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The synthesis of anti-8-tricyclo [3.2.1.0 2,4] octanol and solvolysis of its p-bromobenzenes-ulphonyl… Wells, June I. 1964

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THE SYNTHESIS OF anti.-8-TRICYCLO [3.2 .1.0] OCTANOL AND SOLVOLYSIS OF ITS p-BROMOBENZENESULPHONYL DERIVATIVE by JUNE I. WELLS B.Sc.(Spec.) London, 196I A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in the Department of Chemistry We accept this thesis as conforming to the required standard THE UNIVERSITY OF BRITISH COLUMBIA April, 1964 In p r e s e n t i n g t h i s t h e s i s i n p a r t i a l f u l f i l m e n t of the requirements f o r an advanced degree at the U n i v e r s i t y of • B r i t i s h Columbia, I agree that the L i b r a r y s h a l l make i t f r e e l y a v a i l a b l e f o r reference and study t I f u r t h e r agree that per-mission f o r extensive copying of t h i s t h e s i s f o r s c h o l a r l y purposes may be granted by the Head of my Department or by h i s r e p r e s e n t a t i v e s . I t i s understood that copying or p u b l i -c a t i o n of t h i s t h e s i s f o r f i n a n c i a l gain s h a l l not be allowed without my w r i t t e n permission,. Department of O H £ - H i The U n i v e r s i t y of B r i t i s h Columbia, Vancouver 8, Canada i ABSTRACT The synthesis of a n t i - 8 - t r i c y c l o {3 .2 .1 .O 2'^]octanol has been c a r r i e d out by the cuprous ch l o r i d e catalysed r e a c t i o n of diazomethane on anti-7-norbornenol. X-ray c r y s t a l l o g r a p h i c a n a l y s i s of the £-bromo-benzene sulphonyl (brosylate) d e r i v a t i v e has unambiguously shown the cyclopropyl group to be exo. Methylene a d d i t i o n to norbornene and 7-norbornadienyl acetate was achieved by the above method? f o r the l a t t e r , the two isomers whose presence was detected by n.m.r. could not be sep-arated. The slow rate of the a c e t o l y s i s of the brosylate of a n t i - 8 -2 4 t r i c y c l o {3.2.1.0 ' joctanol suggests that t h i s d e r i v a t i v e resembles 7-norbornyl brosylate i n s o l v o l y s i s reactions, rather than anti-7-norbor-nenyl brosylate. Enthalphy of a c t i v a t i o n c a l c u l a t e d f o r the t r i c y c l i c brosylate s o l v o l y s i s i s of the same order as that f o r the 7-norbornyl case. Product studies on material i s o l a t e d from samples solvolysed up to the h a l f l i f e of the brosylate suggest the f i r s t product probably i s 2 4 a n t i - 8 - t r i c y c l o [3.2.1.0 ' Joctanyl acetate. Prolonged s o l v o l y s i s con-d i t i o n s r e s u l t i n a v a r i e t y of products i n which the cyclopropyl group has rearranged. The structures of these products could not be determined. i i i ACKNOWLEDGEMENT I would like to thank Dr. B. E. Pincock for his encouragement, help and inspiration throughout the course of this work. I also wish to thank the Department of Scientific and Industrial Research, U. K. for the award of a N.A.T.O. Studentship. i i TABLE OP COBTBHTS page I. H i s t o r i c a l A 7-Korbornyl system 1 B Conjugative e f f e c t s of the cyclopropyl group 3 C Effect of cyclopropyl group on rea c t i v i t y of 7-norbornyl system 5 I I . Summary of Experimental Results A Synthetic 7 B K i n e t i c 8 C Product Studies 11 I I I . Discussion 13 IV. Experimental A Synthetic 23 B K i n e t i c 32 C Product Studies 46 References 57 I. HISTORICAL A. 7-NORBORNYL SYSTEM In order to explain the behaviour of some chemical systems Winstein ( l ) introduced the concept of homoconjugation. Norbornenyl (2,3»4) and ch o l e s t e r y l (5) d e r i v a t i v e s underwent s o l v o l y s i s reactions that were s t e r e o s p e c i f i c i n nature and proceeded with enhanced rates compared to the saturated norbornyl (2,3) and cholestanyl (5) d e r i v a t i v e s . These molecules each had an unsaturated group separated from the carbonium i o n centre by a methylene group. The s p e c i a l properties were a t t r i b u t e d to some i n t e r a c t i o n of the TT electrons of the ^-unsaturated group with the developing carbonium i o n . This 1,3 i n t e r a c t i o n , or homoallylic resonance i s represented i n the same way as the more f a m i l i a r a l l y l i c resonance. (Figure l ) . F i g . 1 F i g . 2 An important example of a homoallylic ion i s the anti - 7-norbornenyl (2,3) • c a t i o n . (Figure 2) . Winstein and Woodward (3) found 7-norbornyl t o s y l a t e to 7 be very unreactive, s o l v o l y s i n g about 10 times slower than cyclohexyl t o s y l a t e . In contrast to t h i s anti - 7-norbornenyl t o s y l a t e was found to be 4 11 10 times as re a c t i v e as the cyclohexyl d e r i v a t i v e , hence 10 times as f a s t as the saturated analogue., Complete r e t e n t i o n of configuration was reported i n the product acetate (3). Roberts (6) reported s i m i l a r r e s u l t s f o r the corresponding c h l o r i d e s , i n c l u d i n g the rate f o r syn-7-norbornenyl 2 chloride (Figure 3) , which was unreactive compared to cyclopentyl chloride. The product for this was 3-bicyclo[3.2.6]heptenol-2 with predominant trans configuration, confirmed by independent synthesis (7 ,8). The enhanced rate was attributed* to formation of the rearranged a l l y l cation. OH Fig. 3 In orderv to explain the unprecented effect on the rate by the intro-duction of a double bond into the 7-norbornyl system Winstein (3) formu-lated a bridged or "non-classical" ion, an example of a homoallylic ion. The geometry of the anti-7-norbornenyl cation is uniquely favorable for derealization of the 7T electrons on and C^, and subsequent overlap occurs with the vacant p orbital of the developing carbonium ion at C^, giving rise to a "non-classical" ion (Figure 14a). Roberts (9) prefers to refer to the ion as "bis-homocyclopropenyl" which emphasises its relation-ship with the cyclopropenyl ion, Figure 4b, which M.O. theory predicts to have a stable TT electron system. Fig. 4a Fig. 4b Fig. 4c Fig. 4d The stabilization energy associated with the ion,Figure 4a, has been calculated (9) also by M.O. methods. The net stabilization energy, taking into account"angle strain is greater than that predicted for the most 3 f a v o r a b l e open chain h o m o a l l y l i c i o n (6). A " n o n - c l a s s i c a l " i o n f o r the 7-norbornadienyl carbonium i o n , h i g h l y s t a b i l i z e d by e l e c t r o n d e r e a l i z a t i o n , has been represented by a nonsymmetrical s t r u c t u r e , Figure 4c, or a sym-m e t r i c a l , F i g u r e 4d. I t i s not c l e a r which of the two ( i f e i t h e r ) s t r u c -t u r e s represents the 7-norbornadienyl i o n . Indeed the very existence of t h i s s p e c i a l type of i o n has s e r i o u s l y been questioned by Brown (lOa,b). An a l t e r n a t i v e way of l o o k i n g at the vast d i f f e r e n c e between the r a t e s of 7-norbornyl and anti - 7-norbornenyl i s to consid e r the 7-norbornyl system as unusually i n e r t ; the r a t e of anti - 7-norbornenyl being normal. T h i s theory was f i r s t put forward to e x p l a i n the r a t e d i f f e r e n c e i n s o l v o l y s i s r e a c t i o n s between endo and exo - 2-norbornyl d e r i v a t i v e s (11,36c). The reasons f o r the i n e r t n e s s of 7-norbornyl may be summarised a) s t e r i c hindrance to s o l v a t i o n of the t r a n s i t i o n s t a t e by the exo hydrogens b) increase i n I - s t r a i n (5l) on i o n i s a t i o n : t h i s i s the increase i n s t r a i n i n r i n g systems as a r e s u l t of formation of a carbonium i o n on one carbon atom of the r i n g . These two f a c t o r s are considered i n more d e t a i l i n the D i s c u s s i o n . B. CONJUGATIVE EFFECTS OF THE CYCLOPROPYL GROUP That cyclopropane and c y c l o p r o p y l compounds e x h i b i t p r o p e r t i e s of unsaturated molecules has been known f o r some time (12,13). In p a r t i c u l a r , w i t h respect to i t s resemblance to the double bond, cyclopropane undergoes hydrogenation r e l a t i v e l y e a s i l y to propane. Coulson and M o f f i t (14) have t h e o r e t i c a l l y p r e d i c t e d that d e r e a l i z a t i o n of t h e < 5 e l e c t r o n s i n c y c l o -propane i s p o s s i b l e . M.O. c a l c u l a t i o n s show that the carbon o r b i t a l s are not at angles of 60°, a c o n d i t i o n necessary f o r s t r a i g h t l i n e bonds, but at 106°; thus the o r b i t a l s are not i n a c o n d i t i o n of r e g u l a r sp^ t e t r a h e d r a l . o v e r l a p , but are bent outwards; from the h y p o t h e t i c a l s t r a i g h t l i n e , Fig.5 a . 4 T h i s poor overlap g i v e s a c e r t a i n amount o f ^ e l e c t r o n d e r e a l i z a t i o n and hence imparts s t a b i l i t y to the r i n g . T h i s TT c h a r a c t e r of the r i n g bonds i s o r i e n t a t e d i n the same plane as the r i n g carbons, and not i n two planes p a r a l l e l to the r i n g as i n benzene. In a conjugated system of double bonds, i t i s w e l l known that there i s a t r a n s m i s s i o n of e l e c t r i c a l e f f e c t s along the c h a i n . The t r a n s m i s s i v e e f f e c t s of c y c l o p r o p y l are thought to be l e s s than ethylene, but g r e a t e r than a s a t u r a t e d dimethylene (12,13). There are c o n f l i c t i n g r e p o r t s i n the l i t e r a t u r e as to whether the c y c l o p r o p y l group a c t u a l l y t r a n s m i t s the conjugation, or merely extends i t (12,13). U l t r a v i o l e t s t u d i e s on con-j u g a t i o n with carbonyl compounds (15)» with double bonds ( l 6 ) , with aromatic systems (17) a l l r e v e a l bathochromic s h i f t s i n d i c a t i n g d e r e a l i z a t i o n of e l e c t r o n s . D i p o l e moment ( l 8 ) , i n f r a r e d (19.)» molecular r e f r a c t i o n (20) as w e l l as abundant chemical measurements have been made on c y c l o p r o p y l compounds with respect, to i t s conjugative p r o p e r t i e s . Chemical evidence e x i s t s f o r the conjugation of the c y c l o p r o p y l group with carbonyl ( 2 l ) , . double bond (22), and l a s t l y , but the most important as f a r as the present work i s concerned, with carbonium i o n intermediates (22,23). S o l v o l y s i s of c y c l o p r o p y l c a r b i n y l (22.) d e r i v a t i v e s proceeds f a s t e r than s o l v o l y s i s of •p-methyl-allyl c h l o r i d e , i n d i c a t i n g that the c y c l o p r o p y l r i n g i s more e f f e c t i v e i n the s t a b i l i z a t i o n of the carbonium i o n , than the double bond. P i g . 