c y c l o b u t a n o l Scheme 2 8 : C y c l i z a t i o n p h o t o p r o d u c t s . between one o f the a r y l hydrogens o r t h o t o the c a r b o n a t t a c h e d t o the c y c l o b u t a n e r i n g and the methylene hydrogens a t C 2 and C3. The o t h e r consequence o f such r e s t r i c t e d a r y l group motion i n c i s - c y c l o b u t a n o l s i s the u p f i e l d s h i f t o f the C 2 and C3 p r o t o n s t h a t f a c e the a r y l group t o 8 0.6-0.9 from S 1.1-1.9 i n the t r a n s - c y c l o b u t a n o l s (see T a b l e I V ) . A s i m i l a r t r e n d was o b s e r v e d by Lewis f o r c y c l o b u t a n o l s 60 and 61 (page 57) d e r i v e d from the p h o t o l y s i s o f the m e t h y l - s u b s t i t u t e d b u t y r o p h e -n o n e s . ^ I n c y c l o b u t a n o l 60, H a i s d e s h i e l d e d by the p h e n y l r i n g t o 8 2.9 as compared t o 5 2.6 i n 61. The p h e n y l group a l s o s h i e l d s the CE^0 i n 61 and CH3 e i n 60 and 61 t o 8 0.7-0.92 from t h e i r u s u a l c h e m i c a l s h i f t range o f 8 1.05-1.22 i n t h e s e c y c l o b u t a n o l s . Both c i s and t r a n s - c y c l o b u t a n o l s show an i n t e n s e peak i n t h e i r mass s p e c t r a , t h a t i s a l s o the base peak, c o r r e s p o n d i n g t o the l o s s o f c y c l o h e x e n e by a r e t r o [ 2 + 2 ] c y c l o a d d i t i o n p a t h w a y . 1 0 9 The NMR, IR, MS and e l e m e n t a l a n a l y s e s a r e c o n s i s t e n t w i t h the s t r u c t u r e s a s s i g n e d . We a l s o o b s e r v e d t h a t t r a n s - c y c l o b u t a n o l s have s h o r t e r GC r e t e n t i o n times (on Carbowax column) t h a n the c o r r e s p o n d i n g c i s - i s o m e r s and a r e e l u t e d f i r s t on 5 7 T a b l e IV. NMR Parameters o f C y c l o b u t a n o l s . t r a n s - C y c l o b u t a n o l c i s - C y c l o b u t a n o l S u b s t i t u e n t H A and C 2, C3 p r o t o n s H A and C 2,C3 p r o t o n s (5, ppm) (6, ppm) p - C l ( 2 8 ) 2.26, 1.88-1.14 2.84, 0.88-0.66 p-CH 3 ( 2 9 ) 2.16, 1.78-1.10 2.85, 1.84-0.83 P-OCH3 ( 3 0 ) 2.11, 1.72-1.07 2.75, 0.91-0.70 P-CN ( 3 2 ) 2.11, 1.72-1.25 2.87, 0.80-0.68 column chromatography. A s i m i l a r t o b s e r v e d by W a g n e r 1 1 0 and L e w i s 1 and b i c y c l i c and t r i c y c l i c k e t o n e s . 6 0 5 , ppm H a 2.9 C H 3 b 1.05 C H 3 e 0.72 C H 3 f 1.16 d f o r c y c l o b u t a n o l e l u t i o n was i n t h e i r s t u d i e s on v a l e r o p h e n o n e s HO 6 1 CH 3 S , ppm 2.6 0.92 0.70 1.22 - 58 The r i n g j u n c t i o n o f the b i c y c l o o c t a n o l r i n g system (59c and 59t) was assumed to be c i s - f u s e d based on c o n s i d e r a t i o n o f r i n g s t r a i n . The c i s - f u s e d r i n g system i s more s t a b l e t h a n the t r a n s - f u s e d one by - 6 k c a l / m o l e . 1 1 2 Other workers a l s o found s i m i l a r p h o t o c h e m i c a l l y g e n e r a t e d c y c l o b u t a n o l s to be c i s - f u s e d . 8 6 ' 1 1 3 - 1 1 5 ^ e n a t u r e o f the r i n g f u s i o n i n the p r e s e n t s t u d y c o u l d n o t be d e t e r m i n e d by NMR, as the r i n g j u n c t i o n p r o t o n s are masked by the c y c l o h e x a n e r i n g p r o t o n s . No s u i t a b l e c r y s t a l s o f c y c l o b u t a n o l s c o u l d be grown t o determine the r i n g j u n c t i o n s t e r e o c h e m i s t r y by X - r a y c r y s t a l l o g r a p h y . The c y c l i z a t i o n : c l e a v a g e r a t i o s from the N o r r i s h type I I r e a c t i o n a r e summarized f o r the p h o t o l y s i s o f k etones 28-37 i n T a b l e V. I t i s a p p a r e n t from T a b l e V, t h a t w i t h the e x c e p t i o n o f 35, a l l m o l e c u l e s undergo l e s s c y c l i z a t i o n i n the s o l i d s t a t e compared to the s o l u t i o n s t a t e . The e x t e n t o f t h i s d e c r e a s e i n the c y c l i z a t i o n i s modest to c o n s i d e r a b l e , and v a r i e s w i t h p - s u b s t i t u e n t . T h i s d e c r e a s e i n c y c l i z a -t i o n can be r a t i o n a l i z e d c o n s i d e r i n g the r e q u i r e m e n t s f o r an e f f i c i e n t c l e a v a g e . I t has been d i s c u s s e d i n the I n t r o d u c t i o n S e c t i o n o f t h i s t h e s i s t h a t an e f f i c i e n t c l e a v a g e r e q u i r e s a 1 , 4 - h y d r o x y b i r a d i c a l ( 1 0 , page 33) c o n f o r m a t i o n where t h e r e i s a s i g n i f i c a n t o v e r l a p between the c e n t r a l sigma bond (Cg-Cg) b e i n g b r o k e n and the s i n g l y o c c u p i e d p - o r b i t a l s (see Scheme 13, page 39) . 1 0 ^ Hoffman's c a l c u l a t i o n s a l s o r e v e a l t h a t a 1 , 4 - b i r a d i c a l c o n f o r m a t i o n w i t h e x t e n s i v e o v e r l a p between the p - o r b i t a l s and the c e n t r a l sigma bond o p t i m i z e s the m i x i n g o f 7r and a l e v e l s which promotes c l e a v a g e . 1 1 6 I t can be argued t h a t the 1 , 4 - b i r a d i c a l has the same b a s i c c o n f o r m a t i o n as i t s k e t o n i c p r e c u r s o r i n the s o l i d s t a t e , as any g r o s s changes i n the b i r a d i c a l c o n f o r m a t i o n - 59 T a b l e V: C y c l i z a t i o n : C l e a v a g e R a t i o s f o r the P h o t o l y s i s o f a - C y c l o -h e x y l - p - s u b s t i t u t e d Acetophenones, 28-37. 1 - 3 S u b s t i t u e n t Cleavage (%) S o l i d 0.1 M 0.1 M S t a t e CH 3CN C 6 H 6 C y c l i z a t i o n (%) S o l i d 0.1 M 0.1 M S t a t e CH3CN C 6 H 6 C l , 28 45 31 35 55 69 65 CH 3, 29 52 37 42 48 63 58 OCH3, 30 51 25 39 49 75 61 F, 31 42 39 40 58 61 60 CN, 32 36 32 30 64 68 70 COOH, 33 35 t - b u t a n o l 34 65 t - b u t a n o l 66 C00CH 3, 34 38 34 31 62 66 69 C F 3 , 35 31* 34 34 69* 66 66 t - B u t y l , 36 43 40 43 57 60 57 t - B u t y l 50* 40* 50* 60* H, 37 37 33 34 63 67 66 H 36* 34* 64* 66* * - I r r a d i a t i o n s a t -30°C E x p e r i m e n t a l f o r d e t a i l s ) . u s i n g l i q u i d n i t r o g e n a p p a r a t u s 1. Chromatography f o r p-COOH was done on Carbowax 12 m. column a f t e r m e t h y l a t i o n u s i n g diazomethane. 2. Chromatography f o r a l l o t h e r compounds was a l s o done on Carbowax 12 m. column. p-H (37) and p - t e r t - b u t y l (36) a r e l i q u i d s a t room temparature. - 6 0 -are disfavored by the c r y s t a l l a t t i c e . The short b i r a d i c a l l i f e t i m e s ^ 6 coupled with the r e s t r i c t i o n imposed by the c r y s t a l l a t t i c e on any large change i n the conformation provide c r e d i b i l i t y to the argument that the 1 , 4 - b i r a d i c a l and the s t a r t i n g ketone have the same basic conformation. The angular r e l a t i o n s h i p of the p - o r b i t a l with respect to the ce n t r a l sigma bond (Cg-Cg bond) of the b i r a d i c a l was c a l c u l a t e d with two assumptions: 1 . The r i n g carbon (C^Q) bearing 7-hydrogen changes h y b r i d i z a t i o n from s p 3 to sp 2, and 2. the p - o r b i t a l s at C7 and C^Q l i e normal to the planes defined by O^-C^-Cy and Cg-C^o" cll> r e s p e c t i v e l y . Examination of the b i r a d i c a l s so obtained of the f i v e ketones f o r which c r y s t a l structures were determined reveal that they have the p - o r b i t a l s i n an orthogonal arrangement with the c e n t r a l sigma bond (Cg-Cg) and hence are p e r f e c t l y misaligned for a cleavage process (Table VI). We suggest that the b i r a d i c a l adopts e s s e n t i a l l y the same conformation i n s o l u t i o n as i t does i n the s o l i d state. From t h i s i l l - suited conformation f o r cleavage, extensive molecular and atomic motions are required around the Cy-Cg and Cg-C 1 0 bonds to a l i g n the p - o r b i t a l s on C7 and C^Q with the Cg-Cg bond. The l a t t e r motion i s impeded, as any r o t a t i o n to br i n g the p - o r b i t a l on C^Q into a coplanar arrangement with the Cg-Cg bond i s obviously very d i f f i c u l t , as the Cg-C^Q bond i s part of a stable, chair-shaped cyclohexane r i n g , and any r o t a t i o n around t h i s bond would mean an increase i n the energy of the system. The c y c l i z a t i o n , which i s the major process i n so l u t i o n , i s a r e s u l t of the unfavorable conformation of the 1 , 4 - b i r a d i c a l for cleavage. The b i r a d i c a l conformation i s not p a r t i c u l a r l y i d e a l for c y c l i z a t i o n e i t h e r , but the gauche conformation that i s a r e s u l t of 61 T a b l e VI. B i r a d i c a l Parameters f o r Ketones, 28-33. Ketone <t> (°) ' 2 < ° ) ' l (°) p - C l , 28 p-CH 3, 29 p-OCH 3, 30 p-CN, 32 p-COOH, 33 7 1 6 9 6 8 7 5 6 9 9 5 1 0 1 9 7 9 3 8 2 8 8 8 7 8 9 9 0 8 8 c?l = A n g l e o f p - o r b i t a l on C7 w i t h r e s p e c t t o Cg-Cq bond. 82 - A n g l e o f p - o r b i t a l on C^Q w i t h r e s p e c t t o Cg-Cq bond. 4> = D i h e d r a l a n g l e o f CyCg-Cg-C^Q. a b s t r a c t i o n can c y c l i z e , r e l a t i v e l y e a s i l y , to g i v e a c y c l o b u t a n o l w i t h a p u c k e r e d c y c l o b u t a n e r i n g . Lewis has p o i n t e d out t h a t c y c l i z a t i o n p r oduces c y c l o b u t a n e r i n g s t h a t a r e most p r o b a b l y puckered. T h a t b r i n g s us t o the t a s k o f e x p l a i n i n g the r e d u c e d amount o f - 6 2 cyclobutanol formation i n the s o l i d state. We suggest that the reduced amount of c y c l i z a t i o n i n the c r y s t a l photolysis i s not a r e s u l t of preference for cleavage i n the s o l i d state but a consequence of the c r y s t a l lattice-imposed r e s t r i c t i o n on the b i r a d i c a l c y c l i z a t i o n . I t i s evident that there i s l i t t l e s t r u c t u r a l resemblance between the b i r a d i -c a l precursor, and cyclobutanols (the c y c l i z a t i o n products). In consequence, the formation of cyclobutanols requires extensive atomic and molecular motions i n the b i r a d i c a l , most notably a large permanent displacement of the bulky a r y l group from i t s o r i g i n a l p o s i t i o n . Such a large motion sweeps the a r y l and hydroxy groups through a large volume (Fig. 8) and hence i s disfavored topochemically compared to the r e l a -t i v e l y less-motion pathway required for cleavage i n the s o l i d state. H X Figure 8: Motions involved i n the formation of trans-cyclobutanol from 1 ,4-hydroxybiradical. Another i n t e r e s t i n g part of our study i s the comparison of our - 63 -r e s u l t s with those obtained by C a l d w e l l 1 1 3 and Weiss. 1 1** Caldwell proposed that a conformationally locked c i s o i d (gauche) b i r a d i c a l (62) y i e l d s mainly c y c l i z a t i o n products i n contrast to a conformationally l a b i l e trans b i r a d i c a l (63) that undergoes predominant c l e a v a g e . 1 1 3 On t h i s basis, Weiss r a t i o n a l i z e d the photochemical behavior of four ketones i n l i q u i d c r y s t a l media. 1 1** OH Ph 62 63 Our studies c l e a r l y show that i t i s not n e c e s s a r i l y true that the gauche-biradical conformation should y i e l d mainly c y c l i z a t i o n products. The b i r a d i c a l that i s formed i n a l l the cyclohexyl compounds i s c i s o i d (gauche) with a C 7-Cg-Cq-C 1 0 dihedral angle of the order of 70°. Yet, a l l these molecules undergo both cleavage and c y c l i z a t i o n e f f i c i e n t l y i n the s o l i d as w e l l as i n the s o l u t i o n states. Our r e s u l t s c l e a r l y show that the p - o r b i t a l arrangement on the b i r a d i c a l termini with respect to the c e n t r a l sigma bond being broken plays as s i g n i f i c a n t a ro l e as the conformation of the b i r a d i c a l i t s e l f , and the preferred c y c l i z a t i o n of the cyclohexyl compounds i n the s o l u t i o n state i s already discussed on t h i s b a s i s . - 6 4 -The p r e f e r e n c e f o r c l e a v e g e i n the s o l i d s t a t e i s d i f f e r e n t f o r ke t o n e s and can n o t be e x p l a i n e d on the b a s i s o f c r y s t a l d e n s i t y o r i n t e r p l a n a r distance 1-'- 9 ( T a b l e V I I ) , as these a r e v e r y s i m i l a r f o r a l l f i v e k e tones f o r which c r y s t a l s t r u c u r e s were determined. The p a c k i n g diagrams a l s o do n o t shed any l i g h t on t h i s a s p e c t , as they too are not s i g n i f i c a n t l y d i f f e r e n t . The d i f f e r e n t s e l e c t i v i t i e s i n f a v o r o f c l e a v -age i n d i f f e r e n t m o l e c u l e s i s p r o b a b l y a r e s u l t o f the s u b t l e r a s p e c t s o f the arrangement o f m o l e c u l e s i n the c r y s t a l t h a t a r e n o t y e t under-s t o o d . The i n c r e a s e i n c l e a v a g e p r o d u c t s f o r d i f f e r e n t c y c l o h e x y l compounds i n the s o l i d s t a t e a r e not a r e s u l t o f t h e i r d i f f e r e n t m e l t i n g p o i n t s , as the c y c l i z a t i o n : c l e a v a g e r a t i o s a r e i d e n t i c a l w i t h i n exper-i m e n t a l e r r o r f o r the s o l i d ketones from -40° to +25°C. Such b e h a v i o r can be i n t e r p r e t e d as i n d i c a t i n g t h a t sample m e l t i n g w i t h c o n c o m i t a n t l o s s o f t o p o c h e m i c a l c o n t r o l i s unimportant. However, T a b l e V I I . D e n s i t i e s and I n t e r p l a n a r D i s t a n c e s C a l c u l a t e d f o r Ketones 28-33 From C r y s t a l Data. Ketone P r e f e r e n c e D e n s i t y (g/cm 3) I n t e r p l a n a r f o r c l e a v a g e d i s t a n c e (A) i n s o l i d (%) p - C l , 28 10 - 14 1. 238 3. .54 p-CH 3, 29 10 - 15 1. .121 3. .33 p-0CH 3, 30 12 - 26 1. ,184 3, .55 p-CN, 32 4 - 6 1. .147 3 .44 p-COOH, 33 1 1, .251 - 65 -s i g n i f i c a n t changes were o b s e r v e d i n the s o l i d s t a t e p h o t o p r o d u c t r a t i o s when the c o n v e r s i o n p e r c e n t a g e s were i n c r e a s e d a t room temperature. T h i s i s i l l u s t r a t e d g r a p h i c a l l y ( F i g . 9) f o r ketone 28. As expected, m e l t i n g l e d to more s o l u t i o n - l i k e r e s u l t s . I t i s i n s t r u c t i v e t o examine the s t e r e o s e l e c t i v i t y o f c y c l o b u t a n o l f o r m a t i o n as a f u n c t i o n o f medium ( T a b l e V I I I ) . The d e c r e a s e d s t e r e o -s e l e c t i v i t y i n wet a c e t o n i t r i l e i r r a d i a t i o n s r e l a t i v e t o benzene i r r a d i a t i o n s has been w e l l documented and was e x p l a i n e d by Wagner to be a consequence o f the i n c r e a s e d s t e r i c b u l k o f the h y d r o x y l group caused by i t s hydrogen b o n d i n g to the s o l v e n t m o l e c u l e s . ^ • 1 2 0 The s t e r e o -s e l e c t i v i t y o f c y c l o b u t a n o l f o r m a t i o n i n the s o l i d s t a t e i s s i m i l a r to t h a t o b t a i n e d i n s o l u t i o n e x c e p t i n the case o f 33. The s i m i l a r v a l u e s o f c y c l o b u t a n o l s t e r e o s e l e c t i v i t y i n s o l i d and s o l u t i o n media a l s o s u b s t a n t i a t e the argument d i s c u s s e d i n the p r e c e d i n g p a r a g r a p h , t h a t i s , the 1,4-hydroxy b i r a d i c a l adopts the same b a s i c c o n f o r m a t i o n i n s o l u t i o n as i s p r e s e n t i n the s o l i d s t a t e . The d r a m a t i c r e v e r s a l i n c y c l o b u t a n o l s t e r e o s e l e c t i v i t y i n g o i n g from s o l u t i o n t o the s o l i d s t a t e i r r a d i a t i o n i n the case o f c a r b o x y l i c a c i d (33) i s s u r p r i s i n g a t f i r s t g l a n c e . However, X - r a y c r y s t a l l o g r a p h y shows t h a t t h ese m o l e c u l e s e x i s t as dimers i n the c r y s t a l because o f the hydrogen b o n d i n g between the c a r b o x y l i c a c i d groups. S i n c e none of the o t h e r m o l e c u l e s i n t h i s s e r i e s shows such i n t e r m o l e c u l a r hydrogen bond-i n g , the answer t o the medium-dependent s t e r e o s e l e c t i v i t y s h o u l d come from the hydrogen b o n d i n g p r e s e n t i n 33. The m o l e c u l a r c o n f o r m a t i o n o f 33 i s s i m i l a r t o o t h e r m o l e c u l e s i n the s e r i e s . The a b s t r a c t i o n o f a 7-hydrogen ( H e ) r e s u l t s i n a b i r a d i c a l t h a t has two modes o f c l o s u r e - 66 -59.5 n 59 H 58.5 W 54.5 H 54"1 1 1 1 — r , 0 2 4 6 8 10 12 14 16 Conversion to products (%) Figure 9: Conversion vs percentage of c y c l i z a t i o n f o r the s o l i d stat i r r a d i a t i o n of ketone 28. 67 T a b l e V I I I : c i s - and t r a n s - C y c l o b u t a n o l R a t i o s f o r t h e P h o t o l y s i s o f a - c y c l o h e x y l - p - s u b s t i t u t e d Acetophenones, 2 8 - 3 7 . 1 - 3 S u b s t i t u e n t t r a n s S o l i d S t a t e - C y c l o b u t a n o l 0.1 M 0.1 M CH3CN C 6 H 6 c i s S o l i d S t a t e - C y c l o b u t a n o l 0.1 M 0.1 CH3CN C 6H, C l , 28 54 52 66 46 48 34 CH 3, 29 62 58 70 38 42 30 OCH 3, 30 51 51 64 49 49 36 F, 31 59 55 68 41 45 32 CN, 32 56 55 69 44 45 31 COOH, 33 33 t - b u t a n o l 60 67 t - b u t a n o l 40 COOCH3, 34 55 54 66 45 46 34 C F 3 , 35 63* 57 69 37* 43 31 t - B u t y l , 36 63 62 72 37 38 28 t - B u t y l 65* 61* 35* 39* H, 37 60 57 68 40 43 - 32 H 62* 58* 38* 42* = I r r a d i a t i o n s a t -30 C u s i n g l i q u i d n i t r o g e n a p p a r a t u s (see E x p e r i m e n t a l f o r d e t a i l s ) . 1. Chromatography f o r p-COOH was done on Carbowax 12 m. column a f t e r m e t h y l a t i o n u s i n g diazomethane. 2. Chromatography f o r a l l o t h e r compounds was a l s o done on Carbowax 12 m. column. 3. p-H (37) and p - t e r t - b u t y l (36) a r e l i q u i d s a t room temparature. - 68 (Scheme 29). Path b i s a g r e a t e r m otion pathway compared to p a t h a and y i e l d s the t r a n s - c y c l o b u t a n o l ( 3 3 t ) . Path b i s the predominant p r o c e s s i n the s o l u t i o n s t a t e , as the r e s u l t i n g t r a n s - c y c l o b u t a n o l (33t) i s the OH X= COOH /// Ar-3 3 c Cis-cyclobutanol 33t Trans-cyclobutanol Scheme 29: The r e v e r s a l o f c y c l o b u t a n o l s t e r e o s e l e c t i s t a t e . i v i t y i n the s o l i d - 69 -s t e r i c a l l y l e s s h i n d e r e d isomer. P a t h a i s a l e s s - m o t i o n r o u t e and p r o d u c e s a more h i n d e r e d c i s - c y c l o b u t a n o l ( 3 3 c ) . P a t h a s h o u l d be p r e f e r r e d i n the s o l i d , as the t o p o c h e m i c a l p r i n c i p l e f a v o r s a p r o c e s s o c c u r r i n g w i t h the l e a s t amount o f atomic and m o l e c u l a r m o tions. Indeed, modest i n c r e a s e s i n the f o r m a t i o n o f c i s - c y c l o b u t a n o l s were o b s e r v e d (see T a b l e V I I I , page 67) i n the s o l i d s t a t e i r r a d i a t i o n s compared to t h o s e o b t a i n e d i n benzene f o r a l l the k e t o n e s examined. The r e v e r s a l o f the s t e r e o s e l e c t i v i t y o f c y c l o b u t a n o l f o r m a t i o n i n the s o l i d s t a t e i r r a d i a t i o n o f 33 compared t o t h a t i n the s o l u t i o n s t a t e i s an outcome o f two f a c t o r s : 1. P a t h a ( c i s - c y c l o b u t a n o l f o r m a t i o n ) i s a l e s s -m o t i o n pathway compared to p a t h b ( t r a n s - c y c l o b u t a n o l f o r m a t i o n ) and hence i s a t o p o c h e m i c a l l y f a v o r e d pathway, and 2. more-motion i n v o l v e d i n p a t h b would a l s o mean more d i s r u p t i o n o f h ydrogen b o n d i n g between the n e i g h b o r i n g c a r b o x y l i c a c i d m o i e t i e s . These two f a c t o r s t o g e t h e r make c i s - c y c l o b u t a n o l f o r m a t i o n p a r t i c u l a r l y f a v o r a b l e i n the s o l i d s t a t e f o r the p - c a r b o x y d e r i v a t i v e 33. A f i n a l p o i n t o f d i s c u s s i o n c o n c e r n s the s m a l l i n c r e a s e i n the amount o f c l e a v a g e i n i r r a d i a t i n g a n e a t sample o f l i q u i d k etone 36 ( p - t e r t - b u t y l d e r i v a t i v e ) a t -30°C as a g a i n s t i r r a d i a t i o n a t room temperature. A t -30°C, ketone 36 i s a g l a s s , n o t a s o l i d . Such an o b s e r v a t i o n appears t o s u g g e s t t h a t an i n c r e a s e i n the amount o f c l e a v a g e i s n o t n e c e s s a r i l y r e s t r i c t e d to j u s t c r y s t a l s b u t may r e s u l t from any i n c r e a s e i n the v i s c o s i t y o f the medium. The i r r a d i a t i o n o f a - c y c l o h e x y l acetophenone (37) as a g u e s t i n the c a v i t y o f h o s t D i a n i n ' s compound^ 0 p r o v e s j u s t t h a t p o i n t and i s d e s c r i b e d i n Chapter 8. 7 0 -2. S u b s t r a t e s t h a t Undergo Predominant Cleavage As p a r t o f e s t a b l i s h i n g s t r u c t u r e - r e a c t i v i t y r e l a t i o n s h i p s f o r the N o r r i s h type I I r e a c t i o n , a - c y c l o b u t y l , a - c y c l o p e n t y l and a-exo-2-n o r b o r n y l - p - s u b s t i t u t e d acetophenones were s y n t h e s i z e d and p h o t o l y z e d i n the s o l i d and f l u i d phases to i n v e s t i g a t e the e f f e c t o f the r i n g s i z e i n a l t e r i n g the c o n f o r m a t i o n and p h o t o c h e m i s t r y . A change i n c o n f o r m a t i o n would modify the hydrogen a b s t r a c t i o n geometry and hence p h o t o b e h a v i o r . A t o t a l o f 12 such compounds was s t u d i e d , out o f which c r y s t a l s t r u c -t u r e s o f 5 compounds were determined. The c h e m i s t r y o f these s u b s t r a t e s i s d i s c u s s e d as a f u n c t i o n o f the r i n g s i z e i n v o l v e d . (A) a - C y c l o p e n t y l - p - s u b s t i t u t e d Acetophenones. 38-44 Seven a - c y c l o p e n t y l d e r i v a t i v e s were s y n t h e s i z e d and c r y s t a l s t r u c t u r e s were o b t a i n e d f o r the p - c h l o r o (38) 1 2-'- and p - c a r b o x y l i c a c i d (43) d e r i v a t i v e s . C o n f o r m a t i o n i n th e S o l i d S t a t e The o v e r a l l c o n f o r m a t i o n o f the c y c l o p e n t y l d e r i v a t i v e s i n the c r y s t a l i s s i m i l a r t o t h a t adopted by the c y c l o h e x a n e a n a l o g s . The c a r b o n y l - c o n t a i n i n g s i d e c h a i n i s p s e u d o - e q u a t o r i a l w i t h r e s p e c t to the c y c l o p e n t a n e r i n g . • 1 2 1 The c o n f o r m a t i o n o f the c y c l o p e n t a n e r i n g i s - 71 c l o s e t o h a l f c h a i r , which i s 5 k c a l / m o l e lower i n energy than the p l a n a r a r r a n g e m e n t . 1 2 2 ^ e p u c k e r i n g a m p l i t u d e ( q ) , c a l c u l a t e d as the square r o o t o f the sum o f squares o f the d e v i a t i o n s o f the c y c l o p e n t y l r i n g atoms from the mean p l a n e through the five-membered r i n g , i s a measure o f the d e v i a t i o n from p l a n a r i t y and i s d e t e r m i n e d to be 0.38 A i n a - c y c l o p e n t y l - p - c h l o r o a c e t o p h e n o n e (38).^23,124 ^he t h e r m a l parameters o f the c y c l o p e n t a n e r i n g carbons i n 28 s u g g e s t t h a t the c y c l o p e n t a n e r i n g i s q u i t e r i g i d and a t t e s t t o the absence o f any - I O C pseudorotation-"-'' 1 J i n the c y c l o p e n t a n e r i n g i n the s o l i d s t a t e . G eometric Parameters The g e o m e t r i c d i s p o s i t i o n o f the and 7-hydrogens w i t h r e s p e c t t o the c a r b o n y l oxygen i n the p - c h l o r o d e r i v a t i v e (38) i s s i m i l a r to t h a t found i n the c o r r e s p o n d i n g c y c l o h e x y l s u b s t r a t e ( 2 8 ) . The e q u a t o r i a l 7-hydrogen (H e) i s c l o s e r t o the c a r b o n y l oxygen atom ( T a b l e IX) t h a n the a x i a l 7-hydrogen ( H a ) , and the /3-hydrogen i s b e t t e r l o c a t e d f o r hydrogen a b s t r a c t i o n than the 7-hydrogens, y e t no p r o d u c t s were d e t e c t e d c o r r e s p o n d i n g to such a five-membered /3-hydrogen a b s t r a c t i o n p r o c e s s . The d i s t a n c e o f 2.8 A f o r H e from oxygen atom i s g r e a t e r than t h a t found Thermal parameter i s a measure o f the root-mean-square d e v i a t i o n o f the atoms from t h e i r m e a n - p o s i t i o n s . - 72 -Table IX: Hydrogen Abstraction Parameters f o r a-Cyclopentyl-p-substituted Acetophenones. S u b s t i t u e n t H e H a H^ d ( A ) , r ( ° ) , A ( 8 ) d ( A ) , r ( ° ) , A(°) d ( A ) , r ( ° ) , A(°) p - C l , 38 2.8, 31, 96 3.6, 37, 73 2.5, 17, 78 p-COOH, 43 2.7, 29, 103 3.0, 43, 78 2.6, 17, 80 p-COOH, 43' 2.9, 48, 77 3.2, 61, 68 3.6, 25, 31 There a r e two d i f f e r e n t conformers p r e s e n t i n the asymmetric u n i t o f the p-COOH s u b s t r a t e . i n t h e c y c l o h e x a n e s e r i e s (2.6-2.7 A ) , b u t i s s t i l l c l o s e t o the s u g g e s t e d upper l i m i t o f 2.7 A (van der Waals r a d i i sum f o r oxygen and hydrogen) f o r hydrogen a b s t r a c t i o n by oxygen. 1-* However, the c o r r e -s p o n d i n g a b s t r a c t i o n a n g l e s , r and A o f 31° and 96° i n 38 compare w e l l w i t h the range o f 42-50° f o r r and 88-91° f o r A i n c y c l o h e x y l s u b s t i t u t e d acetophenones. The a b s t r a c t i o n geometry i n v o l v i n g H e i s b o a t l i k e as shown i n F i g . 10 Compound 43 p r o v i d e s an i n t e r e s t i n g c ase where the m o l e c u l e e x i s t s i n two d i f f e r e n t c o n f o r m a t i o n s i n the c r y s t a l . 1 2 6 Moreover, these two c o n f o r m a t i o n s a r e hydrogen bonded t o each o t h e r t h r o u g h the c a r b o x y l i c a c i d groups. The major d i f f e r e n c e s between the two conformers ( t h e s e a r e r e f e r r e d t o as 43 and 43' a r e a f t e r ) a r e the d i h e d r a l a n g l e s O^-Cy-Cg-Co, and Cy-Cg-Cg-C^Q. l n ^ 3> t n e ° l " c 7 a n d c 8 " c 9 b o n d s a r e e s s e n t i a l l y c o p l a n a r (O^-Cy-Cg-Cg = 1 ° ) , whereas t h e y a r e almost a t 7 3 -HO Figure 10: Boatlike abstraction geometry seen i n a-cyclopentyl-p-chloroacetophenone, 38. Figure 11: Stereodiagram depicting two conformers of a-cyclopentyl-p-carboxyacetophenone (43) present i n the c r y s t a l . 7 4 -r i g h t a n g l e s t o each o t h e r i n 43' as a r e s u l t o f a 100° r o t a t i o n around the C-j-C% bond ( F i g . 11). T h i s r o t a t i o n , f u r t h e r m o r e , i n c r e a s e s the d i s t a n c e between Ep and the c a r b o n y l oxygen i n 43' by more than an Angstrom t o 3.6 A and a l s o p l a c e s the 7-hydrogens f u r t h e r away from oxygen, b u t o n l y by 0.2 A . T h i s i s due to the f a c t t h a t the o t h e r d i h e d r a l a n g l e t h a t v a r i e s i n the two c o n f o r m a t i o n s , Cy-Cg-Cp-C^g, i s 53° i n 43' compared t o 65° i n 43. T h i s a c t u a l l y b r i n g s the 7-hydrogen c l o s e r t o oxygen i n 43' r e l a t i v e t o 43. The c o n f o r m a t i o n o f the c y c l o p e n t a n e r i n g and the a b s t r a c t i o n geometry i n 43 a r e s i m i l a r t o those found i n the c o r r e s p o n d i n g c h l o r o compound ( 3 8 ) . P h o t o c h e m i s t r y The s o l i d and s o l u t i o n s t a t e i r r a d i a t i o n s o f compounds 38-44 r e s u l t m a i n l y i n c l e a v a g e p r o d u c t s w i t h o n l y -10% c y c l i z a t i o n ( T a b l e X ) . The s u b s t i t u t i o n o f a c y c l o h e x a n e r i n g by c y c l o p e n t a n e thus r e s u l t s i n s i g n i f i c a n t l y d i f f e r e n t p h o t o r e a c t i v i t y . U n l i k e t h a t o b s e r v e d i n c y c l o h e x y l d e r i v a t i v e s , the v i s c o s i t y o f the medium o f i r r a d i a t i o n e x e r t s no i n f l u e n c e i n a l t e r i n g the p a r t i t i o n o f 1 , 4 - h y d r o x y b i r a d i c a l to the p r o d u c t s . One p o s s i b l e e x p l a n a t i o n t h a t can be advanced t o e x p l a i n the predominant c l e a v a g e i n c y c l o p e n t y l ketones i s t h a t the c y c l i z a t i o n p r o d u c t s a r e h i g h l y s t r a i n e d because o f the c i s - f u s e d r i n g j u n c t i o n between the c y c l o p e n t a n e and c y c l o b u t a n e r i n g s . The c a l c u l a t e d s t r a i n e n e r g i e s i n d i c a t e t h a t the b i c y c l o [ 3 . 2 . 0 ] system i s 6 k c a l / m o l e - 75 Table X: Cyclization:Cleavage Ratios f o r the Photolysis of a-Cyclopentyl-p-substituted Acetophenones, 3 8 - 4 4 . 1 - 3 S u b s t i t u e n t Cleavage (%) S o l i d 0.1M 0.1M S t a t e CH 3CN C 6 H 6 C y c l i z a t i o n (%) S o l i d 0.1M 0.1M S t a t e CH3CN C 6Hg C l , 38 95 93 95 CH 3, 39 99 97 98 OCH3, 40 100 100 100 41 95 93 95 CN, 42 94 94 94 COOH, 43 100 t - b u t a n o l 100 t - b u t a n o l 0 0 H , 44 92 93 92 = I r r a d i a t i o n s were conducted a t -15° to -30°C u s i n g l i q u i d n i t r o g e n a p p a r a t u s (see E x p e r i m e n t a l f o r d e t a i l s ) . No s i g n i f i c a n t d i f f e r e n c e i n the p h o t o p r o d u c t r a t i o s was e v i d e n t . A l l r e s u l t s were o b t a i n e d on a 12 m. Carbowax 20M column. 2. Chromatography f o r p-COOH was done on Carbowax column a f t e r methyla-t i o n u s i n g diazomethane. 3. c i s - and t r a n s - C y c l o b u t a n o l r a t i o s c o u l d n ot be de t e r m i n e d due to s m a l l amounts o f c y c l i z a t i o n c o u p l e d w i t h poor GC s e p a r a t i o n s . - 76 -h i g h e r i n energy than the b i c y c l o [ 4 . 2 . 0 ] s y s t e m . 1 2 7 j f such an i n c r e a s e i n s t r a i n energy i s r e f l e c t e d i 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 , i t i s easy t o r a t i o n a l i z e the p r e f e r e n c e f o r c l e a v a g e . I n a d d i t i o n , a n o t h e r f a c t o r t h a t works i n f a v o r o f c l e a v a g e i n the c y c l o p e n t a n e s e r i e s i s the r e l i e f o f s t r a i n (-0.4 k c a l / m o l e ) t h a t accompanies the f o r m a t i o n o f c y c l o p e n t e n e from c y c l o p e n t a n e . 1 2 8 , 1 2 9 jn c o n t r a s t , c y c l o h e x e n e i s more s t r a i n e d (-1.3 k c a l / m o l e ) compared t o the c y c l o -hexane r i n g , which i s e s s e n t i a l l y s t r a i n - f r e e i n i t s c h a i r f o r m . 1 2 8 , 1 2 9 I t i s i n t e r e s t i n g t o note a t t h i s j u n c t u r e the c o n f l i c t i n g arguments and e v i d e n c e from the l i t e r a t u r e f o r l l l , 130-133 a n o> a g a i n s t 1 1 ^ • the p h o t o p r o d u c t s t a b i l i t i e s a f f e c t i n g 1 , 4 - b i r a d i c a l p a r t i t i o n i n g . I n a d d i t i o n , t h e r e a r e o t h e r p h o t o c h e m i c a l r e s u l t s t h a t c o u l d be i n t e r -p r e t e d e i t h e r way. 1 3^> 1 3-> F u r t h e r s u p p o r t f o r the r e l a t i v e ease o f f o r m a t i o n o f c y c l o p e n t e n e from c y c l o p e n t a n e r e l a t i v e t o the f o r m a t i o n o f c y c l o h e x e n e from c y c l o -hexane comes from I - s t r a i n 1 3 * * • c o n s i d e r a t i o n s . I t has been o b s e r v e d i n a number o f systems t h a t r e a c t i o n s which c o n v e r t an s p 3 c a r b o n t o s p 2 c a r b o n a r e much more f a c i l e i n a c y c l o p e n t a n e r i n g t h a n i n a c y c l o h e x a n e ring.138-141 p o r e x a m p i e j m o l e c u l a r mechanics c a l c u l a t i o n s p e r f o r m e d by S c h n e i d e r and Thomas 1 3** show t h a t a c e t o l y s i s o f c y c l o p e n t y l t o s y l a t e p r o c e e d s w i t h an a c t i v a t i o n energy t h a t i s 3 k c a l / m o l e l e s s t h a n t h a t i n v o l v e d i n the a c e t o l y s i s o f c y c l o h e x y l t o s y l a t e . The f o r m a t i o n o f c y c l o p e n t e n e from c y c l o p e n t a n e i s f a v o r e d by -1.7 k c a l / m o l e over the f o r m a t i o n o f c y c l o h e x e n e from c y c l o h e x a n e by s t r a i n energy c o n s i d e r a -t i o n s . The b i r a d i c a l o r b i t a l geometry d e r i v e d from the c r y s t a l s t r u c t u r e 77 i n a - c y c l o p e n t y l - p - c h l o r o a c e t o p h e n o n e ( 3 8 ) i s n o t s i g n i f i c a n t l y d i f f e r e n t from t h a t f o u nd i n a - c y c l o h e x y l - p - c h l o r o a c e t o p h e n o n e ( 2 8 ) . The 0^ a n c ^ 62 v a l u e s o f 90 and 112° i n 38 a r e v e r y s i m i l a r t o t hose o b s e r v e d (0^ = 87-90° and B2 = 82-101°) i n a - c y c l o h e x y l acetophenones 28-37. However, i t i s s i g n i f i c a n t t h a t the b i r a d i c a l i n 38, which i s n o t v e r y d i f f e r e n t from the b i r a d i c a l i n 28, undergoes predominant c l e a v a g e . T h i s c l e a v a g e from a gauche b i r a d i c a l (C7-Cg-Cq-C^o = 71.1°) p r o v i d e s f u r t h e r s t r e n g t h to the argument t h a t gauche b i r a d i c a l s need n o t undergo o n l y c y c l i z a -t i o n . (B) a - C y c l o b u t y l - p - c h l o r o a c e t o p h e n o n e , 45 The s y n t h e s i s o f t h i s compound s t a r t s from c y c l o b u t a n e c a r b o x y l i c a c i d and i s d e s c r i b e d i n the P r e p a r a t i o n o f S u b s t r a t e s S e c t i o n . C o n f o r m a t i o n i n the S o l i d S t a t e The b a s i c c o n f o r m a t i o n o f t h i s ketone i s s i m i l a r t o t h a t f o u nd f o r the cyclohexane 1 0-'- and c y c l o p e n t a n e 1 2 1 a n a l o g s . The s i d e c h a i n p o s s e s s i n g the c a r b o n y l group i s p s e u d o - e q u a t o r i a l w i t h r e s p e c t to the c y c l o b u t a n e r i n g . The c y c l o b u t a n e r i n g adopts a p u c k e r e d c o n f o r m a t i o n t h a t i s s l i g h t l y more s t a b l e than the p l a n a r f o r m 1 ^ 2 because o f the r e l i e f i n t o r s i o n a l s t r a i n a v a i l a b l e i n the p u c k e r e d arrangement. However, c y c l o b u t a n e r i n g s are known to adopt b o t h p u c k e r e d 1 ^ 3 and p l a n a r 1 ^ • 1 ^ ^ arrangements i n the c r y s t a l , as the energy d i f f e r e n c e - 78 -between the two conformations i s less than 2 kcal/mole. Hydrogen Abstraction Geometry The abst r a c t i o n geometry i n t h i s case i s neither b o a t l i k e nor c h a i r l i k e but a h a l f - c h a i r shaped one. The choice of 7-hydrogen for ab s t r a c t i o n i s not unequivocal as was the case i n the cyclohexyl and cyclopentyl substituted acetophenones. There are two 7-hydrogens that are nearly equidistant from the carbonyl oxygen. The pseudoequatorial hydrogen (H e) i s at 3 .1 A, and pseudoaxial hydrogen (H a) i s at 3 .3 A. The corresponding r and A for H e are 3 3 ° and 78°, and are 3 9 ° and 1 0 1 ° for H a. In both cases, the abstraction geometry remains h a l f - c h a i r l i k e (Fig. 12). I t i s remarkable to note that t h i s compound undergoes a  smooth hydrogen abstraction i n spite of an 0-•-H distance of 3 . 1 - 3 . 