RACEMIZATION AND RESOLUTION IN THE ORGANIC SOLID STATE by KEITH RAINIER WILSON B.Sc. ( H o n s . ) , 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 , 1967 A THESIS SUBMITTED^IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY i n t h e Department of CHEMISTRY We a c c e p t t h i s t h e s i s as c o n f o r m i n g t o t h e required standard THE UNIVERSITY OF BRITISH COLUMBIA J a n u a r y , 1972 In presenting this thesis i n p a r t i a l fulfilment of the requirements for an advanced degree at the University of B r i t i s h Columbia, I agree that the Library s h a l l make i t f r e e l y available for reference and study. I further agree that permission for extensive copying of t h i s thesis for scholarly purposes may by his representatives. be granted by the Head of my Department or It i s understood that copying or publication of t h i s thesis for f i n a n c i a l gain s h a l l not be allowed without my written permission. Department of CHe^CST^V The University of B r i t i s h Columbia Vancouver 8, Canada Date F£&G.Oflrg.-\ -2,7-. t^TT^ ii ABSTRACT Supervisor: Two Dr. R.E. Pincock examples of the s i m p l e s t type of o r g a n i c solid-state reaction - the t h e r m a l i n t e r c o n v e r s i o n of o p t i c a l i s o m e r s - have been e x t e n s i v e l y s t u d i e d by means of p o l a r i m e t r y , 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 , and X-ray powder d i f f r a c t i o n . The and f i r s t r e a c t i o n i n v e s t i g a t e d was the r e v e r s e D i e l s - A l d e r r e a c t i o n r e c o m b i n a t i o n of the c y c l o p e n t a d i e n e - f u m a r i c samples of (+)-enantiomer (m.p. from 130° 14 c a l deg t o 165°. 176°) a c i d adduct. P o l y c r y s t a l l i n e racemize completely F i r s t - o r d e r k i n e t i c s (AH "'"mole "*") are s t r i c t l y obeyed; s i t i v e t o v a r i a t i o n s i n c r y s t a l s i z e and * = 40.0 i n the s o l i d k c a l mole the r a c e m i z a t i o n optical purity. -1 , AS The reaction, to these * AS* = -6.9 c a l deg t o 194°, AH' -1 = 29.7 k c a l mole (m.p. , "Snole "*") o c c u r s throughout the p o l y c r y s t a l l i n e sample r a t h e r than at c r y s t a l l i t e b o u n d a r i e s , d i s l o c a t i o n s , o r o t h e r sites. = rate i s insen- w h i c h i s o n l y f i v e times s l o w e r t h a n the m e l t r a t e e x t r a p o l a t e d t e m p e r a t u r e s ( f o r t h e m e l t from 176° + state preferred Phase s t u d i e s show t h a t the p r o d u c t s e p a r a t e s as a r a c e m i c compound 186°) From 165° w h i c h forms a e u t e c t i c ( a t 165°) t o 176°, the r a c e m i z a t i o n w i t h the r e s o l v e d shows a u t o a c c e l e r a t i o n and enantiomers. sigmoid- shaped k i n e t i c c u r v e s c h a r a c t e r i s t i c of c o n c u r r e n t r e a c t i o n s i n the solid and m e l t phases. The second system s t u d i e d was 1,1'-binaphthyl, and t h a t formed between R - ( - ) - and S-(+)- s u r p r i s i n g l y , r e s o l u t i o n , r a t h e r than r a c e m i z a t i o n , o b s e r v e d t o o c c u r from 76° t o 158°. was This unprecedented s o l i d - s t a t e reso- l u t i o n i s made p o s s i b l e by a s o l i d - s o l i d phase change from a r a c e m i c compound iii (m.p. 145°) to a. e u t e c t i c m i x t u r e (m.p. 158°) o f c r y s t a l s o f pure e n a n t i o - mers, a t t e m p e r a t u r e s where i n t e r c o n v e r s i o n o c c u r s i n the r e a c t a n t - p r o d u c t interface. P o l y c r y s t a l l i n e 1 , 1 - b i n a p h t h y l samples o f v e r y low o p t i c a l 1 a c t i v i t y h a v i n g t h e c o r r e c t phase c o n t e n t (racemate p l u s c r y s t a l s o f o n l y one enantiomer) f o r a c o n t r o l l e d r e s o l u t i o n can be e a s i l y and prepared. These samples r e s o l v e from [ c t ] e i t h e r (+) o r (-) D reproducibly = 2° t o [ a ] = .ca.. 210° ( i n D d i r e c t i o n s ) i n l e s s t h a n one hour a t 150°. The l i m i t o f r e s o l u t i o n ( [ a j ^ = i245°) i s a t t a i n e d s i m p l y by r e c r y s t a l l i z a t i o n o f t h e r e s o l v e d sample from a c e t o n e . The r e s o l u t i o n t h e r e f o r e i n v o l v e s t h e con- v e r s i o n o f a l l o f a r a c e m i c m a t e r i a l t o o n l y one e n a n t i o m e r . o f t h e s o l i d - s t a t e r e s o l u t i o n show a smooth development w i t h time. A Prout-Tompkins Kinetic of o p t i c a l studies activity a n a l y s i s i n d i c a t e s t h a t c r y s t a l l i t e s o f growing enantiomer s p r e a d throughout t h e r a c e m i c sample, r e q u i r i n g 62 k c a l mole activation 1 energy. C r y s t a l l i z a t i o n o f c o m p l e t e l y r a c e m i c 1 , 1 ' - b i n a p h t h y l melt i n a c l o s e d system g i v e s r i s e t o o p t i c a l a c t i v i t y . The p r o b a b i l i t y d i s t r i b u t i o n o f i n d i v i d u a l c r y s t a l l i z a t i o n s i s symmetric about o p t i c a l l y a c t i v e samples [ct] D 200 = 0° and p r o v e s t h a t can be c r e a t e d under a b s o l u t e l y spontaneous condi- t i o n s ( i . e . , i n the complete absence o f e x t e r n a l d i s s y m m e t r i c i n f l u e n c e s ) . iv TABLE OF CONTENTS 1 Introduction 2 R a c e m i z a t i o n o f (+) - B i c y c l o [ 2.2.1 ]hept-5-ene-trans_-2 ,3d i c a r b o x y l i c A c i d i n t h e L i q u i d and S o l i d S t a t e s 17 2.1 Racemization i n the L i q u i d S t a t e 18 2.2 Racemization i n the S o l i d S t a t e 23 2.3 The Phase Diagram 27 2.4 Mechanism i n t h e S o l i d S t a t e 35 2.5 Conclusion 43 3 R e s o l u t i o n o f Racemic 1 , 1 ' - B i n a p h t h y l i n t h e S o l i d S t a t e 45 3.1 The P r e p a r a t i o n o f 1 , 1 ' - B i n a p h t h y l 46 3.2 D i s c o v e r y o f the S o l i d - S t a t e R e s o l u t i o n 49 3.3 Phase Diagram o f t h e System R- and S - 1 , 1 ' - B i n a p h t h y l 55 3.4 P e r f e c t i o n of the S o l i d - S t a t e R e s o l u t i o n 83 3.5 K i n e t i c Study o f t h e S o l i d - S t a t e R e s o l u t i o n 103 3.6 The Spontaneous G e n e r a t i o n o f O p t i c a l l y 1,1'-Binaphthyl 139 3.7 4 1 Active Conclusion 147 Experimental 150 Bibliography 172 Appendix A: The Phase L i m i t o f R e s o l u t i o n Appendix B: C a l c u l a t i o n o f AG 178 L~*H as a F u n c t i o n o f Temperature 184 V LIST OF TABLES I II Ill IV V VI F i r s t - O r d e r Rate C o n s t a n t s f o r R a c e m i z a t i o n o f (+)-29 i n S o l i d , M e l t , and S o l u t i o n . 20 A c t i v a t i o n P a r a m e t e r s f o r R a c e m i z a t i o n o f (+)-29 i n S o l i d , M e l t , and S o l u t i o n . 21 Summary o f I n i t i a l I n v e s t i g a t i o n s o f t h e Development o f O p t i c a l A c t i v i t y i n Neat, P o l y c r y s t a l l i n e 1,1'-Binaphthyl. 51 Examples o f t h e C y c l i n g o f Racemic 1 , 1 ' - B i n a p h t h y l t o High S p e c i f i c R o t a t i o n s . 54 X-Ray Powder D i f f r a c t i o n P a t t e r n s f o r L o w - M e l t i n g (Racemate) 58 and H i g h - M e l t i n g ( E u t e c t i c ) Forms o f 1 , 1 ' - B i n a p h t h y l . S p e c i f i c R o t a t i o n s o f S i n g l e C r y s t a l s O b t a i n e d from t h e R e c r y s t a l l i z a t i o n o f Racemic 1 , 1 ' - B i n a p h t h y l . 61 VII E n t h a l p y o f F u s i o n o f t h e H i g h - M e l t i n g Form o f 1,1'Binaphthyl at Various S p e c i f i c R o t a t i o n s . 76 VIII The Development o f O p t i c a l A c t i v i t y on H e a t i n g P o l y c r y s t a l l i n e , Racemic 1 , 1 ' - B i n a p h t h y l . 85 The Development o f O p t i c a l A c t i v i t y on H e a t i n g P o l y c r y s t a l l i n e , Racemic 1 , 1 ' - B i n a p h t h y l Under a S o l v e n t . 90 The I n f l u e n c e o f Added Seed C r y s t a l s o f O p t i c a l l y A c t i v e 1 , 1 ' - B i n a p h t h y l on t h e S o l i d - S t a t e R e s o l u t i o n o f P o l y c r y s t a l l i n e , Racemic 1 , 1 ' - B i n a p h t h y l . 92 The I n f l u e n c e o f O p t i c a l l y A c t i v e 1 , 1 ' - B i n a p h t h y l Seed C r y s t a l s on t h e R e s o l u t i o n by C r y s t a l l i z a t i o n from a S u p e r c o o l e d , Racemic 1 , 1 ' - B i n a p h t h y l M e l t . 93 IX X XI XII XIII XIV XV XVI F i n a l S p e c i f i c R o t a t i o n s i n the S o l i d - S t a t e R e s o l u t i o n o f 1,1'-Binaphthyl ( K i n e t i c Batches). 109 Low Temperature S o l i d - S t a t e R e s o l u t i o n o f 1 , 1 ' - B i n a p h t h y l . I l l A v r a m i - E r o f e e v Exponents f o r the S o l i d - S t a t e R e s o l u t i o n of 1,1'-Binaphthyl. 131 Prout-Tompkins Rate C o n s t a n t s ( k ) f o r t h e S o l i d - S t a t e Resolution of 1,1'-Binaphthyl. 135 Low Temperature R e c r y s t a l l i z a t i o n o f R- and S-1,1'Binaphthyl. 179 ? vi LIST OF TABLES XVII (continued) Heat C a p a c i t i e s a t C o n s t a n t P r e s s u r e f o r L o w - M e l t i n g (Racemate) and H i g h - M e l t i n g ( E u t e c t i c ) Forms o f 1,1'Binaphthyl. 190 vii LIST OF FIGURES 1. F i r s t - o r d e r k i n e t i c p l o t s f o r r a c e m i z a t i o n o f neat (+)d i a c i d 2_9 i n the m e l t phase. 19 2. R e l a t i o n of l o g 22 ^ /T) t o r e c i p r o c a l t e m p e r a t u r e f o r r a c e m i z a t i o n o f (+)-enantiomer 29. i n m e l t , s o l i d , s o l u t i o n ( i n t e t r a l i n ) phases. and 3. F i r s t - o r d e r k i n e t i c p l o t s f o r racemization of neat, polyc r y s t a l l i n e (+)-29 i n t h e s o l i d phase. 24 4. F i r s t - o r d e r k i n e t i c p l o t s f o r r a c e m i z a t i o n of neat, p o l y c r y s t a l l i n e (+)-29 a t 152° i n the s o l i d phase and a t 161° where m e l t solid. 25 5. K i n e t i c d a t a f o r r a c e m i z a t i o n of n e a t samples o f (+)-29 i n t h e s o l i d (155°), i n t h e b i p h a s e m e l t + s o l i d system (166°), and i n a c o m p l e t e l y m e l t e d system ( a t 176°). 26 6. 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 e r t r a c e s (programming 29 rate: 10 deg min ^) f o r t h e d i a c i d 29_ a t v a r i o u s c o m p o s i t i o n s : (a) 0%, (b) 24.8%, (c) 45.2% and (d) 50% ( - ) - e n a n t i o m e r . 7. Phase r e l a t i o n s h i p o f m i x t u r e s o f (+)- and (-)-enantiomer o f compound 29_. V e r t i c a l b a r s i n d i c a t e the u n c e r t a i n t i e s i n t r a n s i t i o n t e m p e r a t u r e s ( t a k e n a t the b e g i n n i n g o f d . s . c . endotherms). Undetermined phase b o u n d a r i e s ( d o t t e d l i n e s ) are estimated f o r completeness. 31 8. (a) Schematic f r e e e n e r g y - c o m p o s i t i o n p l o t i n the phase system (+)- and (-)-29, a t c o n s t a n t p r e s s u r e ( a t m o s p h e r i c ) and t e m p e r a t u r e (150°). The d o t t e d l i n e s show the l o w e s t f r e e energy s u r f a c e s f o r the two-phase r e g i o n s . (b) Schematic f r e e e n e r g y - r e a c t i o n c o o r d i n a t e p l o t f o r the s o l i d - s t a t e r a c e m i z a t i o n of (+)-29 (shown as A ( y ) ) a t 150°. 39 9. I n f r a r e d spectrum o f 1 , 1 ' - b i n a p h t h y l ( n u j o l m u l l ) . (a) Low-melting form. (b) H i g h - m e l t i n g form. 56 S k e t c h o f the h a b i t o f a s i n g l e c r y s t a l o f pure R- o r S1 , 1 ' - b i n a p h t h y l , showing t h o s e f a c e s w h i c h were apparent under the m i c r o s c o p e , (a) View of a, b, and c f a c e s . (b) View normal t o c f a c e , (c) View normal t o d f a c e . 62 10. viii LIST OF FIGURES ( c o n t i n u e d ) 11. Schematic f r e e e n e r g y - t e m p e r a t u r e p l o t s f o r r a c e m i c 1,1'b i n a p h t h y l , showing l o w - m e l t i n g form ( L ) , h i g h - m e l t i n g form (H) and m e l t (M) s u r f a c e s . (a) M o n o t r o p i c r e l a t i o n ship, (b) E n a n t i o t r o p i c r e l a t i o n s h i p . (c) Phase d i a g r a m w h i c h would r e s u l t from the m o n o t r o p i c r e l a t i o n s h i p , (d) Phase diagram w h i c h would r e s u l t from the e n a n t i o tropic relationship. 67 12. D i f f e r e n t i a l scanning c a l o r i m e t e r traces f o r racemic 1 , 1 ' - b i n a p h t h y l , as a f u n c t i o n o f programming r a t e . 69 (a) 2.5 deg min ^. (b) 10 deg min (c) 40 deg min ^. 13. Schematic e n t h a l p y - and e n t r o p y - t e m p e r a t u r e p l o t s f o r r a c e m i c 1 , 1 ' - b i n a p h t h y l . (a) O r d e r i n g o f l o w - m e l t i n g form ( L ) , h i g h - m e l t i n g form (H) and m e l t (M) e n t h a l p i e s . (b) O r d e r i n g o f e n t r o p i e s of the same phases. 74 14. (a) Phase diagram f o r t h e R- and S - l , 1 ' - b i n a p h t h y l system, showing m e t a s t a b l e e x t e n s i o n s ( d o t t e d l i n e s ) of t h e phase boundaries. (b) Schematic f r e e e n e r g y - c o m p o s i t i o n p l o t a t 130°, showing t h e l o w e s t (dashed l i n e ) and the n e x t - l o w e s t ( d o t t e d l i n e s ) f r e e energy s u r f a c e s . (c) As f o r ( b ) , but a t 150°. 80 15. S p e c i f i c r o t a t i o n as a f u n c t i o n o f t i m e f o r t h e s o l i d s t a t e r e s o l u t i o n o f r a c e m i c 1 , 1 ' - b i n a p h t h y l (L B a t c h ) a t 86 135°. 16. Schematic phase diagram between r a c e m i c 1 , 1 ' - b i n a p h t h y l and a s o l v e n t w i t h b.p. > 160°. D o t t e d l i n e s a r e metas t a b l e e x t r a p o l a t i o n s o f phase b o u n d a r i e s , and show t h e h i g h e r s o l u b i l i t y o f the l e s s s t a b l e forms. 89 17. Schematic r e p r e s e n t a t i o n o f t h e t e r n a r y system formed between s o l v e n t , R- and S - l , 1 ' - b i n a p h t h y l . M e t a s t a b l e e x t r a p o l a t i o n s o f phase b o u n d a r i e s ( s o l u b i l i t y c u r v e s ) a r e shown as d o t t e d l i n e s . (a) Temperature: -78°, (b) Temperature: +25°. 102 18. K i n e t i c d a t a f o r t h e s o l i d - s t a t e r e s o l u t i o n of n e a t , p b l y c r y s t a l l i n e 1 , 1 ' - b i n a p h t h y l , S - l K i n e t i c B a t c h a t 135°. E f f e c t of g r i n d i n g and o f s t o r a g e a t 25° f o r s i x weeks. 104 19. K i n e t i c d a t a f o r the s o l i d s t a t e r e s o l u t i o n of n e a t , p o l y c r y s t a l l i n e 1 , 1 ' - b i n a p h t h y l , S-2 K i n e t i c B a t c h at 125°. E f f e c t o f s t o r a g e of samples a t 0° f o r f o u r months. 105 ix LIST OF FIGURES ( c o n t i n u e d ) 20. K i n e t i c d a t a f o r the s o l i d - s t a t e r e s o l u t i o n o f n e a t , p o l y c r y s t a l l i n e 1 , 1 ' - b i n a p h t h y l , S-2 and R - l K i n e t i c B a t c h e s a t 135°. 106 21. K i n e t i c data f o r the s o l i d - s t a t e r e s o l u t i o n of neat, p o l y c r y s t a l l i n e 1 , 1 ' - b i n a p h t h y l , S-2 and R - l K i n e t i c B a t c h e s a t 115°. 107 22. K i n e t i c data f o r the s o l i d - s t a t e r e s o l u t i o n of neat, p o l y c r y s t a l l i n e 1 , 1 - b i n a p h t h y l , S-3 K i n e t i c B a t c h a t (a) 135 and (b) 115°. 108. 23. C a l i b r a t i o n curve f o r q u a n t i t a t i v e powder photography. by X-ray 121 24. Development o f s p e c i f i c r o t a t i o n w i t h e x t e n t o f phase t r a n s f o r m a t i o n ( X y ) , S-2 K i n e t i c B a t c h a t 125° ( a f t e r f o u r months' s t o r a g e a t 0°). D i a g o n a l r e p r e s e n t s t h e c o n d i t i o n [a]/[o] = %. 123 25. Avrami-Erofeev p l o t s f o r the s o l i d - s t a t e r e s o l u t i o n of neat, p o l y c r y s t a l l i n e 1 , 1 ' - b i n a p h t h y l , S - l K i n e t i c B a t c h a t 135° and 105°. The sample s t o r e d s i x weeks a t 25° i s p l o t t e d a g a i n s t l o g ( t i m e , seconds) + 1. 126 26. Avrami-Erofeev p l o t s f o r the s o l i d - s t a t e r e s o l u t i o n of neat, p o l y c r y s t a l l i n e 1 , 1 ' - b i n a p h t h y l , S-2 K i n e t i c B a t c h a t 135°, 125° ( o r i g i n a l r u n ) , 115°, and 105°. 127 27. Prout-Tompkins p l o t s f o r t h e s o l i d - s t a t e r e s o l u t i o n o f n e a t , p o l y c r y s t a l l i n e 1 , 1 ' - b i n a p h t h y l , S - l K i n e t i c B a t c h a t 135°. E f f e c t o f g r i n d i n g and of s t o r a g e a t 25° f o r s i x weeks. 128 28. Prout-Tompkins p l o t s f o r t h e s o l i d - s t a t e r e s o l u t i o n o f n e a t , p o l y c r y s t a l l i n e 1 , 1 ' - b i n a p h t h y l , S-2, S-3 and R - l K i n e t i c Batches a t 115°. 129 29. R e l a t i o n o f l o g (ky) (from Prout-Tompkins p l o t s ) t o r e c i p r o - 134 c a l temperature f o r the s o l i d - s t a t e r e s o l u t i o n of n e a t , p o l y c r y s t a l l i n e 1,1'-binaphthyl, a l l four k i n e t i c batches. S t r a i g h t l i n e s a r e l e a s t - s q u a r e s f i t s t o d a t a f o r each b a t c h . 