5d F i g . 5a The intermediate i s represented as the "bicyclobutoniura i o n " (22), P i g . 5b, Recent papers on the s o l v o l y s i s of d i and t r i c y c l o p r o p y l c a r b i n y l d e r i v a t i v e s r e p o r t extremely f a s t r a t e s on the i n t r o d u c t i o n of the second and t h i r d r i n g s . Hence by r e p l a c i n g the i_-propyl groups one at a time by cy c l o p r o p y l groups i n t r i i^-propylcarbinyl p_-nitrobenzoate e s t e r s ( p . n . b . ) , Figure 6a, the corresponding r a t e i n c r e a s e s (a):(b):(c):(d) (23) as 1:246:23500:23.5xl0 6 from which i t may be deduced that 0 II ^ HZc i | r i r e l a t i v e r a t e 1 (a) 246 (b) F i g . 6 23500 (c) 23.500x10 (d) each r i n g provides f u r t h e r s t a b i l i z a t i o n of the carbonium i o n . C. EFFECT OF CYCLOPROPYL GROUP ON REACTIVITY OF THE 7-N0RB0RNYL SYSTEM In order to i n v e s t i g a t e the p o s s i b i l i t y of c y c l o p r o p y l conjugative e f f e c t s o c c u r r i n g with a s u b s t i t u t e d 7-norbornenyl d e r i v a t i v e the sy n t h e s i s of a n t i - 8 - t r i c y c l o Q j . 2 . 1 . 0 2 o c t a n o l , Figure 7a,was undertaken. ron F i g . 7a F i g . 7b F i g . 7c Two isomers are p o s s i b l e f o r t h i s molecule, exo, Fig u r e 7b, and endo ( c ) , d i f f e r i n g i n the arrangements of the c y c l o p r o p y l r i n g s . The geometry of the o r b i t a l s of the r i n g would d i f f e r and hence d i f f e r e n t conjugative pro-p e r t i e s could r e s u l t . I f the o r i e n t a t i o n i n one of the isomers was fa v o r a b l e 6 overlap of r i n g o r b i t a l s could occur with the carbonium i o n at the 8-p o s i t i o n formed i n s o l v o l y s i s of a sulphonate e s t e r d e r i v a t i v e of the a l c o h o l (Figure 7a). Hence the i o n would be s t a b i l i z e d and a r e s u l t i n g increase i n the r a t e of s o l v o l y s i s might be expected analogous to the r a t e increase observed f o r the s o l v o l y s i s of anti - 7-norbornenyl d e r i v a t i v e . 7 I.I. SUMMAEY OP .EXPERIMENTAL RESULTS A. SYNTHETIC The s y n t h e s i s of anti - 7-norbornenol V was c a r r i e d out according to the procedure of Story (27). Norbornadiene I obtained commercially, was reacted with t^-butyl perbenzoate i n benzene to give the ether 7-t^butoxynorbor-nadiene I I . A c i d cleavage of the ether with 70$ p e r c h l o r i c a c i d and a g l a c i a l a c e t i c a c i d , a c e t i c anhydride mixture y i e l d e d the e s t e r , 7-norbor-na d i e n y l acetate I I I . L i t h i u m aluminium hydride r e d u c t i o n of the acetate gave e x c l u s i v e l y anti - 7-norbornenol V. Attempts to synthesize the c y c l o p r o p y l a d d i t i o n compound of a n t i - 7 -norbornenoljVI, b y a d d i t i o n of carbene generated from methylene i o d i d e , and zinc-copper couple (Simmonds and Smith method (28)) f a i l e d . " ^ However methylene a d d i t i o n across the double bond was achieved by a cuprous c h l o r i d e c a t a l y s e d r e a c t i o n with diazomethane (32). T h i s r e a c t i o n was c a r r i e d out f i r s t with norbornene and gave the known (28) t r i c y c l o 2 4 [3.2.1.0 ' ] octane. In one r e a c t i o n , where water was present i n the r e a c t i o n f l a s k , 2-norbornanol was formed. Reacting diazomethane and cuprous c h l o r i d e with 7-norbornadienyl acetate I I I (27) gave a product which analysed f o r a d d i t i o n of one methylene u n i t to the d i o l e f i n ; I V . The n.m.r. spectrum showed t h i s to be about a three to one mixture of two compounds a r i s i n g from a d d i t i o n to e i t h e r of the double bonds of the diene. Anti - 7-norbor-^Whilst t h i s work was i n progress a report of the s y n t h e s i s of t h i s com-pound by the Simmonds and Smith method appeared i n the l i t e r a t u r e by Cope (29), but i n such small y i e l d that the m a t e r i a l was not f u l l y c h a r a c t e r i z e d . An exo c o n f i g u r a t i o n was i n f e r r e d (28,29,30) on the b a s i s of p r e f e r r e d approach to norbornene (31). 8 nenol with diazomethane and cuprous c h l o r i d e y i e l d e d (4C$) a n t i - 8 - t r i c y c l o [3.2.1.0. ' ] o c t a n o l VI (29).jThe presence of the c y c l o p r o p y l group was e s t a b l i s h e d by carbon, hydrogen a n a l y s i s , and by the i n f r a r e d and n.m.r. sp e c t r a . An x-ray c r y s t a l l o g r a p h l c a n a l y s i s (33) on the p-bromobenzene sulphonate V I I (made by r e a c t i n g the a l c o h o l with p_-bromobenzene sulphonyl c h l o r i d e i n a l i t t l e p y r i d i n e (34) and r e c r y s t a l l i z i n g from 65 - 110° petroleum ether) e s t a b l i s h e d beyond any doubt that the c y c l o p r o p y l group had the exo c o n f i g u r a t i o n (29). Hydrogenation with a p l a t i n i u m c a t a l y s t of anti-7-norbornenol V to 7~ norborneol V I I I (35) a n d the r e a c t i o n of p-bromobenzene sulphonyl c h l o r i d e with the l a t t e r gave 7-norbornyl b r o s y l a t e IX ( 8 ) . T h i s compound was re q u i r e d i n order to compare d i r e c t l y i t s r a t e 2 4 of s o l v o l y s i s with the r a t e of anti - 8-tricyclo> [ 3 . 2 . 1 . 0 ] octa n y l d e r i v a t i v e . B. KINETIC 2 4 The b r o s y l a t e of a n t i - 8 - t r i c y c l o [3.2.1.0 ' j o c t a n o l , i n an i n i t i a l c o n c e n t r a t i o n of about 0.04 or 0.08 molar s o l u t i o n s was s o l v o l y s e d i n a s o l u t i o n of 0.11N sodium acetate i n g l a c i a l a c e t i c a c i d which had been r e f l u x e d with 1% excess a c e t i c anhydride. Two or three runs at each of the temperatures were made. 7-norbornyl b r o s y l a t e was s o l v o l y s e d only at 206°; t h i s was so a d i r e c t comparison of r a t e s could be made. The r a t e constants determined appear i n Table I together with the a c t i v a t i o n parameters. The l e a s t squares method was used to determine the slopes (36b,37). In the course of the product s t u d i e s i t was discov e r e d t h a t , under prolonged s o l -2 4 v o l y s i s c o n d i t i o n s the c y c l o p r o p y l group of the t r i c y c l o [3.2.1.0 ] o c t a n y l d e r i v a t i v e had rearranged. I t was>then necessary to e s t a b l i s h whether the r a t e of s o l v o l y s i s determined was that of the t r i c y c l i c b r o s y l -ate or of some rearranged b r o s y l a t e . A" s o l v o l y s i s was made at 200° where 10 i n d i v i d u a l samples were taken every h a l f hour up to three hours, worked up and analysed by gas chromatography and i n f r a r e d s p e c t r a . A n t i - 8 - t r i c y c l o 2 4 [3.2.1.0 ' j o c t a n y l b r o s y l a t e was i s o l a t e d from the samples i n c l u d i n g the three hour one. T h i s represents more than the h a l f l i f e . Hence the r a t e constant determined was most probably f o r the s o l v o l y s i s of t r i c y c l i c b r o s y l a t e f o r two very good reasons. 1) the extremely slow r a t e of r e a c t i o n ; any rearranged m a t e r i a l , e s p e c i a l l y unsaturated would be expected to be much f a s t e r . 2) the presence of t r i c y c l o J 3 . 2 . 1 . 0 2 ' 4 j o c t a n y l b r o s y l a t e i n the s o l v o l y s i s mixture up to three hours shows that the rearrangement by r i n g opening ( i f any) to another b r o s y l a t e i s much slower than the s o l v o l y s i s of the t r i -c y c l i c b r o s y l a t e . TABLE I K i n e t i c Data Determined Compound Temperature °C , -1 k sec kcal/mole A S +e.u. 206.3+ 0.4 198. i t 0.1 163.51 0.2 25° extrap. 7 . 9 9 1 0.16x10^ 3.611 0 . l 8 x l 0 ~ 5 3.041 O . l O x l O - 6 1.08 x 10~ 1 3 30.2 + 1.3 -16.4 206.3 25 2 . 9 7 x 10~ 4 1 . 9 x 1 0 ~ 1 4 (3,4) The average value of the r a t e constant i s given together with the mean d e v i a t i o n c a l c u l a t e d from two runs. 11 TABLE I I Comparison Of Rates For B r o s y l a t e s At 25° (36a) Compound Ref. , -1 k sec notes r e l a t i v e : cyc l o h e x y l -ate vs. 7-norbornyl 36,38 1.7lxlO~ 7 a,c 1 3,4,36 1 . 9 1 x l 0 1 4 b,c 1.1 x 1 0 - 7 1 1 . 0 8 x l 0 1 3 b 6.3 x 10~7 S'7 35,36 4 8.1 0.2xl0~ 4 2.7 O.lxlO"^ c 4.7 x lo] 1.6 x 10 4 1.4 x 1 0 1 1 26 1.20 x 10" 6 7.0 6.3 x 10 8 24,25 2.00 x 10~4 d 1.2 x 10 3 1.0 x 1 0 1 0 39 2.38 x 10~4 1.4 x 10 3 2.2 x 1 0 1 0 IS D-CH2-oBa 40 6.4 x 10~5 at 20° 41 4.74 x 10~6 c 28 •2.5 x 10 8 Botesj a) e x t r a p o l a t e d from 35° b) ext r a p o l a t e d from 200° c) c a l c u l a t e d as three times the reported r a t e of the t o s y l a t e (35) d) estimated from ^-napthalene sulphonate d e r i v a t i v e as 4/9 of b r o s y l a t e C. PRODUCT STUDIES 2 4 A n t i - 8 - i r i c y c l o [3.2.1.0 ' ] o c t a n y l b r o s y l a t e was s o l v o l y s e d at 200° up to 50$ decomposition, t a k i n g samples every h a l f hour. On work up and a n a l y s i s , the samples were shown to be a mixture of unreacted b r o s y l a t e and of two other a c e t a t e s , one of which had the same r e t e n t i o n time as authentic a n t i - 8 - t r i c y c l o [3.2.1.0 ' j o c t a n y l a c e t a t e . The r e s u l t s of the i n f r a r e d 12 spectra of the mixtures were not conclusive, although a spectrum of mixed authentic t r i c y c l o octanyl acetate and authentic t r i c y c l o octanyl "brosylate c losely resembled the spectrum of the material recovered from the s o l v o l -y s i s run. There was d i f f i c u l t y i n gett ing enough acetate material to analyse because of the presence of so much c r y s t a l l i n e brosylate. The expected product, a n t i - 8 - t r i c y c l o | 3 . 2 . 1 . 