3 A. Ha TI H a l f - c h a i r Abstraction Geometry d = 3 .1 A r = 2 3 ° A = 1 0 1 ° Figure 12: H a l f - c h a i r l i k e abstraction geometry i n a-cyclobutyl-p-chloroacetophenone, 45. - 79 -which i s much g r e a t e r than the su g g e s t e d upper l i m i t o f 2.7 A f o r hydrogen a b s t r a c t i o n by oxygen. The placement o f the g-hydrogen i s  b e t t e r (d = 2.7 A. r and A a r e 16° and 77°) f o r a b s t r a c t i o n r e l a t i v e t o  the - y-hydrogens. b u t no c o r r e s p o n d i n g p h o t o p r o d u c t s c o u l d be d e t e c t e d . P h o t o c h e m i s t r y The a - c y c l o b u t y l - p - c h l o r o acetophenone, l i k e i t s c y c l o p e n t y l c o u n t e r p a r t 45, r e a c t s p h o t o c h e m i c a l l y t o produce m a i n l y c l e a v a g e p r o d u c t s . The c l e a v a g e p r o d u c t , p - c h l o r o a c e t o p h e n o n e , c o n s t i t u t e s about 90% o f the p h o t o p r o d u c t s i n a l l t h r e e media i n v e s t i g a t e d ( T a b l e X I ) . The arrangement o f the p - o r b i t a l s i n the b i r a d i c a l t h a t i s g e n e r a t e d as a r e s u l t o f a b s t r a c t i o n i s s l i g h t l y d i f f e r e n t from t h a t o b s e r v e d i n the p - c h l o r o c y c l o p e n t y l ( 0 X = 90°, 62 = 112°) and c y c l o h e x y l (£]_ = 88°, 92 95°) d e r i v a t i v e s . The 0^ and t? 2 v a l u e s a r e 90° and 129°, r e s p e c t i v e l y . T a b l e XI: P h o t o c h e m i s t r y o f a - C y c l o b u t y l - p - c h l o r o a c e t o p h e n o n e , 45. Cleavage (%) C y c l i z a t i o n (%) 0.1 M C 6 H 6 90 10 0.1 M CH 3CN 88 12 S o l i d 92 8 - 80 -I t i s i n t r i g u i n g t o compare the p h o t o c h e m i s t r y o f these t h r e e c h l o r o d e r i v a t i v e s , c y c l o h e x y l ( 2 8 ) , c y c l o p e n t y l (38) and c y c l o b u t y l a c e -tophenones (45) w i t h t h e i r u n s u b s t i t u t e d lower homologues, c y c l o h e x y l (64), c y c l o p e n t y l (65) and c y c l o b u t y l p h e n y l ketones (66) (Scheme l a r h ydrogen a b s t r a c t i o n a t a l l i n c o n t r a s t t o a smooth N o r r i s h t y p e I I r e a c t i o n seen i n the c y c l o h e x y l d e r i v a t i v e s o f acetophenone. The p r e s e n c e o f an a d d i t i o n a l methylene group i n a - c y c l o h e x y l a c e t o p h e n o n e s has been s u g g e s t e d t o be r e s p o n s i b l e f o r a l l o w i n g s u f f i c i e n t f l e x i b i l i t y i n p e r m i t t i n g a c c e s s to the 7-hydrogens f o r the e x c i t e d s t a t e carbo-n y l . ^ The absence o f any N o r r i s h type I I p r o d u c t s i n 64 can then 30).115,134,146 C y c l o h e x y l p h e n y l ketone (64) undergoes no i n t r a m o l e c u -0 0 Ph SOLUTION 0 0 Ph SOLUTION 0 Ph hv 66 SOLUTION Scheme 31: P h o t o c h e m i s t r y o f ketones 64-66. - 81 -be a s c r i b e d t o the e q u a t o r i a l c h a i r form o f the c y c l o h e x a n e r i n g t h a t does n o t a l l o w the c a r b o n y l oxygen and 7-hydrogen t o come w i t h i n a b s t r a c t i o n d i s t a n c e . 1 ^ 6 Lewis has r e p o r t e d t h a t p r o l o n g e d i r r a d i a t i o n o f 64 i n degassed 1-propanol d i d r e s u l t i n type I I c l e a v a g e w i t h a quantum y i e l d o f C j . 1 3 . 1 ^ The i r r a d i a t i o n o f c y c l o b u t y l p h e n y l ketone (66) i n benzene a f f o r d s the c y c l i z a t i o n p r o d u c t , 2 - h y d r o x y - 2 - p h e n y l - b i c y c l o ( l . 1 . 1 . ) pentane (67) i n 60% y i e l d 1 1 ^ i n marked c o n t r a s t t o the l e s s t h a n 10% c y c l i z a t i o n o b s e r v e d i n the i r r a d i a t i o n o f a - c y c l o b u t y l - p - c h l o r o acetophenone (45) i n benzene. I n comparison, b o t h c y c l o p e n t y l p h e n y l ketone (65) and a - c y c l o p e n t y l - p - c h l o r o acetophenone (38) e s s e n t i a l l y c l e a v e upon i r r a d i a t i o n . I f the s t r a i n e n e r g i e s o f the c y c l i z a t i o n p r o d u c t s were a l o n e to d e c i d e the f a t e o f the b i r a d i c a l , the h i g h e r s t r a i n energy o f 67 (66.6 k c a l / m o l e ) ' c o m p a r e d t o the s t r a i n energy o f b i c y c l o [ 2 . 2 . 0 ] hexane 68, (52 k c a l / m o l e ) s h o u l d a c t u a l l y reduce the amount o f c y c l i z a t i o n i n the p h o t o l y s i s o f c y c l o b u t y l p h e n y l ketone (66). 68 Scheme 31 The remarkable d i f f e r e n c e i n the p h o t o b e h a v i o r o f 66 as compared to 65 was e x p l a i n e d by Padwa 1 1^ as f o l l o w s : the p r e f e r r e d c o n f o r m a t i o n , as - 82 -has been d i s c u s s e d p r e v i o u s l y , f o r p h o t o e l i m i n a t i o n r e q u i r e s p - o r b i t a l s a t r a d i c a l c e n t r e s o f the b i r a d i c a l t o be c o p l a n a r w i t h the c e n t r a l sigma bond b e i n g b r o ken t o a c h i e v e maximum o v e r l a p . The p r e f e r r e d c l e a v a g e i n 6 5 was then e x p l a i n e d t o be an outcome o f the f e a s i b i l i t y o f a t t a i n i n g a c o n f o r m a t i o n g e o m e t r i c a l l y more s u i t a b l e f o r c l e a v a g e i n a five-membered r i n g t h a n i n a four-membered r i n g (Scheme 32). Scheme 32: P h o t o c h e m i s t r y o f c y c l o b u t y l and c y c l o p e n t y l p h e n y l k e t o n e s . Wagner a l s o a t t r i b u t e d ^ 5 3 the 60% c y c l i z a t i o n o f 66 upon i r r a d i a t i o n t o the i n a b i l i t y o f i t s b i r a d i c a l to r e a c h the n e c e s s a r y c o n f o r m a t i o n f o r c l e a v a g e . S p e c i f i c a l l y , the r e q u i r e d maximum p - o r b i t a l o v e r l a p w i t h the d e v e l o p i n g double bond i s n o t p o s s i b l e , as the p - o r b i -- 83 t a l on i s held almost perpendicular to the 2,3 carbon-carbon bond such that the cleavage product, phenyl pentenone (Scheme 32) must develop with a twisted terminal bond. He also c i t e d t h i s as an example to i l l u s t r a t e how the product s t a b i l i t i e s do not d i c t a t e the p a r t i t i o n -ing of the b i r a d i c a l . There are no surprises on comparing the photochemical behavior of cyclobutyl and cyclopentyl acetophenones as opposed to the remarkable v a r i a t i o n s noticed i n the photoproduct r a t i o s between cycl o b u t y l and cyclopentyl phenyl ketone i r r a d i a t i o n s . This can be reasonably i n t e r -preted to be a consequence of the f l e x i b i l i t y given by an a d d i t i o n a l methylene group that aids i n a t t a i n i n g a transoid b i r a d i c a l conformation s u i t a b l e for cleavage i n cyclobutyl and cyclopentylacetophenone i r r a d i a -tions i n s o l u t i o n . With regard to the cyclization:cleavage r a t i o s that are medium inv a r i a n t i n the i r r a d i a t i o n of the p-chloro d e r i v a t i v e of a-cyclobutyl acetophenone (45), examination of the b i r a d i c a l geometry i s not much help. However, the p - o r b i t a l on cyclobutyl carbon C^Q. has 82 = 1 3 5 ° , and i s r e l a t i v e l y more aligned with the c e n t r a l sigma bond (C3-C9) than i n the case of cyclopentyl or cyclohexane analogs. Some of the argu-ments advanced i n explaining preferred cleavage i n cyclopentyl compounds apply i n cyclobutyl acetophenone too, as the shape and geometry of the b i r a d i c a l derived from photolyzing the cyclohexyl, cyclopentyl and c y c l o b u t y l acetophenones i s very s i m i l a r . S p e c i f i c a l l y , the c y c l i z a t i o n i n the c y c l o b u t y l case r e s u l t s i n a highly strained bicyclo[2.2.0]hexane system, and t h i s makes the l e s s energetic cleavage pathway more favor-able . 8 4 -(C) g - E x o - 2 - b i c v c l o f 2 . 2 . 1 l h e p t y l - p - s u b s t i t u t e d Acetophenones The o v e r a l l c o n f o r m a t i o n o f the p - c h l o r o (46) and p-methoxy (48) s u b s t r a t e s as d e t e r m i n e d by X - r a y c r y s t a l l o g r a p h y i s s i m i l a r to the o t h e r c y c l o a l k y l a n a l ogs o f acetophenones. Hydrogen A b s t r a c t i o n Geometry The hydrogen a b s t r a c t i o n geometry i s h a l f - c h a i r l i k e and the c h o i c e o f 7-hydrogen i s ambiguous, as t h e r e a r e two hydrogens t h a t a r e n e a r l y e q u i d i s t a n t from the c a r b o n y l oxygen. The d i s t a n c e s and geometry i n v o l v e d f o r the exo (H^) and endo (H a) hydrogens o f 46 and 48 a r e g i v e n i n T a b l e X I I . The a b s t r a c t i o n o f the exo hydrogen (H^) s h o u l d be f a v o r e d o v e r endo hydrogen (H a) b a s e d on a b s t r a c t i o n d i s t a n c e s . However, s i g n i f i c a n t c o n t r i b u t i o n from H a to the a b s t r a c t i o n cannot be r u l e d out. I r r e s p e c t i v e o f the 7-hydrogen a b s t r a c t e d , the a b s t r a c t i o n geometry i s h a l f - c h a i r l i k e ( F i g . 13). H^ i s b e t t e r p l a c e d f o r a b s t r a c t i o n compared t o the 7-hydrogens, b u t no p r o d u c t s c o r r e s p o n d i n g to such a b s t r a c t i o n were e v i d e n t . P h o t o c h e m i s t r y The b i r a d i c a l p a r t i t i o n i n g was found to be i n s e n s i t i v e to the medium o f i r r a d i a t i o n as j u d g e d by the c l e a v a g e : c y c l i z a t i o n r a t i o s (see T a b l e X I I I , p a g e 86) ). A comparison o f the p h o t o c h e m i s t r y o f these 85 -Table XII: Hydrogen Abstraction Parameters f o r a-Exo-2-bicyclo-[2.2.l]heptyl-p-substituted Acetophenones. S u b s t i t u e n t H, d(A), r(°), A(°) d(A), r(°), A(°) d(A), r(°), A(°) p - C l , 46 3.0, 44, 75 3.1, 26, 100 2.7, 14, 79 p-0CH 3, 48 3.0, 36, 74 3.1, 19, 98 2.5, 18, 81 Ai\ H 0 H a l f - c h a i r l i k e A b s t r a c t i o n Geometry (H^) F i g u r e 13: P i c t o r i a l diagram o f the hydrogen a b s t r a c t i o n geometry i n 46. k e t o n e s w i t h t h e i r lower homologues, exo-2- (19) and endo-2- (18) b i c y - c l o [ 2 . 2 . 1 ] - h e p t a n e and a l s o w i t h e n d o - 2 - b e n z o y l b i c y c l o [ 2 . 2 . 2 ] o c t a n e (69)°^ sheds l i g h t on how the 0-• -H7 d i s t a n c e can i n f l u e n c e the r a t e and 86 -e f f i c i e n c y o f hydrogen a b s t r a c t i o n (page 88). The b i c y c l o a l k y l p h e n y l k e t o n e s , 18 and 69 undergo an e x t r e m e l y f a s t hydrogen a b s t r a c t i o n , comparable t o the r a t e o f a b s t r a c t i o n i n h i g h l y r e a c t i v e a - a l k o x y a c e t o p h e n o n e s . 1 ^ 0 Such a r a p i d r a t e was a t t r i b u t e d to the v e r y f a v o r a b l e c o n f o r m a t i o n s assumed by 18 and 69 t h a t p e r m i t the c a r b o n y l oxygen t o come w i t h i n -1.7 A o f the 7-hydrogens* w i t h o u t much s t e r i c T a b l e X I I I : P h o t o c h e m i s t r y o f N o r b o r n y l D e r i v a t i v e s o f Acetophenone, 4 6 - 4 9 . 1 - 2 S u b s t i t u e n t C l e avage (%) C y c l i z a t i o n (%) S o l i d 0.1 M 0.1 M S o l i d 0.1 M 0.1 S t a t e CH3CN C 6 H 6 S t a t e CH3CN p - C l , 46 86 88 88 14 12 12 p-CH 3, 47 95 91 91 5 9 9 P-OCH3, 48 95 80 90 5 20 10 p-H, 49 94** 93 91 6** 7 9 ** = I r r a d i a t i o n a t -30°C. 1. A l l r e s u l t s were o b t a i n e d on a 12 m. Carbowax 20 M column. 2. Cleavage p r o d u c t , p - s u b s t i t u t e d acetophenone, was i d e n t i f i e d by c o - i n j e c t i o n method as w e l l by G.C.M.S. A l l the 0"• -H d i s t a n c e s were e s t i m a t e d u s i n g m o l e c u l a r models i n compounds 18, 69 and 69 - 8 7 d e s t a b i l i z a t i o n . The other i n t e r e s t i n g information that was derived from comparing the higher rates i n 18 and 69 r e l a t i v e to valerophenone was the po s t u l a t i o n of a non-planar abstraction geometry 1 5! f o r valerophenone. Such non-planar abstraction geometries involve longer 0---H.y distances compared to planar abstraction geometry. A longer 0---H.y distance probably r e s u l t s i n a smaller hydrogen abstraction rate constant. The smaller hydrogen abstraction rate constant i n 19 was a t t r i b u t e d to a longer 0...H^ distance of 2.2 A, i n the absence of any v a r i a t i o n s i n energetic or s t e r i c considerations between exo-2-(19) and endo-2-(18) bicyclo [ 2 . 2.1]heptanes. The rate constants of 18, 19 and 69 are expected to be much f a s t e r than the rate constant of 46 f o r two important reasons: 1. The number of f r e e l y r o t a t i n g C-C bonds between the carbonyl chromophore and i s two i n a—norbornyl-p-chloroacetophenone (46) as against one i n benzoyl bicyclocompounds (18, 19 and 69). 2. The chloro group present i n 46 i s known to reduce the rate constant by approximately 3 orders of magni-t u d e . 1 0 0 In comparison with ketones 18 and 69, the hydrogen abstraction rate constant i s much slower i n 46,* but i s f a s t e r than the rate determined o c i n 19. Since the hydrogens involved i n a l l cases are secondary norbornyl hydrogens, the large v a r i a t i o n s i n abstrac t i o n rates must r e f l e c t conformational or stereoelectronic requirements f o r hydrogen Rate constant was measured i n benzene. See Experimental Section for d e t a i l s . - 88 -a b s t r a c t i o n . S i n c e the a b s t r a c t i o n g e o m e t r i e s can be a t t a i n e d i n a l l c a s e s w i t h o u t any s i g n i f i c a n t s t e r i c c o n s t r a i n t s , the slower r a t e c o n s t a n t i n 19 compared to 46 might be a r e s u l t o f the r i g i d i t y imposed by the b i c y c l o a l k a n e (norbornane) r i n g t h a t hampers any p o s s i b i l i t y o f a t t a i n i n g oxygen-•-hydrogen c o n t a c t s t h a t a r e l e s s t h a n 2.2 A.* I n a - n o r b o r n y l - p - c h l o r o a c e t o p h e n o n e ( 4 6 ) , d i s t a n c e s much s m a l l e r t h a n 2.2 A ( t h e s h o r t e s t 0-• -H-y d i s t a n c e from c r y s t a l s t r u c t u r e i s 3.0 A) can be a t t a i n e d by f a c i l e r o t a t i o n s around the C Q-C^ (C8"^9) bond,* though a t the expense o f i n c r e a s e d energy. k„ = 100 X 10 8 Sec 1 k„ = A.4 X 10 ? Sec A computer program w r i t t e n by Mr. Stephen Evans o f our Department, s i m u l a t e s the c o n f o r m a t i o n a l motions o f the a - c y c l o a l k y l a c e t o p h e -nones to o b t a i n p l o t s o f the v a r i a t i o n i n d, T, and A as a f u n c t i o n o f t h e se motions. - 89 -Such r o t a t i o n s accompanying the d e c r e a s e i n 0 " • d i s t a n c e a r e n o t p o s s i b l e i n 18, 19 and 69, as the C Q-C^ bond i s p a r t o f a r i g i d b i c y c l o a l k a n e system. The b i r a d i c a l geometry i n 46 i s s i m i l a r t o t h a t p r e s e n t i n the c y c l o b u t y l d e r i v a t i v e . The &i and 0 2 v a l u e s a r e 94° and 140°, r e s p e c t i v e l y . The 0 2 °f 140° means more o v e r l a p o f t h i s p - o r b i t a l w i t h the c e n t r a l sigma bond b e i n g b r o k e n r e l a t i v e t o t h a t f o u n d i n c y c l o p e n -t y l and c y c l o h e x y l acetophenones and s h o u l d f a v o r c l e a v a g e . 3. Compounds t h a t Undergo Cleavage as w e l l as C l o s u r e . C o n f o r m a t i o n i n t h e S o l i d S t a t e C y c l o h e p t y l s u b s t i t u t e d acetophenones b e l o n g t o t h i s c a t e g o r y . The c y c l o h e p t a n e r i n g s i t s i n a c o n f o r m a t i o n i n the c r y s t a l t h a t i s interme-d i a t e between a c h a i r and a t w i s t - c h a i r f o r m . 1 5 2 ^he t w i s t - c h a i r c o n f o r m a t i o n i s the most s t a b l e one f o r a seven membered r i n g and i s about 2.2 k c a l / m o l e lower i n energy than the c h a i r a r r a n g e m e n t . 1 - ^ ^he s i d e c h a i n w i t h the c a r b o n y l i s p s e u d o - e q u a t o r i a l t o the c y c l o h e p t a n e r i n g . The o v e r a l l m o l e c u l a r c o n f o r m a t i o n i s v e r y s i m i l a r t o t h a t found i n the o t h e r c y c l o a l k y l acetophenones d i s c u s s e d . - 90 -Hydrogen A b s t r a c t i o n Geometry Three k e t o n e s , 50-52 were i n v e s t i g a t e d p h o t o c h e m i c a l l y and c r y s t a l s t r u c t u r e s were o b t a i n e d f o r the p - c h l o r o (50) and p-methyl (51) d e r i v a t i v e s t o determine the a b s t r a t i o n p a r a m e t e r s . The a b s t r a c t i o n geometry i s b o a t l i k e ( F i g . 14), as e n c o u n t e r e d i n the c y c l o h e x y l and c y c l o p e n t y l c o u n t e r p a r t s . However, the placement o f p s e u d o - a x i a l h ydrogen (H a) i s q u i t e f a r o f f (more than 4 A, see T a b l e XIV) from oxygen compared to o t h e r systems; p s e u d o - e q u a t o r i a l hydrogen (H e) i s a t 2.7 A, as i s normal i n the o t h e r m o l e c u l e s d i s c u s s e d . The T and A v a l u e s f o r H e a r e 42-49° and 76-82°, r e s p e c t i v e l y . No ^-hydrogen a b s t r a c t i o n p r o d u c t s were d e t e c t e d . Ar 12 1 8 \ X H - e ~ 0 ' 14 B o a t l i k e A b s t r a c t i o n Geometry d = 2.7 A r = 42° A = 82° F i g u r e 14: P i c t o r i a l p r e s e n t a t i o n o f b o a t l i k e hydrogen a b s t r a c t i o n seen i n c t - c y c l o h e p t y l - p - c h l o r o a c e t o p h e n o n e s , 50. - 91 -P h o t o c h e m i s t r y A l l m o l e c u l e s i n t h i s s e r i e s undergo a smooth N o r r i s h type I I r e a c t i o n i n the s o l u t i o n as w e l l as i n the c r y s t a l . I n t e r e s t i n g l y , an T a b l e XIV: Hydrogen A b s t r a c t i o n Parameters f o r a - C y c l o h e p t y l - p -s u b s t i t u t e d Acetophenones, 50 and 51. S u b s t i t u e n t H e H a Ho d(A) , r ( ° ) , A ( ° ) d(A), r ( ° ) , A ( ° ) d(A) , r ( ° ) , A ( ° ) p - C l , 50 p-CH 3, 51 2.7, 42, 82 2.7, 49, 76 >4.0, 33, >4.0, 34, 2.6, 10, 81 2.6, 7, 81 i n c r e a s e i n the amount o f c y c l i z a t i o n p r o d u c t s was o b s e r v e d i n the s o l i d s t a t e i r r a d i a t i o n s ( T a b l e XV). There i s a l s o an i n c r e a s e i n the r a t i o o f t r a n s - c y c l o b u t a n o l to c i s - c y c l o b u t a n o l i n the s o l i d s t a t e p h o t o l y s e s ( T a b l e X V I ) . T h i s c o n s i d e r a b l e p r e f e r e n c e f o r c y c l i z a t i o n i n the s o l i d s t a t e i s r a t h e r p u z z l i n g a t f i r s t g l a n c e , as the b i r a d i c a l geometry i s v e r y s i m i l a r to t h a t o b s e r v e d i n the c y c l o p e n t y l and c y c l o h e x y l d e r i v a -t i v e s . However, the c o n f o r m a t i o n o f the c y c l o h e p t a n e r i n g i s not s u i t a b l e f o r c l e a v a g e . S p e c i f i c a l l y , the t o r s i o n a n g l e around C^5-Cg-C^o" (-'ll l s 67°, so t h a t the r e s u l t i n g c y c l o h e p t e n e would develop w i t h a t w i s t e d double bond. In a d d i t i o n , h i g h t h e r m a l parameters f o r - 92 -Table XV: Photochemistry of a-Cycloheptyl-p-substituted Acetophe-nones . 1 - 3 S u b s t i t u e n t C y c l i z a t i o n (%) X S o l i d S t a t e 0.1 M CH3CN 0.1 M S o l i d S t a t e 0.1 M CH3CN 0.1 M C 6 H 6 p - C l , 50 55 69 64 45 31 36 p-CH 3 > 51 42 59 63 58 41 37 P-OCH3, 52 21 54 66 79 46 34 Table XVI: c i s - and trans- Cyclobutanol Ratios i n the I r r a d i a t i o n of a-Cycloheptyl-p-substituted Acetophenones. 1 - 3 S u b s t i t u e n t X t r a n s - C y c l o b u t a n o l S o l i d 0.1 M 0.1 M S t a t e CH3CN C 6 H 6 c i s - C y c l o b u t a n o l S o l i d 0.1 M 0.1 M S t a t e CH3CN C 6 H 6 p - C l , 50 p-CH 3, 51 P-OCH3, 52 1. 2 . 83 59 77 17 41 23 92 69 85 8 31 15 90 69 85 10 31 15 were kept below 3%. P h o t o p r o d u c t r a t i o s i n the s o l i d s t a t e and a c e t o n i t r i l e were i n v a r i a n t to i r r a d i a t i o n s a t -30° to 20 °C. 3. The p r e f e r e n c e f o r c y c l i z a t i o n (and t r a n s - c y c l o b u t a n o l f o r m a t i o n ) d e c r e a s e r a p i d l y w i t h h i g h e r c o n v e r s i o n s (>3%). - 93 f o r the c y c l o h e p t y l r i n g c arbons, e s p e c i a l l y the 7-carbons ( C^o a n d C15) i n d i c a t e s i g n i f i c a n t d i s o r d e r and p r o b a b l y p s e u d o r o t a t i o n i n the r i n g . Such pse u d o r o t a t i o n - * - ^ , 163 m i g n t be r e s p o n s i b l e i n p a r t f o r i n c r e a s e d c y c l i z a t i o n i n the s o l i d s t a t e , as i t b r i n g s the p - o r b i t a l on CIQ c l o s e enough t o the p - o r b i t a l on Cy f o r c y c l i z a t i o n (70-^l, Scheme 33) t o form a p u c k e r e d c y c l o b u t a n e r i n g from t h e gauche b i r a d i c a l . Such p s e u d o r o t a t i o n i n the c y c l o h e p t a n e r i n g might n o t be as e f f e c t i v e i n 1 3 71 Scheme 33: P s e u d o r o t a t i o n i n the c y c l o h e p t a n e r i n g f a v o r i n g c y c l i z a t i o n . the s o l u t i o n as i n the s o l i d i n b r i n g i n g about c y c l i z a t i o n because f a c i l e r o t a t i o n s around the Cg-Cq bond i n s o l u t i o n r e s u l t i n many c o n f o r m a t i o n s t h a t do n o t p r o v i d e the r e q u i r e d o v e r l a p between the p - o r b i t a l s on the Cy and C^Q carbons n e c e s s a r y f o r c y c l i z a t i o n . These r o t a t i o n s , on the o t h e r hand, can r e s u l t i n a t r a n s o i d - b i r a d i c a l that has the o p t i o n o f o n l y c l e a v a g e . - 9 4 -4 . A C o r r e l a t i o n between Molecular Conformation and B i r a d i c a l P a r t i t i o n i n g to Photoproducts i n the Norrish Type II Reaction. The Norrish type II reaction has been shown to be s e n s i t i v e to solvent p o l a r i t y , 1 2 0 temperature 1 5^ as well as s u b s t i t u t i o n . 1 0 * * I t i s the wealth of information that i s av a i l a b l e for t h i s r e a c t i o n that has lured many investigators to use i t as a probe to investigate the proper-t i e s of r e s t r i c t e d environments. The r e s t r i c t e d media explored include m i c e l l e s , 1 5 5 , 1 5 6 monolayers, 1 5 6 p o l y m e r s , 1 5 ^ - 1 5 8 i n c l u s i o n com-p o u n d s , 1 5 9 - 1 6 0 l i q u i d c r y s t a l s , 1 1 8 - 1 6 1 and c r y s t a l l i n e s o l i d s . 6 8 ' 1 6 2 - 1 6 3 However, there are very few e x a m p l e s 6 8 ' 1 1 3 ' 1 1 8 ' 1 6 1 i n the l i t e r a -ture that u t i l i z e the constrained environment to t h e i r advantage i n a r r i v i n g at some 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 between the photopro-ducts and the ketone conformations f o r the Norrish type II reaction. Even i n cases where such c o r r e l a t i o n s were attempted, the r e s u l t s were marred by t h e i r h i g h l y speculative nature and by t h e i r having no accom-panying concrete evidence f o r the b i r a d i c a l conformations (or configura-tions) a s s u m e d . 1 1 3 ' 1 1 8 - 1 6 1 One of the secondary objectives of t h i s thesis was to c o r r e l a t e the type II photoproducts to the b i r a d i c a l conformations deduced from the X-ray c r y s t a l l o g r a p h i c information about the s t a r t i n g ketones. In the following few pages, an attempt i s made i n t h i s d i r e c t i o n using a-cy-cloalkyl-p-chloroacetophenones as the representative examples of each s e r i e s . Since the r e s u l t s obtained i n i r r a d i a t i n g c r y s t a l s are not greatly d i f f e r e n t from those found i n the s o l u t i o n media, the structure-r e a c t i v i t y f i t f o r b i r a d i c a l p a r t i t i o n i n g a r r i v e d at for the s o l i d state 95 -r e s u l t s may n o t be f a r from the s i t u a t i o n e x i s t i n g i n l i q u i d media. When t h e r e i s a s u b s t a n t i a l d e v i a t i o n i n the s o l i d s t a t e b e h a v i o r as compared t o the s o l u t i o n s t a t e , the medium-dependent p h o t o c h e m i s t r y was r a t i o n a l -i z e d u s i n g the s t r u c t u r a l e v i d e n c e from c r y s t a l l o g r a p h y . I n e v e r y compound s t u d i e d , the s p e c i e s g e n e r a t e d a f t e r the hydrogen a b s t r a c t i o n i s a gauche b i r a d i c a l , y e t i t s p a r t i t i o n t o p r o d u c t s i s q u i t e d i v e r s e . The gauche b i r a d i c a l o b t a i n e d i n our case i s v e r y s i m i l a r t o C a l d w e l l ' s gauche b i r a d i c a l (62,page 6 3 ) 1 1 3 t h a t undergoes o n l y c y c l i z a t i o n . D e s p i t e t h i s we observe p r o d u c t s r a n g i n g from 92% c l e a v a g e t o 96% c y c l i z a t i o n depending on the s u b s t r a t e i n v o l v e d ( T a b l e XVII, page 97). T h i s c o n t r a d i c t s the e x i s t i n g n o t i o n t h a t a gauche or c i s b i r a d i c a l y i e l d s m a i n l y p r o d u c t s r e s u l t i n g from c l o s u r e . However, i t was n o t p o s s i b l e t o r a t i o n a l i z e the v a s t l y d i f f e r i n g p r o d u c t d i s t r i b u -t i o n s f o r t h e s e c h l o r o d e r i v a t i v e s on the s o l e b a s i s o f b i r a d i c a l g e o m e t r i e s t h a t do n o t d i f f e r s u b s t a n t i a l l y ( T a b l e X V I I I , page 96). The no t so d i v e r s e c r y s t a l d e n s i t i e s (d) as w e l l as i n t e r p l a n a r d i s t a n c e s (h) ( T a b l e XIX, page 97) f o r a l l c h l o r o compounds t e n d t o r u l e out the p o s s i b i l i t y o f p a c k i n g e f f e c t s on the p r o d u c t d i s t r i b u t i o n . The answer t o t h i s v a s t l y d i f f e r e n t p h o t o p r o d u c t d i s t r i b u t i o n may come from the c y c l o a l k a n e r i n g c o n f o r m a t i o n s . There e x i s t s a d i r e c t c o r r e l a t i o n between C n-Cg-C^Q-C^^ d i h e d r a l a n g l e , where n v a r i e s from 12-16 f o r c y c l o b u t a n e t o c y c l o o c t a n e , and the c l o s u r e : e l i m i n a t i o n r a t i o s (see T a b l e X I X ) . A d i h e d r a l a n g l e o f 0° s h o u l d be i d e a l f o r the f o r m a t i o n o f o l e f i n s i n c e the CQ-C^Q bond becomes the double bond as a r e s u l t o f c l e a v a g e and wants to be c i s . As t h i s d i h e d r a l a n g l e changes - 9 6 T a b l e X V I I I : B i r a d i c a l Parameters f o r a - C y c l o a l k y l - p - c h l o r o a c e t o p h e -nones. r , Compound d(A) number ( C 7 - C 1 0 d i s t a n c e ) g^") ^ ( 0 ) 4, 45 3.27 5, 38 3.25 6, 28 3.19 7, 50 3.20 8 , 53 3.13 71 90 129 71 90 112 71 8 8 95 75 94 99 69 96 132 *1 = The a n g l e o f p - o r b i t a l on C 7 w i t h Cg-Cg bond. >2 = The a n g l e o f p - o r b i t a l on C 1 0 w i t h Cg-Cg bond. - 97 -Table XVII: S o l i d State I r r a d i a t i o n s of Chloro Substrates. 10 28 55 50 45 53 96 Table XIX: Cr y s t a l Densities (d), Interplanar Distances (h) and c n " c 9 " c 1 0 " c l l Dihedral Angles. r, Compound number n d (Density (g/cm3) h (Interplanar Distance ( A ) ) c n - c 9 - c Dihed: Angle 4, 45 12 1.27 3.55 14 5, 38 13 1.27 3.61 30 6, 28 14 1.12 3.62 55 7, 50 15 1.23 3.66 67 8 , 53 16 1.23 3.50 104 98 -from 14° i n the c y c l o b u t y l d e r i v a t i v e ( i . e . a l l f o u r carbons a r e almost i n the same p l a n e ) to 104° i n the c y c l o o c t y l d e r i v a t i v e , the amount o f e l i m i n a t i o n p r o d u c t s d e c r e a s e s from 92% t o l e s s t h a n 5 % . The r e s u l t s from T a b l e XIX, t h e r e f o r e , s u g g e s t t h a t the amount o f e l i m i n a t i o n p r o d u c t s depend on the ease w i t h which a double bond can be accommodated by the Cg-C^n bond. The double bond t h a t r e s u l t s from c l e a v a g e o f the Cg-Cq bond can be n i c e l y accommodated i n a - c y c l o p e n t y l -p - c h l o r o a c e t o p h e n o n e (38) and a - c y c l o b u t y l - p - c h l o r o a c e t o p h e n o n e (45) because o f t h e i r low C n-Cq-C;L0" C11 d i h e d r a l a n g l e s and i s r e f l e c t e d i n t h e i r predominant c l e a v a g e (-90%). Cleavage p r o d u c t s c o n s t i t u t e r o u g h l y h a l f o f the p h o t o p r o d u c t s i n Q - c y c l o h e x y l - p - c h l o r o a c e t o p h e n o n e (28) and a - c y c l o h e p t y l - p - c h l o r o a c e t o p h e n o n e (50) because the d i h e d r a l a n g l e ^n" c9" <-'10* (-'ll l s 5 5 ° a n < i 67°, r e s p e c t i v e l y , and e l i m i n a t i o n would r e s u l t i n a t w i s t e d double bond i n b o t h c a s e s . S i g n i f i c a n t m o l e c u l a r and atomic motions a r e n e c e s s a r y t o a c h i e v e the i d e a l 0° d i h e d r a l a n g l e t h a t i s p r e s e n t i n the most s t a b l e h a l f - c h a i r c o n f o r m a t i o n s o f c y c l o h e x e n e and c y c l o h e p t e n e . The c y c l o o c t e n e t h a t i s p r o d u c e d as a r e s u l t o f e l i m i n a t i o n i n a - c y c l o o c t y l - p - c h l o r o a c e t o p h e n o n e (53) would have more o f a t r a n s - g e o m e t r y (C^g-Cg-C^Q'Cll = 104") t h a t i s u n f a v o r a b l e e n e r g e t i c a l l y , and t o a t t a i n a c i s - g e o m e t r y f o r the double bond would mean c o n s i d e r a b l e rearrangement i n the c o n f o r m a t i o n o f the c y c l o o c t a n e r i n g . T h i s may e x p l a i n the 96% c y c l i z a t i o n i n ketone 53. E v i d e n c e a l s o comes from i n s p e c t i n g the Cy-C^g d i s t a n c e s ( T a b l e X V I I I , page 96), the d i s t a n c e s between carbons i n v o l v e d i n f o r m i n g c y c l o b u t a n o l s . The d e c r e a s i n g Cy-C^g d i s t a n c e s w i t h i n c r e a s e i n r i n g s i z e p o i n t to more c l o s u r e i n the l a r g e r r i n g acetophenones, the 9 9 -o b s e r v e d t r e n d . However the magnitude o f the d e c r e a s e i n C7-C10 d i s t a n c e s i s v e r y s m a l l . The d i f f e r e n c e between the s m a l l e s t and l a r g e s t Cy---C^Q d i s t a n c e s i n 45 and 53 i s o n l y 0.14 A. The o b s e r v e d t r e n d a l s o resembles the ease o f i n t r o d u c i n g an sp^ c e n t r e i n c y c l o a l k a n e s as e v i d e n c e d by the r a t e c o n s t a n t s d e r i v e d f o r the a c e t o l y s i s o f c y c l o a l k y l t o s y l a t e s . 1 3 9 The f a s t e r r a t e s of s o l v o l y s i s o f c y c l o p e n t y l and c y c l o h e p t y l t o s y l a t e s r e l a t i v e t o c y c l o -h e x y l t o s y l a t e r e f l e c t the r e l a t i v e ease o f i n t r o d u c t i o n o f an s p 2 c e n t r e i n c y c l o p e n t a n e and c y c l o h e p t a n e r i n g s t h a n i n c y c l o h e x a n e r i n g and might, i n p a r t , e x p l a i n the i n c r e a s e d c l e a v a g e i n c y c l o h e p t y l and c y c l o p e n t y l acetophenones compared to c y c l o h e x y l acetophenones. Two t h i n g s become c l e a r when the s t r a i n e n e r g i e s 1 2 ^ " 1 2 9 o f the p h o t o p r o d u c t s , c y c l o b u t a n o l s and c y c l o a l k e n e s (Scheme 34), ar e compared t o the s t a r t i n g k e t o n e s . F i r s t , the i n c r e a s e i n s t r a i n energy i n f o r m i n g c y c l o b u t a n o l s i s 26.2 k c a l / m o l e and does n o t v a r y w i t h the system. Second, the ease o f f o r m a t i o n o f c y c l o a l k e n e from c y c l o a l k a n e seems t o c o r r e l a t e w e l l w i t h the c l e a v a g e p r o p o r t i o n s i n s o l u t i o n e x c e p t f o r the c y c l o b u t y l d e r i v a t i v e . F o r c y c l o b u t y l d e r i v a t i v e 45, c y c l o b u t e n e f o r m a t i o n would mean an i n c r e a s e i n s t r a i n energy o f - 4 k c a l / m o l e , y e t c l e a v a g e i s the major p r o c e s s . Two p o s s i b l e e x p l a n a t i o n s t h a t c o u l d be f o r w a r d e d a r e : a) the c y c l i z a t i o n p r o d u c t s , b i c y c l o b u t a n o l s a r e h i g h l y s t r a i n e d (-52 k c a l / m o l e ) and hence are n o t f a v o r e d , and b) the near p l a n a r CQ-C;LO~ C11"CI2 d i h e d r a l a n g l e f a v o r s the c l e a v a g e p r o c e s s , as the r e s u l t i n g double bond can be e a s i l y accommodated. 100 -• C l e a v a g e • C y c l i z a t i o n 2 9 . 8 2 6 . 2 5 2 . 4 C l e a v a g e 5 . 9 O 6 . 3 C y c l i z a t i o i 3 2 . 5 C l e a v a g e 1 . 4 o - 0 -I v c l i z a t i o n 2 6 . 2 C1 e a v e g i 5 . 4 6 . 4 C v c l i z a t i o n 3 2 . 6 C 1 e a v a g e C y c l i z a t i o n C i s 6.0 T r a n s 1 5 . 3 9 . 9 3 6.1 Scheme 34: S t r a i n energies i n kcal/mole. - 101 -However, the magnitude of both s t r a i n energy and Cy-C^g bond distance arguments i s very minor and may not contribute s i g n i f i c a n t l y to the observed trends. There could be yet another argument to r a t i o n a l i z e the observed trend, that i s to assume that the cyclobutanols formed are not c i s - f u s e d r i n g systems but are trans-fused. That would e a s i l y explain the increase i n the amount of c y c l i z a t i o n products i n the larger r i n g acetophenones r e s u l t i n g from smaller s t r a i n energies involved i n forming large r i n g trans-fused cyclobutanols. This may not be the case as the trans-fused cyclobutanols are more strained than the c i s - f u s e d 1 ^ 8 > ^ 9 and other workers found s i m i l a r photochemically generated cyclobutanols to be c i s - f u s e d . 8 6 ' 1 1 3 " 1 1 5 5. The Importance of Non-minimum Energy Conformations i n the Norrish Type II Reaction The rate constants for intramolecular and enzymatic reactions are generally l a r g e r than for the corresponding bimolecular and non-enzymatic r e a c t i o n s . 1 6 ^ ' 1 6 5 Since the source of rate enhancement has been a t t r i b u t e d to the r e s t r i c t i o n on conformational freedom i n unimo-l e c u l a r and enzymatic reactions, there has been considerable i n t e r e s t i n understanding the e f f e c t of conformational r e s t r i c t i o n on the unimolecu-l a r r e a c t i o n r a t e s . 1 6 6 The Norrish type II reaction represents one such intramolecular reaction, and the rate of 7-hydrogen abstraction involved i n t h i s 102 -reaction, k H ( o b s ) , i s a sum of the rates, k ^ , for each favorable conformation f, times the equilibrium f r a c t i o n of molecules i n that conformation, Xf (eq. 1).75b,167 since the Norrish type II r e a c t i o n i s a photochemical reaction, the ground state Xf f a c t o r can be d i f f e r e n t from the excited state Xf factor. However, for n , 7 r * e x c i t a t i o n of conjugated aromatic carbonyls, the excited state geometries are not much d i f f e r e n t from the ground state g e o m e t r i e s , 1 6 8 " 1 ^ leading to the conclusion that Xf and Xf do not d i f f e r much. kH(0bs)= SxfkH f ( equation 1 } In c y c l i c molecules, the number of possible conformations for a molecule can get quite small such that Xf can approach unity (or zero i f the preferred conformation i s unfavorable f o r r e a c t i o n ) . The study of 2-n-propyl-hexanone^ 1 provides an example for Xf = 0. The conformer with the a x i a l propyl group places the 7-hydrogens f a r away from the carbonyl oxygen for an abstraction making Xf - 0. This was discussed e a r l i e r i n the context of s t e r e o e l e c t r o n i c requirement for hydrogen abstrac t i o n that requires the approach of the C-H bond i n the plane of the carbonyl oxygen's n - o r b i t a l . I t i s now c l e a r from the present study that such a requirement i s not absolute, as smooth abstractions were observed even when r = 62°. Rate enhancements i n intramolecular reactions have been explained i n terms of changes i n entropy of activation, 1 1 1»^2 o r i e n t a t i o n of r e a c t i v e c e n t r e s , 1 ^ 3 and changes i n the reaction mechanism. The rate 103 -c o n s t a n t s f o r t r i p l e t - s t a t e 7 - h y d r o g e n a b s t r a c t i o n i n Scheme 3 5 n i c e l y i l l u s t r a t e how c o n f o r m a t i o n a l m o b i l i t y i n f l u e n c e s the p h o t o c h e m i c a l 70 X 10 Sec Scheme 35: as a f u n c t i o n o f m o l e c u l a r r i g i d i t y . r e a c t i v i t y . I n Scheme 35, the hydrogen a b s t r a c t e d i s secondary i n ev e r y case, so t h a t the l a r g e v a r i a t i o n seen i n the r a t e c o n s t a n t s must r e f l e c t p r i m a r i l y c o n f o r m a t i o n a l e f f e e t s . 