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The synthesis and reactivity of tetracyclo [3.3.1.1³‧⁷.0¹‧³] decane Thorpe, Edward John 1975

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THE SYNTHESIS AND REACTIVITY OF TETRACYCLO ^ 3 . 3 . 1 . 1 3 , 7 . 0 1 , 3 J DECANE by EDWARD JOHN THORPE B.Sc. (Hons.) U n i v e r s i t y o f B r i t i s h C o l u m b i a , 1965 M.Sc. U n i v e r s i t y o f B r i t i s h C o l u m b i a , I968 A THESIS SUBMITTED IN PARTIAL FULFILMENT OF' THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY i n the Department o f C h e m i s t r y We a c c e p t t h i s t h e s i s 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, 1975 In presenting th i s thesis in p a r t i a l fu l f i lment of the requirements for an advanced degree at the Univers i ty of B r i t i s h Columbia, I agree that the L i b r a r y shal l make it f ree ly ava i lab le for reference and study. I further agree that permission for extensive copying of th i s thes is for scho lar ly purposes may be granted by the Head of my Department or by his representat ives . It is understood that copying or p u b l i c a t i o n of th i s thes is for f inanc ia l gain sha l l not be allowed without my wri t ten permission. Department of The Univers i ty of B r i t i s h Columbia Vancouver 8. Canada Date it, H - u ^ j f I V i I - i i -ABSTRACT Supervisor: Dr. R. E. Pincock The structures and some properties of adamantane ( l b ) , strained cyclopropanes ( 2 3 ) , and cert a i n small r i n g p r o p e l l e r -l i k e molecules ( 2 8 ) are reviewed. The synthesis of a new type of compound containing a combination of such structures and properties i s presented. This compound tetracyclo (DHA) contains a very strained cyclopropyl group within an adamantane skeleton and was produced by bonding two bridge-head ( t e r t i a r y ) carbons together across the normally extremely r i g i d structure of adamantane. (This new compound, DHA, i s shown below.) In the synthesis of DHA using a l k a l i metal (or al l o y s ) with 1,3-dibromoadamantane (37)> the reaction times and r e l a t i v e y i e l d s of adamantane and DHA were extremely var i a b l e . The former d i f f i c u l t y was resolved more simply 1,3-dehydroadamantane - i i i -by the a d d i t i o n o f an i n i t i a t o r ( u s u a l l y t _ - b u t y l a l c o h o l ) , w h i l e the y i e l d s were i n c r e a s e d and made c o n s i s t e n t by s u b s t i t u t i n g sodium n a p h t h a l i d e o r n - b u t y l l i t h i u m -hexamethylphosphoramide f o r the a l k a l i m e t a l s . DHA and adamantane were a l s o i s o l a t e d as the major p r o d u c t s from the r e a c t i o n o f 1 , 3 , 5 - t r i - and 1 , 3 , 5 , 7-tetrabromoadamantane w i t h a l k a l i m e t a l s o r a l l o y s . DHA i s one o f the few o r g a n i c m o l e c u l e s w h i c h p o s s e s s e s a s o - c a l l e d i n v e r t e d geometry about the i n t e r n a l l y bonded b r i d g e h e a d ( q u a t e r n a r y ) c a r b o n s . Wiberg, H i a t t and 55 Burgmaier have d e f i n e d an i n v e r t e d carbon as one " i n which a l l atoms j o i n e d t o the b r i d g e h e a d atoms ( i n v e r t e d c a r b o n s ) l i e i n one hemisphere, ( i . e . i n one p l a n e o r on one s i d e o f a p l a n e p a s s i n g t h r o u g h the b r i d g e h e a d a t o m s ) . " The i n v e r s i o n o f the DHA b r i d g e h e a d c a r b o n s r e s u l t s i n a h i g h l y s t r a i n e d bond and an u n u s u a l l y g r e a t r e a c t i v i t y f o r a f o r m a l l y s a t u r a t e d h y d r o c a r b o n . DHA r e a c t s s p o n t a n e o u s l y w i t h oxygen a t room temperature t o g i v e a peroxy polymer Ad - 0 -f 0 - Ad - 0 O A d w h i c h e x p l o d e s a t o X c a . 1A-6 C. DHA a l s o r e a c t s r a p i d l y w i t h h a l o g e n s , a c i d s , and m e r c u r i c a c e t a t e t o y i e l d h a l i d e s , e s t e r s and a l c o h o l s , r e s p e c t i v e l y . A l t h o u g h the d i r e c t r e a c t i o n o f DHA w i t h - i v -alcohols i s slow (more than Zl\ hr to complete), Lev/is acid c a t a l y s t s promoted rapid addition of both alcohols (to give ethers) and benzene (to give phenylated adamantanes). Adam's ca t a l y s t promoted the rapid (30 min) addition of hydrogen to DHA i n n-heptane solution to produce adamantane. o In the s o l i d phase DHA polymerized r e a d i l y at ca. 160 C to give a highly insoluble product, polyadamantane Ad-(Ad) -Ad which possesses great thermal s t a b i l i t y (decomposition point ca. 500° C under nitrogen). In n-octane solution under nitrogen the half l i f e of DHA was if,45 hr at 195 °C, The reaction of DHA with halogens i n ether gives (3-halo-l-adamantanyl)-diethyl oxonium t r i h a l i d e . The reaction of t h i s unstable intermediate with nucleophiles, for example H2O or NaCN, i s discussed as a pot e n t i a l source of unsym-metrical 1,3-disubstituted adamantane deri v a t i v e s . 1 - V -TABLE OF CONTENTS Page INTRODUCTION 1 A. Adamantane 2 B. Cyclopropanes and Small Ring Propellanes 16 C. Adamantane Molecules containing Cyclopropyl Bonds 23 RESULTS 28 A. Preparation of Brominated Adamantanes 28 B. Preparation of 1,3-Dehydroadamantane 30 C. Structure of 1,3-Dehydroadamantane 32 D. Reactions of 1,3-Dehydroadamantane 33 DISCUSSION 46 A. Synthesis i+6 , B. Structure of 1,3-Dehydroadamantane 59 C. Reactions of 1,3-Dehydroadamantane 68 D. Conclusions 103 EXPERIMENTAL 105 A. Preparation of Brominated Adamantanes 109 B. Preparation of 1,3-Dehydroadamantane -Representative Reactions l l i f C. Reactions of 1,3-Dehydroadamantane 129 BIBLIOGRAPHY 161 - v i -LIST OF TABLES Table Page I R e p r e s e n t a t i v e S y n t h e s e s o f 1,3- 55 Dehydroadamantane I I M i c r o a n a l y t i c R e s u l t s f o r the I n t e r m e d i a t e 75 Compound Formed from 1,3-Dehydroadamantane v/i t h Bromine i n E t h e r I I I S u b s t i t u t i o n o f (3-Bromo-l-adamantanyl)- 82 d i e t h y l o x o n i u m t r i b r o m i d e w i t h N u c l e o p h i l e s IV S u b s t i t u t i o n o f (3-Bromo-l-adamantanyl)- 82, 141 d i e t h y l oxonium t r i b r o m i d e i n S o l v e n t M i x t u r e s V N o r m a l i z e d 1,3-Dehydroadamantane Trace 160 Weights f o r Samples a f t e r V a r i o u s Times a t 195°C - v i i -LIST OF FIGURES Figure Page 1. The NMR Spectrum of 1,3-Dehydroadamantane i n Benzene at 100 Mcps 60 2. The NMR Spectrum of 3,7-Dimethy1-1,3-dehydroadamantane i n Benzene at 100 Mcps 61 3. The NMR Spectrum of (3-Bromo-l-adaraantanyl)-d i e t h y l oxonium tribromide i n Acetone-d,-at 100 Mcps " D 77 78 k. The NMR'Spectrum of l-Bromo-3-ethoxyadaman-tane i n CDCl^ at 100 Mcps 5. The NMR Spectrum of l-Bromo-3-hydroxy-adamantane i n CDCl^ at 100 Mcps 81 - v i i i -ACKNOWLEDGEMENTS I would l i k e to express my sincere gratitude to Dr. R. E. Pincock for his patient and continual help during the course of t h i s v/ork. I would also l i k e to thank Dr. R. Stewart, Dr. D. E. McGreer and Dr. E. Piers for t h e i r h e l p f u l suggestions and comments. I dedicate t h i s thesis to my long s u f f e r i n g wife, Bonnie, without whose encouragement and assistance t h i s thesis would not have been f i n i s h e d . INTRODUCTION T h i s t h e s i s r e p o r t s a study of the s y n t h e s i s and r e a c t i o n s o f the compound t e t r a c y c l o j~3.3.1.1^'^.O^'^ decane ( l a ) or more simply 1 ,3-dehydroadaraantane (DHA). T h i s compound can be viewed both as a m o d i f i e d adamantane compound and as a s t r a i n e d cyclopropane compound. Thus, the i n t r o d u c t i o n to t h i s work i s d i v i d e d i n t o three s e c t i o n s . The f i r s t s e c t i o n d e s c r i b e s adamantane, i t s s y n t h e s i s and p r o p e r t i e s . The second s e c t i o n b r i e f l y r e l a t e s the development of the theory o f the c y c l o p r o p y l bond and the a l t e r a t i o n i n the p r o p e r t i e s of t h i s bond when oth e r s m a l l r i n g groups are fused with the cyclopropane molecule. The f i n a l s e c t i o n reviews those adamantane d e r i v e d compounds which c o n t a i n c y c l o p r o p y l groups and are t h e r e f o r e c l o s e l y r e l a t e d to 1 ,3-dehydroadamantane (DHA). - 2 -A. Adamantane Adaraantane i s the common name f o r the roughly 2 s p h e r i c a l or g l o b u l a r molecule, t r i c y c l o decane ( l b ) . 3 . 3 . 1 . 3 3 ' 7 Diagram 1 Two di m e n s i o n a l r e p r e s e n t a t i o n s o f adamantane do not do j u s t i c e to the h i g h symmetry o f t h i s molecular s t r u c t u r e . The molecule possesses a t e t r a h e d r a l symmetry i d e n t i c a l w i t h the bonding o r b i t a l s o f a s p 3 h y b r i d i z e d carbon atom. T h i s symmetry can be v e r i f i e d by drawing imaginary planes through each o f the f o u r cyclohexane r i n g s so th a t these p l a n e s pass through the t e r t i a r y carbon atoms to form an imaginary t e t r a h e d r o n w i t h each o f the b r i d g i n g or t e r t i a r y carbon atoms a t a v e r t e x . T h e o r e t i c a l l y , an adamantane compound wit h f o u r d i f f e r e n t bridgehead s u b s t i t u t e n t s should be r e s o l v a b l e i n t o o p t i c a l l y a c t i v e isomers. F i r s t l y , H a m i l l and McKervey have s y n t h e s i z e d the analogue or adamantalogue (2a) of l a c t i c a c i d ( 2 b ) . They have shown that the bromination product (2a) does indeed possess a s m a l l but measurable increment of o p t i c a l a c t i v i t y . -- 3 -Diagram 2 The s t r u c t u r e o f the o p t i c a l l y a c t i v e adamantalogue (2a) was confirmed by treatment w i t h sodium hydroxide s o l u t i o n . The product (2c) was i d e n t i c a l w i t h a product obtained from an u n r e l a t e d unambiguous s y n t h e s i s . F i n a l l y , S t e t t e r , Bander and Neumann-^ have observed and s t u d i e d a v i c i n a l d i c h l o r o - a l l e n e (2a) type of o p t i c a l isomerism i n the f o l l o w i n g adamantalogue (2b). a b Diagram 3 Rearrangements e n l a r g i n g or b r e a k i n g the adamantane r s k e l e t o n have been r e p o r t e d with i n c r e a s i n g frequency d e s p i t e the g e n e r a l l y acknowledged thermodynamic s t a b i l i t y of t h i s s keleton.7 F' - 4 -By further pursuing the analogy between the t e t r a -hedrally hybridized carbon atom and adamantane, several groups have synthesized adamantalogues of simple a l i p h a t i c hydrocarbons. To date, the adamantalogues for ethane, methane and propane have been synthesized. The synthesis 8a of higher hydrocarbon adamantalogues remains under study. Neither the high symmetry nor the related high thermodynamic s t a b i l i t y ' of adamantane was u t i l i z e d i n the early syntheses and studies of the compound. The y i e l d s of these syntheses were poor. Despite t h e i r low y i e l d s , these t o t a l syntheses were important because they were the only source of secondary and t e r t i a r y substituted adamantane der i v a t i v e s . The importance of these synthetic routes did not diminish s u b s t a n t i a l l y a f t e r Stetter and V/ulf^ developed a method for progressively increased bridgehead substitution of adamantane. The symmetry of adamantane made d i s s i m i l a r s u b stitution d i f f i c u l t to achieve by the Stetter and Wulf approach. Early e f f o r t s to synthesize adamantane were stimulated v/hen i t was r e a l i z e d that the sole source of t h i s i n t e r e s t -ing compound was controlled by a strong monopoly which released i t only i n minute amounts. Since i t s discovery i n the petroleum from the Hodinin f i e l d s of Czechoslovakia, only very small amounts of the compound found t h e i r way out of Landa's l a b o r a t o r y . T o correct t h i s a r t i f i c i a l - 5 -s c a r c i t y many a t t e m p t s were made t o s y n t h e s i z e adamantane. The f i r s t a t t e m pt on r e c o r d i s a t t r i b u t e d t o Meerwein ( 4 ) . 11 CH20+CH2(C02CH3 )2 R=C02Me R Diagram k .12 K l e i n f e l l e r and F r e r c k s a t t e m p t e d two e n t i r e l y d i f f e r e n t approaches t o the problem b o t h o f w h i c h a l s o f a i l e d ( 5 ) . N02C(CH2Cl)3 + | • H 3(Et02C )CH2C Diagram 5 - 6 -B o t t i g e r 1 3 was the f i r s t t o s u c c e s s f u l l y s y n t h e s i z e the adamantane s k e l e t o n ( 6 ) , however, adamantane i t s e l f was not r e a l i z e d . A g a i n , the Meerwein e s t e r was the key i n t e r m e d i a t e i n t h i s scheme. P r e l o g and S e i w e r t h ^ were the f i r s t t o s y n t h e s i z e the p a r e n t h y d r o c a r b o n ( 7 ) . The o v e r a l l y i e l d from t h e P r e l o g and S e i w e r t h y l a t e r were a b l e t o i n c r e a s e the o v e r a l l y i e l d t o 1.5% by i m p r o v i n g the d e c a r b o x y l a t i o n s t e p s ( 8 ) . The H u n s d i e c k e r pathway gave an 1 1 % y i e l d based on the d i a c i d w h i l e the Hoffmann r e a c t i o n gave a Zk% y i e l d from the same s t a r t i n g m a t e r i a l . S t e t t e r , Bander and Neumann - 7 -have reported the best t o t a l synthesis v i a the Meerwein ester route (9). The work of S t e t t e r , Bander and Neumann introduced a modification into the Prelog scheme which increased the o v e r a l l y i e l d of t h i s scheme to 6.5%. Diagram 9 More recently Landa and Kamycek X D have reported improved conditions f o r the synthesis of the Meerwein ester, the key intermediate of almost a l l adamantane t o t a l syntheses. The improved y i e l d of 85% furthers the f e a s i b i l i t y of the e x i s t i n g t o t a l synthesis. 17 Stetter and co-workers also have developed an elegant t o t a l synthesis of 2-substituted adamantanes (10). Their approach resembles the unsuccessful attempt of K l e i n f e l l e r 12 and Frercks. However, the f i n a l product could not be Curran and Angier have developed a method to synthesize 1,2-disubstituted adamantanes. This type of compound was previously very d i f f i c u l t i f not impossible to obtain. - 8 -c o n v e r t e d to adamantane. D e s p i t e t h i s , the sequence p r o v i d e d an e f f i c i e n t s y n t h e s i s o f 2 - s u b s t i t u t e d adamantanes wh i c h p r e v i o u s l y were a v a i l a b l e o n l y from the s y n t h e t i c schemes i n v o l v i n g the Meerwein e s t e r . T h i s was a l s o t r u e f o r the m a j o r i t y o f t e r t i a r y and h i g h e r p o l y s u b s t i t u t e d adamantanes u n t i l adamantane became r e a d i l y a v a i l a b l e . The most e l e g a n t o f a l l adamantane t o t a l s y n t h e s e s were r e p o r t e d by S c h l e y e r ( 1 1 ) . ^ T h i s sequence depended on the adamantane s t r u c t u r e h a v i n g a v e r y low i n t e r n a l ( s t r a i n ) energy. The L e w i s a c i d c a t a l y z e d i s o m e r i z a t i o n o f e n d o - t e t r a h y d r o d i c y c l o p e n t a d i e n e r e s u l t e d i n f a i r y i e l d s o f adamantane i n e s s e n t i a l l y two r e a c t i o n s , a l t h o u g h the mechanism o f the second r e a c t i o n was comprised o f many s t e p s . Diagram 11 The advent o f t h i s n o v e l s y n t h e s i s ended the v i r t u a l monopoly o f Landa on the w o r l d s u p p l y o f adamantane. - 9 -Even b e f o r e the g e n e r a l a v a i l a b i l i t y o f the p a r e n t h y d r o c a r b o n , i t was r e a l i z e d t h a t the g l o b u l a r o r r o u g h l y s p h e r i c a l shape of the adamantane m o l e c u l e gave i t some 2 u n u s u a l p h y s i c a l p r o p e r t i e s such as h i g h v o l a t i l i t y and d i s s o l u t i o n i n a s u r p r i s i n g l y wide range o f s o l v e n t s . Much l a t e r the g l o b u l a r shape o f t h i s s k e l e t o n was used a d v a n t a -g e o u s l y i n s t u d i e s o f s o l v e n t p a r t i c i p a t i o n d u r i n g s o l v o l y t i c r e a c t i o n s . ^ ( C l e a r l y , b i m o l e c u l a r n u c l e o p h i l i c s u b s t i t u -t i o n cannot o c c u r a t the b r i d g e h e a d carbons (12a) and a s i m i l a r mechanism i s s e r i o u s l y impeded a t secondary carbon by the 1 , 5 - a x i a l hydrogen atoms ( 1 2 b ) . ) X a b Diagram 12 The g l o b u l a r s t r u c t u r e a l s o had a marked e f f e c t on the r e a c t i v i t y and s t a b i l i t y o f adamantane and i t s d e r i v a t i v e s . Though s u b s t i t u t i o n o f adamantane o c c u r r e d f a i r l y r e a d i l y , t hese s u b s t i t u t i o n r e a c t i o n s o c c u r r e d p r i m a r i l y i n i n o r g a n i c s o l v e n t s under c o n d i t i o n s w h i c h would d e s t r o y the s t r u c t u r e - 10 -o f most o r g a n i c compounds. For example, exposure o f o most o r g a n i c c h e m i c a l s t o 96% s u l p h u r i c a c i d a t 70 C a l m o s t always r e s u l t e d i n the d e c o m p o s i t i o n o f th e s e compounds i n t o a t a r r y b l a c k mass, but Geluk and Schlatmann n o t e d t h a t adamantane was p r i m a r i l y o x i d i z e d t o the ketone (13) under t h e s e c o n d i t i o n s . a b Diagram 13 A n o t h e r example o f the s t a b i l i t y o f the adamantane o s t r u c t u r e was p r e s e n t e d by S t e t t e r and Wulf. I n l i q u i d bromine a t room t e m p e r a t u r e , adamantane r e a c t e d f a i r l y r a p i d l y t o g i v e 1-bromo-adamantane (l/+a). Even under f o r c i n g c o n d i t i o n s no f u r t h e r s u b s t i t u t i o n took p l a c e u n l e s s L e w i s a c i d c a t a l y s t s were added. A d d i t i o n o f the s u i t a b l e L e w i s c a t a l y s t s t o the above r e a c t i o n m i x t u r e r e s u l t e d p r e -d o m i n e n t l y i n p r o d u c t i o n o f d i o r t r i b r i d g e h e a d b r o m i n a t e d compounds ( l i f b , c r e s p e c t i v e l y ) . - 11 -B B r o — b,X=Br. Y=Z=H A L R , V ^ X = Y = B r ; Z=H ( 2.2°C ) A L U 3 \a,A=Y=Z=Br (forcing conditions) a Diagram Ik The s y n t h e s i s o f the f u l l y " b r i d g e h e a d - s u b s t i t u t e d t e t r a b r o m o d e r i v a t i v e ( l i f d ) r e q u i r e d h i g h t e m p e r a t u r e s and p r e s s u r e s i n a d d i t i o n t o the presence o f the s t r o n g L ewis a c i d c a t a l y s t , A l B r ^ . Diagram 15 The above r e a c t i o n s demonstrated the u n u s u a l s t a b i l i t y o f the adamantane s t r u c t u r e . T h i s s t a b i l i t y was a d i r e c t r e s u l t o f n o t o n l y the e s s e n t i a l l y s t a i n l e s s s t r u c t u r e but a l s o the i n f l e x i b i l i t y o f the adamantane s k e l e t o n . The s k e l e t a l r i g i d i t y o f the r i n g s t r u c t u r e o f adamantane c o u l d be i l l u s t r a t e d by the r e l a t i o n between adamantane (15a) and diamond (15b), a v e r y h a r d and d u r a b l e s u b s t a n c e . Both the s t r u c t u r a l u n i t o f diamond and the s k e l e t o n o f adamantane s h a r e d the same s t r u c t u r e . Models o f t h i s s t r u c t u r e (15a), - 12 -even i f composed o f f l e x i b l e p l a s t i c , d emonstrated a marked r e s i s t a n c e t o compre s s i o n and t o r q u e . Thus, i t i s not s u r p r i s i n g t h a t the adamantane s k e l e t o n was assumed to be b a s i c a l l y a v e r y r i g i d s t r u c t u r e . I n v e s t i g a t i o n s i n the f o l l o w i n g t h r e e a r e a s have a l s o s u p p o r t e d the concept o f a r i g i d adamantane s k e l e t o n . 22 F i r s t l y , nmr s t u d i e s have i n d i c a t e d t h a t r e g a r d l e s s o f the n a t u r e and number o f s u b s t i t u e n t s , the s k e l e t o n i s not d i s t o r t e d s i g n i f i c a n t l y s i n c e c h e m i c a l s h i f t s o f p r o t o n s i n p o l y s u b s t i t u t e d adamantanes a r e c a l c u l a b l e w i t h c o n s i d e r a b l e a c c u r a c y by a d d i t i o n o f the s h i f t s caused by s i n g l e sub-s t i t u e n t s . U n f o r t u n a t e l y , the e x i s t e n c e o f many "W" r e l a t i o n s h i p s ^ ' ^ w h i c h have been i m p l i c a t e d i n l o n g range c o u p l i n g 2 ^ * 3 a p p a r e n t l y was r e s p o n s i b l e f o r o b s c u r i n g the ex p e c t e d w e l l - d e f i n e d c o u p l i n g c o n s t a n t s i n t h i s r i g i d system. I n an e x p l a n a t i o n o f t h i s phenomenon Padwa e t a l . s u g g e s t e d t h a t the " d i r e c t o v e r l a p o f the s m a l l p o s t e r i o r l o b e s " was r e s p o n s i b l e . T h e s e l o n g range c o u p l i n g c o n s t a n t v a l u e s w h i c h appear to v a r y i n v e r s e l y w i t h d i s t a n c e have been i n v o k e d t o e x p l a i n the "washed-out" appearance o f many nmr s p e c t r a i n c y c l i c systems i n c l u d i n g t h a t o f adamantane, ' 4 22 F o r t and S c h l e y e r have a l s o shown t h a t the K a r p l u s e q u a t i o n 2 ^ a g r e e s w i t h the o b s e r v e d c o u p l i n g c o n s t a n t s i n the adamantane system. They c o n c l u d e d t h a t t h i s e x p e r i m e n t a l -t h e o r e t i c a l c o r r e l a t i o n was o b t a i n e d o n l y because the u s u a l - 13 -variations i n bond lengths, i n substituent electronegatives and i n other bond angles were v i r t u a l l y absent i n adamantanes. Secondly, simple 1,2- s h i f t s which occur intramolecularly i n most other compounds have been shown to occur only 25 through a intermolecular route i n adamantane because of 2fi the s t r u c t u r a l r i g i d i t y of t h i s skeleton. Schleyer e_t a l . concluded that unfavourable and fixed dihedral angles were responsible for the a l t e r a t i o n of the 1,2-hydride s h i f t from the normal intramolecular to an unusual intermolecular mechanism. HC0 2 H OH 96% H2SOz, 28°C 26a and / or a Diagram 16 This group observed that d i l u t i o n decreased the rate of an apparent 1,2-hydride s h i f t during a Koch-Haaf reaction (16). At low d i l u t i o n s such as 0.004 M and less i n sub-strate no rearrangement product (16c) was observed. Conversely, at higher concentrations such as 0.21 M and greater i n substrate, only the rearrangement product was observed (16c). A p a r a l l e l r e s u l t was obtained for the e q u i l i b r a t i o n of 2-hydroxyadamantane (13b) to 1-hydroxyadamantane (13a). Majerski, Schleyer and Wolf also showed that an apparent 1,2-methyl s h i f t involved s k e l e t a l rearrangement (17). - 14 -Diagram 17 The reason for these changes of mechanism must be that the dihedral angle between the secondary hydrogen atoms and the p - o r b i t a l of the t e r t i a r y carbonium ion i n adamantane was fixed at 60° (18a) because of the s k e l e t a l r i g i d i t y . c c a b Diagram 18 o Furthermore, an even larger dihedral angle (90 ) existed between a secondary carbonium ion and an adjacent hydrogen atom (18b) than i n the above s i t u a t i o n (18a). It i s well known that 1,2-shifts occurred most e a s i l y when t h i s o dihedral angle was 0 , an angle nearly impossible to a t t a i n i n the adamantane system. F i n a l l y , the unfavourable and fixed secondary-t e r t i a r y dihedral angles i n the r i g i d adamantane skeleton not only prevented 1,2-shifts but also the formation of - 15 ->.3.l] 27 double bonds. Recent s y n t h e s e s o f b i c y c l o non-l-ene (19a) by two groups encouraged f u r t h e r a t t e m p t s 29 t o s y n t h e s i z e adamantene (19b). 7 E v i d e n c e f o r the a p p a r e n t s y n t h e s i s o f t h i s compound was d i s c l o s e d v e r y r e c e n t l y by s e v e r a l l a b o r a t o r i e s . As e x p e c t e d , the compound was not s t a b l e even a t v e r y low t e m p e r a t u r e s . Diagram 19 10 1^ ^2 S e v e r a l groups '-^'^ o b s e r v e d i n d i c a t i o n s o f p o s s i b l e i n t e r a c t i o n between the b r i d g e h e a d carbon atoms o f adamantane compounds. A p o s i t i v e i n t e r n a l energy f o r adamantane might be i n t e r p r e t e d t o r e s u l t from i n t e r n a l c r o w d i n g i n a d d i t i o n 33 t o e x t e r n a l H-H i n t e r a c t i o n . O r i g i n a l l y i t was a s s u m e d ^ t h a t adamantane had a z e r o energy f o r two r e a s o n s . F i r s t l y , a g rowing number o f C]_QH16 i s o m e r s o f adamantane were c o n v e r t e d 5 t o adamantane under c o n d i t i o n s o f thermodynamic e q u i l i b r i u m . ^ S e c o n d l y , the i d e a l sp-^ geometry o f c a r b o n atoms and i d e a l d i h e d r a l a n g l e o f H-C-C-H bonds were p r e s e n t i n t h i s s k e l e t o n . 35 However, r e c e n t s t u d i e s by S c h l e y e r , W i l l i a m s , and B l a n c h a r d ^ have a t t r i b u t e d a s m a l l b u t s i g n i f i c a n t s t r a i n t o adaman-tane (6.48 K c a l / m o l e ) . The c a u s e ' o f t h i s s t r a i n was not d e l i n e a t e d ; however, t h i s d i s c l o s u r e appeared t o c o l l a b o r a t e w i t h o t h e r o b s e r v a t i o n s t o p o s s i b l y i n d i c a t e some form o f - 16 -i n t e r a c t i o n between the f o u r t e r t i a r y c arbon atoms. The most s t r i k i n g example o f t e r t i a r y non-bonding l o b e i n t e r a c t i o n was r e p o r t e d by F o r t and S c h l e y e r T h e n u c l e a r magnetic resonance (nmr) spectrum o f the 1 -adamantanyl carbonium i o n r e v e a l e d the b r i d g e h e a d p r o t o n s t o be d i s p l a c e d f u r t h e r d o w n f i e l d than the a d j a c e n t methylene p r o t o n s ( 2 0 ) . Carbon-carbon h y p e r c o n j u g a t i o n d i d not c o n t r i b u t e s i g n i f i c a n t l y t o t h i s r e s u l t , s o " b a c k s i d e " i n t e r a c t i o n was h y p o t h e s i z e d between the empty p - o r b i t a l and the non-bonding l o b e s o f the t e r t i a r y hydrogen a t o m s . ^ relative areas of the nmr peaks a z H Y 8 Diagram 20 1 2 x S 5 . 5 0 4 . 5 0 4 . 5 8 5 . 4 2 7 . 3 3 2 . 7 7 B. C y c l o p r o p a n e s and S m a l l R i n g P r o p e l l a n e s * The major problem o f t h i s t h e s i s was the s y n t h e s i s o f a compound w i t h a c y c l o p r o p y l m o i ety w i t h i n an adamantane s k e l e t o n . The c a g e - l i k e adamantane s k e l e t o n would be P r o p e l l a n e i s the s i m p l e name g i v e n t o t r i c y c l i c compounds i n w h i c h t h r e e r i n g s s h are a bond i n common.3o F o r example, jl.m.n| p r o p e l l a n e would have the g e n e r a l f o r m u l a shown -low ( 2 1 ) . be Diagram 21 - 17 -s e v e r e l y d i s t o r t e d by the f o r m a t i o n o f the 1 , 3 - c y c l o p r o p y l m o i e t y . Thus c e r t a i n p r o p e r t i e s o f the t i t l e compound, DHA, would be e x p e c t e d t o be s i m i l a r t o those o f s t r a i n e d c y c l o p r o p a n e s . F u r t h e r m o r e , the f o r m a t i o n o f the i n t e r n a l bond might r e s u l t i n an i n v e r t e d c o n f i g u r a t i o n about the p a r t i c i p a t i n g carbon atoms. T h i s second s e c t i o n o f t h e i n t r o d u c t i o n p r e s e n t s t h r e e t y p e s o f s t r u c t u r e s , each type more complex than the p r e c e d i n g one. The f i r s t s u b s e c t i o n r e v i e w s s i m p l e c y c l o p r o p a n e w i t h s p e c i a l emphasis on i t s s t r u c t u r e and b o n d i n g . The second s u b s e c t i o n r e l a t e s the e f f e c t s o f i n c r e a s e d s t r a i n on the r e a c t i v i t y and bonding o f the c y c l o p r o p y l r i n g . The f i n a l s u b s e c t i o n i n t r o d u c e s s m a l l r i n g p r o p e l l a n e compounds whi c h may p o s s e s s i n v e r t e d bonds. Cyclo p r o p a n e The c y c l o p r o p a n e m o l e c u l e f a s c i n a t e d e a r l y c h e m i s t s n o t o n l y because o f i t s Bayer s t r a i n and o l e f i n - l i k e p r o p e r t i e s b u t a l s o because i t s e x i s t e n c e was a s t r o n g c h a l l e n g e to the t h e o r i e s o f c h e m i c a l b o n d i n g o f t h a t t i m e . D u r i n g the 1940's two o p p o s i n g models were proposed f o r c y c l o p r o p a n Walsbr' (22a) s u p p o r t e d the d a t i v e (sp ) o l e f i n - m e t h y l e n e complex model w h i l e R o b i n s o n 3 ^ (22b) s u p p o r t e d the •z t e t r a h e d r a l h y b r i d i z a t i o n (sp ) model i n which the v a l e n c e a n g l e s were d i s t o r t e d because t h i s model b e s t f i t the •50 e x p e r i m e n t a l d a t a . ' - 18 -H —• C —?v ~ C v Diagram 22 Coulson and M o f f i t t ^ 0 resolved these untenable views by reasoning that carbon atoms which do not possess t e t r a -hedral valence angles could not possess tetrahedral hyb r i d i z a t i o n . Their calculations based on t h i s reason-o ing gave a value of 116 for the H - C - H angle which agreed well with experimental o b s e r v a t i o n s . ^ They further reasoned that strained bonds should be l e s s stable than unstrained bonds and should thus have weaker force constants and be longer than unstrained bonds. Saksena^ 2 and S k i n n e r ^ obtained experimental force constants for c-c bond stretching* 1" 2 and thermochemical^ values respectively, which agreed with the predictions of Coulson and M o f f i t t . ^ However, Bastiansen and Hassel^"*" - 19 -showed by e l e c t r o n d i f f r a c t i o n the c-c bond l e n g t h o f 0 c y c l o p r o p a n e (1.54 A) was a l m o s t i d e n t i c a l w i t h t h a t o f ethane (1.55 A ) . C o u l s o n and H o f f i t t Z f 0 b , ^ Z f r e c o n c i l e d t h e s e a p p a r e n t c o n t r a d i c t i o n s by p r o p o s i n g a bent o r "banana" bond model f o r c y c l o p r o p a n e . By s e p a r a t i n g the c o n c e p t s o f bond l e n g t h and i n t e r n u c l e a r d i s t a n c e , t h i s model p e r m i t t e d a bond l o n g e r than 1.54 A w h i l e the i n t e r -n u c l e a r d i s t a n c e may be l e s s t h a n t h i s v a l u e . 