0 2 , 4 J o c t a n y l acetate was shown by infrared and gas chromatography to be f a i r l y stable under the s o l v o l y s i s conditions, only about one f i f t h of the material rearranging i n three hours. However most of the product studies were c a r r i e d out on material i s o l a t e d from prolonged s o l v o l y s i s of the brosylate, i . e . repre-senting the " i n f i n i t y " sample. There was no t r i c y c l i c acetate present*, instead a mixture of rearranged acetate material (unsaturated) was i s o -l a t e d , which on l i t h i u m aluminium hydride reduction and c a t a l y t i c hydro-genation gave a mixture of three separable alcoholsj two c r y s t a l l i n e which analysed for the empirical formula CgH^O.and whose infrared spectra were almost i d e n t i c a l and therefore probably isomers. The main peak, a l i q u i d , did not analyse for t h i s formula. None of the three alcohol products were i d e n t i f i e d . A s i m i l a r product mixture of acetates was obtained from both the rearrangement of the t r i c y c l i c acetate i n sodium acetate- acetic acid at 200°, and from an acid catalysed r i n g opening of a n t i - 8 - t r i c y c l o 2 4 [3.2.1.0 joctanol i . e . with 70$ p e r c h l o r i c a c i d - acetic acid mixture, at room temperature. 13 I I I . DISCUSSION The work of Story ( 2 7 ) i n p r e p a r i n g the 7-t-butoxy ether of norbor-nadiene provides a very easy method f o r s y n t h e s i s of 7-norbornyl and norbornenyl compounds, which p r e v i o u s l y had to be prepared by a D i e l s -A l d e r type a d d i t i o n r e a c t i o n , or condensations with cyclopentadiene. Hence the p r e p a r a t i o n of anti-7-norbornenol was s t r a i g h t forward and the method s u f f e r e d only from the f a c t that the f i r s t step has a 3 0 $ y i e l d . T h i s i s not too great a disadvantage as norbornadiene i s a v a i l a b l e com-m e r c i a l l y . The attempt to prepare the c y c l o p r o p y l d e r i v a t i v e of a n t i - 7 - n o r b o r -nenol VI by the Simmonds and Smith method f a i l e d to give i s o l a t a b l e amounts. Cope (29) r e p o r t s the p r e p a r a t i o n of the compound but i n y i e l d s too small to be f u l l y c h a r a c t e r i z e d . The Simmonds and Smith reagent does not react with aromatic systems and i s s t e r e o s e l e c t i v e i n i t s r e a c t i o n s with norbornene ( 2 8,30 , 3 2 ) . The method employs methylene i o d i d e and a z i n c copper couple, (probably forming iodomethyl z i n c i o d i d e ) and from the h i g h l y s p e c i f i c nature of the products i t seems probable that the reagent e x i s t s i n some coordinated form (43). Reactions with cyclohexene - 3-ol show that t h i s hydroxyl group does not destroy the reagent i n c o n t r a s t to i t s r e a c t i o n with a Grignard reagent. However the reagent i s r a p i d l y de-composed by water (28) and saturated a l c o h o l s and i t seems that there i s P i g . 8 Simmonds & Smith Reaction 14 competition between methylene transfer and destruction of the reagent. Fig. 9 c Fig. 9 a Fig. 9 b The f i r s t step is formation of a complex^9a. This can react to form methyl iodide and alkoxyzinc iodide, 9 h , or i f the geometry is favorable can form 9 c by addition of the methylene group across the double bond. A favorable geometry can be adopted for cyclohexene-3-ol; the hydroxyl can adopt the axial conformation. The hydroxyl group in 7-norbornenol is anti and cannot assume a favorable position with respect to aiding the addition of the methylene across the double bond and hence probably helps to destroy the reagent as shown by the reaction yielding 9 ^ ' In contrast to the Simmonds and Smith reaction, the cuprous chloride catalysed reaction of diazomethane with anti-7-norbornenol readily occurs. Carbene generated by photolysis from diazomethane gas is highly reactive ( 4 4 ) and reacts indiscriminately by insertion and addition reactions. However i f the carbene is deactivated (28 ,45) (Simmonds and Smith reagent is also a deactivated form of carbene) stereospecific addition reactions can occur. The presence of anhydrous cuprous chloride (or bromide) in the reaction mixture deactivates the carbene sufficiently so that stereospecific addition reactions to the olefinic bond have preference over insertion re-actions, and yet the carbene intermediate is s t i l l sufficiently active to react with aromatic systems ( 4 5 )• A mechanism has been proposed ( 4 5 ) in which the nucleophilic carbon from one of the resonance forms of diazo-methane f i l l s up the vacant orbital of Cu*. 15 A . * P i g . 10 Simultaneous or successive s p l i t t i n g o f f of the n i t r o g e n occurs to leave a carbene-copper complex which a t t a c k s the o l e f i n i c bond. P i g . 11 + C u H o L The r e a c t i o n mixture becomes dark and a m e t a l l i c c o a t i n g forms on the s i d e of the f l a s k , a p o s s i b l e i n d i c a t i o n that Cu* accepts e l e c t r o n s and i s r e -duced to Cu°. Predominance of exo-product most l i k e l y occurs because of p r e f e r r e d exo a t t a c k on the norbornene system (31). C o l l e c t i o n of the second major peak from the diazomethane r e a c t i o n with anti - 7-norbornenol by gas chromatography gave some m a t e r i a l (impure) whose n.m.r. and i . r . s p e c t r a showed the presence of the c y c l o p r o p y l group and were s i m i l a r to the spectra of the exo a d d i t i o n product; i t was t e n t a t i v e l y i d e n t i f i e d as the endo_-isomer. The p-bromobenzene sulphonate e s t e r of the e x o - t r i c y c l o octanol was a white c r y s t a l l i n e s o l i d which r e a d i l / y d i s s o l v e d i n a c e t i c a c i d - sodium acetate to give the k i n e t i c s o l u t i o n s . The r a t e constant determined f o r the —5 o s o l v o l y s i s r e a c t i o n was extremely small (7.99 x 10 , t ^ = 2.4 hrs at 206 ). 2 The f a c t that the r a t e was slow i s strong evidence that the r a t e measured was that of the t r i c y c l i c b r o s y l a t e and not of rearranged b r o s y l a t e . 16 Unreacted brosylate could be i s o l a t e d from the s o l v o l y s i s mixture a f t e r a time of three hours at 200°. The cyclopropyl r i n g of the t r i c y c l o o c t a n y l acetate, under s o l v o l y s i s conditions at 200° rearranged very slowly; a f t e r 3 hours only about one f i f t h of the material had rearranged. Therefore i f the cyclopropyl r i n g of the t r i c y c l i c brosylate i s assumed to rearrange at a s i m i l a r r a t e , then at the h a l f l i f e of the s o l v o l y s i s r e a c t i o n (ca 2|- h r s ) , l e s s than one tenth of the t o t a l material has rearranged. This eliminates the possible occurrence of f a s t cyclopropyl r i n g opening to form some other brosylate which then solv o l y s e s . Any co n t r i b u t i o n to the rate by a slow r i n g opening process followed by a f a s t s o l v o l y s i s of the rearranged bros-y l a t e must be small. The enthalpy of a c t i v a t i o n (about 30 kcal/mole) ob-tained f o r the t r i c y c l i c brosylate s o l v o l y s i s was about the same value as f o r 7-norbornyl t o s y l a t e s o l v o l y s i s (35.7 kcal/mole (3)) which i n d i c a t e s that the same type of r e a c t i o n i . e . carbonium ion formation i s involved. Hence the exo-isomer of the t r i c y c l o o c t a n y l brosylate solvolyses very slowly, about four times more slowly than 7-norbornyl brosylate at 200°. This makes i t 1 0 ^ times slower than anti - 7-norbornenyl. The question whether the 7-norbornenyl d e r i v a t i v e r e a l l y solvolyses with an enhanced rate v i a an intermediate non c l a s s i c a l i o n , or that the r e s u l t s should be inter p r e t e d as an unusual inertness i n the norbornyl d e r i v a t i v e i s s t i l l undecided ( 1 0 , l l ) . I t i s proposed to discuss the pre-sent r e s u l t s i n terms of the inertness of the d e r i v a t i v e . The rate constant determined i n t h i s work was comparable to the rate of the 7-norbornyl system, the explanations put forward f o r the inertness of the l a t t e r can be applied to the former. The fa c t o r s often quoted f o r the slowness of 7-norbornyl may be r e i t e r a t e d (50)sl) s t e r i c hindrance to s o l v a t i o n of the t r a n s i t i o n state by the exo hydrogens 2) the increase i n I s t r a i n (51) 17 on i o n i z a t i o n . l ) S t e r i c i n h i b i t i o n to s o l v a t i o n of the t r a n s i t i o n s t a t e would be p a r t i c u l a r l y s trong f o r the t r i c y c l i c o ctanyl system. I f the l e a v i n g group were to take a path remaining perpendicular to the plane of the developing carbonium i o n and acquire a s h e l l of s o l v a t i o n there would be hindrance by the 7-exo as i n the case of 7-norbornyl. There would be an even greater hindrance to s o l v a t i o n of the carbonium i o n with the exo hydrogens of the c y c l o p r o p y l group. Hence i f no other f a c t o r s were i n v o l v e d , t h i s could account f o r some of the r e t a r d a t i o n with respect to 7-norbornyl. 2) Since s t e r i c s t r a i n at the 7-carbon atom i n c r e a s e s on i o n i z a t i o n t h i s could be a very important f a c t o r i n determining the r a t e s of 7-norbornyl d e r i v a t i v e s . I - s t r a i n (51) i s defined by H.C.Brown as "change i n i n t e r n a l s t r a i n which result.s from change i n c o o r d i n a t i o n number of a r i n g atom i n v o l v e d i n chemical r e a c t i o n " . T h i s theory, advanced to e x p l a i n the seeming randomness of s u b s t i t u t i o n r a t e s of c y c l i c systems has met with success, but there are l i m i t a t i o n s , p a r t i c u l a r l y i n the f a i l u r e to p r e d i c t the r a t e s of some SN^ r e a c t i o n s , and i t should be borne i n mind that other important c o n t r i b u t i n g f a c t o r s must be taken i n t o account as w e l l . In a saturated carbon atom, the normal h y b r i d i z a t i o n i s s p 3 , corresponding to a bond angle of 109°28 !„ In a planer carbonium i o n , the h y b r i d i z a t i o n i s s p 2 with bond angles at 120°. In small r i n g compounds where the bond angles are 60° or 90°, there w i l l be r e l u c t a n c e to form a carbonium i o n H P i g . 