30. P e r c e n t a g e of l , l ' - b i n a p h t h y l samples g i v i n g s p e c i f i c r o t a t i o n s between +240°. The c u r v e shows the G a u s s i a n normal d i s t r i b u t i o n c a l c u l a t e d f o r the mean o f +0.14° and t h e s t a n d a r d d e v i a t i o n o f 86.4°. 1 phase a n a l y s i s F 141 X LIST OF FIGURES ( c o n t i n u e d ) 31. R a t i o o f samples h a v i n g p o s i t i v e r o t a t i o n s t o t h e t o t a l number o f samples o f 1 , 1 ' - b i n a p h t h y l c r y s t a l l i z e d a t 150°. The 200 samples a r e t r e a t e d as two s e t s o f 100 each. The c u r v e s a r e c o n f i d e n c e l i m i t s c a l c u l a t e d f o r a 0.99 degree o f c o n f i d e n c e and a p r o b a b i l i t y o f 50% p o s i t i v e and 50% n e g a t i v e f o r each sample. 142 32. S c h e m a t i c r e p r e s e n t a t i o n o f t h e two p o s s i b l e t e r n a r y systems formed between s o l v e n t , R- and S - 1 , 1 ' - b i n a p h t h y l a t -78°. (a) R- and S-enantiomers form a e u t e c t i c m i x t u r e , (b) R- and S-enantiomers form a racemate. A l t h o u g h (b) i s more s t a b l e , (a) can e x i s t f o r i n d e f i n i t e p e r i o d s o f t i m e at -78°. 181 33. R e l a t i o n o f t h e f r e e energy d i f f e r e n c e between racemate 187 and r a c e m i c e u t e c t i c forms o f 1 , 1 ' - b i n a p h t h y l t o t e m p e r a t u r e . L H F i r s t a p p r o x i m a t i o n , assuming C^ = 0 (see t e x t ) . L~*ft D o t t e d l i n e s a r e u n c e r t a i n t i e s i n AG^ ^423 ^ ^423' ^ individually. R e l a t i o n o f t h e f r e e energy d i f f e r e n c e between racemate 189 and r a c e m i c e u t e c t i c forms o f 1 , 1 ' - b i n a p h t h y l t o t e m p e r a t u r e . L H Second a p p r o x i m a t i o n , assuming = constant (see t e x t ) . L~*H D o t t e d l i n e s a r e u n c e r t a i n t i e s i n AG^ caused by e r r o r s i n a n 34. caused by e r r o r s i n AH^ ^ 423 t a e n AsV^?, and C^ - C^, taken 423 p p individually. xi ACKNOWLEDGEMENT I remain most g r a t e f u l t o P r o f e s s o r R i c h a r d E. P i n c o c k , who more than any o t h e r p e r s o n was r e s p o n s i b l e f o r t e a c h i n g me t h e methods and meaning o f c h e m i c a l continuous research. I v e r y much a p p r e c i a t e h i s g u i d a n c e and encouragement o v e r t h e p a s t f o u r y e a r s . I would l i k e t o thank my w i f e f o r h e r l o v e and u n d e r s t a n d i n g , e s p e c i a l l y d u r i n g t h e w r i t i n g o f t h i s t h e s i s , f o r h e r h e l p w i t h some o f the t i n y , t r o u b l e s o m e d e t a i l s d u r i n g i t s p r e p a r a t i o n , and f o r t u r n i n g a deaf e a r t o t h e words emanating from t h e a u t h o r w h i l e bent o v e r t h e typewriter. I would a l s o l i k e t o thank P r o f e s s o r s H a r r i s o n , S t e w a r t , T r o t t e r , B r e e and S c h e f f e r and t h e i r r e s e a r c h groups f o r d i s c u s s i n g s e v e r a l aspects o f t h i s p r o j e c t w i t h me, and f o r a l l o w i n g me t h e l i b e r a l use o f t h e i r instruments and equipment. Thanks a r e a l s o due t o Mr. F. Slawson and Mr. G. S n i d e r f o r h e l p w i t h i l l u s t r a t i o n s and t o M i s s D. Johnson f o r p a r t i a l l y typing this thesis. I s h o u l d a l s o l i k e t o e x p r e s s my a p p r e c i a t i o n t o t h e H.R. MacMillan F a m i l y Fund ( U n i v e r s i t y o f B.C.) f o r a f e l l o w s h i p , and t o t h e N a t i o n a l R e s e a r c h C o u n c i l and t h e Graduate S t u d e n t F e l l o w s h i p Fund f o r f i n a n c i a l assistance. 1 1 INTRODUCTION Modern knowledge o f the o r g a n i c information on t h e s t r u c t u r e and p h y s i c a l p r o p e r t i e s o f a g r e a t of m a t e r i a l s . standing s o l i d state largely consists of variety Not n e a r l y so w e l l - d e v e l o p e d , however, i s o u r under- of chemical r e a c t i v i t y i n organic which are chemically unstable solids. have been a v o i d e d . U s u a l l y , systems F o r example, many o f the t e c h n i q u e s used f o r t h e p h y s i c a l i n v e s t i g a t i o n s o f o r g a n i c s o l i d s - from u l t r a v i o l e t s p e c t r o s c o p y t o s t a b l e c r y s t a l s of high p u r i t y . causing - require Any c h e m i c a l r e a c t i o n c o m p l i c a t e s t h e i n v e s t i g a t i o n , c a u s i n g measured p r o p e r t i e s eventually semiconductor physics t o change w i t h t i m e , and the breakdown o f c a r e f u l l y grown s i n g l e c r y s t a l s . Even i n o r g a n i c c h e m i s t r y , where s o l i d r e a g e n t s a r e e n c o u n t e r e d d a i l y , the s o l u t i o n phase has been t h e medium p r e f e r r e d for investigations. Here, the v i e w i s g e n e r a l l y h e l d t h a t r e a c t i o n s i n o r g a n i c s o l i d s are too s l u g g i s h t o be o f s y n t h e t i c u t i l i t y , o r too complex t o be amenable to common p h y s i c a l o r g a n i c analysis. There a r e , however, some w e l l - e s t a b l i s h e d areas o f endeavour where the r e a c t i v i t y o f t h e o r g a n i c s o l i d s t a t e has been o f g r e a t i n t e r e s t . The d e c o m p o s i t i o n o f s o l i d o r g a n i c to organic compounds, e s p e c i a l l y those r e l a t e d e x p l o s i v e s , have u n t i l f a i r l y r e c e n t l y a c c o u n t e d f o r most of the research with r e a c t i n g organic solids. 1 I n s e v e r a l r e v i e w s from 1963-1966, Morawetz c o n s i d e r e d the r e p o r t e d examples o f r e a c t i o n s i n o r g a n i c s o l i d s , and drew a t t e n t i o n t o the surge o f i n t e r e s t i n s o l i d s t a t e p o l y m e r i z a t i o n s , now b e i n g w i d e l y e x p l o r e d . One f a s c i n a t i n g a s p e c t o f r e a c t i o n s i n o r g a n i c s o l i d s , w h i c h has r e c e i v e d t h e a t t e n t i o n o f s e v e r a l groups, i s the p o s s i b i l i t y of s t e r e o - c h e m i c a l c o n t r o l by the c r y s t a l l a t t i c e . The v e r y e l e g a n t and d e t a i l e d 3 4 i n v e s t i g a t i o n s o f Schmidt and Cohen ' c r y s t a l l i n e monomers a r e w e l l known. i n t o the photodimerizations of These w o r k e r s demonstrated how the g e o m e t r i c a l o r i e n t a t i o n and s p a c i n g o f r e a c t i n g m o l e c u l e s l a t t i c e determines product stereochemistry. e x p l a i n s the observed i n the Such " t o p o c h e m i c a l control" p r o d u c t s i n most p h o t o r e a c t i o n s o f o r g a n i c s o l i d s . More r e c e n t i n v e s t i g a t i o n s ^ have shown t h a t even some o f the e x c e p t i o n s may s t i l l be s u b j e c t t o c o n t r o l s , b u t o f a d i f f e r e n t n a t u r e . A case i n p o i n t i s 9 - c y a n o a n t h r a c e n e w h i c h e x i s t s i n a "head-to-head" arrangement i n the c r y s t a l l a t t i c e , but g i v e s a " h e a d - t o - t a i l " photodimer. apparent f a i l u r e o f l a t t i c e c o n t r o l was understood This w i t h the d i s c o v e r y of s u i t a b l e d i s l o c a t i o n s i n t h e c r y s t a l a c r o s s w h i c h t h e r e a r e " h e a d - t o - t a i l " p a i r s of molecules. forms t h e observed stereoisomer. Reaction across the d i s l o c a t i o n This r e s u l t underscores then the i n f l u e n c e of c r y s t a l l i n e o r d e r , b o t h i n t h e r e g u l a r l a t t i c e and a t some d i s l o c a t i o n s , on t h e c o u r s e o f s o l i d - s t a t e r e a c t i o n s . O t h e r accounts o f t h e c o n t r o l e x e r c i s e d by the s o l i d s t a t e on p r o d u c t d i s t r i b u t i o n and s t e r e o c h e m i s t r y have been g i v e n . Some r e c e n t r e p o r t s demonstrate t h e wide v a r i e t y o f o r g a n i c r e a c t i o n s w h i c h a r e susceptible to s o l i d - s t a t e p e r t u r b a t i o n . examined the t h e r m a l d e c o m p o s i t i o n epimers 1_ and 2_: A l l r e d and Smith*' have o f the h e t e r o - s u b s t i t u t e d norbornene 3 1 3 4 CH„0 T h e r m o l y s i s of the exo epimer 1_ i n t h e gas phase o r p h o t o l y s i s i n s o l u t i o n gave the b i c y c l o p e n t a n e s _3 and 4_, w i t h t h e t r a n s isomer 3^ i n s l i g h t e x c e s s ; however, p h o t o l y s i s of c r y s t a l l i n e 1 produced t o t a l l y the c i s isomer 4_. almost Analogous r e a c t i o n s of the endo epimer _2 showed p r e f e r e n t i a l f o r m a t i o n of h_ i n f l u i d media b u t an e x c e s s o f _3 i n the crystalline state. T h i s r e v e r s a l o f s t e r e o s p e c i f i c i t y was e x p l a i n e d by f o r m a t i o n o f a s h o r t - l i v e d d i r a d i c a l w h i c h was inverted i n f l u i d media but r e t a i n e d i t s c o n f o r m a t i o n i n the r e s t r i c t e d environment the s o l i d s t a t e . of L i k e w i s e , S i t e , ^ i n a s t u d y o f t h e d e c o m p o s i t i o n o f the q u a t e r n a r y ammonium s a l t 5_ i n the m e l t e d and s o l i d s t a t e s , n o t i c e d t h a t 5 3 4 reaction i n the s o l i d gives a higher than r e a c t i o n i n t h e m e l t . proportion of ortho-substitution A s t r i k i n g i l l u s t r a t i o n of c r y s t a l l a t t i c e 8 c o n t r o l has been g i v e n by P e n z i e n and Schmidt, who i n v e s t i g a t e d t h e r e a c t i o n o f bromine v a p o r w i t h s i n g l e c r y s t a l s o f 4 , 4 ' - d i m e t h y l c h a l c o n e ( 6 ) , an a c h i r a l compound w h i c h c r y s t a l l i z e s i n an e n a n t i o m o r p h i c space group. The r e s u l t i n g d i b r o m i d e was o b t a i n e d w i t h one e n a n t i o m e r i n 6 excess. Hence, t h i s p r o c e s s c o n s t i t u t e s an a b s o l u t e synthesis. develops. asymmetric When t h e r e a c t i o n i s performed i n s o l u t i o n , no a c t i v i t y A n o t h e r g a s - s o l i d r e a c t i o n , t h e a i r o x i d a t i o n o f some 9 s t e r o i d s , was r e p o r t e d heating by B r e n n e r e_t aJL. R e a c t i o n o c c u r r e d on o r on i r r a d i a t i o n , b u t depended s t r o n g l y on t h e p o l y m o r p h i c form o f each compound. Some s t e r o i d s were v e r y s u s c e p t i b l e t o o x i d a t i o n i n one c r y s t a l m o d i f i c a t i o n , and t o t a l l y u n r e a c t i v e i n another. S o l i d - s t a t e c o n t r o l s have been demonstrated w i t h f r e e r a d i c a l s generated e i t h e r t h e r m a l l y ^ ' ^ materials. o r under i o n i z i n g r a d i a t i o n ^ i n o r g a n i c Evidence o f the expected greater p r e s e n t e d b o t h i n t h e form o f i n c r e a s e d to hydrogen a b s t r a c t i o n o u t s i d e selectivity''"''" i n an o r g a n i c cage e f f e c t has been r a t i o s of recombination the c a g e , ^ and as i n c r e a s e d 1 glass over that i n s o l u t i o n . r a d i c a l addition polymerizations reactions stereo- In free i n t h e s o l i d s t a t e , w h i c h have r e c e n t l y 5 been r e v i e w e d , the polymer o f t e n b e a r s some o r i e n t a t i o n a l ( " t o p o t a c t i c " ) r e l a t i o n s h i p t o the monomer l a t t i c e . ^ > ^ c o f p r o d u c i n g polymer those produced j_ n f a c t , the v e r y p r o s p e c t c h a i n s w h i c h are more r e g u l a r l y o r i e n t e d than i n s o l u t i o n has been a major r e a s o n f o r t h e renewed interest i n reactions i n organic s o l i d s . From r e v i e w i n g the r e p o r t e d examples o f o r g a n i c s o l i d - s t a t e r e a c t i v i t y , i t seems t h a t most are e i t h e r chance o b s e r v a t i o n s o r e l s e d e t a i l e d e x a m i n a t i o n s o f systems w h i c h t e n d to be r a t h e r complex. If a good u n d e r s t a n d i n g o f the mechanisms of r e a c t i o n s i n o r g a n i c s o l i d s i s t o be a c h i e v e d , t h e n the v e r y s i m p l e s t of r e a c t i o n s s h o u l d be investigated. These s h o u l d p r o v i d e i n s i g h t i n t o t h e most p r o c e s s e s o c c u r r i n g i n the r e a c t i n g o r g a n i c s o l i d . elementary In t h i s thesis the " s i m p l e r e a c t i o n " w i l l be r e g a r d e d as a t h e r m a l ( o r g a n i c ) s o l i d - s t a t e r e a c t i o n w h i c h always c o n s i s t s o f two components. The t y p e s of r e a c t i o n s t h i s d e f i n i t i o n i n c l u d e s and e x c l u d e s can be c o n s i d e r e d as F i r s t of a l l , the o r g a n i c s o l i d - s t a t e r e a c t i o n s w h i c h proceed under i r r a d i a t i o n o r a r e r a d i a t i o n - i n d u c e d and then t h e r m a l l y are r e l a t i v e l y complex p r o c e s s e s . follows. either proceed I n the case of u l t r a v i o l e t r a d i a t i o n , the e l e c t r o n i c energy l e v e l s of the m o l e c u l a r s o l i d must be t a k e n i n t o a c c o u n t , as w e l l as the mechanism of energy w i t h i n the s o l i d . transfer R e l e v a n t t o t h i s i s the d i s c u s s i o n by S a r t i - F a n t o n i 13 1 ' i n c o n n e c t i o n w i t h the p h o t o c h e m i c a l r e a c t i o n s of 9 - s u b s t i t u t e d anthracenes. b r e a k i n g may structure. The I f i o n i z i n g r a d i a t i o n i s u s e d , r a t h e r i n d i s c r i m i n a n t bond r e s u l t , and t h e r e can be c o n s i d e r a b l e damage to the crystal 2 d e f i n i t i o n a l s o r e s t r i c t s the p o s s i b l e systems to those o f 6 two components. T h i s l i m i t a t i o n f o l l o w s from the f a c t t h a t systems o f t h r e e or more components can p o s s e s s e x c e e d i n g l y complex phase relationships. The t a s k of i d e n t i f y i n g the r e a c t i v e phases c o u l d become v e r y d i f f i c u l t i n such systems. Therefore, r e a c t i o n s of a simple compound t o g i v e a t l e a s t two d i f f e r e n t p r o d u c t s decompositions) (such as a r e e x c l u d e d , as a r e r e a c t i o n s o f two m o l e c u l e s t o g i v e one o r s e v e r a l p r o d u c t s . thermal ( o r more) d i f f e r e n t I n t h e l a t t e r c a s e , i f the two r e a c t a n t s are i n s e p a r a t e phases (two s o l i d s , s o l i d and l i q u i d , etc.), any m e c h a n i s t i c d e s c r i p t i o n must a l s o i n c l u d e the p r o c e s s o f d i f f u s i o n i n s o l i d s i f r e a c t i o n i s to p r o c e e d beyond a monolayer o f p r o d u c t molecules a t the i n t e r f a c e between t h e r e a c t a n t s . The " s i m p l e r e a c t i o n s " a r e t h e r e f o r e t h o s e w h i c h have o n l y a s i n g l e r e a c t a n t and a s i n g l e p r o d u c t . The r e a c t a n t must be e i t h e r neat c o n t a i n o n l y the p r o d u c t as an i m p u r i t y . R e a c t i o n s performed or i n inert s o l i d media ( e . g . g l a s s , h o s t c r y s t a l o r polymer m a t r i x ) a r e n o t " s i m p l e " because the i n e r t medium c o n s t i t u t e s a t h i r d component. The "simple r e a c t i o n " can t h e r e f o r e be r e p r e s e n t e d a s : A where n i s a s m a l l i n t e g e r . ** When n e q u a l s one, the s o l i d r e a c t i o n i s an i s o m e r i z a t i o n . When n i s two, dimer c o n v e r s i o n . One isocyanates i n nB the r e a c t i o n i s a t h e r m a l monomer- i l l u s t a t i o n of t h i s i s the d i m e r i z a t i o n o f a r y l the s o l i d s t a t e . ^ The r e v e r s e p r o c e s s , the s i m p l e d e c o m p o s i t i o n of a dimer i n t o i t s monomer f r a g m e n t s , i s e x e m p l i f i e d by the t h e r m a l r e a c t i o n o f 9-cyanoanthracene 14 dimer. P r o c e s s e s where 7 n i s t h r e e or g r e a t e r a r e found i n the f o r m a t i o n o f o l i g o m e r s , b u t the r e s t r i c t i o n s o f " s i m p l i c i t y " makes examples rare. That i s , i f a monomer •> t r i m e r r e a c t i o n proceeds v i a a dimer w i t h a d i s c r e t e e x i s t e n c e , t h e t o t a l s y s t e m becomes one of t h r e e components. Examples of t h e r m a l s o l i d - s t a t e i s o m e r i z a t i o n s a r e somewhat more common t h a n t h o s e o f t h e r m a l monomer-dimer r e a c t i o n s . r e p o r t e d examples Some o f the a r e i n need o f more e x p e r i m e n t a l work, b u t a few have been i n v e s t i g a t e d i n c o n s i d e r a b l e detail. There a r e a few i l l u s t r a t i o n s o f t h e r m a l s o l i d - s t a t e tautomerism. 