1 1 1 S i n c e the a c t i v a t i o n e n e r g i e s r e q u i r e d f o r the hydrogen a b s t r a c t i o n r e a c t i o n s i n Scheme 35 are a l s o the same, the v a r i a t i o n s i n r a t e c o n s t a n t s must be due e n t i r e l y to the d i f f e r e n c e s i n e n t r o p y o f a c t i v a t i o n . As the number o f f r e e l y - 104 -r o t a t i n g C-C bonds between c a r b o n y l chromophore and C-H^ a r e " f r o z e n " , the r a t e c o n s t a n t i n c r e a s e s . Each " f r o z e n " r o t a t i o n i n c r e a s e s kjj(obs) and thus X f by an o r d e r o f magnitude. There i s y e t a n o t h e r way o f f i n d i n g a q u a n t i t a t i v e r e l a t i o n s h i p between and the a b s t r a c t i o n geometry. T h i s method c o n s i s t s o f p h y s i c a l l y r e s t r i c t i n g bond r o t a t i o n s i n c o n f o r m a t i o n a l l y m o b i l e systems such t h a t X f - 1. We have adopted t h i s approach, and " f r e e z i n g " o f the r e a c t a n t m o l e c u l e s i n a s i n g l e r e a c t i v e c o n f o r m a t i o n was a c h i e v e d by i m m o b i l i z i n g them i n t h e i r own c r y s t a l l a t t i c e . The g r e a t advantage o f t h i s a p p r oach i s t h a t the geometry o f the r e a c t i v e m o l e c u l e s i s d e t e r -m i n a b l e by X - r a y d i f f r a c t i o n methods. S i n c e X f = 1, kj^(obs) e q u a l s the i n t r i n s i c r e a c t i v i t y o f the m o l e c u l a r c o n f o r m a t i o n i n the c r y s t a l . T h i s i n t r i n s i c r e a c t i v i t y i n t u r n depends on the hydrogen a b s t r a c t i o n geom-e t r y . S i n c e we a r e n o t aware o f any methods c a p a b l e o f d e t e r m i n i n g hydrogen a b s t r a c t i o n r a t e s i n s o l i d s , we have d e t e r m i n e d the hydrogen a b s t r a c t i o n r a t e c o n s t a n t s f o r f i v e a - c y c l o a l k y l - p - c h l o r o a c e t o p h e n o n e s i n s o l u t i o n and attempted to c o r r e l a t e them to the hydrogen a b s t r a c t i o n geometry d e r i v e d from X-ray c r y s t a l l o g r a p h y . 1 ^ 2 The r a t i o n a l e b e h i n d t h i s attempt i s p r e s e n t e d below. I t i s w e l l e s t a b l i s h e d , w i t h few e x c e p t i o n s , t h a t o r g a n i c and b i o m o l e c u l e s c r y s t a l l i z e i n t h e i r l o w e s t energy conforma-t i o n s . > 1 7 6 " 1 7 8 F o r example, u s i n g ECEPP/2 ( e m p i r i c a l c o n f o r m a t i o n a l energy program f o r p e p t i d e s ) , 1 7 7 a Scheraga and h i s co-workers have shown t h a t out o f the s e v e r a l thousand s t a r t i n g c o n f o r m a t i o n s (-10,000) a v a i l a b l e f o r g r a m i c i d i n S, the r e s u l t i n g g l o b a l minimum-energy s t r u c -t u r e 1 7 7 1 ' was v e r y s i m i l a r to the s t r u c t u r e d e t e r m i n e d by X-ray c r y s t a l -- 105 -l o g r a p h y . 1 7 7 b > 1 7 8 An even more dramatic example comes from the computations in v o l v i n g the ( G l y - P r o - P r o ) p o l y p e p t i d e chain, which constitutes the basic unit of the protein, collagen. The atomic coordi-nates c a l c u l a t e d f or ( G l y - P r o - P r o ) b y the ECEPP/2 method compare well with those from the X-ray c r y s t a l structure. In f a c t , comparison of the atomic coordinates of the computed global-minimum-energy structure with those of the X-ray structure revealed that the two structures are superimposable. 1 7 9 As mentioned e a r l i e r , i t i s not only complex biomolecules that c r y s t a l l i z e i n minimum energy conformations, but also simple organic molecules. Evidence for t h i s statement comes both from previous studies conducted i n our l a b o r a t o r y 6 ^ as well as from the in v e s t i g a t i o n s of 1 80 other workers. o u In studying the s o l i d and s o l u t i o n state photochemis-t r y of the general skeleton cis-4a,5,8,8a-tetrahydronaphtho-quin-l-one-4-ol, i t was r e a l i z e d that these molecules c r y s t a l l i z e exclu-s i v e l y i n the lowest energy conformation predicted by the conformational analysis. The lowest energy conformations i n these molecules are deter-mined by the preference for the b u l k i e r substituent at C 4 to adopt the pseudo-equatorial p o s i t i o n (Scheme 3 6 ) . 6 ^ e Dunitz has shown that out of many conformations possible f o r cyclodecane, one occurred i n a wide v a r i e t y of c r y s t a l l i n e d e r i v a t i v e s , 1 8 0 and f o r c e - f i e l d c a l c u l a t i o n s performed by Ermer have shown i t to be the most stable conformer for c y c l o d e c a n e . 1 8 1 I t i s c l e a r from the work of L e w i s 1 ^ 7 and A l e x a n d e r 1 8 2 that the r a p i d r i n g motions of most cycloalkanes allow conformational e q u i l i b r a -t i o n to be established before excited-state decay. For example, - 106 -Scheme 36: Stable conformations adopted by enone-alcohols. Alexander and Uliana investigated the photochemistry of several benzoyl-cyclobutanes with d i f f e r e n t substituents on the phenyl r i n g that are known to modify the t r i p l e t r e a c t i v i t y and found a l i n e a r r e l a t i o n s h i p between quantum y i e l d and i n t r i n s i c t r i p l e t r e a c t i v i t y (kjj). This l i n e a r i t y was interpreted to indicate an excited state conformational equilibrium c o n t r o l over the quantum e f f i c i e n c y . A ground-state c o n t r o l over quantum e f f i c i e n c y would have r e s u l t e d i n quantum y i e l d s that are p a r t i a l l y dependent of k H. The other i n t e r e s t i n g information that could be derived from t h i s study was the determination of the magnitude of the conformational equilibrium constant that i s too small to be measured by any conventional techniques. This was achieved by using the abstraction rate constant f or exo-5-benzoylbicyclo[2.1.l]hexane that serves as an 107 a p p r o p r i a t e model f o r the r e a c t i v e conformer o f b e n z o y l c y c l o b u t a n e and by a n a l y s i s o f the o b s e r v e d k i n e t i c s u s i n g e q u a t i o n 1 gave a v a l u e f o r X f * c l o s e to 1 0 - 5 . 1 8 2 S i n c e c o n f o r m a t i o n a l e q u i l i b r i u m i s a t t a i n e d b e f o r e the e x c i t e d s t a t e decay i n c y c l o a l k a n e s and hence i n a - c y c l o a l k y l a c e t o p h e n o n e s , and s i n c e o r g a n i c m o l e c u l e s c r y s t a l l i z e i n t h e i r l o w e s t energy conforma-t i o n s , the kjj(obs) d e t e r m i n e d i n the s o l u t i o n s h o u l d r e f l e c t the i n t r i n s i c r e a c t i v i t y o f the l o w e s t energy conformer, p r o v i d e d the r e a c t i o n o c c u r s p r e d o m i n a n t l y from t h i s conformer, making X f n e a r l y 1. I n t r i n s i c r e a c t i v i t y i s i n t u r n dependent on the d i s t a n c e and a n g u l a r r e l a t i o n s h i p between the 7-hydrogen and c a r b o n y l oxygen. I t i s e x p e c t e d t h a t the r a t e o f hydrogen a b s t r a c t i o n s h o u l d d e c r e a s e w i t h an i n c r e a s e i n d, the d i s t a n c e between oxygen and hydrogen, and as A and r , the a b s t r a c t i o n a n g l e s , d e v i a t e from the i d e a l v a l u e s o f 90-120° and 0°, r e s p e c t i v e l y ( F i g . 3, page 34). The i d e a t h a t the c o n f o r m a t i o n p r e s e n t i n the c r y s t a l i s a l s o the predominant one i n s o l u t i o n owing to i t s thermodynamic s t a b i l i t y s h o u l d be t r e a t e d r a t h e r c a u t i o u s l y , as the o c c u r r e n c e o f dimorphs such as the n e e d l e and p l a t e m o d i f i c a t i o n s i n a - a damantyl-p-chloroacetophenone (54n and 54p), w i t h s i g n i f i c a n t l y d i f f e r e n t a b s t r a c t i o n g e o m e t r i e s , a r e not t h a t r a r e . 1 8 3 However, as D u n i t z p o i n t e d o u t , 1 7 6 one can be r e a s o n a b l y s u r e t h a t the c o n f o r m a t i o n p r e s e n t i n the s o l i d s t a t e i s a l s o the predominant conformer (perhaps n o t e x c l u s i v e ) i n the s o l u t i o n i f the same c o n f o r m a t i o n o f a m o l e c u l e , o r a p a r t o f one, i s found i n h a l f a dozen d i f f e r e n t c r y s t a l l i n e environments. T h i s i s p r e c i s e l y the k i n d of s i t u a t i o n we have e n c o u n t e r e d i n s t u d y i n g the a - c y c l o a l k y l a c e t o p h e -108 nones, whose b a s i c c o n f o r m a t i o n was found to be v e r y s i m i l a r i n a l l the d e r i v a t i v e s f o r which c r y s t a l s t r u c t u r e s were det e r m i n e d . I n a d d i t i o n , m o l e c u l a r mechanics c a l c u l a t i o n s p e r f o r m e d by Dr. S a r a A r i e l u s i n g the MMP2 p r o g r a m 1 8 ^ f o r a - c y c l o h e x y l - p - c h l o r o a c e t o p h e n o n e (28) s u p p o r t the assumption t h a t the c o n f o r m a t i o n p r e s e n t i n the s o l i d s t a t e i s the minimum energy c o n f o r m a t i o n . S t a r t i n g w i t h the o r i g i n a l c r y s t a l s t r u c t u r e c o o r d i n a t e s (0°), i n c r e m e n t a l 20° r o t a t i o n s were a p p l i e d t o the C 7 - C 3 and Cg-Cg c a r b o n - c a r b o n bonds i n c l o c k w i s e and c o u n t e r - c l o c k w i s e d i r e c t i o n s and the energy was m i n i m i z e d on the intramo-l e c u l a r c o o r d i n a t e s . The r e s u l t s ( T a b l e XX) i n d i c a t e t h a t the conforma-t i o n and the hydrogen a b s t r a c t i o n geometry d e t e r m i n e d by X - r a y c r y s t a l -l o g r a p h y i n d e e d c o r r e s p o n d to the minimum-energy s i t u a t i o n . To e s t a b l i s h a 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 between the hydrogen a b s t r a c t i o n r a t e c o n s t a n t s i n s o l u t i o n and the a b s t r a c t i o n g e o m e t r i e s , the hydrogen a b s t r a c t i o n r a t e c o n s t a n t s were d e t e r m i n e d i n benzene s o l u t i o n f o r p - c h l o r o d e r i v a t i v e s o f c y c l o h e x y l (28), c y c l o p e n -t y l (38), c y c l o b u t y l ( 4 5 ) , c y c l o h e p t y l (50) and c y c l o o c t y l (53) acetophenone employing s t a n d a r d Stern-Volmer techniques-'- 8 5 ( F i g . 15, page 110) w i t h 2,5-dimethyl-2,4-hexadiene as the quencher. A l s o d e t e r -mined were the quantum y i e l d s i n benzene as w e l l as i n aqueous a c e t o n i -t r i l e s o l u t i o n s ( T a b l e XXI, page 111). The o b s e r v e d i n c r e a s e i n the quantum y i e l d f o r p r o d u c t f o r m a t i o n i n aqueous a c e t o n i t r i l e has been n o t e d b e f o r e and was a t t r i b u t e d t o the i n h i b i t i o n o f the r e v e r s a l o f 1,4 b i r a d i c a l i n t e r m e d i a t e to ground s t a t e ketone by s o l v e n t hydrogen b o n d i n g to the b i r a d i c a l . 7 5 ' - ' - 2 0 I t i s i n t e r e s t i n g t h a t o n l y one o f the k e t o n e s , a - c y c l o h e x y l - p - c h l o r o a c e t o p h e n o n e (28), i n v e s t i g a t e d i n t h i s 1 0 9 Table XX: MMP2 Calculations Performed on a-cyclohexyl-p-chloro-acetophenone, 28. 0 1 0 2 1 - 7 - 8 - 9 7 - 8 - 9 - 1 0 d A T E t o t a l (°) ( ° ) (°) ( ° ) ( A ) (°) ( ° ) (kcai/mo s a 0 0 - 1 7 4 . 9 7 1 . 4 2 . 5 9 6 4 2 9 0 1 8 . 2 8 M b - 1 7 2 . 8 6 9 . 8 2 . 5 8 9 4 5 9 2 7 . 9 3 S 2 0 0 - 1 7 4 . 8 5 1 . 5 2 . 1 3 5 3 4 1 0 1 2 0 . 0 8 M - 1 6 8 . 5 6 6 . 7 2 . 5 8 9 4 5 9 2 7 . 8 6 S - 2 0 0 - 1 7 4 . 9 9 1 . 7 3 . 1 2 8 4 3 8 0 1 9 . 6 2 M - 1 7 7 . 0 7 2 . 5 2 . 6 1 8 4 2 8 8 8 . 0 7 S 0 - 2 0 - 1 5 4 . 7 7 1 . 4 2 . 8 7 7 5 5 7 8 1 9 . 0 2 M - 1 6 2 . 0 6 7 . 7 2 . 6 3 3 5 3 8 7 7 . 8 1 S t a r t i n g values. b Minimized values. <f>\ = Rotation around Cg-Cq bond 4>2 = Rotation around Cy-Cg bond - 1 1 0 -Legend • C y c l o b u t y l d e r i v a t i v e ( 4 5 ) O C y c l o p e n t y l d e r i v a t i v e (38 ) • C y c l o h e x y l d e r i v a t i v e ( 2 8 ) • C y c l o h e p t y l d e r i v a t i v e (50 ) A C^cJ o o c t y l_de r i v a t i y e _ ( 5 3 ) _ A 0.00 0.02 0.04 0.06 0.08 0.10 0.12 0.14 Quencher Concen t ra t i on (Moles) 0.16 F i g u r e 1 5 : S t e r n - V o l m e r p l o t s . I l l Table XXI: Quantum y i e l d , K i n e t i c and S t r u c t u r a l Data f o r p-Chloro Substrates. Compound * C 6 H 6 $CH3CN kH(obs) (sec-1) d(A) TO AC) Q,Y^ 45 0.20 0.49 0.3 x 108 3.10 22.8 100.6 C l ^ ^ 38 0.29 0.62 1.2 x 108 2.80 31.0 96.0 C l ^ ^ 28 0.35 1.0 1.2 x 108 2.60 42.0 90.1 C l ^ ^ 50 0.25 0.76 5.7 x 10 8 2.71 41.8 82.4 C l ^ ^ 53 0.16 0.53 6.7 x 108 2.71 45.5 76.7 - 112 -s t u d y has a quantum y i e l d o f 1 i n a c e t o n i t r i l e . I t i s the same ketone which has the /?- and 7-hydrogens a t e q u a l d i s t a n c e s from the c a r b o n y l oxygen. The r e d u c e d quantum y i e l d i n the o t h e r ketones may a r i s e from u n p r o d u c t i v e ^-hydrogen a b s t r a c t i o n , as the /J-hydrogens a r e n e a r e r to the c a r b o n y l oxygen than the 7-hydrogens i n these k e t o n e s . The d a t a i n T a b l e XXI (page 111) r e v e a l no o b v i o u s r e l a t i o n s h i p between k ^ ( o b s ) and d, r and A. F o r example, a - c y c l o h e x y l (28) and a - c y c l o p e n t y l (38) d e r i v a t i v e s o f p - c h l o r o a c e t o p h e n o n e have i d e n t i c a l h ydrogen a b s t r a c t i o n r a t e c o n s t a n t s but v e r y d i f f e r e n t a b s t r a c t i o n g e o m e t r i e s . a - C y c l o h e p t y l (50) and a - c y c l o o c t y l - p - c h l o r o a c e t o p h e n o n e (53) r e a c t n e a r l y 5-6 times as f a s t a - c y c l o p e n t y l - p - c h l o r o a c e t o p h e n o n e (38), b u t have c o n s i d e r a b l y l e s s f a v o r a b l e a b s t r a c t i o n p a r a m e t e r s . As d i s c u s s e d i n the I n t r o d u c t i o n S e c t i o n , we t e s t e d f o r c o r r e l a -t i o n s between k^ and c o s 2 r and s i n 2 A . We a l s o sought a c o r r e l a t i o n between kjj and S, where S i s the S l a t e r o v e r l a p i n t e g r a l f o r the i n t e r a c t i o n between a hydrogen Is and an oxygen 2p atomic o r b i t a l . 1 8 6 A l l a t tempted c o r r e l a t i o n s , i n c l u d i n g v a r i o u s c o m b i n a t i o n s o f the parameters mentioned above, were u n s u c c e s s f u l . We i n t e r p r e t the absence o f such a c o r r e l a t i o n as s i g n i f y i n g a s u b s t a n t i a l c o n t r i b u t i o n t o the r a t e c o n s t a n t i n s o l u t i o n from non-minimum energy c o n f o r m a t i o n s w i t h more f a v o r a b l e a b s t r a c t i o n g e o m e t r i e s t h a n t h a t a v a i l a b l e f o r minimum energy c o n f o r m a t i o n s p r e s e n t i n the c r y s t a l . 1 7 5 P r e l i m i n a r y c a l c u l a t i o n s p e rformed by Dr. S a r a A r i e l f o r a - c y c l o h e x y l - p - c h l o r o a c e t o p h e n o n e (28) u s i n g a m o d i f i e d v e r s i o n o f CFF p r o g r a m 1 8 7 r e v e a l e d t h a t r o t a t i o n around C3-C9 (C a-Cg) bond i s most - 113 -1 1 1 1 1 I I i l l . -30--20-10* 0' 10- 20" 30' 40' 50* 60* 70* cw a,/?-rotation c c w — F i g u r e 16: V a r i a t i o n i n d, r , and A w i t h r o t a t i o n about the a, ( C o - C o ) bond. The 0° r o t a t i o n c o r r e s p o n d s t o the c r y s t a l conforma-t i o n shown. 114 -e f f e c t i v e i n r e d u c i n g d and i m p r o v i n g the r and A a n g l e s . R i n g i n v e r s i o n s and r o t a t i o n around the Cy-Cg bond are n o t as e f f e c t i v e i n i m p r o v i n g any g e o m e t r i c a l parameter f o r a b s t r a c t i o n . F i g u r e 16 (page 113) shows t h a t a c o u n t e r - c l o c k w i s e r o t a t i o n o f 52° around the Cg-Cq bond r e d u c e s the 0-•-H^ d i s t a n c e from 2.6 A to 1.8 A and improves T to a n e a r - i d e a l 4 ° . The A v a l u e remains i n the i d e a l range o f 90-120° f o r a b s t r a c t i o n . The same 52° r o t a t i o n , w h i l e a c h i e v i n g a b e t t e r geometry f o r a b s t r a c t i o n , i n c r e a s e s the t o t a l energy o f the system c o n s i d e r a b l y . M o l e c u l a r mechanics c a l c u l a t i o n s u s i n g a MMP2 program i n d i c a t e how the energy o f the system i n c r e a s e s as a f u n c t i o n o f r o t a t i o n around the Cg-Cq bond ( F i g . 17, page 115). I n c o n t r a s t to the l a c k o f c o r r e l a t i o n found between the s o l i d s t a t e g e o m e t r i c a l d a t a and the s o l u t i o n s t a t e hydrogen a b s t r a c t i o n r a t e c o n s t a n t s , the hydrogen a b s t r a c t i o n r a t e c o n s t a n t s resemble the w e l l -e s t a b l i s h e d f r e e r a d i c a l hydrogen a b s t r a c t i o n r e a c t i v i t y p a t t e r n , c y c l o o c t a n e > c y c l o h e p t a n e > c y c l o p e n t a n e = c y c l o h e x a n e > c y c l o b u -t a n e . 1 4 0 ' 1 8 8 - 1 8 9 T a b l e XXII compares our r e s u l t s w i t h the o t h e r b i m o l e c u l a r f r e e r a d i c a l hydrogen r e a c t i v i t i e s from the homologous c y c l o a l k a n e s e r i e s . The r e l a t i v e t r i p l e t s t a t e hydrogen a b s t r a c t i o n r a t e s f o r a-cy-c l o a l k y l a c e t o p h e n o n e s a l s o p a r a l l e l the t r e n d found i n a - c y c l o a l k o x y a c e -tophenones ( F i g . 1 8 , page 117) The a b s t r a c t i o n r a t e s found i n the * A n o t h e r f a c t o r t h a t can be c o n s i d e r e d to e x p l a i n the enhanced r e a c t i v i t y i n a - c y c l o a l k o x y a c e t o p h e n o n e s compared to a - c y c l o a l -k y l a c e t o p h e n o n e s i s the absence o f methylene e c l i p s i n g i n t e r a c t i o n s i n the six-membered t r a n s i t i o n s t a t e i n the former cas e . - 115 -13 CO o SH C D 80 7 0 -6 0 -5 0 -4 0 -30 2 0 -10-0 --10 -20 L e g e n d I Total Energy O van der Waals Energy • Torsional Energy • Other Energy V 0----O--O--0---O--O--O"0' ..0--0---0 T - 6 0 - 4 0 -20 0 20 40 60 80 Rota t ion (degrees) " ~ i 100 120 Figure 17: C g - C q Bond r o t a t i o n vs energy. 116 -Table XXII: Relative Hydrogen Abstraction Rate Constants from Cyclo-alkanes by Free Radicals. C y c l o a l k a n e C - H b o n d * energy ( K c a l / m o l ) a CH3« C 6 H 5 * CCI 35 d e our work Cl * • 96.5 0.25 o 94.5 1.2 1.2 1.6 1 1 0 95.5 1 1 1 1 O 92.5 1.5 1.8 3.3 4.8 ^ ^ unavai lable 2.2 2.0 9.2 5.6 2.7 * = bond energies from CRC Handbook ( R e f . 1 9 0 ) ° R e f . 1 4 0 b R e f . 1 8 8 a c R e f . 1 8 8 b <* R e f . •. 1 4 2 • R e f . 1 9 0 n r a t e c o n s t a n t 2 2 x 1 0 8 S e c " 1 3 3 x 1 0 9 S e c " 1 9 - 1 4 7 x 10 Sec 5 9 x 1 0 9 S e c " 1 F i g u r e 18 : Rates o f hydrogen a b s t r a c t i o n i n a - c y c l o a l k o x y a c e t o -phenones. l a t t e r s e r i e s a r e much l a r g e r t h a n i n the case o f the a - c y c l o a l k o x y a c e -tophenones because the hydrogens i n v o l v e d a r e t e r t i a r y and a r e n e x t to a r a d i c a l s t a b i l i z i n g o x y g e n . 7 5 The i n c r e a s e i n the r a t e w i t h the i n c r e a s e i n the c y c l o a l k a n e r i n g s i z e was i n t e r p r e t e d t o be a r e s u l t o f the lower a c t i v a t i o n energy r e q u i r e d i n the h o m o l y s i s o f C-H bonds i n l a r g e r r i n g c y c l o a l k a n e s . ^ 0 There a r e s e v e r a l examples i n the l i t e r a t u r e t h a t p r o v i d e e v i d e n c e f o r the dependence o f t r i p l e t s t a t e hydrogen a b s t r a c t i o n r a t e s on C-H bond s t r e n g t h . 7 5 ' 7 6 ' 3 The absence o f any co r r e s p o n d e n c e between minimum energy conforma-t i o n s and o b s e r v e d a b s t r a c t i o n r a t e s , and more i m p o r t a n t l y , the p o s i t i v e c o r r e l a t i o n found between the b i m o l e c u l a r & u n i m o l e c u l a r hydrogen - 118 a b s t r a c t i o n r a t e c o n s t a n t s c o n v i n c i n g l y argue f o r a p r o c e s s i n which the r e a c t a n t m o l e c u l e s e x p l o r e many a b s t r a c t i o n g e o m e t r i e s d u r i n g t h e i r e x c i t e d s t a t e l i f e t i m e s . 6. The P h o t o c h e m i s t r y o f a-Adamantylacetophenones Of the v a r i o u s ways i n which a c r y s t a l l i n e environment i n f l u e n c e s p h o t o r e a c t i v i t y , one o f the most i n t r i g u i n g i n v o l v e s i t s e f f e c t on the p a r t i t i o n i n g o f a 1 , 4 - b i r a d i c a l . I t has been d i s c u s s e d i n the p r e c e d i n g c h a p t e r s how the c r y s t a l l a t t i c e a l t e r s the c o m p e t i t i o n between the c l e a v a g e and c l o s u r e pathways o f the b i r a d i c a l i n f a v o r o f c l e a v a g e i n c y c l o h e x y l d e r i v a t i v e s 6 ^ and c l o s u r e i n c y c l o h e p t y l and c y c l o o c t y l d e r i v a t i v e s o f acetophenone. The s t u d y o f a-adamantylacetophenones was u n d e r t a k e n w i t h the g o a l o f s p e c i f i c a l l y examining the e f f e c t o f the c r y s t a l l i n e environment on the s t e r e o s e l e c t i v i t y o f c y c l o b u t a n o l f o r m a t i o n i n the N o r r i s h type II r e a c t i o n . a-Adamantylacetophenone and i t s d e r i v a t i v e s comprise an i d e a l system f o r such a study, as a-adamantylacetone-^O > ^ 1 a n ^ a-adamantylacetophenone 1 1-'- were r e p o r t e d t o undergo e x c l u s i v e c y c l i z a t i o n upon i r r a d i a t i o n i n i s o t r o p i c l i q u i d media. G a g o s i a n e t a l . have o b s e r v e d t h a t the i r r a d i a t i o n o f a-adamantyl acetone (72) i n the s o l u t i o n s t a t e l e a d s to two i s o m e r i c c y c l o b u t a n o l s i n q u a n t i t a t i v e y i e l d . ^ 0 ' - ^ l N e i t h e r o f the p h o t o e l i m i n a t i o n p r o d u c t s , acetone o r adamantene was found owing to the p r o h i b i t i v e s t r a i n energy i n v o l v e d i n the f o r m a t i o n o f the c l e a v a g e p r o d u c t , adamantene ( an - 119 -anti-Bredt o l e f i n - 1 - ^ ) . The absence of eli m i n a t i o n products was also a t t r i b u t e d p a r t i a l l y to the i n a b i l i t y of the b i r a d i c a l 73 generated a f t e r the 7-hydrogen abstraction to undergo cleavage. S p e c i f i c a l l y , the Ca-Cp bond i n the b i r a d i c a l 73 i s held i n a r i g i d p o s i t i o n that i s nearly orthogonal to the p - o r b i t a l on the adamantane r i n g r e s u l t i n g i n a very poor overlap between the p - o r b i t a l and the C Q-C^ bond (Scheme 37.) Scheme 37: Photochemistry of a-adamantylacetone, 72. - 120 -However, Gano and E i z e n b e r g have r e p o r t e d 3-6% adamantene from the p h o t o l y s i s o f 1-adamantyl and 2-adamantyl p h n y l a c e t a t e s . 1 ^ The h i g h e r s i n g l e t e x c i t a t i o n energy o f e s t e r s was quoted as a p o s s i b l e f a c t o r to e x p l a i n the d i f f e r e n c e s i n the p h o t o b e h a v i o r o f a-adamantylacetone and adamantyl p h e n y l a c e t a t e s . The i r r a d i a t i o n o f a-adamantylacetophenone i n s o l u t i o n media r e s u l t s e x c l u s i v e l y i n c y c l i z a t i o n p r o d u c t s , but u n l i k e a-adamantylace-tone, i t i s a c r y s t a l l i n e s o l i d w i t h a mp o f 64-65° C . m T h e r e f o r e , the s u b s t r a t e s chosen f o r our s t u d y are a-adamantyl acetophenone and d e r i v a t i v e s o f i t w i t h s u b s t i t u e n t s a t the p a r a p o s i t i o n o f the p h e n y l group. Four such d e r i v a t i v e s were s y n t h e s i z e d by the F r i e d e l - C r a f t s method, and t h e i r p h o t o c h e m i c a l p r o p e r t i e s were i n v e s t i g a t e d i n benzene, m o i s t a c e t o n i t r i l e and c r y s t a l s . The p h o t o p r o d u c t s , two c y c l o b u t a n o l s ( c i s - and t r a n s - ) i n each case ( e x c e p t f o r the p-OCHj d e r i v a t i v e ) , were s e p a r a t e d by column chromatog-raphy and c h a r a c t i z e d by c o n v e n t i o n a l s p e c t r o s c o p i c methods and elemen-t a l a n a l y s e s . I n the case o f P-OCH3 d e r i v a t i v e 56, i r r a d i a t i o n f o l l o w e d by gas chromatogaphic a n a l y s i s showed two peaks i d e n t i f i e d as c y c l o b u t a -n o l s by G.C.M.S. Attempts to i s o l a t e t h e se two c y c l o b u t a n o l s by a s i l i c a g e l column y i e l d e d two p r o d u c t s , one o f which c o r r e s p o n d s to t r a n s - c y c l o b u t a n o l and the o t h e r , to a new compound. No m a t e r i a l c o r r e s p o n d i n g to c i s - c y c l o b u t a n o l c o u l d be i s o l a t e d . The i d e n t i t y o f The d e s i g n a t i o n t r a n s - c y c l o b u t a n o l i s g i v e n to the c y c l o b u t a n o l i n which the hydroxy group i s t r a n s to the a d j a c e n t r i n g j u n c t i o n h ydrogen atom as b e f o r e . - 123 -the new p r o d u c t was e s t a b l i s h e d as the d e h y d r a t i o n p r o d u c t 56d by p r o t o n ( F i g . 19) and 1 3 C NMR (Fi g . 2 0 ) s p e c t r o s c o p y . The pr e s e n c e o f a m o l e c u l a r p l a n e o f symmetry as e v i d e n c e d by 1 3 C NMR and 3 a l l y l i c p r o t o n s shown by the p r o t o n NMR c l e a r l y s u p p o r t the s u g g e s t e d s t r u c t u r e r a t h e r t h a n i t s r e g i o i s o m e r 56e, which l a c k s a p l a n e o f symmetry and would have shown one a l l y l i c and one v i n y l i c p r o t o n . The c y c l o b u t a n o l s 72c and 72t which r e s u l t from the i r r a d i a t i o n o f a-adamantylacetone a l s o d e h y d r a t e w i t h the same r e g i o s e l e c t i v i t y when r e f l u x e d i n benzene w i t h c a t a l y t i c amounts o f p - t o l u e n e s u l f o n i c a c i d . 1 3 1 The t r a n s - c y c l o b u t a n o l 56t o f the P-OCH3 d e r i v a t i v e a l s o r e a d i l y underwent d e h y d r a t i o n upon r e f l u x i n g i n s l i g h t l y a c i d i f i e d benzene o r even s t i r r i n g as a s o l u t i o n i n e t h e r o v e r s i l i c a g e l t o g i v e 56d. The v e r y f a c i l e d e h y d r a t i o n o f th e s e P-OCH3 c y c l o b u t a n o l s r e f l e c t s the s t a b i l i t y p r o v i d e d by the methoxy group t o the c a r b o c a t i o n 1 9 4 t h a t i s g e n e r a t e d i n the d e h y d r a t i o n p r o c e s s . The p r o t o n NMR s p e c t r a o f b o t h c i s - and t r a n s - c y c l o b u t a n o l s show an AB q u a r t e t f o r methylene p r o t o n s H a and H Q. However, the c y c l o b u t a n e -124-- 1 2 5 -methine H c appears as a broad s i n g l e t for the cis-isomer and as a doublet the trans - isomer. The broad doublet that appears at ~ 5 2 . 9 serves as a stereochemical marker to i d e n t i f y the trans-cyclobutanols i n t h i s s e r i e s . In addition, the stereochemistry of trans-cyclobutanol 56t Table XXIII: NMR Parameters of c i s - and trans-cyclobutanols. OH I H c H b + Protons cis-cyclobutanol trans -cyclobutanol H, 2 . 0 8 ( 1 . 9 5 ) 2 . 7 5 ( 2 . 6 5 ) 2 . 4 1 ( 2 . 5 ) 2 . 0 3 ( 2 . 1 ) 2 . 1 8 ( 2 . 2 ) 2 . 9 2 ( 2 . 9 ) CH 3 "a Hb 2 . 0 5 2 . 7 2 2 . 4 0 2 . 1 2 2 . 2 6 2 . 9 2 OCH^ H a  H b 2 . 1 2 2 . 2 1 2 . 9 3 C l H a Hb 2 . 0 7 2 . 7 1 2 . 3 8 2 . 1 1 2 . 2 3 2 . 8 9 The values i n parentheses are from Lewis et a l 1 1 1 - 126-which shows a c h a r a c t e r i s t i c doublet at 8 2.93 (see F i g . 2 1 , page 124) was confirmed by X-ray c rys t a l lography . The longer r e t e n t i o n times of the c i s - c y c l o b u t a n o l s on s i l i c a ge l due to the l e s s -h indered nature of the hydroxyl group and t h e i r lower melt ing points r e l a t i v e to the trans-cyclobutanols are cons i s tent with previous o b s e r v a t i o n s . 1 1 1 , 1 - ^ 1 The NMR s igna l s were ass igned for protons H a , H D and H c by comparing our cyc lobutanol spectra with those der ived from a-adamantylacetophenone (57). Assignments were made by L e w i s 1 1 1 (Table XXIII) for the cyclobutanols der ived from the i r r a d i a t i o n of a-adamantylacetophenone. The v a l i d i t y of these assignments were confirmed i n some cases by proton decoupl ing experiments (see Experimental ) . A) A Reversa l of S t e r e o s e l e c t i v i t y of Cyclobutanol Formation i n the  S o l i d State The s o l i d and s o l u t i o n media i r r a d i a t i o n r e s u l t s for p -H, P-CH3 and P-OCH3 de r iva t ive s were conducted i n benzene, moist a c e t o n i t r i l e and c r y s t a l s and are presented i n Table XXIV. Al so deter-mined were the quantum y i e l d s of cyc lobutanol formation for the P-OCH3 compound. The t o t a l quantum y i e l d us ing valerophenone actinometry was 0.08 i n benzene and increased to 0.12 i n aqueous a c e t o n i t r i l e . Such increases i n the quantum y i e l d accompanying i r r a d i a t i o n s i n po lar so lvents have been observed by other workers for photo ly s i s of Norr i sh II systems, and have been discussed i n the preceding chapters . The - 127 Table XXIV: Photochemistry of a-Adamantyl-p-substituted Acetophenones. X Compound Trans - C y c l o b u t a n o l (%) C i s - C y c l o b u t a n o l (%) Number S o l i d O.IM O.IM S o l i d O.IM O.IM S t a t e CH3CN S t a t e CH3CN C 6 H 6 H 57 77 69 75 23 31 25 CH 3 55 60 66 73 40 34 27 OCH 3 56 34 66 72 60 34 28 r e s u l t s i n T a b l e XXIV r e v e a l no s i g n i f i c a n t d i f f e r e n c e i n the c y c l o b u t a -n o l s t e r e o s e l e c t i v i t y between s o l i d and s o l u t i o n p h o t o l y s e s f o r the p-H and p-CH 3 d e r i v a t i v e s . However, t h e r e i s a complete r e v e r s a l o f c y c l o b u t a n o l s t e r e o s e l e c t i v i t y f o r the s o l i d s t a t e i r r a d i a t i o n o f the P-OCH3 d e r i v a t i v e compared t o the s o l u t i o n r e s u l t s . I n c o n t r a s t t o the s o l u t i o n r e s u l t s , which a f f o r d the l e s s h i n d e r e d t r a n s - c y c l o b u t a n o l as the major p r o d u c t , the s o l i d s t a t e i r r a d i a t i o n p r o v i d e s the more h i n -d e r e d c i s - c y c l o b u t a n o l as the major p h o t o p r o d u c t . 1 8 3 To probe the re a s o n s f o r t h i s d r a m a t i c r e v e r s a l , the c r y s t a l and m o l e c u l a r s t r u c t u r e s o f the p-H and P-OCH3 s u b s t r a t e s were determined. No c r y s t a l s s u i t a b l e f o r X - r a y c r y s t a l l o g r a p h y c o u l d be grown f o r the P-CH3 d e r i v a t i v e . The r e s u l t s show t h a t the c o n f o r m a t i o n adopted by - 128 -these molecules i s such that the equatorial 7-hydrogen (H e) i s most accessible and forms a six-atom c h a i r l i k e arrangement with the carbonyl oxygen and the intervening carbon atoms. This stands i n contrast to the b o a t l i k e and h a l f - c h a i r l i k e abstraction geometries observed i n the other a-cycloalkylacetophenones discussed previously. The distance of 2 . 5 - 2 . 8 A between H e and the carbonyl oxygen i s s i g n i f i c a n t l y l e s s than the range of 3 . 0 - 3 . 3 A for a x i a l H a (Table XXV). The angle r, by which the H e l i e s outside the mean plane of the carbonyl group, i s 4 6 - 6 2 ° and t h i s indicates the non-planar (r * 0 ° ) nature of the hydrogen abstraction. Turning to the medium dependent cyclobutanol s t e r e o s e l e c t i v i t y i n the i r r a d i a t ion of the p-OCH^ substrate (56), i f we make a reasonable assumption that the intermediate b i r a d i c a l has the same basic conforma-t i o n as i t s ketonic precursor, a possible explanation emerges to explain the phenomenon. The X-ray data reveal that the O^-CyCg-Cg dihedral angle i s 8 2 - 8 3 ° and indicate that the b i r a d i c a l r e s u l t i n g from abstrac-t i o n would have a 9 0 , 0 geometry ( the d i s p o s i t i o n of p - o r b i t a l s on Cj and C]^Q with respect to the Ca-Cp bond) as shown i n Scheme 3 8 ( b i r a d i c a l A, page 1 3 0 ) . This b i r a d i c a l i s born i n a conformation to y i e l d the more hindered cis-cyclobutanol upon closure. Isomerization of conforma-t i o n A by r o t a t i o n about Cy-Cg bond r e s u l t s i n conformation B, closure of which leads to the less hindered trans-cyclobutanol. The predominance of s t e r i c a l l y less-hindered trans-cyclobutanol i n the s o l u t i o n state i r r a d i a t i o n s of a l l a-adamantylacetophenones must r e f l e c t a preference for conformer B over A or a f a s t e r rate of c y c l i z a t i o n from conformer B or both. With regard to the complete r e v e r s a l of - 129 T a b l e XXV: Hydrogen A b s t r a c t i o n Parameters f o r a-Adamantyl-p-s u b s t i t u t e d Acetophenones. X Compound H e Number (d(A), r(°), A ( D ) ) (d(A), r(°), A(°)) H OCH 3 C l ( n e e d l e s ) C l ( p l a t e s ) 57 56 54n 54p 2.7 2.7 2.8 2.5 46 59 62 43 87 80 77 92 3.2 3.0 3.2 3.3 53 32 35 15 54 88 83 87 s t e r e o s e l e c t i v i t y o f c y c l o b u t a n o l f o r m a t i o n i n the s o l i d s t a t e f o r the P-OCH3 s u b s t r a t e , the p r e f e r e n t i a l f o r m a t i o n o f c i s - c y c l o b u t a n o l i n the s o l i d s t a t e appears l o g i c a l c o n s i d e r i n g the b u i l t - i n - b i a s o f b i r a d i c a l A towards c i s - c y c l o b u t a n o l f o r m a t i o n (Scheme 38). We su g g e s t t h a t such r e v e r s a l i s o n l y o b s e r v e d f o r the P-OCH3 d e r i v a t i v e because the c r y s t a l l a t t i c e r e t a r d a t i o n o f c o n f o r m a t i o n a l i s o m e r i z a t i o n i s pronounced o n l y i n t h i s c a s e . The reasons f o r t h i s become apparent i n examining the p a c k i n g diagrams o f the P-OCH3 and p-H compounds. The p a c k i n g diagram o f the P-OCH3 d e r i v a t i v e ( F i g . 22, page 131) shows t h a t the n e i g h b o r i n g 130 -Abstraction Dislonce He 2 . 6 6 & Ha 2.96 X H c 3 . 1 7 A A OCH. OH 5 6 c OH cis —cyclobutanol favored in solid state 5 6 1 trans —cyclobutanol favored in solution / 56d v<> 38: Medium dependent photochemistry of a-adamantyl-p-methoxy-acetophenone, 56. - 131 -molecules i n the c r y s t a l l a t t i c e have t h e i r aromatic rings stacked p a r a l l e l and that they would clash i n any attempted r o t a t i o n around the C y C g bond necessary to generate conformation B. Therefore, the c i s -Figure 22: Parallel packing of aromatic groups in 56. isomer i s formed predominantly i n the s o l i d state i r r a d i a t i o n of the P-OCH3 substrate. The absence of the p a r a l l e l arrangement of neighbor-ing aromatic rings i n other adamantyl systems explains the lack of v a r i a t i o n i n the cyclobutanol s e l e c t i v i t y with medium of i r r a d i a t i o n . Table XXVI l i s t s the interplanar, center-to-center, and o f f s e t distances between the aromatic groups as well as the separation distance between adamantyl and aromatic groups i n a-adamantylacetophenones. I t i s c l e a r from examinining the Table XXVI that the aromatic groups are packed much - 1 3 2 more c l o s e l y i n the P-OCH3 d e r i v a t i v e t h a n i n o t h e r adamantylacetophe-nones. Thus, the s o l i d s t a t e p h o t o c h e m i s t r y o f a-adamantvl acetophe- nones demonstrates the importance o f c r y s t a l p a c k i n g i n s t e e r i n g the  c o u r s e o f u n i m o l e c u l a r r e a c t i o n s . T a b l e XXVI. P a c k i n g Parameters f o r a-adamantylacetophenones. Compound O f f s e t I n t e r p l a n a r C e n t e r - t o - c e n t e r A r o m a t i c and d i s t a n c e (A) d i s t a n c e ( A ) d i s t a n c e between adamantyl group p-H, 57 -- 5 . 8 5 . 9 P-OCH3, 56 2 . 1 3 . 6 4 . 2 6 . 0 p - C l , 57n -- -- 5 . 3 5 . 