45 From t h i s model, Ingraham^"^ c a l c u l a t e d the h y b r i d i z a t i o n o f the c y c l o p r o p a n e c a r b o n bonds. The a n n u l a r bonds were found t o be sp 4"* w h i l e the e x t e r n a l bonds e v a l u a t e d t o 2 2R 5^ 2 be sp . C u r r e n t t h e o r y a t t r i b u t e d sp-^ and sp h y b r i d i z a t i o n r e s p e c t i v e l y t o t h e s e b o n d s . ^ The a n n u l a r bonds were thought t o be s p r e a d between 104° and 106 (23).^ 104-6" N Diagram 23 The l a r g e p component i n the c y c l o p r o p y l b o n d i n g o r b i t a l s h e l p e d to e x p l a i n the l o n g o b s e r v e d s i m i l a r i t i e s between c y c l o p r o p a n e s and o r d i n a r y u n s a t u r a t e d g r o u p s , f o r example, e l e c t r o p h i l i c a d d i t i o n , and c a t a l y t i c r e d u c t i o n . 4 ' The p a r t i a l t r a n s m i s s i o n o f e l e c t r o n i c e f f e c t s t h r o u g h - 20 -c y c l o p r o p y l groups 7 and the e f f e c t i v e n e s s o f the t e r m i n a l c y c l o p r o p y l group i n e x t e n d i n g the c o n j u g a t i o n o f an 50 u n s a t u r a t e d group a l s o have been demonstrated by nmr, u l t r a v i o l e t - ^ and Raman s p e c t r o s c o p y . ^ F u r t h e r m o r e , nmr s p e c t r o s c o p y i n d i c a t e d t h a t the c y c l o p r o p a n e r i n g can s u p p o r t a r i n g c u r r e n t as i n d i c a t e d by a 0 . 5 ppni s h i e l d i n g o f the r i n g p r o t o n s and the c o n v e r s e f o r p r o t o n s o r i e n t e d 52 o v e r the f a c e o f the r i n g . S t r a i n e d C y c l o p r o p a n e s The s t r a i n i n a s e l e c t e d bond o f c y c l o p r o p a n e can be i n c r e a s e d by making i t p a r t o f an a d j o i n e d s t r a i n e d r i n g . T h i s s h a r i n g o f a common bond f o r c e s f u r t h e r d e v i a t i o n s o f bo n d i n g c a r b o n o r b i t a l s from t e t r a h e d r a l h y b r i d i z a t i o n a n g l e s t h u s f u r t h e r a l t e r i n g the p r o p o r t i o n o f s and p - o r b i t a l m i x i n g i n the h y b r i d s o f the s h a r e d carbon atoms. These a l t e r a t i o n s i n h y b r i d i z a t i o n have been c o r r e l a t e d i n a g e n e r a l way t o the r e a c t i v i t y o f edge f u s e d o r b r i d g i n g 53 b o n d s . ^ S t u d i e s have shown t h a t d e c r e a s e s i n r i n g s i z e o f ^n.l.cTj b i c y c l a n e s (24) r e s u l t i n an i n c r e a s e o f the i n t e r n a l bond r e a c t i v i t y . Diagram 24 - 21 -This r e a c t i v i t y has been used rather loosely to compare the s t r a i n inherent i n the bridging bonds of these com-pounds with the bridging bonds of other compounds (25). Diagram 25 Small Ring Propellanes A propellane has been defined previously as a compound i n which three rings are fused to a common or i n t e r n a l bond (26). As these rings are reduced i n s i z e , the external Diagram 26 bonds of the bridgehead carbon atoms must deviate from the i d e a l sp^ hybridization angle (109° 28 ) (27a) toward s p 2 hybridization (120°) (27b) and possibly beyond to an inverted hybridization (27c,d). V -Ch •C b' - 22 -Diagram 27 W i b e r g , H i a t t and B u r g m a i e r > y have d e f i n e d an i n v e r t e d c arbon atom as one " . . . i n w h i c h a l l atoms j o i n e d t o the b r i d g e h e a d atoms l i e i n one hemisphere ( i e . i n one p l a n e o r on one s i d e o f a p l a n e p a s s i n g t h r o u g h the b r i d g e h e a d a t o m s ) . " Thus, the l a s t two c a r b o n s shown above (27c,d) may be c l e a r l y c l a s s i f i e d a s i n v e r t e d by t h i s d e f i n i t i o n . Three h y d r o c a r b o n s w h i c h might p o s s i b l y p o s s e s s i n v e r t e d c a r b o n atoms have been s y n t h e s i z e d and s t u d i e d 56a (28a,b,c). U n l i k e the f i r s t compound (28a) shown below, the i n t e r n a l bond o f the second compound (28b)^^13 d i d n o t show an enhanced r e a c t i v i t y compared w i t h b i c y c l o p e n t a n e ( 2 5 ) . ^ " The most r e c e n t l y s y n t h e s i z e d compound 3«3«1 57 — — p r o p e l l a n e ( 2 8 c ) , J ' showed a r e a c t i v i t y somewhere between these two extremes (28a,b) but l e s s than t h a t o f b i c y c l o -pentane . .OAc Diagram 28 - 23 -S u r p r i s i n g l y , oxygen d i d r e a c t a t room temperature o r l o w e r w i t h [3.2.1] p r o p e l l a n e (28a)-^ a but d i d not r e a c t 56c w i t h i t s epoxide analogue (28d).y Such s e n s i t i v i t y t o oxygen by a f o r m a l l y s a t u r a t e d h y d r o c a r b o n i s an u n u s u a l o c c u r r e n c e . T h i s s e n s i t i v i t y was a t t r i b u t e d t o the i n v e r t e d geometry o f the 3^«2.lj p r o p e l l a n e b r i d g e h e a d c a r b o n atoms, but an i n v e r t e d geometry appeared n o t t o be the o n l y r e q u i r e m e n t . A d d i t i o n a l l y , the r e c e n t l y s y n t h e s i z e d 2^.2.2J p r o p e l l a n e (29)^  a l s o b e l i e v e d t o p o s s e s s i n v e r t e d b r i d g e h e a d c a r b o n atoms, d i d n o t r e a c t w i t h 58a oxygen. Thus, the p r e s e n c e o f a c y c l o p r o p y l group appears t o be e s s e n t i a l f o r the r e a c t i o n o f oxygen w i t h an i n v e r t e d carbon o f a s t r a i n e d p r o p e l l a n e . R = CON(CH3)258a = H 5 8 b , c R Diagram 29 C. Adamantane M o l e c u l e s C o n t a i n i n g C y c l o p r o p y l Bonds Other s u p e r s t r u c t u r e s a r e a v a i l a b l e f o r e x t e n d i n g t h e s t u d y o f s t r a i n e d h y d r o c a r b o n atoms and t h e i r bonds. Of t h e s e , the adamantane m o l e c u l e has h e l d the most i n t e r e s t . - 24 -As d e s c r i b e d above (P-14) n e i t h e r the s t r u c t u r e nor the r i g i d i t y o f the system f a v o u r e d the i n t r o d u c t i o n o f a double bond. N o r d l a n d e r , J i n d a l , and K i t k o 7 a t t e m p t e d to homoenolize 2-adamantanone w i t h l i t t l e s u c c e s s ( 3 0 ) . Diagram 30 B a l d w i n and F o g e l s o n g ^ 0 s y n t h e s i z e d the f i r s t dehydroadamantane compound. They sought t o e s t a b l i s h the e x i s t e n c e o f a degenerate carbonium i o n i n t e r m e d i a t e (31c) by s t u d y i n g the s o l v o l y s i s o f a l a b e l e d t o s y l a t e d e r i v a t i v e (31b). Diagram 31 N e x t , Udding, S t r a t i n g and Wynberg r e p o r t e d the s y n t h e s i s o f 2,4-dehydroadamantane (32a) i n h i g h y i e l d . T h i s s y n t h e s i s e l e g a n t l y u t i l i z e d the h i g h symmetry o f adamantane to a - 25 -s i n g u l a r advantage. (The s u b s t i t u t e d secondary carbon atom i s e q u i d i s t a n t from each o f i t s f o u r homoadjacent methylene groups*.) Diagram 3 2 T h i s DHA isomer ( 3 2 a ) responded r a p i d l y t o e l e c t r o -s by u n d e r g o i n g an a< formed dehydro-bond ( 3 3 ) p h i l e a d d i t i o n r e a c t i o n a t the newly 62 X 2 / A g C l O ^ CH, C H 3 C N Diagram 33 O n l y two o f t h e p o s s i b l e t h r e e i s o m e r s were produced i n a l l o f the r e p o r t e d a d d i t i o n r e a c t i o n s , i e . the d i a x i a l (2 a,4 a) a d d i t i o n p r o d u c t v/as c o n s p i c u o u s l y a b s e n t * . I t was found t h a t t he more s t a b l e e q u a t o r i a l - e q u a t o r i a l i s o m e r (2 e,4 e) u s u a l l y predominated over the l e s s s t a b l e a d d i t i o n i s o m e r (2 a,4 e). More r e c e n t l y Geluk and de B o e r ^ 3 have d i s c l o s e d the s y n t h e s i s o f a doubledehydroadamantane compound, 1,2,4,5-didehydroadamantane (34a). C u r i o u s l y j when t h i s compound i s t r e a t e d w i t h hydrogen under c a t a l y t i c c o n d i t i o n s , one o f the o r i g i n a l adamantane c a r b o n - c a r b o n bonds undergoes h y d r o g e n o l y s i s (34t>). R e c e n t l y , L e n o i r and S c h l e y e r ^ and Cuddy, Grant and McKerveyo4h have r e p o r t e d the s y n t h e s i s o f a 2a,4a -d i s b u s t i t u t e d adamantane compound by a roundabout r o u t e . - 26 -Diagram 34 The s y n t h e s e s o f 2 ,4-dehydroadamantane compounds (31a,32a)^0 ,^'J" s u p r a v i d e , p r e s e n t e d a new q u e s t i o n . C o u l d the r i g i d adamantane s k e l e t o n be d i s t o r t e d f u r t h e r ? I t became i n t e r e s t i n g t o i n t r o d u c e a new dehydro bond between a p a i r o f t e r t i a r y c a r b o n atoms o f the adamantane s k e l e t o n . Diagram 35 The new i n t e r n a l b onding carbon atoms o f DHA (35) might p o s s i b l y p o s s e s s an u n u s u a l i f not unique geometry s i m i l a r t o t h a t d e s c r i b e d f o r s m a l l r i n g s . T h i s geometry - 2 7 -would i n d i c a t e , a c c o r d i n g t o the t h e o r y o f C o u l s o n and M o f f i t t , ^ the o c c u r r e n c e o f an u n u s u a l h y b r i d i z a t i o n i n the carbon atoms f o r m i n g the i n t e r n a l bond. E v i d e n c e f o r an u n u s u a l type o f h y b r i d i z a t i o n might appear i n the form o f a h i g h o r u n u s u a l r e a c t i v i t y . To t e s t t h e s e h y p o t h e s e s , the s y n t h e s i s o f t e t r a c y c l o j~3.3.1.1"^,'^.0"I",^j decane (35) was u n d e r t a k e n . The purpose o f t h i s r e s e a r c h work was t o s y n t h e s i z e the new compound t e t r a c y c l o decane (DHA) and t o i n v e s t i g a t e i t s p r o p e r t i e s . When t h i s work was i n i t i a t e d the s y n t h e s i s o f the t h r e e s m a l l r i n g p r o p e l l a n e compounds d e s c r i b e d i n the second s e c t i o n o f t h e i n t r o d u c t i o n (28a,b,d) had n o t y e t been r e p o r t e d . - 28 -RESULTS The f i r s t o f the e n s u i n g s e c t i o n s p r e s e n t s the p r e p a r a -t i o n o f v a r i o u s b r o m i n a t e d adamantane compounds. The second s e c t i o n r e v i e w s the e f f o r t s t o o p t i m i z e the y i e l d o f DHA by t r e a t i n g 1 ,3-dibromoadamantane w i t h a v a r i e t y o f r e a g e n t s under v a r i o u s c o n d i t i o n s . The r e a c t i o n s o f 1 , 3 , 5 - t r i b r o m o -adamantane and l , 3 , 5 > 7-tetrabromoadamantane under s i m i l a r c o n d i t i o n s a r e g i v e n . The f i n a l s e c t i o n r e v i e w s the r e s u l t s o f the t r e a t m e n t o f DHA w i t h v a r i o u s r e a g e n t s and i t s t h e r m a l s t a b i l i t y . I n each s e c t i o n the c h a r a c t e r i z a t i o n o r i d e n t i f i -c a t i o n o f the r e a c t i o n p r o d u c t s i s c i t e d b r i e f l y . A. P r e p a r a t i o n o f B rominated Adamantanes Commercial adamantane (36a) was t r e a t e d w i t h bromine and aluminum t r i b r o m i d e by a m o d i f i e d p r o c e d u r e of S t e t t e r and q V/ulf. T h i s p r o c e s s gave a h i g h y i e l d o f a n a l y t i c a l l y pure 1 ,3-dibromoadamantane (36b) ( 9 2 % ) . ( F u r t h e r r e f i n e m e n t o f t h i s m o d i f i e d procedure by S c o t t ^ showed t h a t a f i v e - f o l d r e d u c t i o n i n the c a t a l y s t c o u l d be made w i t h o u t d e c r e a s i n g the h i g h y i e l d s o f the d i b r o m i d e . ) The r e p o r t e d compound appeared t o have two d i f f e r e n t m e l t i n g p o i n t s ( 108 -109°C, 1 1 2 - 1 1 3°C),^ b o t h these extremes were obse r v e d on v a r i o u s o c c a s i o n s ; however m e l t i n g p o i n t s w i t h ranges between the two extremes were most common. For b; X=Br, Y=Z=H c, X= Y=Br, Z=H d X=Y=Z=Br example, the m e l t i n g p o i n t f o r an a n l y t i c a l l y pure sample o f 1,3-dibromoadamantane r e s u l t i n g from the m o d i f i e d r e a c t i o n o was found t o be between those r e p o r t e d (mp, 108-111 C ) . The compound 1,3,5-tribromoadamantane (36c) was p r e p a r e d by the p r e v i o u s l y d e s c r i b e d m o d i f i e d p r o c e d u r e o f S t e t t e r and Wulf f o l l o w e d by s t i r r i n g a t room tem p e r a t u r e u n t i l t he 1,3-dibromoadaraantane was c o n v e r t e d e n t i r e l y t o the d e s i r e d t r i b r o m o d e r i v a t i v e (3 d a y s ) . Due to the f o r m a t i o n o f by-p r o d u c t s , a reduced y i e l d o f the a n a l y t i c a l l y pure t r i b r o m i d e (73%) v/as o b t a i n e d . None o f the many b y - p r o d u c t s was i d e n t i -f i a b l e , and 1,3,5,7-tetrabromoadamantane was shown t o be absent by g l p c s u p e r p o s i t i o n . The s y n t h e s i s o f 1,3,5,7-tetrabromoadamantane (36d) was performed by a n o t h e r m o d i f i e d S t e t t e r and Wulf p r o c e d u r e ( s u p r a v i d e ) so t h a t the t r a n s f o r m a t i o n c o u l d o c c u r d i r e c t l y from 65 c o m m e r c i a l adamantane as the s t a r t i n g m a t e r i a l . ^ U s i n g t h i s p r o c e d u r e , the o v e r a l l y i e l d o f 1,3,5,7-tetrabromoadamantane Q o b t a i n e d by S t e t t e r and W u l f 7 was r e a l i z e d but o n l y one r e a c t i o n v e s s e l was us e d . The s u b s t i t u t i o n o f the t e r t i a r y hydrogens o f adamantane under L e w i s a c i d c a t a l y z e d c o n d i t i o n s has been w e l l e s t a b l i s h e d ; however, i n a d d i t i o n , each o f the above s t r u c t u r e s was c o n f i r m e d by nmr s p e c t r o s c o p y . Diagram 36 - 30 -B. P r e p a r a t i o n o f 1,3-Dehydroadamantane a, X=Br b, X = I X= B r , Na -K c Diagram 37 The t i t l e compound o f t h i s t h e s i s , DHA (37c) was f i r s t s y n t h e s i z e d i n n-heptane by the a c t i o n o f l i q u i d p o t a s s i u m m e t a l on 1,3-dibromoadamantane (37a). The pre s e n c e o f a v e r y r e a c t i v e i n t e r m e d i a t e (37c) i n the p r o d u c t s o l u t i o n c o u l d be d e t e c t e d by r a p i d t i t r a t i o n w i t h i o d i n e o r bromine t o g i v e c o l o r l e s s s o l u t i o n s o f 1,3-di-iodo and 1,3-dibromo-adamantane (37a,b), r e s p e c t i v e l y . The r e d u c t i o n b y - p r o d u c t , adamantane (37d), was n o t a f f e c t e d by t i t r a t i o n o f the r e a c t i o n s o l u t i o n w i t h h a l o g e n . The c o n d i t i o n s o f the above r e a c t i o n were m o d i f i e d when a l i q u i d s odium-potassium a l l o y was i n t r o d u c e d as the d e b r o m i n a t i n g a g e n t . The use o f t h i s a l l o y a l l o w e d the de b r o r a i n a t i o n t o o c c u r a t room t e m p e r a t u r e , t h e r e f o r e more v o l a t i l e s o l v e n t s c o u l d be used. The change o f r e a c t i o n s o l v e n t from n-heptane t o e t h e r f a c i l i t a t e d the i s o l a t i o n o f the v o l a t i l e p r o d u c t s , adamantane and DHA, by a vacuum d i s t i l l a t i o n - s u b l i m a t i o n p r o c e d u r e . The i n i t i a l r e a c t i o n s u s i n g the suspended a l k a l i m e t a l s as the d e b r o m i n a t i n g agent had v a r i a b l e i n d u c t i o n and r e a c t i o n t i m e s . * T h e r e f o r e , an a l c o h o l i n i t i a t o r ( u s u a l l y t _ - b u t y l a l c o h o l ) was added. The a d d i t i o n o f the i n i t i a t o r e l i m i n a t e d b o t h o f the above i n c o n s i s t e n c i e s i n the above d e b r o m i n a t i o n r e a c t i o n . The degree o f r e d u c t i o n v e r s u s i n t e r n a l bond f o r m a t i o n was a n o t h e r i m p o r t a n t v a r i a b l e w h i c h was beyond c o n t r o l . F u r t h e r m o r e , the i n t e r m o l e c u l a r o r V/urtz c o u p l i n g p r o d u c t l , l ' - b i a d a m a n t a n e was i d e n t i f i e d many t i m e s i n v a r y i n g amounts by g l p c c o m p a r i s o n . ( A u t h e n t i c 1,1'-biadamantane was p r e p a r e d a s a g l p c r e f e r e n c e m a t e r i a l from the 1-bromo-adamantane by the Wurtz c o u p l i n g method.) I n many r e a c t i o n s the above f a c t o r s were r e s p o n s i b l e f o r r e d u c e d y i e l d s o f DHA. The s y n t h e s i s o f DHA by sodium n a p h t h a l i d e o r n - b u t y l l i t h i u m - h e x a m e t h y l p h o s p h o r a m i d e ^ i n e t h e r improved the y i e l d o f DHA ( c a . 7 2 % ) , b u t d i d n o t a l l o w the i s o l a t i o n o f DHA and adamantane by a s p e c i a l l y d e v e l o p e d d i s t i l l a t i o n -s u b l i m a t i o n p r o c e d u r e . A c h r o n o l o g i c a l s u r v e y o f t y p i c a l DHA s y n t h e s e s w i t h t h e i r v a r i o u s m o d i f i c a t i o n s t o improve y i e l d s i s p r e s e n t e d i n the DISCUSSION s e c t i o n (TABLE I ) . X a,X=Y=Br c. X= Br. Y=H b Diagram 38 - 32 -Treatment o f 1,3,5,7-tetrabromoadamantane (33a) w i t h sodium-potassium a l l o y i n e i t h e r heptane o r e t h e r d i d n o t g i v e any d e t e c t a b l e amounts o f 1,3,5,7-didehydroadamantane ("Double DHA") (38b). The major p r o d u c t s were adamantane and DHA. S i m i l a r l y , t r e a t m e n t o f 1 ,3,5-tribromoadamantane i n n-heptane o r i n e t h e r w i t h sodium p o t a s s i u m a l l o y a l s o gave a m i x t u r e o f adamantane and DHA as the major p r o d u c t s . Treatment o f an a l i q u o t o f 1,3,5,7-tetrabromoadamantane-Na/K a l l o y p r o d u c t s o l u t i o n w i t h i o d i n e f o l l o w e d by g l p c d i d n o t i n d i c a t e t h a t 1,3,5,7-tetraiodoadamantane was a p r o d u c t ; t h u s , Double DHA (38b) was n o t l i k e l y p r e s e n t i n t h e s o l u t i o n . C. S t r u c t u r e o f 1,^-Dehydroadamantane The new compound was i s o l a t e d as an adamantane-DHA m i x t u r e (39a,b) ( c a . if00 mg) by a vacuum d i s t i l l a t i o n -s u b l i m a t i o n p r o c e d u r e . DHA (39b) a l s o was i s o l a t e d on a s m a l l s c a l e ( c a . 10 mg) by p r e p a r a t i v e g l p c u s i n g a 10 f t column packed w i t h f r e s h base washed Chromosorb " W " s u p p o r t e d Carbowax 20M (10%) a t 110°C. DHA c o u l d be s t o r e d b Diagram 39 - 33 -i n d e f i n i t e l y as a s o l i d o r i n s o l u t i o n i f oxygen was absent from the s e a l e d c o n t a i n e r . The nmr spectrum o f DHA i n benzene showed an u n u s u a l l y lov; resonance v a l u e , 1.66 S , f o r the c y c l o p r o p y l p r o t o n s . The p r o t o n s o f car b o n s a d j a c e n t t o those i n v o l v e d i n the new i n t e r n a l bond r e s o n a t e d a t 1.15 and 1.91 & . These a s s i g n m e n t s were s u p p o r t e d by double resonance nmr s t u d i e s Op o f DHA and by the nmr spectrum o f 5 , 7-dimethyl-DHA. The s e n s i t i v i t y o f DHA t o oxygen p r e v e n t e d a c c u r a t e m i c r o a n a l y s i s o f samples; however DHA was c o n v e r t e d t o a polymer w i t h the same e m p i r i c a l f o r m u l a by h e a t i n g an i s o l a t e d sample o f DHA i n a s e a l e d tube a t a p p r o x i m a t e l y o 160 C. M i c r o a n a l y t i c r e s u l t s f o r t h i s m o d i f i e d DHA sample were c o n s i s t e n t w i t h the e m p i r i c a l f o r m u l a C-j_o^l4* F u r t h e r -more, t h i s e m p i r i c a l f o r m u l a f o r DHA was c o n f i r m e d by h i g h r e s o l u t i o n mass s p e c t r o s c o p y o f a DHA specimen. An m/e+ o f 134.1086 i 0.001 was o b s e r v e d f o r t h i s specimen and was con-s i s t e n t w i t h the v a l u e c a l c u l a t e d f o r the e m p i r i c a l f o r m u l a C10H14# D. R e a c t i o n s o f 1,3-Dehydroadamantane R=0H,H, or solvent. x= 1,2,3,4... Diagram 40 - 34 -Treatment o f DHA i n n-heptane w i t h oxygen gave a w h i t e waxy p o l y m e r i c p r e c i p i t a t e (40) (46%) w h i c h d i d not m e l t o b u t e x p l o d e d on h e a t i n g (ep c_a. 146 C ) . Glpc of the f i l t e r e d s u p e r n a t a n t l i q u i d i n d i c a t e d many minor b y - p r o d u c t s were p r e s e n t . The foremost o f t h e s e was i d e n t i f i e d a s 1 , 3-dihydroxyadamantane ( d i o l ) by s u p e r p o s i t i o n w i t h a u t h e n t i c m a t e r i a l . * When the polymer was t r e a t e d w i t h l i t h i u m aluminum h y d r i d e , d i o l (50%) was i d e n t i f i e d as the major p r o d u c t i n the above manner.* F u r t h e r m o r e , an i s o l a t e d , r e c r y s t a l i z e d sample o f the major polymer r e d u c -t i o n p r o d u c t had nmr and i n f r a r e d s p e c t r a i d e n t i c a l t o thos e o f a u t h e n t i c d i o l . Treatment o f DHA i n n-heptane w i t h bromine a t room temp e r a t u r e gave 1 ,3-dibromoadamantane ( 4 1 a , X = B r ) i n h i g h y i e l d . (Treatment w i t h i o d i n e gave the c o r r e s p o n d i n g d i - i o d o p r o d u c t (41b, X = I ) . ) S i n c e the r e a c t i o n proceeded v e r y r a p i d l y , the r e a g e n t c o u l d be used as a s e l f - i n d i c a t o r when added i n a t i t r i m e t r i c f a s h i o n . No n o t i c e a b l e d e c r e a s e o f r e a c t i o n r a t e was ob s e r v e d when DHA o was t i t r a t e d w i t h bromine a t - 7 5 C . The. low s o l u b i l i t y o f 1 , 3-dibromoadamantane a t t h i s t e mperature was u s e f u l f o r i s o l a t i n g the r e a c t i o n p r o d u c t i n h i g h y i e l d by s u c t i o n o f i l t r a t i o n . The b r o m i n a t i o n o f DHA i n e t h e r a t - 7 5 C r e s u l t e d i n the i n s t a n t a n e o u s f o r m a t i o n o f a f l o c u l e n t l e m o n - y e l l o w p r e c i p i t a t e i n a v e r y h i g h y i e l d . * A u t h e n t i c d i o l was p r e p a r e d from 1 ,3-dibromoadamantane by the method o f S t e t t e r and Wulf.9 I n s t a b i l i t y above -25 C and a s s o c i a t e d t e c h n i c a l d i f f i -c u l t i e s p r e v e n t e d the a c c u r a t e m i c r o a n a l y s i s o f the above compound (42a). The q u a n t i t y o f m o l e c u l a r bromine r e l e a s e d d u r i n g the t h e r m a l r e a c t i o n o f the p r e c i p i t a t e was d e t e r m i n e d by u l t r a v i o l e t (UV) s p e c t r o s c o p y t o be 0.905 moles f o r each i n i t i a l mole o f DHA. HBr fumes a l s o were d e t e c t e d ( m o i s t b l u e l i t h m u s t u r n e d r e d ) . The major t h e r m a l d i s p l a c e -ment p r o d u c t from the l e m o n - y e l l o w p r e c i p i t a t e suspended i n e t h e r was shown t o be l-bromo - 3-ethoxyadamantane (42b) by nmr s p e c t r o s c o p y . T h i s s t u d y r e v e a l e d the presence o f the e t h o x y methylene group i n t e g r a t i n g f o r 2 p r o t o n s a t 3.45 £ i n the nmr spectrum and the ethoxy m e t h y l group a t 1.03 <£ . ' The r e l a t i o n s h i p between the two r e s o n a n c e s was c o n f i r m e d by t h e i r i d e n t i c a l c o u p l i n g c o n s t a n t s . The e l e m e n t a l a n a l y s i s showed the p r e s e n c e o f one atom o f bromine i n the m o l e c u l e . The s t r u c t u r e o f t h i s compound was c o n f i r m e d as l- b r o m o - 3 -ethoxyadamantane by a c i d c l e a v a g e o f the e t h e r t o g i v e 1,3-dibromoadamantane i n e x c e l l e n t y i e l d (74.8%). - 36 -The low temperature nmr o f the l e m o n - y e l l o w i n t e r m e d i a t e (43) i n acetone-dg showed the presence o f a q u a r t e t i n t e g r a t i n f o r f o u r p r o t o n s a t 5.19 £ and a r e s o l v e d t r i p l e t superimposed on an u n r e s o l v e d m u l t i p l e t i n t e g r a t i n g f o r 6 and 2 p r o t o n s r e s p e c t i v e l y a t 1.71 C? • The q u a r t e t a t 5.19 £ and t r i p l e t a t 1.71 ^ had i d e n t i c a l c o u p l i n g c o n s t a n t s . The magnitude of the d o w n f i e l d s h i f t o f the q u a r t e t s u g g e s t e d t h a t the ethoxy methylene and m e t h y l group was r e s p e c t i v e l y OC and y3 t o a p o s i t i v e l y c harged atom, most p r o b a b l y oxygen. T h i s 22 r e s u l t was c o n s i s t e n t w i t h the nmr spectrum e x p e c t e d f o r the compound ( 3 - b r o m o - l - a d a m a n t a n y l ) - d i e t h y l oxonium t r i b r o m i d e shown below (43). g r ~ Diagram 43 S i m i l a r and g r e a t e r c h e m i c a l s h i f t s have been r e p o r t e d f o r s e c o n d a r y ^ 3 , and p r i m a r y ^ * 3 a l k y l oxonium i o n p r o t o n s r e s p e c t i v e l y , compared t o the c h e m i c a l s h i f t s found f o r the p r o t o n s o f the ethoxy group o f the oxonium compound (43). The oxonium s a l t (42a) r e a c t e d i n v a r i o u s s o l v e n t m i x t u r e s when warmed t o room t e m p e r a t u r e . U n l i k e the r e a c t i o n i n d i e t h y l e t h e r where the bromo-ethoxy compound exceeded - 37 -the dibromo compound (42c) by a p p r o x i m a t e l y 2:1 (67:33%), i n 95% e t h a n o l w i t h K^CO-^ l-bromo-3-ethoxyadamantane (42b) was the p r i m a r y p r o d u c t (93%). I n acetone s o l u t i o n s the oxonium s a l t (42a) r e a c t e d a t -75°C i n the presence o f sodium c y a n i d e o r i o d i d e t o g i v e q u a n t i t a t i v e y i e l d s o f the bromo-ethoxy p r o d u c t (42b). When a s o l u t i o n o f the oxonium s a l t (42a) was a l l o w e d t o r e a c h room t e m p e r a t u r e , t h e 3-bromo-l-adamantanyl m o i e t y showed o n l y a modest tendency (33%) t o be d i s p l a c e d by the a n i o n o f t h i s s a l t , B r ^ ~ . However, o t h e r s t r o n g n u c l e o p h i l e s , f o r example, PL^ O ( 1 0 % ) , HOAc (0.7%), and H^SO^ (0.4%) i n aqueous ( c a . 10%) a c e t o n e s o l u t i o n s o f the s a l t were more s u c c e s s f u l (43, 53 and 6 1 % , r e s p e c t i v e l y ) y i e l d i n g the bromo hydroxy compound (44a). The q u a n t i t a t i v e f o r m a t i o n o f l-bromo-3-hydroxy-adamantane was demonstrated when DHA was b r o m i n a t e d i n aqueous a c e t o n e a t room t e m p e r a t u r e (44). 0 b C H 2 Diagram 44 - 38 -The s t r u c t u r e o f t h i s compound (44a) was v e r i f i e d by e l e m e n t a l a n a l y s i s by i n f r a r e d and by nmr s p e c t r o s c o p y and f i n a l l y c o n f i r m e d by a r a p i d base c a t a l y z e d r e a r r a n g e -ment t o 3 - k e t o - 7 - m e t h y l e n e b i c y c l o j j ^ ' - ^ ' l j n o n a n e (44b). U s i n g two d i f f e r e n t columns, an enhancement o f the g l p c t r a c e was o b s e r v e d a f t e r e nrichment o f the r e a c t i o n s o l u t i o n w i t h the a u t h e n t i c compound. A minor compound r e s u l t i n g from the t h e r m a l d i s p l a c e m e n t o f the 3-bromo-l-adamantanyl m o i e t y from the oxonium s a l t (42a) i n acetone -HOAc (25%) was t e n t a t i v e l y i d e n t i f i e d u s i n g two d i f f e r e n t g l p c columns as l-acetoxy-3-bromoadamantane (45) by comparison w i t h the a u t h e n t i c m a t e r i a l . Diagram 45 A u t h e n t i c l-acetoxy-3-bromoadamantane was p r e p a r e d by t r e a t m e n t o f l-bromo-3-hydroxyadamantane w i t h c o n c e n t r a t e d s u l f u r i c a c i d ( c a . 0.05 ml) and a c e t i c a n h y d r i d e (1 ml) o v e r n i g h t a t room t e m p e r a t u r e . P u r i -f i c a t i o n by column chromatography gave an o i l (49%) from a s p e c i a l l y s e l e c t e d m i d d l e f r a c t i o n . G l p c , u s i n g two - 39 -d i f f e r e n t columns, showed only one compound was present; the structure was confirmed by nmr and i n f r a r e d spectroscopy. Diagram 46 By io d i n a t i n g DHA i n ether at -75"C, a rusty-brown flo c u l e n t p r e c i p i t a t e (46a) was formed i n a fashion p a r a l l e l to that described i n the bromination reaction (42). An acetone solution of t h i s intermediate oxonium s a l t was o treated with a suspension of sodium cyanide at -75 C. This displacement reaction gave a high y i e l d of a new compound i d e n t i f i e d as l-ethoxy-3-iodoadamantane (46b) by i t s i n f r a r e d and nmr spectra as v/ell as by elemental analysis. The i n f r a r e d spectrum possessed a d i s t r i b u t i o n of absorptions very s i m i l a r to that found for l-bromo-3-ethoxyadamantane. The nmr spectrum displayed the ethoxy methylene resonance at 3.47 & and the methyl resonance at 1.06 £ . Their r e l a t i o n s h i p was established by t h e i r i d e n t i c a l coupling constants. The other resonances of the spectrum were i n 22 accord with the calculated values. - 40 -Diagram 47 S u l f u r i c a c i d c a t a l y z e d h y d r a t i o n o f DHA gave a h i g h y i e l d o f a compound (90 +_ 5%) i d e n t i f i e d as 1-hydroxy-adamantane by g l p c comparison w i t h the a u t h e n t i c p r o d u c t (47)• No compounds c o r r e s p o n d i n g to the r i n g o p ening o f one o f the e x t e r i o r c y c l o p r o p y l bonds were o b s e r v e d ; however, one u n i d e n t i f i e d b y - p r o d u c t ( c a . 