16 Pope and coworkers o b s e r v e d t h a t a n t h r o n e (7) r e a d i l y t a u t o m e r i z e s t o a n t h r a n o l (8) i n the s o l i d - s t a t e from 84° t o 158°. In fact, a n t h r a n o l i s e a s i l y p r e p a r e d by h e a t i n g anthrone a t i t s m e l t i n g p o i n t 0 OH then quenching q u i c k l y t o room t e m p e r a t u r e . No k i n e t i c s were r u n , but the h a l f - l i f e a t room t e m p e r a t u r e i n benzene s o l u t i o n i s about 2 h o u r s . The n i t r o s o p h e n o l 9_, w h i c h c r y s t a l l i z e s from benzene i n a "green form", undergoes a s o l i d - s t a t e c o n v e r s i o n a t 129° t o a " r e d f o r m " (m.p. 154°) 17 w h i c h has been shown by c r y s t a l l o g r a p h i c s t u d i e s monoxime s t r u c t u r e 10. t o have the o_-quinone The same t a u t o m e r i s m e x i s t s i n s o l u t i o n , and b o t h forms have i n t r a m o l e c u l a r hydrogen b o n d i n g . I f the p a l e y e l l o w 8 10 9 c r y s t a l s o f the d i n i t r o b e n z y l p y r i d i n e .11 are i r r a d i a t e d w i t h l i g h t o f o w a v e l e n g t h 4000 A, deep b l u e c r y s t a l s are produced. When the p h o t o - p r o d u c t i s k e p t i n t h e d a r k , t h e r m a l r e c o n v e r s i o n t o L l o c c u r s i n a few H 11 hours. 12 A c r y s t a l s t r u c t u r e d e t e r m i n a t i o n of 11 t o suggest t a u t o m e r i s n s t r u c t u r e s 1_1 and 12. l e d S e f f and T r u e b l o o d ( v i a t h e oxygen of the o - n i t r o group) between Another thermal-photochemical i n t e r c o n v e r s i o n i n 19 the s o l i d s t a t e was photoisomer r e v e a l e d by a c r y s t a l l o g r a p h i c s t u d y ( s t r u c t u r e 13) of b i ( a n t h r a c e n e - 9 , 1 0 - d i m e t h y l e n e ) ( 1 4 ) . The p h o t o i s o m e r L3, w h i c h c o u l d be produced by s o l i d - s t a t e of _14_ or s i m p l y by c r y s t a l l i z a t i o n from c h l o r o f o r m i n the undergoes a dark r e c o n v e r s i o n t o i t s v a l e n c e tautomer state. of the irradiation light, 14_ i n the s o l i d 9 An i n t e r e s t i n g case o f s t e r e o i s o m e r i s m a t an oxygen-carbon bond due to hydrogen bonding i n the s o l i d s t a t e was p u b l i s h e d r e c e n t l y by 20 CurtLn and B y r n . The compound d i m e t h y 1 - 3 , 6 - d i c h l o r o - 2 , 5 - d i h y d r o x y - t e r e p h t h a l a t e e x i s t s i n b o t h a y e l l o w form (m.p. (m.p. 140°) and a w h i t e c a . 185°). S t u d i e s w i t h d e u t e r a t e d p h e n o l i c g r o u p s , and and n u c l e a r q u a d r u p o l e resonance infrared i n v e s t i g a t i o n s are c o n s i s t e n t w i t h s t r u c t u r e 15a and 15b, r e p r e s e n t i n g the y e l l o w and w h i t e 15a respectively. form forms, 15b A t h e r m a l s o l i d - s t a t e c o n v e r s i o n from the y e l l o w t o the w h i t e form o c c u r s at 125°. A k i n e t i c s t u d y o f the i s o m e r i z a t i o n of s o l i d c i s - a z o b e n z e n e 21 has been performed by Tsuda and K u r a t a n i . (16) The c i s - t r a n s c o n v e r s i o n 10 was i n v e s t i g a t e d i n samples w h i c h were powdered and compressed i n KBr N=N^ N=N 16 discs. The r e a c t i o n o c c u r s i n the s o l i d s t a t e , g i v i n g r i s e t o s i g m o i d - , shaped k i n e t i c c u r v e s , w h i c h were s e n s i t i v e t o the method o f sample p r e p a r a t i o n , a n d the e x t e n t of g r i n d i n g . One case o f a s o l i d - s t a t e r e a c t i o n between c o n f o r m a t i o n a l i s o m e r s 22 has been r e p o r t e d . S e v e r a l y e a r s ago Brown and S u j i s h i what they p o s t u l a t e d as t h e c o n v e r s i o n on observed h e a t i n g o f an u n s y m m e t r i c a l isomer 17a t o a s y m m e t r i c a l i s o m e r 17b o f a t r i - a - n a p h t h y l adduct. The s o l i d - s t a t e c o n v e r s i o n was borine-ammonia d i s c o v e r e d by n o t i n g t h a t the 140°C • NH, NH, 17a 17b p r e s s u r e of d i s s o c i a t e d ammonia was q u i t e d i f f e r e n t f o r each m a t e r i a l , and t h a t the h i g h l y d i s s o c i a t e d adduct c o n v e r t e d t o the more s t a b l e adduct on h e a t i n g t o 140°. Some i l l u s t r a t i o n s of t h e r m a l i s o m e r i z a t i o n v i a group m i g r a t i o n s i n the s o l i d s t a t e e x i s t . Almost twenty y e a r s ago, S l u y t e r m a n and 23 coworkers examined the t h e r m a l r e a c t i o n s o f t e t r a g l y d n e m e t h y l e s t e r (18) i n the s o l i d s t a t e . H e a t i n g n e a t 1_8 a t 100° produced sarcosyl 11 H.N-CH.-C-(-N-CH.-C-)--OCH 2 2 |f | 2 || 3 O H 0 triglycine + *• CH -NH -CH -C-(-N-CH -C).-0 3 2 2 || , 2 || 3 O H 0 0 0 ( 1 9 ) , t h e r e s u l t of a m e t h y l m i g r a t i o n , w h i c h i s perhaps most f e a s i b l y e x p l a i n e d by an i n t e r m o l e c u l a r s h i f t from t h e e s t e r end o f one m o l e c u l e t o t h e amino end o f a n e i g h b o u r . A t h i g h e r tempera- t u r e s (185°) and i n s o l u t i o n a t 100° p o l y c o n d e n s a t i o n reaction. i s t h e main A k i n e t i c r u n a t 100° showed S-shaped c h a r a c t e r ; t h e i n d u c t i o n p e r i o d was s h o r t e n e d somewhat by g r i n d i n g t h e sample. A n o t h e r rearrangement i n t h e s o l i d s t a t e has been s t u d i e d i n d e t a i l 24 25 by C u r t i n and c o l l a b o r a t o r s . ' Two d i f f e r e n t arylazotribenzoylmethanes, 20 and 2 1 , undergo m i g r a t i o n o f a b e n z o y l group b o t h t o oxygen ( f o r m i n g the e n o l benzoate 22) and t o n i t r o g e n ( f o r m i n g t h e hydrazone 2 3 ) . The 0 22 N=N 20 X = H 21 X = Br 0 II (C H C-) C=N-N 0 23 study was backed by an x-ray c r y s t a l s t r u c t u r e a n a l y s i s o f the bromod e r i v a t i v e 21_, by d i f f e r e n t i a l t h e r m a l a n a l y s i s , and by o b s e r v a t i o n o f 12 the r e a c t i o n b o t h i n s i n g l e c r y s t a l s on a m i c r o s c o p e h o t s t a g e and i n a p o l y c r y s t a l l i n e sample by powder d i f f r a c t o m e t r y . F o r example, when 20 i s h e a t e d a t 5°/min, m e l t i n g o c c u r s a t c a . 124°, i m m e d i a t e l y by rearrangement accompanied and i s f o l l o w e d t o an e q u i m o l a r m i x t u r e o f 22_ and by the e v o l u t i o n o f h e a t . 23, F u r t h e r h e a t i n g converts the i s o m e r 22_ t o 23_ o v e r a temperature range of 40°, and f i n a l l y the pure hydrazone m e l t s a t 200°. E x a m i n a t i o n o f m i x t u r e s o f the t h r e e compounds 20_, 2_2_ and 2_3 s u g g e s t e d a e u t e c t i c t e m p e r a t u r e above The r e a c t i o n proceeds i n the s o l i d s t a t e i n the temperature 70-105°. 110°. range A l t h o u g h t h e system i s v a s t l y s i m p l e r t h a n most d e c o m p o s i t i o n s , i t u n f o r t u n a t e l y i n v o l v e s t h r e e components, and a more d e t a i l e d d e s c r i p t i o n o f phase r e a c t i v i t i e s and r e l a t i o n s h i p s would be rather difficult. 26 An i n i t i a l r e p o r t by L e f f l e r of the s o l i d - s t a t e isomerization of 2 , 2 ' - d i i o d o d i b e n z o y l p e r o x i d e (24) has r e c e i v e d f u r t h e r a t t e n t i o n 0 0 from a c r y s t a l l o g r a p h i c s t a n d p o i n t by Gougoutas. The r e a c t i o n o c c u r s i n s e v e r a l weeks i n t h e c r y s t a l l i n e s t a t e a t room t e m p e r a t u r e , and o v e r n i g h t a t 110°. The p r o d u c t b e n z i o d o x o l e 25_ produced i n single c r y s t a l s of _24 i s r e m a r k a b l y w e l l - o r d e r e d and b e a r s a t o p o t a c t i c r e l a t i o n s h i p to the r e a c t a n t l a t t i c e . T h i s g e o m e t r i c a l correspondence 13 suggests that h a l f of the phenyl r i n g s f l i p through 180° d u r i n g reaction, a m o l e c u l a r movement w h i c h i s s u r p r i s i n g l y l a r g e i n terms o f t h e s p a c i n g allowed i n the l a t t i c e . A study of the r e l a t e d peroxides X = hydrogen, 2-bromo, 2 - c h l o r o , 2_6^ where 2 - f l u o r o , 3 - c h l o r o and 4 - n i t r o showed 0—0 26 2 7b 28 that a l l react i n the s o l i d s t a t e , and some single c r y s t a l topotactic transformations undergo s i n g l e c r y s t a l - s i m i l a r to the diiodo compound 24. 29-33 Some s i m p l e i s o m e r i z a t i o n s , w h i c h o c c u r e a s i l y on m e l t i n g , may a l s o p r o c e e d i n t h e s o l i d s t a t e . t h e s e systems below R e i n v e s t i g a t i o n of reactions i n the m e l t i n g p o i n t s concerned may r e v e a l some unusual s o l i d - s t a t e behaviour. I n t e r e s t i n c h e m i c a l r e a c t i o n s i n o r g a n i c s o l i d s began i n t h i s 34 35 l a b o r a t o r y w i t h t h e work o f P i n c o c k and K i o v s k y frozen solutions. I t was d i s c o v e r e d occurring i n organic ' on r e a c t i o n s i n t h a t common c h e m i c a l r e a c t i o n s and aqueous s o l v e n t s showed s u r p r i s i n g f e a t u r e s below t h e f r e e z i n g p o i n t o f t h e s o l v e n t . A detailed kinetic proved t h a t these observed changes i n k i n e t i c o r d e r and l a r g e a c c e l e r a t i o n s c o u l d be c o m p l e t e l y concentration study rate accounted f o r s i m p l y by t h e i n c r e a s e d of reactants i n l i q u i d regions I t was u n n e c e s s a r y t o i n v o k e any n o v e l of the frozen solid-state effects. solvent. These 14 l i q u i d r e g i o n s n e c e s s a r i l y e x i s t above the e u t e c t i c t e m p e r a t u r e of s o l v e n t - s o l u t e phase system. I t was t h e r e f o r e emphasized t h a t i n a l l r a t e s t u d i e s i n f r o z e n s y s t e m s , even those as f a r as 70° m e l t i n g p o i n t s c o n c e r n e d , any q u a n t i t a t i v e l y separated the below the r e a c t i o n i n a l i q u i d phase must be out b e f o r e v a l i d c o n c l u s i o n s regarding solid- s t a t e phenomena can be drawn. A l o g i c a l e x t e n s i o n of the i d e a s d e v e l o p e d d u r i n g the work on r e a c t i o n s i n f r o z e n , i n e r t s o l v e n t s was to consider p o i n t thermal r e a c t i o n i n a neat s o l i d r e a c t a n t . product w i l l above the e u t e c t i c of the system. o n l y two In general l o w e r the m e l t i n g p o i n t of the r e a c t a n t , and p o t e n t i a l l y o c c u r i n b o t h the s o l i d and has from a k i n e t i c stand- the r e a c t i o n can the l i q u i d phases a t t e m p e r a t u r e s I f the system i s " s i m p l e " , i . e . , components, the i m p o r t a n t phase r e l a t i o n s h i p s may be easy to e s t a b l i s h . For t h i s r e a s o n , the f i r s t system s t u d i e d was 3A r o t a t i o n of p o l y c r y s t a l l i n e a - D - g l u c o s e . the t h e r m a l muta- 36 Isothermal kinetic runs below the m e l t i n g p o i n t of pure a-D-glucose (146°) p o s s e s s e d an S-shaped c h a r a c t e r . sample, R e a c t i o n began s l o w l y i n the i n i t i a l l y s o l i d but as the p r o d u c t g-D-glucose d e v e l o p e d , the r e a c t i o n a c c e l e r a t e d the sample began to m e l t ; maximum r a t e was whereafter nature o b s e r v e d on complete m e l t i n g , the r a t e d e c r e a s e d as e q u i l i b r i u m was approached. of the k i n e t i c c u r v e s c o u l d be e x p l a i n e d by n e g l e c t i n g r e a c t i o n i n the s o l i d phase, and l i q u i d phase. The and c o n s i d e r i n g o n l y t h a t i n the The sigmoid any developing r e a c t i o n a c c e l e r a t e s because the r e a c t i n g l i q u i d phase i n c r e a s e s i n volume a t the expense o f the u n r e a c t i v e s o l i d phase. 37 A second s t u d y , t h a t of the t h e r m a l endo- and e x o - 5 - n o r b o r n e n e - 2 , 3 - d i c a r b o x y l i c i s o m e r i z a t i o n of p o l y c r y s t a l l i n e a n h y d r i d e s (27 and 28, 15 r e s p e c t i v e l y ) above and below t h e i r m e l t i n g p o i n t s , demonstrated the 27 (m.p. 164°) 28 (m.p. 143°) type o f k i n e t i c s w h i c h can a r i s e from r e a c t i o n o c c u r r i n g s i m u l t a n e o u s l y i n b o t h s o l i d and l i q u i d phases. C h e m i c a l e q u i l i b r i u m i n the two- component systems o c c u r s a t an e q u i m o l a r m i x t u r e o f i s o m e r s , and can be approached from e i t h e r s i d e . S o l i d endo i s o m e r , h e a t e d a t 120-164°, e v e n t u a l l y m e l t e d , b u t u n l i k e a - D - g l u c o s e , the form o f the k i n e t i c c u r v e s was not s i g m o i d , but f i r s t o r d e r . if That i s , r e a c t i o n o c c u r r e d as the system were t o t a l l y m e l t e d , even though the s o l i d phase present. Phase s t u d i e s showed t h a t s o l i d endo i s o m e r was was a "crystalline 37 liquid" above 94°, and t h a t m o l e c u l e s i n t h i s phase p o s s e s s e d m o b i l i t y and c o u l d i s o m e r i z e e q u a l l y as f a s t as t h o s e i n the l i q u i d phase. S o l i d exo a n h y d r i d e c o u l d n o t i s o m e r i z e as r e a d i l y as t h e endo a d d u c t , and t h i s f a c t was curves. r e f l e c t e d i n the shape o f the k i n e t i c Rate e q u a t i o n s f o r b o t h r e a c t i o n s were d e v e l o p e d by t h a t the r e a c t i o n i n the s o l i d phase i s f i r s t o r d e r . assuming The r a t e e q u a t i o n c o u l d be i n t e g r a t e d , and by a s s i g n i n g d i f f e r e n t v a l u e s t o the s o l i d s t a t e r a t e c o n s t a n t , t h e form of b o t h the endo and exo k i n e t i c c u r v e s c o u l d be g e n e r a t e d . A s e p a r a t i o n of the k i n e t i c c o n t r i b u t i o n s of b o t h s o l i d and m e l t phase r e a c t i o n s was In v i e w of the f a c i l i t y therefore accomplished. w i t h w h i c h r e a c t i o n proceeds i n s o l i d endo 16 and exo a n h y d r i d e s , we d e c i d e d t o examine the p o s s i b i l i t y o f s o l i d - s t a t e r a c e m i z a t i o n i n two o p t i c a l l y a c t i v e systems. Diels-Alder b i n a p h t h y l (30). The second was S i n c e the two a enantiomers, a simple hydrocarbon, (+)-l,l'- components i n each o f t h e s e systems are 29 30 the phase r e l a t i o n s h i p s are s i m p l i f i e d . s t a t e r e a c t i o n , i f i t occurs at a l l , The f i r s t , also a d d u c t , was ( + ) - b i c y c l o [ 2 . 2 . l ] h e p t - 5 - e n e - t r a n s - 2 , 3 - d i c a r b o x y l i c a c i d (29). hopefully, The Any true s o l i d - s h o u l d be e a s i l y r e c o g n i z e d and, examined more c l o s e l y . r e s u l t s o f our s t u d y o f the c y c l o p e n t a d i e n e - f u m a r i c a c i d adduct (29) a r e p r e s e n t e d i n S e c t i o n 2 o f the t h e s i s . (and unexpected i n S e c t i o n 3. Our f i n d i n g s ! ) w i t h the 1 , 1 ' - b i n a p h t h y l system investigations are r e p o r t e d 17 2 RACEMIZATION OF (+)-BICYCLO[2.2.1]HEPT-5-ENE-TRANS-2,3-DICARBOXYLIC 38 ACID (29) IN THE LIQUID AND SOLID STATES T h i s m o l e c u l e , w h i c h owes i t s dissymmetry t o two c h i r a l carbon atoms, can c o n c e i v a b l y i n t e r c o n v e r t w i t h i t s enantiomer i n t h e m e l t and i n s o l u t i o n , and p o s s i b l y a l s o i n t h e s o l i d C °2 H A state. C0 H 2 C0 H 2 29, (+)-enantiomer (m.p. 176°), ( i ) - r a c e m a t e The r a c e m i c compound 29_ was p r e p a r e d (m.p. 186°) 3. from t h e addends ( c y c l o 39 p e n t a d i e n e and f u m a r i c a c i d ) u s i n g the method o f Koch. Resolution 40 t o t h e (+)-enantiomer was e f f e c t e d v i a t h e b r u c i n e s a l t , m u l t i p l e r e c r y s t a l l i z a t i o n s from a c e t o n e - w a t e r . using The p u r i f i e d (+)- d i a c i d 29, was more h i g h l y r e s o l v e d ( d i f f e r e n t p r e p a r a t i o n s gave 26 s p e c i f i c r o t a t i o n s o f [ c t ] ^ = +137° and +147° i n acetone) and p o s s e s s e d 40 a h i g h e r m e l t i n g p o i n t (177-179°) than t h a t o r i g i n a l l y reported on ( [ a ] p = +89°, m.p. 166-168°). A l t h o u g h the o p t i c a l p u r i t y o f the The p r e p a r a t i o n and t h e r e s o l u t i o n o f ( + ) - d i a c i d _29 was p e r f o r m e d r e s oi ln v et dh i sd i al ca ibdo r remains t h eb ek fi on re et i cthe r e work s u l t s r pe rp eo sr etnetde di nbelow a t o r y by unknown, M.M. Tong, this t h e s i s was begun. 3. 18 d i d not depend, even i n the s o l i d s t a t e , on the e x t e n t of r e s o l u t i o n . 