8 p - C l , 57p 3 . 1 3 . 5 4.7 6 . 2 * = O f f s e t d i s t a n c e between the n e i g h b o r i n g a r o m a t i c groups. A comparison o f our r e s u l t s w i t h those o b t a i n e d by G a g o s i a n e t a l . f o r the p h o t o r e a c t i o n o f a - a d a m a n t y l a c e t o n e 1 3 0 • 1 3 1 c o n s t i t u t e s a f u r t h e r p o i n t o f i n t e r e s t i n t h i s s t u d y . G a g o s i a n e t a l . i r r a d i a t e d a-adamantylacetone i n benzene and methanol w i t h s u f f i c i e n t 1 , 3 - p e n t a d i e n e added to quench a l l the T^ r e a c t i o n . The quenchable and non-quenchable f r a c t i o n s o f c y c l o b u t a n o l f o r m a t i o n were a s s i g n e d to the T]_ and r e a c t i o n s , r e s p e c t i v e l y . The v a l u e s a r e p r e s e n t e d i n T a b l e XXVII. - 133 -Table XXVII. M u l t i p l i c i t y Dependent Photochemistry of a-adamantylace-tone (72). 72c 72t R = C H 3 Solvent Excited state ^72c / ^72 Benzene S^ ^ g T1 1.0 Both 3.3 Methanol S^ 5.1 T x 1.8 Both 2.3 In order to explain the multiplicity-dependent photochemistry of a-adamantylacetone, they have assumed the abstra c t i o n of 7-hydrogen, (H x). Abstraction followed by r e h y b r i d i z a t i o n 1 1 1 of the 7-carbon from sp-3 to sp^ y i e l d s b i r a d i c a l 73 (Scheme 37, page 119). This b i r a d i c a l has two pathways, the minimum motion pathway a that would lead to the cis - c y c l o b u t a n o l (72c) and the more motion pathway b generating the trans-cyclobutanol (72t). As the motions required f o r the formation of cis-cyclobutanol (pathway a) are less than that required to form 134 -t r a n s - c y c l o b u t a n o l (pathway b ) , the b i r a d i c a l can be c o n s i d e r e d t o have a b u i l t - i n p r e f e r e n c e f o r c i s - c y c l o b u t a n o l f o r m a t i o n . However, the h i g h s t e r e o s e l e c t i v i t i e s i n f a v o r o f c i s - c y c l o b u t a n o l s i n the S^ ( s i n g l e t ) s t a t e i s l o s t i n the ( t r i p l e t ) s t a t e . T h i s i s because the s i n g l e t 1 , 4 - b i r a d i c a l i s q u i t e s h o r t - l i v e d and hence r g R ( b i r a d i c a l l i f e t i m e ) < T bond r o t a t i o n - ^he l o w s t e r e o s e l e c t i v i t y i n the T^ s t a t e i s due to the l o n g e r l i f e t i m e o f 1 , 4 - b i r a d i c a l , which a l l o w s many bond r o t a t i o n s b e f o r e c l o s u r e , thus d i l u t i n g the b i r a d i c a l ' s i n i t i a l p r e f e r e n c e f o r c l o s u r e t o g i v e c i s - c y c l o b u t a n o l . The p r e f e r e n c e f o r c i s - c y c l o b u t a n o l f o r m a t i o n i n a-adamantyl-acetone can a l s o be accommodated n i c e l y u s i n g c o n f o r m a t i o n A (Scheme 38, page 130). The s h o r t e r l i f e t i m e o f conformer A i n the S^ s t a t e p r e c l u d e s i s o m e r i z a t i o n to B, thus r e s u l t i n g i n a r e l a t i v e l y l a r g e c i s / t r a n s r a t i o s . The c i s / t r a n s r a t i o from the l o n g e r l i v e d 1y s t a t e i s q u i t e low because o f the c o n f o r m a t i o n a l e q u i l i b r i u m between A and B. I t i s i n f o r m a t i v e to compare our r e s u l t s i n the a-adamantyl acetophenones w i t h those o b t a i n e d f o r a l k y l phenones by H r o v a t e t a l . i n l i q u i d c r y s t a l s 1 6 - ' - and f o r 5-nonanone by C a s a l e t a l . i n u r e a i n c l u s i o n c o m p l e x e s . 1 5 9 Both have r e p o r t e d an i n c r e a s e i n the f o r m a t i o n o f the l e s s h i n d e r e d t r a n s - c y c l o b u t a n o l i n the o r g a n i z e d media. T h i s i s i n c o n t r a s t t o the p r e s e n t s t u d y as w e l l as our s t u d y o f the N o r r i s h type I I r e a c t i o n i n h o s t D i a n i n ' s c o m p o u n d , 1 6 0 which show l i t t l e v a r i a t i o n i n c y c l o b u t a n o l s t e r e o s e l e c t i v i t y ( e x c e p t i n ketone 56) as a f u n c t i o n of medium. C l e a r l y , a l l o r g a n i z e d media do n o t e x e r t the same i n f l u e n c e . 135 -B) R e a c t i v i t y Differences Between Polymorphs The phenomenon by which a substance c r y s t a l l i z e s i n d i f f e r e n t c r y s t a l l o g r a p h i c unit c e l l s and/or space groups has been termed polymor-phism. When the molecules that make up an organic c r y s t a l pack d i f f e r -e n tly with d i f f e r e n t symmetry r e l a t i o n s h i p s , i t might be expected that these polymorphs should e x h i b i t d i f f e r e n t bimolecular r e a c t i v i t y i n the s o l i d state. A c l a s s i c example of such v a r i a t i o n i n bimolecular chemi-c a l r e a c t i v i t y with c r y s t a l packing was demonstrated elegantly by Schmidt and h i s co-workers i n t h e i r study of the photocycloadditions of the trimorphic cinnamic a c i d system.^ Molecules possessing conformational mobility may e x h i b i t s i g n i f i -c antly d i f f e r e n t molecular conformations i n d i f f e r e n t c r y s t a l modifica-tions because of v a r i a t i o n s i n the t o r s i o n a l parameters that define molecular conformation. Molecules possessing d i f f e r e n t conformations i n d i f f e r e n t polymorphs are termed conformational polymorphs, and the phenomenon has been c a l l e d "conformational polymorphism" by B e r n s t e i n . ^ Any v a r i a t i o n i n chemical r e a c t i v i t y associated with conformational polymorphs may be a consequence not only of d i f f e r e n t molecular packing i n polymorphs but of conformational differences as w e l l . Polymorphs e x h i b i t i n g d i f f e r e n t bimolecular photochemical r e a c t i -v i t y are numerous i n the l i t e r a t u r e . 1 ^ However, examples of changes i n p h o t o r e a c t i v i t y accompanying changes i n packing arrangement or conforma-t i o n f o r unimolecular processes are extremely r a r e . ^ 1 To the best of our knowledge there i s only one report i n the l i t e r a t u r e that describes d i f f e r e n t unimolecular photochemical r e a c t i v i t y f o r polymorphs with some - 136 -c r y s t a l l o g r a p h i c d a t a . ^ 1 Cohen e t a l . found t h a t a n i l s o f s a l i c y l a l d e -hyde c r y s t a l l i z e i n two o r more m o d i f i c a t i o n s : the a-type, which i s p h o t o c h r o m i c and n o t thermochromic, and the y9-type, which i s themo-chromic, b u t n o t p h o t o c h r o m i c . ^ 1 However, no d e f i n i t e 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 was e s t a b l i s h e d f o r these compounds. A second i n v e s t i g a t i o n c o n c e r n e d w i t h the u n i m o l e c u l a r p h o t o r e a c t i o n o f dimorphs was by J a f f e e t a l . 1 ^ 6 These a u t h o r s s t u d i e d the f a t e o f the c y a n o i s o -p r o p y l r a d i c a l g e n e r a t e d i n p a i r s by the p h o t o l y s i s o f a z o b i s i s o b u t y r o -n i t r i l e (AIBN). However, the two c r y s t a l m o d i f i c a t i o n s o f AIBN, n e e d l e s and p l a t e s , r e a c t e d i d e n t i c a l l y i n s p i t e o f s i g n i f i c a n t d i f f e r e n c e s i n m o l e c u l a r c o n f o r m a t i o n and p a c k i n g . The p r e s e n t s t u d y d e s c r i b e s the d i f f e r e n t u n i m o l e c u l a r r e a c t i v i t y e x h i b i t e d by the dimorphs o f Q-adamantyl-p-chloroacetophenone (54). Based on the c r y s t a l and m o l e c u l a r s t r u c t u r e s o b t a i n e d f o r the dimorphs, the r e a c t i v i t y d i f f e r e n c e s between them are i n t e r p r e t e d as b e i n g due p r i m a r i l y t o c o n f o r m a t i o n a l r a t h e r t h a n p a c k i n g e f f e c t s . The d e t a i l e d  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 a r r i v e d a t i n t h i s s t u d y to e x p l a i n  the p h o t o c h e m i c a l r e a c t i v i t y a s s o c i a t e d w i t h the dimorphs are the f i r s t  o f t h e i r k i n d f o r a u n i m o l e c u l a r r e a c t i o n . a-Adamantyl-p-chloroacetophenone (54) c r y s t a l l i z e s from hexane to g i v e n e e d l e s (54n, space group P2]^/n) and from aqueous e t h a n o l to p r o v i d e p l a t e s (54p, space group C2/C) (see F i g . 23). P h o t o l y s i s o f 54 was c o n d u c t e d i n benzene, aqueous a c e t o n t r i l e and i n two c r y s t a l m o d i f i c a t i o n s . I r r a d i a t i o n r e s u l t e d e x c l u s i v e l y i n c y c l o b u t a n o l s 54c and 54t i n a l l media. The absence o f c l e a v a g e p r o d u c t s was n o t e d f o r o t h e r a-adamantylacetophenone d e r i v a t i v e s and has been i n t e r p r e t e d to be a - 137 -r e s u l t o f the p r o h i b i t i v e s t r a i n energy i n v o l v e d i n the f o r m a t i o n o f adamantene. The t o t a l type I I quantum y i e l d i s 0.05 i n benzene and 0.25 i n a c e t o n i t r i l e c o n t a i n i n g 2% water. Quenching s t u d i e s were pe r f o r m e d i n benzene u s i n g 2,5-dimethyl-2,4-hexadiene as the t r i p l e t quencher. Quenching s t u d i e s y i e l d e d a l i n e a r Stern-Volmer p l o t w i t h a kqr ( s l o p e ) o f 42.3 M"1. The r e s u l t s o b t a i n e d i n p h o t o l y z i n g 54 i n d i f f e r e n t media have been summarized i n T a b l e XXVIII The r e p o r t e d s o l i d s t a t e r a t i o s a r e the r e s u l t o f e x t r a p o l a t i o n to 0% c o n v e r s i o n . There i s no e f f e c t o f lower-i n g the p h o t o l y s i s temperature on the p r o d u c t r a t i o s s u g g e s t i n g t h a t Table XXVIII: Photoproduct Ratios as a Function of Reaction Medium. R e a c t i o n Medium c i s : t r a n s - C y c l o b u t a n o l R a t i o benzene (0.1 M) 27:73 m o i s t a c e t o n i t r i l e (0.1 M) 36:64 dimorph 54n ( n e e d l e s ) 26:74 dimorph 54p ( p l a t e s ) 0:100 sample m e l t i n g w i t h c o n c o m i t a n t l o s s o f t o p o c h e m i c a l c o n t r o l i s unimpor-t a n t . However, h i g h e r c o n v e r s i o n s to p r o d u c t s do resemble the s o l u t i o n s t a t e b e h a v i o r i n the case o f the p l a t e m o d i f i c a t i o n ( F i g . 24, page 139) . -138-F l g u r e 23: Photograph of p l a t e s and n e e d l e s m o d i f i c a t i o n o f a-adaman-t y l - p - c h l o r o acetophenone c r y s t a l s . - 139 -Figure 24: Percentage of conversion vs r a t i o of cis-cyclobutanol i n s o l i d state i r r a d i a t i o n of 54p. - 140 The p h o t o p r o d u c t r a t i o s i n d i c a t e t h a t the r e a c t i v i t y o f the n e e d l e c r y s t a l m o d i f i c a t i o n i s i d e n t i c a l w i t h i n e x p e r i m e n t a l e r r o r to t h a t o b t a i n e d i n benzene s o l u t i o n . The r e d u c e d s t e r e o s e l e c t i v i t y seen i n p o l a r media i s t y p i c a l o f the N o r r i s h type I I r e a c t i o n and has been d i s c u s s e d b e f o r e . The s t r i k i n g o b s e r v a t i o n i n the p r e s e n t r e s u l t s i s the t o t a l s t e r e o s e l e c t i v i t y o f c y c l o b u t a n o l f o r m a t i o n f o r the p l a t e - l i k e c r y s t a l m o d i f i c a t i o n . The s t e r e o d i a g r a m s o f the dimorphs r e v e a l t h a t the hydrogen a b s t r a c t i o n geometry i s c h a i r l i k e f o r b o t h , as o b s e r v e d f o r o t h e r d e r i v a t i v e s i n t h i s s e r i e s . However, the m o l e c u l a r c o n f o r m a t i o n i s q u i t e d i f f e r e n t i n the two m o d i f i c a t i o n s . I n the n e e d l e m o d i f i c a t i o n , which y i e l d s b o t h c i s - and t r a n s - c y c l o b u t a n o l s upon i r r a d i a t i o n , the a r o m a t i c r i n g exposes i t s f a c e t o the adamantane m o i e t y r e s u l t i n g i n a more c i s - l i k e r e l a t i o n s h i p between the two r i n g s . The f o r m a t i o n o f c i s - c y c l o b u t a n o l i s r e l a t i v e l y f a v o r a b l e from t h i s c o n f o r m a t i o n because o f the a l r e a d y e x i s t i n g c i s - l i k e r e l a t i o n s h i p between the a r o m a t i c and adamantane r i n g s ( F i g . 25, page 141), even though the l e s s h i n d e r e d t r a n s - c y c l o b u t a n o l i s s t i l l the major p r o d u c t . I n the p l a t e form, which p r o d u c e s t r a n s - c y c l o b u t a n o l s t e r e o s e l e c t i v e l y , the a r o m a t i c r i n g has an edge-on r e l a t i o n s h i p w i t h the adamantane moiet y because o f a 40° r o t a t i o n around the Cy ( c a r b o n y l c a r b o n ) - C ^ ( a r o m a t i c carbon) bond compared t o the c o n f o r m a t i o n p r e s e n t i n the n e e d l e form. T h i s r e s u l t s i n an i n c r e a s e d b i a s towards t r a n s - c y c l o b u t a n o l f o r m a t i o n , as the a r o m a t i c r i n g i s f o r c e d away from the adamantane r i n g . Moreover, one o f the o r t h o a r o m a t i c hydrogens i s wedged between a methylene hydrogen atom a d j a c e n t to the c a r b o n y l group (2.21 A) and an adamantyl hydrogen atom - 141 -Figure 25: Molecular conformation i n needle (54n) and plate (54p) modifications of a-adamantyl-p-chloroacetophnone (2.48 A). Any attempt to form c i s - c y c l o b u t a n o l from t h i s c o n f o r m a t i o n would d r i v e the o r t h o hydrogen i n t o the adamantane r i n g d e v e l o p i n g an i m p o s s i b l e s t e r i c s i t u a t i o n which cannot be r e l i e v e d by r o t a t i o n . Thus, the f o r m a t i o n o f c i s - c y c l o b u t a n o l i s h i g h l y u n f a v o r a b l e , r e s u l t i n g e x c l u s i v e l y i n t r a n s - c y c l o b u t a n o l from the p l a t e m o d i f i c a t i o n . T u r n i n g to the d i f f e r e n c e s i n p h o t o r e a c t i v i t y as w e l l as c r y s t a l -l o g r a p h y between the p - c h l o r o and p-methoxy analogues, the c o n f o r m a t i o n o f p-methoxy analogue (56) i s i n t e r m e d i a t e between the c o n f o r m a t i o n s p r e s e n t i n 54n and 54p. However, n e i t h e r 54n nor 54p pack such t h a t the a r o m a t i c groups o f the n e i g h b o r i n g m o l e c u l e s have a p a r a l l e l , o v e r l a p -- 142 -ping, face-to-face r e l a t i o n s h i p necessary for predominant c i s - c y c l o -butanol formation. A recent attempt i n our laboratory to engineer such p a r a l l e l packing of the neighboring aromatic rings by introducing two chloro groups on the aromatic r i n g of a-cyclopentylacetophenone was not s u c c e s s f u l . 1 9 7 The X-ray c r y s t a l structure revealed that the chlorine atoms of adjacent molecules are l a t e r a l l y , rather than v e r t i c a l l y , r e l a t e d to each other. Not s u r p r i s i n g l y , the photochemistry of t h i s molecule i n the s o l i d state d i d not show any preference f o r the forma-t i o n of c i s - c y c l o b u t a n o l . 7. S o l i d State Asymmetric Synthesis i n Unimolecular Reactions Asymmetric synthesis i n the s o l u t i o n state i s an area of intense a c t i v i t y , and several asymmetric synthetic methods have been developed for preparing o p t i c a l l y active compounds, but only under such asymmetric i n f l u e n c e s 1 9 8 as the use of c h i r a l reagents, a c t i v a t i o n on asymmetric c h i r a l surfaces, i n o p t i c a l l y active solvents or the photolysis with c i r c u l a r l y p o l a r i z e d l i g h t . 1 9 9 However, o p t i c a l l y active compounds can be generated i n the absence of any external c h i r a l influence from a c h i r a l s t a r t i n g materials by c r y s t a l l i z a t i o n i n a c h i r a l space group and subsequent trapping of t h i s c r y s t a l c h i r a l i t y i n a c o n f i g u r a t i o n a l l y stable e n t i t y by means of topochemically c o n t r o l l e d s o l i d state r e a c t i o n s . 8 ' 1 3 ' 1 6 Such a process of generating o p t i c a l a c t i v i t y i n the absence of any outside c h i r a l influence i s r e f e r r e d to as "absolute asymmetric synthesis" and was - 143 -c o n s i d e r e d by O s t r o m i s s l e n s k y as e a r l y as i n 1908.20° I t i s w e l l known t h a t a l l o p t i c a l l y pure compounds c r y s t a l l i z e i n c h i r a l space groups. I t i s l e s s g e n e r a l l y known t h a t many o p t i c a l l y i n a c t i v e s u b s t a n c e s ( i n c l u d i n g r a c e m i c m i x t u r e s ) a l s o form c h i r a l c r y s t a l s by c r y s t a l l i z i n g i n c h i r a l space groups. P a s t e u r ' s s e p a r a t i o n o f r a c e m i c sodium ammonium t a r t r a t e i n t o e n a n t i o m e r i c c r y s t a l s by v i r t u e o f t h e i r morphology i s one such famous e x a m p l e . 2 0 1 I n cases where enantiomers a r e r a p i d l y e q u i l i b r a t i n g under the c r y s t a l l i z a t i o n c o n d i -t i o n s , c r y s t a l l i z a t i o n may l e a d t o a c h e m i c a l l y i n t e r e s t i n g s i t u a t i o n . I t i s sometimes p o s s i b l e t o c o n v e r t the e n t i r e r a c e m i c sample t o c r y s -t a l s composed o f a s i n g l e enantiomer by c r y s t a l l i z a t i o n w i t h no e x t e r n a l asymmetric i n f l u e n c e . E l e g a n t examples o f t h i s "genuine spontaneous r e s o l u t i o n " have been p r o v i d e d by P i n c o c k 2 0 2 . 2 0 3 a n ( j H a v i n g a . 2 0 ^ S e v e r a l examples a r e known where m o l e c u l e s t h a t a r e a c h i r a l i n s o l u t i o n c r y s t a l l i z e i n c h i r a l space groups. T h i s c a n happen even when the i n d i v i d u a l m o l e c u l e has a p l a n e o f symmetry i n the c r y s t a l . 2 0 5 it i s a l s o p o s s i b l e t h a t a c r y s t a l can be c h i r a l and y e t c o n t a i n an e q u a l number o f o p t i c a l a n t i p o d e s . I n such c a s e s , the o p t i c a l a c t i v i t y r e s u l t s from the r e l a t i v e o r i e n t a t i o n s o f the m o l e c u l e s i n the c r y s t a l . 2 0 6 S t u d i e s c o n c e r n e d w i t h a b s o l u t e asymmetric s y n t h e s i s u t i l i z i n g c h i r a l c r y s t a l s o f a c h i r a l m o l e c u l e s a r e i m p o r t a n t n o t o n l y f o r the a t t r a c t i v e s y n t h e t i c methods they p r o v i d e , b u t a l s o f o r the i n s i g h t s t hey g i v e i n u n d e r s t a n d i n g the o r i g i n s o f o p t i c a l a c t i v i t y i n n a t u r e . 2 0 7 From the v i e w p o i n t o f asymmetric s y n t h e s i s , asymmetric i n d u c t i o n i s complete a f t e r the c r y s t a l l i z a t i o n o f the a c h i r a l m o l e c u l e i n a c h i r a l 144 -c r y s t a l ; s o l i d s t a t e r e a c t i o n merely t r a n s f o r m s the c r y s t a l c h i r a l i t y to m o l e c u l a r c h i r a l i t y by v i r t u e o f the asymmetric environment o f the r e a c t i o n c e n t r e i n the s o l i d m a t r i x . The c o n c e p t o f u s i n g c h i r a l c r y s t a l s o f a c h i r a l m o l e c u l e s to a c h i e v e a b s o l u t e asymmetric s y n t h e s i s has been r e a l i z e d by the o u t s t a n d i n g work o f the Weizmann I n s t i t u t e group on g a s / s o l i d r e a c t i o n s , 2 0 ® r e a c t i o n s i n i n c l u s i o n c o m p l e x e s 1 6 ' 2 0 ^ and s o l i d s t a t e [2+2] p h o t o c y c l o a d d i t i o n s . 2 1 0 I n the l a t t e r case, o p t i c a l y i e l d s as h i g h as 100% have been a c h i e v e d . 2 1 0 • 2 1 1 I n s p i t e o f i m p r e s s i v e s u c c e s s e s i n p r o d u c i n g c h i r a l compounds from a c h i r a l s t a r t i n g m a t e r i a l s v i a c h i r a l c r y s t a l s i n b i m o l e c u l a r r e a c t i o n s , no such asymmetric s y n t h e s i s i s r e p o r t e d f o r a u n i m o l e c u l a r photochemi-c a l r e a c t i o n . The s t u d y o f a-3-methyl-l-adamantylacetophenone (58) and  d i e s t e r 74 (Scheme 39) ar e the f i r s t examples o f u n i m o l e c u l a r . s o l i d  s t a t e p r o c e s s e s t h a t produce c h i r a l p r o d u c t s i n h i g h o p t i c a l y i e l d s upon  i r r a d i a t i o n o f t h e i r c h i r a l c r y s t a l s . 2 1 2 Compound 58 was p r e p a r e d from a - 3 - m e t h y l - l - a d a m a n t a n e a c e t y l c h l o r i d e and c h l o r o b e n z e n e by means o f F r i e d e l - C r a f t s a c y l a t i o n . The m o l e c u l e has a mean p l a n e o f symmetry (the C9-C17-C13 p l a n e ) i n s o l u t i o n as shown by i t s . ' ^ C NMR ( F i g . 26) b u t c r y s t a l l i z e s i n a c h i r a l space group P2^2]^2^ w i t h an asymmetric c o n f o r m a t i o n . Large p r i s m s o f t h i s compound w e i g h i n g as much as 300 mg c o u l d be grown from e t h a n o l ( F i g . 27, page 148. a l o n g w i t h a dime f o r c o m p a r i s o n ) . I r r a d i a t i o n s were con d u c t e d i n benzene, a c e t o n i t r i l e c o n t a i n i n g 2% water and c r y s t a l s . In a l l media, i r r a d i a t i o n s r e s u l t e d i n o n l y f o u r o f the s i x p o s s i b l e c y c l o b u t a n o l s . The c y c l o b u t a n o l s 58c, 58t, and 58t' (Scheme 40, page 147) were s e p a r a t e d from the a c e t o n i t r i l e p h o t o l y s i s m i x t u r e by s i l i c a - 145 hi/ Ar 58 crystal conformation Cl regio- and stereoisomers HO Photolysis Medium major solid state product (70%) Specific Rotat ion ee 92,2-1 2, Crystal Solution 21.6* 0 82% 0 iPr0 2 C / C0 2 iPr C0 2 iPr | C0 2 iPr hi/ <10% conversion 74 Photolysis Medium Specific Rotation ee Solution Pbca Crystal P2, 2 , 2, Crystal 0 0 24.2 ± 2.9' 0 0 100% Scheme 39: A b s o l u t e asymmetric s y n t h e s i s i n the s o l i d s t a t e . g e l column chromatography. The c y c l o b u t a n o l 58c' c o u l d n o t be i s o l a t e d i n pure form from a c e t o n i t r i l e i r r a d i a t i o n . However, o p t i c a l l y a c t i v e 58c' from the s o l i d s t a t e i r r a d i a t i o n c o u l d be i s o l a t e d i n pure form, as i t c o n s t i t u t e s 70% o f the p h o t o p r o d u c t s i n the s o l i d s t a t e i r r a d i a t i o n . The predominance o f 58t and 58t' (-80% o f the p h o t o p r o d u c t s ) i n the s o l u t i o n s t a t e i r r a d i a t i o n s , c o u p l e d w i t h t h e i r s h o r t e r r e t e n t i o n times on s i l i c a g e l , and the pr e s e n c e o f a c h a r a c t e r i s t i c d o u b l e t f o r H c a t 5 2 . 6 - 2 . 9 i n t h e i r p r o t o n N M R s p e c t r a , are a l l i n s u p p o r t o f t h e i r t r a n s -c y c l o b u t a n o l (hydroxy and c y c l o b u t a n e b r i d g e h e a d hydrogen a r e t r a n s to each o t h e r ) assignments. A h i g h e r f i e l d m ethyl resonance o f 6 0.51, gure 26: C NMR spectrum of o-3-methyl-l-adamantane-p-chloroacetophenone, 58. -148-F i g u r e 27: Photograph of c r y s t a l s of a-3-methyl-l-adamantane-p-chloro acetophenone, 58. - 149 -a p o s i t i v e enhancement i n the s i g n a l a t 5 7.34 c o r r e s p o n d i n g t o a r o m a t i c p r o t o n s upon i r r a d i a t i o n o f the methyl s i g n a l i n a NOE experiment, and i t s r e l a t i v e l y l o n g e r r e t e n t i o n time on s i l i c a g e l a r e a l l c o n s i s t e n t w i t h the a s s i g n e d s t r u c t u r e f o r 58c. The predominance o f 58c' and 5 8 t r i n the s o l i d s t a t e i r r a d i a t i o n ( n e a r l y 90%) s u p p l i e s v a l u a b l e i n f o r m a -t i o n about the r e g i o i s o m e r s , i n d i c a t i n g 58c' and 58t' s h o u l d c l o s e l y c o r r e s p o n d t o t h e s t a r t i n g ketone c o n f o r m a t i o n i n the s o l i d . The s o l i d s t a t e c o n f o r m a t i o n i s i d e a l l y s u i t e d t o g i v e these two c y c l o b u t a n o l s . The assignments o f p r o t o n s H a and H D were c o n f i r m e d i n each case ( e x c e p t 58c') by d e c o u p l i n g e x p e r i m e n t s . The s o l u t i o n i r r a d i a t i o n p r o d u c t s showed no t r a c e o f o p t i c a l a c t i v i t y . However, when s i n g l e c r y s t a l s o f 58 were p h o t o l y z e d a t low temperatures u s i n g e i t h e r a n i t r o g e n l a s e r or a 450 W mercury lamp and a n a l y z e d f o r o p t i c a l a c t i v i t y , s i g n i f i c a n t o p t i c a l r o t a t i o n s c o u l d be d e t e c t e d . The o p t i c a l a c t i v i t y g e n e r a t e d i n each case was d e t e r m i n e d by d i s s o l v i n g the i r r a d i a t e d samples i n c h l o r o f o r m and measuring t h e i r r o t a t i o n s a t the sodium D l i n e . The measured o p t i c a l r o t a t i o n s were the n c o n v e r t e d t o s p e c i f i c r o t a t i o n s from the weight o f the c r y s t a l and the p e r c e n t c o n v e r s i o n t o p r o d u c t s as det e r m i n e d by c a p i l l a r y gas chromatography. The u n r e a c t e d s t a r t i n g m a t e r i a l i s a c h i r a l i n s o l u t i o n and hence does n o t c o n t r i b u t e t o the o p t i c a l r o t a t i o n s . The c o n v e r s i o n s t o p r o d u c t i n the s o l i d s t a t e were v a r i e d from 10 to 15% and i n s o l u t i o n up t o 20%. Out o f the f o u r experiments performed i n the s o l i d s t a t e w i t h c r y s t a l s w e i g h i n g 15 to 313 mg, 3 samples were l e v o r o t a t o r y and one was d e x t r o r o t a t o r y ( T a b l e XXIX). The c y c l o b u t a n o l 58c', which c o n s t i t u t e s - 150 -70% o f the p h o t o p r o d u c t s , was i s o l a t e d from the i r r a d i a t i o n o f the Table XXIX: Generation of O p t i c a l A c t i v i t y i n S o l i d State I r r a d i a t i o n s . Experiment Weight o f the % C o n v e r s i o n S p e c i f i c R o t a t i o n c r y s t a l ( i n mg) (°) 1 15.6 14.5 -23.0 2 142.0 11.7 -16.7 3 313.0 8.1 -24.5 4 8.6 11.1 +22.7 313 mg c r y s t a l , and i t s e n a n t i o m e r i c p u r i t y was d e t e r m i n e d by the NMR c h i r a l s h i f t r e a g e n t E u ( h f c ) 3 . These c h i r a l s h i f t s t u d i e s were pe r f o r m e d a t 300 MHz and i n d i c a t e d an e n a n t i o m e r i c excess o f 82% by means o f r e s o l v i n g the a r o m a t i c p r o t o n s meta to the c h l o r o group. T a b l e XXX g i v e s AA6 v a l u e s ( e n a n t i o m e r i c s h i f t d i f f e r e n c e s ) w i t h r e s p e c t to the amount o f c h i r a l s h i f t r e a g e n t added to the t e s t sample. S i m i l a r c h i r a l s h i f t a d d i t i o n experiments performed, w i t h 58t t h a t was i s o l a t e d from s o l u t i o n s t a t e i r r a d i a t i o n s , d i d n o t r e v e a l any enan-t i o m e r i c e x cess as e x p e c t e d s i n c e the sample d i d n o t show any o p t i c a l r o t a t i o n i n the p o l a r i m e t e r . I n t e r e s t i n g l y , the c h i r a l s h i f t r e a g e n t a d d i t i o n r e s o l v e d n o t o n l y the a r o m a t i c p r o t o n s meta to the c h l o r o group b u t a l s o the d i s t a n t methyl group ( A A S v a l u e o f 0.02 a t 25 mg o f - 151 Table XXX: Enantiomeric S h i f t Differences (AAS). Compound Weight of Eu(hfc)3 Resonance observed mg AA5 (ppm) »a Ht 58c' 5.4 0.05 0.04 9.0 0.16 0.07 12.6 0.17 0.10 16.2 0.25 0.12 19.8 0.29 0.14 25.0 0.37 0.19 Eu(hfc)3 i n t e s t sample). This experiment indicates not only the racemic nature of the cyclobutanol but also sheds some l i g h t on i t s stereochemistry. The p a r t i a l l y resolved methyl s i g n a l i n t h i s case indicates that the s h i f t reagent binding s i t e , the hydroxyl group, and the methyl group are i n a syn r e l a t i o n s h i p . The absence of any resolu-t i o n i n the methyl s i g n a l of 58c' then implies an anti-arrangement of the hydroxyl and methyl groups. These observations further confirm the - 152 -s t r u c t u r e s a s s i g n e d f o r the c y c l o b u t a n o l s . The l e s s t h a n 100% e n a n t i o m e r i c excess o b s e r v e d i n the c r y s t a l i r r a d i a t i o n o f 58 compared to q u a n t i t a t i v e o p t i c a l y i e l d s o b t a i n e d i n the s o l i d s t a t e t r a n s f o r m a t i o n o f d i e s t e r 7 4 (Scheme 39, page 145) i s due to the v e r y low m e l t i n g p o i n t o f a - 3 - m e t h y l - l - a d a m a n t y l - p - c h l o r o -acetophenone (44-45°C). F o l l o w i n g i r r a d i a t i o n , the c r y s t a l s o f 58 were q u i t e s t i c k y ( F i g . 28), and the l e s s than q u a n t i t a t i v e o p t i c a l y i e l d i s a t t r i b u t e d t o p a r t i a l sample m e l t i n g accompanying the c o n v e r s i o n o f s t a r t i n g m a t e r i a l to the p h o t o p r o d u c t s . I n r e g a r d t o the l a r g e d i f f e r -ences i n the s t e r e o s e l e c t i v i t y o f c y c l o b u t a n o l f o r m a t i o n w i t h change i n the i r r a d i a t i o n medium, the answer comes from examining the c o n f o r m a t i o n o f the m o l e c u l e i n the c r y s t a l . The c o n f o r m a t i o n adopted i n the c r y s t a l by t h i s m o l e c u l e i s s i m i l a r t o t h a t o f the a - a d a m a n t y l - p - c h l o r o a c e t o -phenone n e e d l e m o d i f i c a t i o n (54n, F i g . 25, page 141). A b s t r a c t i o n o f H e s h o u l d be f a v o r e d o v e r H a b a s e d on the d i s t a n c e ( T a b l e XXXI), and the a n g l e r f o r H e i s 62°, q u i t e f a r o f f from the i d e a l v a l u e o f 0 ° . The a b s t r a c t i o n geometry i s c h a i r l i k e i n v o l v i n g H e, and the b i r a d i c a l r e s u l t i n g from the a b s t r a c t i o n w i l l have a 90,0 geometry as shown i n Scheme 40 and i s i d e a l l y p r e d i s p o s e d ( c o n f o r m a t i o n C, page 147) to form c i s - c y c l o b u t a n o l 58c' on c l o s u r e . F o r m a t i o n o f t r a n s - c y c l o b u t a n o l ( 5 8 t r ) r e q u i r e s a 180° r o t a t i o n around the C7-C3 bond to g i v e b i r a d i c a l D and i t s subsequent c l o s u r e . A r o t a t i o n o f the adamantane r i n g (Cg-Cg bond) i n C f o l l o w e d by d i r e c t c l o s u r e ( c o n f o r m a t i o n E) g i v e s 58t. A c o n f o r m a t i o n a l i s o m e r i z a t i o n around the Cy-Cg bond i n the b i r a d i c a l E r e s u l t s i n b i r a d i c a l F s u i t a b l e t o form p r o d u c t 58c upon c l o s u r e . S i n c e the c r y s t a l l a t t i c e r e s t r i c t s the c o n f o r m a t i o n a l i s o m e r i z a t i o n s -153-Figure 28: Crystals of a-3-methyl-l-adamantane-p-chloro-acetophenone,58 after irradiation. 1 5 4 -d e s c r i b e d above, r e g i o i s o m e r s 58c' and 58t' a r e formed i n p r e f e r e n c e o v e r 58c and 58t i n the s o l i d s t a t e . 58c' i s e s p e c i a l l y f a v o r e d , as the c o n f o r m a t i o n adopted by the ketone i n the c r y s t a l needs v e r y l i t t l e T a b l e XXXI: A b s t r a c t i o n Parameters f o r a - 3 - m e t h y l - l - a d a m a n t y l - p -c h l o r o a c e t o p h e n o n e , 58. H e H a D i s t a n c e , d(A) 2 . 7 3 . 1 r ( ° ) 6 2 3 6 A ( ° ) 7 7 8 3 r e o r g a n i z a t i o n t o form i t , hence i t i s a t o p o c h e m i c a l l y f a v o r e d p r o c e s s . S i n c e p r o c e s s e s i n s o l u t i o n a r e n o t s u b j e c t to l a t t i c e c o n s t r a i n t s and r a p i d i s o m e r i z a t i o n s a r e p o s s i b l e among d i f f e r e n t conformers i n s o l u -t i o n , the l e s s - h i n d e r e d t r a n s isomers 58t and 5 8 t ' a r e the major p r o d u c t s ( f a v o r e d ) i n s o l u t i o n . One f i n a l p o i n t o f d i s c u s s i o n i s the advantage o f " a b s o l u t e asym-m e t r i c s y n t h e s i s " s t u d i e s i n v o l v i n g u n i m o l e c u l a r p r o c e s s e s . Unimolecu-l a r r e a c t i o n s o f f e r a t l e a s t t h r e e major advantages over the c o r r e s p o n d -i n g b i m o l e c u l a r r e a c t i o n s . F i r s t , u n i m o l e c u l a r r e a c t i o n s do n o t r e q u i r e s p e c i f i c c r y s t a l p a c k i n g arrangements, and t h i s i n c r e a s e s the chances o f f i n d i n g a s u i t a b l e c h i r a l c r y s t a l s t r u c t u r e . Secondly, each c h e m i c a l event i n a b i m o l e c u l a r s o l i d s t a t e r e a c t i o n i n v o l v e s the d i s t u r b a n c e o f 155 -two l a t t i c e s i t e s r a t h e r t h a n one, and t h i s may l e a d t o a f a s t e r l o s s o f t o p o c h e m i c a l c o n t r o l , w i t h a c o r r e s p o n d i n g d e c r e a s e i n asymmetric i n d u c t i o n . T h i r d , u n i m o l e c u l a r r e a c t i o n s can be s t u d i e d i n media o t h e r t h a n the s o l i d s t a t e , namely, as i n c l u s i o n 1 5 9 > 2 1 3 compounds and i n s o l u t i o n . 1 9 9 8. P h o t o c h e m i c a l S t u d i e s i n D i a n i n ' s Compound The m o d i f i c a t i o n o f p h o t o c h e m i c a l r e a c t i v i t y t h r o u g h the use o f o r g a n i z e d media has been a m a t t e r o f c o n s i d e r a b l e a c t i v i t y i n r e c e n t y e a r s . The o r g a n i z e d media i n which p h o t o c h e m i c a l r e a c t i o n s were s t u d i e d i n c l u d e c r y s t a l s , 8 - 2 1 ' 8 9 ' 1 6 2 ' 1 6 3 l i q u i d c r y s t a l s , 1 1 8 • 1 6 1 m i c e l l e s , 1 5 6 ' 2 1 4 ' 2 1 5 m o n o l a y e r s , 1 5 6 and s u r f a c e s . 2 1 6 A n o t h e r medium which h o l d s g r e a t p o t e n t i a l i n a l t e r i n g p h o t o r e a c t i v i t y i s i n c l u s i o n complexes. Some o f the h o s t s t h a t have been u s e d r e c e n t l y f o r photo-c h e m i c a l s t u d i e s a r e t r i - o - t h y m o t i d e , 2 1 7 d e o x y c h o l i c a c i d , 2 1 8 u r e a , 1 5 9 1 , 1 , 6 , 6 - t e t r a p h e n y l - 2 , 4 - h e x a d i y n - 1 , 6 - d i o l , 2 1 9 and z e o l i t e m o l e c u l a r 220 221 s i e v e s . ' The h o s t chosen f o r the p r e s e n t i n v e s t i g a t i o n was D i a n i n ' s compound ( F i g . 2 9 ) . 1 2 0 The c h o i c e was based on t h r e e f a c t o r s : 1. D i a n i n ' s compound has been shown to form h o s t - g u e s t complexes w i t h a wide v a r i e t y o f o r g a n i c compounds i n c l u d i n g k e t o n e s , 2 2 2 2. the s o l i d h o s t - g u e s t complexes o f l i q u i d k etones w i t h D i a n i n ' s compound p r o v i d e an o p p o r t u n i t y f o r s t u d y i n g these ketones i n the s o l i d s t a t e , and - 156 -10 7 6 8 0 18 C H 3 13 O H 0 3 0 3 0 0 2 I I I I o 0 I 2 3 A 4 - p - h y d r o x y p h e n y l -2 , 2 , 4 - t r i m e t h y l c h r o m a n " c a g e " f o r m e d b y s i x m o l e c u l e s Figure 29: The Dianin's Compound and i t s cage. 3 . the comparison of the photochemical r e s u l t s from the i n c l u s i o n media with those obtained i n the s o l i d state f o r other s i m i l a r guest molecules should y i e l d u seful information about the con-s t r a i n t s imposed by the host. The complexes of Dianin's compound with a-cyclohexyl and a-cyclo-pentylacetophenone were prepared by d i s s o l v i n g the Dianin's compound i n an excess of l i q u i d ketone and by allowing f o r a slow c r y s t a l l i z a t i o n of the complex from the guest. The host/guest r a t i o s were determined by c a p i l l a r y gas chromatography. I r r a d i a t i o n s were conducted i n each case in benzene, a c e t o n i t r i l e with 2% water, and i n the i n c l u s i o n complexes. I r r a d i a t i o n s were also performed f or the guest ketones, a-cyclohexylace-tophenone and a-cyclopentylacetophenone at -40°C i n the form of frozen glasses. The i r r a d i a t i o n r e s u l t s as well as the host/guest r a t i o s are - 157 summarized i n T a b l e XXXII. F i r s t , the h o s t / g u e s t r a t i o s : X -ray c r y s t a l l o g r a p h y 2 2 3 ' 2 2 4 s t u d i e s on D i a n i n ' s compound r e v e a l e d t h a t s i x m o l e c u l e s o f 4-p-hydroxyphenyl 2 , 2 , 4 - t r i m e t h y l c h r o m a n form an h o u r g l a s s shaped cage ( F i g . 