12 18 because of the increase i n s t r a i n i n attempting to go from 60 or 90 to 120° ( s p ^ ) . The C^-C^-C^ angle i n 7-norbornyl systems i s about 98° (52), hence a slow r a t e would be expected i f the above theory holds: the r a t e should s t i l l be f a s t e r than f o r c y c l o p r o p y l and c y c l o b u t y l d e r i v a t i v e s . However c y c l o p r o p y l d e r i v a t i v e s (53) r e a c t two orders of magnitude f a s t e r than 7-norbornyl. The presence of anchimeric a s s i s t a n c e i s suspected i n r e a c t i o n s of c y c l o p r o p y l t o s y l a t e because of e x c l u s i v e formation of r e -arranged product, a l l y l a c e t a t e . Rearranged products are a l s o found f o r c y c l o b u t y l s o l v o l y s i s . The 2-adamantyl (50) system has been compared with 7-norbornyl. Fig.l3« r-Fig.. 13 T h i s molecule i s unique because i t has a r i g i d , s t r a i n f r e e r i n g system being composed of fused c h a i r cyclohexane r i n g s . The same r e l a t i o n s h i p with bridgehead hydrogens i s present, the main d i f f e r e n c e between the mole-c u l e s being the C-C-C angle of the methylene b r i d g e , the angle i n adaman-tane i s 109.5°' 2-adamantyl t o s y l a t e s o l v o l y s e s 10^ times f a s t e r than 7-norbornyl t o s y l a t e showing that the increase i n angle s t r a i n i s of primary importance i n determining r a t e d i f f e r e n c e s f o r the two systems considered. The GI~CQ~C^ angle i n the t r i c y c l i c o c t a n y l d e r i v a t i v e i s 96° (33), s l i g h t l y s maller than the 7-norbornyl, a f a c t which could account f o r the small r e t a r d a t i o n i n r a t e . I t i s of i n t e r e s t to poin t out that f o r the octahydrodimethanonap^thyl (39) system, the r a t e of s o l v o l y s i s i s only f o u r times l e s s than that of the ahti - 7-norbornenyl system and yet the angle C,-C i n-C. i s the same as i n 7-norbornyl. Hence there must be some other 13 F i g . 14 f a c t o r as w e l l as angle s t r a i n f o r the enhanced r a t e of anti - 7-norbornenyl system, and t h i s i s most probably n o n - c l a s s i c a l resonance e f f e c t s . Anchi-meric a s s i s t a n c e i s p o s s i b l e by a cyclopropenyl type i o n , Figure 1$. From the slow r a t e determined f o r the ezo-isomer of t r i c y c l o 2 4 [3.2.1.0 ' ] o c t a n y l b r o s y l a t e , there are no s p e c i a l s o l v o l y s i s p r o p e r t i e s which have to be d e s c r i b e d by a n o n c l a s s i c a l i o n . However a few f a c t o r s might be considered before d i s m i s s i n g completely the idea that the presence of a c y c l o p r o p y l group might i n f l u e n c e the s o l v o l y s i s r a t e by s t a b i l i z a t i o n of the carbonium i o n . I t has been shown (46) that the geometry of the c y c l o p r o p y l group i s important i f overlap of c y c l o p r o p y l e l e c t r o n s with the o r b i t a l s of a carbonyl group i s to occur to any great extent. For a c y c l o -propyl r i n g attached to a r i n g system^overlap. ("Figure 15a) can only occur i f the plane of the c y c l o p r o p y l r i n g and the plane of the p - o r b i t a l s of the carbonyl are p a r a l l e l . F urther evidence (47) f o r t h i s i s i n the t r i -2 6 c y c l o [2.2.2.0 ' ]octene system, Figure 15b, where overlap, detected by a bathochromic s h i f t i n the U.V., occurs, e " the c y c l o p r o p y l r i n g and the o r b i t a l s of the double bond are p a r a l l e l . (b) (a) F i g . 15 (c) 20 The rate of s o l v o l y s i s of 7-quadricyclo [2.2.1.0 2' 6.0 3 ,^Jheptane d e r i v a t i v e (24), Figure 15c, i s accelerated by 1 0 1 0 compared to the corresponding 7-norbornyl d e r i v a t i v e ; one explanation f o r the enhanced rate being the s t a b i l i z a t i o n of the carbonium ion by overlap with the cyclopropyl e l e c -trons. Comparison of the geometries of exo and endo isomers of a n t i - 8 -2 4 t r i c y c l o [3.2.1.0 ' ]octanyl d e r i v a t i v e s i n d i c a t e s that overlap of the cyclopropyl electrons and a developing carbonium i o n may be more e f f e c t i v e i n the l a t t e r case. exo (a) endo (b) OTi C I S F i g . 16 3-bicyclo hexyl c a t i o n n o n c l a s s i c a l The bent-bond model f o r cyclopropane r e s u l t i n g i n p a r t i a l d e r e a l i z a t i o n of the cr electrons imparts a jf character which i s orientated i n the same plane as the r i n g carbons. Hence f o r the exo-isomer the o r b i t a l s of the r i n g are d i r e c t e d away from the p o r b i t a l of the carbonium i o n , Figure 16a, and possible overlap i s greater f o r the endo isomer where the o r b i t a l s are angled towards the p o r b i t a l , Figure 16°« There i s a s i m i l a r i t y between the endo isomer and c i s 3-bicyclo [3.1.0Jhexyl system (48), Figure lfcc; part of the endo molecule having the same ch a i r form as the bicyclohexyl system. The c i s isomer solvolyses with some anchimeric assistance to give the acetate with complete r e t e n t i o n of c o n f i g u r a t i o n , u n l i k e the trans isomer which gives cis-acetate product, as w e l l as o l e f i n , with i n v e r s i o n . An intermediate with the symmetrical non c l a s s i c a l structure has been suggested to e x p l a i n t h i s , supported by 21 quantum mechanical (1,49) c a l c u l a t i o n s of d e r e a l i z a t i o n energy f o r the s t r u c t u r e . Hence q u i t e apart from the s p e c i a l p r o p e r t i e s of d e r e a l i z a t i o n of the c y c l o p r o p y l e l e c t r o n s , the endo t r i c y c l o [3.2.1.0 2' 4] octanyl molecule might be expected to show enhanced r a t e s of s o l v o l y s i s . OB* 2 0 0 ° r\-^-P\. MIXTURE OF REARRftWSfcC' h*5- \ / / IZ hn. RC6tAT£S;UNSflTURATeP. HOI\t ^ " [otK 0LtFliv/«C6T*VTfc Nft-OAc. MXTUR&] F i g . 17 The products of the s o l v o l y s i s r e a c t i o n proved to be more complex than those from the s o l v o l y s i s of 7-norbornyl d e r i v a t i v e s . The presence of a h i g h l y s t r a i n e d c y c l o p r o p y l group together with the high temperature of r e a c t i o n r e s u l t e d i n a v a r i e t y of rearranged products. The f i n a l product from s o l v o l y s i s of e x o - a n t i - 8 - t r i c y c l o J3.2.1.Q 2* 4]octanyl b r o s y l a t e over a p e r i o d of s i x h a l f l i v e s (12 hours) contains no c y c l o p r o p y l group. Although i t has not been d e f i n i t e l y proved, the f a c t that m a t e r i a l with the same r e t e n t i o n time as authentic a n t i - 8 - t r i c y c l o o c t a n y l acetate has been i s o -l a t e d from the s o l v o l y s i s of the b r o s y l a t e up to the h a l f l i f e , and that the i n f r a r e d spectrum of m a t e r i a l i s o l a t e d i s i d e n t i c a l to the spectrum of a mixed sample of authentic t r i c y c l i c o c t a n y l b r o s y l a t e and acetate, i t i s probable that one of the f i r s t products formed i s a n t i - 8 - t r i c y c l o o c t a n y l a c e t a t e . Under prolonged s o l v o l y s i s c o n d i t i o n s (12 hours or more at 200°) the authentic acetate rearranges to give the same products ( i n s l i g h t l y d i f f e r e n t p roportions) as those i s o l a t e d from prolonged s o l v o l y s i s of the b r o s y l a t e . The main product i n the above rearrangements i s a l s o formed i n simple a c i d c a t a l y s e d c y c l o p r o p y l r i n g opening at room temperature (per-c h l o r i c a c i d i n a c e t i c a c i d ) . The main products from c y c l o p r o p y l r i n g 22 opening i n other systems (42) are 1-Me or 2-Me o l e f i n s or a c e t a t e s . The p r o d u c t s , i s o l a t e d from prolonged s o l v o l y s i s of the b r o s y l a t e were unsat-urated acetates (or an acetate, o l e f i n mixture). Therefore i t seems l i k e l y that the main rearranged product from a simple c y c l o p r o p y l r i n g opening could be 2-methyl b i c y c l o [2.2.1J hept-2-ene-7-yl acetate, F i g u r e ljj b . F i g . 18 The other products p o s s i b l y a r i s e from rearrangement of t h i s m a t e r i a l . 23 IV. EXPERIMENTAL A. SYNTHETIC I f solvent used, then s t a t e d , otherwise a neat sample was used. I n f r a r e d s p e c t r a peaks given i n cm (w) = weak; (m) • medium; (s) = strong n.m.r. spe c t r a peaks given i n T values, r e l a t i v e to Tetramethyl s i l a n e at 10 f . D e s c r i p t i o n of the n.m.r. peaks: ( s ) = s i n g l e t or unresolved m u l t i p l e t (m)=multiplet, but incompletely r e s o l v e d (2)=doublet, e t c . l ) 7-t-Butoxynorbornadiene (27) To a s t i r r e d r e f l u x i n g mixture of 149 g.(1.62 moles) of norbornadiene (Matheson, Coleman & B e l l , P r a c t i c a l grade) and 0.325 g. (2.3 moles) of cuprous bromide i n 500 ml benzene, i n a 3-liecked, 2 1. f l a s k , i n a n i t r o -gen atmosphere, was added. 122.5 g« (0.63 mole) of t ^ b u t y l perbenzoate i n 100 ml of benzene over about 1 hour. A d d i t i o n of the perbenzoate was accompanied by formation of a deep green c o l o u r a t i o n of the s o l u t i o n . The mixture was r e f l u x e d f o r 1 hour. A f t e r c o o l i n g to room temperature the mixture was t r a n s f e r r e d to a s e p a r a t i n g funnel and extracted with 10$ sodium bicarbonate to remove the benzoic a c i d . I t was than washed with water and d r i e d over anhydrous magnesium sulphate. A f t e r f i l t e r i n g , most of the benzene was removed on the f l a s h evaporator, care being taken to avoid excessive h e a t i n g of the mixture ,7-t-butoxynorbornadiene was d i s -t i l l e d from a brown t a r . B.pt. 58-60° at 3 mm. Y i e l d 34 g. (33.5$). I n f r a r e d : 2950 ( s ) , 15.40 (w), 1390 (m), 1360 ( s ) , 1320 (m), 1190 ( s ) , 1105 ( s ) , 730 ( s ) . ( n.m.r.: o l e f i n i c 3.45> 3.58 (m), bridge 6.38 (m), bridgehead 6.77 ( s ) » 24 other 8.94 ( s ) . A n a l y s i s : c a l c u l a t e d f o r C^B^gO : C, 80.44 5 H, .9.8.2 found : C, 80.22 j H, 9.69 2) 7-Norbornadienyl Acetate (27) A s o l u t i o n of 28 g.