5%) was o b s e r v e d . T h i s c o u l d have r e p r e s e n t e d the a d d i t i o n p r o d u c t o f the 1-adamantyl carbonium i o n t o the t e t r a h y d r o f u r a n c o s o l v e n t . The t r e a t m e n t o f DHA w i t h d i l u t e HOAc i n a h y d r o c a r b o n s o l v e n t a t room temperature r e s u l t e d i n r a p i d f o r m a t i o n o f a s i n g l e compound which was shown t o be i d e n t i c a l w i t h a u t h e n t i c 1-acetoxyadamantane (48a). b, R=0PNB a,R= OAc Diagram 48 - 41 -\ The f a i r l y strong organic acid, para-nitrobenzoic acid (pK 3.41) reacted s u r p r i s i n g l y slowly (6 hr) with DHA i n benzene to give (l-adamantyl)-para-nitrobenzoate (48b) (82%). The reaction product was i d e n t i f i e d by the following method. F i r s t , enrichment of the reaction solution with authentic (l-adamantyl)-para-nitrobenzoate caused an enhancement of the glpc trace. Second, the compound was i s o l a t e d and the i n f r a r e d and nmr spectra of the reaction product were found to be i d e n t i c a l with those reported. a Diagram 49 Treatment of DHA dissolved i n tetrahydrofuran with an aqueous mercuric acetate solution followed by the rapid addition of 3 N sodium hydroxide and 1 N sodium borohydride aqueous solutions (49) gave 1-hydroxyadamantane (49a) (47.7%) as the major product, 1,3-dihydroxyadamantane (ca. 9%) and an un i d e n t i f i e d by-product (ca. 18%). These values were determined using authentic 1-hydroxyadamantane as an a n a l y t i c a l glpc standard. The i d e n t i t y of these two hydroxy compounds was determined by glpc trace enrichment studies. The major product was i s o l a t e d by column chromato-graphy. The i n f r a r e d spectrum was i d e n t i c a l with that of the authentic compound. - 42 -Me OH OMe a Diagram 50 When DHA (50a) was dissolved i n dry methanol, the addition of the alcohol took place slowly (ca. 24 h r ) . This addition was accelerated by b o r o n t r i f l u o r i d e , so that the addition reaction took place almost instantaneously to give 1-methoxyadamantane (50b) i n high y i e l d . This compound had a c h a r a c t e r i s t i c methoxyl resonance at 3.12 £ which integrated for three protons. Only one other compound with a very small y i e l d was observed by temperature programmed glpc. The i d e n t i t y of 1-methoxyadamantane was confirmed by an in f r a r e d s p e c tral comparison with that of the authentic sample. This authentic compound (69%) was prepared from a sodium hydride promoted reaction of 1-hydroxyadamantane with methyl iodide and p u r i f i e d by f r a c t i o n a l d i s t i l l a t i o n . a H 2 / Pt02 Diagram 51 - 43 -C a t a l y t i c h y d r o g e n a t i o n o f DHA (51a) i n n-heptane was marked by a r a p i d uptake o f hydrogen. The major p r o d u c t (79.5%) was i d e n t i f i e d as adamantane (51b) u s i n g g l p c t r a c e s u p e r p o s i t i o n w i t h a u t h e n t i c m a t e r i a l as w e l l as by the i n f r a r e d spectrum o f the s i x - f o l d r e c r y s t a l l i z e d p r o d u c t . The i n f r a r e d spectrum o f the p r o d u c t was the same as the i n f r a r e d spectrum o f the a u t h e n t i c compound. A g l p c u n r e s o l v a b l e m i x t u r e (16.9%) c o n s i s t i n g o f a t l e a s t f o u r minor p r o d u c t s a l s o were o b s e r v e d . The nmr spectrum o f t h i s m i x t u r e showed a v e r y s h a r p d o u b l e t i n the m e t h y l r e g i o n . Diagram 52 The aluminum c h l o r i d e c a t a l y z e d p h e n y l a t i o n o f DHA (52a) i n benzene proceeded r a p i d l y (10 min) to g i v e 1-phenyladaman-tane (52b) ( 3 9 . 8 % ) . Under these c o n d i t i o n s , i t was shown t h a t an e q u i l i b r a t i o n o f 1-phenyladamantane o c c u r r e d t o g i v e adamantane ( c a . 5-10%) and a compound ( c a . 15-20%) w h i c h - Mi- -i s i d e n t i f i e d as 1,3-diphenyladamantane (5-c) by g l p c and nmr. A g l p c r e c o r d a l s o showed a t r a c e i n the a r e a e x p e c t e d f o r 1,3,5-triphenyladamantane (52d) ( < 5%). The major p r o d u c t o f the r e a c t i o n was i d e n t i f i e d by enhance-ment of the g l p c t r a c e upon e n r i c h i n g the s o l u t i o n w i t h a u t h e n t i c 1-phenyladamantane and by t h e i r i d e n t i c a l i n f r a r e d s p e c t r a . A u t h e n t i c 1-phenyladamantane (38%) was p r e p a r e d by the t r e a t m e n t o f 1-bromoadamantane w i t h aluminum c h l o r i d e i n benzene s o l u t i o n . Diagram 53 The p o l y m e r i z a t i o n o f DHA i n the s o l i d phase was a c h i e v e d by h e a t i n g a t 145° C o v e r n i g h t (53)« The v o l a t i l e compounds ( p r i m a r i l y adamantane) were s u b l i m e d out l e a v i n g a o w h i t e m a t e r i a l w i t h a d e c o m p o s i t i o n p o i n t o f c a . 450 C o i n a i r , c a . 500 C under a n i t r o g e n atmosphere. A n a l y s i s showed a h i g h e r v a l u e f o r hydrogen than i s normal ( i e . 0.3%) but the d i s c r e p a n c y was e x p l a i n e d by the r e c o g n i t i o n t h a t the o l i g o m e r o c c u r s as a d i s t r i b u t i o n o f medium and s h o r t c h a i n s . The c a l c u l a t e d v a l u e s f o r C 1 0 L , , however, a r e f o r an i n f i n i t e c h a i n . - 45 -Thermal s t a b i l i t y of DHA was studied i n p u r i f i e d n-o octane at 195.3 i 0.2 C under oxygen free conditions. The i n i t i a l concentration of DHA was 8.56 x 10" m o l e s / l i t r e . The extent of decomposition i n each sample was determined by a n a l y t i c a l glpc and normalized with respect to the constant value of an unreactive i n t e r n a l standard. The values of the glpc traces so normalized gave excellent f i r s t order p l o t s . Two products of the thermolysis reaction, adamantane (54a) and biadamantane, were i d e n t i f i e d by a n a l y t i c a l glpc trace superposition with authentic materials on two d i f f e r e n t columns. The unidentifed products probably resulted from a reaction between a r a d i c a l or d i r a d i c a l intermediate and a solvent molecule to give a mixture of n-(octyl)-adamantane (54b) isomers. A preliminary inves t i g a t i o n of DHA thermolysis i n cumene agreed with the above r e s u l t s . In addition to a new u n i d e n t i f i e d product and previously i d e n t i f i e d products, the presence of a major amounts of dicumene was demonstrated by glpc trace superposition with authentic material. a -*2 b Diagram 54 - 46 -DISCUSSION For the purpose o f c l a r i t y t h i s d i s c u s s i o n i s d i v i d e d i n t o f o u r s e c t i o n s . The f i r s t s e c t i o n d e s c r i b e s the s y n t h e s i s o f t e t r a c y c l o 3.3.1.13,7.01'5 decane (DHA). i— — The second s e c t i o n p r e s e n t s the e v i d e n c e f o r the proposed s t r u c t u r e of DHA. The t h i r d s e c t i o n i n v e s t i g a t e s the r e a c t i o n s o f the t i t l e compound. A. S y n t h e s i s The f i r s t d i r e c t i n t r o d u c t i o n o f a s t r a i n e d c y c l o p r o p y l bond i n t o the adamantane s k e l e t o n was demonstrated by U d d i n g , 61 S t r a t i n g and Wynberg i n t h e i r e l e g a n t s y n t h e s i s o f 2,4-dehydroadamantane (32a); however, t h i s s t r a i n e d bond was e s t a b l i s h e d between two sec o n d a r y c a r b o n atoms. I n DHA the proposed bond would connect two t e r t i a r y o r b r i d g e h e a d carbon atoms and i n o r d e r t o form t h i s i n t e r n a l bond, the geometry about the b r i d g e h e a d c a r b o n atoms might be e x p e c t e d t o be i n v e r t e d . T h e r e f o r e i t must be c o n c l u d e d t h a t the s t r a i n i n the i n t e r n a l bond o f DHA would be s i g n i f i c a n t l y g r e a t e r than i n the s t r a i n e d c y c l o p r o p y l bond o f the 2,4-dehydroadamantane i s o m e r v/here no i n v e r s i o n i s r e q u i r e d . Because the s t r a i n i n DHA would be much l a r g e r than i n 2,4-dehydroadamantane, i t was h i g h l y u n c e r t a i n whether the - V7 -i n t e r n a l bond o f DHA c o u l d be formed a t a l l from a s u i t a b l e adamantane d e r i v a t i v e and once formed whether the compound 67 would be s u f f i c i e n t l y s t a b l e to be d e t e c t e d . The r e p o r t s ' t h a t an adamantane d e r i v a t i v e (56a) had undergone a F a v o r s k i i rearrangement (56) encouraged an attempt t o i n s e r t the i n t e r n a l bond i n t o the adamantane s k e l e t o n s i n c e the i n t e r m e d i a t e o f t h i s rearrangement (56b) was b e l i e v e d t o c l o s e l y resemble DHA (56c). a b c Diagram 56 One o f the most r e a d i l y a v a i l a b l e and s u i t a b l e d i s u b -s t i t u t e d adamantane d e r i v a t i v e s was 1 , 3-dibromoadamantane ( 57 ) . T h i s compound was s y n t h e s i z e d r e c e n t l y i n good y i e l d by S t e t t e r and W u l f ^ who used a boron t r i b r o m i d e c a t a l y s t i n l i q u i d b romine. I n l i q u i d bromine aluminum t r i b r o m i d e was found t o be too r e a c t i v e r e s u l t i n g i n the predominence o f 1 , 3 , 5 -tribromoadamantane. S i n c e the boron t r i f l u o r i d e c a t a l y s t method was found u n r e l i a b l e , o t h e r groups performed e x t e n -s i v e s t u d i e s i n t h i s a r e a . These s t u d i e s , however, r e s u l t e d o n l y i n m a r g i n a l improvements i n the r e p r o d u c t i o n o f t h i s r e a c t i o n . T h i s m a t t e r was r e s o l v e d when c o n s i s t e n t l y h i g h - 43 -y i e l d s o f the d i b r o m i d e were o b t a i n e d by u s i n g aluminum t r i b r o m i d e i n l i q u i d bromine a t 0°C. ( S y n t h e s i s o f t e t r a -bromine (57c) r e q u i r e d extreme c o n d i t i o n s . ) Warming t h i s r e a c t i o n m i x t u r e t o room temperature o r above o w i t h o u t f i r s t decomposing the c a t a l y s t a t 0 C r e s u l t e d i n the s y n t h e s i s o f t r i b r o m i d e as r e p o r t e d by S t e t t e r and W u l f 9 (58). D e h a l o g e n a t i o n r e a c t i o n s have been used i n a l a r g e v a r i e t y o f h a l o g e n compounds t o i n t r o d u c e s t r a i n e d bonds (59). W i b e r g ^ has r e c e n t l y r e v i e w e d t h i s r e a c t i o n as a means f o r the s y n t h e s i s o f s t r a i n e d bonds i n s m a l l r i n g s . U n f o r t u n a t e l y , the mechanism o f the d e h a l o g e n a t i o n r e a c t i o n has n o t been e s t a b l i s h e d c o n c l u s i v e l y . a; X = Br,Y=Z=H b; X=Y=Br, Z=H c; X=Y=Z = Br YJ Diagram 57 Diagram 58 Diagram 59 - 50 -The reaction mechanism of the electrochemical dehalogena-75 tion previously had been assigned a concerted mode;'-^  however, recent studies u t i l i z i n g o p t i c a l l y active compounds have been interpreted to favour a Y - h a l o carbanion i n t e r -77 mediate involved i n a stepwise mechanism. These r e s u l t s were sim i l a r for the electrochemical as well as for the magnesium and sodium naphthalide dehalogenations. Notably, the r e s u l t s of these experiments depended on the free rotation of the reacting carbon atoms. Another factor complicated the i l l u c i d a t i o n of the dehalogenation mechanism. This complication can be i l l u s t r a t e d by the conclusions about dehalogenation by magnesium. The reaction between magnesium and a halogenated hydrocarbon r e s u l t s i n the well known Grignard reagent. These compounds are represented cannonically with R X + M g M g X ^  *" R * " M g X , a 1 R - - M g X b Diagram 60 p a r t i a l p o s i t i v e and negative charges respectively on the metal and carbon atom (60a); however, Dagonneau, Metzer 78 and V i a l l e have shown hemolytic cleavage can also occur (60b). This group has used t h i s homolytic reaction to synthesize bicyclobutane. - 51 -It i s also known that diatomic halogen, oxygen, and heavy metals promote t h i s homolytic f i s s i o n of Grignard reagents (61). 79 eg« M 0 Br. PX R Mg Br M ox * R-R • MgBr, Diagram 61 Therefore i t appears that the mechanism for the described dehalogenation reactions (59) has yet to be established conclusively, e s p e c i a l l y i n the case of constrained, i d e a l l y oriented molecules such as 1,3-dibromoadamantane. + —'n n * 4,5,6, Diagram 62 The treatment of 1,3-dibromoadamantane with magnesium catalyzed by iodine appeared to y i e l d only adamantane and a white insoluble s o l i d with a melting point i n excess of o 350 C and an empirical formula of ^Q^lZf* ^he v i r t u a l absence of DHA from t h i s reaction was shown afte r synthesis of DHA with sodium and potassium reagents to be due to the - 52 -c o n t a m i n a t i o n o f the g l p c column by a c i d s . Much l a t e r the r e a c t i o n was r e p e a t e d w i t h a t e n - f o l d d e c r e a s e i n sub-s t r a t e c o n c e n t r a t i o n t o m i n i m i z e polymer f o r m a t i o n . At 5 0 % c o m p l e t i o n , the compound thought t o be DHA was shown to be p r e s e n t by a n a l y t i c g l p c u s i n g a f r e s h base-washed Carbowax column. U n f o r t u n a t e l y , the c o n c e n t r a t i o n o f t h i s p r o d u c t was l e s s than t h a t of the d i f f i c u l t t o s e p a r a t e r e d u c t i o n b y - p r o d u c t , adamantane. F o r t h i s r e a s o n , i n v e s t i g a t i o n o f magnesium as a r e a g e n t f o r d e b r o m i n a t i o n was d i s c o n t i n u e d i n f a v o u r o f m o l t e n sodium or p o t a s s i u m . Treatment o f the d i b r o m i d e w i t h t h e s e a l k a l i m e t a l s gave a much b e t t e r y i e l d o f the d e s i r e d compound and a g r e a t l y r e d u c e d y i e l d o f adamantane ( 6 3 ) . Diagram 63 The r e a c t i o n o f m o l t e n sodium w i t h 1,3-dibromo-adamantane i n heptane proceeded over a few h o u r s r e s u l t i n g i n the l o s s o f d i b r o m i d e and the appearance o f two new peaks a t low r e t e n t i o n time i n the g l p c t r a c e . One o f - 53 -t h e s e peaks was i d e n t i f i e d a s adamantane. The o t h e r peak r e p r e s e n t e d a v e r y r e a c t i v e c o m p o u n d w h i c h was s e n s i t i v e t o a c i d s , h a l o g e n s and a i r . * The p r o d u c t s o f th e s e r e a c t i o n s s u g g e s t e d t h a t t h i s new h i g h l y s e n s i t i v e compound was i n d e e d the d e s i r e d t i t l e compound, t e t r a c y c l o J 3 , 3 . 1 . 1 5 , 7 , 0 1 » 5 decane o r DHA ( 6 4 a ) . 8 0 a F o r example, t i t r a t i o n o f the d e h a l o g e n a t i o n r e a c t i o n s o l u t i o n w i t h e i t h e r bromine o r i o d i n e s o l u t i o n s r e s u l t e d i n compounds i d e n t i f i e d as 1 ,3-dibromoadamantane and 1 , 3 - d i - i o d o -adamantane r e s p e c t i v e l y ( 6 4 ) . ^ X = Br,I. Diagram 64 S u r p r i s i n g l y , the new compound, DHA had f a i r t h e r m a l s t a b i l i t y . I t was i s o l a t e d i n s m a l l q u a n t i t i e s by o p r e p a r a t i v e g l p c a t 1 1 0 C w h i l e the c o l l e c t o r and d e t e c t o r m a n i f o l d s were h e l d i n e x c e s s o f 2 0 0 C. u u c* These r e a c t i o n s w i l l be d e t a i l e d i n the t h i r d s e c t i o n o f the DISCUSSION.• - 54 -The s y n t h e s i s o f DHA was performed many t i m e s (TABLE I ) . The d u r a t i o n and y i e l d o f the a l k a l i m e t a l ( s ) d e b r o m i n a t i o n r e a c t i o n was found t o v a r y w i d e l y w i t h o u t any a p p a r e n t r e a s o n s . A t t i m e s r e d u c t i o n p r e d o m i n a t e d g i v i n g l a r g e amounts o f adamantane. A t o t h e r t i m e s a v e r y t u r b i d s o l u t i o n r e s u l t e d , presumably due to polymer f o r m a t i o n . (The presence o f l , l ' - b i a d a m a n t a n e was demon-s t r a t e d i n s e v e r a l o f t h e s e s o l u t i o n s and s u b l i m a t i o n r e s i d u e s by a n a l y t i c a l g l p c comparison w i t h a u t h e n t i c m a t e r i a l . ) A t s t i l l o t h e r t i m e s i n d u c t i o n p e r i o d s o f up to s e v e r a l h o u r s were o b s e r v e d b e f o r e p r o d u c t i o n o f DHA commenced. D u r i n g t h i s p e r i o d e i t h e r no n o t i c e a b l e r e a c t i o n o r a v e r y s l o w one o c c u r r e d . The i n d u c t i o n phenomenon was e s p e c i a l l y n o t e d when the r e a c t i o n s o l v e n t was changed from n-heptane t o e t h e r t o a l l o w s u b l i m a t i v e i s o l a t i o n o f the v o l a t i l e r e a c t i o n p r o d u c t s . A t t e m p t s t o c o n t r o l t h i s e r r a t i c b e h a v i o u r s u g g e s t e d t h a t t r a c e s o f m o i s t u r e might have a c a t a l y t i c e f f e c t on the r e a c t i o n . M o i s t u r e most l i k e l y r e a c t e d w i t h the m e t a l o r a l l o y t o remove the s u r f a c e f i l m b ut t h i s was n o t e s t a b l i s h e d c o n c l u s i v e l y . A s e a r c h f o r a l e s s r e a c t i v e i n i t i a t o r f i n a l l y ended i n the s e l e c t i o n o f t.-butanol as the most e f f e c t i v e a d d i t i v e . I t s slow r e a c t i o n w i t h the a l l o y r e q u i r e d the a d d i t i o n o f o n l y s e v e r a l d rops a t the s t a r t o f the r e a c t i o n . Experi- Substrate Reagent Solvent Lag I n i t i a t o r Temp. Time Yield 0/ /o mental 34 x 10-3M (g) (50 ml) (min). (ml) °C (min) ADAa DHA Sublimate sec. (t-BuOH) weight (g) B .4.(a) DBAb K n-hep- 5-10 YES 100 35 0.3 59.2 __ (b) (2.5) tane (0.05 ml) DBA Na/K n-hep- 25 YES 100 43 4.8 50 (c) (0.76) tane (0.05) • DBA Na/K ether — NO 23 60 25.5 59 (0.392) (d) (0.74) (60) DBA Na/K ether 30 YES 23 55 16.7 60.5 (0.352) (0.74) (30 min) (e) Na/K, (2) dropwise DBA ether — NO -75 240 ca3-5 72.5 (f) (0.66,2. 1) DBA n-BuLi ether NO -32 8 C cal-2 72 (20%) HMPA (4 ml) 5.(a) TTBAd Na/K n-hep- NO 100 600 14.4 35 (1.215) tane (b) (60 m l )e TTBA Na/K ether E10 YES 23 90 5.8 33.8 f (0.176) (1.301) (75 ml) (0.03) (8.6) f 6.(a) TBAg Na/K n-hep- _ _ NO 23 60 6.5 47.8 , (b) (0.94D tane (8.3) f TBA Na/K ether 20 YES (2) 23 65 9.9 63.5 (0.264) (2.67 x (0.74) dropwise 10-3M) v n a b c d e f 8 1,3-dibromoadamantane The time of dropwise addition of the reagent. 1,3,5,7-tetrabromoadamantane The quantity of tetrabromide used i s insoluble i n 50 ml of these solvents, This y i e l d was determined by treatment of the d i s t i l l a t e with bromine. 1,3,5-tribromoadamantane TABLE I. Representative Syntheses of 1,3-Dehydroadamantane - 56 -I n these r e a c t i o n s c a r e was taken t o e x c l u d e oxygen; however, t r a c e s o f o x i d e and i m p u r i t i e s i n the m e t a l s c o u l d n o t be a v o i d e d . I t i s w e l l known t h a t i n t e r m o l e c u l a r c o u p l i n g v i a f r e e r a d i c a l i n t e r m e d i a t e s i s promoted by 79 t r a c e s o f h a l o g e n , t r a n s i t i o n and heavy m e t a l a t o m s / 7 and oxygen. Thus, m e t a l l i c i m p u r i t i e s o r o x i d e s may have been r e s p o n s i b l e f o r a s p e c t s o f the i r r e p r o d u c a b i l i t y o f some o f the s e r e a c t i o n s . The u n p r e d i c t a b l e b e h a v i o u r o f the two phase a l l o y d e b r o m i n a t i o n c o u l d be overcome by f i r s t f o r m i n g an a l k a l i m e t a l n a p h t h a l i d e . The y i e l d o f t h i s r e a c t i o n w h i c h r e q u i r e d k h o u r s t o complete a t Dry I c e temperature was s l i g h t l y b e t t e r ( c a . 72%) than t h a t o f the normal a l l o y d e b r o m i n a t i o n a t room temperature ( c a . 6 0 % ) ; however t h i s r e a c t i o n was n o t a g r e a t improvement over the a l l o y r e a c t i o n s i n c e the n a p h t h a l e n e a l s o s u b l i m e d d u r i n g the s u b l i m a t i v e i s o l a t i o n o f adamantane-DHA. F u r t h e r m o r e , the f l o c u l e n t n a p h t h a l i d e tended n ot o n l y t o e n t r a p the d e s i r e d p r o d u c t b u t a l s o t o be a f i r e h a z a r d n-BuLi / HMPA - 3 0 ° C Diagram 65 - 57 -d u r i n g the m a n i p u l a t i o n s d u r i n g c o n t a c t v / i t h oxygen o r 65 m o i s t u r e . F o r these r e a s o n s , the d i s c o v e r y by S c o t t t h a t d e b r o m i n a t i o n by n - b u t y l l i t h i u m o c c u r r e d a t low te m p e r a t u r e s i n ether-hexamethylphosphoramide (HMPA) s o l u t i o n (65) was welcomed. T h i s r e a c t i o n n o t o n l y o c c u r r e d i n one phase, t h u s a v o i d i n g the e r r a t i c n a t u r e o f two phase r e a c t i o n s , b u t a l s o r e s u l t e d i n an improved y i e l d o f DHA ( c a . 72.%) v / i t h o n l y t r a c e s o f the d i f f i c u l t t o s e p a r a t e s i d e p r o d u c t , adamantane. I n t h i s r e a c t i o n , o n l y one o t h e r s i g n i f i c a n t b y - p r o d u c t * was ob s e r v e d by a n a l y t i c g l p c i n s m a l l amounts (5%). The p r i m a r y d i s -advantage o f t h i s s y n t h e t i c method was the c o n t a m i n a t i o n o f the s u b l i m a t e w i t h HMPA and low b o i l i n g l i q u i d by-p r o d u c t s , f o r example, n - b u t y l bromide. F o r many s t u d i e s t h i s was a major pr o b l e m . * The b y - p r o d u c t ( c a . 5%) was i s o l a t e d by column chromato-graphy and t e n t a t i v e l y i d e n t i f i e d by nmr s p e c t r o s c o p y as l - b r o m o - 3 - ( n - b u t y l ) adamantane (66). Diagram 66 The p o s i t i o n s o f i t s nmr r e s o n a n c e s compared w e l l w i t h the r e s o n a n c e s c a l c u l a t e d f o r t h i s d e r i v a t i v e from t h e d a t a g i v e n by S c h l e y e r and F o r t . 2 2 - 53 -The s y n t h e s i s o f the compound, 1 , 3 , 5 , 7 - d i d e h y d r o -adamantane, was at t e m p t e d (TABLE I ; 5,6). T h i s compound was dubbed w i t h the s i m p l e r name, doubledehydroadamantane (67a). I t c o u l d not be d i r e c t l y d e t e c t e d by e i t h e r a n a l y t i c a l g l p c o f the r e a c t i o n m i x t u r e o r i n d i r e c t l y d e t e c t e d by temperature programmed a n a l y t i c g l p c * o f an a l i q u o t t r e a t e d w i t h i o d i n e . No compound w i t h r e t e n t i o n time c o r r e s p o n d i n g t o 1 , 3 , 5 , 7 - t e t r a i o d o a d a m a n t a n e c o u l d be o b s e r v e d . The major p r o d u c t o f i o d i n e t i t r a t i o n i n n-heptane was 1 , 3-di-ioadamantane. Two minor peaks v / i t h r e t e n t i o n t i m e s c o r r e s p o n d i n g t o those e x p e c t e d f o r l-bromo - 3 ,5-di-iodoadamantane and l , 3 - d i b r o m o - 5 , 7 - d i -iodoadamantane were o b s e r v e d . * A s i m i l a r i o d i n a t i o n r e a c t i o n was performed on the l» 3 » 5-tribromoadamantane d e b r o m i n a t i o n p r o d u c t s . T h i s time o n l y the t r a c e s c o r r e s p o n d i n g t o 1 , 3 - d i - i o d o -adamantane (major p r o d u c t ) and t o the compound t e n t a t i v e l y * I n a d d i t i o n t o g l p c on the carbowax column, these a l i q u o t s were a l s o checked on the s i l i c o n e e l a s t o m e r column programmed t o r e a c h i t s maximum temperature (275°C). A g a i n , no peaks c o r r e s p o n d i n g to the tetr a i o d o - c o m p o u n d were o b s e r v e d . - 59 -i d e n t i f i e d as l-bromo - 3 , 5-di-iodoadamantane (minor p r o d u c t ) were o b s e r v e d . F u r t h e r i s o l a t i o n o f these compounds was not p u r s u e d . The r e s u l t s from the debrom-i n a t i o n o f b o t h t e t r a and tribromoadamantane (67b,c r e s p e c t i v e l y ) i n d i c a t e d t h a t DHA and adamantane were the major p r o d u c t s (TABLE I , 5 and 6 ) . B. S t r u c t u r e o f 1 ,3-Dehydroadamantane D e s p i t e the s u r p r i s i n g s t a b i l i t y o f DHA t o h e a t ( i s o l a t i o n by p r e p a r a t i v e g l p c a t 110°C), the i s o l a t e d compound d i d not me l t b u t p o l y m e r i z e d a t a p p r o x i m a t e l y l60°C.^ 0 a Due to t e c h n i c a l d i f f i c u l t i e s ( s e n s i t i v i t y t o o x y g e n ) , the m i c r o a n a l y s i s o f the i s o l a t e d compound was not s u c c e s s f u l . However, the h i g h r e s o l u t i o n mass spectrum o f t h i s compound was s u f f i c i e n t t o i d e n t i f y the new compound as a h y d r o c a r b o n w i t h the e m p i r i c a l f o r m u l a o f C-J_QH^. The new compound was i d e n t i f i e d more c o n c l u s i v e l y as DHA (68a) by nmr i n oxygen f r e e benzene c o n t a i n e d i n a s e a l e d t u b e . (The nmr spectrum i s shown i n f i g u r e 1 ) . Diagram 68 1—~" 1 I I -2.5 2.0 1.5 1.0 S FIG. 1. The NMR Spectrum of 1,3-Dehydroadamantane in Benzene at 100 Mcps - 62 -The i n i t i a l assignment o f the nmr re s o n a n c e s i n f i g u r e 1 proved d i f f i c u l t . Because most h y d r o c a r b o n c y c l o p r o p y l p r o t o n s were l o c a t e d u p f i e l d from h y d r o c a r b o n methylene 81* and m e t h y l r e s o n a n c e s , i n i t i a l l y i t was assumed t h a t the f u r t h e s t u p f i e l d peak v/as due t o the c y c l o p r o p y l p r o t o n s . Hov/ever, d e c o u p l i n g s t u d i e s q u i c k l y proved t h i s a s s umption i n c o r r e c t . When a d e c o u p l i n g s i g n a l v/as a p p l i e d a t 2.73 S s i m p l i f i c a t i o n o f the 2.05 S t r i p l e t t o a s i n g l e t o c c u r r e d . The 1.66 S m u l t i p l e t was a l s o sharpened. S i n c e the t r i p l e t c o u l d o n l y r e s u l t from the resonance o f H^, the 2.73 S resonance was a s s i g n e d t o H^. (These a s s i g n m e n t s were c o n f i r m e d by the nmr spectrum o f 5,7-dimethyl-DHA (68b) 82 ( f i g u r e 2 ) . I n t h i s spectrum the resonance i s ab s e n t and the r e s o n a n c e , though s h i f t e d s l i g h t l y , i s a s i n g l e t as would be ex p e c t e d . ) When a d e c o u p l i n g s i g n a l was a p p l i e d a t 1.15 S , a d o u b l e t (11Hz) a t l . Q l o b e came a s i n g l e t . Some s i m p l i -f i c a t i o n o f the 1.66 S resonance a l s o o c c u r r e d . * * T h i s experiment i n d i c a t e d t h a t the p a i r o f c o u p l e d d o u b l e t s The p r o t o n s o f c y c l o p r o p a n e r e s o n a t e a t 0.22 ** T h i s s i m p l i f i c a t i o n i s the r e s u l t o f through-space c o u p l i n g to remote methylenes o r i e n t e d i n "W" r e l a t i o n s h i p 2 2 - 2 q -to the c y c l o p r o p y l p r o t o n s as d e s c r i b e d i n the INTRODUCTION, p - 12. - 63 -were r e l a t e d ; thus they were a s s i g n e d t o H^ a ^. By the p r o c e s s o f e l i m i n a t i o n the c y c l o p r o p y l h y drogens, EL,, v/ere a s s i g n e d to the resonance a t 1.66 £ , an u n u s u a l l y low v a l u e compared t o c y c l o p r o p a n e (0.22 £ ) . Warner, LaRose and S c h l i e s ^ ^ s u g g e s t e d t h a t t h i s de-s h i e l d i n g o f the DHA c y c l o p r o p y l h y drogens, H 2, was due t o the H^ e x o - a x i a l hydrogens. ( I n the INTRODUCTION the s e hydrogens .were shown t o i n t e r f e r e w i t h S^2 r e a c t i o n s a t a secondary carbon o f adamantane by s t e r i c h i n d r a n c e (12) -20 a p o s s i b l y a n a l o g o u s s i t u a t i o n . ) The s u g g e s t i o n o f Warner et_ a l . - ^ was based on the l a c k o f s t r o n g d e s h i e l d i n g o f c y c l o p r o p y l p r o t o n s i n the c o n f o r m a t i o n a l l y m o b i l e compounds, 3 . 3 . l j p r o p e l l a n e (69) and J ^ 3 . 