2.1 R a c e m i z a t i o n i n the L i q u i d S t a t e 2.1.1 The M e l t Phase K i n e t i c runs i n the m e l t phase were p e r f o r m e d from 176- 194°. method i n v o l v e d h e a t i n g i n d i v i d u a l s e a l e d ampules c o n t a i n i n g C+)-29 i n a c o n s t a n t occurred, was temperature bath. and a l t h o u g h t h e r e was not s i g n i f i c a n t b e f o r e The purified R a c e m i z a t i o n to [ c t j ^ = 0° a s l i g h t y e l l o w i n g of s a m p l e s , t h i s the m a t e r i a l was essentially racemic. P r o d u c t s t u d i e s showed t h a t a t l o n g r e a c t i o n times ( g r e a t e r than 15 h a l f - l i v e s ) , some p o l y m e r i z a t i o n o c c u r r e d , but was the i n i t i a l reaction s i m p l y an i n t e r c o n v e r s i o n of e n a n t i o m e r s . When the r e s u l t s were p l o t t e d as f i r s t - o r d e r r e a c t i o n s ( l o g [a] / [CX]Q b v s . t i m e ) , s t r a i g h t l i n e s were o b t a i n e d t o o v e r 90% r e a c t i o n ( F i g u r e 1 ) . The are l i s t e d i n T a b l e observed f i r s t - o r d e r r a t e constants H a l f - l i v e s f o r r a c e m i z a t i o n v a r i e d from 3 min 176°. The a t 194° I. t o 12 min at ease o f r e a c t i o n a t the m e l t i n g p o i n t of (+)-29 s u g g e s t s t h a t any s o l i d - s t a t e r e a c t i o n , even i f s l o w e r by one or two orders of magnitude, might s t i l l be m e a s u r a b l e . 2.1.2 The The S o l u t i o n Phase racemization of (+)-29 was also studied i n t e t r a l i n s o l u t i o n , a t t e m p e r a t u r e s where the pure d i a c i d 2_9_ would be s o l i d Again, f i r s t - o r d e r p l o t s were s t r a i g h t l i n e s , and constants k (131-152°). the o b s e r v e d r a t e are shown i n T a b l e I. A l l of our s p e c i f i c r o t a t i o n s [a] were measured at the sodium D The s u b s c r i p t D w i l l h e r e a f t e r be o m i t t e d f o r s i m p l i c i t y . line. 19 TIME MINUTES F i g u r e 1. F i r s t - o r d e r k i n e t i c p l o t s f o r r a c e m i z a t i o n o f neat 29 i n t h e m e l t phase. (+)-diacid 20 Table I First-Order Rate C o n s t a n t s f o r R a c e m i z a t i o n o f (+)-29 i n S o l i d , M e l t and Temperature, °C k obs Solution Phase x 10"*, s e c ^ 194.3 380 melt 189.1 248 II 181.8 147 II 176.6 103 II melt + s o l i d 166.2 8.3 161.2 7.09 155.4 4.23 solid 152.4 2.76 II 140.2 0.654 II 130.9 0.227 II 152.4 6.98 143.7 2.93 II 131.3 0.834 II a ti II a solution I n i t i a l rate constant. The a c t i v a t i o n parameters f o r r a c e m i z a t i o n i n t h e m e l t and i n s o l u t i o n were o b t a i n e d from a p l o t o f l o g k ^ /T by t h e E y r i n g e q u a t i o n : v s * 1/1 a s required 21 where K and h a r e Boltzmann's and P l a n c k ' s c o n s t a n t s , r e s p e c t i v e l y , t T i s the a b s o l u t e t e m p e r a t u r e , and AS enthalpy of a c t i v a t i o n . f and AH a r e the e n t r o p y and The f r e e energy o f a c t i v a t i o n , AG^, i s obtained from the r e l a t i o n : [2] AG* = AH* - TAS* and the temperature chosen f o r comparison of the r e a c t i o n i n d i f f e r e n t phases was 150°. The r e s u l t s a r e l i s t e d i n T a b l e I I and p l o t t e d i n F i g u r e 2. The r a t e i n t e t r a l i n s o l u t i o n i s seen t o be some 2.0-2.5 t i m e s Table I I A c t i v a t i o n Parameters f o r R a c e m i z a t i o n o f (+)-29 i n S o l i d , M e l t , and Solution k (150°), Q b g sec 1 AG* (150°), k c a l mole melt 11.3 x I O - 5 solid 2.05 x 1 0 - 5 solution 5.14 x 10~ 5 a 32.6 1 AH* AS* k c a l mole 1 c a l mole "'"deg 29.7 -6.9 34.0 40.0 +14 33.2 33.6 1 +0.8 E x t r a p o l a t e d from the t e m p e r a t u r e range 176-194' s l o w e r than t h a t i n the m e l t ( e x t r a p o l a t e d ) . This small difference i s r e f l e c t e d i n a m a r g i n a l l y h i g h e r f r e e energy o f a c t i v a t i o n i n t e t r a l i n solution. Such a s m a l l s o l v e n t e f f e c t i s t y p i c a l o f r e v e r s e D i e l s - A l d e r I90° 180° 170° 2.20 160° 2.30 150° i I40 • c ~2AO '/ xlCT T F i g u r e 2. R e l a t i o n of l o g ^ /T) t o r e c i p r o c a l temperature f o r a c e m i z a t i o n of (+)-enantiomer 2_9_ i n m e l t , s o l i d , and s o l u t i o n (in tetralin) phases. 23 r e a c t i o n s and r e c o m b i n a t i o n s . A l s o , t h e magnitude o f t h e a b s o l u t e r a t e c o n s t a n t s i n b o t h l i q u i d media i s c l o s e t o t h a t o f s i m i l a r nD i e l1 s - AA lU d e r 2.2 reactions. Racemization The 4 2 » 4 reverse 3 i n the S o l i d State r a c e m i z a t i o n o f t h e ( + ) - d i a c i d .29 was e x p l o r e d below i t s m e l t i n g p o i n t (176°). P o l y c r y s t a l l i n e samples o f r e s o l v e d 29 were s e a l e d i n ampules and h e l d a t v a r i o u s t e m p e r a t u r e s below 176°. I t was found t h a t r a c e m i z a t i o n c o u l d i n d e e d o c c u r as low as 130°. M o r e o v e r , t h e k i n e t i c form o f t h e r e a c t i o n from 130° t o 155° was first-order. P l o t s o f l o g [ a ] / [ a ] Q v s . time were a g a i n l i n e a r t o a t l e a s t 90% r a c e m i z a t i o n ( s e e F i g u r e s 3 and 4 ) . There were no i n h i b i t i o n p e r i o d s as have been v i r t u a l l y always o b s e r v e d for solid-state 1 organic 44a and i n o r g a n i c decompositions. The k i n e t i c r e s u l t s were i n - s e n s i t i v e t o g r i n d i n g , d i f f e r e n t b a t c h p r e p a r a t i o n s o r sample h i s t o r y . A l s o absent was any dependence on t h e e x t e n t o f r e s o l u t i o n o f t h e samples. The k i n e t i c s i m p l i c i t y o f the r e a c t i o n from 130° t o 155° p e r m i t t e d treatment o f t h e observed rate constants ( T a b l e I ) i n t h e same manner as those f o r r e a c t i o n i n t h e m e l t and i n s o l u t i o n . The p l o t o f l o g k ^ /T a g a i n s t r e c i p r o c a l t e m p e r a t u r e i s shown i n F i g u r e 2. Activation parameters (Table I I ) were o b t a i n e d from t h e r e s u l t i n g s t r a i g h t The r a t e c o n s t a n t a t 150° i s seen t o be o n l y about 5 times line. smaller than t h a t o b t a i n e d from the m e l t e x t r a p o l a t e d t o 150°. I n the t e m p e r a t u r e range 161°to 166°, a d e p a r t u r e f i r s t - o r d e r k i n e t i c s was observed ( F i g u r e s 4 and 5 ) . from simple A sigmoid shape 24 1 2000 1 4000 I 6000 i 8000 I IO.OOO i TIME MINUTES F i g u r e 3. F i r s t - o r d e r k i n e t i c p l o t s f o r racemization of neat, poly- crystalline (+)-29 i n the s o l i d phase. 25 < O ' 200 1 400 1 600 i 800 i i IOOO 1200 i 1400 TIME MINUTES F i g u r e 4. F i r s t - o r d e r k i n e t i c p l o t s f o r racemization of neat, p o l y - crystalline (+)-2_9 a t 152° i n t h e s o l i d phase and a t 161° where melt „ * i s o l i d . 26 20 40 60 80 IOO 120 TIME M I N U T E S F i g u r e 5. the solid K i n e t i c d a t a f o r r a c e m i z a t i o n o f neat samples o f (+)-29 i n (155°), i n t h e b i p h a s e m e l t + s o l i d system (166°), and i n a c o m p l e t e l y m e l t e d system ( a t 176°) . 27 was q u i t e e v i d e n t i n the f r a c t i o n u n r a c e m i z e d v s . time p l o t s a t t h e s e two t e m p e r a t u r e s ( F i g u r e 5 a t 166°). linearity ( F i g . 4 a t 161°). The l o g p l o t s d e v i a t e d from Rate c o n s t a n t s w e r e , however, o b t a i n e d from the i n i t i a l s l o p e s of the l o g p l o t s ( T a b l e I ) f o r comparison t o the o b s e r v e d f i r s t - o r d e r c o n s t a n t s from l o w e r t e m p e r a t u r e r u n s . S i g n i f i c a n t y e l l o w i n g o f the samples o c c u r r e d , much more r a p i d l y t h a n w i t h the m e l t r e a c t i o n a t t e m p e r a t u r e s as h i g h as 194°. Some sintering indicated p a r t i a l melting. 2.3 The Phase 2.3.1 Diagram The D e t e r m i n a t i o n of the Phase Diagram I n o r d e r t o i n t e r p r e t c o r r e c t l y the k i n e t i c r e s u l t s below the m e l t i n g p o i n t , i t was n e c e s s a r y t o a s c e r t a i n the t e m p e r a t u r e below w h i c h the system of e n a n t i o m e r s i s t o t a l l y s o l i d . b i n a r y phase diagram was To t h i s end, the determined using d i f f e r e n t i a l scanning c a l o r i m e t r y and X-ray powder d i f f r a c t i o n . I n g e n e r a l t h e r e a r e o n l y t h r e e t y p e s of b i n a r y phase diagrams 45a 46 formed between e n a n t i o m e r s . ' These a r e the s i m p l e e u t e c t i c , the f o r m a t i o n of a "phase r u l e " compound, and f o r m a t i o n of a s o l i d at a l l compositions. solution I n the s i m p l e e u t e c t i c the c r y s t a l form of one enantiomer does not accommodate the o t h e r and the r a c e m i c m o d i f i c a t i o n i s a two-phase m i x t u r e o f i n d i v i d u a l c r y s t a l s o f pure e n a n t i o m e r s . The "phase r u l e " compound d i a g r a m i s s i m i l a r i n t h a t c r y s t a l l i n e forms a r e i m m i s c i b l e , b u t the r a c e m i c m o d i f i c a t i o n i s a s i n g l e phase ( t h e racemate) c o n t a i n i n g b o t h e n a n t i o m e r s i n a 1:1 r a t i o . c e x c e p t a t t h e extreme edges of the diagram. I n the s o l i d 28 s o l u t i o n t y p e of d i a g r a m , t h e c r y s t a l l a t t i c e o f one e n a n t i o m e r can c o n t a i n t h e o t h e r i n a l l p r o p o r t i o n s , and a s i n g l e s o l i d phase e x i s t s at a l l c o m p o s i t i o n s . The s i n g l e o b s e r v a t i o n t h a t t h e r a c e m i c d i a c i d 29_ m e l t s h i g h e r than the r e s o l v e d m a t e r i a l i m m e d i a t e l y r e s t r i c t s t h e c h o i c e s o f diagrams t o two: (a) f o r m a t i o n o f a phase r u l e compound o r (b) f o r m a t i o n of a s o l i d s o l u t i o n m e l t i n g h i g h e r when r a c e m i c than when r e s o l v e d . The c h o i c e between t h e s e two i s e a s i l y made w i t h t h e d i f f e r e n t i a l 47 scanning and c a l o r i m e t e r ( d . s . c ) . The method i s a n o n e q u i l i b r i u m one, can be used t o measure phase changes w h i c h a r e r a p i d , s u c h as melting or fast s o l i d - s o l i d transitions. The p r o c e d u r e i n v o l v e s h e a t i n g a s m a l l amount o f sample i n a pan and an empty r e f e r e n c e pan at a constant rate. Any energy r e l e a s e o r a b s o r p t i o n i n the sample i s compensated by t h e c a l o r i m e t e r so t h a t t h e a r e a o f t h e r e c o r d e d i s d i r e c t l y p r o p o r t i o n a l to the enthalpy of the t r a n s i t i o n . peak Transition t e m p e r a t u r e s a r e e a s i l y d e t e r m i n e d once t h e d . s . c . i s c a l i b r a t e d . Samples o f t h e d i a c i d 29_ r a n g i n g i n s p e c i f i c r o t a t i o n from +137° t o 0° were h e a t e d on t h e d s . c . and t h e t e m p e r a t u r e s and e n t h a l p i e s of t r a n s i t i o n were d e t e r m i n e d . Some r e p r e s e n t a t i v e d.s.c. t r a c e s a r e shown i n F i g u r e 6. The r e s o l v e d and r a c e m i c d i a c i d 29_ gave no peaks from room temperature up t o t h e r e s p e c t i v e m e l t i n g p o i n t s (176° and 186°) , where sharp endotherms were r e c o r d e d . The e n t h a l p i e s o f fusion (AH ) were 5.38+ 0.16 k c a l m o l e " (29.5 ± 0.9 c a l g ) fusion 1 _ 1 J f o r t h e (+) e n a n t i o m e r 29_ and 7.13 ± 0.24 k c a l m o l e " f o r the racemic m a t e r i a l . calculated from: The c o r r e s p o n d i n g 1 (39 ± 1 . 3 c a l g e n t r o p i e s o f f u s i o n were _ 1 ) 29 F i g u r e 6. 10 deg min (b) 24.8%, D i f f e r e n t i a l scanning f o r the d i a c i d (c) 45.2%, and c a l o r i m e t e r t r a c e s (programming 2_9_ a t v a r i o u s c o m p o s i t i o n s : (d) 50% (-)-enantiomer. (a) 0%, rate: 30 AS. [3] . fusion AH. ^ = . U S 1 ° n T m.p. w h i c h h o l d s o n l y a t t h e m e l t i n g p o i n t where t h e f r e e e n e r g i e s o f s o l i d and m e l t a r e i d e n t i c a l . The AS,, . f o r the r e s o l v e d d i a c i d 29 was fusion — 12.0 ± 0.3 c a l deg "'"mole "*" and f o r t h e r a c e m i c d i a c i d , 15.5 ± 0.5 c a l deg "'"mole \ Samples i n t e r m e d i a t e i n a c t i v i t y , however, gave a s i n g l e at 165°, sometimes f o l l o w e d by a second endotherm temperatures. The endotherm endotherm at s l i g h t l y higher a t 165° i n samples h a v i n g a range o f compositions s t r o n g l y i m p l i e s that t h i s i s a e u t e c t i c temperature. endotherm The i s l a r g e s t f o r a sample h a v i n g a s p e c i f i c r o t a t i o n o f +68°. These o b s e r v a t i o n s a r e t h o s e e x p e c t e d f o r a phase system w i t h r a c e m i c compound f o r m a t i o n . A e u t e c t i c p o i n t ( t e m p e r a t u r e : 165°, c o m p o s i t i o n : h a l f r e s o l v e d ) e x i s t s between t h e r e s o l v e d and r a c e m i c d i a c i d 29. The t e m p e r a t u r e s a t w h i c h t h e d.s.c. peaks appeared a r e p l o t t e d i n F i g u r e 7. The appearance o f a second endotherm 48 49a c o n s i s t e n t w i t h t h e phase system. ' f o r some samples i s At appropriate compositions, t h e s e samples w i l l p a r t l y m e l t a t t h e i n v a r i a n t e u t e c t i c t e m p e r a t u r e , then f i n i s h m e l t i n g o v e r a range o f t e m p e r a t u r e s from t h e e u t e c t i c t o the l i q u i d u s c u r v e . The appearance o f a second peak i n d i c a t e s the maximum r a t e o f t h i s s e c o n d a r y m e l t i n g . The p o i n t a t w h i c h t h e second peak r e t u r n s t o t h e base l i n e i s sometimes t a k e n as t h e p o s i t i o n 48 of the l i q u i d u s c u r v e , b u t i n o u r samples t h e m e l t was t o o v o l a t i l e to a l l o w a p r e c i s e d e t e r m i n a t i o n o f t h i s p o i n t . l i q u i d u s c u r v e s have been For completeness, the s k e t c h e d i n t h e phase diagram (dotted lines) 31 \ 180 MELT \ \ PHASE 1 / / 170 \ \ \ \ / PHASE / \ * / \ / 1 V—1^- u o MELT x / /\ '' w ai 160 SOLID SOLUTION (y) PHASE H RACEMATE PHASE 150 140 j I J 20 L _L _L J 40 60 80 L 100 PERCENTAGE (-)-ENANTIOMER Figure 7. Phase relationship of mixtures of (+)- and (-)-enantiomers of compound 29_. V e r t i c a l bars indicate the uncertainties in transition temperatures (taken at the beginning of d.s.c. endotherms). Undetermined phase boundaries (dotted lines) are estimated f o r completeness. A l s o drawn i n i s a t e r m i n a l s o l i d s o l u t i o n , y> w h i c h must e x i s t , but may have a c o m p o s i t i o n range w h i c h i s s m a l l and d i f f i c u l t determine w i t h the d.s.c. ' to The second h a l f o f the diagram ( ( - ) - s i d e ) i s a m i r r o r image of the (+) s i d e , and i s shown i n F i g u r e 7 f o r completeness. The (-)-enantiomer 29 was not isolated. The d . s . c . r e s u l t s were v e r i f i e d by X-ray powder p h o t o g r a p h y . Photographs o f the r e s o l v e d a c i d were d i f f e r e n t from those o f the racemate. A sample w h i c h had been h a l f r a c e m i z e d showed b o t h s e t s o f c h a r a c t e r i s t i c d i f f r a c t i o n r i n g s , and no o t h e r s . two s o l i d phases a t t h i s c o m p o s i t i o n . No There a r e t h e r e f o r e metastable intermediate phases a r e formed d u r i n g the r e a c t i o n . 2.3.2 The I d e n t i f i c a t i o n and S t a b i l i t y o f R e a c t i v e Knowing the phase diagram ( F i g u r e 7 ) , we a r e now the phases i n w h i c h r a c e m i z a t i o n o c c u r s . From 130° Phases able to consider t o 155°, s o l i d phases a r e i n v o l v e d i n the f i r s t - o r d e r r e a c t i o n . p r o c e e d s , an u n r e a c t i v e racemate s e p a r a t e s only As r a c e m i z a t i o n from t h e r e a c t i v e s o l i d (+)-enantiomer. Between the e u t e c t i c t e m p e r a t u r e and the m e l t i n g p o i n t s c o n c e r n e d , the m e l t and s o l i d c o e x i s t , and r e a c t i o n o c c u r s s i m u l t a n e o u s l y i n b o t h phases. S o l i d samples w i l l t u r e s i n t h i s range. e v e n t u a l l y m e l t when h e l d a t As r a c e m i z a t i o n p r o c e e d s , the l i q u i d tempera- phase 37 grows i n volume a t t h e expense of the s o l i d phase. I t can be shown t h a t a f i r s t o r d e r r e a c t i o n i n a d i s a p p e a r i n g s o l i d phase combined w i t h a f a s t e r r e a c t i o n i n a g r o w i n g m e l t e d phase, w i l l g i v e r i s e t o 33 an S-shaped k i n e t i c c u r v e . and 166° ( F i g u r e 4,5). Such c u r v e s a r e o b s e r v e d i n runs a t The i n d i v i d u a l c o n t r i b u t i o n s of s o l i d 161° and 37 m e l t e d phase r e a c t i o n s can, i n p r i n c i p l e , be s e p a r a t e d . However, i n t h i s case the a v a i l a b i l i t y o f k i n e t i c d a t a a t t e m p e r a t u r e s where the system i s t o t a l l y m e l t e d o r t o t a l l y s o l i d makes such a s e p a r a t i o n unnecessary. Our use o f the phase diagram to c h a r t the c o u r s e of a c h e m i c a l r e a c t i o n s h o u l d perhaps be e x p l a i n e d more f u l l y . The meaning o f such a diagram i s not e n t i r e l y c l e a r from the d i s c u s s i o n t h i s f a r , s i n c e the phases d e s c r i b e d a r e n o t i n c h e m i c a l e q u i l i b r i u m . Systems of d y n a m i c a l l y i n t e r c o n v e r t i n g i s o m e r s such as t h e e n a n t i o m e r i c d i a c i d s 29_ a r e t r e a t e d i n s t a n d a r d t e x t s on phase e q u i l i b r i a as " p s e u d o b i n a r y s y s t e m s " . ' T h i s term means t h a t s t r i c t l y under e q u i l i b r i u m c o n d i t i o n s , the system would behave as a s i n g l e component. However, under n o n e q u i l i b r i u m c o n d i t i o n s ( s u c h as w i t h a d.s.c.) i t i s p o s s i b l e t o d e t e r m i n e a b i n a r y phase diagram. The n e c e s s a r y c o n d i t i o n h e r e i s t h a t the c o m p o s i t i o n o f t h e sample s h o u l d n o t change d u r i n g the time t a k e n f o r the e x p e r i m e n t . I n t h i s c a s e , a t the u s u a l d.s.c. h e a t i n g r a t e s (10°/min), the m e l t i n g r e g i o n i s c o v e r e d i n l e s s than two m i n u t e s , d u r i n g w h i c h time v e r y l i t t l e r a c e m i z a t i o n occurs (Figure 5). The methods f o r d e t e r m i n i n g such " n o n e q u i l i b r i u m " phase diagrams 52 seem w e l l u n d e r s t o o d , but the meaning of such diagrams becomes c l e a r e r from the p o i n t of v i e w of free energy. Consider f i r s t of a l l a A l t h o u g h 161 i s below the b i n a r y e u t e c t i c , the r e l a t i v e l y r a p i d d a r k e n i n g o f samples i n d i c a t e s t h a t o t h e r components are formed. These can l o w e r the b i n a r y e u t e c t i c temperature,53 c a u s i n g the appearance o f a l i q u i d phase. 