2 9 ) . The approximate l e n g t h o f t h i s h o u r g l a s s i s 11 A w i t h a m i d - p o i n t w i d t h o f 4.2 A and a maximum upper and lower w i d t h o f 6.3 A . The ends o f the cage a r e 2.8 A w i d e r and a r e made up o f 6 hyd r o x y groups o f s i x d i f f e r e n t chroman m o l e c u l e s . The cage was shown to i n c l u d e a l a r g e g u e s t o r two s m a l l m o l e c u l e s . 2 2 2 I f a l l c a v i t i e s i n the h o s t compound ar e f i l l e d w i t h the guest, a h o s t / g u e s t r a t i o o f 6 i s e x p e c t e d . The o b s e r v e d h o s t / g u e s t v a l u e o f 6 i n a - c y c l o h e x y l a c e t o p h e n o n e i n d i c a t e s t h a t a l l c a v i t i e s a r e f i l l e d w i t h the g u e s t s . The h i g h e r r a t i o o f 9 seen i n the c y c l o p e n t y l case i n d i c a t e s t h a t some o f the h o s t c a v i t i e s a r e n o t f i l l e d w i t h g u e s t s . T h i s might s u g g e s t t h a t t h e s e m o l e c u l e s were i n c l u d e d w i t h s m a l l d i s t o r t i o n i n the h o s t c r y s t a l l a t t i c e , thus i n c r e a s i n g the h o s t / g u e s t r a t i o . However a h o s t / g u e s t r a t i o o f 9 i s q u i t e normal f o r the i n c l u s i o n o f ketones i n D i a n i n ' s c o m p o u n d . 1 6 0 I n the case o f a - c y c l o h e x y l a c e t o p h e n o n e , s o l i d s t a t e magic a n g l e s p i n n i n g 1 3 C NMR was used t o determine i f the guest m o l e c u l e s were p r o p e r l y i n c l u d e d i n the h o s t c a v i t i e s . R i p m e e s t e r has shown t h a t the f o r m a t i o n o f h o s t / g u e s t complexes causes c e r t a i n c h a r a c t e r i s t i c changes i n the h o s t spectrum i n the complex as compared t o the "empty" f o r m . 2 2 5 S p e c i f i c a l l y , the c h e m i c a l s h i f t d i f f e r e n c e o f 5.7 ppm between the C^g and C^g m e t h y l groups i n the uncomplexed h o s t d e c r e a s e s t o 3.3-4.7 ppm i n the complex depending on the i n c l u d e d guest m o l e c u l e . The NMR spectrum ( F i g . 30) o f the i n c l u s i o n complex w i t h a - c y c l o h e x y l a c e t o - 158 -T a b l e XXXII: Host/Guest R a t i o s and P h o t o c h e m i s t r y o f I n c l u s i o n Complexes. Host/Guest r a t i o C l e a v a g e : C y c l i z a t i o n 0.1 M CH3CN 0.1 M C 6 H 6 G l a s s (-40°C) I n c l u s i o n complex ( s o l i d ) 33:67 34:66 36:64 52:48 92:8 93:7 93:7 100:0* t r a n s : c i s - C y c l o b u t a n o l 0.1 M CH3CN 0.1 M C 6 H 6 G l a s s (-40°C) I n c l u s i o n complex ( s o l i d ) 57:43 68:32 62:38 66:34 * No c y c l i z a t i o n p r o d u c t s c o u l d be d e t e c t e d i n the i r r a d i a t i o n o f C K - c y c l o p e n t y l a c e t o p h e n o n e complex w i t h D i a n i n ' s compound. 159 -phenone (37) shows the presence of two u p f i e l d methyl s i g n a l s . This might indi c a t e the presence of two non-equivalent complexation s i t e s . The chemical s h i f t differences of 4.0 ppm (major) and 3.4 ppm (minor) are consistent with f u l l complexation. "empty" Dianin's compound. Dianin's compound with host -cyclohexylacetophenone, 37. Figure 30: P a r t i a l 1 3 C CPMAS s o l i d state NMR spectrum of Dianin's compound with a-cyclohexylacetophenone, 37. Turning to the differences i n p h o t o r e a c t i v i t y caused by the i n c l u -sion i n the host l a t t i c e , i t i s c l e a r from Table XXXII that the trends observed i n i n c l u s i o n complexes resemble those obtained f o r s i m i l a r molecules i n the s o l i d state. S p e c i f i c a l l y , cleavage i s preferred, rather modestly, i n the host c a v i t i e s , as c y c l i z a t i o n i s a s t e r i c a l l y more demanding process under the r e l a t i v e l y r e s t r i c t e d environment of the host cages. Similar explanations were forwarded by us i n explaining the modest increases i n cleavage accompanying s o l i d state i r r a d i a t i o n s - 160 -o f a - c y c l o h e x y l a c e t o p h e n o n e s 6 8 • 2 2 6 and by T u r r o and W a n 2 2 0 to r a t i o n a l i z e the h i g h e r type I I c l e a v a g e s i n s i l i c a l i t e m o l e c u l a r s i e v e s . The t r a n s / c i s c y c l o b u t a n o l r a t i o o f 66:34 found i n the i n c l u s i o n complex f o r 37 compares w e l l w i t h 68:32 o b t a i n e d i n benzene i r r a d i a t i o n s . No s i g n i f i c a n t d i f f e r e n c e i n the s t e r e o s e l e c t i v i t y o f c y c l o b u t a n o l forma-t i o n was seen i n i r r a d i a t i n g o t h e r a - c y c l o h e x y l acetophenone s u b s t r a t e s i n the s o l i d s t a t e e i t h e r . 6 8 The s i m i l a r c y c l o b u t a n o l s t e r e o s e l e c t i v i -t i e s i n benzene and i n c l u s i o n complex i n d i c a t e the n o n - p o l a r n a t u r e o f the g u e s t c a v i t y . T h i s c o n c l u s i o n i s s u p p o r t e d by X - r a y c r y s t a l l o g r a -p h y 2 2 3 ' 2 2 4 which shows t h a t the major p o r t i o n o f the c a v i t y i s bound by h y d r o c a r b o n groups. I t i s i n t e r e s t i n g t o no t e t h a t the i r r a d i a t i o n o f a - c y c l o h e x y l (37) and a - c y c l o p e n t y l (44) acetophenones a t -40°C i n the form o f f r o z e n g l a s s e s does n o t cause any change i n the p h o t o r e a c t i v i t y compared t o the r e s u l t s i n i s o t r o p i c l i q u i d media. I t i s n o t n e c e s s a r y t h a t o t h e r i n c l u s i o n media i n f l u e n c e the N o r r i s h type I I r e a c t i o n i n the same way. F o r example, i r r a d i a t i o n s i n u r e a i n c l u s i o n c o m p l e x e s 1 5 9 f a v o r c y c l i z a t i o n over c l e a v a g e and c i s - c y c l o b u t a n o l over t r a n s - c y c l o b u t a n o l i n c o n t r a s t t o the o p p o s i t e e f f e c t i n z e o l i t e s . 2 2 0 In a v e r y r e c e n t p a p e r , 2 2 7 S i n g h e t a l . r e p o r t e d t h a t i r r a d i a t i o n o f a r a l k y l ketones as i n c l u s i o n complexes w i t h c y c l o -d e x t r i n s e x h i b i t e d a p r e f e r e n c e f o r c y c l i z a t i o n i n v a l e r o p h e n o n e and butyrophenone b u t a d e c r e a s e i n c y c l i z a t i o n f o r a and 7 s u b s t i t u t e d butyrophenones and v a l e r o p h e n o n e s . 161 -9. Geometric Requirements f o r Hydrogen Abstraction There are three main ways i n which a 7-hydrogen i s abstracted by an oxygen r a d i c a l . Each of these paths i s associated with a name reac t i o n and the ste r e o e l e c t r o n i c requirements f o r each of these reactions are examined i n the following pages. McLafferty rearrangement / u The e l e c t r o n impact-induced 7-hydrogen trans f e r to carbonyl oxygen attended by Ca-C^g bond cleavage i s termed the McLafferty rearrangement. I t has been mentioned previously i n the Introduction Section that the maximum allowable distance between the 7-hydrogen and oxygen atom i s 1.8 A based on the studies of Dje r a s s i on ketosteroids.® 5 The maximum allowable angle between the 7-hydrogen and the plane of the carbonyl group (defined as r) was suggested to be about 50° by Henion and Kingston.® 7 Thomas and Willhalm 2 2® have found i n t h e i r mass s p e c t r a l studies on exo and endo a c e t y l - and formylnorbornanes that only the endo epimers gave fragment ions (Scheme 41) corresponding to 7-hydrogen abstraction. Exo epimers, on the other hand, showed ions corresponding to the expul-sion of formyl and a c e t y l groups. In the case of the endo isomers, the minimum oxygen -•'hydrogen distance was estimated by Dreiding models to be 1.2 A and i n exo epimers the corresponding distance was 2 A (Scheme 41). - 162 -Similar conclusions were drawn from the mass s p e c t r a l s t u d i e s 2 2 9 on t r i c y c l i c keto-esters 75 and 76 (Scheme 42). The keto-ester 75 exh i b i t s an ion peak corresponding to the loss of the CH3OH from the molecular ion i n contrast to the loss of CH3O group from the molecular ion of 76. The loss of methanol only i n 75 was a t t r i b u t e d to the a v a i l a b i l i t y of a bridgehead t e r t i a r y gamma-hydrogen within 1.6 A. Scheme 41: McLafferty rearrangement of exo and endo a c e t y l - and formyl-norbornanes. In a se r i e s of gibberelins studied by Gray and P r y c e , 2 3 0 i t was discovered that c e r t a i n a c t i v a t e d 7-hydrogens are abstracted at distances greater than the suggested maximum of 1.8 A. For example, i n compound 77, the distance between the bridgehead t e r t i a r y hydrogen and oxygen was estimated to be over 2 A. The observed McLafferty rearrange-Scheme 43: McLafferty rearrangement of g i b b e r e l i n s . - 164 -merit i n t h i s compound was a t t r i b u t e d to the d e c r e a s e d C-H bond s t r e n g t h . The absence o f the i o n c o r r e s p o n d i n g to the l o s s o f CH3COOH i n 78 was t a k e n t o i n d i c a t e the t r a n s arrangement o f the b e n z y l i c t e r t i a r y h ydrogen and carbomethoxy groups (Scheme 43) . There are examples i n the l i t e r a t u r e 2 3 1 f o r the a b s t r a c t i o n o f a /9-hydrogen by a five-membered t r a n s i t i o n s t a t e and a 6-hydrogen by a seven-membered t r a n s i t i o n s t a t e . However, the d i s t a n c e r e q u i r e m e n t s f o r t h e s e a b s t r a c t i o n s were det e r m i n e d to be the same as t h a t f o r 7-hydrog-ens. The s t e r e o e l e c t r o n i c r e q u i r e m e n t s f o r the M c L a f f e r t y rearrangement were i n v e s t i g a t e d u s i n g a n o n - e m p i r i c a l m o l e c u l a r o r b i t a l method by Boer e t a l . 1 5 1 T h e i r c a l c u l a t i o n s r e v e a l , f o r the c o n f o r m a t i o n a l l y f l e x i b l e 2-pentanone, a p r e f e r e n c e f o r the p l a n a r t r a n s i t i o n s t a t e o v e r non-p l a n a r t r a n s i t i o n s t a t e s . The rearrangement p r o c e e d s t h r o u g h a C-H---0 d i s t a n c e o f 1.6 A (79, Scheme 44) and the t r a n s i t i o n s t a t e i s t h e n a t t a i n e d by a 60° r o t a t i o n around the C^-C-y bond to g e n e r a t e a p l a n a r s p e c i e s 80 i n which hydrogen i s l o c a t e d 1.3 A from c a r b o n and 1.2 A from oxygen. B a r t o n r e a c t i o n ' - 3 The g e n e r a t i o n o f an a l k o x y r a d i c a l by the i r r a d i a t i o n o f a l k y l n i t r i t e s f o l l o w e d by an i n t r a m o l e c u l a r hydrogen t r a n s f e r to the a l k o x y r a d i c a l has been termed the B a r t o n r e a c t i o n (Scheme 45) i n r e c o g n i t i o n o f the p i o n e e r i n g c o n t r i b u t i o n s by D.H.R. B a r t o n to t h i s r e a c t i o n . 7 3 ON \ 0 H HR \// C _ OH hu NO + 0 OH R N H HR \// C RH NO \ \ / OH C H / 0 N O R H V / c Scheme 45: The Barton reaction. - 166 The a b s t r a c t i o n o f hydrogen i s f o l l o w e d by r e c o m b i n a t i o n o f the n i t r o x y l r a d i c a l w i t h the a l k y l r a d i c a l t o g i v e n i t r o s o and/or oxime compounds. T h i s a c c o m p l i s h e s , i n e f f e c t , f u n c t i o n a l i z a t i o n o f a s p e c i f i c c a r b o n i n the m i d s t o f many carbons o f comparable r e a c t i v i t y toward an e x t e r n a l r e a g e n t . Many h y p o h a l i t e s have a l s o been used t o g e n e r a t e a l k o x y r a d i c a l s p h o t o c h e m i c a l l y . 2 ^ 2 • The B a r t o n r e a c t i o n i s o f d i r e c t r e l e v a n c e t o the N o r r i s h type I I r e a c t i o n , as the c h e m i c a l b e h a v i o r o f a l k o x y r a d i c a l s p a r a l l e l s t h a t o f the n,7r e x c i t e d s t a t e o f k e t o n e s . a The p r e f e r e n c e f o r t e r t i a r y > seco n d a r y > p r i m a r y hydrogens f o r a b s t r a c t i o n as w e l l as the p r e f e r e n c e f o r six-membered t r a n s i t i o n s t a t e s o v e r the o t h e r s a r e s h a r e d by a l k o x y r a d i c a l s and n,7r e x c i t e d s t a t e s o f k e t o n e s . C o n s e q u e n t l y , i r r a d i a t i o n o f 5 - p h e n y l - 1 - p e n t y l n i t r i t e (81)yields p r o d u c t s c o r r e s p o n d i n g o n l y to six-membered t r a n s i t i o n s t a t e hydrogen a b s t r a c t i o n even though the r a d i c a l g e n e r a t e d by seven-membered t r a n s i t i o n s t a t e a b s t r a c t i o n would be more s t a b l e (Scheme 46). 234-The major s y n t h e t i c achievements o f t h i s r e a c t i o n have been r e a -l i z e d i n the s t e r o i d f i e l d . S p e c i f i c a l l y , the r e a c t i o n has been used w i t h g r e a t s u c c e s s i n f u n c t i o n a l i z i n g C^g and C^g carbons w i t h a l k o x y r a d i c a l s a t C2r), C3, Cg o r C ^ i and C ^ i , Cg, C4 or C2, r e s p e c t i v e l y ( F i g . 31). The d i s t a n c e measured between the 7-hydrogens and the oxygen r a d i c a l was e s t i m a t e d t o be about 2.1 A by D r e i d i n g m o d e l s . T h i s d i s t a n c e i s s i g n i f i c a n t l y l o n g e r t h a n the s u g g e s t e d maximum o f 1.8 A f o r the M c L a f f e r t y rearrangement. The s e l e c t i v i t y o f the B a r t o n r e a c t i o n i s a r e s u l t o f i t s s t e r i c r e q u i r e m e n t i n the t r a n s i t i o n s t a t e l e a d i n g to the hydrogen t r a n s f e r . I t - 167 -Figure 31: FunctionalIzation of C^g and C^q carbons with alkoxy r a d i c a l s . i s w e ll known that s i x atom abstraction i s preferred over f i v e or seven atom abstraction. Nevertheless, abstractions are known to proceed through seven-membered t r a n s i t i o n states i n favorable circumstances. 7 3 The r e l a t i v e d i s p o s i t i o n of the 7-hydrogen with respect to the alkoxy r a d i c a l i s not apparent i n conformationally mobile systems. However, i t can be quite apparent i n r i g i d p o l y c y c l i c frameworks. For example, i n 168 -m o l e c u l e 83, i t i s c l e a r t h a t a c h a i r l i k e s i x atom arrangement i s i n v o l v e d i n the a b s t r a c t i o n . Other r i g i d s t e r o i d a l k e t o n e s undergo the M c L a f f e r t y rearrangements v i a 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 , t o o . 8 5 C H O 8 6 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 was a l s o s u g g e s t e d by Green e t a ] _ 2 3 4 b , c f o r t ^ e B a r t o n r e a c t i o n i n c o n f o r m a t i o n a l l y m o b i l e a l k o x y r a d i c a l s . By d e u t e r i u m l a b e l l i n g , the p r e f e r e n c e f o r a b s t r a c t i o n o f H a over H D was d e t e r m i n e d t o be 1.2, when R = CH3, and 1.3, when R = c y c l o h e x y l . I n 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 , a b s t r a c t i o n o f H a r e q u i r e s an e q u a t o r i a l R group, and a b s t r a c t i o n o f H D i n v o l v e s the R group i n an a x i a l p o s i t i o n ( F i g . 32). R = C H 3 or Cyclohexyl F i g u r e 32: S t e r e o s e l e c t i v i t y In the B a r t o n r e a c t i o n . - 169 -Walling and Padwa2-^ suggested the t r a n s i t i o n state 86 to account f o r the hydrogen abstraction following the generation of an alkoxy r a d i c a l from hypochlorites. The important aspect of t h i s t r a n s i t i o n state i s that the C-H bond undergoing homolysis i s c o l l i n e a r with the oxygen atom. The r e s t r a i n t of c o l l i n e a r i t y of the C-H bond with the oxygen atom was introduced to accommodate the f a c t that t r a n s i t i o n states smaller than s i x membered were not observed. 7^ There has been some t h e o r e t i c a l support for t h i s model, too.2^5 This model i s u n l i k e l y , however, considering that such a t r a n s i t i o n state should favor seven membered abstraction over s i x . In addition, the c o l l i n e a r arrangement described above cannot be attained i n a number of r i g i d p o l y c y c l i c systems undergoing smooth hydrogen abstraction. For example, the abstraction of a hydrogen from C^ by an alkoxy r a d i c a l at C ^ a or abstraction of a Cg hydrogen by a C^a cannot be c o l l i n e a r (see 82, page 167) because of the r i n g constraints, and hence the abstraction geometries resemble chair or boat l i k e arrangements. Angular Relationships i n Hydrogen Atom Abstraction The distance d, between the oxygen and hydrogen, although impor-tant, i s not the only factor that determines the geometry of hydrogen abstraction. Also important i s the angular r e l a t i o n s h i p of the hydrogen with respect to the oxygen. I t i s w e l l - e s t a b l i s h e d i n both the McLafferty and Norrish type II reactions that the abstracting o r b i t a l i s - 170 -a non-bonding n atomic o r b i t a l on oxygen. Depending on the model c o n s i d e r e d , t h i s n o r b i t a l makes an a n g l e o f 90° o r 120° w i t h the C=0 1 0? a x i s . Kasha-"-"'6 has s u g g e s t e d t h a t the l o n e p a i r c o n t a i n i n g atomic o r b i t a l s o f c a r b o n y l groups are n o n - e q u i v a l e n t and t h a t one o f them i s l a r g e l y 2s and the o t h e r e s s e n t i a l l y 2p i n n a t u r e ( F i g . 33a). I t i s the l a t t e r n - o r b i t a l t h a t makes an a n g l e o f 90° w i t h the C=0 a x i s and i s i n v o l v e d i n the a b s t r a c t i o n . The a l t e r n a t e model-'- 0 3 c o n s i d e r s the two l o n e p a i r s as e q u i v a l e n t and t h a t they r e s i d e i n two " r a b b i t e a r " sp2 h y b r i d o r b i t a l s ( F i g . 33b). There i s e v i d e n c e f o r the l a t t e r model from X - r a y c r y s t a l l o g r a p h i c s t u d i e s d e a l i n g w i t h the d i r e c t i o n a l i t y o f the h ydrogen bonds w i t h c a r b o n y l g r o u p s . 1 0 3 c F i g u r e 33: Arrangement o f Atomic O b i t a l s i n C a r b o n y l Groups, (a) Kasha Model, (b) R a b b i t E a r Model. I t i s c l e a r from the work o f D j e r a s s i 8 5 t h a t the a b s t r a c t i o n of hydrogen i s most f a c i l e when the H atom approaches the c a r b o n y l group such t h a t i t makes maximum o v e r l a p w i t h the a b s t r a c t i n g n - o r b i t a l . The a b s t r a c t i o n , b a s e d on the models c o n s i d e r e d ( v i d e s u p r a ) , i s most f a c i l e - 171 -when T , the a n g l e o f hydrogen w i t h r e s p e c t t o the c a r b o n y l p l a n e , i s 0° and A, the C-0-•*H a n g l e i s 90° o r 120°. A c c o r d i n g l y , the a b s t r a c t i o n i s l e a s t f a c i l e when r i s 90° and A i s 180°. These c o n s i d e r a t i o n s l e d Wagner 7 5* 5 t o s u g g e s t a p o s s i b l e c o s 2 r dependence and us t o s u g g e s t a p o s s i b l e s i n 2 A d e p e n d e n c e 2 2 6 on the e f f i c i e n c y o f hydrogen a b s t r a c t i o n . N o r r i s h Type II Reaction S i m i l a r t o what i s found i n the M c L a f f e r t y and B a r t o n r e a c t i o n s , six-membered t r a n s i t i o n s t a t e s a r e the most f a v o r e d i n the N o r r i s h type I I r e a c t i o n as w e l l . 7 5 C o n s i d e r a t i o n s which l e d t o r u l i n g out the c o l l i n e a r approach o f the C-H bond t o oxygen a p p l y h e r e t o o . Boer e t a l . 1 5 1 s u g g e s t t h a t b o t h the N o r r i s h type I I r e a c t i o n and i t s ground s t a t e e q u i v a l e n t , the M c L a f f e r t y rearrangement, p r o c e e d t h r o u g h a p l a n a r t r a n s i t i o n s t a t e . However, L e w i s ® 6 and Wagner®"* have shown t h a t t h i s i s n o t the case f o r the N o r r i s h type I I r e a c t i o n , as the hydrogen a b s t r a c t i o n r a t e c o n s t a n t s i n a p l a n a r t r a n s i t i o n a r e e x p e c t e d to be d i m i n i s h e d s i g n i f i c a n t l y by s u b s t i t u e n t s a t the a and £3 p o s i t i o n s . The u n f a v o r a b l e e c l i p s i n g i n t e r a c t i o n s o f s u b s t i t u e n t s a t a o r /3 p o s i t i o n s w i t h methylene hydrogens i n a p l a n a r t r a n s i t i o n s t a t e are e x p e c t e d t o r e s u l t i n h i g h e r a c t i v a t i o n e n e r g i e s , and hence, i n lower hydrogen a b s t r a c t i o n r a t e c o n s t a n t s f o r i n t r a m o l e c u l a r h ydrogen a b s t r a c -t i o n s . No such e f f e c t was found and t h i s l e d to the p o s t u l a t i o n o f a s t r a i n - f r e e c h a i r l i k e t r a n s i t i o n s t a t e by Wagner. 7 5 T h i s c h a i r l i k e t r a n s i t i o n s t a t e , w h i l e r e l i e v i n g the s t e r i c i n t e r a c t i o n s p r e s e n t i n the - 172 -p l a n a r t r a n s i t i o n s t a t e , does i n c r e a s e the 0-•-H^ d i s t a n c e c o n s i d e r a b l y i n comparison. R e c e n t l y , m o l e c u l a r o r b i t a l c a l c u l a t i o n s p e r f o r m e d by S a l e m 7 0 ' 2 3 6 r e v e a l e d t h a t hydrogen a b s t r a c t i o n proceeds from the n - o r b i t a l o f the n , 7 r * e x c i t e d s t a t e o f ketones, and the a b s t r a c t i o n parameters c o n s i d e r e d by him were d = 1.56 A, A = 120°, and T = 0 ° . From the work co n d u c t e d i n our l a b o r a t o r y 1 5 on ene-diones and e n o n e - a l c o h o l s , the maximum d i s t a n c e f o r hydrogen a b s t r a c t i o n by the oxygen atom was su g g e s t e d t o be 2.7 A, the sum o f van der Waals r a d i i o f the oxygen and hydrogen atoms. No maximum l i m i t c o u l d be s e t f o r e i t h e r r o r A, as these v a l u e s were c l o s e t o the i d e a l v a l u e s i n the compounds examined. In the p r e s e n t i n v e s t i g a t i o n . smooth h v d r o E e n a b s t r a c t i o n s were  n o t e d a t d i s t a n c e s as h i g h as 3.1 A . a d i s t a n c e s i g n i f i c a n t l y g r e a t e r  t h a n the su g g e s t e d upper l i m i t o f 2.7 A . and a t a n g l e s as u n f a v o r a b l e as  62° f o r r and 77" f o r A. i n a d d i t i o n , the o c c u r r e n c e o f t r a n s i t i o n s t a t e s as v a r i e d as c h a i r , boat, and h a l f - c h a i r d i s p r o v e s the r i g i d r e q u i r e m e n t o f 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 arrangement f o r a b s t r a c t i o n . The o c c u r e n c e o f N o r r i s h type I I r e a c t i o n i n a - c y c l o a l k y l a c e t o p h e n o n e s a t d i s t a n c e s much g r e a t e r than 2.7 A might i n p a r t a r i s e from the g r e a t e r c o n f o r m a t i o n a l freedom a v a i l a b l e t o them compared t o the b i c y -c l i c e ne-diones and e n o n e - a l c o h o l s d i s c u s s e d i n I n t r o d u c t i o n (pages 26-31). The f a c i l e r o t a t i o n s about the Ca-Cp and c a r b o n y l c a r b o n - C Q s i n g l e bonds and weaker l a t t i c e f o r c e s (as r e f l e c t e d i n t h e i r low m e l t i n g p o i n t s ) may c o n t r i b u t e t o g r e a t e r range o f a b s t r a c t i o n d i s t a n c e s (0...H d i s t a n c e s ) i n a - c y c l o a l k y l a c e t o p h e n o n e s . - 173 -A range o f 87-120" ( T a b l e XXXIII) was found f o r the a n g l e 6 (the C-H-•-0 a n g l e ) i n a - c y c l o a l k y l a c e t o p h e n o n e s . T h i s d i f f e r s from the v a l u e o f 0>15O° s u g g e s t e d by Green e t a l . 2 ^ 4 b f o r the B a r t o n r e a c t i o n o f the 2-hexyloxy r a d i c a l s . N o r r i s h Type I I v s M c L a f f e r t y R e a c t i o n s I t i s o b v i o u s from the p r e c e d i n g d i s c u s s i o n t h a t p h o t o c h e m i c a l i n t r a m o l e c u l a r hydrogen a b s t r a c t i o n can o c c u r o v e r d i s t a n c e s much l o n g e r t h a n the s u g g e s t e d upper l i m i t o f 1.8 A f o r the M c L a f f e r t y r e a r r a n g e -T a b l e X X X I I I . 6 V a l u e s ( C-H*••0-angle) f o r a - c y c l o a l k y l - p - c h l o r o -acetophenones. Compound 0 a - c y c l o b u t y l - p - c h l o r o a c e t o p h e n o n e , 45 87 a - c y c l o p e n t y l - p - c h l o r o a c e t o p h e n o n e , 38 102 a - c y c l o h e x y l - p - c h l o r o a c e t o p h e n o n e , 2 8 116 Q - c y c l o h e p t y l - p - c h l o r o a c e t o p h e n o n e , 50 120 o - c y c l o o c t y l - p - c h l o r o a c e t o p h e n o n e , 53 108 a - e x o - 2 - n o r b o r n y l - p - c h l o r o a c e t o p h e n o n e , 46 90 a-ada m a n t y l - p - c h l o r o a c e t o p h e n o n e ( n e e d l e ) , 54n 106 a-ada m a n t y l - p - c h l o r o a c e t o p h e n o n e ( p l a t e ) , 54p 116 - 174 -merit. A s i d e from the crudeness w i t h which these d i s t a n c e s were measured f o r the m o l e c u l e s u n d e r g o i n g M c L a f f e r t y rearrangement, what are the o t h e r p o s s i b l e s o u r c e s f o r the remarkable d i f f e r e n c e s between the M c L a f f e r t y and N o r r i s h type I I r e a c t i o n s ? F a c t o r s t h a t can p o s s i b l y c o n t r i b u t e to t h i s d i f f e r e n c e a r e : 1. The e l o n g a t i o n o f the C=0 bond l e n g t h and the changes i n the geometry a s s o c i a t e d w i t h the e x c i t e d s t a t e , 2. U n d e r e s t i m a t i o n o f C-H bond l e n g t h s by X - r a y c r y s t a l l o g r a p h y , 3. The p o s s i b i l i t y o f sample m e l t i n g accompanying hydrogen a b s t r a c t i o n i n the systems s t u d i e d f o r N o r r i s h type I I r e a c t i o n , and 4. The s h r i n k a g e o f the o r b i t a l s a s s o c i a t e d w i t h a p o s i t i v e charge on the oxygen atom i n the M c L a f f e r t y rearrangement. Each o f these f a c t o r s i s examined below. About the r e l e v a n c e o f the g e o m e t r i c a l parameters o b t a i n e d i n the ground s t a t e to the e x c i t e d s t a t e o f k e t o n e s , Dewar's MINDO/3 c a l c u l a -t i o n s 8 4 0 on b u t a n a l r e v e a l t h a t the c a r b o n y l group undergoes p y r a m i d a l -i z a t i o n upon e x c i t a t i o n , an e x p e r i m e n t a l l y w e l l documented o c c u r r e n c e i n the case o f f o r m a l d e h y d e . 2 3 7 F i g . 34 p r e s e n t s the c a l c u l a t e d g e o m e t r i e s o f the s i n g l e t and t r i p l e t n,n* e x c i t e d s t a t e s a l o n g w i t h the ground s t a t e geometry o f b u t a n a l . The r e s u l t s a l s o i n d i c a t e t h a t t h e r e i s an e l o n g a t i o n o f the C=0 bond i n the e x c i t e d s t a t e . I f p y r a m i d a l i z a t i o n o c c u r s i n the n , 7 r * e x c i t e d s t a t e o f a - c y c l o a l k y l a c e t o p h e n o n e s , the a n g u l a r r e l a t i o n s h i p o f the hydrogen w i t h the n - o r b i t a l would be c o n s i d -e r a b l y d i f f e r e n t i n the e x c i t e d s t a t e compared to the ground s t a t e . - 175 -H 7 H e - , . J , - H 6 C v " - H « H 2 H 3 So S i Ti C i O 1.193 1.251 1.230 H , C i O 120.2- 102.3- 95.5-C 2 C i O 131.0- 136.3- 134.4-C J C T O H , 180.0' 156.V 131.0-C 3 C 2 C 1 O 9.2- 10.V 10.2-C4C3C 2 Ci 312.9- 290.2" 296.6-0 . . . - H a . . . . . ^ H 6 I T H 2 H H 5 S i T i 0 H 6 1.600 1.500 d o 1.273 1.280 HBOCT 110.3- 110.0-C J C T O H , 156.6' 1 6 2 . T C 3 C 2 C I O 27.3- 21.5* C 4 C J C 2 C I 337.3- 339.0' F i g u r e 34: Ground and e x c i t e d s t a t e g e o m e t r i e s o f b u t a n a l c a l c u l a t e d by Dewar. However, Hoffmann and Swenson- 1"" have shown u s i n g extended H u c k e l and CNDO/2 c a l c u l a t i o n s the p l a n a r n a t u r e o f the c a r b o n y l group o f benzophenone i n i t s e x c i t e d s t a t e . E s s e n t i a l l y the same c o n c l u s i o n was r e a c h e d by W a g n e r 1 6 9 i n h i s s t u d y on the v i s c o s i t y dependent d u a l phosphorescence o f p h e n y l a l k y l k e t o n e s . There are o t h e r s t u d i e s , b o t h e x p e r i m e n t a l 1 7 ^ and t h e o r e t i c a l , 1 7 1 c o n f i r m i n g the e s s s e n t i a l l y p l a n a r n a t u r e o f the n,7r* e x c i t e d s t a t e s o f a,fi-unsaturated ketones thus i n d i c a t i n g the same a n g u l a r r e l a t i o n s h i p between the 7-hydrogen and the c a r b o n y l group i n the e x c i t e d s t a t e as i n the ground s t a t e . The second f a c t o r t h a t might i n f l u e n c e the r e s u l t s i s the under-e s t i m a t i o n o f C-H bond l e n g t h s by X - r a y c r y s t a l l o g r a p h y . 2 3 8 T h i s i s because hydrogen atoms, b e i n g v e r y l i g h t , have m i n i m a l e l e c t r o n d e n s i t y and the e l e c t r o n map f o r these atoms i s s h i f t e d toward the carbon n u c l e u s g i v i n g s l i g h t l y l e s s t h a n a c t u a l C-H bond l e n g t h s . I f a gener-ous c o r r e c t i o n f a c t o r o f 0.1 A f o r each o f the e l o n g a t i o n o f the C=0 bond l e n g t h i n the n , 7 r * e x c i t e d s t a t e and the u n d e r e s t i m a t i o n o f the C-H 176 -bond l e n g t h by X - r a y c r y s t a l l o g r a p h y i s g i v e n , the a c t u a l a b s t r a c t i o n d i s t a n c e s c o u l d be lower by -0.2 A. However, t h i s i s o n l y t r u e when the C=0 and C-H bonds are c o l l i n e a r . S i n c e X - r a y c r y s t a l l o g r a p h y o f a l l the a - c y c l o a l k y l a c e t o p h e n o n e s c l e a r l y r e v e a l s the n o n - c o l l i n e a r arrangement o f C-H w i t h C=0 bond, the a b s t r a c t i o n d i s t a n c e 'd' s h o u l d n o t be a f f e c t e d i n t h e s e systems. W i d e l y d i f f e r e n t s o l i d s t a t e p h o t o c h e m i c a l r e a c t i v i t i e s (compared t o s o l u t i o n s t a t e r e a c t i v i t i e s ) t h a t a r e c o n t r o l l e d by t o p o c h e m i s t r y , the o c c u r r e n c e o f smooth N o r r i s h type I I r e a c t i o n s f o r p - c a r b o x y l i c a c i d d e r i v a t i v e s t h a t have v e r y h i g h m e l t i n g p o i n t s , the absence o f any v a r i a t i o n between the p h o t o r e a c t i v i t y a t -40°C and room temperature, and the h i g h o p t i c a l y i e l d s r e a l i z e d i n the a - 3 - m e t h y l - l - a d a m a n t y l - p - c h l o r o -acetophenone system a l l s u p p o r t the t r u e s o l i d s t a t e n a t u r e o f the r e a c t i o n o f a - c y c l o a l k y l a c e t o p h e n o n e s and r u l e out the p o s s i b i l i t y o f s i g n i f i c a n t m e l t i n g d u r i n g the a b s t r a c t i o n . One e x p l a n a t i o n t h a t can be forwarded f o r the s h o r t e r 0-•-H d i s t a n c e s r e q u i r e d i n the M c L a f f e r t y rearrangement i s t h a t the oxygen atom i n v o l v e d i n the M c L a f f e r t y rearrangement, b e i n g p o s i t i v e l y charged, causes a s h r i n k a g e o f the o r b i t a l s a s s o c i a t e d w i t h the a b s t r a c t i o n . T h i s s h r i n k a g e i n o r b i t a l s i z e would c e r t a i n l y r e q u i r e a c l o s e r approach o f hydrogen f o r an a b s t r a c t i o n . I n o r d e r to compare the e f f i c i e n c i e s o f the M c L a f f e r t y r e a a r r a n g e -ment w i t h the N o r r i s h type I I r e a c t i o n , the mass s p e c t r a o f the w e l l -c h a r a c t e r i z e d c h l o r o d e r i v a t i v e s t h a t a l s o undergo N o r r i s h type I I r e a c t i o n were examined. The mass s p e c t r a r e v e a l e d an e f f i c i e n t McLaf-f e r t y rearrangement i n a l l s u b s t r a t e s w i t h the e x c e p t i o n o f the adaman-- 177 t y l and cyclobutyl compounds (Table XXXIV). The absence of any appreciable McLafferty fragments i n the adaman-t y l compounds should c e r t a i n l y be re l a t e d to the formation of high energy adamantene 1^ 2 i n the CQ-C^} bond s c i s s i o n following the abstraction. The i n a b i l i t y of adamantylacetone to undergo McLafferty rearrangement was reported previously by Sauers et a l . 1 - * 2 The base peak i n the mass spectra of the remaining chloro compounds excepting i n cyclobutyl d e r i v a t i v e , i s also the ion peak corresponding to the McLafferty reaction. In the cyclobutyl case, there was apprecia-ble fragmentation assigned to McLafferty reaction. However, the base peak at mass 139 corresponds to the loss of the cycl o b u t y l methyl group from the molecular ion (a-cleavage). The e f f i c i e n t McLafferty r e a c t i o n seen i n these chloro compounds cannot be considered as evidence f o r i t s occurrence at distances longer than the supposed upper l i m i t of 1.8 A. This i s so because a l l the C=0 - -'H distances reported previously i n the l i t e r a t u r e f o r the McLafferty rearrangement were measured at the c l o s e s t approach of oxygen to hydrogen using molecular models. The distances obtained from X-ray crystallography f o r the chloro derivatives i n question do not correspond to the cl o s e s t approach values. Rotations around the carbo-n y l carbon to a-carbon bond, the a-carbon to /3-carbon bond, or a combination of the two bring about, as we have seen, a decrease i n the C=0---H^ distances. Computer simulation of the a ) r3 carbon-carbon bond rotations performed by Mr. Stephen Evans indicate that distances closer than 1.9 A can be achieved i n cyclobutyl to cyclooctyl-p-chloro 1 7 8 Table XXXIV: McLafferty Fragmentation of a-Cycloalkyl-p-chloro-acetophenones. m/e = 154 Ketone M c L a f f e r t y Base peak m/e ( i n t e n s i t y ) (m/e i n t e n s i t y ) r = 4, 45 154 (24) 139 (100) r = 5, 38 154 (100) 154 (100) r = 6, 28 154 (100) 154 (100) r = 7, 50 154 (100) 154 (100) r = 8, 53 154 (100) 154 (100) r = n o r b o r n y l , 46 154 (100) 154 (100) r = adamantyl, 54 154 (4) 253 (100) r = 3-methyl-1-adamantyl, 58 154 (3) 267 (100) The r e p o r t e d i n t e n s i t i e s o f M c L a f f e r t y peaks a r e r e l a t i v e i n t e n s i -t i e s w i t h r e s p e c t t o the most i n t e n s e peak (base peak) taken as 100%. - 179 -d e r i v a t i v e s o f acetophenone w i t h c l o s e t o i d e a l r and A v a l u e s ( T a b l e XXXV). I t i s i n t e r e s t i n g t o examine the M c L a f f e r t y and N o r r i s h type I I r e a c t i o n s o f the t e t r a c y c l i c ene-diones (Scheme 47) s t u d i e d by Mandel-T a b l e XXXV: V a r i a t i o n o f G" •-H7 D i s t a n c e s and A b s t r a c t i o n A n g l e s by R o t a t i o n Around CQ-C^g Bond. Ketone C l o s e s t 0-•-H7 X - r a y ( d ( A ) , r ( ° ) , A(°) from c r y s t a l l o g r a p h y a f t e r r o t a t i o n about ca" c/3 bond (°) Degree o f r o t a t i o n around co.-c/S bond (°) = 4, 45 = 5, 38 = 6, 28 = 7, 50 = 8, 53 3.1, 23, 101 2.8, 31, 96 2.6, 42, 90 2.7, 42, 82 2.7, 46, 77 1.7, 0, 110 1.7, 0, 112 1.8, 0, 115 1.8, 0, 109 1.5, 0, 113 -80 +90 +100 +60 +60 + = c l o c k w i s e r o t a t i o n = c o u n t e r c l o c k w i s e r o t a t i o n - 180 -baum and h i s co-workers.239-241 ^ Q I m o l e c u l e s i n Scheme 47 undergo a smooth McLafferty rearrangement. In the McLafferty rearrangement i n v o l v i n g very s i m i l a r molecules, two 5-hydrogens were shown to be t r a n s f e r r e d s t e r e o s p e c i f i c a l l y . 2 4 2 When the c r y s t a l s of 8 7 , 8 8 , 8 9 , 9 0 , and 9 1 were i r r a d i a t e d as s o l i d s , only 9 1 underwent a S-hydrogen abstra c t i o n to give an enone- alcohol (Scheme 4 7 ) . 