2 . l J p r o p e l l a n e ( 7 0 ) . The r e s o n a n c e s o f the c y c l o p r o p y l hydrogens were 0.45 and 0.68 £ , r e s p e c t i v e l y . I n t h e s e compounds the f i v e membered r i n g s presumably e x i s t i n the boat form t h u s removing the homoadjacent a x i a l hydrogen i n t e r a c t i o n i n the c h a i r c onformer. I n c o n t r a s t , DHA (68) i s r e s t r i c t e d t o the double c h a i r c o n f o r m a t i o n by the b r i d g i n g C-6 m e t h y l e n e . The d i f f e r e n c i a t i o n between the H. ( e x o - a x i a l ) £+a and H ^ ( e n d o - e q u a t o r i a l ) hydrogens p r o v e d d i f f i c u l t . The H. ( e x o - a x i a l ) hydrogens appeared t o be p o s i t i o n e d c l o s e r M-a — — t o the s h i e l d i n g a r e a o f the c y c l o p r o p y l group^"*" than were the H ( e n d o - e q u a t o r i a l ) hydrogens. Thus, the 1.15 & d o u b l e t was a s s i g n e d t o H^ a and the 1.91 £ d o u b l e t t o H ^ ; hov/ever t h i s assignment was t e n t a t i v e and may be r e v i s e d s u b j e c t to the r e s u l t s o f f u r t h e r i n v e s t i g a t i o n s . - 64 -Diagram 70 - 65 -The i n f r a r e d spectrum for the new compound was compiled from a large number of rap id scans i n d i f f e r e n t solvents by observing the disappearance of the ^ m a x as decomposition occurred. The most c h a r a c t e r i s t i c frequency for cyc lopropy l hydrogen s t re tch i s between 3040 and 3060 -1 83 cm . A weak but sharp absorpt ion was observed at 3040 cm"""*". Other absorptions which were observed within or c lose to areas deemed c h a r a c t e r i s t i c of the cyc lopropy l moiety were at 2900, 1450, 1035 (unsymmetrical r i n g v ib ra t ions ) and 8 9 5 cm""*". Diagram 71 DHA proved too react ive for X-ray a n a l y s i s , however, 3 . 3 . 1 . 1 3 > 7 . 0 1 } 3 34 the recent ly synthesized 5-cyanotetracyclo decane (71) was s u f f i c i e n t l y stable for t h i s type of study. 35 Two i n t e r e s t i n g points were made i n t h i s study. ' F i r s t l y , 0 the i n t e r n a l bond distance was found to be 1.643 A , the - 66 -l o n g e s t c a r bon-carbon bond on r e c o r d ! S e c o n d l y , the i n t e r n a l bonding carbon atoms v/ere found to be 0.11 A from a p l a n e p a s s i n g through t h e i r a d j a c e n t methylene carbons c o n f i r m i n g the i n v e r t e d geometry o f the q u a t e r n a r y c a r b o n s . The o n l y o t h e r compound r e p o r t e d to have a s i m i l a r geometry around the c o r r e s p o n d i n g atoms was the r e c e n t l y s y n t h e s i z e d 8 , 8 - d i c h l o r o t r i c y c l o 3.2.1.0 octane (72a). In t h i s case the d i s t a n c e was 0.09 A. Diagram 72 Wiberg et a l . O D d e c i d e d t h a t no c o n c l u s i o n s about the n a t u r e o f the i n t e r n a l bond o f the above compound c o u l d be drawn because the e x a c t p o s i t i o n o f the carbons c o u l d n o t be f i x e d p r e c i s e l y , a s i t u a t i o n w hich appeared t o be p a r a l l e l e d i n the cyano-DHA X-ray r e s u l t . T h e r e f o r e , no c o n c l u s i o n s about the n a t u r e o f the i n t e r n a l bond i n DHA c o u l d be drawn from the X-ray s t u d y o f 5-cyano-DHA (71). D e s p i t e the l a c k o f p r e c i s e i n f o r m a t i o n about the n a t u r e o f the i n t e r n a l bond i n DHA a g e n e r a l assumption can be f o r m u l a t e d . I t may be s a f e l y assumed t h a t the i n t e r n a l bond o f DHA and i t s d e r i v a t i v e s would p o s s e s s a h i g h degree o f p o r b i t a l c h a r a c t e r . A s i m i l a r a s sumption has been used f o r the s t r a i n e d bonds o f b i c y c l a n e s t o e x p l a i n the s t a b i l i t y o f bonds w i t h l a r g e bond d i s t a n c e s o r awkward ( l a r g e ) a n g l e s between bond i n g o r b i t a l s and On OO the i n t e r n u c l e a r d i s t a n c e . S t u d i e s have s u p p o r t e d t h i s a s s u m p t i o n . An i m p o r t a n t consequence o f g r e a t e r p o r b i t a l c o n t e n t i n a s t r a i n e d c y c l o p r o p y l bond i s the i n c r e a s e i n " s i z e " o r e l e c t r o n c o n t e n t o f the non-bonding l o b e s o f t h i s bond compared t o the non-bonding l o b e s o f the carbons o f s i m p l e c y c l o p r o p a n e . T h i s i n c r e a s e i n non-bonding l o b e s i z e appears t o have a b e a r i n g on an a d d i t i o n r e a c t i o n mechanism - edge v e r s u s c o r n e r and e l e c t r o p h i l i c v e r s u s f r e e r a d i c a l a d d i t i o n mechanisms i n t h e s e c y c l o p r o p a n e compounds. S t r a i n e d c y c l o p r o p y l p r o p e l l a n e s do not p r e s e n t as many c o m p l i c a t i o n s as o n l y c o r n e r a d d i t i o n t o a s t r a i n e d i n t e r n a l bond seems l i k e l y . T h i s seems e s p e c i a l l y so i n the case o f the DHA s t r u c t u r e . Recent OO Og s t u d i e s * ' p r e d i c t a l a r g e p o r b i t a l component i n the i n t e r n a l bonds o f s t r a i n e d b i c y c l a n e s and p r o p e l l a n e s . °2 Diagram 73 m - q , s independent o f the q u e s t i o n whether the p r o t o n ^ o t h e / f l e r t r o p h i l e f i r s t a t t a c k s a b r i d g i n g bond ed, then s l i d e s to a c o r n e r and r e s u l t s i n the observed p r o d u c t . 9 0 a r s The hy d r o c a r b o n p r o p e l l a n e s , DHA and J~3.2.] p r o p e l l a n e (68a and 72b r e s p e c t i v e l y ) , s hare s i m i l a r f a t e s when exposed t o the same r e a g e n t s and c o n d i t i o n s . I n c o n t r a s t , the v e r y r e c e n t l y s y n t h e s i z e d 3 . 3 . l j p r o p e l l a n e , t r i c y c l o 3 . 3 . 1 . 0 1 , - M nonane (73), appe 57 t o be v e r y s u b s t a n t i a l l y l e s s r e a c t i v e , ' T h e r e f o r e , i n the f o l l o w i n g s e c t i o n the comparison of the r e s p o n s e s o f c y c l o p r o p y l p r o p e l l a n e compounds when t r e a t e d w i t h v a r i o u s r e a g e n t s v / i l l be examined and compared w i t h DHA. C. R e a c t i o n s o f 1 ,3-Dehydroadamantane From the b e g i n n i n g DHA was found t o be h i g h l y r e a c t i v e . I n a d d i t i o n t o a v e r y r a p i d r e a c t i o n w i t h h a l o g e n s , the new compound r e a c t e d v e r y r a p i d l y w i t h a c i d s and somewhat more s l o w l y v / i t h h y d r o x y l i e s o l v e n t s . However, the most s u r p r i s i n g o b s e r v a t i o n was the s e n s i t i v i t y o f DHA t o oxygen. T h i s was a most u n u s u a l s e n s i t i v i t y f o r a f o r m a l l y s a t u r a t e d h y d r o c a r b o n . I t - w a s p r i m a r i l y t h i s s e n s i t i v i t y w h i c h p r e v e n t e d the i s o l a t i o n o f DHA by a normal workup p r o c e d u r e and r e s u l t e d i n the development o f the d i s t i l l a t i o n - s u b l i m a t i o n method f o r the i s o l a t i o n o f DHA (see Experiment B . 3 . c ) . R e a c t i o n w i t h Oxygen-Peroxide F o r m a t i o n On exposure o f DHA s o l u t i o n s to a i r the s e s o l u t i o n s r a p i d l y became c l o u d y , l a t e r r e s u l t i n g i n a w h i t e f l o c u l e n t p r e c i p i t a t e . The f o r m a t i o n o f the c l o u d i n e s s was found t o - 69 -be due t o oxygen and not m o i s t u r e i n the a i r . The f r e e r a d i c a l n a t u r e o f t h i s r e a c t i o n was i n d i c a t e d when 0.1/6 3 , 5 - d i - t - b u t y l - 4 - h y d r o x y t o l u e n e markedly r e t a r d e d the i n c i d e n c e o f c l o u d i n e s s . At t h a t time the o n l y i n c i d e n c e o f an oxygen m e d i a t i n g h y d r o c a r b o n p o l y m e r i z a t i o n on r e c o r d was m e t h y l b i c y c l o 1.1.0 butane c a r b o x y l a t e (74) r e p o r t e d by Wiberg e t a l . T h i s r e a c t i o n (74) a l s o c o u l d be c o n t r o l l e d by f r e e r a d i c a l i n h i b i t o r s ; t h e r e f o r e i t was s u r p r i s i n g t h a t t h e m i c r o a n a l y s i s o f the i s o l a t e d polymer i n d i c a t e d two atoms o f oxygen f o r each DHA m o l e c u l e i n c o r p o r a t e d i n t o t h i s polymer (75). The p o l y m e r i c s u b s t a n c e (75) d i d n o t m e l t b u t e x p l o d e d o a t a p p r o x i m a t e l y 146 C - a c h a r a c t e r i s t i c o f many p e r -92 o x i d e s . 7 T h i s e x p l o s i o n p o i n t was n o t f i x e d b u t v a r i e d w i t h the c o n d i t i o n s under w h i c h the polymer was formed. F o r example, when t h e h y d r o c a r b o n s o l v e n t was s u b s t i t u t e d w i t h e t h e r o r a l c o h o l s n o t o n l y was a d e c r e a s e d y i e l d o f p r e c i p i t a t e o b t a i n e d b u t a l s o much h i g h e r e x p l o s i o n p o i n t s ( c a . 170°C) were o b t a i n e d . F u r t h e r m o r e , t h e s e R = COoMe Diagram 74 - 70 -h i g h e r e x p l o s i o n p o i n t s (ep) were much more dependent on the r a t e o f h e a t i n g than were the ep o f p r o d u c t s from n-heptane s o l u t i o n s . 02/n-heptane £gS3> R = 0 H , H , or solvent n =1,2,3,4,... Diagram 75 The p o l y m e r i c m a t e r i a l (75) was und o u b t e d l y composed o f s h o r t c h a i n s because the m i c r o a n a l y s i s was s l i g h t l y h i g h f o r hydrogen. The b a s i c s t r u c t u r e o f the polymer was c o n f i r m e d by t r e a t m e n t w i t h l i t h i u m aluminum h y d r i d e (LAH) t o g i v e 1 , 3-dihydroxyadamantane as t h e major p r o d u c t . U n s u c c e s s f u l e f f o r t s v/ere made t o d e t e c t the i n t e r -m e d i a tes o f the p o l y m e r i z a t i o n r e a c t i o n by e l e c t r o n s p i n s p e c t r o s c o p y * s i n c e f r e e r a d i c a l s had been o b s e r v e d i n o t h e r p r e c i p i t a t e d p o l y m e r s . D e t a i l e d k i n e t i c s t u d i e s Op by Schmidt c o n f i r m e d the f r e e r a d i c a l n a t u r e o f t h i s r e a c t i o n (75). S h o r t l y a f t e r t he c o m p l e t i o n o f the polyperoxyadaman-55 tane s t u d i e s , Wiberg, H i a t t and Bur g m a i e r ^ ^ r e p o r t e d t h a t t r i c y c l o 3.2 .1 .0 1,5 polymer by r e a c t i o n w i t h oxygen the r e c e n t l y s y n t h e s i z e d t r i c y c l o o c tane a l s o formed a p e r o x y -89c I n c o n t r a s t , n e i t h e r 2.2 .2 .0 1,4 o c t a n e T h i s s t u d y was e x p e d i t e d by D. Kennedy. - 71 -d e r i v a t i v e (76a) nor the v e r y r e c e n t l y s y n t h e s i z e d t r i c y c l o 3.3.1.0 1,5 57; nonane h y d r o c a r b o n (76b) r e a c t e d w i t h o x y g e n . y ' ' R= C O N ( C H 3 ) 2 58a 57 Diagram 76 However, the most s u r p r i s i n g o c c u r r e n c e was the r e s i s t a n c e o f 5-cyano t e t r a c y c l o 3.3.1.1 3^.O 1' 3 decane (76c) t o pi —' a t t a c k by o x y g e n . 4 " 3 T h i s u n u s u a l s t a b i l i t y was the major f a c t o r w h i c h p e r m i t t e d a s u c c e s s f u l X - r a y a n a l y s i s o f t h i s 85 DHA d e r i v a t i v e . ^  No e x p l a n a t i o n f o r t h i s u n u s u a l s t a b i l i t y o f the cyano compound (76c) was advanced. Thus, o n l y t h r e e f o r m a l l y s a t u r a t e d h y d r o c a r b o n s a r e known t o r e a c t w i t h oxygen t o g i v e a peroxy polymer DHA, 8 0 and 5,7-dimethyl-DHA. 8 2 , 3.2.1 p r o p e l l a n e , 89d A d d i t i o n o f Halogens I n c o n n e c t i o n w i t h f u r t h e r c o n f i r m i n g the s t r u c t u r e as w e l l as d e t e r m i n i n g the c h e m i c a l p r o p e r t i e s o f the new dehydroadamantane, t r e a t m e n t o f DHA w i t h h a l o g e n was under-t a k e n (77). Because the a d d i t i o n t o DHA o c c u r r e d a t the b r i d g e h e a d c a r b o n s , the r e s u l t was e a s i l y v e r i f i e d by compari-- 72 -son w i t h a r e a d i l y a v a i l a b l e w e l l known compound, 1,3-dibromoadamantane (77a). B r 2 o r I 2 -78 C, very rapid Diagram 77 a, X=Br b, X=I Simple c y c l o p r o p a n e s and s m a l l r i n g b i c y c l a n e s were thought t o add bromine p r i m a r i l y v i a a broraoniura i o n mechanism ( 7 8 ) . ^ , ( ^ 3 The l a t t e r compounds were a l s o known to undergo rearrangement and l y s i s o f b r i d g e as w e l l as b r i d g e h e a d - b r i d g e h e a d bonds (78b). B i B r B r B r Cr* B r Diagram 78 B r I n one o f the few examples o f b r o m o l y s i s o f p r o p e l l a n e (59) i n t e r n a l bonds, A p p l e q u i s t and S e a r l e 7 ^ had e s t a b l i s h e d a f r e e r a d i c a l mechanism by f r e e r a d i c a l i n h i b i t o r - a c c e l l e r a t o r s t u d i e s . Eaton and N y i 7 ^ i n v o k e d - 73 -the above mechanism f o r the b r o m o l y s i s o f . 2 . 2 3.2.2 and p r o p e l l a n e s i n c e t h e s e compounds f a i l e d t o r e a c t w i t h hydrogen h a l i d e s ( 7 8 ) . V/iberg-^ n o t e d a l a r g e d e c r e a s e i n the e l e c t r o p h i l i c mode o f r e a c t i o n between s i m i l a r l y s t r a i n e d c y c l o p r o p y l and c y c l o b u t y l b i c y c l a n e s . T h i s decrease was a t t r i b u t e d t o d i f f e r e n c e s i n the h y b r i d i z a t i o n o f the s t r a i n e d carbon atoms. (CH 9 ) - 2 n JpH 2>n B r . HBr ( C H 2 ) n n=3,4. Diagram 78 Most r e c e n t l y , 3«3. lJ p r o p e l l a n e (69) was shown t o add bromine r e a d i l y ; however, Warner, LaRose and S c h l e i s ' ^ s t a t e d t hey had e v i d e n c e t h a t the a d d i t i o n mechanism p r i m a r i l y i n v o l v e d f r e e r a d i c a l s . The t i t l e compound o f t h i s t h e s i s was the f i r s t 3.3.1 p r o p e l l a n e t ype compound r e p o r t e d t o add bromine. Even a t Dry I c e t e m p e r a t u r e , a hydrocarbon s o l u t i o n o f t h i s compound c o u l d be t i t r a t e d w i t h bromine t o y i e l d o n l y 1 , 3-dibromoadamantane (77a). T i t r a t i o n w i t h i o d i n e r e s u l t e d i n o n l y the c o r r e s p o n d i n g iodo-compound (77b). - 74 -Both r e a c t i o n s v/ere too r a p i d t o a l l o w a t e s t i n g o f the mechanism w i t h f r e e r a d i c a l i n h i b i t o r s by the method o f 71 A p p l e q u i s t and S e a r l e ; ' however, b r o m i n a t i o n o f DHA i n e t h e r a t Dry I c e temperature r e s u l t e d i n a f l o c u l e n t l e m o n - y e l l o w p r e c i p i t a t e . Bromine, 1,3-dibromoadamantane, and the new major b r o m i n a t i o n p r o d u c t were shown t o be s o l u b l e i n e t h e r under i d e n t i c a l c o n d i t i o n s . A f t e r the p r e c i p i t a t e formed, no s i g n i f i c a n t amount o f 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 s u p e r n a t a n t l i q u i d . T h i s p r e c i -o p i t a t e was found t o decompose v e r y r a p i d l y above -20 C but i t c o u l d be i s o l a t e d e a s i l y and k e p t f o r f o u r days i n s o l u t i o n w i t h o u t n o t i c e a b l e d e c o m p o s i t i o n w e l l below o -20 C. The y e l l o w c o l o u r o f t h i s i n t e r m e d i a t e compound s u g g e s t e d an i o n i c n a t u r e , A l i t e r a t u r e s e a r c h d i s c l o s e d the e x i s t e n c e o f b o t h a c h l o r o n i u m i o n s t a b l e a t low te m p e r a t u r e s (79a) 7 and a b r i g h t y e l l o w i n s o l u b l e brominium i o n s t a b l e i n r e f l u x i n g CC1. ( 7 9 b ) , ^ Diagram 79 - 75 -The s t r u c t u r a l i l l u c i d a t i o n o f .the i s o l a t e d y e l l o w i n t e r m e d i a t e was encouraged f u r t h e r by the d i s c o v e r y o f thes e two i o n i c compounds (79a,b). Due t o t e c h n i c a l d i f f i c u l t i e s , the m i c r o a n a l y s i s o f the i n t e r m e d i a t e compound was not s u c c e s s f u l ; however, i t r e v e a l e d the presence o f more than t e n carbon atoms and more than two bromine atoms. TABLE I I . M i c r o a n a l y t i c R e s u l t s f o r the I n t e r m e d i a t e  Compound formed from 1,3-Dehydroadamantane w i t h Bromine i n E t h e r C H Sample Temp. °C Found: 30.4 6.80 -75 33.47 7.30 -75 33.04 4.81 23 31.82a 4.54 a C a l c u l a t e d f o r C ^ H ^ B r ^ . E t p O Br \E t 0 — =-« -75°C Diagram 80 - 76 -An nmr spectrum o f the i n t e r m e d i a t e i n acetone-dg c l a r i f i e d the s t r u c t u r e o f the p r e c i p i t a t e ( f i g u r e 3). The u n m i s t a k a b l e q u a r t e t (4 p r o t o n s ) a t 5.19 § and the t r i p l e t a t 1.71 8 w i t h i d e n t i c a l c o u p l i n g c o n s t a n t s (7Hz) s t r o n g l y i n d i c a t e d t h a t the i n t e r m e d i a t e r e s u l t e d from the a d d i t i o n o f the e t h e r oxygen t o the " r e m o t e l y g e n e r a t e d " adamantyl carbonium i o n (80a). The d o w n f i e l d s h i f t o f the e t h e r methylenes was n o t e d t o be more th a n 1. 8 g r e a t e r than i n a r e p r e s e n t a t i v e sample o f s i m i l a r 98 i o n i c compounds. 7 98c The f i r s t oxonium compound v/as r e c o r d e d by Meerwein. More r e c e n t l y , K l a g e s e t a l . ,98a a n ^ L amt> e rt and Johnson* 7"^ 3 have s y n t h e s i z e d and s t u d i e d t h i s type o f m o l e c u l e . B o t h o f the l a t t e r groups have u t i l i z e d e i t h e r antimony p e n t a h a l i d e s o r boron t r i f l u o r i d e t o cause oxonium s a l t f o r m a t i o n i n s o l u t i o n . The i n t e r m e d i a t e was shown t o p o s s e s s a t r i b r o m i d e 97 a n i o n a k i n t o Wynberg's bromonium i o n compound. 7 T h i s was made p o s s i b l e by the i s o l a t i o n and c h a r a c t e r i z a -t i o n o f the major d e c o m p o s i t i o n p r o d u c t o f the i n t e r m e d i a t e (80b). The nmr spectrum o f t h i s major new p r o d u c t ( f i g u r e k) a g r e e d w i t h the m i c r o a n a l y t i c r e s u l t s . The spectrum i n d i c a t e d the presence o f an ethoxy s u b s t i t u e n t on a d i s u b s t i t u t e d adamantane s k e l e t o n . The l-ethoxy-3-bromoadamantane s t r u c t u r e o f the compound was co n -f i r m e d by HBr c l e a v a g e t o y i e l d 1,3-dibromoadaman-tan e . D e c o m p o s i t i o n o f the i n t e r m e d i a t e suspended i n acetone solvent FIG. 3. The NMR Spectrum of (3-Bromo-1-adamantyl) diethyl oxonium tribromide in Acetone-d 6 at 100 Mcps - 78 -FIG. 4. The NMR Spectrum of 1-Bromo-3-ethoxyadamantane in CDCl 3 at 100. Mcps - 79 -CCl^ by r a i s i n g to room temperature resulted i n a red-brown solution of molecular bromine. The r a t i o of bromine to the organic decomposition products (80b,c) was shown to be 0.905:1.0 by u l t r a v i o l e t spectroscopy and analytic glpc respectively. The missing bromine could probably be accounted for by further reaction with the by-products of decomposition. The presence of acid fumes i n the decomposition mixture could be explained by the abstraction of a hydrogen atom from one of the methyl groups by a bromine anion (81) and possibly by hydrogen-bromine exchange at saturated carbons. C l e a r l y , either HBr or B r 0 could add to the unsaturated molecule. Most recently, t h i s proposed mechanism has been given further credence by the studies of Richmond and Spendel.^ In s i t u generated benzyne was found to cleave ethers i n just t h i s manner to give unsaturated carbon products ( 8 2 ) ; however, nmr studies showed that more products than those suggested above (81) were formed when the oxonium s a l t reacted. A Diagram 81 - 80 -Et OEt + Et 20 40% + C H 2 AO •/• Diagram 82 The d i e t h y l e t h e r adduct o f the oxonium compound c o u l d n o t be d i s p l a c e d r e a d i l y (TABLE I I I ) . The a t t e m p t s a t d i s p l a c e m e n t l e d p r i m a r i l y t o v e r y h i g h y i e l d s o f 1-bromo-3-ethoxyadamantane (80b); t h u s the oxonium compound was n o t l i k e l y t o be u s e f u l i n s y n t h e s i s . A l t e r n a t e l y , b r o m i n a -t i o n o f DHA i n acetone s o l u t i o n s c o n t a i n i n g n o n - a c i d i c n u c l e o p h i l e s r e s u l t e d i n the d e s i r e d s u b s t i t u t e d adamantane. F o r example, b r o m i n a t i o n o f DHA i n w a t e r - a c e t o n e s o l u t i o n r e s u l t e d i n a q u a n t i t a t i v e y i e l d o f l-bromo-3-hydroxyadamantane (83a). The s t r u c t u r e o f t h i s p r o d u c t was c o n f i r m e d by a base c a t a l y z e d r e a c t i o n t o g i v e 3-methylene b i c y c l o 3.3.lJ nonane (83b), B r 2 / H 2 0 acetone 0 H / H 2 0 Diagram 83 - 81 -I I I I H2 H4J0 H5,9 H H ~ i — i — i — | — i — i — i — i — | — i — i — i — i — — 1 1 1 r 5.0 4.0 3.0 2.0 1.0 0 S FIG. 5. The NMR Spectrum of 1-Bromo-3-hydroxyadamantane in. inCDCl 3at 100 Mcps - 82 -TABLE I I I . S u b s t i t u t i o n o f ( 5 - B r o m o - l - a d a m a n t a n y l ) - d i e t h y l o x o n i u m t r i b r o m i d e w i t h N u c l e o p h i l e s a b Decomposing S o l v e n t Scavenger DBA Y i e l d o f % EA3 e t h e r N i l 28.7 67.8 e t h a n o l 9 5 % K 2 C 0 3 1.5 93.0 acetone (wet) N a l — 100 NaCN — 100 a 1,3-Dibromoadamantane b S m a l l amounts o f l-bromo-3-hydroxyadamantane c o u l d n o t be d e t e c t e d on the carbowax column due t o d e c o m p o s i t i o n . TABLE I V . S u b s t i t u t i o n o f the (3-Bromo-l-adamantanyl)- d i e t h y l o x o n i u m t r i b r o m i d e i n S o l v e n t M i x t u r e s A d d i t i v e s ' % Y i e l d o f P r o d u c t s a l-bromo-3-e t h o x y -adamantane l-bromo-3-h y d r o x y -adamantane l - a c e t o x y - 3 -bromo-adamantane 1) 2% H 2 0 b 22.3 54.7 — 2) 10% H 2 0 C 27.1 53.1 — 3) 0.7% H0Ac b 33.1 43.8 0 4) 2 5 % H0Ac c 33.4 6.1 d 6.3 5) 0.4% H^O^ 6 32.8 61.2 — a by a n a l y t i c a l g l p c o f p r o d u c t s o l u t i o n s , b w i t h complex from 0.1698 g DHA. c w i t h complex from 0.171 g DHA. d decomposes under b a s i c c o n d i t i o n s o f the workup, e w i t h complex from 0.157 g DHA. - 83 -Comparison w i t h the a u t h e n t i c compound by a n a l y t i c g l p c on two d i f f e r e n t columns s t r o n g l y i n d i c a t e d i d e n t i t y f o r the two compounds. E f f o r t s t o i n c r e a s e the y i e l d o f l - b r o m o - 3 -hydroxyadamantane from t h e oxonium s a l t by i n c r e a s i n g the w a t e r c o n t e n t o f o r a d d i n g a c i d s t o acetone s o l u t i o n s were not e n c o u r a g i n g (TABLE I V ) . (The d e c o m p o s i t i o n i n 25% a c e t i c a c i d (HOAc) d i d produce a compound i n a p p r o x i m a t e l y 6% y i e l d w h i c h appeared t o be l-acetoxy - 3-bromoadaraantane.) I" n =lor3 Diagram 84 Both c h l o r i n a t i o n and i o d i n a t i o n o f DHA i n e t h e r l e d t o the e x p e c t e d r e s p e c t i v e oxonium s a l t s . F o r example, the i o d i n a t i o n p r o d u c t v/as a d a r k red-brown p r e c i p i t a t e w h i c h o s l o w l y underwent a d i s p l a c e m e n t r e a c t i o n even a t -75 C. A h i g h y i e l d o f l-ethoxy - 3-iodoadamantane c o u l d be o b t a i n e d by d i s s o l v i n g the p r e c i p i t a t e i n a c e t o n e and a d d i n g NaCN (84). Other r e a c t i o n s o f the i o d o a d a m a n t y l oxonium s a l t were not i n v e s t i g a t e d because the e x c e s s i o d i n e was v e r y i n s o l u b l e a t -75 C making the iodo-oxonium compound d i f f i c u l t t o i s o l a t e . - 84.-The c h l o r o oxonium compound appeared to be q u i t e s t a b l e . The compound r e q u i r e d o v e r 2.5 h r t o decompose a t room t e m p e r a t u r e . The e x a c t n a t u r e o f the a n i o n i n each case was not e s t a b l i s h e d . I t c o u l d o n l y be c o n c l u d e d t h a t bromine added to the 1,3 bond o f DHA i n p o l a r s o l v e n t s p r e f e r e n t i a l l y by a two- s t e p e l e c t r o p h i l i c mechanism and t h a t the r e s u l t i n g carbonium i o n i n t e r m e d i a t e was t r a p p e d by e t h e r t o g i v e an i n s o l u b l e ( 3 - h r o m o a d a m a n t a n e - l - y l ) - d i e t h y l o x o n i u m ' t r i b r o m i d e s a l t (80a). A d d i t i o n o f A c i d s To date overwhelming e v i d e n c e has been accumulated i n f a v o u r o f the edge p r o t o n a t i o n t h e o r y f o r s i m p l e c y c l o -propanes."*" 0 0 I f s t e r i c f a c t o r s a r e not i n v o l v e d , g e n e r a l l y the degree o f bond s t r a i n would be r e p r e s e n t e d a p p r o x i m a t e l y by the r e a c t i v i t y o f the bond toward p r o t o n s . Thus, i n b i c y c l o p e n t a n e and b i c y c l o b u t a n e , the t r a n s a n n u l a r bond was thought t o be the u s u a l s i t e o f r e a c t i o n (85).69,101 However, the o r i g i n a l mechanism o f edge p r o t o n a t i o n appeared d o u b t f u l f o r some o f thes e compounds ( 8 5 c ) S t u d i e s w i t h the com-pound l - m e t h y l - 3 - c y a n o - b i c y c l o j ^ l . l . o j butane (85) i n d i c a t e d t h a t b o t h the p r o t o n and the h y d r o x y l group added t o the same s i d e o f the r i n g p o s s i b l y by a c o l l a p s e o f the i n t e r m e d i a t e to a carbonium i o n . Such an i n t e r m e d i a t e would r e s u l t i n two - 85 -ft OH + CN CN Me OH H Diagram 85 i s o m e r s b u t o n l y one i s o m e r was produced. Thus, p o s s i b l y the a d d i t i o n o c c u r r e d a l m o s t s i m u l t a n e o u s l y from the und e r - s i d e ( a c u t e d i h e d r a l a n g l e ) o f the r i n g . The p r o p e l l a n e r i n g s u p e r s t r u c t u r e would p r o h i b i t edge p r o t o n a t i o n of the s t e r i c a l l y h i n d e r e d i n t e r n a l bond; thus the o n l y r e a s o n a b l e mode o f p r o t o n a d d i t i o n would i n v o l v e the non-bonding l o b e s o f t h i s i n t e r n a l bond. As d i s c u s s e d p r e v i o u s l y , a t t e m p t s t o qi, add hydrogen h a l i d e s t o p r o p e l l a n e s had f a i l e d ^ w h i l e f r e e r a d i c a l b r o m i n a t i o n d i d o c c u r r e a d i l y . 7 1 » 9 4 As i n d i c a t e d above, the t i t l e compound o f t h i s t h e s i s can a l s o be c o n s i d e r e d a p r o p e l l a n e - t y p e compound. I t has been e s t a b l i s h e d t h a t DHA added bromine by an e l e c t r o p h i l i c mechanism; t h u s , the a d d i t i o n o f a c i d s would be f a v o u r e d more - 86 -by t h i s compound than by the p r o p e l l a n e s . Exposure o f DHA t o 8.13 M s u l f u r i c a c i d d i d r e s u l t i n the r a p i d (30 min) c o n v e r s i o n o f the compound t o a d a m a n t a n - l - o l . Exposure t o lo w e r c o n c e n t r a t i o n s o f s u l f u r i c a c i d r e s u l t e d i n p r o g r e s s i v e l y l o n g e r r e a c t i o n t i m e s . F o r 10""^"M and 5 x 10~ 3M a c i d r e a g e n t s a l m o s t 'two days and o v e r f o u r d a y s , r e s p e c t i v e l y , were r e q u i r e d , and the y i e l d s o f th e s e r e a c t i o n s were p r o g r e s s i v e l y l o w e r . 56a Wiberg and Burgmaier^ r e p o r t e d t h a t t r i c y c l o 3.2.1.0 1 ,^~J octane r e a c t s v e r y r a p i d l y w i t h HOAc (86). H 0 A C •• OAc Diagram 86 E x p l i c i t c o n d i t i o n s were n o t g i v e n so a p r e c i s e comparison w i t h the r e a c t i v i t y o f DHA c o u l d be made. The compound DHA r e a c t s t o t a l l y ( w i t h i n 10 min) a t room temperature i n an ex c e s s o f 0.1M HOAc. The c o r r e s p o n d i n g "fragment" b i c y c l o j ^ # l # ^ J n e x a n e (87a) was r e l a t i v e l y s t a b l e i n g l a c i a l a c e t i c a c i d . - 87 -( I t s b e h a v i o u r i s v e r y s i m i l a r t o t h a t o f c y c l o p r o p a n e under i d e n t i c a l c o n d i t i o n s . ) The most s i m i l a r and t h e r e f o r e s i g n i f i c a n t "fragment" o f DHA would be t r i c y c l o nonane o r 5.3.1.0lj ]^ £3.3.lj p r o p e l l a n e (87b).^  T h i s compound had a h a l f l i f e o f 8 h r a t 100 C when d i s s o l v e d i n a c e t i c a c i d . ^ ^ HOAc » Diagram 87 The major p r o d u c t (53.5%) was 1-acetoxybicyclo |~3.3.1~j nonane (87c), b u t the a l t e r n a t e r i n g opening p r o d u c t (46.5%) (87d) w h i c h was r e a d i l y e l i m i n a t e d (87©) a l s o was formed. The ' ^ • ^ • • ^ J P r o p e l l a n e was much l e s s r e a c t i v e toward HOAc than was DHA. T h i s p r o p e l l a n e appeared t o be much l e s s r e a c t i v e than b i c y c l o p e n t a n e (87b,f, r e s p e c t i v e l y ) . R= C 0 2 E t R R Diagram 88 - 88 -102 The d e r i v a t i v e s (88) have been shown t o be q u i t e r e s i s t a n t t o d i l u t e a c i d s . The f i r s t compound ( 8 8 a ) 1 0 2 a was a l s o s t a b l e t o heat as the s o l v o l y s e s were c a r r i e d o out a t 100-130 C. Gassman i n t i m a t e d t h a t f o r t h i s compound h i g h e r t e m p e r a t u r e s and h i g h e r c o n c e n t r a t i o n s o f a c i d s , i e . g r e a t e r than 7 x 10~^M, y i e l d e d "a s m a l l amount o f a d d i t i o n a l p r o d u c t s . " U n f o r t u n a t e l y the n a t u r e o f t h e s e p r o d u c t s was not d i s c l o s e d . The t i t l e compound, DHA, a l s o r e a c t e d t o t a l l y w i t h 6 x 10 M p a r a - n i t r o b e n z o i c a c i d w i t h i n 6 h r t o g i v e the c o r r e s p o n d i n g e s t e r . T h i s a c i d has made an e x c e l l e n t l e a v i n g group and has been used w i d e l y i n s o l v o l y t i c s t u d i e s . " ^ 3 A l t h o u g h i n a p p r o x i m a t e l y t e n - f o l d e x c e s s o v e r the normal c a t a l y t i c c o n c e n t r a t i o n s , the r a t e o f t h i s r e a c t i o n i n d i c a t e d t h a t i t s p r e s ence would c e r t a i n l y c o m p l i c a t e s o l v o l y t i c s t u d i e s i n v o l v i n g d e r i v a t i v e s o f DHA, a s u g g e s t i o n Haywood-F a r m e r ^ 3 made i n a p r e c e e d i n g d i s s e r t a t i o n . As f o r the r e a c t i o n w i t h oxygen and the r e a c t i o n w i t h bromine, the p r o t o n a t i o n o f DHA pr o c e e d s e x c l u s i v e l y v i a i n t e r a c t i o n w i t h a non-bonding l o b e . R e c e n t l y t h i s type o f a d d i t i o n has been s u g g e s t e d " ^ " o r demonstrated f o r l e s s 105 s t r a i n e d and l e s s h i n d e r e d compounds (89). - 89 -Both L a l o n d e e_t a l . ' L u : 3 a and H e n d r i c k s o n and Boeckman,""""^" have s u g g e s t e d t h a t c o r n e r p r o t o n a t i o n was f a v o u r e d i n the above compounds due t o s t e r i c h i n d r a n c e by the endo and exo hydrogen atoms, r e s p e c t i v e l y ; t h u s t h e y c o n c l u d e d t h a t t h e t r a n s i t i o n energy d i f f e r e n c e between t h e two i n t e r m e d i a t e c o u l d n o t be v e r y l a r g e . Most r e c e n t l y , a t h e o r e t i c a l s t u d y o f two s m a l l r i n g s t r a i n e d b i c y c l a n e s has i n d i c a t e d t h a t the c o r n e r p r o t o n a t i o n would be the p r e f e r r e d mode i n t h e s e compounds. - 90 -A d d i t i o n o f M e r c u r i c A c e t a t e The mechanism o f c y c l o p r o p a n e o x i d a t i o n by heavy m e t a l 107 s a l t s has g e n e r a t e d p a r t i c u l a r i n t e r e s t . T h i s i n t e r e s t was i n i t i a t e d by the o l e f i n i c c h a r a c t e r o f the t h r e e LR membered r i n g . The t r e a t m e n t o f o l e f i n s w i t h v a r i o u s o r g a n o m e t a l l i c a c e t a t e r e a g e n t s o f the g e n e r a l f o r m u l a M(OAc) (M = H^ . , P d 2 + , T l 3 + , Pb4'*) has an e x t e n s i v e h i s t o r y . 