34 two-component system o f i s o m e r s , w i t h no p o s s i b l e i s o m e r i z a t i o n At c o n s t a n t p r e s s u r e , o f t e m p e r a t u r e and the f r e e energy of each phase w i l l be a composition. temperature - c o m p o s i t i o n - f r e e reaction. function A t h r e e - d i m e n s i o n a l p l o t of energy w i l l t h e r e f o r e i n d i v i d u a l f r e e energy s u r f a c e s - one consist of f o r each phase - suspended o v e r the t e m p e r a t u r e - c o m p o s i t i o n p l a n e ( i . e . the phase d i a g r a m ) . The stable phase ( o r phases) a t each p o i n t on the d i a g r a m i s d e t e r m i n e d by l o w e s t f r e e energy s u r f a c e point. the ( o r c o m b i n a t i o n of s u r f a c e s ) - ^ ' ^ above t h a t Hence the e q u i l i b r i u m phase diagram i s g e n e r a t e d . If the phases a t e v e r y p o i n t are always the most s t a b l e ones ( i . e . a l l phase changes a r e r a p i d ) , then a l l p o i n t s on the phase d i a g r a m are attainable experimentally. Now l e t us a l l o w f o r the i n t e r c o n v e r s i o n of components. Even though the phases are r e a c t i v e , a l l w i l l have i n d i v i d u a l f r e e energy surfaces as b e f o r e . It s t i l l , t h e r e f o r e , makes sense t o speak of the l o w e s t - l y i n g f r e e energy s u r f a c e s , but t h e s e d e t e r m i n e i s not the phase diagram w h i c h an e q u i l i b r i u m d i a g r a m . For example, the e melting p o i n t o f a pure isomer can be d e f i n e d as the t e m p e r a t u r e a t w h i c h the f r e e e n e r g i e s o f the pure s o l i d and pure l i q u i d i s o m e r e q u a l , but such a p o i n t i s not i t s f r e e energy f u r t h e r by i n equilibrium. system can changing i t s c o m p o s i t i o n u n t i l chemical e q u i l i b r i u m i s reached. t e m p e r a t u r e and The are lower final I f the phases e x i s t i n g a t any c o m p o s i t i o n are always those h a v i n g the l o w e s t f r e e e n e r g i e s at t h a t p o i n t , then the phase changes are f a s t . The diagram can then be d e t e r m i n e d e x p e r i m e n t a l l y , p r o v i d e d the i s o m e r i z a t i o n r e a c t i o n Such a p o i n t has been c a l l e d an " i d e a l c o n s t a n t " and the p s e u d o b i n a r y system has been r e f e r r e d t o as a system i n " f a l s e e q u i l i b r i u m " 4 5 b b t. the r e l a t i o n s h i p to f r e e energy s u r f a c e s , a l t h o u g h i m p l i e d , s h o u l d be e x p l i c i t l y s t a t e d . e u 35 i s s u f f i c i e n t l y slow. I f the r e a c t i o n i s t o o f a s t , some p o i n t s , such as t h e pure isomer m e l t i n g p o i n t s , may be i m p o s s i b l e t o a t t a i n (see S e c t i o n 3.3.2.1). I n t h i s manner, by assuming t h a t phase changes a r e more r a p i d t h a n t h e i s o m e r i z a t i o n , t h e course o f a r e a c t i o n may be mapped on a phase diagram. F o r example, when a r e a c t i o n i s " p a s s i n g t h r o u g h " two-phase s o l i d + m e l t r e g i o n a t c o n s t a n t the c o m p o s i t i o n to our treatment 2.4 t e m p e r a t u r e and p r e s s u r e , o f t h e s o l i d and m e l t phases w i l l be c o n s t a n t to t h e s o l i d u s and l i q u i d u s c o m p o s i t i o n s . a and e q u a l Such an approach i s b a s i c of r e a c t i o n s i n n e a t o r g a n i c m a t e r i a l s . Mechanism i n t h e S o l i d State I n v i e w of t h e many c o m p l e x i t i e s a s s o c i a t e d w i t h r e a c t i o n s i n f the s o l i d s t a t e surprising. the k i n e t i c s i m p l i c i t y o f t h i s r a c e m i z a t i o n i s Reactions i n o r g a n i c s o l i d s commonly show i n d u c t i o n p e r i o d s , a u t o c a t a l y t i c e f f e c t s , " ^ o r a dependence on a g i n g and on particle size."^ A l l o f these f e a t u r e s are conspicuously absent below t h e e u t e c t i c of t h e system o f e n a n t i o m e r s w h i c h we have s t u d i e d . The f i r s t - o r d e r k i n e t i c s mean t h a t t h e r a t e - d e t e r m i n i n g step i n the s o l i d - s t a t e r a c e m i z a t i o n can o c c u r w i t h e q u a l p r o b a b i l i t y a t any p o i n t i n the p o l y c r y s t a l l i n e s o l i d . That i s , t h e l o c a t i o n o f t h e d i a c i d m o l e c u l e s 2_9_ (whether they a r e a t t h e edges o f c r y s t a l l i t e s , a t defects o r d i s l o c a t i o n s , o r deeply imbedded i n a r e g i o n o f p e r f e c t l a t t i c e ) makes no d i f f e r e n c e t o t h e i r r e a c t i v i t y . Consistent w i t h t h i s i s the ^ A c o l l e c t i o n of papers d e a l i n g g e n e r a l l y w i t h r e a c t i o n s i n s o l i d s may be found i n the p u b l i s h e d symposia on t h e R e a c t i v i t y o f S o l i d s . 36 o b s e r v a t i o n t h a t g r i n d i n g o r use o f d i f f e r e n t b a t c h p r e p a r a t i o n s no e f f e c t on the k i n e t i c r e s u l t s . has I n t h e s e d i f f e r e n t samples t h e r e w i l l be a w i d e l y d i f f e r e n t p o l y c r y s t a l l i n e g r a i n s i z e and d e f e c t o r d i s l o c a t i o n d e n s i t y i n the r e a c t a n t . The r e a c t i o n i s a l s o not c a t a l y z e d by the p r e s e n c e of the ( r a c e m i c compound). As the p r o d u c t phase grows, the i n t e r f a c e w i l l i n c r e a s e , pass through reactant disappears. product at due reactant-product a maximum, then d e c r e a s e as I n some o r g a n i c d e c o m p o s i t i o n s t h e s u r f a c e causes a c c e l e r a t i o n o f the r e a c t i o n and of sigmoid-shaped k i n e t i c curves. product the developing the production I n our s y s t e m , maximum r a t e o c c u r s the b e g i n n i n g of the s o l i d r e a c t i o n . Such a r a t e maximum i s not t o a v e r y s h o r t a c c e l e r a t i o n p e r i o d and the p r e s e n c e o f product phase, because X - r a y r e s u l t s c l e a r l y show o n l y the pure e n a n t i o m e r at the s t a r t o f the r e a c t i o n . T h e r e f o r e , the n e c e s s i t y o f h a v i n g t o grow a p r o d u c t a r e a c t a n t cannot c o n t r o l the r a c e m i z a t i o n r e a c t i o n . The phase from change o f phase a s s o c i a t e d w i t h the r e a c t i o n must be f a s t compared t o the r a t e g determining step. C o n s i d e r a t i o n w i l l now step. be g i v e n t o the n a t u r e o f the rate-determining I n the m e l t , the r a c e m i z a t i o n w i l l c o n s i s t o f a r e v e r s i b l e first-order reaction: o ° There i s one s p e c i a l i z e d case of f i r s t - o r d e r k i n e t i c s i n a r e a c t i o n c o n t r o l l e d by a phase change. Some i n o r g a n i c d e c o m p o s i t i o n s show f i r s t - o r d e r b e h a v i o u r because of a v e r y f i n e p a r t i c l e s i z e . 5 8 However, the s o l i d - s t a t e r e a c t i o n o f the d i a c i d 2_9_ i s independent of the s t a t e of s u b d i v i s i o n of the s o l i d , so t h a t our o b s e r v e d f i r s t o r d e r k i n e t i c s are not due to t h i s e f f e c t . 37 k A (melt) l „ B (melt) k 2 where A and B a r e the e n a n t i o m e r i c adducts proceeds 29_- to 0° s p e c i f i c r o t a t i o n , k^ = k^. S i n c e the r a c e m i z a t i o n The o b s e r v e d first-order r a t e c o n s t a n t w i l l , as i s u s u a l i n such e q u i l i b r i a , c o n s i s t o f the sum o f t h e f o r w a r d and r e v e r s e r a t e c o n s t a n t s , o r : k obs (melt) k = 1 n + k„ 2 = 2k, 1 In the a c t i v a t i o n p l o t ( F i g u r e 2 ) , k k of k ^ Q s s ( m e l t ) = 2k^ i n E q u a t i o n 1 (p (melt) was used. Substitution 20 ) w i l l make no d i f f e r e n c e t o ± the e n t h a l p y o f a c t i v a t i o n , AH , b u t w i l l a f f e c t the i n t e r c e p t and hence A s i n a s m a l l way. To c o r r e c t f o r t h i s , t h e e n t r o p y o f a c t i v a t i o n s h o u l d be augmented by 2.303R l o g 2 } o r 1.4 c a l deg "'"mole "'". T h i s c o r r e c t i o n i s s m a l l compared t o the l a r g e e n t r o p y between r e a c t i o n i n t h e m e l t and i n t h e s o l i d In difference (21 c a l deg "'"mole "'") . t h e s o l i d , t h e mechanism cannot be t h i s s i m p l e , i n v i e w o f t h e phase r e l a t i o n s h i p s between e n a n t i o m e r s . However, any mechanism must i n c o r p o r a t e t h e o b s e r v a t i o n o f f i r s t - o r d e r k i n e t i c s . sequence o f events c o n s i s t s o f the f o l l o w i n g : k 3 k 4 5 A(y) B( ) Y k A(y) + B( ) Y C(Y) C( ) Y • C ( s e p a r a t e phase) A reasonable 38 C r e p r e s e n t s the p r o d u c t compound, w h i c h i s c o n s i d e r e d as a hydrogen bonded p a i r o f e n a n t i o m e r s . A l l species are f i r s t contained i n the Y phase ( F i g u r e 7 ) . A t low c o n v e r s i o n s , t h e f i r s t p r o d u c t s formed from a f i r s t - o r d e r p r o c e s s i n a s i n g l e r e a c t a n t phase w o u l d e x i s t i n s o l i d s o l u t i o n w i t h the r e a c t a n t , s i n c e a s u f f i c i e n t l y s m a l l number of product molecules randomly s c a t t e r e d throughout the r e a c t a n t m a t r i x h c o u l d n o t form a s e p a r a t e phase. As r e a c t i o n p r o c e e d s , the reactant phase would e v e n t u a l l y become s u p e r s a t u r a t e d i n p r o d u c t , and u n s t a b l e w i t h r e s p e c t t o a two-phase r e a c t a n t - p r o d u c t system. The l a s t r e a c t i o n t h e r e f o r e shows t h e compound C s e p a r a t i n g ( r e l a t i v e l y q u i c k l y , as d i s c u s s e d above) from t h e y phase. The r e v e r s i b l e i n t e r c o n v e r s i o n o f enantiomers rate constants ( i . e . , m e l t phase. w i l l n o t have e q u a l k^ ^ k^) i n t h e y phase as i s the case i n t h e The y c r y s t a l s w i l l p r e s e n t a d i s s y m m e t r i c environment t o the enantiomer B, c a u s i n g a d i f f e r e n c e i n t h e f r e e e n e r g i e s o f A and B i n t h e y phase. The a d d i t i o n o f B e n a n t i o m e r t o pure A w i l l first lower^^'^''" then r a i s e t h e t o t a l f r e e energy o f t h e y phase (see Figure 8 ( a ) ) . The f r e e e n e r g i e s o f t h e s p e c i e s B and C r e l a t i v e t o A are shown s c h e m a t i c a l l y i n F i g u r e 8 ( b ) . B and C a r e a t a h i g h e r energy than A because they a r e n o t e x p e c t e d to f i t i n t o the y l a t t i c e as e a s i l y as A. The f i r s t p a i r of r a t e c o n s t a n t s w i l l t h e r e f o r e l i k e l y be o r d e r e d k. < k.. Once a B m o l e c u l e i s formed, i t w i l l be surrounded 3 4 w i t h A m o l e c u l e s , and w i l l p r o b a b l y be e a s i l y a b l e t o move i n t o p o s i t i o n to form hydrogen bonds w i t h A, t h e r e b y c r e a t i n g compound C. I f this k I n some p h o t o d i m e r i z a t i o n s , t h e p r o d u c t i s c o n s i d e r a b l y s o l u b l e i n the r e a c t a n t l a t t i c e . ' * TEMPERATURE: 150° RACEMATE PHASE o w •z w W W MIRROR IMAGE OF (y) PHASE' 100 50 PERCENTAGE (-)-ENANTIOMER O W Z w w w Pi REACTION COORDINATE F i g u r e 8. (a) Schematic f r e e e n e r g y - c o m p o s i t i o n system ( + ) - and (-)-29, a t c o n s t a n t e r a t u r e (150°) . pressure p l o t i n t h e phase (atmospheric) The d o t t e d l i n e s show t h e l o w e s t and temp- f r e e energy s u r f a c e s f o r t h e two-phase r e g i o n s . (b) Schematic f r e e e n e r g y - r e a c t i o n coordinate plot f o r the s o l i d - s t a t e r a c e m i z a t i o n o f (+)-29 (shown as A ( y ) ) a t 150°. 40 r e a c t i o n i s f a s t , then perhaps k^ << k,. A(y) throughout w i l l be s u f f i c i e n t l y l a r g e to a l l o w most o f the r e a c t i o n . f r a c t i o n of t o t a l d i a c i d w h i c h i s A and i n y. at This quantity i s unity the b e g i n n i n g o f the r a c e m i z a t i o n , and z e r o a t t h e end.) e q u a t i o n f o r the d i s a p p e a r a n c e [ 4 ] (A(y) i s the mole _ dA£r)_ = ^ k rate o f A(y) i s : _ k^B (y) A ( y ) The + k A(y)B(y) 5 and i f k^ < k^ << k ^ A ( y ) , B(y) i s a s h o r t - l i v e d r e a c t i v e i n t e r m e d i a t e i n t h e y phase. A s t e a d y - s t a t e t r e a t m e n t [5] = 0 = k A(y) - k B(y) 3 = 4 + k A(y) - ~ 5 S u b s t i t u t i o n of [5] i n t o 5 k J k k A(y)B(y) 4 k A(y) B(y) [6] on B(y) g i v e s : J k 5 [4] y i e l d s : = k A(y) - ^ 3 + k A(y) = 3 2k A(y) I n t e g r a t i o n w i l l g i v e the r e s u l t k ^ g ( s o l i d ) = 2k^. 3 Therefore, the above assumptions about t h e r e l a t i v e magnitudes o f the r a t e c o n s t a n t s l e a d t o t h e c o n c l u s i o n t h a t as soon as one A c o n v e r t s t o B, immediately d i s a p p e a r s i n the f o r m a t i o n of another C. As w i t h the m e l t r e a c t i o n , the s u b s t i t u t i o n of k . ( s o l i d ) = obs 2k^ i n E q u a t i o n 1 (p 20 ) does n o t a l t e r AH' f o r the s o l i d , and changes the c a l c u l a t e d AS ± o n l y by a s m a l l amount (1.4 c a l deg -1 mole -1 ) 41 The a c t i v a t i o n parameters d e s c r i b e i n the s o l i d - the reverse t h e same p r o c e s s i n t h e m e l t as D i e l s - A l d e r r e a c t i o n and r e c o m b i n a t i o n t o form the enantiomer - and can be compared f o r t h e two phases. the f r e e e n e r g i e s o f a c t i v a t i o n a r e c l o s e J. AH Although (Table I I ) , the c a l c u l a t e d 4. and AS T a r e markedly d i f f e r e n t . Passage o f t h e adduct from t h e ground s t a t e t o t h e t r a n s i t i o n s t a t e a p p a r e n t l y increase i n v o l v e s an e n t r o p y (a l o c a l d i s r u p t i o n i n the h i g h l y ordered c r y s t a l l a t t i c e ) , at t h e c o s t o f a h i g h e r energy o f a c t i v a t i o n than i n t h e m e l t . The s i m i l a r i t y o f r a t e c o n s t a n t s i n t h e s o l i d and m e l t (k , ( m e l t ) / obs k k ( s o l i d ) = 5 a t 150°C) i s r a t h e r s u r p r i s i n g c o n s i d e r i n g t h a t t h e Q g few examples i n w h i c h t h i s comparison can be made show much l a r g e r 3 4 2a r a t i o s ( c a . 10 -10 ) . However, t h e endo c y c l o p e n t a d i e n e - m a l e i c a n h y d r i d e adduct 27 (p 15 ) a l s o has a f a c i l e s o l i d - s t a t e i s o m e r i z a t i o n but t h i s r e a c t i v i t y can be a t t r i b u t e d t o a p l a s t i c c r y s t a l l i n e solid 37 state. Such m o b i l e s o l i d s a r e c h a r a c t e r i z e d by a low e n t r o p y o f -1 -1 59a f u s i o n ( c a . 