(0.172 mole) of 7-;t-butoxynorbornadiene i n 5.5 ml of a c e t i c anhydride and 275 ml of g l a c i a l a c e t i c a c i d mixture, was cooled i n i c e to 0° . The mixture was added to 38.5 g. (0.261 mole) of 70$ p e r c h l o r i c a c i d which had a l s o been cooled to 0°. A deep red c o l o u r -a t i o n was produced. The s o l u t i o n was allowed to stand f o r 1 minute i n the i c e bath, before being t r a n s f e r r e d to a s e p a r a t i n g funnel which contained about 800 ml of i c e and water. The product was e x t r a c t e d with 3 x 50 ml of dichloromethane, and the combined e x t r a c t s were washed with a saturated sodium bicarbonate s o l u t i o n and a saturated sodium c h l o r i d e s o l u t i o n before being d r i e d over anhydrous magnesium sulphate. The d i -chloromethane was removed on the f l a s h evaporator and d i s t i l l a t i o n of the product, from a deep red t a r y i e l d e d 17.34 g. (68$) of 7-norborna-d i e n y l acetate, a c o l o u r l e s s l i q u i d , with a r a s p b e r r y - l i k e odor. B.pt. 70° at 12 mm. I n f r a reds 2950 (m), 1730 ( s ) , 1540 (w), 1370 (m), 1320 (m), 1245 ( s ) , 1040 ( s ) , 910 (m), 835 (m), 735 ( s ) . n.m.r.: o l e f i n i c 3- 35 > 3.55 (n>), bridge 5»55 ( s ) ? b r i d g e -head 6.45 ( m)» other 8.14 (m). A n a l y s i s : c a l c u l a t e d f o r C^H^O^ : C, 71.98; H, 6.71 . found C, 72.04; H, 6.67 • 3) Anti - 7-norbornenol (27) 10 g. (0.066 M) of 7-norbornadienyl acetate i n 150 ml of anhydrous ether was slowly added to a s t i r r e d s o l u t i o n of I .89 g. (0.05 M) of 25 L i A l H ^ i n 150 ml of anhydrous ether, i n an atmosphere of n i t r o g e n . The a d d i t i o n was complete a f t e r about h a l f an hour. The s o l u t i o n was s t i r r e d overnight, a f t e r which excess water, and then enough 10$ s u l p h u r i c a c i d s o l u t i o n j u s t to d i s s o l v e the p r e c i p i t a t e d s a l t s , was added. The pro-duct was then e x t r a c t e d with 3 x 100 ml ether and the combined e x t r a c t s washed with water, 10$ NaHCO^ and again with water. A f t e r d r y i n g over anhydrous MgSO^ the ether was slowly removed on the f l a s h evaporator; the l a s t b i t of ether was taken o f f by the high vacuum pump. 5 S> (68$) of s o l i d anti - 7-norbornenol remained which melted at l l6°-117°/ ' a f t e r p u r i f i c a t i o n by gas chromatography on a 5* , 20$ Apiazon J , on 60/80 f i r e b r i c k column at 150°. No syn - 7-norbornenol i s formed i n t h i s r e a c t i o n . I n f r a r e d : 3300 ( s ) , 1330 (m), 1120 ( s ) , 1070 ( s ) , 870 (m), 710 (s) . n.m.r.: o l e f i n i c 4.13 (3), bridge 6.10 ( s ) , hydroxyl 6.55 (m), b r i d g e -head 7.55 (m), exo and endo 8.23 (m) 9.05 (m). A n a l y s i s : c a l c u l a t e d f o r C^H.^0 : C, 76.33 5 H, 9.15 . found : C, 76.17 ; H, «?.05 . 4) C a t a l y t i c Hydrogenation of Anti - 7-norbornenol to 7-norborneol 1.75 S- of anti - 7-norbornenol i n 50 ml of 95$ ethanol together with 0.2 g. of p l a t i n i u m oxide c a t a l y s t , consumed about 400 ml of hydrogen ( c a l c u l a t e d amount 360 ml). The c a t a l y s t was f i l t e r e d o f f and the ethan-o l removed and the crude product r e c r y s t a l l i z e d from 30°-60° petroleum ether, m.p. 150°. I n f r a r e d : 3250 (w), 1140 (m), 1060 (m), 835 (w), 725 (w). n.m.r.: (CCl^) bridge 6.11 ( s ) , hydroxyl 7.52 ( s ) , other 8.1 (m) 8.7 (m) A n a l y s i s : c a l c u l a t e d f o r C^H'^O : C, 75.00 ; H, 10.72 found : C, 75.13 5 H, 11.25 26 5) Preparation of 7-Norbornyl Brosylate (34) 1.28 g. (0.005 M) of £-bromobenzene sulphonyl chloride (recrystal-lized from 60°-110° petroleum ether m.p. 75—76 sharp) was dissolved in 5 ml of dry pyridine. This was added to O.56 g. (0.005 l ) of 7-norbor-neol, also in a l i t t l e pyridine; the mixture became warm. Crystals of pyridine hydrochloride appeared on standing overnight in the fridge. A large excess of water was added, which dissolved the crystals and an oily material appeared, which on scratching with a glass rod, crystal-lized. This was filtered off, and dried by suction before being recrys-tallized from 30-60° petroleum ether, m.p. 5 1 ° - 5 2 ° ,yield 1.52 g. (92$). n.m.r.: aromatic 2.28 (m), bridge 5.5 (s), 7.9 (s),~~ 8.5 (m) Analysis: calculated for C^H^O^SBr : C, 47.43 ; H, 4-53 found : C, 47.02 5 H, 4.37 6) Methylene Addition to Bicyclic Olefins a) Simmonds and Smith reaction (28) i) preparation of a zinc-copper couple A simple procedure was used; about 5 g m of Zn dust was washed suc-cessively with 2 x 10 ml of 3$ hydrochloric acid, 2 x 12 ml water, 2 x 10 ml of 2$ copper sulphate solution. The couple was filtered and dried in a desciccator. i i ) attempted preparation of the cyclopropyl derivative of anti-7-norbornenol 0.9 g. (.008M) zinc-copper couple and 0.12 g. (.0005 M) iodine (Mallinckrodt.A.R.) were stirred together with 10 ml of anhydrous ether in a flask, fitted with a reflux condenser. When the iodine colour had faded, 1.87 g. (0.007 M) of methylene iodide (Matheson, Coleman & Bell, 27 distilled before use) and anti-7-norbornenol, in a l i t t l e ether, were added and the mixture refluxed for 48 hours. No polour change occurred. The couple was filtered off and the f i l t r a t e washed with 5$ hydrochloric acid, 5$ sodium bicarbonate solution and water. After drying over anhy-drous magnesium sulphate, a sample of the reaction mixture was analysed by gas phase chromatography on 10 foot, 20$ didecyl phthalate on f i r e -brick column at 140°. No peaks, other than starting materials were pre-sent. The reaction was repeated at a higher temperature by using diglyme (bis-(2-methoxyethyl) ether Eastman Organic Chemicals) and after 72 hours, the grey couple had been replaced by finely divided copper. Anal-ysis by gas phase chromatography using the same conditions as above showed that there was present, in very small quantities (less than 3$) two components other than the starting materials, but attempted col-lection of these peaks failed. b) Copper catalysed reaction of diazomethane with olefins (32) General. Procedure Diazomethane gas was generated in a 230 ml, 3 necked flask, fitted with a magnetic stirrer, and gas inlet and outlet tubes, by the reac-tion of N-methyl-N-nitrosourea (55) a n < l a 50$ potassium hydroxide solu-tion. One hundred ml of diethyl ether formed an.upper layer in the flask, and the diazomethane gas dissolved in this layer as i t was generated by the addition of one gram lots of the urea. This addition was carried out over a period of seven to eight hours so that at no time was there a high concentration of diazomethane in the ether; the yellow colour of the solution acted as a guide to the concentration. A continuous stream of nitrogen bubbled through the ether layer, carrying the diazomethane 28 through a drying tube, packed with KOH pellets and through an inlet tube to the bottom of the reaction flask. This contained the olefin in a stirred solution of 50 ml of anhydrous diethyl ether together with @ 0.3 g. of cuprous chloride (B.D.H.,A.R.). Both generator and reaction flasks were cooled in ice. No attempt was made to retain high concen-trations of diazomethane in the reaction flask by condensing leaving vapours at dry-ice temperatures. Although this is wasteful on diazometh-ane and ether, the danger of explosions i s , in our experience, elimin-ated. Ether was replenished from time to time in both the generator and reaction flask, as i t was being swept out by the nitrogen stream. The reaction was monitored by gas-phase chromatography, samples being taken out about every hour. The copper chloride was filtered off and some of the ether removed before injection of the sample. In this way the pro-gress of the reaction could be followed. It was noticed that after \\ to 2 hours, the green cuprous chloride suspension was replaced by a dark-brown black suspension, which after about 3 hours, coated the flask and gas inlet tube with a black mettalic film. On exposure to the air this film slowly reverted to the green colour of cuprous chloride. When the olefin was completely consumed after about eight hours, the solution was filtered to remove the cuprous chloride and the ether evap-orated. If the product was crystalline, then sometimes crystals appeared in the ether solution and were filtered off. Purification by gas phase chromatography was employed i f the product was a liquid. 2 4 i) diazomethane and norbornene: preparation of tricyclo [3.2.1.0 ' j octane (28) 4.2 g. (0.1 M) of diazomethane generated from 15.5 g» of N-methyl-29 N-nitroso urea and 45 ml of 50$ KOH was bubbled through a solution con-taining 2.82 g. (0.03 M) of norbornene i n 50 ml ether and 0.3 g. CuCl. The reaction was monitored by gas phase chromatography on a 10 foot, 20$ carbowax 20-1 on f i r e b r i c k column at l30°-135°. The main peak was collected and identified by n.m.r. and infrared spectra as t r i - c y c l o 2 A-[3.2.1.0 ' Joctane. In one run 2-norbornahol was formed when water was present in the reaction flask. Infrared: 2880 (s), 1450 (m), 1320 (m), 1040 (m), 1000 (m), 970 (m), 811 (m), 722 (s). n.m.r.: (CCl^) 7.8 (s), 2.7 (m), cyclopropyl 9.4 (m). Analysis : calculated for CgH 1 2 : C, 88.90; H, 11.11 found : C, 88.63; H, 11.37 i i ) diazomethane and 7-norbornadienyl acetate 6.3 g. (0.15 M) of diazomethane generated from 67.5 ml of 50$ KOH solution and 23.23 g. of U-methyl-N-nitrosourea was reacted with 9«0 g. (0.06M) of 7-norbornadienyl acetate i n the presence of 0.8 g. of cuprous chloride. A 5 foot, 20$ Apiazon J , on 60/80 f i r e b r i c k column at 110° was used to monitor the reaction and to separate the product from starting material. The n.m.r. spectrum showed the product to be a mix-ture of two components, i n the ratio of three to one, arising from addition to either of the double bonds of the diene. This was apparent' from the presence of d i s t i n c t sets of peaks for different o l e f i n i c and acetate protons. Separation of the isomers on a 5 foot Ucon polar c o l -umn at 110° was attempted, but without success. Infrared: 2950 U ) , 1730 (s), 1360 (s), 1240 (s), 1040 (s), 905 (w), 785 (w), 725 (m), 689 (m). 30 n.m.r.: olefinic 3.65 (3), 4.32 (3), bridge 5.55 (s), 6.02 (s), 7.10 (m), 7.65 (m), acetate 8.08 (m), 8.12 (m), cyclopropyl @ 9.0 (m). Analysis: calculated for ^ H 0 . C, 73.14; H, 7.37 found : C, 73.40; H, 7.25 i i i ) diazomethane and anti-7-norbornenol: preparation of anti-8-2 4 tricyclo [ 3 . 