1 0 8 The u s u a l t r a n s mechanism o f a d d i t i o n i s g e n e r a l l y n o t e d but i n c a s e s o f s t r a i n e d and s t e r i c a l l y h i n d e r e d o l e f i n s v a r y i n g amounts o f b o t h c i s and t r a n s a d d i t i o n p r o d u c t s a r e e n c o u n t e r e d . 109 Bach and R i c h t e r 7 p o s t u l a t e d a c y c l i c t r a n s i t i o n s t a t e f o r s t r a i n e d o l e f i n s on the b a s i s o f r a t e enhancement by sodium a c e t a t e , but the a d d i t i o n o f s o l v e n t m o l e c u l e s t o th e s e bonds i m p l i e s the e x i s t e n c e o f a t l e a s t a p a r t i a l carbonium i o n (90). F u r t h e r m o r e , B e r g e r and V o g e l 1 1 0 n o t e d the a d d i t i o n o f s o l v e n t m o l e c u l e s t o u n s t r a i n e d o l e f i n s a t t a c k e d by m e r c u r i c s a l t s ; t h e r e f o r e , t h e y s u p p o r t e d the p a r t i a l carbonium i o n mechanism. H g ( N 0 3 ) 2 R ' H R HgON0 2 • R C N R ^ N T V 0 N 0 2 Diagram 90 - 91 -T h i s h o s p i t a l i t y o f o l e f i n s toward s o l v e n t m o l e c u l e s was v e r y s i m i l a r t o the b e h a v i o u r o f DHA d u r i n g e l e c t r o -p h i l i c a d d i t i o n o f bromine i n e t h e r ; however, the m e t a l a t i o n o f DHA w i t h aqueous m e r c u r i c a c e t a t e produced an u n u s u a l l y complex r e s u l t . A d d i t i o n a l t o the major p r o d u c t , 1-adamantanol, 1,3-dihydroxyadamantane, an u n i d e n t i f i e d b y - p r o d u c t and many minor b y - p r o d u c t s were obse r v e d i n the r e a c t i o n s o l u t i o n by g l p c . C u r i o u s l y , a d a r k p r e c i p i t a t e was always o b s e r v e d w i t h i n 3 min o f a d d i n g the s a l t . T h i s p r e c i p i t a t e was i d e n t i f i e d as f r e e mercury by i t s c o a l e s e n c e i n t o a c h a r a c t e r i s t i c bead o f s h i n y s i l v e r l i q u i d m e t a l . F u r t h e r -more, the r a t i o o f the r e a c t i o n p r o d u c t s to one a n o t h e r was found t o depend s t r o n g l y on the procedure used. The r e p e t i t i o n o f t h i s r e a c t i o n w h i l e v a r y i n g the d u r a t i o n o f the i n t e r v a l between the a d d i t i o n o f m e r c u r i c a c e t a t e and i n i t i a t i o n o f r e d u c i n g c o n d i t i o n s , l e d t o the f o l l o w i n g o b s e r v a t i o n s . An i n v e r s e c o r r e l a t i o n was n o t e d between the l e n g t h o f t h i s i n t e r v a l and the y i e l d o f the d e s i r e d p r o d u c t , 1-hydroxyadamantane. A d i r e c t c o r r e l a t i o n was n o t e d between the d u r a t i o n o f t h i s i n t e r v a l and the y i e l d o f 1,3-dihydroxyadamantane. These o b s e r v a t i o n s c o u l d be e x p l a i n e d p r i m a r i l y by a tendency p e c u l i a r to secondary and t e r t i a r y m e r c u r i c e s t e r s . - 92 -E i s c h 1 1 1 n o t e d t h a t t - b u t y l and i - p r o p y l m e r c u r i c t o s y l a t e s were r e m a r k a b l y r e a c t i v e and t h a t a r e d u c t i o n - o x i d a t i o n s o l v o l y t i c c l e a v a g e . o f the a l k y l m e t a l bond c o n s t i t u t e d the mode o f t h i s r e a c t i v i t y ( 9 1 ) . The h a l f l i f e o f t - b u t y l R 9^^^ 2 ^ C + - - - H g - " O T s »• Hg** ^t-OTs R3 "a Diagram 91 m e r c u r i c a c e t a t e i n a m i x t u r e o f dio x a n e and water a t 25 C was e s t i m a t e d t o be 3.5 i 0.5 h r s . x The h a l f l i f e o f the c o r r e s p o n d i n g adamantanyl d e r i v a t i v e was a p p r o x i -11^ m a t e l y 5 min. W i t t i g y r e p o r t e d t h i s r e a c t i o n t o be s t r o n g l y s o l v e n t dependent and t h a t doner s o l v e n t s promoted t h i s d i s s o c i a t i o n by a l t e r i n g the s t r e n g t h o f the a l k y l -m e t a l bond. The s o l v o l y z i n g i n t e r m e d i a t e p o s s e s s e d a s i g n i f i c a n t amount o f carbonium i o n c h a r a c t e r as was seen by the p r e f e r -e n t i a l f o r m a t i o n o f 1 , 3 - d i h y d r o x y adamantane, b u t t h i s p o s i t i v e charge was n o t s u f f i c i e n t t o f a v o u r t h e g e n e r a l r i n g o p e n i n g rearrangement (2,Mt).^'^ Undoubtedly, s m a l l amounts - 9 3 -o f p r o d u c t s c o r r e s p o n d i n g b o t h t o a t t a c k by a c e t a t e and the e t h e r s o l v e n t a l s o were formed d u r i n g the c l e a v a g e . Coupled w i t h the p o s s i b i l i t y o f a t t a c k by the s o l v e n t and a c e t a t e on the f i r s t carbonium i o n , and the f a c t t h a t the r e d u c t i o n r e a c t i o n was i n i t i a t e d b e f o r e c o m p l e t i o n o f the m e t a l a t i o n o f DHA, the y i e l d of 1-hydroxyadamantane v/as s u r p r i s i n g l y h i g h ( 4 7 . 7 % ) . Other r e a c t i o n s a l s o c o u l d reduce t h i s y i e l d , most n o t a b l y d i s p r o p o r t i o n a t i o n ( 9 2 ) . 1 1 4 ' Diagram 9 2 The r e s u l t i n g compounds would be most d i f f i c u l t t o reduce due t o the f o r m i d a b l e s t e r i c h i n d r a n c e o f the t w i n a d a m a n t y l s u b s t i t u e n t s . A f t e r s e v e r a l months the r e d u c t i o n r e a c t i o n p r o d u c t s d i d d i s p l a y new e v i d e n c e o f m e t a l i c mercury, presumably from the d e c o m p o s i t i o n o f the s e compounds. I n any case the r e a c t i o n o f H g ( 0 A c ) 2 w i t h DHA i s s u r p r i s i n g l y complex. A d d i t i o n o f A l c o h o l An attempt was made t o p u r i f y the adamantane-DHA m i x t u r e s by r e c r y s t a l l i z a t i o n from methanol. Not o n l y was the f r a c t i o n r e c r y s t a l l i z a t i o n p r o c e d u r e not e f f e c t i v e , but a l s o DHA was found t o r e a c t s l o w l y w i t h the s o l v e n t t o g i v e a h i g h y i e l d o f 1-methoxyadamantane ( 9 3 ) . The a d d i t i o n o f 2 RHgX - 94 -Diagram 93 b o r o n t r i f l u o r i d e a c c e l e r a t e d the r e a c t i o n d r a s t i c a l l y so t h a t t o t a l c o n v e r s i o n o c c u r r e d w i t h i n m i n u t e s . A s i m i l a r r e s u l t was o b t a i n e d i n e t h a n o l . T h i s r e a c t i o n c o u l d be slowed b u t n o t stopped by a d d i n g t r a c e amounts o f sodium b i c a r b o n a t e t o the s o l v e n t s e v e r a l h o u r s p r i o r t o the d i s s o l u t i o n o f DHA. T h i s a t t e m p t t o c o n t r o l the a d d i t i o n o f a l c o h o l was p a r t o f a s p e c i f i c e f f o r t t o f i n d a more s u i t a b l e medium than n-octane f o r s t u d y i n g the h y d r o g e n o l y s i s of DHA. Hy d r o g e n a t i o n 115 I n h i s r e v i e w , Newham ^ p r e s e n t e d t h r e e g e n e r a l mechanisms f o r h y d r o g e n o l y s i s o f c y c l o p r o p y l r i n g s . He e n v i s i o n e d the p o s s i b i l i t y o f one, two and p o s s i b l y t h r e e adsorbed carbon r a d i c a l s 1 1 ^ i n t e r a c t i n g w i t h the s u r f a c e o f the c a t a l y s t (94)» H y d r o g e n o l y s i s has tended t o o c c u r a t s t r a i n e d bonds (95) »^"^ u n l e s s s t e r i c h i n d r a n c e e x i s t e d . 1 1 ' ' ' U n f o r t u n a t e l y d e f i n i t i v e s t u d i e s o f the mode f o r h y d r o -g e n a t i o n o f t h e s e compounds has not y e t been performed. - 95 -Mechanism Type a b e Diagram 94 The r e s u l t s from the s t u d y o f a s m a l l number o f compounds seemed t o i n d i c a t e h y d r o g e n o l y s i s o c c u r s by a d s o r p t i o n o n t o the c a t a l y s t from the t o p o r bo n d i n g l o b e s o f the s t r a i n e d bond (96); r a t h e r than the bottom i e _ . non-bonding l o b e s o f the s t r a i n e d bond. However, c o n c l u s i v e d i f f e r e n t i a t i o n between mechanisms A and B has not been a c c o m p l i s h e d . A t t e m p t s t o h y d r o g e n o l y z e the i n t e r n a l bond o f p r o p e l l a n e m o l e c u l e s was u n s u c c e s s f u l i n the l i m i t e d number o f compounds reported;^°k>57,94 however h y d r o g e n o l y s i s o f the i n t e r n a l bond o f DHA o c c u r r e d r e a d i l y i n n-octane n e a r the s t a n d a r d c o n d i t i o n s . Diagram 96 - 97 -A h i g h y i e l d o f adamantane was o b t a i n e d . S e v e r a l by-p r o d u c t s ( t o t a l y i e l d c a . 15%) w i t h a g l p c r e t e n t i o n time l e s s than t h a t o f adamantane were a l s o p r e s e n t . In many r e p e t i t i o n s o f t h i s e xperiment w i t h s e v e r a l d i f f e r e n t n o b l e m e t a l c a t a l y s t s i t was found d i f f i c u l t to r e p r o d u c e e i t h e r the r a t e o f hydrogen uptake o r the q u a n t i t y and d i s t r i b u t i o n o f the b y - p r o d u c t m i x t u r e . A d i r e c t r e l a t i o n s h i p was n o t e d between the d u r a t i o n o f the r e a c t i o n and the y i e l d o f by-p r o d u c t s . The nmr spectrum o f t h i s i n t r a c t a b l e b y - p r o d u c t m i x t u r e ( i s o l a t e d by p r e p a r a t i v e g l p c ) showed two s h a r p r e s o n a n c e s i n the m e t h y l r e g i o n , d o u b t l e s s l y , the r e s u l t o f a m o l e c u l a r rearrangement (97). 127 I n an e f f o r t t o i n c r e a s e the r e a c t i o n r a t e ' the e x p e r i m e n t s were r e p e a t e d w i t h e t h a n o l as the s o l v e n t because the r e a c t i o n o f DHA w i t h s o l v e n t was e x p e c t e d t o be v e r y s l o w . The i n c r e a s e i n the h y d r o g e n a t i o n r e a c t i o n r a t e was o b s e r v e d ; however, i n c r e a s e s i n the y i e l d as w e l l as a change i n the c h a r a c t e r o f the b y - p r o d u c t s a l s o was n o t e d . Most n o t a b l y , the r e a c t i o n r a t e between the s o l v e n t and DHA was a c c e l e r a t e d . * A d d i t i o n o f sodium b i c a r b o n a t e t o t h e s e r e a c t i o n s had l i t t l e n o t i c e a b l e e f f e c t on the e t h e r - p r o d u c i n g s i d e r e a c t i o n ; however, the s h o r t r e t e n t i o n time b y - p r o d u c t m i x t u r e was * The u s u a l r e a c t i o n time was c a . 24 h r but under hydrogena-t i o n c o n d i t i o n s i n e t h a n o l r e a c t i o n was complete w i t h i n 30 min. The y i e l d o f e t h e r was e s t i m a t e d t o be 31 i , 5% by nmr i n t e g r a t i o n . - 98 -reduced somewhat. A g a i n as w i t h the s y n t h e s i s o f DHA, d i f f i c u l t i e s were encountered i n r e p r o d u c i n g the r e a c t i o n r a t e s . The c h a r a c t e r and q u a n t i t y o f the b y - p r o d u c t s a l s o v a r i e d among r e p e a t e d r e a c t i o n s . The r e s u l t s o f these r e a c t i o n s were most c o n s i s t e n t w i t h a m o d i f i e d TYPE A mechanism (no d - ff s t a b i l i z a t i o n ) . The b y - p r o d u c t s which showed the presence o f m e t h y l groups c o n c e i v a b l y c o u l d a r i s e from a TYPE B a d s o r p t i o n mechanism (97a) f o l l o w e d by h o m o l y t i c f i s s i o n o f a b r i d g e - b r i d g e h e a d bond; however, a TYPE A mechanism i n v o l v i n g h o m o l y t i c (97b) o r more l i k e l y h e t e r o l y t i c (94a,c) f i s s i o n would a l s o be p o s s i b l e . ^ h K Diagram 97 The P l a t i n u m group m e t a l c a t a l y z e d rearrangement o f s t r a i n e d compounds has been w e l l documented. The p e r s i s t e n t - 99 -slow uptake o f hydrogen a f t e r the d i s a p p e a r a n c e o f DHA c o u l d be i n t e r p r e t e d as e v i d e n c e for, the e x i s t e n c e o f such a rearrangement. The f o r m a t i o n o f the e t h y l - a d a m a n t y l e t h e r might be a t t r i b u t e d i n p a r t t o t r a c e s o f HC1 r e m a i n i n g i n the c a t a l y s t o r more l i k e l y the p o i s o n i n g o f the c a t a l y s t by t r a c e s o f bromoadamantane compounds. T h i s e t h e r a l s o might a r i s e from p l a t i u m c a t a l y z e d a d d i t i o n o f e t h a n o l t o DHA, p o s s i b l y v i a a carbonium i o n i n t e r m e d i a t e o r f r e e r a d i c a l i n t e r m e d i a t e (98). Diagram 98 A d d i t i o n o f Benzene The a d d i t i o n o f benzene t o DHA o c c u r r e d r e a d i l y when c a t a l y z e d by aluminum t r i c h l o r i d e ( 9 9 ) . Under the c o n d i t i o n s o f the r e a c t i o n , o n l y a modest y i e l d o f 1-phenyladamantane was o b t a i n e d . T h i s was due t o the e x i s t e n c e o f many s i d e r e a c t i o n s . F i r s t , L e w i s a c i d c a t a l y s t s have been known t o c o - p o l y m e r i z e w i t h c y c l o p r o p y l compounds. Upon the workup o f the r e a c t i o n , p o l y m e r i c m a t e r i a l was i s o l a t e d . M i c r o -a n a l y s i s o f t h i s m a t e r i a l i n d i c a t e d t h a t the carbon and the hydrogen c o n t e n t were l o w e r than t h a t e x p e c t e d f o r polyadamantane; f u r t h e r m o r e , a n o n - c o m b u s t i b l e r e s i d u e - 100 -remained. Presumably, t h i s r e s i d u e was composed o f aluminum s a l t s . Second, the r e a c t i o n was f u r t h e r c o m p l i c a t e d by the e q u i l i b r a t i o n o f the r e a c t i o n p r o d u c t . Not o n l y was 1-phenyladamantane d e p h e n y l a t e d g i v i n g adamantane b u t a l s o a n o t h e r p h e n y l group was added r e s u l t i n g i n the com-pound, 1,3-diphenyladamantane. F u r t h e r m o r e , mass s p e c t r o -s c o p i c e v i d e n c e i n d i c a t e d the p r e s e n c e o f 1 , 3 , 5 - t r i p h e n y l -adamantane. A s i m i l a r d i s t r i b u t i o n o f the p r o d u c t s was o b t a i n e d i n the p r e p a r a t i o n o f a u t h e n t i c 1-phenyladamantane from 1-bromoadamantane under s i m i l a r c o n d i t i o n s . The l o w e r s o l u b i l i t y o f 1,3-diphenyladamantane compared w i t h 1-phenyladamantane r e q u i r e d e x t e n s i v e f r a c t i o n a l r e c r y s t a l l i z a t i o n f o r p u r i f i c a t i o n of the 1-phenyl-compound. I n a s i m i l a r f a s h i o n , the p u r i f i c a t i o n of 1 , 3 - d i p h e n y l -adamantane was e x t r e m e l y t e d i o u s . The b e s t e l e m e n t a l a n a l y s i s o f t h i s compound was n o t w i t h i n the r e q u i r e d l i m i t s ; however, the nmr spectrum d i d i n t e g r a t e f o r 10 p r o t o n s i n the a r o m a t i c r e g i o n . The mass spectrum showed a s t r o n g peak w i t h m/e + a t 288 mass u n i t s and a v e r y s m a l l peak w i t h m/e+ a t 364 presumably due t o the 1,3,5-triphenyladamantane i m p u r i t y ( m o l e c u l a r w e i g h t , 364). - 101 -T h e r m o l y s i s o f DHA The mixed s u b l i m a t e o r pure samples o f DHA d i d n o t o m e l t b u t p o l y m e r i z e d r a p i d l y a t c a , 160 C t o g i v e a s o l i d o . which d i d not m e l t up t o 350 C ( 1 0 0 ) . I n a i r t h i s s o l i d o began t o t u r n brown and decompose a t c a . 450 C but was s t a b l e up t o 500°C under n i t r o g e n . A s u b l i m a t e s i m i l a r t o t h a t of adamantane was o b s e r v e d t o form on the c o v e r s l i p d u r i n g d e c o m p o s i t i o n . T h i s p r o d u c t (100) had s u p e r i o r heat r e s i s -tance ( s u p r a v i d e ) t o the polyadamantane compound p r e p a r e d by R e i n h a r d t from 3,3'-dibromobiadamantane v i a a Wurtz o 131 r e a c t i o n ( d e c o m p o s i t i o n p o i n t 325 0 ) . n i 2 Diagram 100 A d i l u t e s o l u t i o n o f s u b l i m e d DHA i n degassed n-octane was s t u d i e d a t 195 0. Wiberg r e p o r t e d t h a t t r i c y c l o 3.2.1.0 o c t a n e p o s s e s s e d a h a l f l i f e o f c a . 20 h r a t t h i s t e mperature The h a l f l i f e o f DHA was found t o be 4.45 h r . Both adaman-tane and l , l ' - b i a d a m a n t a n e v/ere i d e n t i f i e d i n the p r o d u c t s o l u t i o n s . An u n i d e n t i f i e d major p r o d u c t most p r o b a b l y r e s u l t e d from r e a c t i o n o f DHA w i t h s o l v e n t . The a n a l y t i c a l g l p c r e t e n t i o n time and the b r e a d t h o f the t r a c e were co n -s i s t e n t w i t h the e x p e c t e d m i x t u r e o f i s o m e r s . - 102 -P r e l i m i n a r y s t u d i e s w i t h d i l u t e s o l u t i o n s o f DHA i n cumene gave two new compounds i n a d d i t i o n t o adamantane and l , l ' - b i a d a m a n t a n e . One o f t h e s e v/as i d e n t i f i e d as dicumene (101a) by comparison w i t h an a u t h e n t i c sample and the o t h e r (101b) was a p p a r e n t l y a g a i n the p r o d u c t o f s o l v e n t r e a c t i o n w i t h the 1 , 3 - d i r a d i c a l i n t e r m e d i a t e . The y i e l d o f adamantane from p y r o l y s i s o f DHA i n t h i s s o l v e n t was i n c r e a s e d s u b s t a n t i a l l y . Diagram 101 The 1 , 3 - d i r a d i c a l s p e c i e s has been o f i n t e r e s t f o r a l m o s t twenty y e a r s . Both c a l c u l a t i o n s and e x p e r i m e n t a l c s t u d i e s agree t h a t t h i s s p e c i e s v/as the u s u a l i n t e r m e d i a t e i n t h e r m o l y s e s and p y r o l y s e s o f s i m p l e and s t r a i n e d c y c l o -p ropanes. There c o u l d be l i t t l e doubt t h a t DHA undergoes h o m o l y t i c c l e a v a g e d u r i n g t h e r m o l y s i s t o y i e l d such an i n t e r m e d i a t e d i r a d i c a l ( 1 0 2 ) . ®» products Diagram 102 - 103 -D. C o n c l u s i o n s The m o l e c u l e t e t r a c y c l o Jj5.3.1.1^,''.01'^J decane has been s y n t h e s i z e d by d e h a l o g e n a t i o n o f 1,3-dibromo, 1,3,5-tribromo, and 1,3,5,7-tetrabromoadamantane w i t h a v a r i e t y o f m e t a l s and organo m e t a l l i c compounds. T h i s m o l e c u l e b e l o n g s to a new c l a s s o f compounds w i t h i n v e r t e d b r i d g e h e a d c a r b o n atoms. T h i s membership has been demon-s t r a t e d by the h i g h r e a c t i v i t y o f t h e new h y d r o c a r b o n compound toward b o t h f r e e r a d i c a l and e l e c t r o p h i l i c r e a g e n t s . T h i s r e a c t i v i t y makes the new compound a u s e f u l i n t e r m e d i a t e f o r the s y n t h e s i s o f 1 , 3 - d i s u b s t i t u t e d adaman-tane compounds. The s t r u c t u r e and r e a c t i v i t y o f the compound a l s o s u g g e s t s t h a t the i n t e r n a l bond p o s s e s s e s a h i g h degree o f p-charac±er and t h a t the r e a c t i v i t y must be due t o an i n c r e a s e d e l e c t r o n d e n s i t y i n the non-bonding l o b e e x t e r i o r t o the s k e l e t o n . T h i s e x p l a n a t i o n i s r e -e n f o r c e d by an X-ray c r y s t a l l o g r a p h i c s t u d y o f a d e r i v a t i v e w h i c h shows the i n t e r n a l bond o f the new compound t o be v e r y l a r g e (1.643 A ) . The DHA t h e r m a l polymer has proven t o be s t a b l e a t h i g h t e m p e r a t u r e . T h i s s t a b i l i t y c o u l d f u r t h e r be i n c r e a s e d by e n a b l i n g c r o s s l i n k a g e between c h a i n s t o o c c u r . Compounds such as double-dehydroadamantane o r l , l ' - b i - D H A e a s i l y would promote c r o s s l i n k i n g d u r i n g DHA p y r o l y s i s . - 10k -R e c e n t l y adamantane d e r i v a t i v e s have been shown t o 132 p o s s e s s m e d i c i n a l p r o p e r t i e s . The s i m p l e compound 1-aminoadamantane as w e l l as c e r t a i n o t h e r o f i t s d e r i v a t i v e s have shown b o t h a n t i v i r i a l and a n t i - P a r k i n s o n ' s syndrome e f f e c t i v e n e s s . The a d d i t i o n o f the adamantanyl group t o e x i s t i n g d r ugs and a n t i b i o t i c s has r e s u l t e d i n s i g n i f i c a n t l y a l t e r e d s p e c t r a o f a c t i v i t y and p o t e n c y . F o r t h e s e r e a s o n s , the r e a d y a v a i l a b i l i t y and r e a c t i v i t y o f DHA may prove u s e f u l i n the a r e a o f m e d i c i n a l c h e m i s t r y . - 105 -EXPERIMENTAL I n f r a r e d s p e c t r a were r e c o r d e d on the P e r k i n - E l m e r model 137-B I n f r a c o r d s p e c t r o p h o t o m e t e r equipped w i t h sodium c h l o r i d e o p t i c s . L i q u i d s were r u n as neat samples, s o l i d s , as n u j o l m u l l s o r as s o l u t e s i n c h l o r o f o r m . S o l u t i o n s p e c t r a were o b t a i n e d u s i n g 0.523 am sodium c h l o r i d e c e l l s . N u c l e a r magnetic resonance (nmr) s p e c t r a were r e c o r d e d by Mr. R. B u r t o n and M i s s P. Watson o f t h i s department on V a r i a n A s s o c i a t e s A-60, HA-100 and T-60 s p e c t r o m e t e r s . Resonance peaks a r e g i v e n i n & u n i t s , r e l a t i v e t o t e t r a m e t h y l s i l a n e ( i n t e r n a l s t a n d a r d ) . The samples were u s u a l l y run as 15-20% (w/v) s o l u t i o n s i n d e u t e r o c h l o r o f o r m o r c a r b o n t e t r a c h l o r i d e . S p e c t r a were a l s o r u n i n a r o m a t i c s o l v e n t s t o t a k e advantage o f the ob s e r v e d c h e m i c a l s h i f t s by s u s c e p t i b l e p r o t o n s . P y r i d i n e and benzene were used f o r t h i s purpose and f o r the d i s -s o l u t i o n o f compounds w h i c h were i n s o l u b l e i n the non-a r o m a t i c s o l v e n t s . C o m m e r c i a l l y a v a i l a b l e 5 mm g l a s s nmr tubes were used i n a l l c a s e s . H y d r o x y l peaks were i d e n t i f i e d by o b s e r v i n g t h e i r d i s a p p e a r a n c e a f t e r a d d i t i o n o f d e u t e r i u m - 106 -o x i d e o r by o b s e r v i n g the r e s u l t i n g change i n t h e i r c h e m i c a l s h i f t f o l l o w i n g the a d d i t i o n o f p y r i d i n e . A c c e p t a b l e i n t e g r a t e d peak a r e a r a t i o s were o b t a i n e d f o r a l l compounds s t u d i e d . M i c r o a n a l y s e s were performed by Mr. P. Borda o f t h i s department. M e l t i n g p o i n t s ( c o r r e c t e d ) were o b t a i n e d i n g l a s s c a p i l l a r y tubes u s i n g an e l e c t r i c a l l y h e a t e d , c i r c u i t i n g o i l b a t h . D i s t i l l a t i o n s , u n l e s s o t h e r w i s e s p e c i f i e d , were c a r r i e d out u s i n g a Bantom-ware s h o r t - p a t h d i s i l l a t i o n u n i t . I t was n oted t h a t the b o i l i n g p o i n t s ( u n c o r r e c t e d ) were a f f e c t e d by the s t i l l p ot t e m p e r a t u r e ; hence were not v e r y a c c u r a t e . P r e p a r a t i v e g a s - l i q u i d phase chromatography ( g l p c ) was performed w i t h a V a r i a n - A e r o g r a p h 90-P, a W i l k i n s -Aerograph A-90-P and a W i l k i n s - A e r o g r a p h A-700 A u t o p r e p . A l l used h e l i u m as the c a r r i e r gas and a t h e r m a l c o n d u c t i v i t y u n i t as a d e t e c t o r . ; These i n s t r u m e n t s used s t a n d a r d c o m m e r c i a l l A i n o r 3/8 i n copper o r aluminum columns ( A e r o g r a p h ) . A n a l y t i c g l p c was performed w i t h a P e r k i n -Elmer model 900 chromatograph u s i n g h e l i u m as the c a r r i e r gas and flame i o n i z a t i o n as the d e t e c t i o n method. The columns were s t a n d a r d c o m m e r c i a l l y a v a i l a b l e 6 i t by 1/8 i n s t a i n l e s s s t e e l columns ( P e r k i n - E l m e r ) . These a n a l y t i c columns a l l used Chromosoro "W" 8u/100 mesh as the i n e r t - 107 -s u p p o r t medium. Three a n a l y t i c a l columns v/ere used almost e x c l u s i v e l y . These v/ere: Carbov/ax 20M (10%) on base washed Chromosorb "W"; P h e n o x y s i l i c o n e grease (8%) on a c i d washed Chromosorb "W"; and S i l i c o n e e l a s t o m e r - 3 0 (8%) on a c i d washed Chromosorb "W". The s u p p o r t i n each case v/as 80/100 mesh. The model 900 P e r k i n - E l m e r i n s t r u m e n t was c a p a b l e o f b e i n g temperature programmed. For the Carbowax column the most u s e f u l program c o n s i s t e d o f the f o l l o w i n g : h o l d a t o o 8 0 C f o r 8 min; then i n c r e a s e the temperature by 32 C per o o min t o 200 C; and then h o l d a t 200 C the maximum recommended temperature ( u s u a l l y 10 min) b e f o r e r e t u r n i n g the temperature to 80°C ( 8 0°C / 8 min ? 2 G / m i r W 2 0 0 ^ / 1 0 m i n ) . U n l e s s o t h e r -w i s e s p e c i f i e d t h i s i s the temperature program used. The h e l i u m f l o w r a t e v a r i e d w i t h v a r y i n g temperature but i n a l l c a s e s c i t e d i t remained betv/een 4 0 and 65 a i l per min. Bromine ( J . T . B a k e r ) (used b o t h as s o l v e n t and r e a g e n t ) was used d i r e c t l y from the b o t t l e . D r y i n g by s n a k i n g w i t h c o n c e n t r a t e d s u l p h u r i c a c i d and/or phosphorous p e n t o x i d e and d i s t i l l a t i o n was not found n e c e s s a r y . D i e t h y l e t h e r ( M a l l i n c k r o d t AR Anhydrous) was used d i r e c t l y o r s t o r e d o v e r SA - 5 m o l e c u l a r s i e v e s u n t i l used. Benzene was d r i e d by a z e o t r o p i n g o f f tne w a t e r and r e f l u x i n g o v er sodium. D i s t i l l a t i o n was e f f e c t e d by u s i n g an u p r i g h t condenser and s t i l l h e a d w i t h s t o p c o c k e d s i d e arm. - 1 0 8 -n-Heptane (BDH) was p u r i f i e d by s h a k i n g tnree t i m e s w i t h 1 0 % ( v / v ) o f c o n c e n t r a t e d s u l p h u r i c a c i d washing w i t h v/ater then d r y i n g o v e r c a l c i u m c h l o r i d e . The n-heptane was d r i e d f i n a l l y by r e f l u x o v e r and d i s t i l l a t i o n from sodium m e t a l w i t h the a i d o f the m o d i f i e d s t i l l h e a d d e s c r i b e d above. Glyme was d r i e d by r e f l u x o v er and d i s t i l l e d from sodium. n-Pentane (Eastman) was p u r i f i e d and d r i e d i n the same manner as n-heptane. T e t r a h y d r o f u r a n was p u r i f i e d by r e f l u x o v e r sodium and d i s t i l l e d . Sodium h y d r i d e (a 54% d i s p e r s i o n i n m i n e r a l o i l from M e t a l H y d r i d e s I n c . ) was washed f r e e o f o i l w i t h anhydrous d i e t h y l e t h e r q u i c k l y weighed and then used i m m e d i a t e l y . P o t a s s i u m (BDH) was p u r i f i e d under an atmosphere o f n i t r o g e n i n n-heptane by h e a t i n g the m e t a l p a s t i t s m e l t i n g p o i n t g e n t l y s w i r l i n g the m e t a l f r e e o f i t s o x i d e " s k i n " and l e t t i n g i t s o l i d i f y a g a i n . The m e t a l was removed, weighed and then used i m m e d i a t e l y . (An a l t e r n a t e but w a s t e f u l method o f p u r i f i c a t i o n was to c u t the o x i d e c o a t i n g away under x y l e n e ) . Sodium ( J . T . B a k e r ) m e t a l c o u l d be s i m i l a r l y p u r i f i e d . Sodium-potassium a l l o y was p r e p a r e d by m e l t i n g t o g e t h e r sodium ( 2 3 g) and p o t a s s i u m ( 1 1 9 g ) . The a l l o y was t r a n s -f e r r e d to a ground g l a s s E r l e n m e y e r and s t o r e d under 1 cm - 109. -of p a r a f f i n o i l u n t i l needed. This a l l o y referred to as "stock a l l o y " was used for a l l debrominations of the adamantane bromides. A l l other chemicals used were reagent grade or better and were used d i r e c t l y , as received. A. Preparation of Brominated Adamantanes 1. Preparation of 1,3-Dibromoadamantane An anhydrous s t i r r e d solution of aluminum tribromide (1.7 g) i n bromine (105 ml) v/as prepared i n a 250 ml two-necked round bottomed flask f i t t e d witn a stopper and a condenser topped with a drying tube*. Due to the high exothermicity of tne reaction, the solution was cooled between 0 6 0 C and 7 0 i n an ice-bath while commercial grade adamantane (32.0 g) was added (1.3 hr;. The excess bromine v/as decom-posed v/ith excess sodium D i s u i f i t e (120 g) af t e r pouring the reaction solution into i c e water (900 ml) and carbon-tetrachloride (4/5 ml). The phases were separated, the aqueous layer back-extracted v/ith carbontetrachloride and the pooled organic phases dried over anhydrous calcium chloride. Rotary evaporation gave a s l i g h t l y yellow, c r y s t a l l i n e product (c_a. 69 g). Analytic glpc, using the o Carbov/ax column at 200 C, 52 ml per min, shov/ed only one A hydrogen oromide gas trap v/as connected to the drying tube or paper towelling was wrapped in a cylinder around the end and the reaction v/as performed i n the fume hood. - 110 -major p r o d u c t , 7.0 min, i n the t r a c e . 