5 c a l deg mole ), much s m a l l e r than t h e e n t r o p y o f f u s i o n o b s e r v e d (12 c a l deg "'"mole "'") f o r the ( + ) - c y c l o p e n t a d i e n e f u m a r i c a c i d adduct 29_, r e p o r t e d there here. U n l i k e t h e endo a n h y d r i d e 27, i s t h e r e f o r e a d i s t i n c t energy d i f f e r e n c e between the ( + ) - d i a c i d 29_ i n t h e m e l t and i n the s o l i d state. S e v e r a l y e a r s ago H i n s h e l w o o d ^ c o n s i d e r e d t h i s energy i n r e l a t i o n to the rate constants i n both s t a t e s . difference Assuming t h a t t h e t r a n s i t i o n s t a t e i s t h e same i n b o t h s o l i d and m e l t , he s u g g e s t e d that the r a t e d i f f e r e n c e might be r e l a t e d q u a n t i t a t i v e l y t o t h e e n t h a l p y o f fusion: AH. w f7i 1 n J k(melt) k(solid) _ ~ . fusion RT However, s u b s t i t u t i o n o f our determined AH^ . (5.38 k c a l mole ^) fusion 2 l e a d s t o a r a t i o of k ( m e l t ) / k ( s o l i d ) o f 6 x 10 a t 150°, considerably g r e a t e r than the o b s e r v e d f a c t o r o f 5. An improved r e l a t i o n s h i p 37 c o n s i d e r s the f r e e energy d i f f e r e n c e i n the ground s t a t e (i.e., a c c o u n t s f o r b o t h e n t h a l p y and e n t r o p y d i f f e r e n c e s ) : r o , [ 8 ] „ £ n k(melt) k(solid) G(melt) RT = G(solid) Near the m e l t i n g p o i n t , t h e f r e e energy d i f f e r e n c e between the phases can be approximated by the e n t h a l p y and e n t r o p y o f f u s i o n : ^ roi 1 J o l n . . k(melt) k(solid) _ w AH . fusion RT ~ fusion R AS. , fusion R ,1_ 1_ . ^T ~ T m.p. } where t h e r e l a t i o n A s . . = AH. . /T „ fusion f u s i o n m.p, been t a k e n i n t o t h e e q u a t i o n . S u b s t i t u t i n g n y i e l d s k ( m e l t ) / k ( s o l i d ) = 1.5 1 e a t 150°, ( E q u a t i o n 3, p 30) has ^ » ^ . = 5 . 3 8 k c a l mole fusion v considerably c l o s e r t o the observed r a t i o of 5. I n t h e above d i s c u s s i o n , the r a t e d i f f e r e n c e was t a k e n as a r e f l e c t i o n of the d i f f e r e n c e i n ground s t a t e f r e e e n e r g i e s o n l y . In g e n e r a l , however, b o t h the t r a n s i t i o n and ground s t a t e s i n the s o l i d r e a c t i o n may be d i f f e r e n t from t h o s e i n the l i q u i d s t a t e . The r e s t r i c t i o n s imposed on the r e a c t i n g m o l e c u l e i n t h e s o l i d s t a t e can A3 be l i k e n e d to a cage e f f e c t . The a c i d ) produced as i n t e r m e d i a t e s w i l l be h e l d i n p o s i t i o n by d i f f u s i n g apart. addends ( c y c l o p e n t a d i e n e i n the r e v e r s e Diels-Alder the s u r r o u n d i n g l a t t i c e r a t h e r fumaric reaction than I f the r e s t r i c t i o n i s s e v e r e enough, such a cage e f f e c t c o u l d be s t e r e o s p e c i f i c ; i n t h i s be r e v e a l e d and case s t e r e o s p e c i f i c i t y would i n a reduced r a t e of r a c e m i z a t i o n i n the s o l i d , the d i s s o c i a t e d addends would r e t a i n o r i e n t a t i o n . since Since rate retardation i s o n l y s l i g h t , such a mechanism i s e s s e n t i a l l y i n o p e r a t i v e . Rather, the addends a r e f r e e t o r o t a t e q u i c k l y and the enantiomer 2.5 recombine, forming 29. Conclusion This s o l i d - s t a t e r e a c t i o n i n d i c a t e s that c e r t a i n thermal t i o n r e a c t i o n s may solid state. The not be a p p r e c i a b l y higher reorganiz- k i n e t i c a l l y hindered i n the energy needed t o approach a t r a n s i t i o n s t a t e i n a c r y s t a l l a t t i c e can be o f f s e t p a r t i a l l y by a f a v o u r a b l e entropy of a c t i v a t i o n , f a c i l i t a t i n g the s o l i d - s t a t e r e a c t i o n . R e a c t i o n s i n s o l i d s can be k i n e t i c a l l y s i m p l e even though a phase change o c c u r s d u r i n g 37 i n neat organic solids reaction. Examples of f i r s t - o r d e r r e a c t i o n s 62 ' a r e r a r e , but t h i s i s perhaps o n l y a r e f l e c t i o n on the s m a l l number of systems t h a t have been s t u d i e d a kinetic from standpoint. O b s e r v a t i o n i n s i n g l e c r y s t a l s of a p r o d u c t phase a p p e a r i n g a t 2 A 63 d e f e c t s , d i s l o c a t i o n s or i n t e r f a c e s ' t h a t r e a c t i o n o c c u r s a t such s i t e s . Instead, p r o d u c t has does not n e c e s s a r i l y i n d i c a t e i t may mean t h a t a l r e a d y been formed by a s i m p l e p r o c e s s i n s i d e the the reactant crystal, and i s o n l y s e p a r a t i n g out a t such i r r e g u l a r i t i e s . studies with polycrystalline between the two Kineti samples can be used t o d i f f e r e n t i a t e possibilities. 3 RESOLUTION OF RACEMIC 1,1'-BINAPHTHYL IN THE SOLID STATE The compound 1 , 1 ' - b i n a p h t h y l i s one o f t h e s i m p l e s t carbons. I t s dissymmetry i s m o l e c u l a r i n n a t u r e , c h i r a l hydro- and enantiomer i n t e r c o n v e r s i o n i s p o s s i b l e s i m p l y by r o t a t i o n about t h e i n t e r a n n u l a r bond, r a t h e r than by any b o n d - b r e a k i n g p r o c e s s . The r o t a t i o n i s s u f f i c i e n t l y r e s t r i c t e d t o a l l o w i s o l a t i o n o f e i t h e r enantiomer. First r e s o l v e d i n 1961, S - ( + ) - 1 , 1 ' - b i n a p h t h y l has been used i n s o l u t i o n racemization studies.^ ^ The h a l f - l i f e f o r r a c e m i z a t i o n s o l v e n t s i s c a , 15 min a t 50°. Recently, i n several R-(-)-1,1'-binaphthyl was 67 a l s o r e s o l v e d and s t u d i e d i n s o l u t i o n . The a b s o l u t e configuration 68 of 1 , 1 ' - b i n a p h t h y l was deduced from a c r y s t a l l o g r a p h i c s t u d y i n 1968. 46 3.1 The P r e p a r a t i o n o f 3.1.1 1,1'-Binaphthyl S-(+)-1,1'-Binaphthyl Racemic from the D i a s t e r e o m e r i c R e s o l u t i o n o f Naphthidine S-(+)-1,1'-Binaphthyl has been s u c c e s s f u l l y r e s o l v e d v i a the (+•)- naphthidine p r e c u r s o r . ^ ' ^ We t h e r e f o r e began our p r e p a r a t i o n o f o p t i c a l l y a c t i v e 1 , 1 ' - b i n a p h t h y l by s y n t h e s i z i n g r a c e m i c n a p h t h i d i n e The f i r s t p r e p a r a t i o n o f n a p h t h i d i n e w h i c h we attempted was (31). that 69 g i v e n by Sah and Y u i n . naphthalene by f e r r i c I t i n v o l v e d the o x i d a t i v e c o u p l i n g o f 1-aminooxide: NH 2 31 The r e p o r t e d y i e l d o f p u r i f i e d n a p h t h i d i n e was hands t h e method gave poor y i e l d s was 60%. However, i n our (<10%) o f n a p h t h i d i n e , and the procedure abandoned i n f a v o u r o f a n o t h e r w h i c h seemed more p r o m i s i n g . T h i s second p r e p a r a t i v e r o u t e was 1-Aminonaphthalene was azonaphthalene naphthalene was developed by Cohen and d i a z o t i z e d then r e d u c t i v e l y c o u p l e d t o form ( 3 2 ) , w h i c h was i s o l a t e d i n a crude form. The azo- suspended i n b o i l i n g e t h a n o l and reduced w i t h stannous c h l o r i d e i n h y d r o c h l o r i c a c i d to hydrazonaphthalene, rearranged Oesper.^ to naphthidine h y d r o c h l o r i d e . hydroxide regenerates the f r e e base. The which immediately Treatment w i t h sodium y i e l d of recrystallized 47 naphthidine was stated as 33.5%. The procedure worked w e l l , and we were 32 able to prepare 45 g of pure naphthidine (m.p. the sequence eight times. was 201-202°) by repeating Average y i e l d of the l a s t f i v e preparations 26%. Racemic naphthidine was then resolved by forming the s a l t with (+)-ammonium a-bromo-D-camphor—iT-sulfonate. performed this r e s o l u t i o n . Theilacker and Hopp^ have 1 Use of two moles of resolving agent for each mole of naphthidine gave 65% material a f t e r r e c r y s t a l l i z a t i o n from ethanol-water. 33, We carried this resolution as far as the s a l t obtaining the material i n somewhat lower y i e l d s but comparable s p e c i f i c rotations ([a] = +80°). 48 The ( + ) - n a p h t h i d i n e a-bromo-D-camphor-ir-sulf onate s a l t (33) can be d i r e c t l y deaminated t o S - ( + ) - l , l ' - b i n a p h t h y l , w i t h o u t h a v i n g t o i s o l a t e 33 free (+)-naphthidine. T h i s p r o c e d u r e was d e v i s e d by C o l t e r and Clemens, and gave ( + ) - 1 , 1 ' - b i n a p h t h y l ( [ a ] = +145-165°) i n 40-55% y i e l d . adopted t h i s method, w i t h a s l i g h t l y m o d i f i e d p u r i f i c a t i o n p r o c e d u r e , and were a b l e t o o b t a i n S - ( + ) - 1 , 1 ' - b i n a p h t h y l 3.1.2 We Racemic 1 , 1 ' - B i n a p h t h v l ( [ a ] = +97°) i n 55% y i e l d . from O p t i c a l l y I n a c t i v e Reagents I n o r d e r t o c h a r a c t e r i z e f u l l y t h e phase system formed between r e s o l v e d and racemic b i n a p h t h y l ( o r , more c o r r e c t l y , between R- and S - l , 1 ' - b i n a p h t h y l e n a n t i o m e r s ) , some r a c e m i c 1 , 1 ' - b i n a p h t h y l was p r e p a r e d . 72 The p r e p a r a t i o n f o l l o w e d was t h a t o f S a k e l l a r i o s and K y r i m i s . The G r i g n a r d reagent from 1-bromonaphthalene was c o u p l e d by c u p r i c c h l o r i d e , forming 1,1'-binaphthyl: 49 The reaction proceeded easily, and starting materials were readily available, so that large quantities of racemic 1,1'-binaphthyl could be obtained (our yield of purified binaphthyl was 20%). 3.2 Discovery of the Solid-State R e s o l u t i o n 111 Having obtained some 1,1'-binaphthyl which was optically active, we then prepared to look for any racemization below the melting point 73 (158°) of the solid. Since there was good evidence for the existence of two crystalline forms of 1,1'-binaphthyl (m.p. 145° and 158°), i t was of interest to check for racemization in both forms. These "low-melting" and "high-melting" forms could be obtained by slow and fast recrystallizations, respectively, from petroleum ether (b.p. 73 30-60°). Accordingly, half of the prepared optically active 1,1'- binaphthyl ([a] = +97°) was recrystallized rapidly (giving crystals of [a]= +99°), and half slowly (giving material with [a] = +79°) from pentane. At the boiling point of pentane (36°) a l i t t l e racemization of the dissolved 1,1'-binaphthyl w i l l occur.^ Our i n i t i a l check for the presence of any solid-state racemization was to heat 20 mg of the polycrystalline 1,1'-binaphthyl sample with activity [a] = +99° for one hour at 120°. When the sealed ampule was opened and analyzed, the specific rotation was [a] = +108°. Racemization had not occurred, and the apparent increase in rotation caused us to check the precision of the polarimetric method of analysis. learned that the figure should be correct to within ±2°. therefore seemed genuine, but needed verification. It was The increase A second sample of the same material was therefore heated, along with a sample of [a] = +79° 50 m a t e r i a l , f o r 36 h a t 120°. changed A n a l y s i s showed t h a t t h e l a t t e r had n o t a t a l l from [a] = +79°, b u t t h e o r i g i n a l m a t e r i a l had i n c r e a s e d from [ a ] = +99° t o +114°. Even a f t e r such p r o l o n g e d h e a t i n g t h e sample remained a w h i t e , c r y s t a l l i n e s o l i d and gave t h e s i n g l e 1 , 1 ' - b i n a p h t h y l peak when a n a l y z e d by g a s - l i q u i d chromatography. The b i n a p h t h y l was e v i d e n t l y r e s o l v i n g , not r a c e m i z i n g , i n the s o l i d state. T h i s i n c r e d i b l e r e s u l t was soon v e r i f i e d r a t h e r d r a m a t i c a l l y . In o r d e r t o f i n d t h e range o f t e m p e r a t u r e s i n w h i c h t h i s phenomenon might o c c u r , t h e second t e m p e r a t u r e chosen was 150°, n e a r e r t h e h i g h e r m e l t i n g p o i n t o f 158°. Samples o f b o t h b a t c h e s o f o p t i c a l l y active 1 , 1 ' - b i n a p h t h y l , a l o n g w i t h some c o n t r o l samples o f r a c e m i c 1 , 1 ' - b i n a p h t h y l (which had a l s o been r e c r y s t a l l i z e d r a p i d l y and s l o w l y from were h e a t e d f o r v a r i o u s l e n g t h s o f t i m e ( T a b l e I I I ) . pentane) The o r i g i n a l ( f a s t r e c r y s t a l l i z e d ) sample o f a c t i v e 1 , 1 ' - b i n a p h t h y l i n c r e a s e d s t e a d i l y from [ a ] = +99° t o +163° o v e r a p e r i o d o f 2.5 days. Samples from t h e s l o w l y r e c r y s t a l l i z e d b a t c h , w h i c h had remained a t [ a ] = +79° a t 120°, i n c r e a s e d t o [ a ] = +205° w i t h i n two hours and remained a t t h i s r o t a t i o n f o r 2.5 days. The r a c e m i c sample which had been r e c r y s t a l l i z e d q u i c k l y remained a t [ a ] = 0° t h r o u g h o u t . However, t h e s l o w l y l i z e d r a c e m i c sample, s u r p r i s i n g l y , d e v e l o p e d o p t i c a l activity. R o t a t i o n s were somewhat s c a t t e r e d , b u t a l l e l e v e n i n d i v i d u a l were p o s i t i v e . recrystal- samples T h i s s e l f - r e s o l u t i o n o f l , l ' - b i n a p h t h y l can a p p a r e n t l y o c c u r even i n m a t e r i a l w h i c h i s r a c e m i c ( [ a ] = 0.0 JT 0.5°). T h i s u n u s u a l b e h a v i o u r o f s o l i d 1 , 1 ' - b i n a p h t h y l prompted a search f o r a method o f p r e p a r i n g b a t c h e s o f b i n a p h t h y l w h i c h would r e s o l v e t o a h i g h r o t a t i o n from a low i n i t i a l r o t a t i o n s i m p l y on h e a t i n g . Since a l l 51 Table I I I Summary o f I n i t i a l I n v e s t i g a t i o n s o f t h e Development of Optical Activity i n Neat, P o l y c r y s t a l l i n e 1,1'-Binaphthyl 1 , 1 ' - B i n a p h t h y l Used M a t e r i a l o f [ a ] = +99° II it b Temperature, °C 120 it 149.6 Time, hours [ a ] , degrees 1 +108 36 +114 1 +126 II tt 2 +130, it II 5 +135, +133° it II 24 +157, + 1 5 2 " II 63.5 M a t e r i a l o f [ a ] = +79° II 120 149.6 +129° c +163 36 +79 1 +105 " it 2 +193, II it 5 +208, +206° II it 24 +208, +210° II II 63.5 +207 12.5 0, 0° 0, o c Racemic Batch A 149.6 II II 37.5 II it 63.5 ^Racemic B a t c h B 149.6 +205° 0 0.017 +4 II it 0.083 +41, +47 C II " 0.5 +98, +90 C II it 1.0 +79 52 (Table I I I , continued) Racemic B a t c h B, c o n t i n u e d 149.6 12.5 II II 37.5 II II 63.5 +119, +79 +93, C +83 +97 From a f a s t r e c r y s t a l l i z a t i o n ( p e n t a n e ) . k From a s l o w r e c r y s t a l l i z a t i o n ( p e n t a n e ) . S p e c i f i c r o t a t i o n s o f two i n d i v i d u a l samples h e a t e d f o r t h e same l e n g t h o f t i m e a t t h e same t e m p e r a t u r e . s o l i d samples o f 1 , 1 ' - b i n a p h t h y l had been r e c r y s t a l l i z e d , t h e n e x t s e v e r a l weeks were devoted t o t r y i n g t o d e v e l o p a method o f r e c r y s t a l l i z i n g racemic or p a r t i a l l y a c t i v e 1,1'-binaphthyl " s u c c e s s f u l l y " pentane. from V a r i a t i o n s were made i n t h e r a t e o f r e c r y s t a l l i z a t i o n , t h e c o n c e n t r a t i o n o f 1 , 1 ' - b i n a p h t h y l i n t h e pentane s o l v e n t , and t h e method of seeding. No d e l i b e r a t e attempt was made t o add seeds o f f o r e i g n d i s s y m m e t r i c m a t e r i a l ; i t was d e s i r a b l e t o r e s t r i c t t h e system to R- and S - l , 1 ' - b i n a p h t h y l . entirely Once a r e s o l v a b l e b a t c h ( i . e . , one w h i c h would i n c r e a s e s i g n i f i c a n t l y i n s p e c i f i c r o t a t i o n on h e a t i n g ) was o b t a i n e d , however, c a r e f u l r e p e t i t i o n o f t h e c r y s t a l l i z a t i o n procedure would n o t produce a second b a t c h w h i c h was e q u a l l y as s u c c e s s f u l . From t h i s e x p e r i m e n t a t i o n t h e f o l l o w i n g i m p o r t a n t f a c t was l e a r n e d . A l l samples o f 1 , 1 - b i n a p h t h y l , r e g a r d l e s s o f t h e p a r t i c u l a r method o f 1 p r e p a r a t i o n , e i t h e r r e t a i n e d o r i n c r e a s e d s p e c i f i c r o t a t i o n when h e a t e d i n t h e s o l i d s t a t e below 158°. No r a c e m i z a t i o n e v e r o c c u r r e d on h e a t i n g p u r e , a c t i v e 1 , 1 ' - b i n a p h t h y l below i t s m e l t i n g p o i n t . Also, we o b s e r v e d t h a t c o o l i n g a sample t o room t e m p e r a t u r e o r below then r e h e a t i n g d i d not produce any a d d i t i o n a l i n c r e m e n t i n r o t a t i o n . Re- 53 c r y s t a l l i z a t i o n from pentane d i d n o t cause a p p r e c i a b l e l o s s o f a c t i v i t y . Combining t h e s e o b s e r v a t i o n s , we d e v i s e d a c y c l i n g p r o c e d u r e w h i c h was c a p a b l e of producing l a r g e r q u a n t i t i e s of w e l l - r e s o l v e d S t a r t i n g w i t h e i t h e r s l i g h t l y resolved 1,1'-binaphthyl m a t e r i a l which gained 1,1'binaphthyl. or a racemic some o p t i c a l a c t i v i t y on h e a t i n g , a s p e c i f i c r o - t a t i o n a t l e a s t as g r e a t as [a] = +190° c o u l d e v e n t u a l l y be o b t a i n e d . (The is l i m i t o f r e s o l u t i o n , as we l a t e r d i s c o v e r e d [ct]p = i245°,) 1 (Appendix A, p 1 7 8 ) , F i r s t , t h e sample ( u s u a l l y ca_. 