2 . 1 . 0 ^ ^ octanol 3.15 8' (0.075 M) of diazomethane from 11.63 g. of N-methyl-N-nit-roso urea with 33 ml of 50$ K0H solution reacted with 3.3 g. (0.03 M) of anti-7-norbornenol (purified by sublimation) in the presence of 0.3 g. of cuprous chloride in 50 ml of ether. The reaction was followed by gas chromatography on a 5 foot, 20$ Apiazon J, on 60/8O firebrick column at 130°, at least two other peaks besides the starting material peak were present. In subsequent runs by using a 5 foot carbowax (on 60/8O Chrom.W, acid washed) the presence of at least four components was shown. However, collection of the largest two peaks only, (ratio 10:l) was ac-complished. The major product, a white crystalline solid, m.p. 75° - 76°, after recrystallization from 65°-110° petroleum ether, was identified as the exo-isomer of anti - 8 -tricyclo [3.2.1 .0 2 ' 4 ] octanol. In some runs the material crystallized out from the ether solution, and so was f i l -tered off. The mother liquor contained more exo-isomer as well as the second major component,a liquid, which was collected and identified 2 4 tentatively as the endo isomer of anti-8-tricyclo [3.2.1.0 Joctanol from the n.m.r. However this was formed only in very small yield. Yield of exo-isomer, 1.49 g. (40$) after recrystallization. exo-isomer: Infrared: (CC14) 3400 (s), 1450 (w), 1260 (m), 1130 (s), 1090 (s), 1040 (s), 1000 (m), 955 (m), 810 (m), 740 (m). 31 n.m.r.: (CC14) bridge 6.47 (s.), hydroxyl 7.13 (s), bridgehead 7.?7 (s), exo/endo @ 8.3 (m), 8.7 (m), cyclopropyl 6 9.4 (m), 10.04 (m). Analysis: c a l c u l a t e d f o r CgH^O : C, 77.37; H, 9.74 found : C, 77.25; H, 9.71 endo-isomer, (impure sample, not f u l l y characterized) Infrared: 3 4 0 0 (w), 2900 ( s ) , 1720 (w), 1450 (w), 1260 (w), l l 8 0 (w), 1.14.0 (m), 1120 (s),, 1010 (w), 8 1 0 (m), 745 (m). n.m.r. j (CCl^) 6.85 (m), 7.79 ( s ) , cyclopropyl 1,0.1 (m) Anal y s i s : calculated f o r CgH^O » C, 77.37; H, 9.74 found : C, 78.76} H, 9 . 9 3 . eja- _ o A 7) Preparation Of The Brosylate O f ^ A n t i - 8 - T r i c y c l o [3.2.1.0 '^lOotanol (34) O.85I ( 0 . 0 0 3 M) of r e c r y s t a l l i z e d p_-bromdbenzene sulphonyl c h l o r -i d e , i n a l i t t l e p yridine was added to .0.413 g. (0.003 M) o f ^ a n t l - 8 -t r i c y c l o [ 3 . 2 . 1 . 0 2 ' 4 J o c t a n o l i n py r i d i n e , and the mixture worked up i n the same way as described f o r 7-norbornyl brosylate. The product was re -c r y s t a l l i z e d from 65-110° petroleum ether and melted at 83-83.5°. Infraredr ( C H C l ^ 2900 (w), 1570 (ra), 1450 (w), 1350 ( s ) , 1260 (w), 1170 ( s ) , 1095 (m), 1065 ( s ) , 985 ( s ) , 905 (m), 880 (m),865(m). n.m.r.: aromatic 2 . 3 3 ( s ) , bridge 5.86 ( s ) , bridgehead 7.74 ( s ) , exo/endo 8.5 (m), 9.2 (m). . Analysis: c a l c u l a t e d f o r C^H^O^SBrs C, 48.98; H, 4.40 found : C, 49-17; H, 4.50 X-ray anal y s i s on the brosylate showed that the cyclopropyl group had the exo configuration (33) 32 B. KINETIC General Procedure K i n e t i c s t u d i e s on the a c e t o l y s i s of the b r o s y l a t e s of a n t i - 8 -2 4 t r i c y c l o [3.2.1.0 ' ] o c t a n o l , and of 7-norborneol were c a r r i e d out ac-c o r d i n g to the procedure of Giddings (36). Conditions had been chosen, which were s i m i l a r to those of Norton (4) and Woodward (3), which i n t u r n had been chosen to be s i m i l a r to Winstein (4l) and of Roberts (6). Samples of b r o s y l a t e were weighed out i n t o 25 ml volumetric f l a s k s , so that the r e s u l t i n g s o l u t i o n would be about 0.04 molar (a few runs were made with 0.08 molar s o l u t i o n s to check on the f i r s t order r a t e ) . 0.11 molar s o l u t i o n of stock sodium acetate i n g l a c i a l a c e t i c a c i d was added to the 25 ml mark. About 1.5 nil of t h i s s o l u t i o n was p i p e t t e d out i n t o glass i n d i v i d u a l , t h i c k walled^tubes, which were seal e d . These were put i n t o brass bombs, f i t t e d with pressure caps before being placed i n a constant temperature s i l i c o n e bath, with temperatures around 200°. I t was nec-essary to preheat the o i l bath to about 25° above the temperature at which the run was to be made, i n order to o f f s e t part of the l a r g e tem-perature drop which occurred when the bombs were put i n . About h a l f an hour was r e q u i r e d before c o n d i t i o n s e q u i l i b r a t e d , a f t e r which time (t=0) the f i r s t sample was removed, cooled under the tap, and the tube opened. A 1 ml a l i q u o t was p i p e t t e d out i n t o an erlenmeyer f l a s k c o n t a i n i n g 10 ml of about 0.02 molar s o l u t i o n of p e r c h l o r i c a c i d i n g l a c i a l a c e t i c a c i d , and four or f i v e drops of i n d i c a t o r (a s a t u r a t e d s o l u t i o n of brom-phenol blue i n g l a c i a l a c e t i c a c i d ) added. The s o l u t i o n which was c o l o r -l e s s was t i t r a t e d a g ainst a standard 0.02 molar s o l u t i o n of sodium acetate i n g l a c i a l a c e t i c a c i d to the f i r s t yellow c o l o u r . A f t e r the 3 3 f i r s t three or four samples, c h a r r i n g of the s o l u t i o n s took p l a c e , and v a r y i n g amounts of c a r b o n - l i k e m a t e r i a l were deposited on the s i d e s of the tube, which had to be f i l t e r e d o f f before the 1 ml a l i q u o t could be p i p e t t e d out. For most of the runs the i n f i n i t y sample was so dark that the end point c o u ld not be determined a c c u r a t e l y and so the t h e o r e t i c a l end point was used. 1) P r e p a r a t i o n of 0.02 N P e r c h l o r i c A c i d S o l u t i o n The p e r c h l o r i c a c i d s o l u t i o n was made by adding, to a mixture of 16.5 ml of a c e t i c anhydride (B.D.H. AR) and 15Q0 ml of g l a c i a l a c e t i c a c i d (Nichols Chem.Co., reagent grade), 4-26 g. ( 0 . 0 3 M) of 7 0 $ per-c h l o r i c a c i d ( N i c h o l s Chemical Co., reagent grade) and r e f l u x i n g f o r 5 hours. T h i s was standardized against sodium acetate s o l u t i o n , prepared from primary standard sodium carbonate (below). The normality of the a c i d was, f o r the f i r s t p r e p a r a t i o n , 0.02055». and f o r the second, 0 .02009. 2) P r e p a r a t i o n of Standard Sodium Acetate S o l u t i o n 1.0607 g. of primary standard sodium carbonate ( M a l l i n c k r o d t AR) was weighed out i n t o a 1000 ml volumetric f l a s k and the s o l u t i o n made up to the mark with reagent g l a c i a l a c e t i c a c i d . T h i s gave a s o l u t i o n of 0.02001 N. For a second p r e p a r a t i o n a s o l u t i o n of 0.02007 N was ma.de :.up.-. 3 ) P r e p a r a t i o n of the Stock Sodium Acetate S o l u t i o n T h i s was made by d i s s o l v i n g 79«5 g- (0.75 M) of sodium carbonate ( M a l l i n c k r o d t AR) i n 1400 ml of reagent grade g l a c i a l a c e t i c a c i d ( N i c h o l s Chemical Co.) and 85 ml of a c e t i c anhydride (B.D.H. AR) and making the t o t a l volume of the s o l u t i o n 1500 ml by adding more g l a c i a l a c e t i c a c i d . I t was r e f l u x e d f o r 5 hours. 10 ml of t h i s s o l u t i o n , 34 (approximately 1 N|) was pipetted out and diluted to 1.00 ml, with reagent glacial acetic acid and titrated against the perchloric acid solution. The strength of the diluted sodium acetate was 0.11+ 0.004 N, so the stock solution was 1.1t 0.004 N. The rate constants were deter-mined by the infinity titer method. It was necessary to use the theor-etical infinity point because excessive charring of the solution made an end point determination d i f f i c u l t . Subtraction of the sample titer from the infinity titer , and the difference -V^  divided by the difference between the zero point titer and the infinity -V^ was V -V done for each point. The value j« t was multiplied by 100 giving the V -V percentage of unreacted substrate and the logarithm of this was plotted as ordinate against time as abcissa. The slope of the straight line mul-tiplied by 2.303 and divided by 60 to convert the minutes-* to seconds-* is the negative of the rate constant. The slopes were determined by the least squares method according to the equation (37). -, n £xy - £x £y 3 l o p e - n JLZ ( where n is the number of points. The activation parameters were deter-mined from the equation . = AH + - T AS* which, in a more usable form is R.2.303.log 1 ( ) = -AH* + A S* + R.2.303.| kr 1 By plotting log-^o T~~ aS a i n s' f c rj-T » ^ be slope of the line multiplied by R x 2.303 gives -AH* in kcal/mole. A S^ in e.u. is calculated by sub-stituting the value of AH^ in the above equation, for one value of k r and T. Extrapolation of the rate constant to 25° was made by use of the 35 equation J _ = G " V ) ^ - T 2 The mean d e v i a t i o n i s given with the va l u e s of the r a t e constants. For =fc k the AHT"both values of l o g _*L f o r each temperature were p l o t t e d , and two l i n e s were drawn through the worst p o s s i b l e combination of p o i n t s and A H values obtained from the slopes of these l i n e s . The mean d e v i -a t i o n was c a l c u l a t e d from these values of A H ^ . 36 RUN I l) 7-norbornyl brosylate 0.077 M brosylate in 0.11 N NaOAc at 206.31 .1° time (min) base titer (ml) $ unreacted log^$ unreacted 0 4.828 3.649 100 2.000 10.14 5-470 3.007 82.41 1.916 20.15 5.960 3.517 68.98 1.839 30.24 6.305 2.172 59.52 1.775 40.08 6.747 1.730 47.41 I.696 50.17 7.056 1.421 38.94 1.590 00 8.477 k = 2.97 x 10~4 sec" 1 t i = 39.8 min 2 38 HUH II 2) exo-anti-8-tricyclo [3.2.1.Q2'4] octanyl brosylate 0.41 M brosylate in 0.11 N NaOAc was used at 206.4 1 . 1 ° time (min) base titer (ml) $ unreacted log^Q^ unreacted 0 4.643 1.907 100 2.000 30.22 4.879 1.671 87.62 1.943 62.95 5.135 1.415 74.20 1.870 91.38 5.330 1.220 63.97 1.806 120.04 5.475 1.075 56.37 1.751 152.37 5.642 0.908 47.61 1.678 oO 6.550 k = 8.15 x 10" 5 -1 sec t i = 2.36 hours 2 RUN III .041 M brosylate in 0.11 N NaOAc at 2 0 6 . 4 ± . 