'Four r e c r y s t a l l i z a t i o n s from c y c l o h e x a n e gave a n a l y t i c a l l y pure w h i t e c r y s t a l l i n e s o l i d (35 g, 92%), mp ( s e a l e d c a p i l l a r y tube) 108-111°C ( r e p o r t e d 112-113°C, a l s o 108-109°C). 9 The i n f r a r e d spectrum (CHC1,) s h o w e d ^ „ a t : 2880 ( s ) , 1450 ( s ) , 1340 ( s ) , 1320 ( s ) , 1280 ( s ) , 1100 (w), 1020 ( s ) , 995 (m), 983 (w), and 955 cm" 1 ( s ) . The nmr spectrum ( c h l o r o f o r r a - d ) showed the f o l l o w i n g r e s o n a n c e s : 2.86, s i n g l e t , 2 p r o t o n s o f the C-2 methylene; 2.30, s i n g l e t , 10 p r o t o n s o f the C-4,8,9 and 10 methylenes and C-5 and 7 b r i d g e h e a d s ; and 1.72 S, s i n g l e t , 2 p r o t o n s of the C-6 methylene. A n a l . C a l c d . f o r c 1 0 H 1 ^ B r 2 : C, 40.84; H, 4.73; B r , 54.36. Found: C, 40.61; H, 4.83; B r , 54.54. 2. P r e p a r a t i o n o f 1 , 3 , 5-Tribromoadamantane In the same a p p a r a t u s used f o r the p r e p a r a t i o n o f 1,3-dibromoadamantane an anhydrous s o l u t i o n o f aluminum t r i b r o m i d e o (3.8 g) i n bromine (63 ml) was c o o l e d to 0 C b e f o r e commercial adamantane (17.5 g) was added o v e r 2 h r so t h a t the tempera-o t u r e d i d not exceed 6 C. The r e a c t i o n was a l l o w e d to r e a c h room temperature and c o n t i n u e d f o r 3 days b e f o r e a n a l y t i c g l p c showed no 1 , 3-dibromoadamantane, 7 min, remained.. o The base-washed Carbowax column a t 200 C i n d i c a t e d the presence o f o n l y one major p r o d u c t , 19 min. A minor - I l l -b y - p r o d u c t , 34 min, was shown not to be s u p e r i m p o s a b l e upon the a u t h e n t i c 1,3,5,7-tetrabromoadamantane t r a c e . The r e a c t i o n p r o d u c t was poured i n t o i c e water (1000 ml) and c a r b o n t e t r a c h l o r i d e (350 m l ) . The e x c e s s bromine was decomposed w i t h sodium b i s u l f i t e (80 g) by a d d i n g s m a l l p o r t i o n s (c_a. 1 g) over 4 h r so t h a t the temperature d i d o not r i s e above 6 C. The two phases were s e p a r a t e d , d r i e d , and the s o l v e n t d i s t i l l e d o f f as 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 1,3-dibromoadamantane. A p a l e y e l l o w c r y s t a l l i n e s o l i d (47.8 g) was o b t a i n e d . Four r e c r y s t a l l i z a t i o n s from methanol and two from n-hexane gave an a n a l y t i c a l l y pure w h i t e c r y s t a l l i n e s o l i d (36.1 g, 75%) , mp ( s e a l e d tube) 121.5-124°C ( r e p o r t e d 126-127°C). 9 The i n f r a r e d spectrum (KBr d i s c ) showed 1? a t : 2880 max ( s ) , 1450 ( s ) , 1345 (m), 1325 (w), 1310 ( s ) , and 1280 cm" 1 ( s ) . The nmr spectrum (chloroform-d-^) showed the f o l l o w i n g r e s o n a n c e s : 2 . 7 8 , s i n g l e t , 6 p r o t o n s o f C-6,8 and 10 methylenes; 2.35, s i n g l e t , 1 p r o t o n o f C-7 b r i d g e h e a d ; and 2 . 2 5 5 , s i n g l e t , 6 p r o t o n s o f C-4,6 and 8 m e t h y l e n e s . A n a l . C a l c d . f o r ^ 1Q\^y c , 32 . 2 6 ; H, 3 . 3 8 ; B r , 6 4 . 3 5 . Found: C, 32 . 2 8 ; H, 3 . 5 1 ; B r , 64.28. 3. P r e p a r a t i o n o f l t | 3 , 5,7-Tetrabromoadarnantane The compound 1,3,5,7-tetrabromoadamantane was p r e p a r e d - 112 -d i r e c t l y from adamantane by a m o d i f i c a t i o n o f the S t e t t e r and W u l f 9 method, developed by S c o t t . ^ The a p p a r a t u s and the f i r s t p a r t of t h i s p r o c e d u r e v/a i d e n t i c a l to t h a t 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 1,3-dibromoadamantane. Commercial grade adamantane (10 g) was added t o a s o l u t i o n o f aluminum t r i b r o m i d e (0.18 g) i n bromine (45 ml) which was c o o l e d s u f f i c i e n t l y to c o n t r o l the v i g o r o u s l y e x o t h e r m i c r e a c t i o n . 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 (6 h r ) and a l l o w e d to s t a n d o v e r n i g h t . A n a l y t i c g l p c u s i n g the P h e n o x y s i l i c o n e g r ease column*, o a t 240 C, 54 ml/min, o f an a l i q u o t decomposed by sodium b i s u l f i t e and n e u t r a l i z e d w i t h sodium b i c a r b o n a t e showed o n l y one major p r o d u c t , 3.2 min. A u t h e n t i c 1,3,5-tribromo adamantane had an i d e n t i c a l r e t e n t i o n t i m e . The bromine s o l u t i o n c o n t a i n i n g the 1,3,5-tribrorno-adamantane was q u i c k l y t r a n s f e r r e d w i t h a m i c r o p i p e t t e to anhydrous, n i t r o g e n f i l l e d C a r i u s t u b e s o f two s i z e s . Each o f the two l a r g e tubes was f i l l e d t o 1/3 o f c a p a c i t y (15 ml) as were the e i g h t s m a l l tubes (1.5 m l ) . The r e m a i n i n g p o r t i o n o f t h i s r e a c t i o n s o l u t i o n (5.5 : f o r w hich no tubes were a v a i l a b l e was t r e a t e d as 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 1,3,5-tribromoadamantane and t h i s * The maximum recommended temperature f o r t h i s column was 275 0. T h i s column was used f o r compounds which had an i n c o n v e n i e n t l y l o n g r e t e n t i o n time or decomposed on the Carbowax column. - 113 -crude t r i b r o m i d e compound (5.43 g) was i s o l a t e d . A f t e r f r e e z i n g the c o n t e n t s i n l i q u i d n i t r o g e n , the tubes were s e a l e d under h i g h vacuum and were e n c l o s e d i n b r a s s bombs. o The bombs were h e a t e d t o 165 i 2 C (2 .5 da) b e f o r e a n a l y t i c a l g l p c i n d i c a t e d the r e a c t i o n was c omplete. The tubes were opened a f t e r f r e e z i n g t h e i r c o n t e n t s once a g a i n i n l i q u i d n i t r o g e n . The p r o d u c t s u s p e n s i o n was d i v i d e d i n t o two p a r t s . Each was emptied i n t o i c e w a t e r (900 ml) and c a r b o n t e t r a c h l o r i d e (1500 m l ) . Sodium b i s u l f i t e (30 g) was added (1 h r ) w h i l e k e e p i n g the c o n t e n t s c o o l w i t h an i c e b a t h . The workup was i d e n t i c a l t o t h a t 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 1 ,3-dibromoadamantane. T h i s p r o c e d u r e y i e l d e d crude 1 , 3 , 5 , 7-tetrabromoadamantane. A n a l y t i c a l o g l p c u s i n g the P h e n o x y s i l i c o n e g r e a s e column a t 240 C, 54 ml/min, showed one major p r o d u c t , 4 .6 rain. S e v e r a l minor p r o d u c t s ; 3 .2 ( 1 , 3 , 5 - t r i b r o m o a d a m a n t a n e ) , 7.0 and 9.5 min were a l s o o b s e r v e d . F r a c t i o n a l r e c r y s t a l l i z a t i o n from c a r b o n t e t r a c h l o r i d e gave (18.3 g, 46%) o f an a n a l y t i c a l l y pure w h i t e g r a n u l a r s o l i d , mp ( s e a l e d tube) 246-8°C ( r e p o r t e d 2 4 6 - 7°C). 9 The i n f r a r e d spectrum ( n u j o l ) showed the f o l l o w i n g 1) : 1320 ( s ) , 1220 (m), 990 (m), 848 ( s ) , and 720 cm"*1 ( s ) . The nmr spectrum (chloroforra-d-^) showed o n l y one r e s o n a n c e : 2 .70 £ , s i n g l e t , 12 p r o t o n s of the m e t h y l e n e s . - 114 -A n a l . C a l c d . f o r C ^ H ^ B i y C, 26.55; H, 2.65; B r , 70.79. Found: C, 26.73; H, 2.56; B r , 70.51. B. P r e p a r a t i o n o f 1 ,5-Dehydroadamantane - R e p r e s e n t a t i v e R e a c t i o n s 1. Treatment of 1,5-Dibronioadamantane i - n fflyme w i t h  L i t h i u m aluminum h y d r i d e An anhydrous t h r e e - n e c k e d f l a s k (100 ml) was f i t t e d w i t h a condenser and a d r y i n g tube and s t o p p e r s . L i t h i u m aluminum h y d r i d e (1.0 g) was added t o a s o l u t i o n o f dibromoadamantane (2.0 g) i n glyme (50 m l ) . A f t e r s e v e r a l days o f r e f l u x o n e - h a l f o f the s t a r t i n g m a t e r i a l had been consumed. The o n l y v i s i b l e p r o d u c t o f t h i s r e a c t i o n was i d e n t i f i e d as adamantane by s u p e r p o s i t i o n v / i t h the a u t h e n t i c compound. 2. Treatment o f l,3-Di"bromoadamantane w i t h Magnesium A s o l u t i o n o f 1,3-dibromoadamantane (0.50 g) i n anhydrous e t h e r (5.0 ml) v/as added from a d r o p p i n g f u n n e l w i t h s i d e arm i n t o a d r y , n i t r o g e n f l u s h e d t h r e e - n e c k e d 100 ml f l a s k c o n t a i n i n g powdered magnesium m e t a l (0.15 g) and a s t i r r e r . Anhydrous c o n d i t i o n s v/ere m a i n t a i n e d by a d r y i n g tube on the condenser. A c r y s t a l o f i o d i n e ( c a . 10 mg) was r e q u i r e d to i n i t i a t e the r e a c t i o n ; then the r e a c t i o n - 115 -m i x t u r e was d i l u t e d w i t h anhydrous e t h e r (45 m l ) . The r e a c t i o n was f o l l o w e d by a n a l y t i c g l p c u s i n g the Carbowax o o column a t 80 C and a t 200 C. The r e a c t i o n was a l m o s t h a l f completed (15 h r ) when g l p c showed the r a t i o o f the d e s i r e d compound to t h a t o f the r e d u c t i o n b y - p r o d u c t was l e s s than u n i t y ; t h u s , the r e a c t i o n was abandoned i n f a v o u r o f tne a l k a l i m e t a l d e b r o m i n a t i o n method v/hich a l r e a d y had produced much b e t t e r y i e l d s o f the d e s i r e d compound. 5. P r e p a r a t i o n o f DHA from 1,5-Dibromoadamantane The f o l l o w i n g r e a c t i o n s were r e p e a t e d many times f o r the p r e p a r a t i o n and s t u d y o f DHA. Only those r e a c t i o n s which gave the most r e p r e s e n t a t i v e y i e l d s were r e c o r d e d below as r e p r e s e n t a t i v e r e a c t i o n s . a) P o t a s s i u m m e t a l i n n-heptane An anhydrous 250 ml t h r e e - n e c k e d r l a s k was f i t t e d w i t h a d r y i n g tube and dry n i t r o g e n i n l e t ; each was s e p a r a t e d from the f l a s k w i t h a 10 cm " e x t e n s i o n " t u b e . The c e n t r a l B-24 j o i n t r e c e i v e d the water c o o l e d c o l l a r o f the r h e o s t a t -c o n t r o l l e d h i g h speed s t i r r e r * . The above a p p a r a t u s w i l l De r e f e r r e d to as the u s u a l a p p a r a t u s i n the f o l l o w i n g r e l a t e d e x p e r i m e n t s . Lab L i n e I n s t r u m e n t s , I n c . - 116 -The system was purged w i t h n i t r o g e n . Under these a n o x i o u s and anhydrous c o n d i t i o n s , 1 ,3-dibromoadamantane (1.00 g) was d i s s o l v e d i n d r y n-heptane ( 5 0 ml) b e f o r e f r e s h l y c u t p o t a s s i u m (2.5 g) was added. The temperature o v/as r a i s e d above the m e l t i n g p o i n t o f the m e t a l (100 + 3 C) which v/as then d i s p e r s e d by h i g h speed s t i r r i n g , then s t i r r e d more s l o w l y . The r e a c t i o n was f o l l o w e d by a n a l y t i c a l g l p c u s i n g the base-washed Carbowax column* v/ith a tempera-o t u r e program, (80°C / 6 min 3 2 C/ m i rW200°C)**. No s i g n i f i c a n t r e a c t i o n t o o k p l a c e u n t i l t e r t i a r y -b u t y l a l c o h o l ( c a . 0.05 nil) v/as added. A n a l y t i c a l g l p c o (35 min) w i t h temperature programming (80°C / 6 min , J>- C / m i n ^ o 200 C) showed the r e a c t i o n was complete by the absence of 1,3-dibromoadamantane, 17.2 min***, and the appearance of two major peaks, 4.3*** and 5.3 min. The second peak, 5.3 min, d i s a p p e a r e d when the system was t i t r a t e d w i t h o bromine a t -75 0. 1,3-Dehydroadamantane decomposed on a l l a c i d washed o r con t a m i n a t e d columns. ** The c a r r i e r f l o w r a t e was found t o v a r y v/ith t e m p e r a t u r e . *** E s t a b l i s h e d w i t h a u t h e n t i c 1,3-dibromoadamantane and adamantane r e s p e c t i v e l y . - 117 -A n a l y t i c a l glpc using the Carbbwax and the Phenoxysilicone grease columns, i d e n t i f i e d the bromination product as 1 , 3 -dibromoadamantane by superposition of the respective traces with authentic material. The y i e l d s of adamantane (0.060 g, 13.0%) and 1 , 3 -dibromoadamantane (0.593 g, 59.2%) were determined by comparison with solutions of the authentic compounds. From the above data the y i e l d of the new compound DHA (0.270 g, 59.2%) was calculated. This compound, 9.5 min, was separated from the adamantane by-product by preparative glpc using a 10 f t x 3/8 i n Carbowax 20M (10%) on base washed (60/80 mesh) Chromosorb "W" i n an aluminum column at 110°C, 86 ml/min. Each injected aliquot (2 ml) of the product solution (ca. 4 x 10~3M) allowed the i s o l a t i o n of a c o l o r l e s s v o l a t i l e s o l i d (4-6 mg) having no d i s t i n c t melting point (sealed tube). o When heated, the neat compound polymerized at ca. 160 C o giving a c o l o r l e s s s o l i d which did not melt below 350 C. o This s o l i d turned brown i n a i r above 450 C. Under nitrogen o and above 500 C, i t remained c o l o r l e s s , but a white sublimate condensed on the cover s l i p , showing decomposition occurred. The compound decomposed i n a l l solvents used (for example, CS^, C ^, CHCl^, CCl^) for i n f r a r e d a n a l y s i s . - 118 -The i n f r a r e d spectrum ( C S p ) showed the f o l l o w i n g 1? 3040 (w), 2900 ( s ) , 2055 (m), 1285 ( s ) , 1270 (w), nicix 1100 (m), 1080 ( s ) , 1030 (m), 995 (m), 942 (m), 900 (m), 790 ( s ) , 745 cm" 1 ( s ) . The i n f r a r e d spectrum (CC1, ) showed The nmr spectrum (degassed benzene) showed the f o l l o w i n g r e s o n a n c e s : 2.73, broad s i n g l e t , 2 p r o t o n s o f the C-5,7 b r i d g e h e a d s ; 2.05, t r i p l e t , J = 1.2 Hz, 2 p r o t o n s o f the C-6 methylene; 1.66, c l o s e l y spaced m u l t i p l e t , 2 p r o t o n s o f the C-2 methylene; 1.91, d o u b l e t , J = 11 Hz, 4 p r o t o n s o f C-4,8,9 and 10 ( e n d o - e q u a t o r i a l p r o t o n s ) m e t h y l e n e s ; and 1.15 £ , d o u b l e t , J = 11 Hz, 4 p r o t o n s o f 0-4,8,9 and 10 ( e x o - a x i a l p r o t o n s ) . The h i g h r e s o l u t i o n mass spectrum showed a peak w i t h m/e+ a t 134.1086 + 0,001; c a l c u l a t e d f o r c 1 0 H l i f * 134.1095. The h i g h r e a c t i v i t y o f DHA w i t h oxygen p r e c l u d e d a c c u r a t e and c o n s i s t e n t a n a l y t i c r e s u l t s . However, a n a l y s i s o f the t h e r m a l l y t r e a t e d DHA sample compound gave the f o l l o w i n g r e s u l t s : b) Sodium-potassium a l l o y i n n-heptane The u s u a l a p p a r a t u s was d r i e d and purged w i t h n i t r o g e n . I n t h i s a p p a r a t u s a s o l u t i o n o f 1,3-dibromoadamantane A n a l . C a l c d . f o r C 1 0 H 1 4 ; Found: C, 89.49; H, 10.51. C, 89.30; H, 10.90. - 1 1 9 -(1.00 g) was p r e p a r e d i n n-heptane (50 ml) near i t s b o i l i n g p o i n t . Sodium-potassium a l l o y (0.76 g, 1:5.17 by w e i g h t ) v/as d e l i v e r e d from a t a r r e d n i t r o g e n f i l l e d a r y m i c r o p i p e t t e and was d i s p e r s e d . The r e a c t i o n p r o g r e s s was m o n i t o r e d by a n a l y t i c a l o g l p c u s i n g the P h e n o x y s i l i c o n e g rease column a t 240 C to observe the d i s a p p e a r a n c e o f 1,3-dibromoadamantane, c a . 1.2 min. No r e a c t i o n o c c u r r e d (25 rain) u n t i l t e r t i a r y - b u t y l a l c o h o l ( c a , 0.05 ml) v/as added. Only a t r a c e o f the 1,3-dibromo compound remained (35 min) a f t e r the r e a c t i o n was i n i t i a t e d . F u r t h e r r e a c t i o n (8 min) removed t h i s t r a c e . The y i e l d o f DHA (0.23 g, 50.3%) was d e t e r m i n e d by t i t r a t i o n v/ith i o d i n e (0.43 g) and by a n a l y t i c a l g l p c comparison o f tne r e a c t i o n p r o d u c t w i t h a s t a n d a r d s o l u t i o n o f a u t h e n t i c 1,3-di-iodoadamantane u s i n g the base-washed o Carbowax column a t 200 C. The y i e l d o f adamantane (0.0224 g, 4.8%) was de t e r m i n e d i n a s i m i l a r f a s h i o n . c) Sodium-potassium a l l o y i n d i e t h y l e t h e r A s o l u t i o n o f 1,3-dibromoadamantane (1.01 g) and d r y d i e t h y l e t h e r (60 ml) v/as p r e p a r e d under n i t r o g e n i n the u s u a l a p p a r a t u s . T h i s s o l u t i o n v/as t r e a t e d a t room temperature v/ith sodium-potassium a l l o y (0.74 g, 1:5.17 by w e i g h t ) which was d i s p e r s e d by h i g h speed s t i r r i n g . A n a l y t i c a l g l p c (1 h r ) showed t h a t no 1,3-dibromoadamantane remained. - 120 -The p r o c e d u r e d e s c r i b e d i n the f o l l o w i n g two pa r a g r a p h s w i l l be h e n c e f o r t h r e f e r r e d to as d i s t i l l a t i o n - s u b l i m a t i o n . The r e a c t i o n f l a s k was a t t a c n e d t o the d i s t i l l a t i o n - s u b -l i m a t i o n a p p a r a t u s * , then c o o l e d t o D r y - I c e t e m p e r a t u r e . The e t h e r was d i s t i l l e d from tne r e a c t i o n v e s s e l under a h i g h vacuum a t room temperature and lo w e r as e v a p o r a t i o n o c c u r r e d . The e n t r a i n m e n t o f tne v o l a t i l e r e a c t i o n p r o d u c t and b y - p r o d u c t was m i n i m i z e d by a m i x t u r e o f c a r b o n -o t e t r a c h l o r i d e and Dry Ice (a temperature o f c a . -15 C) i n the t i p o f the condenser. The s u b l i m a t i o n was performed i n the same a p p a r a t u s i m m e d i a t e l y a f t e r d i s t i l l a t i o n by r e p l a c i n g the c a r b o n -t e t r a c h l o r i d e - D r y I c e i n the t i p o f the condenser w i t h acetone-Dry I c e . The s u b l i m a t i o n ( c a . L h r ) c o u l d be to vacuum ^—B-19 to hose-adaptor l-*—high vacuum hose m a g n e t i c V—~~^ reaction mixture st irr ing bar L- _ i :  clam ps tip , i III — ^ — * • • • — T h i s m o d i f i e d Dry Ice condenser and f l a s k was used whenever d i s t i l l a t i o n - s u b l i m a t i o n was pe r f o r m e d . - 121 -a c c e l e r a t e d by a p p l i c a t i o n o f warm water b a t h s . Upon c o m p l e t i o n , the t i p was a l l o w e d t o r e a c h room temperature i n i s o l a t i o n b e f o r e b r e a k i n g the vacuum, s c r a p i n g o f f the s u b l i m a t e , w e i g h i n g w i t h o u t d e l a y , and s t o r i n g under an i n e r t atmosphere. The w e i g h t o f the c r y s t a l l i n e v o l a t i l e w h i t e s u b l i m a t e (0.392 g, 84.5%) was d e t e r m i n e d . Repeated i n j e c t i o n s showed t h a t the r a t i o o f adamantane t o DHA was 1:2.28; t h u s , the y i e l d s o f adamantane (0.119 g, 25.5%) and DHA (0.272 g, 2 9 % ) * v/ere c a l c u l a t e d . d) Sodium-potassium a l l o y i n e t h e r i n i t i a t e d by a l c o h o l * * The u s u a l a p p a r a t u s v/as assembled. Under anhydrous and a n o x i o u s c o n d i t i o n s , a s o l u t i o n o f 1,3-dibromoadamantane (1.00 g) i n e t h e r (50 ml) was t r e a t e d v / i t h a l a r g e e x c e s s o f f i n e l y d i s p e r s e d sodium-potassium a l l o y (0.739 g, 1:5.17 by w e i g h t ) . No s i g n i f i c a n t r e a c t i o n took p l a c e (30 m i n ) ; t h e r e f o r e t - b u t y l a l c o h o l ( c a . 2 ml) was added (0.05 ml/15 s e c ) from a d r o p p i n g f u n n e l w i t h a s i d e arm. A n a l y t i c a l g l p c showed no 1,3-dibromoadamantane v/as p r e s e n t (55 m i n ) . *• The a c c u r a c y o f these f i g u r e s depends upon two assump-t i o n s : 1,3-dehydroadamantane does not decompose o r r e a c t s i g n i f i c a n t l y d u r i n g g l p c a n a l y s i s , and i o n i z e s to the same e x t e n t as adamantane wnen combusted by the hydrogen f l a m e . Tne v a l i d i t y o f these a s s u m p t i o n s was c o n f i r m e d by b r o m i n a t i o n o f DHA and i s o l a t i o n o f the d i b r o m i d e . The hydrogen flame was found to be s u f f i c i e n t l y hot to i o n i z e even O C l ^ to a s m a l l but s i g n i f i c a n t e x t e n t . ** S m a l l amounts of h y d r o x l i c s o l v e n t s removed the e r r a t i c i n i t i a t i o n and r e a c t i o n t i m e s f o r t h i s r e a c t i o n . .- 122 -D i s t i l l a t i o n - s u b l i m a t i o n y i e l d e d a w h i t e v o l a t i l e s o l i d m i x t u r e (0.352 g, 7 7 % ) . Gas chromatography e s t a b l i s h e d the r a t i o o f adamantane to DHA (1:3 . 6 4 ) . The y i e l d o f DHA (0.276 g, 60.5%) and t h a t o f adamantane (0 .076 g, 16.7%) was c a l c u l a t e d from the above d a t a . o e) Sodium n a p h t h a l i d e i n e t h e r a t -75 0 The n a p h t h a l i d e was p r e p a r e d a t room temperature from d i s p e n s e d a l l o y (0 .633) and na p h t h a l e n e ( 2 , 1 g) i n the u s u a l a p p a r a t u s e x c e p t f o r a l a r g e r f l a s k (250 m l ) . The u s u a l d r y an a n o x i o u s c o n d i t i o n s were m a i n t a i n e d t h r o u g h o u t the e x p e r i -o ment. A t -75 0 t h e 1,3-dibromoadamantane (0.50 g) i n anhydrous e t h e r (5.0 ml) v/as added (5 m i n ) . The r e a c t i o n (4 h r ) was f o l l o w e d by a g l p c u s i n g t h e Carbov/ax column. The y i e l d o f -DHA (0.165 S» 72.5%) was de t e r m i n e d by a n a l y t i c a l g l p c t r a c e comparison o f the r e a c t i o n s o l u t i o n v / i t h a s t a n d a r d s o l u t i o n o f adamantane, s i n c e d i s t i l l a t i o n - s u b l i m a t i o n was not f e a s i b l e due t o c o - s u b l i m a t i o n o f n a p h t h a l e n e . An e q u a l l y e f f i c i e n t and c o n s i s t e n t y i e l d i n g method f o r the s y n t h e s i s o f DHA u t i l i z e d the n - b u t y l l i t h i u m and hexamethylphosphoramide (HMPA) d e b r o m i n a t i n g r e a g e n t i n e t h e r i n f r a v i d e ; however s i m i l a r t o the above r e a c t i o n , c o n t a m i n a -t i o n o f the s u b l i m a t e o c c u r r e d by HMPA and l o w - b o i l i n g by-p r o d u c t s so t h a t the s u b l i m a t e a t t i m e s was a s e m i - s o l i d . F o r s t u d i e s w h i c h r e q u i r e d the p u r i s t p o s s i b l e s u b l i m a t e , eg. t h e r m a l d e c o m p o s i t i o n k i n e t i c s , the l o w e r y i e l d i n g l e s s c o n s i s t e n t more time consuming Na-K a l l o y i n e t h e r debroraina-- 123 -t i o n r e a c t i o n v/as used. The g l p c a n a l y s i s o f the l a t t e r s u b l i m a t e showed o n l y adamantane as the o n l y s i g n i f i c a n t b y - p r o d u c t . f ) n - B u t y l l i t h i u m and hexamethylphosphoramide i n d i e t h y l e t h e r An anhydrous s o l u t i o n o f 1,3-dibromoadamantane i n e t h e r (25 ml) and HMPA (3.0 ml) v/as p r e p a r e d i n 100 ml t h r e e - n e c k e d round bottomed f l a s k under an i n e r t atomosphere. The s o l u t i o n was c o o l e d t o -30°C b e f o r e 0.88 M n - b u t y l l i t h i u m i n n-hexane (5.0 ml) v/as added (5 min) to the r a p i d l y s t i r r e d s o l u t i o n by s y r i n g e t h r o u g h a serum cap. A f t e r a d d i n g n - b u t y l l i t h i u m s o l u t i o n (1.5 m l ) , a t h i c k and m i l k y phase formed, o n l y t o d i s a p p e a r a f t e r more n - b u t y l l i t h i u m s o l u t i o n (4.0 ml) was added. The r e a c t i o n m i x t u r e v/as a l l o w e d to r e a c h room tempera-t u r e b e f o r e i t v/as e x t r a c t e d f o u r t i m e s w i t h d eoxygenated, n i t r o g e n s a t u r a t e d w a t e r ( t o t a l , 40 m l ) . The o r g a n i c l a y e r was d i l u t e d (50.0 ml) i n a v o l u m e t r i c f l a s k a f t e r d r y i n g v / i t h magnesium s u l f a t e under a n i t r o g e n atmosphere and f i l t e r i n g o f f the d r y i n g a g e n t . Comparison o f t h i s s o l u t i o n w i t h an a u t h e n t i c adamantane s o l u t i o n by a n a l y t i c a l g l p c u s i n g a base-washed Carbowax column a t 80°C, d i s c l o s e d the y i e l d o f DHA (0.328 g, 7 2 % ) . U s i n g t h i s p r o c e d u r e , o n l y a t r a c e o f adamantane was produced. I n a t y p i c a l experiment 1 t o 2% o f the s t a r t i n g m a t e r i a l remained. A b y - p r o d u c t - 124 -( c a . 5%) was i s o l a t e d by column chromatography on Woelm grade I n e u t r a l a l u m i n a . I t s nmr spectrum ( C C l ^ ) had the f o l l o w i n g r e s o n a n c e s : 2.24, s h a r p s i n g l e t , 4 p r o t o n s o f C-8 and 9 m e t h y l e n e s ; 2.16, ob s c u r e d s i n g l e t , 2 p r o t o n s o f C-2 methylene; 2.06, s h a r p s i n g l e t , 2 p r o t o n s o f C-6 methylene; 1.66, u n r e s o l v e d m u l t i p l e t , 2 p r o t o n s o f C-5 and 7 b r i d g e h e a d s ; 1.50, s h a r p s i n g l e t , 4 p r o t o n s o f the C-4 and 10 m e t h y l e n e s ; 1.20, s h a r p u n r e s o l v e d m u l t i p l e t , 6 p r o t o n s o f the n - b u t y l m e t h y l e n e s ; and 0.88 £ , t r i p l e t , 3 p r o t o n s o f the n - b u t y l m e t h y l group. 4. P r e p a r a t i o n o f DHA from l,5,5»7-Tetrabromoadamantane a) Sodium-potassium a l l o y i n n-heptane The u s u a l a p p a r a t u s was d r i e d , a s sembled, and purged w i t h n i t r o g e n gas. A s o l u t i o n o f 1,3,5,7-tetrabromoadamantane (1.537 g, 3.4 x 10*~ 3 moles) i n d r y n-heptane (60.0 ml) a t o 100 + 3 C was p r e p a r e d i n t h i s a p p a r a t u s b e f o r e the sodium-p o t a s s i u m a l l o y (1.215 g, 1:5.17 by w e i g h t ) was added t o the f l a s k from a d r y n i t r o g e n gas f i l l e d m i c r o p i p e t t e . The a l l o y was d i s p e r s e d i n t o a v e r y f i n e s u s p e n s i o n by h i g h speed s t i r r i n g (3-4 m i n ) . T h i s u n i n i t i a t e d r e a c t i o n (10 h r s ) was m o n i t o r e d by o b s e r v i n g the d i s a p p e a r a n c e o f s t a r t i n g m a t e r i a l by a n a l y t i c a l g l p c u s i n g the P h e n o x y s i l i c o n e g r e a s e o column a t 240 C # - 125 -Upon c o m p l e t i o n , a n a l y t i c a l g l p c u s i n g the Carbowax o column a t 80 C, i n d i c a t e d t h a t adamantane (O.O664 g, and DHA (0.155 g, 35%) were tne o n l y v i s i b l e compounds produced. These peaks v/ere i d e n t i f i e d by s u p e r p o s i t i o n w i t h a u t h e n t i c m a t e r i a l . The presence o f the sought s y m m e t r i c a l 1,3,5,7-dehydroadamantane compound was not o b s e r v e d . S i m i l a r l y , no compounds c o r r e s p o n d i n g to 5,7-dibromo-DHA o r 5-bromo-DHA were obse r v e d by g l p c . D u r i n g the r e a c t i o n , o n l y the g l p c t r a c e s o f 1-bromoadaraantane, 1,3-dibromoadamantane and 1 , 3 , 5 - t r i b r o m o -adamantane were obse r v e d and i d e n t i f i e d by s u p e r i m p o s i t i o n w i t h the a u t h e n t i c compounds. Temperature programmed g l p c v/as performed u s i n g the P h e n o x y s i l i c c n e g rease column, 0 (240°C/20 min 2 0 C / m x r W 2 7 5 ° C ) , and the s i l i c o n e e l a s t o m e r column (240°C/15 min 2 0 C / m i n » » . 2 7 5 0 C ) , and the b a s e -o washed Carbowax column a t 200 C f o r more than 90 min. A n a l y t i c a l temperature programmed and r e g u l a r g l p c o f a l i q u o t s t r e a t e d w i t n i o d i n e showed no peak v/ i t h a r e t e n t i o n time c o r r e s p o n d i n g to t h a t o f the 1 , 3 , 5 , 7 - t e t r a i o d o a d a m a n t a n e . The major p r o d u c t , 1,3-di-iodoadamantane, was i d e n t i f i e d on the Carbowax column by s u p e r i m p o s i t i o n w i t h a u t h e n t i c m a t e r i a l . b) Sodium-potassium a l l o y i n d i e t h y l e t h e r A s o l u t i o n o f 1,3,5,7-tetrabromoadamantane (1.537 g) i n d r y d i e t h y l e t h e r (75 ml) was p r e p a r e d i n the u s u a l - 126 -a p p a r a t u s . Under anhydrous and o x y g e n - f r e e c o n d i t i o n s sodium-potassium a l l o y (1.301 g, 1:5.17 by w e i g h t ) was d e l i v e r e d from a d r y n i t r o g e n f l u s h e d m i c r o p i p e t t e and d i s p e r s e d i n t o a f i n e s u s p e n s i o n . T e r t i a r y - b u t y l a l c o h o l ( c a . 