2 4 0 The occurrence of hydrogen Compound Ring 1 Ring 2 0...H distance 0 Photoreaction McLafferty rearrangement 87 5 5 3.2 no yes 88 5 6 4.1 no yes 89 6 6 4.8 no yes 90 6 7 4.0 no yes 91 7 7 2.7 yes yes Scheme 4 7 : The McLafferty and Norrish type II reactions of t e t r a c y c l i c ene-diones. - 181 -abstra c t i o n only i n 91 i s consistent with Scheffer's s u g g e s t i o n 1 5 of 2.7 A as the upper l i m i t f o r hydrogen abstraction by o xygen. 2 4 1 The occurrence of smooth McLafferty rearrangement i n a l l ene-diones i n s p i t e of very high 0-•-Hg distances seems to ind i c a t e (1) H-transfer i n the McLafferty rearrangement from a conformation d i f f e r e n t from that present i n the c r y s t a l , or (2) a migration terminus other than oxygen. Much less l i k e l y i s the p o s s i b i l i t y that mass spectrometric H-transfers occur over greater distances than that involved i n the photochemical process. - 182 EXPERIMENTAL GENERAL INFORMATION Melting Points (MP) A l l melting points except those indicated by an a s t e r i s k were taken on a Fisher-Johns hot stage melting point apparatus and are uncorrected. Melting Point (MP*) The melting points of the compounds whose melting point i s below ambient temperature were determined by sea l i n g the sample i n a c a p i l l a r y tube and subjecting them to several freeze-thaw cycles u n t i l the walls of the c a p i l l a r y tube were evenly coated with s o l i d . The c a p i l l a r y tube was then immersed i n an a c e t o n i t r i l e - l i q u i d nitrogen bath and the bath was allowed to warm slowly to room temperature. The melting point of the compound was noted from a thermometer capable of measuring low temperatures. Infrared Spectra (IR) Infrared spectra were recorded on a Perkin-Elmer 710B i n f r a r e d spectrophotometer, and were c a l i b r a t e d using the 1601 cm"1 band of polystyrene or on a Perkin-Elmer 1710 Fourier Transform i n f r a r e d 183 -s p e c t r o p h o t o m e t e r i n one o f the two f o l l o w i n g ways: a) from neat l i q u i d samples between sodium c h l o r i d e p l a t e s , b) from KBr p e l l e t s made u s i n g a P e r k i n - E l m e r p o t a s s i u m bromide e v a c u a t e d d i e 186-0002 and a C a r v e r l a b o r a t o r y p r e s s model B. The p e l l e t s c o n t a i n e d 1 t o 2 mg o f compound i n 150 to 200 mg o f KBr. Nuclear Magnetic Resonance (NMR) P r o t o n n u c l e a r magnetic resonance (-*-H NMR) s p e c t r a were r e c o r d e d i n d e u t e r o c h l o r o f o r m on Br u k e r WP-80 (80 MHz), V a r i a n XL-300 (300 MHz) and Bru k e r WP-400 (400 MHz) s p e c t r o m e t e r s , o r a t 270 MHz on a u n i t composed o f an O x f o r d i n s t r u m e n t s 63.4 KG magnet, N i c o l e t 16K computer, and a Bruker TT.23 c o n s o l e . S i g n a l p o s i t i o n s a r e g i v e n i n p a r t s p e r m i l l i o n (6) d o w n f i e l d from the t e t r a m e t h y l s i l a n e s i g n a l , which was used as an i n t e r n a l s t a n d a r d . The m u l t i p l i c i t y , number o f p r o t o n s , c o u p l i n g c o n s t a n t s and assignments a l l f o l l o w the s i g n a l p o s i t i o n i n p a r e n t h e s e s . The a b b r e v i a t i o n s used t o i n d i c a t e m u l t i p l i c i t i e s o f p r o t o n s i g n a l s a r e : s = s i n g l e t , b r s = b r o a d s i n g l e t , d •= d o u b l e t , dd = d o u b l e t o f doub-l e t s , b r d = b r o a d d o u b l e t , t = t r i p l e t , q = q u a r t e t and m = m u l t i p l e t . A l l the c a r b o n n u c l e a r magnetic resonance s p e c t r a (^C NMR) were r e c o r d e d e i t h e r on V a r i a n XL-300 (75.4 MHz) o r on Bruker WP-400 (100.5 MHz) i n s t r u m e n t s . S i g n a l p o s i t i o n s a r e r e p o r t e d i n p a r t s p e r m i l l i o n (5) r e l a t i v e t o the t e t r a m e t h y l s i l a n e and assignments f o l l o w the s i g n a l p o s i t i o n i n p a r e n t h e s e s . S o l i d s t a t e c a r b o n n u c l e a r magnetic resonance (^•-'C CPMAS) were o b t a i n e d w i t h a Bruker CXP-200 FT NMR s p e c t r o m e t e r o p e r a t i n g a t an - 184 -a p p l i e d f i e l d s t r e n g t h o f 4.7T or a 1 3 C resonance f r e q u e n c y o f 50.3 MHz. 1 3 The i J C s i g n a l o f l i q u i d benzene l y i n g 128.5 d o w n f i e l d from t e t r a m e t h y l -s i l a n e was u s e d as an e x t e r n a l r e f e r e n c e t o determine the c h e m i c a l s h i f t v a l u e s . U l t r a v i o l e t S p e c t r a ( U V ) U l t r a v i o l e t s p e c t r a were r e c o r d e d on a Pye-Unicam PU 8800 UV/Vis s p e c t r o m e t e r , and a b s o r p t i o n maxima (A m a x) and e x t i n c t i o n c o e f f i c i e n t s (e) a r e r e p o r t e d f o r a b s o r p t i o n peaks. Mass S p e c t r a (MS) Low r e s o l u t i o n mass s p e c t r a were r e c o r d e d w i t h a Varian/MAT CH4B mass s p e c t r o m e t e r and the h i g h r e s o l u t i o n mass s p e c t r a were r e c o r d e d w i t h a K r a t o s / A E l MS50 or MS902 s p e c t r o m e t e r . Chromatography T h i n l a y e r chromatography ( t i c ) was c a r r i e d out u s i n g 20 x 20 cm aluminum s h e e t s c o a t e d w i t h 0.2 mm o f s i l i c a g e l p l a t e s (Eastman chromatogram s h e e t type 13181 and E. Merck t i c s h e e t s No. 5554). P r e p a r a t i v e t i c was c a r r i e d out on 20 x 20 cm g l a s s p l a t e s c o a t e d w i t h a 0.9 mm l a y e r o f s i l i c a g e l (E. Merck, s i l i c a g e l 60 GF 254). C o n v e n t i o n a l ( g r a v i t y ) column chromatography and f l a s h chromato-g r a p h y 2 4 3 were pe r f o r m e d u s i n g 70-230 and 230-400 mesh s i l i c a g e l (E. 185 -Merck), r e s p e c t i v e l y . A n a l y t i c a l gas chromatography (gas l i q u i d chromatography) was p e r f o r m e d on H e w l e t t - P a c k a r d gas chromatograph models 5880A and 5890A f i t t e d w i t h flame i o n i z a t i o n d e t e c t o r s . The H e w l e t t - P a c k a r d 5880A i n s t r u m e n t was equipped w i t h a b u i l t - i n i n t e g r a t o r and the 5890A i n s t r u -ment had an 3392A i n t e g r a t o r . A l l t h e chromatography was c a r r i e d out on one o f the f o l l o w i n g f u s e d s i l i c a c a p i l l a r y columns: a) a 12m x 0.21 mm Carbowax 20 M column; b) a 50 m x 0.21 mm Carbowax 20 M column; c) a 12m x 0.21 mm OV-101 column. A l l the above-mentioned columns were s u p p l i e d by H e w l e t t - P a c k a r d . A l s o used were two o t h e r columns: d) a 15m x 0.25 mm DB-1 column w i t h 100% d i m e t h y l p o l y s i l o x a n e f i l m o f 0.25 /im t h i c k n e s s ; and e) a 15 m x 0.25 mm DB-5 column w i t h 95% d i m e t h y l -( 5 % ) - d i p h e n y l - p o l y s i l o x a n e f i l m o f 0.25 pm t h i c k n e s s , s u p p l i e d by J & W S c i e n t i f i c , I n c . O p t i c a l R o t a t i o n s O p t i c a l r o t a t i o n s were measured on a P e r k i n - E l m e r 141 p o l a r i m e t e r o p e r a t e d a t the sodium D l i n e (589 nm). Large s i n g l e c r y s t a l s o f compound 5 8 were grown from 95% e t h a n o l and were checked under a p o l a r i z i n g m i c r o s c o p e t o determine i f they were s i n g l e . C r y s t a l s i z e s range from 1 x 1 cm to 2 x 2 cm and weighed between 140 and 313 mg. These c r y s t a l s were s e a l e d i n Pyrex tubes a f t e r s e v e r a l freeze-pump-thaw c y c l e s , and were i r r a d i a t e d a t -38 ± 3°C u s i n g a n i t r o g e n l a s e r (337 nm) or a t 7 ± 2°C w i t h a 450 W Hanovia medium p r e s s u r e mercury lamp. L a s e r i r r a d i a t i o n s were c a r r i e d out f o r 1-2 h, a f t e r which the c r y s t a l was 186 s t i l l i n t a c t , b u t showed some m e l t i n g . To r e a c h the same degree o f c o n v e r s i o n w i t h the Hanovia lamp i r r a d i a t i o n s , i t took about 48 h o u r s . The c r y s t a l s were d i s s o l v e d i n a n a l y t i c a l l y pure c h l o r o f o r m t o make up 1.0 mL s o l u t i o n s . The i n s t r u m e n t was c a l i b r a t e d t o 0° w i t h a n a l y t i c a l l y pure c h l o r o f o r m and o p t i c a l r o t a t i o n s o f the t e s t samples were measured. In a d d i t i o n , the temperature a t which the o p t i c a l r o t a t i o n was measured was r e c o r d e d . The p e r c e n t a g e c o n v e r s i o n t o the p r o d u c t s was de t e r m i n e d by c a p i l l a r y gas chromatography. The s p e c i f i c r o t a t i o n was c a l c u l a t e d from the o p t i c a l r o t a t i o n u s i n g the e q u a t i o n : t a [ « h = SL x c t = the temperature a t which the o p t i c a l r o t a t i o n was measured. A = 589 nm, the sodium D l i n e . a = the o b s e r v e d o p t i c a l r o t a t i o n i n deg r e e s . Z = p a t h l e n g t h i n d e c i m e t e r s . c = the c o n c e n t r a t i o n o f the s o l u t i o n i n grams p e r mL. U s i n g a s i m i l a r p r o c e d u r e , o p t i c a l r o t a t i o n s were measured f o r the p h o t o p r o d u c t s from i r r a d i a t i o n s i n benzene and aqueous ( 2 % water) a c e t o n i t r i l e a t ambient temperatures. A n a l y s i s A l l e l e m e n t a l a n a l y s e s were performed by the d e p a r t m e n t a l micro-1 8 7 analyst, Mr. P. Borda. X-ray Analysis A l l x-ray c r y s t a l structures were determined by Mr. Stephen Evans, Dr. Sara A r i e l and Dr. James Tr o t t e r . Solvents and Reagents Unless otherwise indicated, a l l the solvents and substituted benzenes were p u r i f i e d by previously reported methods 2 4 4 and the solvents required dry were stored over Linde 4 A ° molecular sieves. Thiophene-free benzene was obtained by shaking benzene several times with concentrated H 2 S O 4 u n t i l no bluish-green c o l o r a t i o n appeared i n the a c i d layer, then with water, d i l u t e NaOH and water again u n t i l the aqueous layer was neutral to litmus, followed by drying over P 2 O 5 and d i s t i l l a t i o n . 2 4 5 Cyclohexene and cyclopentene were freed of peroxides by washing with successive portions of a c i d i f i e d ferrous s u l f a t e s o l u t i o n . A l l reagents were purchased from A l d r i c h Chemicals, unless other-wise indicated. A l l c y c l o a l k y l substituted a c e t i c acids, except cyclo-butane and cycloheptane a c e t i c acids, were used as received. Cyclo-butane and cycloheptane a c e t i c acids were synthesized by known m e t h o d s . ^ 5 • ^ 7 Straight chain alkanes, tetradecane to tetracosane, were A l d r i c h reagents, and were used without further p u r i f i c a t i o n as i n t e r n a l standards for gas chromatographic analyses. Valerophenone was p u r i f i e d - 188 -by a r e d u c e d p r e s s u r e d i s t i l l a t i o n f o l l o w e d by c r y s t a l l i z a t i o n from pentane. Acetophenone was p u r i f i e d by r e d u c e d p r e s s u r e d i s t i l l a t i o n . 4 - C h l o r o , 4-methyl and 4-methoxyacetophenones were p r e p a r e d by F r i e d e l -C r a f t s a c y l a t i o n method u s i n g a c e t y l c h l o r i d e and m o n o s u b s t i t u t e d benzenes. 2,5-Dimethyl-2,4-hexadiene was p u r i f i e d by low temperature c r y s t a l l i z a t i o n from p e t r o l e u m e t h e r . 4 - A c e t y l b e n z o n i t r i l e was c r y s -t a l l i z e d from hexane. SYNTHESIS Synthesis of 2-Cyclohexyl-1-(4-substituted phenyl)-ethanones a) P r e p a r a t i o n o f C y c l o h e x a n e a c e t v l C h l o r i d e from C y c l o h e x a n e a c e t i c  A c i d C y c l o h e x a n e a c e t i c a c i d (5.0 g, 35.2 mmol) was d i s s o l v e d i n 15 mL o f t h i o n y l c h l o r i d e and the r e s u l t i n g s o l u t i o n was r e f l u x e d f o r 1 h. T h i o n y l c h l o r i d e was removed i n vacuo u s i n g a r o t a r y e v a p o r a t o r , and the r e m a i n i n g c y c l o h e x a n e a c e t y l c h l o r i d e was d i s t i l l e d under r e d u c e d p r e s -s u r e . T h i s was u s ed immediately w i t h o u t f u r t h e r p u r i f i c a t i o n ; y i e l d 4.72 g ( 8 4 % ) ; bp 62°C, 0.5 T o r r . b) G e n e r a l P r o c e d u r e f o r Making 2 - C y c l o h e x v l - l - ( 4 - s u b s t i t u t e d p h e n y l ) - ethanones by F r i e d e l - C r a f t s Method 189 The f o l l o w i n g s i x compounds, 28-31, 36 and 37 were p r e p a r e d by u s i n g a s l i g h t l y m o d i f i e d p r o c e d u r e o f Wamser and Wagner.^ 4 The method i s d e s c r i b e d f o r the s y n t h e s i s o f the p - C l d e r i v a t i v e , 28. F r e s h l y p r e p a r e d c y c l o h e x a n e a c e t y l c h l o r i d e (4.7 g, 29.4 mmol) was s l o w l y added from an a d d i t i o n f u n n e l to a m i x t u r e o f anhydrous aluminum c h l o r i d e (5.7 g, 42.9 mmol) and excess c h l o r o b e n z e n e (15 mL) i n a t h r e e -necked f l a s k f i t t e d w i t h a r e f l u x condenser and p r o t e c t e d by CaCl2 d r y i n g t u b e s . T h i s a d d i t i o n was c a r r i e d out so t h a t a l l the a c e t y l c h l o r i d e was consumed i n about 30 mins. The r e a c t i o n m i x t u r e was r e f l u x e d f o r 5 h, and was c a u t i o u s l y poured i n t o 30 mL o f c o l d water w i t h s t i r r i n g . The y e l l o w o r g a n i c l a y e r was e x t r a c t e d w i t h 3 x 30 mL p o r t i o n s o f e t h e r . The combined o r g a n i c e x t r a c t s were washed w i t h 2 x 20 mL o f 10% NaOH s o l u t i o n , 2 x 20 mL o f water, d r i e d o v e r sodium s u l f a t e , and the e t h e r was removed i n vacuo. The r e s u l t i n g brown r e a c t i o n m i x t u r e on re d u c e d p r e s s u r e d i s t i l l a t i o n p r o v i d e d two f r a c t i o n s . F r a c t i o n 1 (9.8 g) was c o l l e c t e d a t 46°C, 0.5 T o r r , and f r a c t i o n 2 (6.3 190 -g) a t 140-150°C, 0.5 T o r r . F r a c t i o n 1 d i d n o t show any i n f r a r e d ( O O ) a b s o r p t i o n and was i d e n t i f i e d as c h l o r o b e n z e n e ; f r a c t i o n 2 showed the p r e s e n c e o f a s t r o n g ( O O ) a b s o r p t i o n i n i t s i n f r a r e d spectrum and c o n s i s t e d o f one compound i n more than 90% p u r i t y a c c o r d i n g to gas chromatography. T h i s m a t e r i a l was d i s s o l v e d i n 5:95 (V/V) e t h a n o l : p e t r o l e u m e t h e r s o l v e n t m i x t u r e , and slow c r y s t a l l i z a t i o n p r o v i d e d l a r g e , c o l o r l e s s p l a t e s ; y i e l d 5.9 g ( 8 2 % ) . MP: 60-61°C. IR ( K B r ) : 1687 ( O O ) cm" 1. 1 H NMR (CDC1 3, 400 MHz): 6 7.92, (d, 2H, J = 8.5 Hz, a r o m a t i c s meta to C l ) , 7.43 (d, 2H, J = 8.5 Hz, a r o m a t i c s o r t h o t o C l ) , 2.79 (d, 2H, J = 7 Hz, C0CH 2), 1.96 (m, IH, m e t h i n e ) , 1.80-1.59 (m, 5H), 1.37-1.10 (m, 3H) , 1.10-0.95 (m, 2H). 1 3 C NMR (CDCI3, 75.4 MHz)*: 8 198.1 ( C 7 ) , 138.8 ( C 4 ) , 135.4 (C]_) , 129.2 ( C 2 and C 6 ) , 128.4 ( C 3 and C 5 ) , 45.7 ( C g ) , 34.0 ( C 9 ) , 33.0, 25.9 and 25.8 ( C 1 0 - C 1 4 ) . MS, m/e ( r e l a t i v e i n t e n s i t y ) : 236 (M+, 3.4), 201 ( 4 . 0 ) , 156 (36), 154 (100), 141 ( 4 . 0 ) , 139 (44), 111 (18); e x a c t mass c a l c d . 236.0968; found 236.0970. UV (methanol) A (max) : 326 (£ 102, n - n*) , 251 (e 20,400, *r - *•*) . A n a l . C a l c d . f o r C 1 4 H 1 7 C 1 0 : C, 71.03; H, 7.24; 0, 6.76. Found: C, 71.29; H, 7.27; 0, 6.59. F o r ease o f comparing p h o t o c h e m i c a l r e s u l t s w i t h c r y s t a l l o g r a p h y r e s u l t s , we have adopted the numbering scheme used by c r y s t a l l o -g r a p h e r s . In the e x p e r i m e n t a l s e c t i o n , the compound names were g i v e n the f o l l o w i n g the Chemical A b s t r a c t Index r u l e s . - 191 -2-C y c l o h e x y l - l - ( 4 - m e t h y l p h e n y l ) - e t h a n o n e * , 29 R e f l u x time, 2 h; y i e l d 79%. MP: 45-46°C ( p l a t e s from p e t r o l e u m e t h e r ) . IR ( K B r ) : 1684 (C-0) cm" 1. ^ NMR (CDC1 3 > 400 MHz): 5 7.83 (d, 2H, J = 8.5 Hz, a r o m a t i c s meta t o C H 3 ) , 7.24 (d, 2H, J = 8.5 Hz, a r o m a t i c s o r t h o t o C H 3 ) , 2.79 (d, 2H, J - 7 Hz, C0CH 2), 2.41 ( s , 3H, C H 3 ) , 1.97 (m, IH, m e t h i n e ) , 1.80-1.61 (m, 5H), 1.35-1.10 (m, 3H), 1.10-0.95 (m, 2H). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 216 (M +, 12), 201 (2.7), 135 (14), 134 (100), 120 (5.4), 119 (61), 92 (79), 91 (26), 65 (7.5), 55 (4.0); e x a c t mass c a l c d . 216.1514; found 216.1512. A n a l . C a l c d . f o r C 1 5H 2oO: C, 83.29; H, 9.32. Found: C, 83.22; H, 9.40. 2- C y c l o h e x y l - l - ( 4 - m e t h o x y p h e n y l ) - e t h a n o n e , 30 R e f l u x time, 2 h; y i e l d 86%. MP: 40-41°C ( p r i s m s from 95:5 (V/V) p e t r o l u e m e t h e r : e t h a n o l ) . IR ( K B r ) : 1679 (C=0) cm" 1. 1 H NMR (CDC1 3, 400 MHz): 6 7.94 (d, 2H, J = 8.5 Hz, a r o m a t i c s meta t o 0CH 3), 6.94 (d, 2H, J = 8.5 Hz, a r o m a t i c s o r t h o t o 0CH 3), 3.87 (s, 3H, OCH3), 2.76 (d, 2H, J = 7 Hz, C0CH 2), 1.95 (m, IH, met h i n e ) , I. 81-1.61 (m, 5H), 1.34-1.10 (m, 3H), 1.10-0.94 (m, 2H). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 232 (M +, 4.1), 189 (0.7), 151 (8.8), - 192 -150 (100), 136 ( 5 . 3 ) , 135 (63), 107 (5. 5 ) , 77 ( 7 . 0 ) , 64 ( 1 3 ) , 55 ( 2 . 9 ) ; e x a c t mass c a l c d . 232.1463; found 232.1465. A n a l . C a l c d . f o r C15H2o02: C, 77.55; H, 8.68. Found: C, 77.40; H, 8.55. 2 - C y c l o h e x y l - 1 - ( 4 - f l u o r o p h e n y l ) - e t h a n o n e , 31 R e f l u x time, 2 h; y i e l d 77%. MP: 31-32°C ( n e e d l e s from p e t r o l u e m e t h e r ) . IR ( K B r ) : 1686 (C=0) cm" 1. -^H NMR (CDC1 3, 400 MHz): 5 7.98 (m, 2H, a r o m a t i c s meta to F) , 7.09 (m, 2H, a r o m a t i c s o r t h o t o F ) , 2.79 (d, 2H, J = 7 Hz, C0CH 2), 1.97 (m, IH, m e t h i n e ) , 1.79-1.61 (m, 5H), 1.37-0.95 (m, 5H). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 220 (M +, 6.0), 139 (19), 138 (100), 123 (53), 95 (18); e x a c t mass c a l c d . 220.1263; found 220.1261. A n a l . C a l c d . f o r C 1 4 H 1 7 F 0 : C, 76.36; H, 7.73. Found: C, 76.57; H, 7.80. 2 - C y c l o h e x y l - 1 - ( 4 - t e r t - b u t y l p h e n y l ) - e t h a n o n e , 36 R e f l u x time, 2 h; y i e l d 60%. BP: 150-155°C (0.3 T o r r ) . MP: -7 to -5°C. IR ( n e a t ) : 1670 (C=0) cm - 1. - 193 -rE NMR (CDC1 3 > 400 MHz): S 7.91 (d, 2H, J = 8.5 Hz, a r o m a t i c s meta t o t e r t - b u t y l g r o u p ) , 7.41 (d, 2H, J = 8.5 Hz, a r o m a t i c s o r t h o to t e r t - b u t y l g r o u p ) , 2.80 (d, 2H, J = 8 Hz, C0CH 2), 1.99 (m, IH, m e t h i n e ) , 1.35 ( s , 9H, t e r t - b u t y l ) , 1.80-1.60 (m, 5H), 1.40-0.95 (m, 5H). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 258 (M +, 0.5), 201 (26), 177 (14), 176 (100), 162 ( 1 2 ) , 161 ( 9 9 ) , 91 ( 6 ) ; e x a c t mass c a l c d . 258.1990; found 258.1965. A n a l . C a l c d . f o r C l g H 2 6 0 : C, 83.67; H, 10.14. Found: C, 83.90; H, 10.20. 2 - C y c l o h e x y l - l - p h e n y l e t h a n o n e , 37 R e f l u x time, 30 min; y i e l d 85%. BP: 110-118°C (0.4 T o r r ) . MP: 5-6°C. IR ( n e a t ) : 1665 (C=0) cm" 1. 1 H NMR (CDC1 3, 400 MHz): 6 7.95 (m, 2H, a r o m a t i c s o r t h o t o c y c l o h e x y l a c e t y l ) , 7.55 (d, IH, a r o m a t i c p r o t o n p a r a t o c y c l o h e x y l a c e t y l ) , 7.46 (m, 2H, a r o m a t i c s meta to c y c l o h e x y l a c e t y l ) , 2.82 (d, 2H, J = 7 Hz, C0CH 2), 1.98 (m, IH, me t h i n e ) , 1.80-1.61 (m, 5H) , 1.37-0.95 (m, 5H). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 202 (M +, 11), 121 (20), 120 (100), 105 ( 5 4 ) , 77 (23); e x a c t mass c a l c d . 202.1358; found 202.1352. A n a l . C a l c d . f o r C 1 4 H l g 0 : C, 83.12; H, 8.97. Found: C, 83.30; H , 8.96. - 194 -2-Cyclohexyl-l-(4-cyanophenyl)-ethanone, 32 Sodium c y a n i d e (5.0 g, 0.10 moles) and 2 - c y c l o h e x y l - l - ( 4 - f l u o r o -p h e n y l ) -ethanone , (13.5 g, 0.06 moles) were added t o 75 mL o f d i m e t h y l s u l f o x i d e and h e a t e d a t 110-130°C f o r 8 h . 2 4 5 The r e a c t i o n m i x t u r e was p o u r e d i n t o 150 mL o f water and e x t r a c t e d s e v e r a l times w i t h e t h e r . The combined o r g a n i c e x t r a c t s were washed w i t h water, 5% sodium b i c a r b o n a t e s o l u t i o n , and d r i e d o v e r sodium s u l f a t e . Removal o f s o l v e n t i n vacuo p r o v i d e d 11.5 g o f l i g h t brown s o l i d t h a t showed the p r e s e n c e o f a cyano group i n i t s i n f r a r e d spectrum. The s o l i d was d i s s o l v e d i n p e t r o l e u m e t h e r , some i n s o l u b l e m a t e r i a l was f i l t e r e d and a slow e v a p o r a t i o n o f the s o l v e n t p r o v i d e d 9.7 g (70%) o f compound 32 as c o l o r l e s s p l a t e s . MP: 47-48°C. IR ( K B r ) : 2180 (C-N), 1675 (C-0) cm' 1. 1 H NMR (CDC1 3, 400 MHz): 5 8.02 (d, 2H, J - 8.5 Hz, a r o m a t i c s meta t o CN), 7.75 (d, 2H, J = 8.5 Hz, a r o m a t i c s o r t h o t o CN), 2.82 (d, 2H, J = 7 Hz, C0CH 2), 1.97 (m, IH, m e t h i n e ) , 1.79-1.62 (m, 5H), 1.36-1.10 (m, 3H), 1.09-0.95 (m, 2H). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 227 (M +, 4.0), 146 (31), 145 (42), 130 (18), 67 ( 6 . 0 ) ; e x a c t mass c a l c d . 227.1310; found 227.1312. A n a l . C a l c d . f o r C 1 5 H l y N 0 : C, 79.25; H, 7.54; N, 6.17. Found: C, 79.46; H, 7.53; N, 6.14. 195 -2 - C y c l o h e x y l - l - ( 4 - c a r b o x y p h e n y l ) - e t h a n o n e , 33 A s o l u t i o n o f compound 32 (7.5 g, 33.0 mmol) i n 35 mL o f 30% p o t a s s i u m h y d r o x i d e and 7 mL o f e t h a n o l was r e f l u x e d f o r 10 h. The r e a c t i o n m i x t u r e was a c i d i f i e d w i t h d i l u t e h y d r o c h l o r i c a c i d . T h i s r e s u l t e d i n p r e c i p i t a t i o n o f 7.0 g o f c a r b o x y l i c a c i d 33. R e c r y s t a l l i -z a t i o n from 10% aqueous e t h a n o l gave l o n g , c o l o r l e s s n e e d l e s ; y i e l d 6.3 g ( 7 8 % ) . MP: 185-186°C. IR ( K B r ) : 3300 (OH), 1684 (broad, k e t o and c a r b o x y l i c a c i d carbo-n y l ) cm" 1. X H NMR (CDC1 3, 400 MHz): 6 8.20 (d, 2H, J = 8.5 Hz, a r o m a t i c s o r t h o to COOH), 8.02 (d, 2H, J - 8.5 Hz, a r o m a t i c s meta t o COOH), 2.87 (d, 2H, J = 7 Hz, C0CH 2), 1.98 (m, IH, m e t h i n e ) , 1.80-1.62 (m, 6H), 1.36-1.10 (m, 3H), 1.09-0.96 (m, 2H). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 246 (M +, 1.2), 201 ( 2 0 ) , 164 (100), 149 (51), 121 (38), 65 (24); e x a c t mass c a l c d . 246.1256; found 246.1257. A n a l . c a l c d . f o r C 1 5 H 1 8 0 3 : C, 73.15; H, 7.46. Found: C, 73.35; H, 7.46. 2 - C y c l o h e x y l - l - ( 4 - a c e t y l o x y p h e n y l ) - e t h a n o n e , 34 M e t h y l i o d i d e (3.8 g, 260 mmol) was added w i t h c o n t i n u o u s s t i r r i n g t o a s o l u t i o n c o n t a i n i n g 1.7 g (6.9 mmol) o f compound 33 and 2.0 g (23 - 196 -mmol) o f sodium b i c a r b o n a t e i n 10 mL o f d r y d i m e t h y l formamide. The r e a c t i o n m i x t u r e was s t i r r e d f o r 18 h a t room temperature under anhy-drous c o n d i t i o n s . The m i x t u r e was poured i n t o 50 mL o f water and e x t r a c t e d w i t h 4 x 40 mL p o r t i o n s o f e t h e r . The combined e t h e r l a y e r s were washed w i t h water, d i l u t e h y d r o c h l o r i c a c i d , and d r i e d o v e r sodium s u l f a t e . E v a p o r a t i o n o f s o l v e n t i n vacuo gave 1.5 g o f methyl e s t e r 34; y i e l d 89%. MP: 67-68°C ( n e e d l e s from e t h a n o l ) . IR ( K B r ) : 1723 ( e s t e r C-0), 1685 (ketone C=0) cm' 1. % NMR (CDC1 3, 400 MHz): 6 8.12 (d, 2H, J = 8.5 Hz, a r o m a t i c s o r t h o to COOCH3), 7.98 (d, 2H, J = 8.5 Hz, a r o m a t i c s meta t o COOCH3), 3.94 ( s , 3H, COOCH3), 2.83 (d, 2H, J = 8 Hz, C0CH 2) , 1.97 (m, IH, me t h i n e ) , 1.99-0.98 (m, 10H). . MS, m/e ( r e l a t i v e i n t e n s i t y ) : 260 (M +, 19), 201 (20 ) , 179 (23), 178 (100), 147 (20 ) , 135 (11); e x a c t mass c a l c d . 260.1413; found 260.1418. A n a l . c a l c d . f o r C 1 6H 2 o 0 3 : C, 73.82; H, 7.74. Found: C, 73.56; H, 7.66. 2 - C y c l o h e x y l - 1 - ( 4 - t r i f l u o r o m e t h y l ) - e t h a n o n e , 35 To a f l a s k c o n t a i n i n g c y c l o h e x y l m e t h y l magnesium bromide ( p r e p a r e d by r e a c t i o n o f 1.0 g (41.2 mmol) o f magnesium w i t h 4.4 g (24.8 mmol) o f c y c l o h e x y l m e t h y l bromide i n 20 mL anhydrous e t h e r , i o d i n e was used as the r e a c t i o n i n i t i a t o r ) was added 2.5 g (58.4 mmol) o f 4 - t r i f l u o r o -- 197 m e t h y l b e n z o n i t r i l e i n 20 mL o f dry benzene. The r e a c t i o n m i x t u r e was r e f l u x e d f o r 4 h, c o o l e d and h y d r o l y z e d w i t h s a t u r a t e d ammonium c h l o r i d e s o l u t i o n . The o r g a n i c l a y e r was s e p a r a t e d and washed w i t h d i l u t e h y d r o c h l o r i c a c i d , water, and d r i e d over sodium s u l f a t e . E v a p o r a t i o n and subsequent d i s t i l l a t i o n under r e d u c e d p r e s s u r e p r o v i d e d two f r a c t i o n s . F r a c t i o n 1 (1.1 mL) was c o l l e c t e d a t 114-130°C, 0.5 T o r r and d i d not show an (C=0) a b s o r p t i o n i n i t s i n f r a r e d spectrum. F r a c t i o n 2 (2.3 mL) was c o l l e c t e d a t 132-134°, 0.5 T o r r and showed a s t r o n g peak f o r (C=0) i n i t s i n f r a r e d spectrum. T h i s f r a c t i o n was f u r t h e r p u r i f i e d by c o n v e n t i o n a l column chromatography u s i n g 10% (V/V) e t h y l a c e t a t e : p e t r o l e u m e t h e r as the e l u t i n g s o l v e n t . MP: 22°C. IR ( K B r ) : 1692 (C=0) cm - 1. 1 H NMR (CDC1 3, 400 MHz): 5 8.05 (d, 2H, J •= 8.5 Hz, a r o m a t i c s o r t h o t o C F 3 ) , 7.75 (d, 2H, J = 8.5 Hz, a r o m a t i c s meta to CF3), 2.85 (d, 2H, J = 7 Hz, C0CH 2), 1.98 (m, IH, m e t h i n e ) , 1.81-1.63 (m, 5H) , 1.38-0.98 (m, 5H). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 270 (M +, 3.6), 251 ( 3 . 1 ) , 201 (12), 189 ( 4 4 ) , 188 (100), 173 (61), 145 (30), 67 ( 8 . 4 ) , 55 ( 8 . 5 ) ; e x a c t mass c a l c d . 270.1232; found 270.1228. A n a l , c a l c d . f o r C 1 5 H 1 7 F 3 0 : C, 66.64; H, 6.34. Found: C, 66.65; H, 6.31. - 198 -S y n t h e s i s o f 2 - C y c l o p e n t y l - l - ( 4 - s u b s t i t u t e d p h e n y l ) - e t h a n o n e s a) P r e p a r a t i o n o f C v c l o p e n t a n e a c e t y l C h l o r i d e C y c l o p e n t a n e a c e t y l c h l o r i d e was p r e p a r e d from c y c l o p e n t a n e a c e t i c a c i d and t h i o n y l c h l o r i d e u s i n g the p r o c e d u r e employed f o r the p r e p a r a -t i o n o f c y c l o h e x a n e a c e t y l c h l o r i d e ; bp 42-44°C, 0 . 8 t o r r ; y i e l d 8 3 % . b) P r e p a r a t i o n o f 2 - C y c l o p e n t y l - l - ( 4 - s u b s t i t u t e d p h e n y l ) - e t h a n o n e s by  F r i e d e l - C r a f t s A c y l a t i o n F i v e compounds, 38-41 and 44, were s y n t h e s i z e d from c y c l o p e n t a n e -a c e t y l c h l o r i d e , anhydrous aluminum c h l o r i d e and m o n o s u b s t i t u t e d benzenes employing the method used f o r the s y n t h e s i s o f compound 28. 2 - C y c l o p e n t y l - l - ( 4 - c h l o r o p h e n y l ) - e t h a n o n e , 38 .12 199 -R e f l u x time, 3 h; y i e l d 81%. MP: 60-61°C ( p l a t e s from p e t r o l e u m e t h e r ) . IR ( K B r ) : 1686 (C=0) cm - 1. XH NMR (CDC1 3, 400 MHz): 6 7.89 (d, 2H, J •= 8.5 Hz, a r o m a t i c s meta to C l ) , 7.43 (d, 2H, J = 8.5 Hz, a r o m a t i c s o r t h o t o C l ) , 2.95 (d, 2H, J = 7 Hz, C0CH 2), 2.36 ( s e p t e t , IH, J = 7.5 Hz, m e t h i n e ) , 1.94-1.81 (m, 2H), 1.70-1.50 (m, 4H), 1.23-1.10 (m, 2H). 1 3 C NMR (CDCI3, 75.4 MHz): 5 198.2 ( C 7 ) , 138.7 ( C 4 ) , 135.2 (Cj_) , 129.1 ( C 2 and C 6 ) , 128.4 ( C 3 and C 5 ) , 44.3 ( C 8 ) , 35.6 (Cq), 32.3, 24.6 ( C 1 0 - c 1 3 ) . MS, m/e ( r e l a t i v e i n t e n s i t y ) : 222 (M+, 1.1), 156 (31), 155 (14), 154 (100), 139 (17), 110 (24), 70 (27); e x a c t mass c a l c d . 222.0810; found 222.0810. UV (methanol) A(max) : 322 (e 92, n T T * ) , 250 (e 21,500, * • - » * • * ) . A n a l . c a l c d . f o r C 1 3H 1 5C10: C, 70.09; H, 6.79; 0, 7.19. Found: C, 70.07; H, 6.86; 0, 7.12. 2 - C y c l o p e n t y l - l - ( 4 - m e t h y l p h e n y l ) - e t h a n o n e , 39 R e f l u x time, 2 h; y i e l d 90%. MP: 30-31°C ( p l a t e s from p e t r o l e u m e t h e r ) . IR ( K B r ) : 1679 (C=0) cm' 1. % NMR (CDCI3, 400 MHz): 5 7.85 (d, 2H, J = 8.5 Hz, a r o m a t i c s meta t o CH3), 7.23 (d, 2H, J = 8.5 Hz, a r o m a t i c s o r t h o t o CH3), 2.96 (d, 2H, J = 7 Hz, C0CH 2), 2.41 ( s , 3H, CH3) , 2.38 (m, IH, m e t h i n e ) , 1.93-1.82 200 -(m, 2H), 1.70-1.60 (m, 4H), 1.24-1.13 (m, 2H). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 202 (M +, 15), 134 (9 2 ) , 119 (100), 91 ( 3 4 ) , 65 (8 . 6 ) ; e x a c t mass c a l c d . 202.1358; found 202.1360. A n a l , c a l c d . f o r C 1 4 H 1 8 0 : C, 83.12; H, 8.97. Found: C, 83.31; H, 8.95. 2 - C y c l o p e n t y l - l - ( 4 - m e t h o x y p h e n y l ) - e t h a n o n e , 40 R e f l u x time, 3 h; y i e l d 71%. MP: 23-24°C (prisms from p e t r o l e u m e t h e r ) . IR ( K B r ) : 1677 (C=0) cm" 1. 1H NMR (CDC1 3, 400 MHz): 6 7.95 (d, 2H, J = 8.5 Hz, a r o m a t i c s meta t o OCH3), 6.94 (d, 2H, J = 8.5 Hz, a r o m a t i c s o r t h o t o OCH3), 3.87 ( s , 3H, OCH3), 2.93 (d, 2H, J = 7 Hz, C0CH 2), 2.38 ( s e p t e t , IH, met h i n e ) , I. 93-1.83 (m, 2H), 1.70-1.59 (m, 2H), 1.59-1.50 (m, 2H), 1.24-1.13 (m, 2H) . MS, m/e ( r e l a t i v e i n t e n s i t y ) : 218 (M+, 4.7), 152 (1 0 ) , 150 (100), 135 (93), 92 ( 6 . 1 ) , 77 (10); e x a c t mass c a l c d . 218.1307; found 218.1313. A n a l , c a l c d . f o r C 1 4 H 1 8 0 2 : C, 77.03; H, 8.31. Found: C, 77.29; H, 8.31. 2 - C y c l o p e n t y l - l - ( 4 - f l u o r o p h e n y l ) - e t h a n o n e , 41 R e f l u x time, 2 h; y i e l d 91%. - 201 MP: 28-29°C ( n e e d l e s from p e t r o l e u m e t h e r ) . IR ( K B r ) : 1683 (C=0) cm - 1. X H NMR (CDCI3, 400 MHz): 6 7.98 (m, 2H, a r o m a t i c s meta to F ) , 7.12 (m, 2H, a r o m a t i c s o r t h o t o F ) , 2.37 ( s e p t e t , IH, J = 7.5 Hz, me t h i n e ) , 2.96 (d, 2H, J = 7 Hz, C0CH 2), 1.93-1.83 (m, 2H), 1.70-1.49 (m, 4H), 1.22-1.08 (m, 2H). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 206 (M +, 5 3 ) , 139 (18), 138 ( 1 0 0 ) , 123 (87); e x a c t mass c a l c d . 206.1107; found 206.1107. A n a l , c a l c d . f o r C 1 3 H 1 5 F O : C, 75.69; H, 7.33. Found: C, 75.70; H, 7.28. 2 - C y c l o p e n t y l - l - p h e n y l e t h a n o n e , 44 R e f l u x time, 30 min; y i e l d 86%. BP: 118°C, 0.35 T o r r . MP: 3-5°C. IR ( n e a t ) : 1686 (C=0) cm" 1. XH NMR (CDCI3, 400 MHz): 6 7.94 (m, 2H, a r o m a t i c s o r t h o t o c y c l o p e n t y l a c e t y l ) , 7.53 (m, IH, a r o m a t i c p r o t o n p a r a t o c y c l o p e n t y l a c e t y l ) , 7.43 (m, 2H, a r o m a t i c s meta to c y c l o p e n t y l a c e t y l ) , 2.97 (d, 2H, J = 7 Hz, C0CH 2), 2.38 ( s e p t e t , IH, J = 7.5 Hz, m e t h i n e ) , 1.92-1.81 (m, 2H), 1.68-1.49 (m, 4H), 1.22-1.11 (m, 2H). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 188 (M +, 14), 121 (16), 120 (87.3), 105 ( 1 0 0 ) , 77 ( 4 8 ) . A n a l . c a l c d . f o r C 1 3 H 1 6 0 : C, 82.94; H, 8.57. Found: C, 82.60; H, 8.40. 2 0 2 2 - C y c l o p e n t y l - l - ( 4 - c y a n o p h e n y l ) - e t h a n o n e , 42 The s y n t h e s i s o f t h i s m o l e c u l e was a c h i e v e d by u s i n g the p r o c e d u r e d e s c r i b e d f o r the p r e p a r a t i o n o f compound 32; y i e l d 90%. MP: 49-50°C ( f l a k y n e e d l e s from 5:95 (V/V) e t h a n o l : p e t r o l e u m e t h e r ) . IR (KBr) : 2229 (ON), 1686 (C-0) cm - 1. X H NMR (CDC1 3, 400 MHz): 6 8.03 (d, 2H, J = 8.5 Hz, a r o m a t i c s meta to CN), 7.76 (d, 2H, a r o m a t i c s o r t h o t o CN), 2.99 (d, 2H, J = 7 Hz, C0CH 2), 2.37 ( s e p t e t , IH, m e t h i n e ) , 1.95-1.85 (m, 2H), 1.71-1.51 (m, 4H), 1.25-1.11 (m, 2H). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 213 (M +, 9.9), 185 ( 1 . 5 ) , 170 (3.2), 146 (59), 145 (100), 130 (81), 123 (17), 102 (43), 55 (16); e x a c t mass c a l c d . 213.1154; found 213.1146. A n a l , c a l c d . f o r C 1 4 H 1 5 N 0 : C, 78.84; H, 7.09; N, 6.57. Found: C, 79.00; H, 7.07; N, 6.45. 2 - C y c l o p e n t y l - l - ( 4 - c a r b o x y p h e n y l ) - e t h a n o n e , 43 2 - C y c l o p e n t y l - l - ( 4 - c a r b o x y p h e n y l ) - e t h a n o n e was s y n t h e s i z e d by f o l l o w i n g the p r o c e d u r e employed f o r the s y n t h e s i s o f the c o r r e s p o n d i n g c y c l o h e x a n e a n a l o g , 33. MP: 180-181°C ( n e e d l e s from 10% aqueous e t h a n o l ) . IR ( K B r ) : 3400-3300 (OH), 1705 (ketone 0 0 ) , 1673 ( c a r b o x y l i c a c i d 0 0 ) cm' 1. lU NMR ( C D C I 3 , 400 MHz): 8 8.20 (d, 2H, J = 8.5 Hz, a r o m a t i c s o r t h o - 203 to COOH), 8.04 (d, 2H, J - 8.5 Hz, a r o m a t i c s meta to COOH), 3.03 (d, 2H, J = 7 Hz, C0CH 2), 2.40 ( s e p t e t , IH, J - 7.5 Hz, m e t h i n e ) , 1.96-1.86 (m, 2H), 1.69-1.53 (m, 5H), 1.29-1.15 (m, 2H). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 232 (M +, 2.7), 188 ( 2 . 1 ) , 187 (19), 165 ( 2 7 ) , 164 (100), 149 (87), 121 (19), 70 (11); e x a c t mass c a l c d . 232.1100; found 232.1090. A n a l . c a l c d . f o r C 1 4 H 1 6 0 3 : C, 72.39; H, 6.94. Found: C, 72.19; H, 7.16. S y n t h e s i s o f 2 - C y c l o b u t y l - 1 - ( 4 - c h l o r o p h e n y l ) - e t h a n o n e , 45 a) P r e p a r a t i o n o f C y c l o b u t a n e a c e t i c A c i d ^ 5 . 9 6 C y c l o b u t a n e a c e t i c a c i d was p r e p a r e d by a f o u r s t e p s y n t h e s i s c o m p r i s i n g ( i ) the r e d u c t i o n o f c y c l o b u t a n e c a r b o x y l i c a c i d t o c y c l o -butanemethanol w i t h l i t h i u m aluminum h y d r i d e , ^ 5 ( i i ) the c o n v e r s i o n o f c y c l o b u t a n e m e t h a n o l t o c y c l o b u t a n e m e t h a n o l , p - t o l u e n e s u l f o n a t e , ^ 6 ( i i i ) the n u c l e o p h i l i c d i s p l a c e m e n t o f t o s y l a t e by c y a n i d e , and ( i v ) the h y d r o l y s i s o f c y c l o b u t a n e m e t h y l c y a n i d e t o c y c l o b u t a n e a c e t i c a c i d . ^ 6 ( i ) L i t h i u m aluminum h y d r i d e (7.4 g, 0.19 mole) was added to a s o l u t i o n o f c y c l o b u t a n e c a r b o x y l i c a c i d (25.0 g, 0.22 mole) i n 600 mL of dry e t h e r a t a r a t e s u f f i c i e n t t o produce a g e n t l e r e f l u x . A f t e r the a d d i t i o n was complete, the r e a c t i o n m i x t u r e was r e f l u x e d f o r an a d d i t i o n a l 2 h. Excess l i t h i u m aluminum h y d r i d e was d e s t r o y e d by - 204 the a d d i t i o n o f ammonium c h l o r i d e s o l u t i o n . The o r g a n i c l a y e r was s e p a r a t e d and the aqueous l a y e r was e x t r a c t e d w i t h f u r t h e r p o r t i o n s o f e t h e r . The combined e t h e r e x t r a c t s were washed w i t h water, d r i e d over sodium s u l f a t e , and the e t h e r was removed i n vacuo. D i s t i l l a -t i o n o f the r e m a i n i n g m a t e r i a l p r o v i d e d 15.2 g (142-145°C, 1 atm; 80% y i e l d ) o f c y c l o b u t a n e m e t h a n o l . ) A s o l u t i o n o f p - t o l u e n e s u l f o n y l c h l o r i d e (79.0 g, 0.41 mole) i n 70 mL o f anhydrous p y r i d i n e was added to a s o l u t i o n o f c y c l o b u t a n e -methanol (18.0 g, 0.21 mole) i n 30 mL o f anhydrous p y r i d i n e i n a 250 mL round bottomed f l a s k . The c o n t e n t s o f the f l a s k were l e f t o v e r n i g h t i n a r e f r i g e r a t o r , the r e s u l t i n g c r y s t a l s were f i l t e r e d , and the f i l t r a t e was poured i n t o 200 g o f i c e water. The m i x t u r e was e x t r a c t e d w i t h 3 x 50 mL p o r t i o n s o f e t h e r , and the combined o r g a n i c e x t r a c t s were washed w i t h 50 mL o f d i l u t e h y d r o c h l o r i c a c i d , and d r i e d over sodium s u l f a t e . S o l v e n t removal p r o v i d e d 29.1 g (58% y i e l d ) o f t o s y l a t e which was u sed w i t h o u t f u r t h e r p u r i f i c a t i o n . i ) C y c l o b u t a n e m e t h a n o l , p - t o l u e n e s u l f o n a t e (18.2 g, 75.8 mmol) was c o n v e r t e d t o c y c l o b u t a n e a c e t o n i t r i l e (6.5 g, 82% y i e l d ) by u s i n g the same method as f o r the p r e p a r a t i o n o f compound 32. ) C y c l o b u t a n e a c e t o n i t r i l e (3.0 g, 29 mmol), 5 mL o f 30% aqueous p o t a s s i u m h y d r o x i d e , and 7 mL o f e t h a n o l were r e f l u x e d o v e r n i g h t . A c i d i f i c a t i o n o f the r e a c t i o n m i x t u r e u s i n g d i l u t e h y d r o c h l o r i c a c i d p r o v i d e d c y c l o b u t a n e a c e t i c a c i d i n 85% y i e l d . IR ( n e a t ) : 3300-3200 (OH), 1700 ( b r , C=0) cm' 1. 