1 ° time (min) base titer (ml) V - v . , (ml) oO t ' % unreacted log^$ unreacted 0 4.690 1.860 100 2.000 42.37 4.990 1.560 83.87 I.9236 80.34 5.214 1.236 66.45 1.8225 120.10 5.470 1.080 58.06 1.7638 158.46 5.658 0.892 47.96 1.6808 200.09 5.826 0.724 38.92 1.5901 00 4»550 k = 7.82 x 10~"sec~ t^ «. 2.46 hours —5 -1 mean k = 7.99 ± 0.16 x 10 vsec 39 o o 40 RUN IV 2 4 3) e x o - a n t i - 8 - t r i c y c l o [3.2.1.0 ' J o c t a n y l b r o s y l a t e 0.0795 M s o l u t i o n i n 0.11 M NaOAc at 1 9 8 . 3 * 0 . 1 ° time (min) base t i t e r (ml) ^ -V t (ml) % unreacted l o g ^ Q $ unreacted 0 4.592 4.154 100 2.000 96.21 5.322 3.424 82.44 1.916 191.88 5-975 2.771 66.73 1.824 271.42 6.356 2.390 57.54 1.760-00 8.726 k = 3.43 x 10"-^  sec" t A = 5.61 hours RUN V 0.0795 M s o l u t i o n i n 0.11 M NaOAc at 1 9 8 . 3 ± 0 . 1 ° time (min) base t i t e r (ml) ^ -V t (ml) $ unreacted log^Q$ unreacted 0.00 4.680 4.066 100 2.000 91.46 5-490 3.256 79.98 1.903 186.85 6.035 2.711 66.53 1.823 240.70 6.433 2.313 56.68 1.753 oO 8.726 k = 3.79 x l O ^ s e c t A = 5.O8 hours . • 2 _*S -1 mean k = 3 . 6 l t 0 . l 8 x 10 J sec 42 RUN VI 2 4 4) exo-anti-8-tricyclo [ 3 . 2 . 1 . 0 ' Joctanyl brosylate O.0469 M of brosylate in 0.11 N NaOAc at 1 6 3 . 5 1 . 0 . 2 ° time (hrs) base titer (ml) V* -v t (ml) f> unreacted log^$ unreacted 0.00 4.770 I.898 100 2.000 6.997 4.970 I.698 89.46 1.952 18.582 5.162 1 . 5 0 6 79.35 1.900 29.082 5.297 1 . 3 7 1 72.23 1.859 39-582 5 . 4 4 1 1.227 64.65 1 . 8 1 1 46.332 5.562 1.106 58.27 1.765 6 6 . 0 8 2 5.787 0.881 4 6 . 4 2 1.667 oO .6.668 k = 3.14 x 10~ sec" t i = 60.5 hours RUN VII 0.0402 M brosylate in 0.11 N NaOAc at 163.5^ 0.2° time (hrs) base titer (ml) V -V. (ml) * X $ unreacted log^Q$ unreacted 0.00 4.748 1.756 100 2.000 8.00 4.928 1.576 89.45 1.953 17.00 5.105 1.401 79.78 1.902 41.50 5.251 1.255 71.47 1.854 48.08 5.541 1.082 61 . 6 2 1.790 00 6.506 k = 2.94 x 10" sec t i = 65.5 hours 2 k = 3.04 £ Oil x 10~ Dsee" 44. Activation Parameters for the Solvolysis of antii-8-tricyclo (3.2.1.Q 2' 4] Octanyl Brosylate T(°A) k (sec -1) k/T , r k 1 0 g 1 0 T | x l 0 3 436.5 471.3 479.4 3.04 x 10~6 3.61 x 10" 5 7.99 x 10~5 6.965 X 7.660 X I.669 x IO" 8" 16-T -8.157 -7.115 -6.778 2.293 2.123 2.087 AH* = 30.2 11.3 kcal/mole A S* = A | * + 4.575 l o g i o I _ 4 7 . 2 i i = - 16.4 e.u. Extrapolation to 25 . - 298, T g » 436.5 o ™ ? 1 k i _ , 298.0 29.7 x 10 : 2 - 3 0 3 l o g 1 0 3.14 1 10-6' - 2 - 3 0 3 l 0 g 436T5 - 1.98 k x = 1.08 x 1 0 " 1 3 sec" 1 1 1 298" " 43675 46 C. PRODUCT STUDIES l ) S o l v o l y s i s of A n t i - 8 - T r i c y c l o [3 .2.1.0 , 4 ] Octanyl B r o s y l a t e at 200  f o r 3 Hours - • 2 4 0.4 g. of a n t i - 8 - t r i c y c l o [3 .2.1.0 J o c t a n y l b r o s y l a t e was d i s -solved i n 10 ml of 0.11 N- sodium acetate - a c e t i c a c i d s o l u t i o n to give a 0.125 N s o l u t i o n of b r o s y l a t e . F i v e 2 ml samples of t h i s s o l u t i o n were sealed i n g l a s s tubes and put i n the brass pressure bombs i n the s i l i -cone o i l bath at 200°. When the temperature had e q u i l i b r a t e d , the f i r s t sample was removed, cooled, the tube broken and the contents poured i n t o excess water. The mixture was e x t r a c t e d with 3 x 15 ml p o r t i o n s of ether and the e x t r a c t s washed with water, 10$ NaHCO^ s o l u t i o n , and b r i n e before being d r i e d over anhydrous magnesium sulphate. Removal of the ether y i e l d e d a mixture of unreacted b r o s y l a t e ( i n f r a r e d i d e n t i c a l to s t a r t i n g m a t e r i a l ) and two a c e t a t e s . The remaining samples were r e -moved from the o i l . b a t h at h a l f hour i n t e r v a l s up to three hours and worked up i n the same way. A n a l y s i s of the products by gas chromatography on a 25$ carbowax 20-M on 60/80 chromosorb W (and washed) column at 130° showed two peaks of about the same i n t e n s i t y ; one with a r e t e n t i o n time corresponding to a u t h e n t i c a n t i - 8 - t r i c y c l o [ 3 . 2 . 1 . Q 2 , 4 j o c t a n y l acetate f o r a l l the samples. A q u a n t i t i v e a n a l y s i s of the samples was not pos-s i b l e because of the presence of a l a r g e amount of unreacted c r y s t a l l i n e b r o s y l a t e on which the small amount of acetate m a t e r i a l tended to s t i c k . To get enough acetate m a t e r i a l f o r gas chromatography i t was necessary to wash the c r y s t a l l i n e m a t e r i a l wit'h a l o t of ether, decant and con-ce n t r a t e the ether s o l u t i o n . The b r o s y l a t e does not come through a gas chromatography column, so i t was not p o s s i b l e to monitor the r e a c t i o n 47 by noting the decrease i n the b r o s y l a t e peak with a corresponding i n -crease i n acetate peak as the r e a c t i o n proceeded. The i n f r a r e d s pectra of crude m a t e r i a l i s o l a t e d from the samples was i d e n t i c a l to the s p e c t r a of a mixed sample of a u t h e n t i c t r i c y c l i c b r o s y l a t e with t r i c y c l i c ace-t a t e . I t was assumed that one of the f i r s t products i n the s o l v o l y s i s 2 4i r e a c t i o n s was a n t i - 8 - t r i c y c l o [3.2.1.0 ' J o c t a n y l a c e t a t e . I n f r a r e d (crude mixture): 2950 (m), 1740 ( s ) , 1580 (w), 1470 (w), 1365 ( s ) , 1250 ( s ) , 1190 ( s ) , 1140 (w), 1095 (w), 1070 (w), 1045 (w), 1015 (w), 994 (m), 915 (m), 885 (m), 8 2 5 (m), 7 4 2 ( s ) . 2) S o l v o l y s i s of T r i c y c l o r3.2.1.O 2 ' 4 ]0ctanyl B r o s y l a t e at 200° f o r 12hrs. 0.688 g. (0.166 H) of t r i c y c l o [3.2.1.6 2 , 4 ] o c t a n y l b r o s y l a t e i n .15 ml of 0.55 N sodium a c e t a t e , g l a c i a l a c e t i c a c i d s o l u t i o n was put i n t o a sealed g l a s s tube and heated f o r about twelve hours i n a constant tem-perature bath at 200°. A f t e r which time the contents had turned dark, with black p a r t i c l e s i n the s o l u t i o n . I t was poured i n t o excess water and extracted three times with ether. The ether e x t r a c t was washed with water, 10$ sodium bicarbonate s o l u t i o n , with a saturated sodium c h l o r i d e s o l u t i o n before being d r i e d over anhydrous magnesium sulphate. A f t e r f i l -t e r i n g , the solvent was removed to y i e l d an o i l y , f r u i t y s m e l l i n g pro-duct A. A n a l y s i s of t h i s by gas chromatography u s i n g a 5 . f o o t , 20$ Apiazon J on 60/80 f i r e b r i c k at 180° showed i t to be a mixture of at l e a s t two components, d i f f e r i n g i n both n.m.r. and i . r . s p e ctra from au t h e n t i c t r i c y c l o [ 3.2.l.O 2' 4] oct a n y l acetate D (see below) and which were incompletely separated by the above c o n d i t i o n s . R a t i o of the two peaks heights 2:1. Y i e l d of t o t a l product, (A) c o l l e c t e d (two peaks) was 0.12 g. (35$)« 48 Infrared: 2870 (m), 1730 (s), 1350 ( s ) , 1240 (s), 1080, 1060, 1040, 1010 (broad unresolved), 965 (w), 900 (w), 730 (w), 710 (m). n.m.r.: (CC1 4): 4-5 (m), 5-35 U ) , 8.15 (m), 8.4 (m). There were no characteristic peaks aroundlOl for the cyclopropyl group. 3) Hydrogenation of the Product ( A ) Isolated From the Solvolysis of  Tricyclo [3.2.1.0 'jOctanyl Brosylate 5.1 mg. (.00003 M) based on C^QH^Og °^ crude product acetate ( A ) was hydrogenated i n the presence of 2.8 mgs. of platinium oxide catalyst i n 95$ ethanol at atmospheric pressure and room temperature. The hydro-gen uptake was 0.71 ml, which agreed with the amount 0.74 ml, calculated for one double bond. In subsequent hydrogenations, the uptake varied from the calculated amount by @ 10$. In a l l cases the uptake was less than the amount calculated for one double bond, and the variation was attributed to the other components present i n the crude acetate, which could vary in concentration and effect the i n i t i a l weight of the o l e f i n present. After f i l t e r i n g off the catalyst and removal of most of the solvent, a sample was analysed by gas chromatography on a 23$ carbowax 20-M on 60/80 chromosorb W (acid washed) column at 150°. The presence of at least two components, incompletely separated was shown; ratio of the two peak heights was 5*2 (b). Infrared (CHC1 3): 2940 (s), 1730 (s), 1440 (w), 1250 (s), 1105 (m),1020(m) n.m.r.: (CHCl^) : 8.1 (m), 8.5 (m) 4) Preparation of Cyclooctanyl Acetate C This was prepared so that i t could be compared with the hydrogenated product acetate from the solvolysed brosylate .(B). 5 g« (0.04 M) of cyclooctanol (Aldrich Chemical Co.,Inc.) i n 25 ml of acetic anhydride 49 was r e f l u x e d overnight, a f t e r which a l a r g e excess of water was added and the product - e x t r a c t e d with ether. The e x t r a c t was washed with water, 10$ sodium bicarbonate and with b r i n e and d r i e d over anhydrous mag-nesium sulphate. Removal of the solvent gave an o i l y , sweet s m e l l i n g product. I n f r a r e d : 2940 ( s ) , 1745 ( s ) , 1480 (w) 1460 (w) 1370 (m), 125.0 ( s ) , 1040 (m), 1020 (m), 950 (w). A n a l y s i s by gas chromatography on 25$ carbowax 20-M on 60/80 chromosorb W ( a c i d washed) column of t h i s and of the hydrogenated product acetate (B) from the b r o s y l a t e s o l v o l y s i s i n a 50/50 mixture showed that they were not the same m a t e r i a l ; two peaks, d i f f e r i n g i n r e t e n t i o n time by about 8 minutes were observed. C y c l o o c t a n y l a c e t a t e had the longer r e -t e n t i o n time. 5) Hydride Reduction of Product Acetate (A) from S o l v o l y s i s of B r o s y l a t e O.38 g. (0.002 M based on C^QH^O^) °f crude product a c e t a t e A i n 20 ml of anhydrous ether was slowly added to a s t i r r e d mixture of 0.066 g. (0.002 M) of l i t h i u m aluminium hydride i n 50 ml of dry ether and l e f t o vernight. Water was added slowly to decompose any excess hydride and the p r e c i p i t a t e d s a l t s were d i s s o l v e d up i n 10$ s u l p h u r i c a c i d , and the mixture e x t r a c t e d with 3 x 20 ml of ether. The ether e x t r a c t was washed with water, 10$ sodium bicarbonate s o l u t i o n , and b r i n e and d r i e d over anhydrous magnesium sulphate. Some of the ether was removed and a concen-t r a t e d s o l u t i o n of product (B) was analysed by gas chromatography on the carbowax column at 150°, and found to co n t a i n one main component, with a second component present as a shoulder to the main peak, and a t h i r d i n about the same c o n c e n t r a t i o n as the second with a s l i g h t l y ' 5.0 longer r e t e n t i o n time. Ratio of the peak heights was 21 :5:4. C o l l e c t i o n of 80 mgs. of a s t i c k y l i q u i d , unsaturated produce a l c o h o l E (at l e a s t three components) was achieved. I n f r a r e d : 3400 ( s ) , 2950 ( s ) , 1450 (m), 1350 (m), 1190 (w), 1140 (w), 1080 (m), 1060 (m), 1000 (m), 965 (w), 710 (m). 