0.05 ml) was added to i n i t i a t e the r e a c t i o n . The r e a c t i o n was m o n i t o r e d by a n a l y t i c a l g l p c u s i n g o the P h e n o x y s i l i c o n e g rease column a t 2^0 C. D u r i n g the r e a c t i o n , d e c r e a s i n g t r a c e a r e a s were o b s e r v e d f o r 1,3,5-tribromoadamantane, 1,3-dibromoadamantane, and 1-bromoadamantane. A t c o m p l e t i o n (1.5 h r ) no companion peaks which might i n d i c a t e the presence o f 5,7-dibromo-1,3-dehydroadamantane and 5-bromo-l,3-dehydroadamantane were o b s e r v e d u s i n g the base-washed Carbowax column a t o 200 C. Adamantane and DHA were o b s e r v e d u s i n g t h i s o Carbowax column a t 80 C. The prime o b j e c t o f t h i s e x p e r i -ment, 1,3,5,7-didehydroadamantane was n o t o b s e r v e d . An e x a m i n a t i o n o f a l i q u o t , t i t r a t e d w i t h i o d i n e and bromine i n the manner d e s c r i b e d i n the p r e c e d i n g e xperiment f a i l e d t o i n d i c a t e the p r e s e n c e o f 1 , 3 , 5 , 7 - t e t r a i o d o a d a m a n t a n e , o r 1,3,5,7-tetrabromoadamantane on e i t h e r the carbowax o r s i l i c o n e l a s t o m e r columns a t t h e i r maximum t e m p e r a t u r e s . The r e a c t i o n p r o d u c t (0.176 g) was i s o l a t e d by d i s t i l l a -t i o n - s u b l i m a t i o n . A n a l y t i c a l g l p c u s i n g the Carbowax o column a t 80 C de t e r m i n e d the y i e l d o f adamantane - 127 -(0.026 g, 5.8%) and DHA (0.150 g, 33.8%). A d d i t i o n a l DHA (8.6%) was found i n the d i s t i l l a t e . 5. P r e p a r a t i o n o f DHA from 1 , 3 , 5-Tribromoadamantane a) Sodium-potassium a l l o y i n d i e t h y l e t h e r w i t h o u t  i n i t i a t o r Dry n i t r o g e n was used t o c l e a r the oxygen from the anhydrous a p p a r a t u s w h i c h i s d e s c r i b e d i n the pr o c e d u r e f o r p r e p a r i n g DHA from 1 ,3-dibromoadamantane w i t h p o t a s s i u m i n n-heptane. A s o l u t i o n o f 1 , 3 , 5-tribromoadamantane (1.265 g, 3.4 x 10*~3 moles) i n d r y e t h e r (50.0 ml) was p r e p a r e d i n t h i s a p p a r a t u s . A d r y o x y g e n - f r e e m i c r o p i p e t t e was used t o d e l i v e r the sodium-potassium a l l o y (0.941 g, 1:5.17 by w e i g h t ) i n t o the r e a c t i o n f l a s k . S e v e r a l m i n u t e s o f h i g h speed s t i r r i n g d i s p e r s e d the a l l o y i n t o a f i n e s u s p e n s i o n . The d i s a p p e a r a n c e o f 1 , 3 , 5-tribromoadamantane, 3.1 min, was f o l l o w e d by a n a l y t i c a l g l p c u s i n g the Phenoxy-O o / s i l i c o n e g r e a s e column a t 240 C, 48 ml/min. No 1 ,3,5-tribromoadamantane was e v i d e n t i n the g l p c t r a c e (1 h r ) . The r e a c t i o n p r o d u c t s were i s o l a t e d by d i s t i l l a t i o n -s u b l i m a t i o n . The u s u a l c r y s t a l l i n e w h i t e s o l i d (0.248 g) was o b t a i n e d . By a n a l y t i c a l g l p c , u s i n g the Carbowax column, the r a t i o o f adamantane (0.031 g, 6.5%) to DHA - 128 -(0.218 g, 47.8%) i n the s u b l i m a t e was found t o be 1:7.21. E n t r a i n m e n t by the d i s t i l l a t e a c c o u n t e d f o r an a d d i t i o n a l amount o f DHA ( 8 . 3 % ) . b) Sodium-potassium a l l o y i n d i e t h y l e t h e r v / i t h an  i n i t i a t o r Anhydrous and oxy g e n - f r e e c o n d i t i o n s v/ere e s t a b l i s h e d i n the u s u a l a p p a r a t u s . The 1,3,5-tribromoadamantane (1.00 g, 2.67 x 1 0 " 3 moles) was d i s s o l v e d i n d r y e t h e r (50.0 m l ) . The sodium-potassium a l l o y (0.74 g> 1:5.17 by w e i g h t ) was added to the a p p a r a t u s from a d r y i n e r t atmosphere f i l l e d m i c r o p i p e t t e . A f t e r n e g l i g i b l e p r o g r e s s (20 m i n ) , the t e r t i a r y - b u t y l a l c o h o l i n i t i a t o r ( c a . 2 ml) was added (0.05 ml/15 s e c ) from a d r o p p i n g f u n n e l w i t h s i d e arm. The r e a c t i o n was s t i r r e d f o r a f u r t h e r p e r i o d (25 min; t o t a l , 65 min) b e f o r e a n a l y t i c a l g l p c , u s i n g the o P h e n o x y s i l i c o n e grease column a t 240 C, 48 ml/min, showed no s t a r t i n g m a t e r i a l , 3.1 min, remained. The c o l o r l e s s v o l a t i l e m i x t u r e (0.264 g) was i s o l a t e d by d i s t i l l a t i o n - s u b l i m a t i o n . A t i n y sample was d i s s o l v e d 0 i n e t h e r . U s i n g the Carbov/ax column a t 80 C, a n a l y t i c g l p c o f t h i s s o l u t i o n shov/ed the r a t i o o f adamantane (0.036 g, 9.9%) and DHA (0.228 g, 63.5%) to be 1:6.5. The y i e l d s were c a l c u l a t e d from t h i s r a t i o and the s u b l i m a t e w e i g h t . - 129 -C. R e a c t i o n s o f 1,3-DQhydroadamantane 1. R e a c t i o n o f DHA v/i t h Oxygen - P r e p a r a t i o n o f  Polyperoxyadamantane A s o l u t i o n o f adamantane (0.033 g) and DHA (0.367 g) i n n-heptane (50.0 ml) v/as p r e p a r e d i n a 100 ml s i n g l e necked round bottom f l a s k . Oxygen (25 ml/min) v/as bub b l e d t h r o u g h t h i s s o l u t i o n f o r 15 h r s . The s u p e r n a t a n t l i q u i d was s e p a r a t e d from the f l o c u l e n t w h i t e p r e c i p i t a t e by s u c t i o n f i l t r a t i o n t h r o u g h a s i n t e r e d g l a s s f u n n e l o f medium c o a r s e n e s s . By u s i n g the Carbowax column (80°C/6 min 3 2 • C / / m : L n a » 2 0 O C ) , t h i s s u p e r n a t a n t l i q u i d v/as shown t o c o n t a i n o n l y one major compound and many minor compounds. T h i s major compound v/as a p p a r e n t l y formed by the t h e r m a l d e c o m p o s i t i o n o f the s o l u b l e f r a c t i o n o f the peroxypolymer i n the i n p u t m a n i f o l d o f the g l p c . T h i s major compound v/as found t o be s u p e r -p o s a b l e w i t h a u t h e n t i c 1,3-dihydroxyadamantane*, 90 min, u s i n g the above Carbowax column a t 200°C, 68 ml/min. No assymmetry o r b r o a d e n i n g o f the major compound g l p c t r a c e A u t h e n t i c 1,3-dihydroxyadamantane was p r e p a r e d from 1,3-dibromoadamantane by a method S t e t t e r and Wulf9 used t o p r e p a r e 1-hydroxyadamantane from 1-bromoadamantane. A poor y i e l d o f 1,3-dihydroxyadamantane was o b t a i n e d . R e c r y s t a l l i z a t i o n s e v e r a l t i m e s c h l o r o f o r m gave an a n a l y t i c a l l y pure sample o f 1,3-dihydroxyadamantane. - 130 -compared w i t h the a u t h e n t i c compound t r a c e was n o t e d . T h i s t h e r m a l d e c o m p o s i t i o n a l s o was the s o u r c e o f many of the minor g l p c t r a c e s . By comparison w i t h an a u t h e n t i c s o l u t i o n an e s t i m a t e was made o f 1,3-dihydroxyadamantane (0.045 g, 10.4%) i n the s u p e r n a t a n t l i q u i d (0.211 g, 46%). The f l u f f y w h i t e s o l i d (0.211 g, 46%) was t r i t u r a t e d o i n benzene, s u c t i o n f i l t e r e d and d r i e d i n vacuo a t 50 C o v e r n i g h t t o g i v e an a n a l y t i c a l sample, ep ( e x p l o s i o n o p o i n t ) 146 C. The polymer was n o t s o l u b l e i n any o f the common o r g a n i c s o l v e n t s . The i n f r a r e d spectrum ( n u j o l m u l l ) showed a t : ill 3 .X 3400 (m), 1755 ( s h o u l d e r ) , 1720 ( s ) , 1360 ( s ) , 1320 ( s ) , 1280 ( s ) , 1240 (w), 1150 (w), 1115 ( s ) , 1097 ( s h o u l d e r ) , 1040 (w), 995 ( s ) , 940 (m), 895 (m), 835 (w), 800 (w), and 775 era" 1 (w). A n a l . C a l c d . f o r c 1 0 H l i f 0 2 : C, 72.26; H, 8.49. Found: C, 72.55; H, 8 . 2 8 . 7 9 a a) R e d u c t i o n o f the peroxypolymer The r e a c t i o n was c a r r i e d out i n a d r y s i n g l e necked 100 ml round bottomed f l a s k f i t t e d w i t h an e t h e r condenser and d r y i n g t u b e . The peroxypolymer (0.052 g) was t r e a t e d w i t h a s u s p e n s i o n o f l i t h i u m aluminum h y d r i d e (1.0 g) i n - 131 -d r y r e f l u x i n g e t h e r (60.0 ml) f o r 45 h r . Water (1.0 ml) then 1 5 % sodium h y d r o x i d e (1.0 ml) f o l l o w e d a g a i n by water (3»1 ml) was added d r o p w i s e t o s t o p the r e a c t i o n . The g r a n u l a r p r e c i p i t a t e o f i n o r g a n i c s a l t s was s u c t i o n f i l t e r e d from the s u p e r n a t a n t l i q u i d . Tne e t h e r l a y e r was e x t r a c t e d w i t h w a t e r (15 m l ) , d r i e d o v er anhydrous sodium s u l f a t e , and f i l t e r e d . The s o l v e n t was removed by r o t a r y e v a p o r a t i o n t o g i v e a c r y s t a l l i n e w h i t e s o l i d (0.029 g ) . A n a l y t i c a l g l p c u s i n g the Carbowax column a t o 200 C, 68 ml p e r min, snowed one major compound, 9.0 m i n , ; a n d many v e r y minor ones. The i d e n t i c a l r e t e n t i o n time o f a u t h e n t i c 1,3-dihydroxyadamantane and the major r e d u c t i o n p r o d u c t as w e l l as the o b s e r v e d a n a l y t i c a l g l p c t r a c e enhancement on t h i s same column r e s u l t i n g from enrichment o f the p r o d u c t s o l u t i o n w i t h a u t h e n t i c d i h y d r o x y compound i d e n t i f i e d t h i s p r o d u c t . Two r e c r y s t a l l i z a t i o n s from c h l o r o f o r m y i e l d e d f i n e w n i t e n e e d l e - l i k e c r y s t a l s (0.021 g) whose i n f r a r e d and nmr s p e c t r a were i d e n t i c a l w i t h the s p e c t r a o f the a u t h e n t i c 1,3-dihydroxyadamantane. 2. H a l o g e n a t i o n o f DHA o a) B r o m i n a t i o n o f DHA i n n-Heptane a t -75 0 A r a p i d l y s t i r r e d s o l u t i o n o f DHA (0.260 g) i n n-o heptane (10.0 ml) a t -75 0 under an i n e r t atmosphere was - 132 -t i t r a t e d w i t h bromine (0.668 g ) . The r e s u l t i n g f l o c u l e n t p a l e - y e l l o w p r e c i p i t a t e was c o l l e c t e d i n a s i n t e r e d g l a s s Buchner f u n n e l , c o o l e d by p a s s i n g n-heptane (5 n i l ) a t o -75 0 through the f u n n e l , f o l l o w e d by a few ml of l i q u i d a i r . D u r i n g the f i l t r a t i o n , the f u n n e l was c o o l e d by c o l d a i r g e n e r a t e d by p a s s i n g a i r t h r o u g h l i q u i d a i r . Passage o f warm a i r t h r o u g h the p a l e y e l l o w f l u f f y p r e c i p i t a t e caused a c o l o u r change from y e l l o w t o orange. F u r t n e r passage o f a i r l e f t a w h i t e s o l i d (0.527, 91.8%) i d e n t i f i e d as 1,3-dibromoadamantane by g l p c t r a c e s u p e r p o s i t i o n and i n f r a r e d and nmr s p e c t r a l comparison w i t h s p e c t r a o f an a u t h e n t i c sample. A n a l y s i s o f the f i l t r a t e by a n a l y t i c a l g l p c ( a f t e r r e m o v a l o f e x c e s s bromine w i t h s o l i d p o t a s s i u m c a r b o n a t e ) d i s c l o s e d the presence o f more 1,3-dibromoadamantane (0.042 g, 7.3%; t o t a l y i e l d ; 9 9 % ) . b) B r o m i n a t i o n o f DHA i n D i e t h y l E t h e r a t -75°C i ) D e c o m p o s i t i o n o f the i n t e r m e d i a t e i n e t h e r A r a p i d l y s w i r l e d e t h e r s o l u t i o n (25.0 ml) c o n t a i n i n g DHA (0.167 g) a t -75°C was t i t r a t e d w i t h bromine (0.775 g). The r e s u l t i n g f l o c u l e n t l e m o n - y e l l o w p r e c i p i t a t e was o resuspended t w i c e w i t h e t h e r (50 ml) a t -75 0, s e t t l e d by - 133 -c e n t r i f u g a t i o n , and the s u p e r n a t a n t l i q u i d p i p e t t e d o f f to remove the e x c e s s bromine. The s o l i d was suspended i n e t h e r (250 ml) and p o t a s s i u m o c a r b o n a t e (4 g) a t -75 0 was added b e f o r e a l l o w i n g the s t i r r e d s u s p e n s i o n to r e a c h room t e m p e r a t u r e . The i n o r g a n i c s o l i d s were removed by f i l t r a t i o n and the f i l t r a t e c o n c e n t r a t e d by r o t a r y e v a p o r a t i o n . The r e s u l t a n t brown o i l was d i l u t e d (25.0 ml) w i t h oenzene. o Q u a l i t a t i v e g l p c u s i n g the u s u a l Carbowax column a t 200 C, 51.5 ml/min, i n d i c a t e d the presence o f 1,3-dibromoadamantane (0.113 g, 28.7%), 7.0 min, and a n o t h e r p r o d u c t (0.24 g, 67.8%), 5.5 min assaye d by comparison o f t h i s p r o d u c t w i t h a s t a n d a r d 1,3-dibromoadamantane s o l u t i o n . The major p r o d u c t , l-bromo-3-ethoxyadamantane, was i s o l a t e d by column chromatography o f the r e a c t i o n m i x t u r e on V/oelm grade I n e u t r a l a l u m i n a (15 g ) . 1,3-Dibromoaaamantane (0.109 g) was e l u t e d w i t h c y c l o h e x a n e (250 m l ) . The major p r o d u c t (0.077 was e l u t e d w i t h 9:1 cyclohexane:benzene (80 ml) and then 1:1 cyclohexane:benzene (200 ml) e l u t e d more major p r o d u c t (0.048 g ) . F l u s h i n g the column w i t h c h l o r o f o r m (100 ml) gave a brown o i l (0.050 g) c o n s i s t i n g m a i n l y o f the major p r o d u c t . The i n f r a r e d spectrum o f the neat compound showed the f o l l o w i n g V m a x : 2940 ( s ) , 1480 (w), 1388 (w), 1360 (w), - 134 -1340 (m), 1320 (m), 1295 (m), 1280 (w), s h o u l d e r , 1233 (w), 1158 (w), 1113 ( s ) , 1090 ( s ) , 1050 (m), 964 ( s ) , 940 (w), 972 (m), 824 ( s ) , 788 (w), and 738 cm" 1 (m). The nmr spectrum ( c h l o r o f o r m - d ) gave the f o l l o w i n g r e s o n a n c e s : 3.47 q u a r t e t , J = 7.0 Hz, 2 p r o t o n s o f the e t h o x y l methylene; 2.29, u n s y m m e t r i c a l d o u b l e t , 8 p r o t o n s o f the C-5 and 7 b r i d g e h e a d and C-3,9 and 10 m e t h y l e n e s ; 1.27, u n s y m m e t r i c a l d o u b l e t , 6 p r o t o n s o f the C-4,6 and 8 methylenes; and 1.148 > t r i p l e t , J = 7.0 Hz, 3 p r o t o n s o f the etnoxy m e t h y l . The nmr spectrum (benzene) gave the f o l l o w i n g r e s o n a n c e s : 3.19, q u a r t e t , J = 7.0 Hz, 2 p r o t o n s o f the e t h o x y l methylene; 2.29, s i n g l e t , 2 p r o t o n s o f the C-2 methylene; 2.03, u n s y m m e t r i c a l d o u b l e t , 4 p r o t o n s o f the C-9 and 10 methylenes; 1.79, u n r e s o l v e d m u l t i p l e t , 2 p r o t o n s o f the C-5 and 7 b r i d g e h e a d s ; 1.47, u n s y m m e t r i c a l d o u b l e t , 4 p r o t o n s o f the C-4 and 8 m e t h y l e n e s ; 1.17, u n r e s o l v e d m u l t i p l e t , 2 p r o t o n s o f the C-6 methylene; and 1.0b6, t r i p l e t , J = 7.0 Hz, 3 p r o t o n s o f the ethoxy m e t h y l . I n the mass spectrum o f the compound ( m o l e c u l a r w e i g h t , 258, 260) no p a r e n t peak was seen: m-45 were the f i r s t peaks o b s e r v e d . A n a l . C a l c d . f o r C^H-^OBr: C, 55.7; H, 7.34; B r , 30.9. Found: C, 55.50; H, 7.21; B r , 30.79. - 135 -a) C o n v e r s i o n of l-bromo~3-cthoxyadamantane to 1,3-dibromoadainantane To l-bromo-3-ethoxyadamantane (O.298 g) i n benzene (0.2 ml) c o n t a i n e d i n - a 10 ml round bottomed f l a s k a s o l u t i o n o f kS% hydrogen bromide i n c o n c e n t r a t e d s u l f u r i c a c i d (10.0 ml) was added and the r e a c t i o n v/as h e a t e d on a steam b a t h (5.75 h r ) v/ith o c c a s i o n a l s v / i r l i n g and a l l o w e d to s t a n d a t room temperature o v e r n i g h t . Sodium b i c a r b o n a t e was added u n t i l t h e . a c i d was n e u t r a l i z e d . The r e m a i n i n g s a l t s and o r g a n i c r e a c t i o n p r o d u c t s v/ere d i s s o l v e d i n water (15 n i l ) and benzene (15 m l ) . The phases v/ere s e p a r a t e and the w a t e r l a y e r was b a c k - e x t r a c t e d w i t h benzene (5 m l ) . The p o o l e d benzene s o l u t i o n was d r i e d o v er anhydrous sodium s u l f a t e , s u c t i o n f i l t e r e d and d i l u t e d (25.00 ml) w i t h benzene. Comparison o f t h i s s o l u t i o n w i t h one c o n t a i n i n g a u t h e n t i c 1,3-dibromoadamantane gave the y i e l d o f the c o n v e r s i o n o f l-bromo-3-ethoxyadamantane to 1,3-dibromo-adamantane (0.253 g | 74.8/o) a f t e r c o r r e c t i n g f o r the 1,3-dibromoadamantane (0.013 g) i n the l-bromo-3-ethoxyadamantan p r e p a r a t i o n . The i d e n t i t y o f the r e a c t i o n p r o d u c t , 7.3 min, v/as e s t a b l i s h e d i n the f o l l o w i n g manner. F i r s t , u s i n g the 0 Carbowax column a t 200 C, 45 ml per min, the r e a c t i o n p r o d u c t was e n r i c h e d w i t h a u t h e n t i c 1,3-dibromoadamantane and enhancement o f the r e a c t i o n p r o d u c t peak was o b s e r v e d . Second, the crude r e a c t i o n p r o d u c t (0.287 g) was i s o l a t e d - 136 -by r o t a r y e v a p o r a t i o n and r e c r y s t a l l i z e d once from n-hexane. The i n f r a r e d spectrum of the c r y s t a l s was i d e n t i c a l to the i n f r a r e d spectrum of a u t h e n t i c 1,3-dibromoadamantane. b) C h a r a c t e r i z a t i o n o f the l e m o n - y e l l o w  p r e c i p i t a t e , (l-bromoadamant-3-yl) d i e t h y l oxonium  t r i b r o m i d e The l e m o n - y e l l o w p r e c i p i t a t e was p r e p a r e d under n i t r o g e n from 1,3-dehydroadamantane (0.157 g) i n e t h e r o (25.0 ml) a t -75 0 by the a d d i t i o n o f bromine. The e x c e s s bromine was removed by r e s u s p e n d i n g the f i n e l y d i s p e r s e d o s o l i d i n e t h e r a t -75 0, c e n t r i f u g i n g , and p o u r i n g o f f the s u p e r n a t a n t l i q u i d , u n t i l the f i n a l s u p e r n a t a n t l i q u i d was c o l o r l e s s . The p r e c i p i t a t e was d r i e d by e v a p o r a t i n g the o r e s i d u a l e t h e r under vacuum a t -75 C The p r e c i p i t a t e was suspended i n c a r b o n t e t r a c h l o r i d e (50 ml) and a l l o w e d to d i s s o l v e w h i l e r e a c h i n g room t e m p e r a t u r e . The s o l u t i o n was d i l u t e d (100.0 ml) and compared s p e c t r o p h o t o m e t r i c a l l y a t 415 mjj ( o p t i c a l d e n s i t y i n a 0.2 cm q u a r t z c e l l , 0.43 u n i t s ) w i t h a u t h e n t i c s o l u t i o n o f bromine i n c a r b o n -t e t r a c h l o r i d e (0.211 g/100.0 ml; o p t i c a l d e n s i t y i n a 0.2 cm q u a r t z c e l l , 0.54 u n i t s ) . Care was taken to m a i n t a i n d a r k c o n d i t i o n s , e.g. v o l u m e t r i c f l a s k s were wrapped i n aluminum f o i l and m a n i p u l a t i o n s were performed i n darkened rooms. By t h i s method i t was shown t h a t m o l e c u l a r bromine (0.169 g, 90.5%) was r e l e a s e d from the t r i a l k y i oxonium compound by i t s t h e r m a l d e c o m p o s i t i o n . - 137 -The m i c r o a n a l y s i s o f the i n t e r m e d i a t e i t s e l f was not s u c c e s s f u l . These v a r i a b l e r e s u l t s were o b t a i n e d due t o d e c o m p o s i t i o n b e f o r e a n a l y s i s c o u l d be c a r r i e d o u t . The i s o l a t e d p r e c i p i t a t e was found to be s o l u b l e i n m o d e r a t e l y p o l a r s o l v e n t s such as a c e t o n e , n i t r o m e t h a n e ana a c e t o n i t r i l e . The compound c o u l d oe r e p r e c i p i t a t e d from these s o l u t i o n s o by a d d i t i o n o f d i e t n y l e t h e r a t -75 C Low temperature o nmr (acetone-dg) under a n i t r o g e n atmosphere a t -65 C showed the f o l l o w i n g r e s o n a n c e s : 5.19, q u a r t e t , J = 7.0 Hz, 4 p r o t o n s o f the oxonium e t h e r m e t h y l e n e s ; 3*37, q u a r t e t , methylene o f the t r a c e o f e t h e r s o l v e n t ; 3 . 0 7 , s i n g l e t , 2 p r o t o n s o f the C-2 methylene; 2.59, s i n g l e t , 6 p r o t o n s o f the C-9 and 10 methylenes and C-5 and 7 b r i d g e h e a d s ; 2 . 3 6 , s i n g l e t , 4 p r o t o n s o f the C-4 and 10 methylenes; 2.15, q u i n t e t , t r a c e o f acetone i n s o l v e n t ; 1.71, complex t r i p l e t , 8 p r o t o n s o f the oxonium e t h e r m e t h y l s and C-6 methylene; and 1.10 S, t r i p l e t , m e t h y l o f the t r a c e o f e t h e r s o l v e n t . By r a i s i n g the temperature s l o w l y the spectrum o f the o i n t e r m e d i a t e compound was shown t o change r a p i d l y a t -25 C ( o v e r 10 m i n ) . At -35 C v e r y l i t t l e change was.observed. i i ) D e c o m p o s i t i o n o f the i n t e r m e d i a t e i n 9 5 %  e t h a n o l A r a p i d l y s w i r l e d e t h e r s o l u t i o n (250 ml) o f DHA (0 .165 g) a t -75-0 under n i t r o g e n was t i t r a t e d w i t h bromine - I j o -(0.58 g ) . The s u p e r n a t a n t l i q u i d was removed and the o p r e c i p i t a t e was washed t w i c e w i t h e t h e r (50 ml) a t -75 C.< The r e s i d u a l e t h e r was removed by e v a p o r a t i o n i n vacuo a t o -75 0. The l e m o n - y e l l o w s o l i d was suspended, s t i r r e d i n 9 5 % e t h a n o l (950 ml) c o n t a i n i n g anhydrous powdered p o t a s s i u m c a r b o n a t e (4 g ) , and a l l o w e d to r e a c h room temperature o v e r n i g h t . T h i s m i x t u r e was f i l t e r e d then r e d u c e d to an o i l by r o t a r y e v a p o r a t i o n . The r e s i d u e v/as t a k e n up i n c h l o r o f o r m , washed v/ith w ater and the o r g a n i c l a y e r d r i e d o v er anhydrous sodium s u l f a t e f i l t e r e d and the l i q u i d e v a p o r a t e d . The r e s i d u e was d i l u t e d w i t h benzene (25.0 m l ) . A n a l y t i c a l g l p c showed t h a t an e x c e l l e n t y i e l d o f 1-bromo-3-ethoxyadamantane (0.298 g, 93.0%) had been o b t a i n e d . A n a l y t i c g l p c r e v e a l e d more 1,3-dibromoadamantane (0.056, 1.5%) and l-bromo-3-ethoxyadamantane (0.0072 g, 2.2%) i n the p o o l e d e t h e r v/ashings. i i i ) D e c o m p o s i t i o n o f the i n t e r m e d i a t e i n a c e t o n e - sodium i o d i d e s o l u t i o n A r a p i d l y s w i r l e d e t h e r s o l u t i o n (25.0 ml) o f DHA o (0.134 g) a t -75 0 was t i t r a t e d w i t h bromine (0.445 g ) . The l e m o n - y e l l o w p r e c i p i t a t e was v/ashed t h r e e t i m e s w i t h o e t h e r a t -75 0, and the s u p e r n a t a n t l i q u i d v/as removed. The r e s i d u a l e t h e r was removed by h i g h vacuum pumping (8 h r ) a t o o -75 0. Acetone (25 ml) a t the same temperature (-75 0) was used to d i s s o l v e the d r y s o l i d . T h i s a cetone s o l u t i o n - 139 -was added r a p i d l y to a s o l u t i o n o f acetone (200 ml) a t o -75 0 c o n t a i n i n g sodium i o d i d e (1.0 g ) . An immediate change (3 min) from y e l l o w to a deep wine c o l o r r e s u l t e d . The c r y s t a l s o f i o d i n e s e t t l e d out c o m p l e t e l y (0.5 h r ) . The s u p e r n a t a n t l i q u i d was decanted and s t i r r e d (16 h r ) v/i t h anhydrous sodium s u l f i t e (5 g) t o remove the f r e e i o d i n e . The s o l v e n t was removed by r o t a r y e v a p o r a t i o n and the r e s i d u e p a r t i t i o n e d betv/een water-benzene. The o r g a n i c l a y e r was d r i e d and c o n c e n t r a t e d (25.0 m l ) . Q u a n t i t a t i v e g l p c o f t h i s s o l u t i o n , i n d i c a t e d t h a t o n l y l-bromo-3-ethoxyadamantane (0.277 g, 100%) was p r e s e n t i n a q u a n t i -t a t i v e amount. No o t h e r compound was v i s i b l e i n the g l p c o t r a c e u s i n g the Carbowax column (80°C/6 min 3 2 C/min ^ o 200 C ) . The i d e n t i t y o f the r e a c t i o n p r o d u c t v/as c o n f i r m e d by s u p e r i m p o s i t i o n o f a u t h e n t i c l-bromo-3-ethoxyadamantane on two d i f f e r e n t a n a l y t i c a l g l p c columns*, as w e l l as by i t s i n f r a r e d spectrum w h i c h v/as i d e n t i c a l v / i t h t h a t o f a n a l y t i c a l l y pure l-bromo-3-ethoxyadamantane. i v ) D e c o m p o s i t i o n o f the i n t e r m e d i a t e i n acetone-sodium c y a n i d e s o l u t i o n The complex was p r e p a r e d by t i t r a t i n g DHA (0.134 g) o d i s s o l v e d i n e t h e r (25.0 ml) a t -75 0 under a n i t r o g e n * o The Carbowax column a t 200 C and P h e n o x y s i l i c o n e g r ease column a t 170 €C were used. - 140 -atmosphere w i t n bromine (0.560 g ) . The p r e c i p i t a t e was washed and d r i e d as d e s c r i b e d i n the p r e v i o u s e x p e r i m e n t . o The s o l u t i o n o f the complex i n acetone (25 ml) a t -75 C was added to a s u s p e n s i o n o f sodium c y a n i d e (0.34 g) i n acetone (200 ml) and s t i r r e d a t - 7 5 ° C The s o l u t i o n became c o l o r l e s s (4 h r ) . The s o l v e n t was removed by r o t a r y e v a p o r a t i o n and the r e s i d u e p a r t i t i o n e d between w a t e r and benzene. The o r g a n i c l a y e r was d r i e d and c o n c e n t r a t e d (25.0 m l ) . Q u a l i t a t i v e g l p c * i n d i c a t e d o n l y l-bromo-3-ethoxyadamantane (0.271 g) was p r e s e n t . The i d e n t i t y o f the r e a c t i o n p r o d u c t was c o n f i r m e d by peak enhancement s t u d i e s * * w i t h a n a l y t i c a l l y pure l-bromo-3-ethoxyadamantane. F u r t h e r m o r e , the i n f r a r e d spectrum o f the r e a c t i o n p r o d u c t and t h a t o f a n a l y t i c a l l y pure l-bromo-3-ethoxyadamantane were found t o be the same. No g l p c t r a c e w h i c h might i n d i c a t e the presence o f l-bromo-3-cyanoadamantane was o b s e r v e d . v) D e c o m p o s i t i o n o f the i n t e r m e d i a t e i n acetone  s o l u t i o n s o B r o m i n a t i o n o f DHA i n d i e t h y l e t h e r a t -75 C under n i t r o g e n was performed. The y e l l o w p r e c i p i t a t e was i s o l a t e d * The Carbowax column v/as used w i t h the u s u a l temperature program. ** o The above column a t 200 C and the P h e n o x y s i l i c o n e grease column a t 170 C were used. - 1 4 1 -o a t - 7 5 C by s w i r l i n g , s e t t l i n g the p r e c i p i t a t e by c e n t r i -f u g a t i o n and then p i p e t t i n g o f f the s u p e r n a t a n t l i q u i d and a d d i n g more c o l d e t h e r u n t i l the f i n a l s u p e r n a t a n t l i q u i d was c o l o r l e s s . The r e s i d u a l s o l v e n t was removed by o e v a p o r a t i o n a t -30 C under h i g h vacuum. The l e m o n - y e l l o w s o l i d was d i s s o l v e d i n acetone ( 5 0 ml) a t - 7 5 ° 0 and then d i l u t e d w i t h acetone s o l u t i o n s ( t o 2 5 0 ml) a t the same temp e r a t u r e c o n t a i n i n g v a r i o u s s o l v e n t a d d i t i v e s (TABLE I V ) , b e f o r e b e i n g a l l o w e d t o r e a c h room t e m p e r a t u r e . U s i n g the S i l i c o n e e l a s t o m e r column* a t 1 7 0°C, 4 5 . 4 ml p e r min, the major p r o d u c t , 4 . 6 min, was shown t o be s u f f i c i e n t l y s e p a r a t e d from i t s c o - p r o d u c t t o d e t e r m i n e the y i e l d s by comparison w i t h a u t h e n t i c s o l u t i o n s . TABLE IV . S u b s t i t u t o n o f (3-Bromo-l-adamantanyl)d i e t h y l oxonium t r i b r o m i d e i n S o l v e n t M i x t u r e s A d d i t i v e s % Y i e l d o f P r o d u c t s a l - b r o m o - 3 -e t h o x y -adamantane l - b r o m o - 3 -h y d r o x y -adamantane l - a c e t o x y - 3 -bromo-adamantane 1) 2 % H 2 0 b 2 2 . 3 5 4 . 7 — 2 ) 10% H 2 0 C 2 7 . 1 5 3 . 1 — 3 ) 0 . 7 % H0Ac b 3 3 . 1 4 3 . 8 0 4 ) 2 5 % H0Ac c 3 3 . 4 6 . 1 d 6 . 3 5 ) 0 . 4 % H 2 S 0 ^ e 3 2 . 8 6 1 . 2 a by a n a l y t i c a l g l p c o f p r o d u c t s o l u t i o n s , b w i t h complex from 0 . 1 6 9 8 g DHA. c w i t h complex from 0 . 1 7 1 g DHA. d decomposes under b a s i c c o n d i t i o n s o f the workup, e w i t h complex from 0 . 1 5 7 g DHA. The major p r o d u c t was o b s e r v e d t o decompose on base washed columns. On the P h e n o x y s i l i c o n e grease a c i d washed column, the r e t e n t i o n t i m e s of the ethoxy and the h y d r o x y compounds were i d e n t i c a l . - 142 -c) B r o m i n a t i o n o f DHA i n Acetone A s o l u t i o n o f c a , 5% aqueous acetone (150 ml) c o n t a i n -i n g DHA (0,128 g) was t i t r a t e d w i t h bromine under a n i t r o g e n atmosphere. The orange c o l o u r due to e x c e s s bromine q u i c k l y f a d e d (5 m i n ) . A n a l y t i c g l p c * i n d i c a t e d o n l y one r e a c t i o n p r o d u c t . The r e a c t i o n p r o d u c t was c o n c e n t r a t e d by r o t a r y e v a p o r a t i o n , r e d i s s o l v e d i n c h l o r o f o r m (40 m l ) , washed w i t h 1 0 % sodium b i c a r b o n a t e d r i e d o v er anhydrous sodium s u l p h a t e and f i l t e r e d . R o t a r y e v a p o r a t i o n gave d a r k r e d -brown o i l c o n t a m i n a t e d c r y s t a l l i n e m a t e r i a l s (0.320 g ) . A b l a n k r u n showed t h i s v i s c o u s o i l to r e s u l t from a r e a c t i o n between bromine and a c e t o n e . By f r a c t i o n a l r e c r y s t a l l i z a t i o n from c y c l o h e x a n e : benzene - 1 : 9 and once from benzene, the major p r o d u c t o f the oxonium i o n d e c o m p o s i t i o n s i n a c e t o n e , was i s o l a t e d o as a w h i t e chunky c r y s t a l l i n e compound, mp 157-158 C. o T h i s compound s u b l i m e d r e a d i l y a t 70 C under a p r e s s u r e o f 1.0 mm o f Hg. The i n f r a r e d spectrum ( n u j o l m u l l ) showed 1/... a t : nicix 3300 ( s ) , 1338 (m), 1315 (m), 1285 (m), 1205 (w), 1138 (w), 1102 ( s ) , 1090 (w), 1075 ( s ) , 1022 (w), 948 ( s ) , 933 (w), 910 ( s ) , 803 ( s ) , 772 (m), 728 ( s ) , and 665 cm""1 ( s ) . * The Carbowax and the S i l i c o n e e l a s t o m e r columns were used w i t h the f o l l o w i n g temperature programs: 0 _ (80°C/6 min ?