1 H NMR (CDC1 3, 80 MHz): 6 12.2 (br s, IH, exchangeable, COOH), 2.49 - 205 -(d, 2H, J = 7.5 Hz, COCH 2), 2.4-1.5 (m, 7H). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 114 (M +, 0.3), 96 ( 4 . 8 ) , 85 (100), 69 (15), 68 (20), 58 (52). b) P r e p a r a t i o n o f Compound 45 by F r i e d e l - C r a f t s A c y l a t i o n C y c l o b u t a n e a c e t i c a c i d was c o n v e r t e d to c y c l o b u t a n e a c e t y l c h l o r i d e by t r e a t m e n t w i t h t h i o n y l c h l o r i d e , and the c y c l o b u t a n e a c e t y l c h l o r i d e was d i s t i l l e d i n vacuo a t 38-40°C, 30 T o r r (71% y i e l d ) . 2 - C y c l o b u t a n e - l - ( 4 - c h l o r o p h e n y l ) - e t h a n o n e was p r e p a r e d by the g e n e r a l p r o c e d u r e d e s c r i b e d f o r the s y n t h e s i s o f compound 28 w i t h the e x c e p t i o n t h a t a f t e r the removal o f c h l o r o b e n z e n e , the crude compound was d i s t i l l e d a t 110-120°C, 0.3 T o r r u s i n g a K u g e l r o h r a p p a r a t u s . MP: 50-51°C ( p l a t e s from p e t r o l e u m e t h e r ) . IR ( K B r ) : 1683 (C=0) cm - 1. 1 H NMR (CDC1 3, 400 MHz): 5 7.85 (d, 2H, J = 8.5 Hz, a r o m a t i c s meta to C l ) , 7.41 (d, 2H, J = 8.5 Hz, a r o m a t i c s o r t h o to C l ) , 3.05 (d, 2H, J = 7 Hz, C0CH 2), 2.83 ( s e p t e t , IH, J = 7 Hz, m e t h i n e ) , 2.24-2.13 (m, 2H), - 206 2.01-1.92 (m, 2H), 1.79-1.66 (m, 2H). 1 3 C NMR (CDC1 3, 75.4MHz): 6 198.3 ( C y ) , 139.1 ( C 4 ) , 135.3 ( C L ) , 129.3 ( C 2 and C 6 ) , 128.7 <C 3 and C 5 ) , 45.4 ( C 8 ) , 31.8 ( C 9 ) , 29.6, 28.5, and 18.8 ( C 1 0 - C 1 2 ) • MS, m/e ( r e l a t i v e i n t e n s i t y ) : 208 (M +, 1.2), 179 (14), 173 (26), 154 (24), 139 (100), 111 (31), 75 (14); e x a c t mass c a l c d . 208.0655; found 208.0633. A n a l , c a l c d . f o r C 1 2 H 1 3 C 1 0 : C, 69.06; H, 6.24; 0, 7.67. Found: C, 69.29; H, 6.33; 0, 7.71. S y n t h e s i s o f 2 - B i c y c l o [ 2 . 2 . l ] h e p t - 2 - y l - e x o - l - ( 4 - s u b s t i t u t e d p h e n y l ) - e t h a n o n e s a) P r e p a r a t i o n o f B i c y c l o \ 2 . 2 . 1 I h e p t a n e - e x o - 2 - a c e t v l c h l o r i d e B i c y c l o [ 2 . 2 . 1 ] h e p t a n e - e x o - 2 - a c e t i c a c i d was r e f l u x e d w i t h t h i o n y l c h l o r i d e . T h i o n y l c h l o r i d e removal and re d u c e d p r e s s u r e d i s t i l l a t i o n (58-60°C, 0.3 T o r r ) p r o v i d e d t i t l e compound i n 83% y i e l d . b) P r e p a r a t i o n o f 2 - B i c y c l o \ 2 . 2 . l l h e p t - 2 - y l - e x o - 1 - ( 4 - s u b s t i t u t e d p h e n y l ) - e t h a n o n e s by F r i e d e l - C r a f t s A c y l a t i o n Method 207 The f o l l o w i n g f o u r compounds 46-49, were p r e p a r e d u s i n g the p r o c e -dure d e s c r i b e d f o r the p r e p a r a t i o n o f compound 28. 2 - B i c y c l o [ 2 . 2 . l ] h e p t - 2 - y l - e x o - 1 - ( 4 - c h l o r o p h e n y l ) - e t h a n o n e , 46 R e f l u x time, 2 h; y i e l d 76%. MP: 54-55°C (p r i s m s from p e t r o l e u m e t h e r ) . IR ( K B r ) : 1681 (C=0) cm" 1. 1 H NMR (CDC1 3, 400 MHz): 6 7.88 (d, 2H, J = 8.5 Hz, a r o m a t i c s meta to C l ) , 7.42 (d, 2H, J = 8.5 Hz, a r o m a t i c s o r t h o t o C l ) , 2.92 (dd, IH, J = 1 5 . 5 and 8 Hz, C0CH 2), 2.86 (dd, IH, J = 15.5 and 8 Hz, C0CH 2), 2.24 (br s, IH, methine 0 to CO), 2.10-1.98 (m, 2H), 1.64-1.43 (m, 3H), 1.39-1.32 (m, IH), 1.30-1.05 (m, 4H). 1 3 C NMR (CDCI3, 7 5 . 4 M H z ) : S 198.1 ( C y ) , 138.8 ( C 4 ) , 135.2 ( C x ) , 129.1 ( C 2 and C 6 ) , 128.4 ( C 3 and C 5 ) , 45.3 ( C 8 ) , 41.0 ( C 9 ) , 37.4 ( C n or C 1 4 ) , 36.4 ( C n o r C 1 4 ) , 37.9, 35.1, 29.6, and 28.2, ( C 1 0 , C 1 2 , C 1 3 , and 0^5). - 208 -MS, m/e ( r e l a t i v e i n t e n s i t y ) : 248 (M +, 21), 213 (13), 156 (31), 154 (100), 141 (29), 139 (90), 113 (8. 0 ) , 111 (24); e x a c t mass c a l c d . 248.0968; found 248.0963. UV (methanol) A(max) : 326 (e 93, n / ) , 249 (e 21,000, T T - + * * ) . A n a l . c a l c d . f o r C 1 5 H 1 7 C 1 0 : C, 72.14; H, 7.21; 0, 6.41. Found: C, 71.96; H, 7.19; 0, 6.20. 2 - B i c y c l o [ 2 . 2 . l ] h e p t - 2 - y l - e x o - l - ( m e t h y l p h e n y l ) - e t h a n o n e , 47 R e f l u x time, 2 h; y i e l d 76%. MP: 63-64°C ( p l a t e s from p e t r o l e u m e t h e r ) . IR ( K B r ) : 1676 (C=0) cm" 1. 1 H NMR (CDC1 3, 400 MHz): 5 7.84 (d, 2H, J - 8.5 Hz, a r o m a t i c s meta to C H 3 ) , 7.23 (d, 2H, J = 8.5 Hz, a r o m a t i c s o r t h o t o CH3), 2.91 (dd, IH, J = 15.5 and 8 Hz, C0CH 2), 2.87 (dd, IH, J = 15.5 and 8 Hz, C0CH 2), 2.41 ( s , 3H, C H 3 ) , 2.22 (br s, IH, methine 0 t o CO), 2.09-2.00 (m, 2H), 1.60-1.42 (m, 3H), 1.37 (m, IH), 1.29-1.06 (m, 4H). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 228 (M +, 21), 213 ( 9 . 2 ) , 134 (84), 119 (100), 91 (35), 65 (11); e x a c t mass c a l c d . 228.1514; found 228.1518. A n a l . c a l c d . f o r C 1 6 H 2 0 0 : C, 84.16; H, 8.83. Found: C, 83.96; H, 8.76. 2 - B i c y c l o [ 2 . 2 . l ] h e p t - 2 - y l - e x o - 1 - ( 4 - m e t h o x y p h e n y l ) - e t h a n o n e , 48 R e f l u x time, 3 h; y i e l d 90%. - 209 -MP: 74-75°C ( f l a k y n e e d l e s from 5:95 (V/V) e t h a n o l : p e t r o l e u m e t h e r ) . IR ( K B r ) : 1667 (C-0) cm" 1. I-H NMR ( C D C 1 3 , 400 MHz): 6 7.93 (d, 2H, J = 8.5 Hz, a r o m a t i c s meta to OCH3), 6.92 (d, 2H, a r o m a t i c s o r t h o to OCH3), 3.87 ( s , 3H, 0CH 3), 2.90 (dd, IH, J = 15.5 and 8 Hz, C 0 C H 2 ) , 2.85 (dd, IH, J = 15.5 and 8 Hz, C 0 C H 2 ) , 2.23 (m, IH, methine jS to CO), 2.10-2.00 (m, 2 H ) , 1.61-1.45 (m, 3H) , 1.38 (m, IH), 1.30-1.05 (m, 4 H ) . MS, m/e ( r e l a t i v e i n t e n s i t y ) : 244 (M +, 14), 151 ( 8 . 0 ) , 150 (82), 135 (100), 77 (1 5) ; e x a c t mass c a l c d . 244.1467; found 244.1462. A n a l , c a l c d . f o r C 1 6 H 2 0 O 2 : C, 78.65; H, 8.25. Found: C, 78.75; H, 8.15. 2 - B i c y c l o [ 2 . 2 . l ] h e p t - 2 - y l - e x o - l - p h e n y l e t h a n o n e , 49 R e f l u x time, 30 min; y i e l d 65%. BP: 140-144°C, 0.3 T o r r . MP: -8 to -6°C. IR ( n e a t ) : 1671 (C=0) cm" 1. 1 H NMR ( C D C I 3 , 400 MHz): 6 7.96 (m, 2H, a r o m a t i c s o r t h o to b i c y c l o h e p t y l a c e t y l ) , 7.56 (m, IH, a r o m a t i c p r o t o n p a r a to b i c y c l o -h e p t y l a c e t y l ) , 7.45 (m, 2H, a r o m a t i c s meta to b i c y c l o h e p t y l a c e t y l ) 2.96 (dd, IH, J = 15 and 9 Hz, C 0 C H 2 ) , 2.79 (dd, IH, J - 15 and 9 Hz, C 0 C H 2 ) , 2.23 (m, IH, methine to CO), 2.11-1.99 (m, 2H), 1.66-1.43 (m, 3H), 1.38 (m, IH), 1.30-1.06 (m, 4 H ) . MS, m/e ( r e l a t i v e i n t e n s i t y ) : 214 (M +, 4 3 ) , 160 ( 3 . 9 ) , 146 ( 5 . 4 ) , - 210 -145 ( 5 . 4 ) , 121 (12), 120 (88), 105 (100), 77 (63), 67 ( 1 3 ) . A n a l , c a l c d . f o r C 1 5 H 1 8 0 : C, 84.07; H, 8.47. Found: C, 84.41; H, 8.63. S y n t h e s i s o f 2 - c y c l o h e p t y l - 1 - ( 4 - s u b s t i t u t e d p h e n y l ) - e t h a n o n e s a) S y n t h e s i s o f C y c l o h e p t a n e a c e t i c A c i d 9 ^ C y c l o h e p t a n e a c e t i c a c i d was p r e p a r e d by a method i n v o l v i n g t h r e e s t e p s : ( i ) the c o n d e n s a t i o n o f c y c l o h e p t a n o n e w i t h c y a n o a c e t i c a c i d f o l l o w e d by d e c a r b o x y l a t i o n , ( i i ) the h y d r o l y s i s o f c y c l o h e p t e n y l a c e t o n i t r i l e t o c y c l o h e p t e n y l a c e t i c a c i d , and ( i i i ) the h y d r o g e n a t i o n o f c y c l o h e p t e n y l a c e t i c a c i d to c y c l o h e p t a n e a c e t i c a c i d . ( i ) C y c l o h e p t a n o n e (120.0 g, 1.07 mole), c y a n o a c e t i c a c i d (85.0 g, 1 mole) and ammonium a c e t a t e (3.0 g, 0.04 mole) were d i s s o l v e d i n 100 mL o f d r y benzene and p l a c e d i n a Dean-Stark a p p a r a t u s . A f t e r r e f l u x i n g f o r 36 h, 22 mL o f water was c o l l e c t e d . Benzene was removed i n vacuo and the r e m a i n i n g c y c l o h e p t y l i d e n e c y a n o a c e t a t e was d e c a r b o x y l a t e d by h e a t i n g a t 165-175°, 15 T o r r f o r 3 days. The r e a c t i o n m i x t u r e was then d i l u t e d w i t h 50 mL o f e t h e r and washed w i t h 5% sodium c a r b o n a t e s o l u t i o n , and water. The o r g a n i c l a y e r was d r i e d over sodium s u l f a t e and the s o l v e n t removal i n vacuo p r o v i d e d c y c l o h e p t e n y l a c e t o n i t r i l e i n 88% y i e l d ; bp 110-120°, 15 T o r r . - 211 -( i i ) C y c l o h e p t e n y l a c e t o n i t r i l e was c o n v e r t e d t o c y c l o h e p t e n y l a c e t i c a c i d by f o l l o w i n g the p r o c e d u r e used f o r p r e p a r i n g compound 33; bp 80-90°C, 13 T o r r , y i e l d 81%. ( i i i ) C y c l o h e p t e n y l a c e t i c a c i d (15.4 g, 0.1 mole) i n 30 mL o f anhydrous methanol was h y d r o g e n a t e d under a p r e s s u r e o f 50 pounds/sq. i n c h o f hydrogen f o r 14 h a t room temperature u s i n g 2.0 g o f 10% Pd/C as the c a t a l y s t . Removal o f methanol a f f o r d e d c y c l o h e p t a n e a c e t i c a c i d i n q u a n t i t a t i v e y i e l d . IR ( n e a t ) : 3400-3200 (OH) and 1700 ( b r , C-0) cm - 1. ^H NMR (CDC1 3, 400MHz): fi 10.6 (br s, IH, exchangeable, COOH), 2.50 (d, 2H, J = 7.5 Hz, C0CH 2), 2.01 (m, IH, m e t h i n e ) , 1.80-1.10 (m, 12H) . MS, m/s ( r e l a t i v e i n t e n s i t y ) : 156 (M +, 2.2), 138 ( 1 . 9 ) , 97 ( 9 5 ) , 96 (35), 81 (38), 69 (16), 67 (37), 60 (65), 55 (100). b) P r e p a r a t i o n o f C y c l o h e p t a n e a c e t y l C h l o r i d e C y c l o h e p t a n e a c e t i c a c i d was r e f l u x e d w i t h excess t h i o n y l c h l o r i d e f o r 30 min. Removal o f t h i o n y l c h l o r i d e and r e d u c e d p r e s s u r e d i s t i l l a -t i o n (94-96"C, 0.5 T o r r ) p r o v i d e d c y c l o h e p t a n e a c e t y l c h l o r i d e i n 92% y i e l d . P r e p a r a t i o n o f 2 - C y c l o h e p t a n e - l - ( 4 - s u b s t i t u t e d p h e n y l ) - e t h a n o n e s by F r i e d e l - C r a f t s A c y l a t i o n - 212 -Compounds 50-52 were p r e p a r e d by the p r o c e d u r e employed f o r the p r e p a r a t i o n o f compound 28. 2 - C y c l o h e p t y l - l - ( 4 - c h l o r o p h e n y l ) - e t h a n o n e , 50 R e f l u x time, 5 h; y i e l d 72%. MP: 42-43°C ( p l a t e s from p e t r o l e u m e t h e r ) . IR ( K B r ) : 1689 (C=0) cm - 1. X H NMR (CDC1 3, 400 MHz): 5 7.89 (d, 2H, J = 8.5 Hz, a r o m a t i c s meta to C l ) , 7.43 (d, 2H, J = 8.5 Hz, a r o m a t i c s o r t h o t o C l ) , 2.83 (d, 2H, J = 7 Hz, C0CH 2), 2.19 (m, IH, m e t h i n e ) , 1.80-1.69 (m, 2H), 1.69-1.55 (m, 4H), 1.55-1.42 (m, 4H), 1.35-1.20 (m, 2H). 1 3 C NMR (CDCI3, 7 5 . 4 M H z ) : S 198.0 ( C 7 ) , 138.7 ( C 4 ) , 135.3 ( C x ) , 129.1 ( C 2 and C 6 ) , 128.4 ( C 3 and C 5 ) , 46.2 ( C 8 ) , 35.4 (Cq), 34.4, 27.9, and 25.9 ( C 1 0 - C 1 5 ) • MS, m/e ( r e l a t i v e i n t e n s i t y ) : 250 (M +, 1.4), 215 ( 1 . 8 ) , 193 ( 1 . 2 ) , - 213 179 ( 0 . 5 ) , 156 (32), 154 (100), 139 (51), 111 (22); e x a c t mass c a l c d . 250.1125; found 250.1127. UV (methanol) A (max) : 327 (e 88, n -» «*) , 252 (e 20,600, ir -» ir*) . A n a l , c a l c d . f o r C 1 5 H 1 9 C 1 0 : C, 72.00; H, 8.00; 0, 6.40. Found: C, 71.86; H, 8.00; 0, 6.49. 2 - C y c l o h e p t y l - l - ( 4 - m e t h y l p h e n y l ) - e t h a n o n e , 51 R e f l u x time, 1 h; y i e l d 78%. MP: 38-39°C ( p l a t e s from p e t r o l e u m e t h e r ) . IR ( K B r ) : 1676 (C=0) cm" 1. T-H NMR (CDC1 3, 400 MHz): 6" 7.89 (d, 2H, J = 8.5 Hz, a r o m a t i c s meta t o C H 3 ) , 7.19 (d, 2H, J = 8.5 Hz, a r o m a t i c s o r t h o t o C H 3 ) , 2.83 (d, 2H, J = 7 Hz, C0CH 2), 2.40 ( s , 3H, 0CH 3), 2.20 (m, IH, m e t h i n e ) , 1.80-1.70 (m, 2H), 1.70-1.55 (m, 4H), 1.55-1.40 (m, 4H), 1.32-1.20 (m, 2H). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 230 (M+, 4.4), 215 ( 1 . 4 ) , 173 ( 1 . 0 ) , 134 (100), 119 (63), 91 (35), 65 (13); e x a c t mass c a l c d . 230.1671; found 230.1679. A n a l . c a l c d . f o r C 1 6 H 2 2 0 : C, 83.43; H, 9.65. Found: C, 83.63; H, 9.84. 2 - C y c l o h e p t y l - l - ( 4 - m e t h o x y p h e n y l ) - e t h a n o n e , 52 214 -R e f l u x time, 2 h; y i e l d 91%. MP: 27-28°C (prisms from p e t r o l e u m e t h e r ) . IR ( K B r ) : 1676 (C-0) cm - 1. 1 H NMR (CDC1 3, 400 MHz): S 7.94 (d, 2H, J = 8.5 Hz, a r o m a t i c s meta to OCH3), 6.94 (d, 2H, J = 8.5 Hz, a r o m a t i c s o r t h o t o OCH3), 3.96 ( s , 3H, OCH 3), 2.81 (d, 2H, J = 7 Hz, C0CH 2), 2.20 (m, IH, m e t h i n e ) , 1.80-1.70 (m, 2H), 1.70-1.56 (m, 4H), 1.55-1.40 (m, 4H), 1.34-1.21 (m, 2H). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 246 (M +, 2.7), 189 ( 2 . 2 ) , 150 (100), 135 ( 4 . 8 ) ; e x a c t mass c a l c d . 246.1620; found 246.1619. A n a l , c a l c d . f o r C 1 6 H 2 2 0 2 : C, 78.01; H, 9.00. Found: C, 78.11; H, 8.97. S y n t h e s i s o f 2 - C y c l o o c t y l - l - ( 4 - c h l o r o p h e n y l ) - e t h a n o n e , 53 2 - C y c l o o c t y l - l - ( 4 - c h l o r o p h e n y l ) - e t h a n o n e was p r e p a r e d i n our l a b o r a t o r y by Mr. B. Harkness u s i n g the F r i e d e l - C r a f t s a c y l a t i o n method. S p e c t r a l c h a r a c t e r i s t i c s and p h o t o c h e m i s t r y o f compound 53 a r e d e s c r i b e d e l s ewhere. S y n t h e s i s o f 2 - T r i c y c l o [ 3 . 3 . 1 . 1 J • ' ] d e c - l - y l - 1 - ( 4 - s u b s t i t u t e d p h e n y l ) - e thanone s 215 2 - T r i c y c l o [ 3 . 3 . 1 . 1 J • ' ] d e c - 1 - y l - a c e t i c a c i d (adamantaneacetic a c i d ) was c o n v e r t e d t o the c o r r e s p o n d i n g a c i d c h l o r i d e by r e f l u x i n g w i t h t h i o n y l c h l o r i d e ; bp 100-103°C, 0.3 T o r r ; y i e l d 91%. A l l compounds i n t h i s s e r i e s were p r e p a r e d by F r i e d e l - C r a f t s a c y l a t i o n method as d e s c r i b e d f o r the s y n t h e s i s o f compound 2 8 . 2 - T r i c y c l o [ 3 . 3 . 1 . 1 J • ' ] d e c - l - y l - l - ( 4 - c h l o r o p h e n y l ) - e t h a n o n e , 54n and 54p R e f l u x time, 2 h; y i e l d 59%. MP: 73-74°C ( n e e d l e s (54n) from p e t r o l e u m e t h e r ) . 72-73°C ( p l a t e s (54p) from 10% aqueous e t h a n o l ) . IR ( K B r ) : 1665 (C=0) cm - 1; n e e d l e s (54n). 1660 (C=0) cm - 1; p l a t e s (54p). I-H NMR (CDC1 3, 400 MHz): 6 7.88 (d, 2H, J = 8.5 Hz, a r o m a t i c s meta to C l ) , 7.42 (d, 2H, J = 8.5 Hz, a r o m a t i c s o r t h o to C l ) , 2.68 ( s , 2 H , C0CH 2), 1.85 (m, 3H, m e t h i n e ) , 1.74-1.59 (m, 12H, m e t h y l e n e s ) . - 216 -1 3 C NMR (CDCI3, 75.4 MHz): 5 198.6 ( C y ) , 139.0 ( C 4 ) , 136.9 (C]_) , 129.7 ( C 2 and C 6 ) , 128.5 ( C 3 and C 5 ) , 51.0 ( C g ) , 42.8 ( C 1 0 , C 1 6 , C 1 8 o r C 1 2 , C 1 4 , C 1 7 ) , 36.5 ( C 1 0 , C 1 6, C 1 8 o r C 1 2, C 1 4 , C 1 7 ) , 33.8 ( C 9 ) , 28.5 ( cll. c 1 3 a n d c 1 5 ) • MS, m/e ( r e l a t i v e i n t e n s i t y ) : 288 (M +, 3.6), 253 (100), 235 (2.3), 213 ( 1 . 9 ) , 154 ( 4 . 3 ) , 141 (20), 139 (55). UV (methanol) A(max): 327 (e 95, n -+ n*) , 251 (e 21,000, ir - n*) . A n a l . c a l c d . f o r C 1 8 H 2 1 C 1 0 : C, 74.86; H, 7.33; 0, 5.54. Found: C, 74.85; H, 7.28; 0, 5.50. 2 - T r i c y c l o [ 3 . 3 . 1 . 1 J • ' ] d e c - 1 - y l - l - ( 4 - m e t h y l p h e n y l ) - e t h a n o n e , 55 R e f l u x time, 2 h; y i e l d 78%. MP: 73-74°C ( n e e d l e s from p e t r o l e u m e t h e r ) . IR ( K B r ) : 1655 (C=0) cm - 1. •^H NMR (CDCI3, 400 MHz): S 7.85 (d, 2H, J = 8.5 Hz, a r o m a t i c s meta to C H 3 ) , 7.26 (d, 2H, J = 8.5 Hz, a r o m a t i c s o r t h o t o CH3), 2.69 ( s , 2H, C0CH 2), 2.41 ( s , 3H, CH3), 1.94 (m, 3H, m e t h i n e s ) , 1.70-1.61 (m, 12H, m e t h y l e n e s ) . MS, m/e ( r e l a t i v e i n t e n s i t y ) : 268 (M +, 31), 253 (61), 239 (4.4), 135 ( 1 4 ) , 120 (11), 119 (100), 91 (39), 79 (10); e x a c t mass c a l c d . 268.1827; found 268.1830. UV (methanol) A(max): 327 (e 126, n -•*•*) , 246 (e 18,600, TT *•*) . A n a l , c a l c d . f o r C 1 9 H 2 4 0 : C, 85.03; H, 9.01. Found: C, 84.86; H, 9.07. - 217 2 -Tr icyclo[3.3.1.1 J'']de c-1-y1-1-(4-methoxypheny1)-ethanone, 56 R e f l u x time, 3 h; y i e l d 81%. MP: 80-81°C (p r i s m s from e t h a n o l ) . IR ( K B r ) : 1660 cm" 1 (C=0). 1 H NMR (C D C ] 3 , 400 MHz): 6 7.64 (d, 2H, J = 8 . 5 Hz , a r o m a t i c s meta to 0 C H 3 ) , 6.94 (d, 2H, J = 8.5 Hz, a r o m a t i c s o r t h o t o OCH3), 3.87 ( s , 3H, OCH3), 2.66 ( s , 2H, C0CH 2), 1.95 (m, 3H, m e t h i n e s ) , 1.65-1.51 (m, 12H, m e t h y l e n e s ) . 1 3 C NMR (CDCI3, 7 5 . 4 M H z ) : 6 198.4 ( C ? ) , 163.4 ( C 4 ) , 132.4 ( C x ) , 130.7 ( C 2 and C g ) , 113.8 (C3 and C5), 55.4 (Cg), 51.1 (Cg), 43.2 ( C 1 0 , c16> c 1 8 o r c12> c14> c 1 7 ) - 3 7 - ° ( c10> c16> c 1 8 o r c12> c14> c 1 7 ) • 3 4 - ° ( C 1 9 ) , 29.0 ( C n , C 1 3 and C 1 5 ) . MS, m/e ( r e l a t i v e i n t e n s i t y ) : 284 (M +, 1 2 ) , 283 ( 8 . 5 ) , 266 ( 7 . 9 ) , 253 ( 2 0 ) , 150 ( 4 . 0 ) , 135 ( 1 0 0 ) , 107 ( 1 1 ) , 92 ( 7 . 2 ) , 77 (16); e x a c t mass c a l c d . 284.1777; found 284.1774. - 218 UV (methanol) A(max): 324 (e 257, n - n*) , 274 (e 15,800, n - TT*) . A n a l , c a l c d . f o r C 1 9 H 2 4 0 2 : C, 80.24; H, 8.51. Found: C, 80.34; H, 8.46. 2 - T r i c y c l o [ 3 . 3 . 1 . 1 J »']dec-l-yl-l-phenylethanone, 1 1 1 57 R e f l u x time, 2 h; y i e l d 80%. MP: 64-65°C ( l i t . 6 4 - 6 5 ° C ) . m IR ( K B r ) : 1660 (C=0) cm - 1. X H NMR (CDC1 3, 400 MHz): 6 7.95 (m, 2H, a r o m a t i c s o r t h o to adamantyl a c e t y l , 7.53 (m, IH, a r o m a t i c p r o t o n p a r a t o adamantyl a c e t y l ) , 7.44 (m, 2H, a r o m a t i c s meta to adamantyl a c e t y l ) , 2.72 ( s , 2H, C0CH 2), 1.95 (m, 3H, m e t h i n e s ) , 1.73-1.55 (m, 12H, m e t h y l e n e s ) . MS, m/e ( r e l a t i v e i n t e n s i t y ) : 254 (M +, 84), 253 (15), 236 (17), 135 (31), 105 (100), 79 (13), 77 (37); e x a c t mass c a l c d . 254.1671; found 254.1673. UV (methanol) A(max) : 329 (e 75, n - T T * ) , 242 (e 17,800, TT - TT*) . A n a l , c a l c d . f o r C 1 8 H 2 2 0 : C, 84.99; H, 8.72. Found: C, 85.04; H, 8.62. - 219 S y n t h e s i s o f 2 - ( 3 - M e t h y l t r i c y c l o [ 3 . 3 . 1 . 1 J • ' ] d e c - l - y l - 1 -( 4 - c h l o r o p h e n y l ) - e t h a n o n e , 58 3 - M e t h y l t r i c y c l o [ 3 . 3 . 1 . 1 J • 1 ] d e c a n e - l - a c e t i c a c i d ( 3 - m e t h y l - l - a d a -m a n t a n e a c e t i c a c i d ) was c o n v e r t e d i n t o the c o r r e s p o n d i n g a c i d c h l o r i d e by r e f l u x i n g i n t h i o n y l c h l o r i d e . Removal o f t h i o n y l c h l o r i d e i n vacuo and d i s t i l l a t i o n a t reduced p r e s s u r e gave a c i d c h l o r i d e (110-125°C, 0.3 T o r r ) i n 84% y i e l d . T h i s was used w i t h o u t any f u r t h e r p u r i f i c a t i o n . 3 - M e t h y l t r i c y c l o [ 3 . 3 . 1 . 1 3 > 7 ] d e c a n e - l - a c e t y l c h l o r i d e (2.74 g, 12.1 mmol), aluminum c h l o r i d e (3.0 g, 22.5 mmol), and 10 mL o f c h l o r o b e n z e n e were r e f l u x e d f o r 2 h. Work up i n the u s u a l way p r o v i d e d 4.1 g o f crude ketone, which was f u r t h e r p u r i f i e d by a column chromatography u s i n g p e t r o l e u m e t h e r as e l u e n t , y i e l d 57%. MP: 45-46°C (pr i s m s from 5% aqueous e t h a n o l ) . IR ( K B r ) : 1670 (C=0) cm - 1. XH NMR (CDC1 3, 400 MHz): 5 7.88 (d, 2H, J = 9 Hz, a r o m a t i c s meta to C l ) , 7.42 (d, 2H, J = 9 Hz, a r o m a t i c s o r t h o to C l ) , 2.70 ( s , 2H, C0CH 2), 2.99 (m, 2H, m e t h i n e s ) , 1.52-1.48 (m, 6H, m e t h y l e n e s ) , 1.45-1.31 (m, 6H, 220 m e t h y l e n e s ) , 0.78 ( s , 3H, C H 3 ) . 1 3 C NMR (CDCI3, 75.4MHz): 5 198.6 ( C 7 ) , 139.0 ( C 4 ) , 136.9 ( C x ) , 129.7 ( C 2 and C 6 ) , 128.6 ( C 3 and C 5 ) , 50.6, (Cg), 49.6, 43.5, 42.1, and 35.7 ( C 1 0 , C 1 2 , C 1 4 , C 1 6 - C 1 8 ) , 34.6, 30.5 ( C 9 and C 1 3 ) , and 30.8 ( C n and C 1 5 ) , 29.0 ( C 1 9 ) . MS, m/e ( r e l a t i v e i n t e n s i t y ) : 302 (M +, 5.7), 284 ( 4 . 5 ) , 267 (100), 139 (66), 111 (15), 93 (24); e x a c t mass c a l c d . 302.1437; found 302.1453. A n a l . c a l c d . f o r C 1 9 H 2 3 C 1 0 : C, 75.36; H, 7.65. Found: C, 75.28; H, 7.43. S y n t h e s i s o f I n c l u s i o n Complexes w i t h 4-p-hydroxyphenyl-2 , 2 , 4 - t r i m e t h y l c h r o m a n (the D i a n i n ' s Compound). D i a n i n ' s compound was p r e p a r e d and p u r i f i e d i n our l a b o r a t o r y by Mr. H. Wong u s i n g the method o f Baker e t a l . 2 2 2 U n s o l v a t e d D i a n i n ' s compound was o b t a i n e d by s u b l i m a t i o n o f the e t h a n o l complex a t 140° and 1 T o r r (mp 166-167°C). The i n c l u s i o n complexes o f D i a n i n ' s compound w i t h ketone 37 and 44 were p r e p a r e d by d i s s o l v i n g the u n s o l v a t e d D i a n i n ' s compound i n the a p p r o p r i a t e ketone a t 80°C, f o l l o w e d by slow c r y s t a l l i z a t i o n . The complexes were d r i e d a t 50-55°C, 0.05 T o r r and the d r y i n g was t e r m i n a t e d when the l o s s o f weight was l e s s than 1 0 " 5 g/h. The h o s t / g u e s t r a t i o s were d e t e r m i n e d by c a p i l l a r y gas chromatography from i n t e g r a t i o n o f the peaks due to the ketone and D i a n i n ' s compound. - 221 -PHOTOCHEMICAL PROCEDURES a) A n a l y t i c a l Photolyses A l l a n a l y t i c a l runs f or both the s o l i d and s o l u t i o n state i r r a d i a -tions were conducted using a minimum of 3 samples, and f o r each photo-l y s i s at l e a s t 3 gas chromatographic runs were performed. The tabulated cyclization:cleavage and c i s : t r a n s cyclobutanol r a t i o s are s t a t i s t i c a l averages from the gas chromatographic r e s u l t s , which are c a l i b r a t e d f o r detector response with appropriate i n t e r n a l standards. The o v e r a l l p r e c i s i o n of the reported r e s u l t s i s ±5%. i ) S o l i d State I r r a d i a t i o n s A n a l y t i c a l runs were c a r r i e d out by i r r a d i a t i n g s i n g l e c r y s t a l s or p o l y c r y s t a l l i n e samples (powders) i n 3 mm sealed pyrex or quartz tubes under i n e r t atmosphere. The i r r a d i a t i o n s were conducted e i t h e r at 337 nm using the output from a Molectron UV 22 pulsed nitrogen l a s e r (330 mW average power) or at A> 290 nm or A> 200 nm using a 450 W Hanovia lamp housed i n a pyrex or quartz jacket, r e s p e c t i v e l y . The r e s u l t s obtained with the l a s e r and lamp i r r a d i a t i o n s were found to be i d e n t i c a l within experimental error . A l l the s o l i d state conversions to products were l i m i t e d to 5% to minimize the e f f e c t s of sample melting on product d i s t r i b u t i o n . - 222 i i ) S o l u t i o n S t a t e I r r a d i a t i o n s A l l s o l u t i o n s t a t e a n a l y t i c a l runs were c o n d u c t e d i n 3 mm pyrex tubes which were s e a l e d a f t e r s e v e r a l freeze-pump-thaw c y c l e s . The s o l v e n t was e i t h e r anhydrous benzene o r a c e t o n i t r i l e c o n t a i n -i n g 2% water, and the c o n c e n t r a t i o n was 0.1 M. C o n v e r s i o n t o p r o d u c t s was 15% o r l e s s . The i r r a d i a t i o n s o u r c e s were the same as those used f o r c r y s t a l p h o t o l y s e s . i i i ) Low Temperature I r r a d i a t i o n s A l l low temperature i r r a d i a t i o n s were c a r r i e d out u s i n g s i n g l e c r y s t a l s o r p o l y c r y s t a l l i n e samples o r 0.1 M s o l u t i o n s i n a c e t o -n i t r i l e i n one o f the f o l l o w i n g two ways: 1. s o l i d o r s o l u t i o n samples were s e a l e d i n 3 mm p y r e x o r q u a r t z tubes a f t e r s e v e r a l freeze-pump-thaw c y c l e s and were p l a c e d i n a windowed t e f l o n c e l l c o o l e d by p a s s i n g v a p o r i z e d l i q u i d n i t r o g e n through the c e l l . The i n s i d e temperature o f the c e l l was m a i n t a i n e d a t the d e s i r e d v a l u e by a d j u s t i n g the l i q u i d n i t r o g e n b o i l - o f f r a t e , and the tempera-t u r e was measured v i a a c o p p e r - c o n s t a n t a n thermocouple a t t a c h e d to a d i g i t a l m i l l i v o l t m e t e r , o r (2) s o l i d samples were a l s o i r r a d i -a t e d a t -40°C by p l a c i n g them i n an a c e t o n i t r i l e - l i q u i d n i t r o g e n b a t h . S o l i d or s o l u t i o n samples were i r r a d i a t e d a t 0°C u s i n g an i c e - w a t e r b a t h . I r r a d i a t i o n s were a l s o c o n d u c t e d a t d i f f e r e n t t emperatures below 0°C u s i n g a p p r o p r i a t e s o l v e n t - l i q u i d n i t r o g e n b a t h s . These b a t h s were c o n s t a n t l y s t i r r e d w i t h a magnetic - 223 -s t i r r i n g b a r to m a i n t a i n a u n i f o r m temperature t h r o u g h o u t the b a t h . Temperatures were r e c o r d e d d i r e c t l y from a low temperature thermometer c a p a b l e o f measuring temperatures down t o -100°C. i v ) A n a l y t i c a l I r r a d i a t i o n s o f C a r b o x y l i c A c i d D e r i v a t i v e s 33 and 43 S o l i d s t a t e i r r a d i a t i o n s were c a r r i e d o ut as b e f o r e . However, the s o l u t i o n s t a t e p h o t o l y s e s c o u l d n o t be p e r f o r m e d i n benzene or aqueous a c e t o n i t r i l e because o f l i m i t e d s o l u b i l i t y . T h e r e f o r e , the s o l u t i o n s t a t e a n a l y t i c a l runs were c o n d u c t e d i n t e r t - b u t y l a l c o h o l (0.1 M). P r o d u c t r a t i o s c o u l d n o t be d e t e r m i n e d u s i n g gas chromatography, as these c a r b o x y l i c a c i d s a r e r e t a i n e d on the gas ch r o m a t o g r a p h i c columns. A f t e r i r r a d i a t i o n i n s o l i d o r s o l u t i o n s t a t e , samples were c o n v e r t e d t o t h e i r m e t h y l e s t e r s by r e a c t i o n w i t h e x c e s s diazomethane i n e t h e r . These samples were th e n a n a l y z e d by gas chromatography and the p r o d u c t r a t i o s were r e c o r d e d . b) Preparative Scale Photolysis S o l u t i o n S t a t e I r r a d i a t i o n s The f o l l o w i n g p r o c e d u r e f o r the p r e p a r a t i v e s c a l e s o l u t i o n photo-l y s i s o f 2 - c y c l o h e x y l - 1 - ( 4 - c y a n o p h e n y l ) - e t h a n o n e , 32, i s t y p i c a l . A s o l u t i o n o f 500 mg (2.2 mmol) o f s u b s t r a t e 32 i n 180 ml o f - 224 r e a g e n t grade a c e t o n i t r i l e was p l a c e d i n a s t a n d a r d w a t e r - c o o l e d immersion w e l l . The s o l u t i o n was degassed w i t h h i g h p u r i t y n i t r o g e n gas f o r 45 min w i t h c o n t i n u o u s s t i r r i n g and a p o s i t i v e p r e s s u r e o f n i t r o g e n was m a i n t a i n e d t h r o u g h o u t the i r r a d i a t i o n . The s o l u t i o n was p h o t o l y s e d w i t h a 450 W H anovia medium p r e s s u r e lamp f i t t e d w i t h a p y r e x f i l t e r s l e e v e ( t r a n s m i t t i n g a t A> 290 nm). The r e a c t i o n was f o l l o w e d by gas chromatography. The p h o t o l y s i s was s t o p p e d when a l l the s t a r t i n g m a t e r i a l had d i s a p p e a r e d (3 h ) . The p r e s e n c e o f c y c l o h e x e n e was con-f i r m e d by comparing i t s gas c h r o m a t o g r a p h i c r e t e n t i o n time w i t h t h a t o f an a u t h e n t i c sample (50 metre carbowax 20 M column). S o l v e n t was removed i n vacuo. f o l l o w e d by passage o f the r e s i d u e t h r o u g h a 15 x 5 cm column o f s i l i c a g e l u s i n g an e t h y l a c e t a t e - p e t r o l e u m e t h e r s o l v e n t system as the e l u e n t . The s o l v e n t p o l a r i t y v a r i e d from 0:100 to 10:90 (V/V) ( e t h y l a c e t a t e : p e t r o l e u m e t h e r ) . 4 - A c e t y l b e n z o n i t r i l e (150 mg, 50%) was e l u t e d w i t h 2:98 ( e t h y l a c e t a t e : p e t r o l e u m e t h e r ) , t r a n s -c y c l o b u t a n o l (32t) (130 mg, 26%) was e l u t e d w i t h 4:96 (V/V) ( e t h y l a c e t a t e : p e t r o l e u m e t h e r ) and c i s - c y c l o b u t a n o l (32c) (102 mg, 20%) was e l u t e d w i t h 8% (V/V) e t h y l a c e t a t e i n p e t r o l e u m e t h e r . 4 - A c e t y l b e n z o n i t r i l e was i d e n t i f i e d by comparing i t s s p e c t r a l c h a r a c t e r i s t i c s w i t h t h a t o f an a u t h e n t i c sample. S p e c t r a l c h a r a c t e r i s t i c s o f t r a n s - c y c l o b u t a n o l , 7 - ( l a , 6a, 7/3) -( 4 - c y a n o p h e n y l ) - b i c y c l o [ 4 . 2 . 0 ] o c t a n - 7 - o l (32t) IR ( n e a t ) : 3435 (OH), 2200 ( O N ) cm" 1. - 225 -X H NMR (CDCI3, 400 MHz): <5 7.61 (d, 2H, J = 8 Hz, a r o m a t i c s meta to CN), 7.45 (d, 2H, J = 8 Hz, a r o m a t i c s o r t h o t o CN), 2.29 (dd, IH, J = 6.5 and 4 Hz, H A ) , 2.11 (m, IH), 1.95 (br s, IH, exchangeable OH), 1.90-1.78 (m, 4H), 1.72-1.55 (m, 2H), 1.42-1.25 (m, 4H) . MS, m/e ( r e l a t i v e i n t e n s i t y ) : 227 (M +, 13), 158 (35), 145 (100), 130 ( 8 . 0 ) , 119 (11), 102 (33), 85 (15), 82 (31); e x a c t mass c a l c d . 227.1310; found 227.1313. A n a l , c a l c d . f o r C 1 5 H 1 7 N 0 : C, 79.25; H, 7.54; N, 6.17. Found: C, 79.00; H, 7.78; N, 6.05. S p e c t r a l c h a r a c t e r i s t i c s o f c i s - c y c l o b u t a n o l , 7 - ( l a , 6 a , 7 a ) -( 4 - c y a n o p h e n y l ) - b i c y c l o [ 4 . 2 . 0 ] o c t a n - 7 - o l (32c) IR ( n e a t ) : 3420 (OH), 2200 (C=N) cm" 1. 1 H NMR (CDCI3, 400 MHz): 5 7.65 (d, 2H, J = 8 Hz, a r o m a t i c s meta to CN), 7.55 (d, 2H, J = 8 Hz, a r o m a t i c s o r t h o t o CN), 2.87 (dd, IH, J = 6.5 and 4 Hz, H A ) , 2.01-1.90 (m, 2H), 1.87-1.64 (m, 4H), 1.56 (br s, IH, exchangeable OH), 1.40-0.95 (m, 4H), 0.80-0.68 (m, IH). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 227 (M +, 5.5), 184 (23), 158 (22), 146 (78), 145 (100), 130 (48), 102 (24), 82 (28), 67 (34); e x a c t mass c a l c d . 227.1310; found 227.1311. A n a l , c a l c d . f o r C 1 5 H 1 7 N 0 : C, 79.25; H, 7.54; N, 6.17. Found: C, 79.45; H, 7.50; N, 6.12. - 226 -Photolysis of 2-Cyclohexyl-l-(4-chlorophenyl)-ethanone, 28 4-Chloroacetophenone was eluted with petroleum ether and i d e n t i f i e d by comparing i t s sp e c t r a l c h a r a c t e r i s t i c s with that of an authentic sample. Trans-cyclobutanol, 7 -(la,6a,7/9)-(4-chlorophenyl)-bicyclo[4.2. 0] -octan-7-ol (28t) was eluted with 4% (V/V) et h y l acetate i n petroleum ether, and i t s s p e c t r a l c h a r a c t e r i s t i c s are as follows: IR (neat): 3380 (br, OH) cm - 1. XH NMR (CDC1 3, 270MHz): 5 7.36-7.22 (m, 4H, aromatics), 2.33-2.19 (m, IH), 2.06 (br d, IH, J - 9 Hz), 1.89 (br s, IH), 1.88-1.14 (m, 10H). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 236 (M +, 0.8), 218 (0.6), 201 (8.9), 167 (13), 154 (100), 139 (69), 119 (8.9); exact mass calcd. 236.0968; found 236.0961. Anal. calcd. f o r C 1 4H 1 7C10: C, 71.03; H, 7.24; 0, 6.76. Found: C, 70.80; H, 7.15; 0, 6.90. Cis-cyclobutanol, 7-(la,6a,7a)-(4-chlorophenyl)-bicyclo[4.2.0]-octan-7-ol (28c) was eluted with 8% (V/V) ethylacetate i n petroleum ether, and i t s s p e c t r a l c h a r a c t e r i s t i c s are as follows: IR (neat): 3340 (br, OH) cm - 1. -^H NMR (C D C I 3 , 270 MHz): 8 7.37-7.32 (m, 4H, aromatics), 2.84 (dd, IH, J =6.5 and 4 Hz, H A), 2.03 (br s, IH, exchangeable OH), 2.02-1 . 4 8 (m, 7H), 0.88-0.66 (m, 4H). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 236 (M +, 0.6), 218 (0.8), 167 (13), 154 (100), 139 (72), 111 (30); exact mass calcd. 236.0968; found 236.0958. 227 A n a l , c a l c d . f o r C 1 4 H 1 7 C 1 0 : C, 71.03; H, 7.24; 0, 6.76. Found: C, 70.85; H, 7.29; 0, 6.87. P h o t o l y s i s o f 2 - C y c l o h e x y l - 1 - ( 4 - m e t h y l p h e n y l ) - e t h a n o n e , 29 4-Methylacetophenone was e l u t e d w i t h p e t r o l e u m e t h e r and i d e n t i f i e d by comparing i t s s p e c t r a l c h a r a c t e r i s t i c s w i t h t h a t o f an a u t h e n t i c sample. T r a n s - c y c l o b u t a n o l , 7 - ( l a , 6 a , 7 / 9 ) - ( 4 - m e t h y l p h e n y l ) - b i c y c l o [ 4 . 2 . 0 ] -o c t a n - 7 - o l (29t) was e l u t e d w i t h 2% (V/V) e t h y l a c e t a t e i n p e t r o l e u m e t h e r , and i t s s p e c t r a l c h a r a c t e r i s t i c s a r e as f o l l o w s : IR ( n e a t ) : 3380 ( b r , OH) cm" 1. 1 H NMR (CDC1 3, 400 MHz): 6 7.13 (d, 2H, J = 8 Hz, a r o m a t i c s meta to C H 3 ) , 7.04 (d, 2H, J = 8 Hz, a r o m a t i c s o r t h o to CH3), 2.23 ( s , 3H, C H 3 ) , 2.16 (dd, IH, J - 6.5 and 4 Hz, H A ) , 1.97 (m, IH), 1.90 (br s, IH, exchangeable, OH), 1.78-1.10 (m, 10H). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 216 (M +, 2.2), 201 (19), 198 ( 1 . 9 ) , 183 ( 6 . 0 ) , 147 (17), 134 ( 9 4 ) , 119 (100), 91 ( 3 9 ) ; e x a c t mass c a l c d . 216.1512; found 216.1516. A n a l , c a l c d . f o r C 1 5 H 2 0 0 : C, 83.29; H, 9.32. Found: C, 82.99; H, 9.28. C i s - c y c l o b u t a n o l , 7 - ( l a , 6 a , 7 a ) - ( 4 - m e t h y l p h e n y l ) - b i c y c l o [ 4 . 2 . 0 ] -o c t a n - 7 - o l (29c) was e l u t e d w i t h 5% (V/V) e t h y l a c e t a t e i n p e t r o l e u m e t h e r , and i t s s p e c t r a l c h a r a c t e r i s t i c s a r e as f o l l o w s : IR ( n e a t ) : 3330 ( b r , OH) cm" 1. - 228 -XE NMR ( C D C I 3 , 400 MHz): S 7.30-7.19 (m, 4H, aromatics), 2.85 (dd, IH, J = 6.5 and 4 Hz, H A), 2.35 (s, 3H, C H 3 ) , 2.03 (br s, IH, exchange-able, OH), 1.90 (m, IH), 1.84-0.83 (m, 10H). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 216 (M +, 6.0), 201 (13), 198 (5.6), 147 (15), 134 (100), 119 (98); exact mass calcd. 216.1512; found 216.1509. Anal. calcd. f o r C 1 5H 2 oO: C, 83.29; H, 9.32. Found: C, 82.50; H, 9.55. Photolysis of 2-Cyclohexyl-l-(4-methoxyphenyl)-ethanone, 30 4-Methoxyacetophenone was eluted with 2% (V/V) et h y l acetate i n petroleum ether and i d e n t i f i e d by comparing i t s s p e c t r a l c h a r a c t e r i s t i c s with that of an authentic sample. Trans-cyclobutanol, 7 -(la,6a,7/3)-(4-methoxyphenyl)-bicyclo-[4.2.0]-octan-7-ol (30t) was eluted with 7% (V/V) ethyl acetate i n petroleum ether, and i t s s p e c t r a l c h a r a c t e r i s t i c s are as follows: IR (neat): 3400 (br, OH) cm"1. 