1 g i n s i z e ) was r e c r y s t a l l i z e d from pentane. To c o n s e r v e m a t e r i a l , t h e pentane was removed i n vacuo a f t e r t h e r e c r y s t a l l i z a t i o n was c o m p l e t e . The s o l i d was t h e n h e a t e d a t 150°, and an i n c r e m e n t i n r o t a t i o n a l m o s t always occurred. A second r e c r y s t a l l i z a t i o n o f t h i s more a c t i v e m a t e r i a l a g a i n produced c r y s t a l s w h i c h c o u l d r e s o l v e even f u r t h e r on h e a t i n g . By c y c l i n g i n t h i s manner, t h e o p t i c a l a c t i v i t y o f any sample o f 1,1'b i n a p h t h y l c o u l d be s y s t e m a t i c a l l y enhanced. Racemic s t a r t i n g m a t e r i a l w h i c h d i d n o t change on h e a t i n g c o u l d be made t o r e s o l v e by d i s s o l v i n g i n some a c t i v e m a t e r i a l a t t h e r e c r y s t a l l i z a t i o n s t a g e . An example o f an e x p e r i m e n t t h a t produced a s p e c i f i c r o t a t i o n o f [a] = +194° i n f o u r c y c l e s , and one g i v i n g [a] = -194° a f t e r t h r e e c y c l e s a r e shown i n i' Table IV. One s h o r t c o m i n g o f t h i s p r o c e d u r e was t h a t a l t h o u g h some i n c r e m e n t i n r o t a t i o n was a s s u r e d , we were u n a b l e t o p r e d i c t how l a r g e i t would be. i Some samples would i n c r e a s e o n l y a few degrees on h e a t i n g ; others ° The h i g h e s t s p e c i f i c r o t a t i o n a t t h e sodium D l i n e , 5893 A, r e p o r t e d f o r samples o f o p t i c a l l y a c t i v e l , l ' - b i n a p h t h y l o b t a i n e d by t h e c l a s s i c a l r e s o l u t i o n p r o c e d u r e i s [O]D +192°.65 Other v a l u e s a r e [a] = +245° at 5791 X and [a] = -250°at 4360 A . T h i s c o n v e r s i o n o f e s s e n t i a l l y a l l o f a r a c e m i c m a t e r i a l t o o n l y one ^ e n a n t i o m e r i s sometimes r e f e r r e d t o as an "asymmetric t r a n s f o r m a t i o n , " but we p r e f e r t h e more g e n e r a l term, " r e s o l u t i o n . " = 6 4 6 7 54 T a b l e IV Examples o f t h e C y c l i n g o f Racemic 1 , 1 ' - B i n a p h t h y l t o H i g h Specific Rotations [a] A f t e r Recrystallization, [a] A f t e r H e a t i n g a t 150° C y c l e Number degrees degrees ( +41, 0 1 +44) +44) 2 ( +42, (+109, + 1 1 6 ) 3 3 (+110, + 1 1 2 ) a (+186, + 1 8 5 ) 3 4 (+175, + 1 7 9 ) a (+197, + 1 9 0 ) 3 1 0 ( -52, - 4 5 ) 2 -34 -79 3 -49 3 b a a -194 Duplicate analyses of the batch being cycled. T h i s l o s s i n a c t i v i t y on r e c r y s t a l l i z a t i o n o c c u r r e d because dec o l o u r i z i n g carbon was used i n t h e pentane s o l u t i o n . 1,1'-Binaphthyl r a c e m i z a t i o n i n pentane i s c a t a l y z e d by c e r t a i n c a r b o n b l a c k s . jumped some 150° i n r o t a t i o n . T h e r e f o r e , t h e number o f c y c l e s required t o a c h i e v e [ a ] = ±190-220° v a r i e d from one t o g r e a t e r than f o u r i n t h e experiments attempted. T h i s r e m a r k a b l e a b i l i t y o f l , l ' - b i n a p h t h y l t o r e s o l v e s i m p l y on h e a t i n g r e f l e c t s an u n u s u a l s t e r e o s p e c i f i c i t y i n t h e s o l i d s t a t e . thorough knowledge o f t h e phase r e l a t i o n s h i p s o f t h e R- and S-1,1'b i n a p h t h y l system i s an e s s e n t i a l p a r t o f any e x p l a n a t i o n o f t h e A 55 phenomenon. Our attempts to establish the nature and r e l a t i v e s t a b i l i t y of the phases are reported i n the following section. 3.3 3.3.1 Phase Diagram of the System R- and S-l,1'-Binaphthyl Nature of the Phases The low- and high-melting forms of l , l ' - b i n a p h t h y l reported by 73 Badar ejt a l were also obtained i n our r e c r y s t a l l i z a t i o n s of racemic and p a r t i a l l y active material. Contrary to t h e i r observations with racemic 1,1'-binaphthyl, we found no good c o r r e l a t i o n between the r a p i d i t y of r e c r y s t a l l i z a t i o n and the form obtained."' Both low- and high-melting forms resulted from both slow and rapid r e c r y s t a l l i z a t i o n s . Most often, mixtures of the two forms were obtained. That i s , perhaps half of a sample would melt at 145°, the rest melting at 158°. Occasionally, r e c r y s t a l l i z a t i o n would y i e l d one form with very l i t t l e , i f any, of the other, and these batches allowed a study of both forms. 73 In agreement with Badar and coworkers, each form had a character- i s t i c infrared spectrum when taken i n a nujol mull (Figure 9). The s t r i k i n g difference at 769 cm ^ and also the smaller differences from 940-980 cm ^ reported by these investigators are quite apparent. When 73 either form i s taken into solution, these differences disappear. The fact that the most marked difference was i n the C-H out-of-plane v i b r a t i o n region of the spectrum led these authors to suggest that within each R or S configuration, a c i s (30a) conformation might exist i n one c r y s t a l l i n e modification, and a trans (30b) conformation i n the other. ^ or, as just presented, any r e l a t i o n to the speed of r e c r y s t a l l i z a t i o n and the a b i l i t y of the material to resolve on heating. Figure (a) 9. I n f r a r e d spectrum of 1 , 1 - b i n a p h t h y l ( n u j o l m u l l ) , L o w - m e l t i n g form. 1 (b) H i g h - m e l t i n g form. 57 30b 30a R-C-)-1,1'-Binaphthyl, R-(-)-1,1'-Binaphthyl, c i s conformation trans conformation X-Ray powder d i f f r a c t i o n also d i f f e r e n t i a t e s between the two forms. Table V l i s t s the two patterns we obtained for the low- and high-melting forms on a Debye-Scherrer powder camera, alongside a pattern for 1,1'-binaphthyl determined by Hofer e_t a l . For each interplanar d spacing i s l i s t e d the i n t e n s i t y of the l i n e r e l a t i v e to the most i n tense l i n e i n the photograph.(designated l i n e s are indicated. 100). The three strongest This format i s that of the American Society for 76a Testing Materials and allows a comparison between our r e s u l t s (obtained with Cu Ka r a d i a t i o n , wavelength 1.54178 X) and those of Hofer (obtained with Fe Ka r a d i a t i o n , wavelength of his reported melting point (159.5-160°), 1.93728 X ) . there i s l i t t l e In s p i t e correspondence between our pattern for the high-melting form and the 1,1'-binaphthyl pattern of Hofer. Rather, the four strongest l i n e s on his pattern and on ours for the low-melting form are i n close agreement. Similarities among the weaker l i n e s are d i f f i c u l t to f i n d , but at these low intens i t i e s comparison i s d i f f i c u l t because our figures represent integrated i n t e n s i t i e s whereas his are v i s u a l estimates. 58 Table V X-Ray Powder D i f f r a c t i o n P a t t e r n s f o r L o w - M e l t i n g (Racemate) and H i g h M e l t i n g ( E u t e c t i c ) Forms of 1,1' - B i n a p h t h y l L o w - M e l t i n g Form High-Melting Form d, A I/I, d, X u 25 6.9 3rd 45 6.4 2nd 80 5.6 4.65 5 5.0 4.07 5 4.74 3.94 20 4.39 100 3.14 10.1 5.3 5.0 3 Literature 75 d, £ h 10 10.2 50 2nd 70 6.0 25 3rd 55 5.4 3rd 75 5 5.0 2nd 80 50 4.66 25 100 4.39 10 4.07 5 4.11 50 5 3.72 70 3.98 50 2.97 20 3.46 10 3.69 2.92 5 3.33 10 3.52 5 2.79 5 3.20 10 3.20 25 2.54 5 3.11 10 3.00 50 2.48 5 3.00 5 2.95 25 2.34 5 2.91 5 2.81 35 2.28 5 2.84 5 2.68 10 2.16 5 2.78 30 2.56 35 2.08 5 2.21 5 2.49 35 2.03 5 2.35 25 2.29 25 2.25 25 2.18 25 2.14 25 2.08 35 2.04 10 3.67 1st Unresolved doublet. 3 1st 1st 100 59 The for f a c t w h i c h i s most apparent from T a b l e V i s t h a t the p a t t e r n s t h e low- and h i g h - m e l t i n g forms a r e c o n s i d e r a b l y d i f f e r e n t . t o t a l absence o f t h e s t r o n g e r l i n e s o f one The form o f 1 , 1 - b i n a p h t h y l in 1 the p a t t e r n of the o t h e r a t t e s t s t o t h e h i g h "phase p u r i t y " o f our samples. The l o w - m e l t i n g form a n a l y z e d was r a c e m i c , but the h i g h - m e l t i n g form, w h i c h we c o u l d o b t a i n i n a l l a c t i v i t i e s (from [a] = 0 to +245°) , gave t h e same p a t t e r n r e g a r d l e s s of t h e s p e c i f i c r o t a t i o n o f the sample a n a l y z e d . F o r t u n a t e l y , a f u l l c r y s t a l l o g r a p h i c s t u d y o f the low-melting form has r e c e n t l y been performed by K e r r and R o b e r t s o n . ^ m o d i f i c a t i o n belongs to a m o n o c l i n i c , centrosymmetric 8 = 105.7°. There a r e f o u r m o l e c u l e s u n i t s i n b o t h R and S molecules The The S molecules c = 10.13 two two 1 of naphthalene a r e c i s d i s p o s e d , w i t h an a n g l e o f 68° between them, and a r e v e r y c l o s e t o the dimensions itself. X, t o each u n i t c e l l , w h i c h have the R c o n f o r m a t i o n , the o t h e r s b e i n g S. crystal space group ( C 2 / c ) , w i t h l a t t i c e parameters a = 20.98 X, b = 6.35 and This of naphthalene e x i s t e n c e o f an o r d e r e d a r r a y o f e q u a l numbers of R and e s t a b l i s h e s the l o w - m e l t i n g form as a "phase r u l e " compound (see S e c t i o n 2.3.1, p 27) i n the b i n a r y system R- and S - l , 1 ' - b i n a p h t h y l . L e t us now c o n s i d e r t h e n a t u r e o f the h i g h - m e l t i n g form. The fact t h a t the X-ray powder photographs o f t h i s form a r e the same a t a l l s p e c i f i c r o t a t i o n s e l i m i n a t e s a "phase r u l e " compound (which would have been a polymorph of the l o w - m e l t i n g form) as a p o s s i b i l i t y . ^ ' ^ T h i s l e a v e s a c h o i c e of e i t h e r a e u t e c t i c m i x t u r e o f i n d i v i d u a l R and S c r y s t a l s o r a s o l i d s o l u t i o n c a p a b l e o f c o n t a i n i n g b o t h enantiomers a l l proportions. in I f the l a t t e r i s t r u e , then the s o l i d s o l u t i o n must 60 be c l o s e t o i d e a l s i n c e t h e d s p a c i n g s remain unchanged as a f u n c t i o n o f composition. I n a n o n i d e a l s o l u t i o n one would expect a m o l a r volume change (and hence a change i n d s p a c i n g s ) as t h e c o m p o s i t i o n i s v a r i e d . The c h o i c e between t h e r e two a l t e r n a t i v e s was means o f a r a t h e r f o r t u i t o u s r e s u l t . e a s i l y made by One b a t c h o f r a c e m i c l,l'-binaphthyl happened t o c r y s t a l l i z e from acetone o v e r a few days i n e s p e c i a l l y large crystals (2-4 mm i n d i a m e t e r ) which were shown by i n f r a r e d t o be the h i g h - m e l t i n g form. analysis We were t h e r e f o r e g i v e n the o p p o r t u n i t y o f h a n d - p i c k i n g the w e l l - f o r m e d c r y s t a l s f o r p o l a r i m e t r i c analysis. I f the h i g h - m e l t i n g form i s a e u t e c t i c m i x t u r e of i n d i v i d u a l R and S c r y s t a l s , then each s i n g l e c r y s t a l s h o u l d p o s s e s s a h i g h o p t i c a l in either direction. I f i t i s an i d e a l s o l i d s o l u t i o n , then the l a t t i c e can accommodate e i t h e r a n t i p o d e w i t h e q u a l ease. would rotation then grow by s e l e c t i n g randomly r a c e m i c s o l u t i o n , and would The s i n g l e crystals e i t h e r R o r S m o l e c u l e s from a t h e r e f o r e p o s s e s s , most p r o b a b l y , a r o t a t i o n of zero. The c r y s t a l s were examined under t h e p o l a r i z i n g m i c r o s c o p e . h e m i h e d r a l f a c e s were d i s t i n g u i s h a b l e . A l t h o u g h such No enantiomorphous f a c e s a r e always p r e s e n t i n e u t e c t i c m i x t u r e s o f e n a n t i o m e r s , they a r e 46 not always s u f f i c i e n t l y w e l l d e v e l o p e d t o be e a s i l y o b s e r v e d . How- e v e r , the s i n g l e c r y s t a l s were r e a d i l y r e c o g n i z e d under the m i c r o s c o p e The p i c k i n g a p a r t o f s i n g l e c r y s t a l s , t h e o l d e s t method of r e s o l v i n g r a c e m i c m a t e r i a l s , ^ has n e v e r been w i d e l y used and remains somewhat o f a n o v e l t y . However t h i s p r o c e d u r e , which i s not s y n t h e t i c a l l y u s e f u l because o f the s m a l l q u a n t i t i e s i n v o l v e d , can g i v e v a l u a b l e i n f o r m a t i o n about the n a t u r e o f the r a c e m i c m o d i f i c a t i o n , o r even the v e r y e x i s t e n c e of o p t i c a l a c t i v i t y i n a g i v e n m a t e r i a l . Very r e c e n t l y Wynberg79 has used t h i s method to r e s o l v e s e v e r a l h e t e r o helicenes. 61 by l o o k i n g f o r t o t a l e x t i n c t i o n on r o t a t i o n o f t h e m i c r o s c o p e s t a g e between c r o s s e d p o l a r s . shown i n F i g u r e 10. A sketch of the habit of these c r y s t a l s i s The c r y s t a l would e x t i n g u i s h p o s i t i o n o t h e r than normal t o t h e c and d f a c e s . extinguish when viewed i n any Such a f a i l u r e t o w i l l a r i s e when an o p t i c a l l y a c t i v e c r y s t a l i s b e i n g viewed 80 a l o n g an o p t i c a x i s , a preliminary i n d i c a t i o n t h a t each c r y s t a l b e i n g examined c o n t a i n s m o l e c u l e s o f o n l y one e n a n t i o m e r . Ten w e l l formed s i n g l e c r y s t a l s were c a r e f u l l y s e p a r a t e d from t h e mixture, dissolved i n benzene, and a n a l y z e d f o r a c t i v i t y . ( T a b l e V I ) show t h a t each c r y s t a l was h i g h l y The r e s u l t s r e s o l v e d ( n i n e out o f t e n Table VI Specific Rotations of Single Crystals O b t a i n e d from t h e R e c r y s t a l l i z a t i o n of Racemic 1 , 1 ' - B i n a p h t h y l C r y s t a l Number W e i g h t , mg [ a ] , degrees 1 2.45 +222 2 6.20 +208 3 6.45 +203 4 6.25 +207 5 11.10 -199 6 11.30 +212 7 7.85 -164 8 8.55 -204 9 5.30 +222 9.55 +197 10 62 Figure 10. Sketch of the h a b i t of a s i n g l e c r y s t a l o f pure R- or S - l , 1 ' b i n a p h t h y l , showing those f a c e s which were apparent under the microscope. to c f a c e . (a) (c) View o f a, b, and c f a c e s . View normal to d f a c e . (b) View normal 63 were a t l e a s t 80% r e s o l v e d ) , a n d ' t h a t b o t h R and S c r y s t a l s were present i n the mixture. The h i g h - m e l t i n g form i s t h e r e f o r e a e u t e c t i c m i x t u r e o f i n d i v i d u a l R and S c r y s t a l s . I n t h i s t h e s i s , the words " e u t e c t i c form" w i l l be synonymous w i t h " h i g h - m e l t i n g form," and w i l l a p p l y t o m i x t u r e s of R and S c r y s t a l s i n any r a t i o , from 100% R, through the racemic c o m p o s i t i o n (where an e q u i m o l a r m i x t u r e o f R and S c r y s t a l s e x i s t ) , to 100% S. The eutectic form i s n o t a s i n g l e s o l i d phase l i k e t h e racemate ( l o w - m e l t i n g f o r m ) , but c o n s i s t s i n s t e a d o f two s o l i d phases, an R phase and as S phase. The h i g h - m e l t i n g form i s not c o n s i d e r e d a p o l y m o r p h ^ * melting 3 o f the low- form. A l t h o u g h the n a t u r e of b o t h the low- and h i g h - m e l t i n g m o d i f i c a t i o n s o f c r y s t a l l i n e 1 , 1 ' - b i n a p h t h y l a r e now diagram cannot y e t be c o n s t r u c t e d . e r a t u r e ranges problem known, the phase Some i n f o r m a t i o n as to the temp- over which each form i s s t a b l e , must be o b t a i n e d . and i t s c o n n e c t i o n to the s o l i d - s t a t e r e s o l u t i o n w i l l This be considered next. 3.3.2 R e l a t i v e S t a b i l i t y o f t h e Phases The s i m p l e s t way i n f r e e energy to d e t e r m i n e which o f two phases l i e s a t a g i v e n temperature and c o m p o s i t i o n ( i . e . , a t a g i v e n p o i n t on the phase diagram) i s t o observe t o a n o t h e r a t the p o i n t i n q u e s t i o n . lowest the c o n v e r s i o n o f one W i t h f a s t t r a n s f o r m a t i o n s (such as m e l t i n g ) t h i s o b s e r v a t i o n i s e a s i l y made. slow the problem becomes more d i f f i c u l t . I f the phase changes a r e I n the c o u r s e o f t h i s work, s e v e r a l approaches were n e c e s s a r y i n d e t e r m i n i n g the r e l a t i v e stability 64 of a l l 1 , 1 ' - b i n a p h t h y l phases. 