£°C7fTli-rW000C) and (90°C/6 min 20 C/min^, 275 C) r e s p e c t i v e l y . - 143 -The nmr spectrum (benzene) showed the f o l l o w i n g r e s o n a n c e s : 2.17, s i n g l e t , 2 p r o t o n s o f tne C-2 methylene; 1.98, u n s y m m e t r i c a l d o u b l e t , 4 p r o t o n s o f the C-8 and 10 methylenes; 1.68, broad u n r e s o l v e d m u l t i p l e t , 2 p r o t o n s o f the C-5 and / b r i d g e h e a d s ; 1.35, u n s y m m e t r i c a l d o u b l e t , 4 p r o t o n s o f the C-4 and 8 methylenes; 1.19, s i n g l e t , 1 p r o t o n o f the h y d r o x y l - d i s a p p e a r e d i n the presence o f d e u t e r i u m o x i d e ; and 1.08 , t r i p l e t - p a r t l y o b s c u r e d , 2 p r o t o n s o f the C-6 methylene. F o r the nmr spectrum i n acetone-dg the f o l l o w i n g r e s o n a n c e s were o b s e r v e d : 2.22, b r o a d d o u b l e t , 7 p r o t o n s o f the C-2,9 and 10 methylenes and h y d r o x y l ; 2.05, broad m u l t i p l e t o f the C-5 and 7 b r i d g e h e a d s - o b s c u r e d by s o l v e n t , 2 p r o t o n s ; and 1.67 & , broad m u l t i p l e t , 6 p r o t o n s o f the C-4 and 10 methylenes and tne C-6 methylene. The mass spectrum showed p a r e n t peaks w i t h m/e+ a t 230, 232, i d e n t i c a l w i t h the v a l u e s c a l c u l a t e d f o r C-^H^^-OBr. A n a l . C a l c d . f o r O ^ H ^ B r : C, 52.00; H, b.48; B r , 34.60. Found: C, 52.00; H, 6.6; B r , 34.90. i ) R i n g o p e n i n g o f l-bromo-5-hydroxyadamantane  t o the "enone" ( 3 - k e t o - 7 - m e t h y l e n e B i c y c l o ,5. ,3.1 nonane) The compound, 3-keto-7-metnylene b i c y c l o [£ , 3 ,-^J nonane, had r e s u l t e d from case c a t a l y z e d r i n g o p e ning o f 1 , 3 - d i s u b s t i t u t e d adamantane compounds v/ith l a b i l e hydrogens - 144 -on one of these substituents. The compound, l-bromo-3-hydroxyadamantane, formed from the addition of water during the bromination of DHA would s a t i s f y t h i s c r i t e r i o n ; thus base catalyzed treatment of th i s compound was undertaken to further prove the structure of the compound which spectroscopic evidence indicated to be l-bromo-3-hydroxy-adamantane. An ether solution (10.0 ml) containing l-bromo-3-hydroxyadamantane (0.110 g) was s t i r r e d (4.5 hr) with aqueous sodium hydroxide (0.5 ml; 0.093*0; then more of the same base (0.1 ml, IN) was added and the reaction continued to completion (1 h r ) . The progress of the reaction was followed using the Phenoxysilicone grease column at 180°C, 47.6 ml/min, to note the disappearance of l-bromo-3-hydroxyadamantane, 6.1 min, and the appearance of 3-keto-7-methylene bicyclo |^«5.lj nonane, 2.2 min. The ether was removed by rotary evaporation and the o i l y residue was diluted with benzene (10.00 ml). o Analytic glpc using the Carbowax column at 160 C indicated that the (0.0716 g, 100%) enone v/as present i n the reaction product sol u t i o n . The i d e n t i t y of the reaction product v/as v e r i f i e d by superimposition v/ith authentic "enone"* on 2 d i f f e r e n t glpc columns**. The minor product formed i n the presence of 2 5 % HoAc * This compound v/as kindly donated by Dr. V/. B. Scott. ** The columns used are the ones mentioned above at the given temperatures and flov/rates. was i d e n t i f i e d by s u p e r i m p o s i t i o n w i t h a u t h e n t i c l - a c e t o x y -3-bromoadamantane* on 2 d i f f e r e n t g l p c columns**. i i ) A c e t y l a t i o n o f l-bromo-3-hydroxyadamantane The a u t h e n t i c l-acetoxy-3-bromoadamantane was p r e p a r e d by a c e t y l a t i o n o f l-bromo-3-hydroxyadamantane (0.130 g) i n a c e t i c a n h y d r i d e (1 ml) c a t a l y z e d by 1 drop ( c a . 0.05 ml) o f c o n c e n t r a t e d s u l f u r i c a c i d . The r e a c t i o n m i x t u r e was poured i n t o i c e w a t e r and e x c e s s 1 0 % sodium b i c a r b o n a t e s o l u t i o n was added. Column chromatography o f the n e u t r a l r e a c t i o n p r o d u c t (0.136 g) was performed on grade I Woelm n e u t r a l a l u m i n a (15 g ) . A c e n t r a l f r a c t i o n on the peak e l u t e d w i t h e q u a l p a r t s o f c h l o r o f o r m e t h e r y i e l d e d an o i l (0.075 g) w h i c h was shown to c o n s i s t o f o n l y one compound; 9.2 and 11.9 min by a n a l y t i c a l g l p c u s i n g the S i l i c o n e e l a s t o m e r column a t 170°C, 45.6 ml/min o r the P h e n y l s i l o x a n e grease column a t o _ 170 C, 48.O ml/min, r e s p e c t i v e l y . . The i n f r a r e d spectrum showed a t : 1745 ( s ) s a t u r a t e d c a r b o n y l s t r e t c h i n g , 1345 (w), 1320 (w), 1230 ( s ) , 1160 (w), 1100 (w), 1062 ( s ) , 1020 (w), 1010 (w), 967 ( s ) , 940 (m), 872 (w), 824 ( s ) , 790 (m), 748 (w), 739 (m), and 694 cm" 1 (m). * R e f e r t o experiment 2 . c ) i i ) . ** The f o l l o w i n g columns were used: The P h e n o x y s i l i c o n e g r ease a t 170°C, 47.7 ml per min, and the Carbowax a t 200°C, 52 ml/min. The nmr spectrum (benzene) showed the f o l l o w i n g r e s o n a n c e s : 2.74, s i n g l e t , 2 p r o t o n s of the C-2 methylene; 1.98, s h a r p complex m u l t i p l e t , 8 p r o t o n s of the C-4,8,9 and 10 m e t h y l e n e s ; 1.70, p a r t l y o b s c u r e d b r o a d m u l t i p l e t , 2 p r o t o n s o f the C-5 and 7 b r i d g e h e a d s ; I . 6 4 , s h a r p s i n g l e t , 3 p r o t o n s o f the a c e t y l ; and 1.15 & , broad m u l t i p l e t , 2 p r o t o n s o f the C-6 methylene. o d) I o d i n a t i o n o f DHA a t -75 0 - P r e p a r a t i o n of  l-etnoxy-3-iodoadamantane A s o l u t i o n o f i o d i n e (0 .867 g) i n e t h e r (5.0 ml) v/as used to t i t r a t e DHA (0.171 g) i n e t h e r (25.0 ml) a t -75°C under a n i t r o g e n atmosphere. Analogous to the b r o m i n a t i o n o f DHA, a d a r k r u s t c o l o r e d p r e c i p i t a t e formed. Due t o i t s low s o l u b i l i t y i n e t h e r , the e x c e s s i o d i n e was not removed p r i o r t o e v a p o r a t i o n of the r e s i d u a l e t h e r under o h i g h vacuum (10 h r ) a t -75 0. The d r y r e s i d u e was d i s s o l v e d i n acetone (250 ml) c o n t a i n i n g suspended sodium 0 c y a n i d e (0.50 g) and was s t i r r e d a t -75 0 u n t i l the s o l u t i o n became c o l o r l e s s (24 h r ) . The f l o c u l e n t w h i t e p r e c i p i t a t e o f i n o r g a n i c s a l t s was removed by vacuum f i l t r a t i o n and c a r e f u l l y f l u s h e d down the s i n k w i t h generous amounts of w a t e r . The s o l v e n t i n the s u p e r n a t a n t s o l u t i o n was removed by r o t a r y e v a p o r a t i o n , and the r e s i d u e s were p a r t i t i o n e d - 147 -between water (10 ml) and c h l o r o f o r m (20 m l ) . The o r g a n i c l a y e r was d r i e d o v e r g r a n u l a r anhydrous sodium s u l f a t e and reduced to an o i l once more a f t e r f i l t e r i n g out the d r y i n g a g e n t . The o i l was d i l u t e d (25.0 ml) w i t h benzene. The y i e l d o f l-ethoxy-3-iodoadamantane (0.395 g> 7 4 « 3 % ) j 7.0 min, and 1,3-di-iodoadamantane, 19.3 min, ( 2 % ) , was d e t e r m i n e d by comparing t h i s p r e p a r e d s o l u t i o n w i t h a benzene s o l u t i o n o f a u t h e n t i c 1,3-dibromoadamantane*, o 7.0 min, u s i n g the Carbowax column a t 200 C, 52 ml/min. o The P h e n o x y s i l i c o n e g rease column a t 170 C, 51.3 ml/min, a l s o was used to d e t e c t l - e t h o x y - 3 - i o d o a d a m a n t a n e , 7.9 min. The major p r o d u c t c o u l d be i s o l a t e d by column chromatography o f the r e a c t i o n p r o d u c t on Woelm grade I n e u t r a l a l u m i n a (20.0 g ) . The f i r s t f r a c t i o n w i t h c y c l o -hexane (100 ml) gave o n l y a v e r y s m a l l amount ( c a . 0.005 g) o f the 1,3-di-iodoadamantane b y - p r o d u c t . The major p r o d u c t (0.051 g) was o b t a i n e d w i t h cyclohexane-benzene ( 4 : 1 ) a f t e r removing t r a c e s o f s o l v e n t i n vacuo. ( F u r t h e r d e c r e a s i n g amounts of l-ethoxy.-3-iodoadamantane were o b t a i n e d w i t h i n c r e a s i n g l y p o l a r s o l v e n t s ) . T h i s sample Due t o d i f f e r e n c e s i n degrees o f i o n i z a t i o n i n the hydrogen f l a m e , a c o n v e r s i o n r a t i o o f 1.45 was e s t a b l i s h e d by comparing benzene s o l u t i o n s o f the a u t h e n t i c compounds. - 1 4 8 -of major product was i s o l a t e d and sublimed to give o a n a l y t i c a l l y pure white c r y s t a l s , mp 3 5 - 3 7 C, d i s t i l l a t i o n o point (uncorrected) 1 1 5 C at 1 . 0 mm of Hg. The i n f r a r e d spectrum of the unsublimed o i l showed the following V ' . 2 9 5 0 ( s ) , 1 4 5 0 (m), 1 3 9 0 (w), 1 3 6 0 (w), 1 3 4 0 (m), 1 3 2 0 (m), 1 2 9 0 (w), 1 2 7 5 (m), 1 2 6 5 (m), 1 2 3 3 (w), 1 1 5 5 (w), 1 1 1 0 ( s ) , 1 0 8 8 ( s ) , 1 0 4 8 (m), 9 5 8 ( s ) , 9 3 7 (m), 8 7 0 (m), 8 1 5 (m), 7 8 5 (w), and 7 3 1 cm"1 (m). The nmr spectrum (benzene) showed the following resonances: 3 . 1 7 , quartet, J = 7 . 0 Hz, 2 protons of the ethoxy methylene; 2 . 5 7 , s i n g l e t , 2 protons of the C - 2 methylene; 2 . 2 5 , unsymmetrical doublet, 4 protons of the C - 4 and 8 methylenes; 1 . 5 4 , s i n g l e t with a shoulder, 6 protons of the C - 5 and 7 bridgeheads and C - 9 and 1 0 methylenes; 1 . 3 5 , p a r t l y obscured unresolved mul t i p l e t , 2 protons of the C - 6 methylene; and 1 . 0 5 £ , t r i p l e t J = 7 . 0 Hz, 3 protons of the ethoxy methyl. Anal. Calcd. for C 1 6 H l g I : C, 4 7 . 0 0 ; H, 6 . 2 1 ; I, 4 1 . 5 7 . Founds C, 4 7 . 2 9 ; H, 6 . 3 3 ; I, 4 1 . 3 1 . 3. Reaction of DHA with Acids a) Acid Catalyzed Hydration of DHA - Preparation  of 1-Hydroxyadamantane A solution of adamantane ( 0 . 0 7 0 g) and DHA ( 0 . 5 8 0 g ) i n f r eshly opened tetrahydrofuran was prepared i n a 5 0 ml three-necked round bottomed fl a s k which was cleared of - V-i-9 -oxygen. S u l f u r i c a c i d (3.5 m l , 8 .35 M) was added to the s t i r r e d s o l u t i o n . The r e a c t i o n was f o l l o w e d (35 min) by a n a l y t i c a l g l p c o u s i n g the Carbowax column a t 80 C, u n t i l the 1 , 3-dehydro-adamantane peak was no l o n g e r e v i d e n t . U s i n g the same column w i t h the temperature program, the g l p c t r a c e showed o n l y one major and one minor p r o d u c t . The aqueous phase was s a t u r a t e d w i t h p o t a s s i u m c a r b o n a t e (7.5 g) and s e p a r a t e d from the o r g a n i c phase. The aqueous phase was back e x t r a c t e d t w i c e w i t h t e t r a h y d r o f u r a n ( c a . 5 m l ) . The p o o l e d o r g a n i c s o l u t i o n was d r i e d , f i l t e r e d and d i l u t e d i n a v o l u m e t r i c f l a s k (50.0 m l ) . A n a l y t i c a l g l p c u s i n g the above Carbowax column a t o 160 C showed the f o l l o w i n g r e s u l t s . F i r s t , s u p e r p o s i t i o n o f the major p r o d u c t w i t h a u t h e n t i c 1-hydroxyadamantane e s t a b l i s h e d the p r o d u c t s i d e n t i t y . Second, comparison o f the r e a c t i o n s o l u t i o n w i t h an a u t h e n t i c s o l u t i o n o f 1-hydroxyadamantane i n d i c a t e d the a c i d c a t a l y z e d h y d r a t i o n r e a c t i o n proceeded i n h i g h y i e l d (90 +_ 5 % ) . b) R e a c t i o n w i t h A c e t i c A c i d - P r e p a r a t i o n o f  1-Ace toxyadaman tane An n-octane s o l u t i o n (10.0 ml) c o n t a i n i n g DHA (0 .096 g) was t r e a t e d w i t h g l a c i a l a c e t i c a c i d ( c a . 50 mg). W i t h i n - 150 -10 min the DHA had r e a c t e d to g i v e one compound. The i d e n t i t y o f t h i s compound was e s t a b l i s h e d by comparison . w i t h a u t h e n t i c 1-acetoxyadamantane p r e p a r e d by s u l p h u r i c a c i d c a t a l y z e d a d d i t i o n o f 1-hydroxyadamantane to a c e t i c a n h y d r i d e . c) R e a c t i o n w i t h P a r a - n i t r o b e n z o i c A c i d -P r e p a r a t i o n o f l-Adamantanyl p a r a - n i t r o b e n z o a t e An e t h e r s o l u t i o n (25.0 ml) c o n t a i n i n g DHA (0.141 g) was s t i r r e d (6 h r ) w i t h p a r a - n i t r o b e n z o i c a c i d (0.300 g) under n i t r o g e n . The e t h e r s o l v e n t was r e p l a c e d w i t h benzene and the i n s o l u b l e a c i d was f i l t e r e d o f f . The c l e a r s o l u -t i o n was e x t r a c t e d t w i c e w i t h 1% sodium b i c a r b o n a t e (20 m l ) , d r i e d o v e r sodium s u l f a t e and s e p a r a t e d from the d r y i n g agent by vacuum f i l t r a t i o n . T h i s s o l u t i o n was d i l u t e d (25.0 w i t h benzene and compared to an a u t h e n t i c s o l u t i o n o f 1-adamantyl p a r a - n i t r o b e n z o a t e , 7.2 min, u s i n g the Phenoxy-o s i l i c o n e grease column a t 275 0, 37.5 ml p e r min*. The i n f r a r e d spectrum ( n u j o l m u l l ) showed the f o l l o w -i n g \ax: 1715 ( s ) , 1605 (w), 1515 (m), 1340 (m), 1270 (m), 1105 (m), 1050 (m), 1015 (w), 965 (w), 895 (w), 878 (w), 845 (m), 785 (w) and 718 cm" 1 ( s ) . The nmr spectrum ( C C l ^ r C D C l ^ - 2 : 1 ) * * showed the * T h i s compound was p r e p a r e d by W. B. S c o t t . ** T h i s compound was i n s u f f i c i e n t l y s o l u b l e i n CC1,. - 151 -f o l l o w i n g r e s o n a n c e s : 9.20, complex m u l t i p l e t , 4 p r o t o n s o f the a r o m a t i c r i n g ; 2 . 2 9 , s h a r p s i n g l e t , 9 p r o t o n s o f the C-2,9 and 10 and C - 3 , 5 and 7 b r i d g e h e a d s ; and 1 . 7 8 5, broad s i n g l e t , 6 p r o t o n s o f the C-4,6 and 8 m e t h y l e n e s . The mass spectrum showed a p a r e n t peak w i t h m/e+ a t 301, c a l c u l a t e d f o r C-^H-^O^N, 301. A n a l . C a l c d . f o r C^H^O^N: C, 67.75; H, 6.32; N, 4 . 6 5 . Found: C, 67.62; H, 6.41; N, 4 . 6 3 . 4. R e a c t i o n o f DHA w i t h M e r c u r i c A c e t a t e - P r e p a r a t i o n o f 1-Hydroxyadamantane A s o l u t i o n o f m e r c u r i c a c e t a t e (1 . 3 5 g) i n wat e r (4 . 3 ml) was added t o a s o l u t i o n o f adamantane and DHA (0 . 5 8 g, 1:12.5) i n t e t r a h y d r o f u r a n (4 . 3 m l ) . A f t e r 2.5 m i n u t e s the p r e c i p i t a t i o n o f f r e e mercury was o b s e r v e d . Q u i c k l y , sodium h y d r o x i d e (4 . 3 m l , 3N) and sodium b o r o h y d r i d e (4 . 3 m l , IN) were added s u c c e s s i v e l y to reduce the o r g a n o m e r c u r i c a l p r o d u c t s . The m i x t u r e was s t i r r e d ( 5 min) b e f o r e sodium c h l o r i d e was added to s a l t out the w a t e r . The o r g a n i c l a y e r was drawn o f f and the aqueous l a y e r washed 4 t i m e s w i t h e t h e r ( 5 m l ) . The combined o r g a n i c l a y e r s were d r i e d o v e r sodium s u l f a t e . R o t a r y e v a p o r a t i o n a f t e r f i l t e r i n g out the d r y i n g agent f o l l o w e d by d r y i n g i n vacuo (15 min) gave a w h i t e o i l ( U . / U l g ) . T h i s o i l was d i l u t e d w i t h methanol ( t o 50.0 ml) and - 152 -compared to an authentic sample of 1-nydroxyadamantane 0 using the Carbowax column at I6u C. The major product 1-hydroxyadamantane (0.291 g, 47.7%), together with an unknown by-product (ca. 18%) and 1,3-dihydroxyadaman-cane (ca. 9%) accounted for 75% of the s t a r t i n g material. Both hydroxy compounds were i d e n t i f i e d by superposition with authentic materials using the above Carbowax column at o o 160 C for the single hydroxy compound and at 200 C for the double hydroxy compound. The major product also was is o l a t e d by column chromatography on Woelm grade III neutral alumina. Elution with 2% methanol i n chloroform (25 ml) gave 1-hydroxyadamantane ( 0 . 3 1 0 g). Further elution with t h i s solvent mixture (75 ml) yielded a mix-ture (0.075 g) containing some adamantanol but primarily adamantane-l,3-diol. A flush of the column with 10% methanol gave a mixture (0.068 g) of at lea s t f i v e compounds. The major product was further i d e n t i f i e d as 1-hydroxy-adamantane by i t s i n f r a r e d spectrum which was i d e n t i c a l to the inf r a r e d spectrum of the authentic compound (Aldrich l a b o r a t o r i e s ) . 5. Reaction of DHA witn Methanol - Preparation of  1-Methoxyadamantane A freshly prepared mixture of adamantane (0.138 g) and DHA (0.602 g) was dissolved i n dry methanol (10 ml) and ether (20 ml). Boron t r i f l u o r i d e etherate (0.25 ml) - 153 -was added to t h i s s t i r r e d s o l u t i o n which was p r o t e c t e d by an i n e r t atmosphere. The c o m p l e t i o n o f the r e a c t i o n (2 min) was i n d i c a t e d by a n a l y t i c a l g l p c o f the r e a c t i o n o s o l u t i o n u s i n g the Carbowax column a t 80 C. Water (0.2 ml) •was added to r e a c t w i t h the b o r o n t r i f l u o r i d e . A f t e r t h i s s i m p l e workup, the o r g a n i c s o l u t i o n was d r i e d o v e r sodium s u l f a t e , f i l t e r e d and d i l u t e d (50.0 ml) w i t h m ethanol. The y i e l d o f 1-methoxyadamantane (0.794 g) was de t e r m i n e d by comparison w i t h the a u t h e n t i c compound u s i n g the above o Carbowax column a t 160 C. Only one o t h e r compound v/as observed i n the methanol a d d i t i o n r e a c t i o n , but i t s y i e l d v/as v e r y s m a l l . A u t h e n t i c methoxyadamantane was p r e p a r e d from 1-hydroxyadamantane (0.608 g) by r e f l u x (24 d a y s ) v/ith m e t h y l i o d i d e (40 ml) i n a s u s p e n s i o n o f sodium h y d r i d e (10.8 g) and e t h e r (75 m l ) . (The r e a c t i o n was f o l l o w e d by g l p c u s i n g the Carbowax column). A d d i t i o n o f methanol (15 ml) decomposed the sodium h y d r i d e . The r e a c t i o n m i x t u r e was p a r t i t i o n e d between w a t e r (70 ml) and c h l o r o -form (100 ml) i n a s i m p l e workup. The o r g a n i c l a y e r was d r i e d o v er sodium s u l f a t e , the d r y i n g agent f i l t e r e d o u t , and the s o l v e n t removed by r o t a r y e v a p o r a t i o n t o g i v e a y e l l o w o i l (0.613 g ) . D i s t i l l a t i o n a t 95-100°C - 1.4 mm o f mercury gave a c o l o r l e s s a n a l y t i c a l l y pure sample o f 1-methoxyadamantane (4.6 g, 6 9 % ) . - 154 -The i n f r a r e d spectrum o f the neat o i l showed the f o l l o w i n g 2900 ( s ) , 2680 (w), 1450 (m), 1350 (m), 1300 (m), 1285 (w), 1203 (w), 1180 (m), 1115 (w), 1085 ( s ) , 1050 (m), 985 (w), 973 (w), 937 (v/), 897 (m), 818 (w), 777 (w), and 715 cm" 1 (w). The nmr spectrum ( c a r b o n t e t r a c h l o r i d e ) showed the f o l l o w i n g r e s o n a n c e s : 3*12, s i n g l e t , 3 p r o t o n s o f the me t h o x y l ; 2,11 broad s i n g l e t , 3 p r o t o n s o f the C-3,5 and 7 b r i d g e h e a d s ; and 1,67 S , s h a r p m u l t i p l e t , 12 p r o t o n s of the t o t a l m e t h y l e n e s . The nmr spectrum (benzene) showed the f o l l o w i n g r e s o n a n c e s : 3.12, s i n g l e t , 3 p r o t o n s o f the m e t h o x y l ; 2.00, s i n g l e t , 3 p r o t o n s o f the C-3,5 and 7 b r i d g e h e a d s ; 1.83, m u l t i p l e t , 6 p r o t o n s o f the a d j a c e n t C-2,9 and 10 m e t h y l e n e s ; and 1.77 S , m u l t i p l e t , 6 p r o t o n s o f the C-4,6 and 8 m e t h y l e n e s . The mass spectrum showed a p a r e n t peak a t m/e+ 166 ( c a l c u l a t e d f o r C 1 1 H 1 3 0 , 166). A n a l . C a l c d . f o r C^H^O: C, 79.50; H, 10.84. Found: C, 79 . 5 6 ; H, 10.94. 6. The C a t a l y t i c H y d r o g e n a t i o n o f DHA - P r e p a r a t i o n  o f Adamantane a) i n n-heptane A s u s p e n s i o n o f Adam's c a t a l y s t (0.120 g) i n d r y n-heptane (10.0 ml) was s a t u r a t e d w i t h hydrogen ( 2 1 . 5 ml) - 155 -by r a p i d s t i r r i n g i n a 50 ml Erlenmeyer f l a s k , m o d i f i e d w i t h a serum cap s t o p p e r e d s i d e arm. A s o l u t i o n o f adamantane (0.023 g) and DHA (0 .216 g) i n d r y n-heptane (10.0 ml) was i n j e c t e d i n t o the h y d r o g e n a t i o n f l a s k . The uptake o f the hydrogen gas (41.5 m l , c o r r e c t e d ) proceeded f o r 30 min a t which time a second a l i q u o t ( c a , 0.20 ml) was w i t h d r a w n . The a n a l y t i c a l g l p c t r a c e u s i n g the Carbowax column a t 80°C, 52 ml/min, i n d i c a t e d the t o t a l absence o f DHA, 6.0 min; one major peak (79.5%) a t 5.5 min; and an o v e r l a p p i n g group o f peaks (16.9%) a t 3-4 min. The major peak was i d e n t i f i e d as adamantane by a n a l y t i c a l g l p c t r a c e s u p e r i m p o s i t i o n w i t h an a u t h e n t i c sample as w e l l as by i n f r a r e d s p e c t r o s c o p y . The i n f r a r e d spectrum o f the r e a c t i o n p r o d u c t r e c r y s t a l l i z e d s i x t i m e s from e t h a n o l v/as i d e n t i c a l w i t h the i n f r a r e d spectrum o f a u t h e n t i c adamantane. b) i n E t h a n o l Adam's c a t a l y s t (0 . 04 g) was suspended i n E t h a n o l (10 ml) under an atmosphere o f hydrogen a t room t e m p e r a t u r e . When the uptake o f hydrogen c e a s e d , an e t h a n o l s o l u t i o n (25.0 ml) o f adamantane (0.32 g) and DHA (0.32 g) v/as added. The r a p i d uptake o f hydrogen (38.9 m l , c o r r e c t e d ) ceased a g a i n a f t e r 38 min. A n a l y t i c g l p c u s i n g the o Carbov/ax column a t 80 C, 54 ml/min showed a modest - 1 5 6 -c o n v e r s i o n o f DHA i n t o adamantane ( c a . 5 0 % ) when compared t o an a u t h e n t i c adamantane s o l u t i o n . , An a l t e r a t i o n a l s o v/as n o t e d i n the c o m p o s i t i o n o f the b y - p r o d u c t t r a c e s , 3 - 4 min, but the a r e a s of these t r a c e s d i d not account f o r the d e c r e a s e d y i e l d o f adamantane; however, g l p c a t o . 2 0 0 C i n d i c a t e d a n o t h e r compound ( c a . 3 1 i 5 % , by i n t e g r a t i o n o f the ethoxy methylene group nmr t r a c e i n the crude r e a c t i o n p r o d u c t ) v/as formed whose t r a c e was s u p e r p o s a b l e w i t h the o n l y o b s e r v e d compound r e s u l t i n g from the r e a c t i o n o f DHA v/ith n eat e t h a n o l . 7 . The R e a c t i o n o f DHA w i t h Benzene C a t a l y z e d by Aluminum C h l o r i d e - P r e p a r a t i o n o f 1-Phenyladamantane Aluminum c h l o r i d e ( 2 . 0 g) v/as added t o an anhydrous, o x y g e n - f r e e benzene s o l u t i o n ( 3 1 0 ml) c o n t a i n i n g adamantane ( 0 . 1 7 7 g) and DHA ( 0 . 6 9 3 g) which was s t i r r e d r a p i d l y o under a n i t r o g e n atmosphere a t 60 C. The Carbov/ax column o a t 80 C, showed no DHA was e v i d e n t i n the a n a l y t i c g l p c t r a c e ( 1 0 m i n ) . Water ( 1 5 ml) was added r a p i d l y c a u s i n g the s o l v e n t to r e f l u x i n the condenser. The r e a c t i o n m i x t u r e was v/ashed v/ith w ater ( 5 0 m l ) , 5% sodium b i c a r b o n a t e ( 3 0 ml) and once more w i t h w a t e r ( 5 0 m l ) . A f t e r d r y i n g o v e r sodium s u l f a t e and f i l t e r i n g out the d r y i n g a g e n t , the s o l u t i o n was c o n c e n t r a t e d . T h i s benzene s o l u t i o n - 1 5 7 -(50.0 ml) was compared to a solution of authentic 1-phenyladamantane to determine the y i e l d ( 0 . 4 3 7 g, 39.8%) i n the Lewis acid catalyzed phenylation of DHA. This comparison was performed using the S i l i c o n e elastomer o o column at 180 C. By using t h i s column at 180 C and the Carbowax column at 200°C, the reaction product v/as further i d e n t i f i e d by observing an enhancement of the phenylation reaction product trace on each of these columns, a f t e r enrichment with authentic 1-phenyladamantane. Authentic 1-phenyladamantane v/as prepared from 1-bromoadamantane (4.0 g) by tne action of aluminum cnloride (268 g) i n benzene (120 ml) at 0°C. The reaction mixture was allowed to reach room temperature (2 hr) before v/ater (20 ml) was added (over 5 min). The reaction mixture was partitioned between water (50 ml) before being dried over anhydrous sodium s u l f a t e . The drying agent was f i l t e r e d out and the solvent removed by rotary evaporation to give a red-brown semicrystalline o i l ( 3 . 9 g). R e c r y s t a l l i z a t i o n twice from methanol and o sublimation at 60 C (25 mm mercury) yielded (1.46 g, 38%) yellow c r y s t a l s . Eight more r e c r y s t a l l i z a t i o n s yielded flaky white c r y s t a l s (0.6y g) with mp (sealed tube) 79-81°C (reported, 8 2 ° C ) . 1 2 8 The nmr spectrum (chloroform-d) showed the following resonances: 7.26, multiplet, 5 protons of the aromatic - 158 -r i n g ; 2 . 0 6 , b r o a d s i n g l e t , 3 p r o t o n s o f the C - 3 , 5 and 7 b r i d g e h e a d s ; 1 . 9 3 , s h a r p s i n g l e t , 6 p r o t o n s o f the C - 2 , 9 and 1 0 m e t h y l e n e s ; and 1 . 7 7 & , s h a r p c l o s e l y spaced m u l t i p l e t , 6 p r o t o n s o f the C-Zf,6 and 8 m e t h y l e n e s . The mass spectrum showed an m/e+ a t 2 1 2 w h i c h v/as i d e n t i c a l v / i t h t h a t c a l c u l a t e d f o r C ]_6^20* A n a l . C a l c d . f o r C l 6 H 2 0 : C, 9 0 . 5 2 ; H, 9 . 4 8 . Found: C, 9 0 . 3 2 ; H, 9 . 5 3 . 8 . The P y r o l y s i s o f DHA a) I n the s o l i d phase A 5 ml K i m b l e "break s e a l " ampule c o n t a i n i n g adamantane ( 0 . 1 4 1 g) and DHA (0 .556 g) was sea'led under h i g h vacuum. The ampule v/as immersed i n an o i l b a t h o o v e r n i g h t a t 1 4 5 C. V o l a t i l e m a t e r i a l s (0 .106 g) were a l l o w e d t o s u b l i m e i n t o the t i p o f t h e ampule f o r 8 h o u r s and e l i m i n a t e d upon o p e n i n g the ampule. The non-v o l a t i l e i n s o l u b l e w h i t e s o l i d (0 .565 g, 9 8 . 5 % ) c o a t i n g the w a l l s was c a r e f u l l y removed. D i f f e r e n t i a l s c a n n i n g c a l o r i m e t r y under an i n e r t atmosphere, i n d i c a t e d t h i s s o l i d p o s s e s s e d no d i s t i n c t m e l t i n g p o i n t , but a f r a c t i o n o o o f i t d i d s u b l i m e a t t e m p e r a t u r e s g r e a t e r than 450 C ( c a . 5 0 0 C ) , o o I n a i r , i t t u r n e d y e l l o w a t 4 5 0 C, over 1 2 5 0 h i g h e r t h a n f o r the polyadamantane compound p r e p a r e d by Wurtz c o u p l i n g o f 3 , 3 l - d i b r o m o b i a d a m a n t a n e . x - 7 X The polymer was i n s o l u b l e i n a l l common s o l v e n t s . - 159 -Tne i n f r a r e d spectrum ( n u j o l m u l l ) showed the f o l l o w i n g V' : 2770 (rn), 1365 ( s ) , 1300 ( s ) , 1100 ( s ) , 1060 (w), 1035 ( s ) , and 825 cm" 1 (w). A n a l . C a l c d . f o r ^ 1 Q \ L - C, 89.49; H, 10.51. Found: C, 89.30; H, 10.90. b) I n s o l u t i o n A s o l u t i o n o f DHA (0.287 g) and an i n t e r n a l s t a n d a r d , o r t h o x y l e n e (0.1445 g)> i n d r y deoxygenated n-octane (25.00 ml) was p r e p a r e d i n an ox y g e n - f r e e n i t r o g e n f i l l e d d r y box. An a l i q u o t (5.00 ml) o f t h i s s o l u t i o n was withdrawn and d i l u t e d ( t o 50.00 ml) f o r o t h e r e x p e r i m e n t s . A s e r i e s o f 1 ml Ki m b l e c o l o u r - s e a l v i a l s w i t h s e v e r e l y c o n s t r i c t e d necks were h a l f - f i l l e d w i t h the above s o l u t i o n u s i n g a s y r i n g e w i t h a f i n e l o n g ( 8 - i n ) n e e d l e and i m m e d i a t e l y s t o p p e r e d w e l l w i t h nmr tube serum c a p s . The s t o p p e r e d v i a l s were removed and s e a l e d i n a v e r y s m a l l hot o x y g e n - n a t u r a l gas f l a m e . A s e r i e s o f samples were immersed i n a s i l i c o n e o i l b a t h t h e r m o s t a t i c a l l y o c o n t r o l l e d a t 195.3 i 0.2 C f o r v a r y i n g p e r i o d s o f t i m e . - 160 -Each v i a l was opened and ass a y e d f o r DHA u s i n g the Carbowax column a t 80°C. The t r a c e w e i g h t o f DHA was n o r m a l i z e d v / i t h r e s p e c t t o an i n t e r n a l s t a n d a r d . The r a t e -5 -1 c o n s t a n t , k = 4.315 x 10 sec , was det e r m i n e d from the s l o p e o f the graph o f the l o g t r a c e v a l u e s v e r s u s time o f exposure a f t e r c o n v e r s i o n t o n a t u r a l l o g a r i t h m s . The h a l f l i f e , t ^ = 4.45 h r , was c a l c u l a t e d from t h e f o l l o w i n g e q u a t i o n s . From the graph: s l o p e = -k TABLE V. 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