1H NMR ( C D C I 3 , 270 MHz): 6 1.11 (d, 2H, J = 8 Hz, aromatics meta to O C H 3 ) , 6.69 (d, 2H, J = 8 Hz, aromatics ortho to O C H 3 ) , 3.64 (s, 3 H , O C H 3 ) , 2.11 (dd, IH, J = 6.5 and 4 Hz, H A), 1.92 (m, IH), 1.59 (br s, IH, exchangeable, OH), 1.72-1.57 (m, 6H), 1.24-1.07 (m, 4H) . MS, m/e ( r e l a t i v e i n t e n s i t y ) : 232 (M+, 2.5), 230 (6.0), 214 (4.5), 201 (6.5), 163 (17.6), 150 (95), 135 (100), 121 (1.1), 107 (10.3), 77 (23); exact mass calcd. 232.1463; found 232.1459. - 229 -A n a l , c a l c d . f o r C 1 5H 2o02: C, 77.55; H, 8.68. Found: C, 76.84; H, 8.72. C i s - c y c l o b u t a n o l , 7 - ( l a , 6 a , l a ) - ( 4 - m e t h o x y p h e n y l ) - b i c y c l o [ 4 . 2 . 0 ] -o c t a n - 7 - o l ( 3 0 c ) was e l u t e d w i t h 12% (V/V) e t h y l a c e t a t e i n p e t r o l e u m e t h e r , and i t s s p e c t r a l c h a r a c t e r i s t i c s a r e as f o l l o w s : IR ( n e a t ) : 3340 ( b r , OH) cm" 1. 1 H NMR (CDC1 3, 270 MHz): 6 7.28 (d, 2H, J «= 8 Hz, a r o m a t i c s meta t o OCH3), 6.77 (d, 2H, J = 8 Hz, a r o m a t i c s o r t h o t o OCH3), 3.74 ( s , 3H, OCH3), 2.75 (dd, IH, J - 6.5 and 4 Hz, H A ) , 1.99 ( b r , s, IH, exchange-a b l e , OH), 1.85-1.52 (m, 6H), 1.29-1.15 (m, 3H), 0.91-0.70 (m, 2H). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 232 (M+, 1.8), 230 (11 ) , 214 (15), 150 ( 9 2 ) , 135 (100), 77 (36); e x a c t mass c a l c d . 232.1465; found 232.1461. A n a l , c a l c d . f o r C 1 5 H 2 0 O 2 : C, 77.55; H, 8.68. Found: C, 77.16; H, 8.81. P h o t o l y s i s o f C y c l o b u t y l , C y c l o p e n t y l and [2.2.1]-Bicycloheptyl s u b s t i t u t e d acetophenones, 3 8 - 4 9 . The major photo p r o d u c t , 4-chloroacetophenone, was i s o l a t e d i n the l a r g e s c a l e p h o t o l y s e s o f compounds, 3 8 , 45 and 46. The o t h e r c l e a v a g e p r o d u c t s , c y c l o p e n t e n e from 38 and norbornene from 4 6 , were i d e n t i f i e d by gas c h r o m a t o g r a p h i c c o - i n j e c t i o n w i t h a u t h e n t i c samples on a 50 meter Carbowax 20 M column. I n a l l o t h e r c a s e s , the major p r o d u c t o f c l e a v -age, a 4 - s u b s t i t u t e d acetophenone, was i d e n t i f i e d by gas chr o m a t o g r a p h i c - 230 -c o - i n j e c t i o n w i t h an a u t h e n t i c sample and by gas chromatography-mass s p e c t r o m e t r y . P h o t o l y s i s o f 2 - C y c l o h e p t y l - l - ( 4 - c h l o r o p h e n y l ) - e t h a n o n e , 50 4-Chloroacetophenone was e l u t e d w i t h p e t r o l e u m e t h e r and i d e n t i f i e d by comparing i t s s p e c t r a l c h a r a c t e r i s t i c s w i t h t h a t o f an a u t h e n t i c sample. T r a n s - c y c l o b u t a n o l , 8 - ( l a , 7 a , 8 / 9 ) - ( 4 - c h l o r o p h e n y l ) - b i c y c l o - [ 5 . 2 . 0 ] -nonan-8-ol (50t) was e l u t e d w i t h 4% (V/V) e t h y l a c e t a t e i n p e t r o l e u m e t h e r , and i t s s p e c t r a l c h a r a c t e r i s t i c s a r e as f o l l o w s : IR ( n e a t ) : 3442 ( b r , OH) cm" 1. I-H NMR (CDCI3, 400 MHz): 5 7.50-7.20 (m, 4H, a r o m a t i c s ) , 2.70 (m, IH), 2.45-2.20 (m, 4H), 2.05-1.05 (m, 10H). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 250 (M +, 2.0), 232 ( 1 . 0 ) , 215 (4. 7 ) , 167 (12), 156 (34), 154 (100), 141 (21), 139 ( 5 4 ) . A n a l . c a l c d . f o r C 1 5 H 1 9 C 1 0 : C, 71.85; H, 7.64; 0, 6.38. Found: C, 72.00; H, 7.64; 0, 6.29. C i s - c y c l o b u t a n o l , 8 - ( l a , 7 a , 8 a ) - ( 4 - c h l o r o p h e n y l ) - b i c y c l o - [ 5 . 2 . 0 ] -nonan-8-ol (50c) was e l u t e d w i t h 8% (V/V) e t h y l a c e t a t e i n p e t r o l e u m e t h e r , and i t s s p e c t r a l c h a r a c t e r i s t i c s a r e as f o l l o w s : IR ( n e a t ) : 3320 ( b r , OH) cm" 1. *H NMR (CDCI3, 400 MHz): S 7.40 (d, 2H, J = 8.5 Hz, a r o m a t i c s meta t o C l ) , 7.30 (d, 2H, J = 8.5 Hz, a r o m a t i c s o r t h o t o C l ) , 2.83 (dd, IH, J - 7 and 4 Hz, H A ) , 2.33 (m, IH), 2.00-1.85 (m, 2H), 1.91 ( s , - 231 IH, exchangeable, OH), 1.75-1.19 (m, 9H), 0.51 (m, IH). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 250 (M +, 1.2), 232 ( 1 . 3 ) , 215 ( 2 . 4 ) , 154 (100), 111 (15). A n a l , c a l c d . f o r C 1 5 H 1 9 C 1 0 : C, 71.85; H, 7.64; 0, 6.38. Found: C, 71.66; H, 7.71; 0, 6.50. P h o t o l y s i s o f 2 - C y c l o h e p t y l - 1 - ( 4 - m e t h y l p h e n y l ) - e t h a n o n e , 51 4-Methylacetophenone was e l u t e d w i t h 2% (V/V) e t h y l a c e t a t e i n p e t r o l e u m e t h e r and i d e n t i f i e d by comparing i t s s p e c t r a l c h a r a c t e r i s t i c s w i t h t h a t o f an a u t h e n t i c sample. T r a n s - c y c l o b u t a n o l , 8 - ( l a , 7 a , 8 / 9 ) - ( 4 - m e t h y l p h e n y l ) - b i c y c l o - [ 5 . 2 . 0 ] -nonan-8-ol (52t) was e l u t e d w i t h 2% (V/V) e t h y l a c e t a t e i n p e t r o l e u m e t h e r , and i t s s p e c t r a l c h a r a c t e r i s t i c s a r e as f o l l o w s : IR ( n e a t ) : 3410 ( b r , OH) cm" 1. X H NMR (CDC1 3, 400 MHz): 5 7.23 (d, 2H, J - 8.5 Hz, a r o m a t i c s meta to CH3), 7.12 (d, 2H, J = 8.5 Hz, a r o m a t i c s o r t h o t o CH3), 2.33 ( s , 3H, CH 3 ) , 2.26 (m, IH), 2.00-1.35 (m, 12H), 1.53 ( s , IH, exchangeable, OH), 0.85 (m, IH). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 230 (M +, 2.0), 215 ( 6 . 6 ) , 212 (1. 1 ) , 197 ( 2 . 0 ) , 169 ( 1 . 8 ) , 134 (100), 119 (74), 91 (30). A n a l . c a l c d . f o r C 1 6 H 2 2 0 : C, 83.43; H, 9.63. Found: C, 83.40; H, 9.80. C i s - c y c l o b u t a n o l , 8 - ( l a , 7 a , 8 a ) - ( 4 - m e t h y l p h e n y l ) - b i c y c l o - [ 5 . 2 . 0 ] -nonan-8-ol (51c) was e l u t e d w i t h 5% (V/V) e t h y l a c e t a t e i n p e t r o l e u m - 232 -e t h e r , and i t s s p e c t r a l c h a r a c t e r i s t i c s a r e as f o l l o w s : IR ( n e a t ) : 3370 ( b r , OH) cm" 1. 1 H NMR (CDCI3, 400 MHz): S 7.25 (d, 2H, J = 8.5 Hz, a r o m a t i c s meta t o C H 3 ) , 7.17 (d, 2H, J = 8.5 Hz, a r o m a t i c s o r t h o t o CH3), 2.84 (dd, IH, J = 7 and 4 Hz, H A) , 2.35 ( s , 3H, CH 3) , 1.90-0.80 (m, 13H) , 0.60-0.41 (m, IH). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 230 (M +, 5.3), 215 ( 6 . 0 ) , 212 (1.4), 134 (100), 119 (73), 105 ( 6 . 3 ) , 91 (27). A n a l , c a l c d . f o r C 1 6 H 2 2 0 : C, 83.43; H, 9.63. Found: C, 82.10; H, 9.30. P h o t o l y s i s o f 2 - C y c l o h e p t y l - l - ( 4 - m e t h o x y p h e n y l ) - e t h a n o n e , 52 4-Methoxyacetophenone was e l u t e d w i t h 3% (V/V) e t h y l a c e t a t e i n p e t r o l e u m e t h e r and i d e n t i f i e d by comparing i t s s p e c t r a l c h a r a c t e r i s t i c s w i t h t h a t o f an a u t h e n t i c sample. T r a n s - c y c l o b u t a n o l , 8 - ( l a , 7 a , 8 / 9 ) - ( 4 - m e t h o x y p h e n y l ) - b i c y c l o - [ 5 . 2 . 0 ] -o c t a n - 8 - o l (52t) was e l u t e d w i t h 6% (V/V) e t h y l a c e t a t e i n p e t r o l e u m e t h e r , and i t s s p e c t r a l c h a r a c t e r i s t i c s a r e as f o l l o w s : IR ( n e a t ) : 3425 ( b r , OH) cm" 1. 1 H NMR (CDCI3, 400 MHz): 5 7.26 (d, 2H, J = 8.5 Hz, a r o m a t i c s meta to OCH3), 6.86 (d, 2H, J = 8.5 Hz, a r o m a t i c s o r t h o t o OCH3), 3.80 ( s , 3H, OCH3), 2.40-2.20 (m, 2H), 1.98-1.85 (m, 2H), 1.80-1.52 (m, 5H), I. 50-1.09 (m, 5H), 0.91-0.80 (m, IH). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 246 (M +, 2.0), 228 ( 4 . 3 ) , 185 (4.0 ) , - 233 171 ( 4 . 1 ) , 150 ( 1 0 0 ) , 135 (55). A n a l . c a l c d . f o r C 1 6 H 2 2 0 2 : C, 78.01; H, 9.00. Found: C, 77.80; H, 9.09. C i s - c y c l o b u t a n o l , 8 - ( l a , 7 a , 8 a ) - ( 4 - m e t h o x y p h e n y l ) - b i c y c l o - [ 5 . 2 . 0 ] -nonan-8-ol (52c) was e l u t e d w i t h 10% (V/V) e t h y l a c e t a t e i n p e t r o l e u m e t h e r , and i t s s p e c t r a l c h a r a c t e r i s t i c s a r e as f o l l o w s : IR ( n e a t ) : 3350 (b r , OH) cm" 1. lH NMR (CDC1 3, 400 MHz): 5 7.28 (d, 2H, J = 8.5 Hz, a r o m a t i c s meta t o OCH3), 6.90 (d, 2H, J = 8.5 Hz, a r o m a t i c s o r t h o t o OCH3), 3.81 ( s , 3H, OCH3), 2.84 (dd, IH, J - 7 and 4 Hz, H A ) , 2.33 (m, IH), 1.97 (br s, IH, exchangeable OH), 1.95-1.82 (m, 2H), 1.80-1.20 (m, 9H), 0.64-0.51 (m, IH). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 246 (M +, 2.0), 228 ( 4 . 3 ) , 185 ( 4 . 0 ) , 171 ( 4 . 1 ) , 150 ( 1 0 0 ) , 135 (55). A n a l . c a l c d . f o r C 1 6 H 2 2 0 2 : C, 78.01; H, 9.00. Found: C, 77.80; H, 9.09. P h o t o l y s i s o f 2 - T r i c y c l o [ 3 . 3 . 1 . I 3 • 7 ] d e c - l - y l - l - p h e n y l e t h a n o n e , 57 P r e p a r a t i v e s c a l e i r r a d i a t i o n o f ketone 57 was p r e v i o u s l y p erformed i n p r o p a n o l - b e n z e n e s o l v e n t m i x t u r e and photo p r o d u c t s , c i s - c y c l o b u t a n o l (57c) and t r a n s - c y c l o b u t a n o l ( 5 7 t ) were s e p a r a t e d by column chromato-g r a p h y . 1 1 1 The i r r a d i a t i o n o f compound 57 was r e p e a t e d i n a c e t o n i t r i l e t o g e n e r a t e c y c l o b u t a n o n e 57c and 5 7 t , whose s p e c t r a have been used f o r p r o t o n assignments i n o t h e r c l o s e l y r e l a t e d p - s u b s t i t u t e d adamantyl 234 -compounds by way o f comparison. Trans - 3-phenyl - t e t r a c y c l o [5.3.1.1-',9.0-'- >4] dodecan- 3 - o l (57t) was e l u t e d w i t h 4% (V/V) e t h y l a c e t a t e i n p e t r o l e u m e t h e r , and i t s s p e c t r a l c h a r a c t e r i s t i c s a r e as f o l l o w s : MP: 81-82°C ( l i t . 8 2 - 8 3 0 C ) . 1 1 : L IR ( K B r ) : 3400 (OH) cm - 1. X H NMR (CDC1 3, 400 MHz): 6 7.35 (m, 4H, a r o m a t i c s ) , 7.25 (m, IH, a r o m a t i c s ) , 2.92 (br d, IH, J = 12 Hz, H c ) , 2.18 (d, IH, J = 11 Hz, H b ) , 2.03 (d, IH, J - 11 Hz, H a ) , 2.40-1.59 (m, 13H), 1.75 ( s , IH, exchange-a b l e OH) . MS, m/e ( r e l a t i v e i n t e n s i t y ) : 254 (M +, 26), 236 ( 7 . 1 ) , 179 (50), 149 (23), 135 (16), 106 (10), 105 (100), 90 (22), 77 ( 4 0 ) . A n a l , c a l c d . f o r C 1 8 H 2 2 0 : C, 84.99; H, 8.72. Found: C, 84.71; H, 8.70. C i s - 3 - p h e n y l - t e t r a c y c l o [ 5 . 3 . 1 . I 5 ' ^ . 0 1 > 4 ] d o d e c a n - 3 - o l (57c) was e l u t e d w i t h 8% (V/V) e t h y l a c e t a t e i n p e t r o l e u m e t h e r , and i t s s p e c t r a l c h a r a c t e r i s t i c s a r e as f o l l o w s : MP: 106-107°C ( l i t . 1 0 6 - 1 0 7 ° C ) . 1 1 1 IR ( K B r ) : 3600 (OH) cm - 1. lti NMR (CDCI3, 400 MHz): 5 7.43 (m, 2H, a r o m a t i c s ) , 7.36 (m, 2H, a r o m a t i c s ) , 7.28 (m, IH, a r o m a t i c s ) , 2.75 (d, IH, J = 12 Hz, H b ) , 2.41 (m, IH, H c ) , 2.08 (d, IH, J = 12 Hz, H a ) , 2.00-1.31 (m, 13H), 1.95 (br s, IH, exchangeable, OH). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 254 (M+, 24), 236 (12), 179 (6.0), 149 (17), 135 (17), 105 (100), 91 (20), 77 ( 4 2 ) . A n a l , c a l c d . f o r C 1 8 H 2 2 0 : C, 84.99; H, 8.72. Found: C, 84.85; H, 8.61. P h o t o l y s i s o f 2 - T r i c y c l o [ 3 . 3 . 1 . 1 J > ' ] d e c - l - y l - l - ( 4 - c h l o r o p h e n y l ) -ethanone, 54n and 54p Trans - 3 - ( 4 - c h l o r o p h e n y l ) - t e t r a c y c l o [ 5 . 3 . 1 . 1 5 > 9.0 1> 4]dodecan-3 - o l (54t) was e l u t e d w i t h 3% (V/V) e t h y l a c e t a t e i n p e t r o l e u m e t h e r , and i t s s p e c t r a l c h a r a c t e r i s t i c s a r e as f o l l o w s : MP: 91-93°C. IR ( K B r ) : 3550 (OH) cm - 1. XH NMR (CDC1 3, 400 MHz): 8 7.29 (m, 4H, a r o m a t i c s ) , 2.89 (br d, IH, J - 12 Hz, H c ) , 2.39-1.98 (m, 5H), 2.23 (d, IH, J = 11 Hz, H b ) , 2.11 (d, IH, J = 11 Hz, H a ) , 1.90-1.76 (m, 9H). D e c o u p l i n g a t 8 2.89 (H c) causes a r e d u c t i o n i n the c o m p l e x i t y o f the m u l t i p l e t a t 8 1.90-1.76 (adamantyl r i n g p r o t o n s ) , d e c o u p l i n g a t 8 2.23 (H b) causes the s i g n a l a t 6 2.11 (H a) to c o l l a p s e . MS, m/e ( r e l a t i v e i n t e n s i t y ) : 288 (M +, 3.8), 270 ( 6 . 1 ) , 253 (100), 235 (12), 149 (54), 141 (24), 139 (64), 93 (27), 79 ( 2 1 ) . A n a l , c a l c d . f o r C 1 8 H 2 i C 1 0 : C, 74.86; H, 7.33; 0, 5.54. Found: C, 74.86; H, 7.25; 0, 5.50. C i s - 3 - ( 4 - c h l o r o p h e n y l ) - t e t r a c y c l o [5.3.1. l 5 ' 9 ^ 1 ' 4 ] d odecan-3-ol (54c) was e l u t e d w i t h 5% (V/V) e t h y l a c e t a t e i n p e t r o l e u m e t h e r , and i t s s p e c t r a l c h a r a c t e r i s t i c s are as f o l l o w s : MP: 101-102°C. IR ( K B r ) : 3330 (OH) cm' 1. % NMR (CDCI3, 400MHz): IH), 2.71 (d, IH, J = 11 Hz, H b ) , H c ) , 2.07 (d, IH, J = 11 Hz, H a ) . A n a l , c a l c d . f o r C]_gH2iC10: C, 74.58; H, 7.31; 0, 5.46. 6 7.33 (m, 4H, a r o m a t i c s ) , 3.00 (br s, 2.90-2.35 (m, 13H), 2.38 ( b r s, IH, C, 74.86; H, 7.33; 0, 5.54. Found: P h o t o l y s i s o f 2 - T r i c y c l o [ 3 . 3 . 1 . 1 J • ' ] d e c - l - y l - l - ( 4 - m e t h y l p h e n y l ) -ethanone, 55 T r a n s - 3 - ( 4 - m e t h y l p h e n y l ) - t e t r a c y c l o [ 5 . 3 . 1 . 1 5 > 9 . 0 - * - , 4 ] dodecan-3-ol (55t) was e l u t e d w i t h p e t r o l e u m e t h e r , and i t s s p e c t r a l c h a r a c t e r i s t i c s a r e as f o l l o w s : MP: 63-64°C. IR ( K B r ) : 3500-3400 (OH) cm - 1. 1 H NMR (CDCI3, 400 MHz): S 1. 24 (d, 2H, J = 8 Hz, a r o m a t i c s meta to CH3), 7.15 (d, 2H, J = 8 Hz, a r o m a t i c s o r t h o to CH3), 2.92 (br d, IH, J - 12 Hz, H c ) , 2.34 ( s , 3H, CH3), 2.26 (d, IH, J - 12 Hz, H b ) , 2.12 (d, IH, J = 12 Hz, H a ) , 1.65 ( s , IH, exchangeable, OH), 2.02 (m, 3H), 1.83-1.67 (m, 10H). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 268 (M +, 6.3), 253 (62), 235 (17), 207 ( 1 6 ) , 193 (16), 119 (100), 115 ( 1 8 ) , 105 ( 1 7 ) , 91 (58); e x a c t mass c a l c d . 268.1827; found 268.1823. A n a l , c a l c d . f o r C 1 9 H 2 4 0 : C, 85.03; H, 9.01. Found: C, 85.06; H, 8.93. C i s - 3 - ( 4 - m e t h y l p h e n y l ) - t e t r a c y c l o [ 5 . 3 . 1 . 1 5 • ^ . 0 1 • 4 ] d o d e c a n - 3 - o l - 237 -(55c) was e l u t e d w i t h 3% (V/V) e t h y l a c e t a t e i n p e t r o l e u m e t h e r and i t s s p e c t r a l c h a r a c t e r i s t i c s a r e as f o l l o w s : MP: 79-81°C. IR ( K B r ) : 3400 (OH) cm" 1. X H NMR (CDC1 3, 400 MHz): 5 7.23 (d, 2H, J = 8 Hz, a r o m a t i c s meta to CH3), 7.18 (d, 2H, J = 8 Hz, a r o m a t i c s o r t h o t o CH3), 2.72 (d, IH, J = 12 Hz, H b ) , 2.40 (br s, IH, H c ) , 2.34 ( s , 3H, CH3), 2.05 (d, IH, J = 12 Hz, H a ) , 1.84 (m, IH, exchangeable, OH), 1.86-1.35 (m, 13H) . MS, m/e ( r e l a t i v e i n t e n s i t y ) : 268 (M+, 3.0), 253 (37), 251 (22), 250 (100), 235 ( 4 8 ) , 207 (45), 193 (40), 179 ( 2 3 ) , 165 ( 2 1 ) , 155 (16), 119 (51), 115 (30); e x a c t mass c a l c d . 268.1827; found 268.1826. A n a l , c a l c d . f o r C 1 9 H 2 4 0 : C, 85.03; H, 9.01. Found: C, 85.20; H, 8.70. P h o t o l y s i s o f 2 - T r i c y c l o [ 3 . 3 . 1 . I 3 • 7 ] d e c - l - y l - 1 - ( 4 - m e t h o x y p h e n y l ) -ethanone, 56 I r r a d i a t i o n o f ketone 56 i n a c e t o n i t r i l e and a n a l y s i s by gas chromatography showed two major peaks. However, a f t e r e v a p o r a t i o n o f the s o l v e n t i n vacuo and on r e a n a l y s i s , the gas chromatograph showed two major peaks, one o f which was a new peak. The peak c o r r e s p o n d i n g t o the c i s - c y c l o b u t a n o l (56c) had d i s a p p e a r e d . Column chromatography p r o v i d e d two p r o d u c t s , i d e n t i f i e d as t r a n s - c y c l o b u t a n o l (56t) and the d e h y d r a t i o n p r o d u c t (56d). 3 - ( 4 - M e t h o x y p h e n y l ) - t e t r a c y c l o [ S . S . l . l ^ ' ^ . O 1 • 4 ] d o d e c - 3 - e n e (56d) - 238 -was e l u t e d f i r s t on a s i l i c a g e l column w i t h p e t r o l e u m e t h e r , and i t s s p e c t r a l c h a r a c t e r i s t i c s a r e as f o l l o w s : MP: 110-112°C. IR ( K B r ) : 1605 (C=C) cm" 1. No 'OH' s t r e t c h . -^H NMR (CDCI3, 400 MHz): 6 7.20 (d, 2H, J = 8.5 Hz, a r o m a t i c s meta t o OCH3), 6.83 (d, 2H, J = 8.5 Hz, a r o m a t i c s o r t h o t o OCH3), 3.80 ( s , 3H, OCH3), 3.0 ( s , IH, a l l y l i c m e t h i n e ) , 2.42 ( s , 2H, a l l y l i c m e t h y l e n e ) , 2.08 (m, 2H), 2.0-1.65 (m, 10H). 1 3 C NMR (CDCI3, 400 MHz): S 158.0 ( C 4 ) , 151.8 ( C 1 0 ) , 130.1 ( C y ) , 126.4 ( C 2 and C 6 ) , 122.4 ( C x ) , 113.8 (C3 and C 5 ) , 55.3 ( C 1 9 ) , 42.7, 41.3, 37.3, 36.9 ( C 8 , C 1 2 - c14> c 1 6 - c 1 8 ) - 3 7 - 3 ( c 9 ) - 3 2 - ° . 2 9 - 9 ( c l l > c 1 3 ' c15>-MS, m/e ( r e l a t i v e i n t e n s i t y ) : 266 (M +, 100), 251 (24), 235 (24), 223 (41), 209 ( 3 3 ) , 192 (16), 167 ( 1 0 ) , 165 (24), 153 ( 1 2 ) , 129 (11), 115 ( 2 4 ) . A n a l . c a l c d . f o r C 1 9 H 2 2 0 : C, 85.67; H, 8.32. Found: C, 85.99; H, 8.50. - 239 -Trans - 3 - (4-methoxyphenyl) - t e t r a c y c l o [5.3.1.1- i' 9.0-'-> 4] dodecan- 3-ol (56t) was eluted with 10% ( V / V ) ethyl acetate i n petroleum ether, and i t s s p e c t r a l c h a r a c t e r i s t i c s are as follows: MP: 1 1 7 - 1 1 9 ° C . IR (KBr): 3600 (OH) cm - 1. % NMR (CDC1 3, 400 M H z ) : 5 7 .27 (d, 2H, J = 8 Hz, aromatics meta to OCH3), 6 .87 (d, 2H, J = 8 H z , aromatics ortho to OCH3), 3 . 8 1 (s, 3H, OCH3), 2.93 (br d, I H , J = 12 H z , H c ) , 2.21 (d, I H , J = 12 H z , H b ) , 2 .12 (d, I H , J - 12 H z , H a ) , 2 . 40-2.00 (m, 4H), 1 . 8 5-1 . 6 9 (m, 10H). MS, m/e ( r e l a t i v e i n t e n s i t y ) : 284 ( M + , 3.1), 266 ( 7 6 ) , 251 ( 1 3 ) , 235 ( 1 5 ) , 209 ( 1 7 ) , 165 ( 1 1 ) , 135 ( 3 4 ) , 115 ( 1 7 ) , 91 ( 1 5 ) , 77 ( 1 2 ) . Anal, calcd. f o r C 1 9 H 2 4 0 2 : C , 8 0 . 2 4 ; H , 8 . 5 1 . Found: C , 8 0 . 5 4 ; H , 8 . 6 7 . Photolysis of 2-(3-Methyltricyclo[3.3.1.1. J•' ] d e c - l - y l - 1 -(4-chlorophenyl)-ethanone, 58 I r r a d i a t i o n of compound 58 i n a c e t o n i t r i l e r e s u l t e d i n four cyclobutanols. The cyclobutanols were separated on a s i l i c a gel column. The cyclobutanols 58t and 58t' were eluted f i r s t and second respec-t i v e l y with 2 :98 ( V / V ) ethyl acetate:petroleum ether, 58c' was eluted t h i r d with 3 . 5 : 9 6 . 5 ( V / V ) ethyl acetate:petroleum ether, and 58c was eluted l a s t with 5 :95 ( V / V ) ethyl acetate:petroleum ether. No cyclobu-tanol showed any o p t i c a l r o t a t i o n . The s p e c t r a l c h a r a c t e r i s t i c s of the cyclobutanols are as follows: - 240 -C i s - 3 - ( 4 - c h l o r o p h e n y l ) - 9 - m e t h y l t e t r a c y c l o [ 5 . 3 . 1 . I 5 • ^ . 0 1 • 4 ] d o d e c a n - 3 - o l (58c) IR ( n e a t ) : 3368 ( b r , OH) cm" 1. % NMR (CDC1 3, 400 MHz): 6 1. 34 (m, 4H, a r o m a t i c s ) , 2.69 (d, IH, J - 10 Hz, H b ) , 2.55 (br s, IH, H c ) , 2.43 (br s, IH, m e t h i n e ) , 2.12 (d, IH, J = 10 Hz, H a ) , 2.05 (m, IH, exchangeable, OH), 1.79 (m, 2H), 1.64 (m, 2H), 1.27 (m, 3H), 1.13 (m, 3H), 0.89 (m, IH), 0.51 ( s , 3H, CH3) . D e c o u p l i n g a t 5 2.69 (H b) caused the c o l l a p s e o f the d o u b l e t a t 6 2.12 (H a) . NOE d i f f e r e n c e experiment (400 MHz): I r r a d i a t i o n a t 5 0.51 (methyl group) r e s u l t e d i n p o s i t i v e enhancement a t 5 7.34 ( a r o m a t i c p r o t o n s ) . MS, m/e ( r e l a t i v e i n t e n s i t y ) : 302 (M +, 3.0), 287 ( 4 . 8 ) , 284 (12), 267 (90), 249 (11), 163 (29), 149 (47), 139 (100), 115 (49), 105 (47); e x a c t mass c a l c d . 302.1437; found 302.1415. Trans-3 - ( 4 - c h l o r o p h e n y l ) - 9 - m e t h y l t e t r a c y c l o [ 5 . 3 .1.1-* * ^  . 0 1 » 4 ] dodecan-3 - o l ( 5 8 t ) IR ( K B r ) : 3433 (OH) cm - 1. X H NMR (CDCI3, 400 MHz): 6 7.28 (m, 4H, a r o m a t i c s ) , 2.60 (br d, IH, J = 12 Hz, H c ) , 2.35 (br s, IH, m e t h i n e ) , 2.27 (d, IH, J = 11 Hz, H b ) , 2.25 (br s, IH, m e t h i n e ) , 2.08 (d, IH, J = 11 Hz, H a ) , 2.06 (m, 2H), 1.92 (m, IH), 1.67 (m, 4H), 1.45 (m, 4H), 0.89 ( s , 3H, CH3). D e c o u p l i n g a t 6 2.60 (H c) r e d u c e d the m u l t i p l i c i t y o f m u l t i p l e t c e n t r e d 241 a t 6 1.67 (adamantyl r i n g p r o t o n s ) , and i r r a d i a t i o n a t 6 2.08 (H a) cause d the c o l l a p s e o f the s i g n a l a t 5 2.25 ( H b ) . MS, m/e ( r e l a t i v e i n t e n s i t y ) : 302 (M +, 6.3), 295 ( 1 . 8 ) , 284 (8. 0 ) , 267 (100), 249 ( 8 . 9 ) , 163 ( 5 1 ) , 149 ( 4 6 ) , 139 ( 9 1 ) , 107 ( 3 9 ) , 93 (56); e x a c t mass c a l c d . 302.1437; found 302.1419. A n a l , c a l c d . f o r C 1 9 H 2 3 C 1 0 : C, 75.36; H, 7.65. Found: C, 75.86; H, 7.71. T r a n s - 3 - ( 4 - c h l o r o p h e n y l ) - 7 - m e t h y l t e t r a c y c l o [ 5 . 3 . 1 . I 5 • 9 . 0 1 > 4 ] d o d e c a n - 3 - o l ( 5 8 f ) • IR ( n e a t ) : 3431 ( b r , OH) cm - 1. XH NMR (CDC1 3, 400 MHz): 5 7.28 (m, 4H, a r o m a t i c s ) , 2.84 (br d, IH, J = 12 Hz, H c ) , 2.31 (br s, IH, me t h i n e ) , 2.23 (d, IH, J = 11 Hz, H b ) , 2.20 (m, IH), 2.13 (d, IH, J = 11 Hz, H a ) , 2.11-2.00 (m, IH), I. 68-1.42 (m, 9H), 0.96-0.83 (m, IH), 0.79 ( s , 3H, CH3). I r r a d i a t i o n a t 5 2.80 (H c) and 2.30 (methine) r e d u c e d the m u l t i p l i c i t y o f s i g n a l a t S 1.66 (adamantyl r i n g p r o t o n s ) , and i r r a d i a t i o n a t 2.23 (H b) caus e d the d o u b l e t a t S 2.13 (H a) to c o l l a p s e . MS, m/e ( r e l a t i v e i n t e n s i t y ) : 302 (M +, 3.2), 287 ( 3 . 6 ) , 284 (11), 267 (74), 193 ( 8 . 3 ) , 179 (11), 163 (40), 156 (26), 139 (100), 128 (24), 111 (43), 107 (38); e x a c t mass c a l c d . 302.1437; found 302.1430. A n a l , c a l c d . f o r C 1 9 H 2 3 C 1 0 : C, 75.36; H, 7.65; 0, 5.28. Found: C, 75.62; H, 7.60; 0, 5.15. - 242 -C i s - 3 - ( 4 - c h l o r o p h e n y l ) - 7 - m e t h y l t e t r a c y c l o [ 5 . 3 . 1 . 1 5 » 9 . 0 1 ' 4 ] d o d e c a n - 3 - o l ( 5 8 c ' ) . IR ( K B r ) : 3250 (OH) cm - 1. -^H NMR (CDC1 3, 400 MHz): 5 7.38 (m, 4H, a r o m a t i c s ) , 2.72 (d, IH, J = 11 Hz, H b ) , 2.50 (br s, IH, H c ) , 2.40 (br s, IH, m e t h i n e ) , 2.34 (m, IH), 2.06 (d, IH, J - 11 Hz, H a ) , 1.71-1.10 (m, 11H), 0.96-0.82 (m, IH), 0.79 ( s , 3H, C H 3 ) . MS, m/e ( r e l a t i v e i n t e n s i t y ) : 302 (M +, 4.0), 287 ( 1 . 7 ) , 284 (15), 267 ( 9 8 ) , 249 ( 1 6 ) , 163 ( 3 0 ) , 149 ( 4 1 ) , 139 (100), 111 ( 4 4 ) ; e x a c t mass c a l c d . 302.1437; found 302.1394. P r e p a r a t i v e S c a l e I r r a d i a t i o n o f Compound 58 i n the S o l i d S t a t e Two l a r g e s i n g l e c r y s t a l s w e i g h i n g 313 and 142 mg were p l a c e d i n q u a r t z tubes, degassed, s e a l e d and i r r a d i a t e d e x t e r n a l l y f o r two days a t 6 ± 2°C w i t h a 450 W H anovia medium p r e s s u r e mercury lamp f i t t e d w i t h a Pyrex f i l t e r . The c r y s t a l s were d i s s o l v e d i n 1 mL o f c h l o r o f o r m , and o p t i c a l r o t a t i o n s were measured on a p o l a r i m e t e r . The e x t e n t o f conver-s i o n t o p r o d u c t s was d e t e r m i n e d by gas chromatography. The s o l u t i o n s were combined and most o f the s t a r t i n g m a t e r i a l , ketone 58 was s e l e c -t i v e l y c r y s t a l l i z e d out u s i n g e t h a n o l as the s o l v e n t . The r e m a i n i n g m a t e r i a l c o n s i s t e d m a i n l y o f p h o t o p r o d u c t s , 58c, 58t, 58t' and 58c', w i t h 70% o f the p r o d u c t b e i n g 58c'. T h i s m a t e r i a l was s e p a r a t e d by column chromatography. 243 C h i r a l S h i f t Reagent Studies The determination of enantiomeric p u r i t y of the cyclbutanols 58t and 58c' was c a r r i e d out using the c h i r a l s h i f t reagent, [3-(hepta-fluoropropyl hydroxymethylene)-d-campharato]europium ( I I I ) , abbreviated as Eu(hfc)3. The experiments were performed at room temperature on a Varian XL-300 NMR spectrometer (operating at 300 MHz) by taking -25 mg of cyclobutanol i n -0.5 mL of 50:50 (V/V) deuterochloroform:carbon t e t r a c h l o r i d e solvent. The c h i r a l s h i f t reagent s o l u t i o n was made by d i s s o l v i n g Eu(hfc)3 i n deuterochloroform and t h i s was added to the cyclobutanol s o l u t i o n i n increments. The spectrum was recorded a f t e r each a d d i t i o n of c h i r a l s h i f t reagent. In both cyclobutanols 58t and 58c', a doublet corresponding to phenyl protons could be resolved for the R and S isomers, and the enantiomeric excess was determined from the in t e g r a t i o n of the NMR peaks of the R and S isomers using the following equation. the integrated area of the major isomer % enantiomeric excess = x 100 the integrated area of the major + minor isomers Trans-cyclobutanol (58t, i s o l a t e d from the s o l u t i o n state i r r a d i a -t i o n of ketone 58, 25 mg) was dissolved i n 0.5 mL of 50:50 (V/V) deuterochloroform:carbon t e t r a c h l o r i d e , to which was added 25 mg of Eu(hfc)3 i n 70 uL of deuterochloroform i n three portions of 15, 20 and 35 uL. The integrated areas of the phenyl proton f o r the R and S - 244 -isomers were e q u a l , i n d i c a t i n g the absence o f any e n a n t i o m e r i c e x c e s s . C i s - c y c l o b u t a n o l (58c', i s o l a t e d from the s o l i d s t a t e i r r a d i a t i o n , 25 mg) was a n a l y z e d as d e s c r i b e d f o r 30t, e x c e p t t h a t 25 mg o f E u ( h f c ) 3 i n 70 uL o f d e u t e r o c h l o r o f o r m was added i n 6 i n c r e m e n t s o f 15, 10, 10, 10, 10, and 15 uL. An e n a n t i o m e r i c e x c e s s o f 82% was o b t a i n e d . Quantum Y i e l d s a) Gas Chromatography D e t e c t o r Responses A l l the a l k a n e s used as i n t e r n a l s t a n d a r d s were l i n e a r a l k a n e s and were u s e d as r e c e i v e d from A l d r i c h C h e m i c a l s , w i t h o u t f u r t h e r p u r i f i c a -t i o n . The i n t e r n a l s t a n d a r d s were chosen so t h a t t h e i r peaks would n o t o v e r l a p w i t h any o t h e r peaks e x p e c t e d and y e t have a r e t e n t i o n time c l o s e t o t h a t o f the p h o t o p r o d u c t s s t u d i e d . T e t r a d e c a n e was used as an i n t e r n a l s t a n d a r d f o r acetophenone, and docosane was used f o r 4 - c h l o r o -acetophenone. Docosane was a l s o u s ed as an i n t e r n a l s t a n d a r d f o r the c y c l o b u t a n o l s from compounds 50, 53, 54 and 56. The f o l l o w i n g p r o c e d u r e employed f o r measuring the flame i o n i z a t i o n d e t e c t o r r e s p o n s e o f 4-chloroacetophenone w i t h r e s p e c t t o docosane i s t y p i c a l . A c c u r a t e l y weighed samples o f docosane (15 to 20 mg) and 4 - c h l o r o a c e t o p h e n o n e (15 to 20 mg) were d i s s o l v e d i n and made up t o 5.0 mL o f benzene i n a v o l u m e t r i c f l a s k . The d e t e c t o r r e s p o n s e s were d e t e r m i n e d by comparing the r a t i o s o f area/mg o b t a i n e d from a t l e a s t 5 gas c h r o m a t o g r a p h i c a n a l y s e s o f t h i s benzene s o l u t i o n c o n t a i n i n g - 245 -docosane and 4- c h l o r o a c e t o p h e n o n e . The d e t e c t o r r e s p o n s e s were n o t o n l y measured f o r the c l e a v a g e and c y c l i z a t i o n p r o d u c t s r e l a t i v e t o one another i n ke t o n e s 28-30, 32 and 50 b u t a l s o f o r each p r o d u c t w i t h r e s p e c t t o a p p r o p r i a t e i n t e r n a l s t a n d a r d . b) P r e p a r a t i o n o f Samples f o r I r r a d i a t i o n ( i ) F o r quantum y i e l d s A l l s o l u t i o n s were p r e p a r e d i n benzene, u n l e s s o t h e r w i s e i n d i c a t e d . S e p a r a t e s t o c k s o l u t i o n s c o n t a i n i n g known amounts o f t e t r a d e c a n e (5.0 x 1 0 " 3 M) and docosane (3.2 x 1 0 " 3 M) were made i n 500 mL s t a n d a r d v o l u m e t r i c f l a s k s . These s t o c k s o l u t i o n s were the n u s e d t o make up the s o l u t i o n s c o n t a i n i n g known amounts o f ketone (-0.1 M) i n 25 mL s t a n d a r d v o l u m e t r i c f l a s k s . The s o l u t i o n s o f ketones (-0.1 M) were a l s o p r e p a r e d i n aqueous (2% water) a c e t o n i t r i l e i n 25 mL s t a n d a r d v o l u m e t r i c f l a s k s . No i n t e r n a l s t a n d a r d was added as the r e q u i r e d s t r a i g h t c h a i n a l k a n e s a r e i n s o l u b l e i n a c e t o n i t r i l e o r aqueous a c e t o n i t r i l e . ( i i ) F o r quenching s t u d i e s The quenching s t u d i e s were c a r r i e d o ut i n benzene u s i n g 2,5-dimethyl-2,4-hexadiene as the quencher. The s t o c k s o l u t i o n o f benzene c o n t a i n i n g docosane was used f o r p r e p a r i n g a l l the s o l u t i o n s . A - 246 -stock solution of 250 mL of 2.0 M 2,5-dimethyl-2,4-hexadiene was made and used to make up other stock solutions of varying quencher concentra-tions (10 solutions with concentrations ranging from 0.1 to 0.15 M) by diluting the appropriate pipetted amounts of 2.0 M solution in standard volumetric flasks. Pipetting 1.0 mL of 1.0 M ketone solution that was prepared for quenching studies and 1.0 mL of required quencher solution and making i t up to 10 mL in a standard volumetric flask provided various ketone solutions of 0.1 M cone. with different quencher concentrations. For example, to prepare a solution requiring 0.1 M ketone and 0.15 M quencher, 1.0 mL of 1.0 M ketone solution and 1.0 mL of 1.5 M quencher solutions were pipetted with a 1.0 mL pipette and made up to 10.0 mL in a 10.0 mL standard volumetric flask. Irradiation of samples Three mL aliquots of solutions containing known concentrations of ketone and any other additives (e.g. quenchers) were pipetted into 100 x 13 mm Pyrex test tubes and were degassed by four freeze-thaw-pump cycles at 0.01 Torr. The samples were then sealed with a $ B14 stopper and secured with polyethylene film. A l l irradiations were performed in a "merry-go-round" apparatus with a 450 W Hanovia medium pressure mercury lamp housed in a quartz immersion well. The 313 nm mercury line was isolated by circulating a 0.002 M potassium chromate solution containing 5% potassium carbonate 247 (Wt/Wt) through the q u a r t z immersion w e l l and by p l a c i n g 7.54 C o r n i n g f i l t e r s i n the f i l t e r h o l d e r . T h i s c i r c u l a t i n g s o l u t i o n , i n a d d i t i o n to i s o l a t i n g 313 nm l i n e , c o o l s the q u a r t z immersion w e l l . The whole merry-go-round a p p a r a t u s was immersed i n a water b a t h whose temperature was m a i n t a i n e d a t 20 ± 2°C by p l a c i n g a l a r g e copper c o i l i n s i d e the water b a t h and by p a s s i n g c o l d water through the copper c o i l . The temperature o f the c i r c u l a t i n g s o l u t i o n was a l s o m a i n t a i n e d a t 20 ± 2°C by a w a t e r - c o o l e d copper c o i l i n the same way. A c t i n o m e t r y The quantum y i e l d s were measured f o r the f o r m a t i o n o f 4-chloro-acetophenone i n compounds 28, 38, 45, 46, and 50 and f o r the f o r m a t i o n o f c y c l o b u t a n o l s i n ketones 54 and 56. The quantum y i e l d s were de t e r m i n e d r e l a t i v e to the f o r m a t i o n o f acetophenone from 0.1 M v a l e r -ophenone ( a c t i n o m e t e r ) i n benzene on p a r a l l e l i r r a d i a t i o n s o f i d e n t i c a l volumes. The quantum y i e l d o f acetophenone f o r m a t i o n i s known to be 0.33 i n b e n z e n e . 2 4 5 The c o n v e r s i o n to p r o d u c t s ( a c t i n o m e t e r as w e l l as t e s t samples) was l i m i t e d t o 6%. The i r r a d i a t i o n s were c a r r i e d out u s u a l l y f o r 2-3 hours to a c h i e v e a degree o f c o n v e r s i o n ( t y p i c a l l y 3 to 4%) s u f f i c i e n t to d e t e c t p h o t o p r o d u c t s on the gas chromatograph. I r r a d i a t i o n s were co n d u c t e d f o r 12-48 hours i n the case o f k e t o n e s 54 and 56 because of the v e r y low quantum y i e l d s i n v o l v e d . I n such i r r a d i a t i o n s , a c t i n o m e t e r samples were r e p l a c e d e v e r y 3 hours and the combined c o n v e r s i o n to 248 -p h o t o p r o d u c t s o f the a c t i n o m e t e r s o l u t i o n s was used i n d e t e r m i n i n g the quantum y i e l d o f the t e s t samples. The quantum y i e l d s t u d i e s i n aqueous a c e t o n i t r i l e s o l u t i o n s were p e r f o r m e d as d e s c r i b e d above w i t h one v a r i a t i o n . Because o f the poor s o l u b i l i t y o f the i n t e r n a l s t a n d a r d s i n aqueous a c e t o n i t r i l e , a known amount o f i n t e r n a l s t a n d a r d (-2 mg) i n 2 mL o f benzene was added to the s o l u t i o n a f t e r i r r a d i a t i o n . The quantum y i e l d s were a g a i n d e t e r m i n e d r e l a t i v e t o the f o r m a t i o n o f acetophenone from 0.1 M v a l e r o p h e n o n e i n benzene. R e p o r t e d quantum y i e l d s a r e the r e s u l t o f m u l t i p l e gas chroma-t o g r a p h i c a n a l y s e s f o r a t l e a s t 4 t e s t samples. The e s t i m a t e d o v e r a l l a c c u r a c y i s ±10%. The c y c l i z a t i o n quantum y i e l d s i n the case o f compounds 28, 38, 45, 46, and 50 and the c l e a v a g e quantum y i e l d i n compound 53 were c a l c u l a t e d from the p r e v i o u s l y d e t e r m i n e d c l e a v -age : c y c l i z a t i o n r a t i o s . These c a l c u l a t e d quantum y i e l d s a r e r e l i a b l e , as the measured c l e a v a g e : c y c l i z a t i o n d e t e c t o r r e s p o n s e s a r e n e a r l y i d e n t i c a l i n t h e s e compounds. Quenching s t u d i e s The quantum y i e l d s were det e r m i n e d u s i n g the i d e n t i c a l p r o c e d u r e as d e s c r i b e d above f o r the quantum y i e l d d e t e r m i n a t i o n s i n benzene w i t h the s i n g l e v a r i a t i o n t h a t t h e se s o l u t i o n s c o n t a i n e d v a r i o u s amounts o f quencher (0.01 to 0.20 M) i n a d d i t i o n to the ketone (0.1 M). Two quenching experiments were c a r r i e d out f o r each ketone s t u d i e d , and i n each q u e n c h i n g experiment, 5 to 6 samples (1 sample w i t h no quencher and - 249 -the o t h e r samples w i t h v a r y i n g c o n c e n t r a t i o n s o f quencher; c o n c e n t r a t i o n o f ketone i s 0.1 M i n a l l the samples) were i r r a d i a t e d and $ 0/$ was c a l c u l a t e d f o r each quencher c o n c e n t r a t i o n where $ Q — quantum y i e l d w i t h no quencher, and $ = quantum y i e l d i n the p r e s e n c e o f quencher. The average $ 0/$ v a l u e s f o r two quenching runs were p l o t t e d a g a i n s t the quencher c o n c e n t r a t i o n t o o b t a i n a s t r a i g h t l i n e . From the s l o p e o f the s t r a i g h t l i n e , the l i f e t i m e s o f the t r i p l e t e x c i t e d s t a t e were c a l c u l a t e d . The r a t e o f d i f f u s i o n (kq) i n benzene was p r e v i o u s l y d e t e r m i n e d t o be 5 x 1 0 9 M"^ sec"1.120 Q u a n t i t a t i v e a n a l y s e s A l l a n a l y s e s f o r p h o t o p r o d u c t f o r m a t i o n were p e r f o r m e d on c a p i l l a r y columns on gas chromatographs. The a r e a r a t i o s o f p r o d u c t f o r m a t i o n were c o n v e r t e d t o mole r a t i o s by c a l i b r a t i o n w i t h known amounts of i n t e r n a l s t a n d a r d s p r e s e n t i n the t e s t samples. The r e p o r t e d quantum y i e l d s a r e the s t a t i s t i c a l averages o f a t l e a s t 4 runs. The r e p o r t e d t r i p l e t e x c i t e d s t a t e l i f e t i m e s a r e the average o f two quenching e x p e r i m e n t s . - 250 -BIBLIOGRAPHY 1. F o r re v i e w s summarizing work up t o 1952 and 1966, see a) M u s t a f a , A. Chem. Rev. 1952, 51, 1-23. b) Morawetz, H. S c i e c e 1966, 152, 705-711. 2. Markwald, W. Z. 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