6) Hydrogenation of Unsaturated Product A l c o h o l s E OF r 0.039 g« (0.0003 M based on CgH^O^was hydrogenated i n the presence of 0.035 g of p l a t i n i u m oxide c a t a l y s t i n 95$ ethanol at room temperature and pressure; 7.55 ral of hydrogen was taken up which corresponded to the amount c a l c u l a t e d f o r one double bond (wit h i n 3$ accuracy). A f t e r f i l t e r i n g o f f the c a t a l y s t and removal of s o l v e n t , the remaining mix-ture P was separated on the carbowax column at 150°. The three components were c o l l e c t e d s e p a r a t e l y as a, b, and c. Components a and b i n the f i r s t c o l l e c t i o n at 150° were not separated, but by lowering the tem-perature 10°, s e p a r a t i o n was achieved. Ratio of the peaks a:b:c was 30 :12:13. F r a c t i o n Fa (main peak, a l i q u i d ) I n f r a r e d : 3340 (m), 2940 ( s ) , 1440 (w), 1370 (m), 1330 (w), 1310 (w), 1170 (w), 1120'(B)," 1080 ( s ) , IO4O (m), 945 (w), 845 (w). A n a l y s i s : c a l c u l a t e d f o r CgH.^0: C, 76.14; H, 11.18 found : C, 51.96; H, 9.O8 F r a c t i o n Fb c r y s t a l l i n e compound m.p. 105° I n f r a r e d : 3250 (m), 2900 ( s ) , 1450 ( s ) , 1360 ( s ) , 1150 (w), 1090 (m), 1050 (m), 1025 (m), 955 (m), 843 (w), 815 (w), 765 (w), 723 (w) F r a c t i o n Fc c r y s t a l l i n e compound m.p. 95° I n f r a r e d : 3250 (m), 2900 ( s ) , 1450 ( s ) , 1365 (m), 1320 (w), 1240 (w), 1160 (w), 1095 (m), 1070 (m), 1035 (m), 955 (w), 805 (w),720(w) 51 n.m.r.: 8.5 (m) Analysis: calculated for CgH^O: C, 76.14; H, 11.18 found : C, 75-83; H, 11.40 7) Preparation of Anti-8-Tricyclo [3.2.1.Q 2 , 4]octanyl Acetate D 2 4 0.5 g. (0.004 M) of anti - 8-tricyclo [3.2.I.O 'joctanol was refluxed overnight with 20 ml of reagent acetic anhydride, after which time a large excess of water (150 ml) was added and the solution extracted (3 x 20 ml) with ether. The extracts were washed with water, a 10$ sodium bicarbonate solution and brine, before being dried over anhydrous magnesium sulphate. Removal of the solvent gave a crude o i l , which was purified by gas chromatography, with a 5 foot 20$ Apiazon J on 60/80 firebrick. Yield 0.59 S (88$). Infrared: 2900 (s), 1730 (s), 1450 (w), 1350 (s), 1240 (s), 1140 (m), 1080 (s), 1040 (s), 970 (w), 920 (w), 810 (w), 745 (m). n.m.r.: bridge 5«62 (s), bridgehead 7.7 acetate and exo/endo 8.08(m), exo/endo 2.5 (m), cyclopropyl 9«22 (m) 9-99 (m).. Analysis: calculated for C^H^O^C, 72.25; H, 8.49 found :C, 71.84; H, 8.53 found :C, 71.94; H, 8.05 r 2 4 8) Rearrangement of Anti-8-Tricyclo [3.2.1.0 Octanyl Acetate for 3 hrs. 0.2 g. of anti - 8 -tricyclo [3.2.1.Q 2' 4joctanyl acetate was dissolved in 10 ml of :0.11 IT sodium acetate - acetic acid to give a solution of 0.25 W in acetate. Five 2 ml samples; of this solution were sealed into glass tubes and put in the o i l bath at 200°. Samples were removed every half hour up to three hours and one after 24 hours and worked up in the same way as described for the brosylate run ( l ) . The crude product, an 52 o i l y l i q u i d remained a f t e r ether removal. For t h i s reason l a r g e r amounts of product could be analysed by gas chromatography on the carbowax column at 130°, and i t was p o s s i b l e to monitor the rearrangement of the acet a t e . Hence the peak corresponding to the s t a r t i n g m a t e r i a l was seen to decrease, and a new, lower b o i l i n g peak i n c r e a s e . A f t e r a time of three hours only 1/5 of the m a t e r i a l had rearranged, i . e . the c y c l o p r o p y l group having opened up to give a new ac e t a t e . The i n f r a r e d s p e c t r a of the samples i s o l a t e d a f t e r v a r i o u s times showed a gradual change i n the 1000 and 1100 cm 1 r e g i o n . A band, c h a r a c t e r i s t i c f o r the t r i c y c l o o c t a n y l acetate at 1140 cm """ was observed to decrease and f i n a l l y d i s -appear f o r the 24 hour sample. The two strong bands at IO85 and 1040 cm-''* g r a d u a l l y broadened i n t o one l a r g e band around 1050 and 1040 cm-'*'. The 24 hour sample analysed by gas chromatography c o n s i s t e d only of r e -arranged acetate G. I n f r a r e d : 2950 (m), 1740 ( s ) , 1365 (m), 1240 ( s ) , 1180 (w), 1080 (w), 1050 (m), 1030 (m), 965 (w), 905 (w), 825 (v.w), 735 (w) From t h i s experiment i t was shown that the c y c l o p r o p y l r i n g opening under s o l v o l y s i s c o n d i t i o n s at 200° was not instantaneous, and occurred at q u i t e a slow r a t e compared to the s o l v o l y s i s of the b r o s y l a t e . T r i -c y c l o o c t a n y l a c e t a t e was proved not to be s t a b l e under prolonged s o l -v o l y s i s c o n d i t i o n s . The rearrangement of t r i c y c l o o c t a n y l acetate over 24 hours was repeated on a l a r g e r s c a l e i n order to see i f the product acetate G was the same m a t e r i a l as product acetate A, i s o l a t e d from the b r o s y l a t e s o l v o l y s i s . 53 9) Rearrangement of A n t i - 8 - T r i c y c l o o c t a n y l Acetate D O.4 g. (0.025 M) of D i n about 10 ml of 0 . U N NaOAc i n HOAc i n a sealed g l a s s tube was heated overnight i n a constant temperature bath at 200°, c h a r r i n g of the s o l u t i o n was observed. Excess water was added and the s o l u t i o n e x t r a c t e d with ether. The ether e x t r a c t s were worked up i n the same way as d e s c r i b e d i n 2 ) . 0.4 g. of crude m a t e r i a l G was i s o -l a t e d , and a n a l y s i s or the carbowax column showed i t to c o n s i s t of one major component, with a second component incompletely separated (a shoulder of the main peak) and a t h i r d minor component} r a t i o of peak heights was 7 0 8 : 1 3 . The r e t e n t i o n times and i n f r a r e d corresponded w e l l to the product acetate A from s o l v o l y s i s of the b r o s y l a t e . The i n f r a r e d d i f f e r e d only i n the r e g i o n 725 and 705 cm - 1 from A and d i f f e r e d very much from the i n f r a r e d of authentic D p a r t i c u l a r l y i n the regions 1040-1080 cm - 1 and 1130cm - 1 . I n f r a r e d : 2950 (m), 1740 ( s ) , 1365 (m), 1240 ( s ) , 1180 (w), 1080 (w), 1050 (m), 1030 (m), 965 (w), 905 ( w ) , " ' 8 2 5 (v.w), 735 ( w ) . 10) Hydride Reduction of Product Acetate G 0.4 g. of crude m a t e r i a l G i s o l a t e d from the rearrangement of a n t i -8 - t r i c y c l o J 3 . 2 . 1 . 0 2 o c t a n y l acetate i n 1 5 ml of ether was added to a s t i r r e d ether s o l u t i o n of excess l i t h i u m aluminium hydride and l e f t over-n i g h t . The s o l u t i o n was worked up i n the same way as d e s c r i b e d i n 5) above. A n a l y s i s of the product on the carbowax column at 160° showed the product to be a mixture of at l e a s t two components, r a t i o 5*1. The i n f r a r e d spectrum was taken on the crude mixture H, a s t i c k y s o l i d and d i f f e r e d g r e a t l y from the spectrum of a n t i - 8 - t r i c y c l o [ 3 . 2 . 1 . 0 2 ' 4 ] o c t a n o l : but compared w e l l with the spectrum of the crude unsaturated a l c o h o l E, 54 isolated from the acetolysis and hydride reduction of the "brosylate. The only difference was in the region 940 and 710 cm""1". A small ab-sorption around 1700 cm"1 showed that the mixture contained some un-reacted acetate G. Infrared: 3350 (m), 2900 (s), 1460 (w), 1340 (w), l l 8 0 (w), 1140 (w), 1070 (m), 1060 (m), 1005 (m), 955 (w), 890 (w), 870 (w), 825(w), 805 (w), 735 (w). 11) Hydrogenation of Unsaturated Alcohol H The crude material from the hydride reduction H, was dissolved in ethanol and hydrogenated in the presence of platinium oxide catalyst. After f i l t e r i n g off the catalyst, the product mixture was analysed on a carbowax column at 160°. The presence of two components was indicated, ratio of the peak heights 3"1. No attempt was made to separate the mix-ture of alcohols as very l i t t l e material was present. The infrared spectrum given is that of the crude mixture I from the hydrogenation of H. Infrared: 3340 (m), 2940 (s), 1450 (w), 1350 (m), 1310 (w), 1170 (w), 1120 (m), 1090 (m), 1040 (w), 945 (w), 845 (w). This spectrum is identical to that of the main component Pa isolated from the saturated product alcohol mixture P which originated from the brosylate solvolysis. 12) Anti-8-Tricyclo 3.2.1.0*"*' 4J0ctanol in Acetic Acid and Perchloric Acid 0.31 g. (0.0025 M) of alcohol was stirred overnight at room temper-ature in 25 nil of glacial acetic acid which contained O.665 g. (0.005 M) of 70$ perchloric acid. The solution, which had turned slightly brown, was poured into excess water and extracted with ether. The ether ex-tracts were washed in the usual way. Analysis on the carbowax column at 55 150 showed only one component with a s i m i l a r r e t e n t i o n time to product acetates A and G. The i n f r a r e d spectrum on the crude material was i d -e n t i c a l to that of the product acetate G, which was i s o l a t e d from the rearrangement at 200° of a n t i - 8 - t r i c y c l o J 3 . 2 . 1 . 0 2 , 4 | o c t a n y l acetate. (This d i f f e r s only s l i g h t l y from the product acetate A i s o l a t e d from the brosylate s o l v o l y s i s ). 56 A 01 1 0 < • o o 1K l -a *?. * t*; r S ^ ° *" > ... Hi** r 1 2 it. h o o § a: A* VJ 3 W J O o o J a; 1a a: ft I-< t-<1 10 lit <X 5 . J I t * t 3 IE a o 3 3l 57 ' REFERENCES 1. Winstein,S. and Simmonetta,!.:J.Am.Chem.Soc. J_6,l8 (1954). 2. Winstein,S. and Shatavsky,M.:Chem.andInd. 56(1956). 3. Winstein,S.,Shatavsky,M.,Norton,C.J. and Woodward,R.3. : J.Am. Chem.. S o c , 7 7 , 4 l 8 3 ( l 9 5 5 ) . 4. Norton,C.J.:PhD Thesis, Harvard University, 1955 • 5. 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