3.3.2.1 Melting P o i n t Observations The o r i g i n a l d i s t i n c t i o n between the two c r y s t a l l i n e m o d i f i c a t i o n s 73 of 1 , 1 ' - b i n a p h t h y l was based on m e l t i n g p o i n t s . We c o n f i r m e d t h a t the l o w - m e l t i n g form (a racemate) m e l t s a t 144-145°, and t h a t the h i g h m e l t i n g form (a e u t e c t i c m i x t u r e ) m e l t s a t 157-158°. In fact, a l l samples o f h i g h - m e l t i n g form, from [a] = 0 t o ±245°, m e l t e d a t 157-158°. T h i s o b s e r v a t i o n a t f i r s t appears t o c o n t r a d i c t our e a r l i e r s i n c e e u t e c t i c m i x t u r e s o f enantiomers findings, c h a r a c t e r i s t i c a l l y melt at the r a c e m i c than a t the r e s o l v e d c o m p o s i t i o n . lower However, s i n c e a mechanism e x i s t s f o r the i n t e r c o n v e r s i o n o f e n a n t i o m e r s , the R- and S - l , 1 ' - b i n a p h t h y l i s a p s e u d o b i n a r y system system ( S e c t i o n 2.3.2, p 3 2 ) . I f r a c e m i z a t i o n i n the melt i s r a p i d , the m e l t i n g p o i n t s may be observed to o c c u r f a r below the i d e a l v a l u e s . The p r e s e n c e o f f a c i l e r a c e m i z a t i o n i n the m e l t was verified. A 20 mg easily sample o f 1 , 1 ' - b i n a p h t h y l ( [ a ] = +234°) was s e a l e d i n an ampule and immersed i n a b a t h t h e r m o s t a t t e d a t 160.3°. t h r e e minutes the sample a t t a i n e d t h i s t e m p e r a t u r e and c o m p l e t e l y m e l t e d , and a f t e r a t o t a l o f f i v e minutes i t was temperature. In A n a l y s i s gave [cx]= 0.0 ± 0.5°. r a c e m i z a t i o n of 1 , 1 ' - b i n a p h t h y l ^ ^ a t u r e , the h a l f - l i f e i s l e s s than 0.5 quenched t o room I f s o l u t i o n r a t e s of are e x t r a p o l a t e d to t h i s sec. temper- Racemization i s v i r t u a l l y i n s t a n t a n e o u s , and a r e l a t i v e l y s l o w r a t e of h e a t i n g (1 deg min c a p i l l a r y m e l t i n g p o i n t a p p a r a t u s , o r even 40 deg min 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 e r , as mentioned 1 1 in a with a i n the f o l l o w i n g s e c t i o n ) 65 would account f o r the o b s e r v a t i o n o f a m e l t i n g p o i n t w h i c h i s i n d e pentent of composition. The i d e a l m e l t i n g p o i n t of pure R- o r S- 1 , 1 ' - b i n a p h t h y l i s t h e r e f o r e i m p o s s i b l e t o determine."'" 1 , 1 ' - B i n a p h t h y l w h i c h has been m e l t e d above 158° a great extent. Some m e l t e d samples can be h e l d a t 125° without c r y s t a l l i z a t i o n . indefinitely However, t h e a d d i t i o n o f seed c r y s t a l s o f h i g h - m e l t i n g form t o t h e m e l t j u s t below 158° lization. supercools to r e a d i l y causes S i m i l a r o b s e r v a t i o n s o f the m e t a s t a b i l i t y o f t h e crystal1,1'- 82 b i n a p h t h y l m e l t have been made by B i n n s and S q u i r e , who reported that samples c o u l d be c o o l e d as low as 120° w i t h o u t c r y s t a l l i z a t i o n . Samples o f l o w - m e l t i n g form c o n t a i n i n g v e r y l i t t l e o f the e u t e c t i c m o d i f i c a t i o n m e l t e d e s s e n t i a l l y c o m p l e t e l y a t 144-145°. However, i f the samples c a n t a i n e d l a r g e r q u a n t i t i e s o f the h i g h e r m e l t i n g eutectic, t h e l a t t e r r e a d i l y c r y s t a l l i z e d from t h e m e l t o f t h e former i n t h e t e m p e r a t u r e range 145-158°. I f c r y s t a l l i z a t i o n of t h i s form was e s p e c i a l l y e f f i c i e n t , the sample d i d not appear t o m e l t a t a l l a t 145°. I n such c a s e s , some m e l t i n g c o u l d be o b s e r v e d i f the sample was r a p i d l y immersed i n a t e m p e r a t u r e b a t h between 145-158°. From t h e s e o b s e r v e d t r a n s i t i o n s ( e u t e c t i c form ->- m e l t a t 157-158°, racemate -*• m e l t -*• e u t e c t i c form from 145° t o 158°, and m e l t -*-eutectic form below 158°), some o r d e r i n g of the f r e e energy s u r f a c e s a s s o c i a t e d w i t h each phase can be deduced. 1 The two p o s s i b l e f r e e energy situations The b e h a v i o u r of 1 , 1 - b i n a p h t h y l on m e l t i n g emphasizes the dangers i n u s i n g m e l t i n g p o i n t as a means of d e d u c i n g phase systems between o p t i c a l i s o m e r s . A l t h o u g h commonly used,^6 the m e l t i n g p o i n t diagram can l e a d t o e r r o n e o u s c o n c l u s i o n s i f the e n a n t i o m e r s a r e o p t i c a l l y unstable. 1 66 a r e i l l u s t r a t e d s c h e m a t i c a l l y i n F i g u r e 11 (a) and ( b ) . The f r e e energy- t e m p e r a t u r e diagrams a r e t a k e n a t the r a c e m i c c o m p o s i t i o n and a t c o n s t a n t p r e s s u r e ( a t m o s p h e r i c ) . These c u r v e s resemble t h o s e f o r t h e two ways i n w h i c h the phases of a s i n g l e component e x h i b i t i n g dimorphism can be r e l a t e d : t h e m o n o t r o p i c ( F i g u r e 11 ( a ) ) and t h e e n a n t i o t r o p i c 11 ( b ) ) r e l a t i o n s h i p . ^ * ' ^ ' ^ k 3 in h t e first, (Figure the l o w - m e l t i n g form (L) i s u n s t a b l e r e l a t i v e t o the h i g h - m e l t i n g form (H) a t a l l t e m p e r a t u r e s below 158°. At 145°, L i n t e r s e c t s the m e l t s u r f a c e (M) and m e l t s metastably. Between 145° and 158°, any h i g h - m e l t i n g form i n the sample causes c r y s t a l l i z a t i o n o f t h i s m e l t and a l o w e r i n g of t h e f r e e energy o f the system. At 158°, i b r i u m w i t h the m e l t . the h i g h - m e l t i n g form can e x i s t i n s t a b l e equil- I n the second r e l a t i o n s h i p ( F i g u r e 11 ( b ) ) , the l o w - m e l t i n g form i s s t a b l e below a t r a n s i t i o n t e m p e r a t u r e ( x ) , b u t e x h i b i t s the same m e l t i n g b e h a v i o u r as i n the m o n o t r o p i c c a s e . The c h o i c e between the two p o s s i b i l i t i e s l i e s i n e s t a b l i s h i n g the p r e s e n c e o r absence o f t h e s o l i d - s o l i d t r a n s i t i o n p o i n t x. We now have enough i n f o r m a t i o n t o p o s t u l a t e a mechanism f o r t h e resolution reaction. At 150°, the i n c r e a s e i n o p t i c a l r o t a t i o n evi- d e n t l y o c c u r s because the racemate phase m e l t s , l e a v i n g c r y s t a l s o f R- and S - l , l ' b i n a p h t h y l ( e u t e c t i c form) b e h i n d t o a c t as seeds f o r the e n s u i n g m e l t -* e u t e c t i c form t r a n s f o r m a t i o n . I f t h e e u t e c t i c form i n the o r i g i n a l sample c o n s i s t s o n l y of S c r y s t a l s , then the p r e f e r e n t i a l c r y s t a l l i z a t i o n o n l y of S - l , 1 ' - b i n a p h t h y l can o c c u r , the s u p p l y o f S m o l e c u l e s b e i n g m a i n t a i n e d by the r a p i d enantiomer i n t e r c o n v e r s i o n i n the m e l t phase. C o n v e r s i o n o f the e n t i r e sample t o pure S - l , 1 ' b i n a p h t h y l i s t h e r e f o r e p o s s i b l e , p r o v i d e d the unwanted R c r y s t a l s have been 67 Pi PS W w w w W w 145 158 (a) 145 158 T TEMPERATURE (°C) (b) TEMPERATURE (°C) 158 u o o 145 H 0 (c) F i g u r e 11. 50 100 0 PERCENTAGE S-ENANTIOMER (d) 50 PERCENTAGE S-ENANTIOMER Schematic f r e e e n e r g y - t e m p e r a t u r e p l o t s f o r r a c e m i c 1 , 1 ' - b i n a p h t h y l , showing l o w - m e l t i n g form ( L ) , h i g h - m e l t i n g form (H) and m e l t (M) s u r f a c e s . (b) Enantiotropic (a) M o n o t r o p i c r e l a t i o n s h i p , relationship. ( c ) Phase diagram w h i c h would r e s u l t from t h e m o n o t r o p i c r e l a t i o n s h i p . w h i c h would r e s u l t from t h e e n a n t i o t r o p i c 100 (d) Phase diagram relationship. 68 eliminated. From s t u d y i n g the p o s s i b l e phase diagrams a r i s i n g from the monot r o p i c and important e n a n t i o t r o p i c r e l a t i o n s h i p s ( F i g u r e 11 c o n c l u s i o n can be drawn. (c) and I f the system i s e n a n t i o t r o p i c , then a p a r t i a l l y a c t i v e sample of 1 , 1 ' - b i n a p h t h y l c o n t a i n s o n l y S c r y s t a l s and state. (d).) , an h e l d at point p racemate c r y s t a l s when i n i t s most s t a b l e Such a sample, on h e a t i n g t o 150°, should t h e r e f o r e r e s o l v e to S - l , 1 ' - b i n a p h t h y l because o f the absence o f R totally crystals. Thermodynamics would t h e r e f o r e be o p e r a t i n g so as to f a v o u r the d u c t i o n o f a h i g h l y s t e r e o s p e c i f i c sample o f s o l i d pro- 1,1'-binaphthyl. I t i s v e r y d e s i r a b l e , t h e n , t o know w h i c h phase d i a g r a m d e s c r i b e s R- and S - l , 1 ' - b i n a p h t h y l 3.3.2.2 system. D i f f e r e n t i a l Scanning C a l o r i m e t r y - Q u a l i t a t i v e The mining d i f f e r e n t i a l scanning calorimeter i s very h e l p f u l i n deter- phase diagrams ( S e c t i o n 2.3.1, p 2 7 ) . I n the c o u r s e o f s t u d i e s , many hundreds of samples o f 1 , 1 ' - b i n a p h t h y l d.s.c. I n none o f the samples was apparent. The o n l y peaks o c c u r r e d from 145° t o 158°. Two endotherms and A t y p i c a l d.s.c. (racemate) and an exotherm a r e This i s f o l l o w e d immediately c r y s t a l l i z a t i o n of the pro- melting by the e x o t h e r m i c e u t e c t i c form from the m e l t , ( e n d o t h e r m i c ) m e l t i n g of the e u t e c t i c form. high- discernible. f i r s t endotherm, at 144-145°, c o r r e s p o n d s to the m e t a s t a b l e o f the racemate. the transition ( e u t e c t i c ) forms i s shown i n F i g u r e 12 as a f u n c t i o n o f gramming ( h e a t i n g ) r a t e . The our were run on any s i g n o f a s o l i d - s o l i d t r a c e o f a sample c o n t a i n i n g b o t h the l o w - m e l t i n g melting the The then f i n a l l y by the f i n a l endotherm t h e r e - 69 144-145 157-158 144-145 157-158 (a) w sa H o X w (b) w H o Q z w (c) TEMPERATURE (°C) Figure 12. D i f f e r e n t i a l scanning calorimeter traces f o r racemic 1,1'-binaphthyl, as a function of programming rate. (b) 10 deg min * (c) 40 deg min * (a) 2.5 deg min -1 70 f o r e c o m p r i s e s b o t h t h e e u t e c t i c form o r i g i n a l l y p r e s e n t i n t h e sample p l u s t h a t w h i c h c r y s t a l l i z e d from t h e m e l t o f t h e racemate. At f a s t e r programming r a t e s , t h e d i m i n i s h e d s i z e o f t h e f i n a l endotherm and o f t h e exotherm mean t h a t t h e o r i g i n a l sample d i d n o t c o n t a i n much e u t e c t i c form. R a t h e r , most o f i t c r y s t a l l i z e d from t h e m e l t a t s l o w e r h e a t i n g rates. Pure h i g h - m e l t i n g form ( o b t a i n e d by h o l d i n g any sample o f 1,1'b i n a p h t h y l a t 150°) shows a s i n g l e endotherm t h e s p e c i f i c r o t a t i o n o f t h e sample. e r a t u r e o f t h e endotherm a t 157-158° r e g a r d l e s s o f Even a t 40 deg min \ t h e temp- ( a p p a r e n t l y s l i g h t l y h i g h e r because o f t h e t h e r m a l r e s i s t a n c e o f t h e i n s t r u m e n t ) i s t h e same whether t h e sample i s resolved or racemic. As j u s t e x p l a i n e d ( S e c t i o n 3.3.2.1), c o n s t a n c y o f m e l t i n g p o i n t w i t h c o m p o s i t i o n w i l l o c c u r when e x t r e m e l y r a p i d enantiomer i n t e r c o n v e r s i o n t a k e s p l a c e on m e l t i n g . S i n c e i t i s i m p o s s i b l e t o c r y s t a l l i z e t h e h i g h - m e l t i n g form from t h e m e l t a t 150° w i t h o u t t h e use o f seed c r y s t a l s , t h e appearance o f t h e h i g h e r t e m p e r a t u r e endotherm on d . s . c . a n a l y s i s o f 1 , 1 ' - b i n a p h t h y l i m p l i e s t h a t t h i s form must have been p r e s e n t i n t h e o r i g i n a l i n a t l e a s t t r a c e ("seed") q u a n t i t i e s . sample Thermal a n a l y s e s o f dozens o f d i f f e r e n t samples o f 1 , 1 ' - b i n a p h t h y l p r e p a r e d i n v a r i o u s ways showed t h a t i t was i m p o s s i b l e t o produce w o r k a b l e q u a n t i t i e s o f l o w - m e l t i n g form c o n t a i n i n g a b s o l u t e l y no seed c r y s t a l s o f t h e h i g h - m e l t i n g form. A l l showed endotherms a t 157-158°. Some samples were e s p e c i a l l y low i n t h i s e u t e c t i c c o n t e n t , s i n c e no h i g h - m e l t i n g endotherm was o b s e r v e d a t the u s u a l h e a t i n g r a t e o f 10 deg min ^. t o 2.5 deg rain \ However, on r e d u c i n g the r a t e some e u t e c t i c form c r y s t a l l i z e d then m e l t e d , i n d i c a t i n g 71 traces of this form i n the sample- This method i s therefore a sensitive check of the "phase purity" of low-melting samples. One single procedure did, however, produce absolutely pure lowmelting form i n small quantities. When pure 1,1'-binaphthyl, regardless of i t s phase content or activity, was melted above 160° on the d.s.c, then program cooled (at rates up to 20 deg min ^) to 50-60°, the sample solidified. On reheating at any programming rate, only the racemate endotherm was observed; no eutectic form crystallized from the melt above 145°« In contrast, i f the same sample i s melted above 160° and cooled very quickly by removing the sample planchette and placing i t on a metal surface at room temperature, a glass forms; i f the sample i s replaced i n the holder then reheated, i t solidifies at about 90-100°, then melts at 157-158°, with no indication of any low-melting form. This micro (<5 mg) method of preparing the pure high- and low-melting forms i s surprisingly reproducible - the same sample can be converted back and forth indefinitely to either form, simply by varying the rate of cooling. What do these qualitative d.s.c. observations t e l l us about the relative stability of the two crystalline modifications? First of a l l , they verify the ordering of the free energies of racemic 1,1'-binaphthyl in the region of the melting points (145° to 158°). Secondly, the manner in which the low- and high-melting form can be reproducibly obtained 81c with the d.s.c. i s revealing. In the experience of McCrone, i f two polymorphs are obtained by cooling the melt in different ways, the least stable form i s that which crystallizes -from the most highly supercooled melt. Melts can be highly supercooled when a small amount i s cooled very 72 r a p i d l y , l i k e the way d.s.c. p l a n c h e t t e . i n which t h e h i g h - m e l t i n g form was produced i n the The s u g g e s t i o n i s t h e r e f o r e t h a t a t l o w e r temper- a t u r e s the l o w - m e l t i n g form i s the more s t a b l e m o d i f i c a t i o n . These o b s e r v a t i o n s w i t h a s u p e r c o o l e d m e l t s h o u l d a l s o o b t a i n 81c with a supersaturated solution. That i s , the more h i g h l y s a t u r a t e d s o l u t i o n s h o u l d y i e l d t h e l e s s s t a b l e o f t h e two super- forms. A c c o r d i n g l y , we p r e p a r e d f i l t e r e d s o l u t i o n s o f r a c e m i c 1 , 1 ' - b i n a p h t h y l i n e t h e r , a c e t o n e , and benzene. These were a l l o w e d to. e v a p o r a t e ' s l o w l y at room t e m p e r a t u r e o v e r s e v e r a l days. c r y s t a l s were racemate I n each case the r e s u l t i n g form w i t h v e r y few seeds o f e u t e c t i c form, as r e v e a l e d by d.s.c. a n a l y s i s . S i m i l a r l y p r e p a r e d s o l u t i o n s were o r a t e d q u i c k l y ( i n l e s s than f i v e minutes) evap- i n a stream of dry a i r at room t e m p e r a t u r e . The e u t e c t i c form was (X-ray a n a l y s i s ) . I f i t i s t r u e t h a t the more s u p e r s a t u r a t e d c o n d i t i o n s produce o b t a i n e d i n h i g h phase p u r i t y t h e l e s s s t a b l e form, then a g a i n t h e i m p l i c a t i o n i s t h a t t h e racemate i s s t a b l e a t room t e m p e r a t u r e . F o l l o w i n g t h i s e m p i r i c a l p r i n c i p l e to i t s l i m i t , we d e c i d e d t o s e a r c h f o r any o t h e r c r y s t a l m o d i f i c a t i o n s ( l e s s s t a b l e than the lowand h i g h - m e l t i n g forms) by c r e a t i n g an e x t r e m e l y s u p e r c o o l e d m e l t . To t h i s end, some r a c e m i c 1 , 1 ' - b i n a p h t h y l was c a p i l l a r y then m e l t e d i n a 175° bath. posed The c a p i l l a r y was to X-rays f o r 20 h. i n an X-ray powder The c a p i l l a r y was immersed i n t o a b a t h o f l i q u i d n i t r o g e n . the tube. packed then i m m e d i a t e l y A g l a s s y s u b s t a n c e formed i n then mounted i n the powder camera and W i t h i n f o u r hours the sample s o l i d i f i e d . d i f f r a c t i o n p a t t e r n showed l i n e s due o n l y t o the racemate e u t e c t i c form, and no o t h e r c r y s t a l m o d i f i c a t i o n . and the exThe 73 3.3.2.3 D i f f e r e n t i a l Scanning C a l o r i m e t r y - Q u a n t i t a t i v e A l t h o u g h t h e above o b s e r v a t i o n s suggest an e n a n t i o t r o p i c s h i p , a more q u a n t i t a t i v e approach would be v e r y h e l p f u l . relation- Specifically, i f t h e a c t u a l f r e e energy d i f f e r e n c e between t h e racemate and t h e e u t e c t i c forms c o u l d be c a l c u l a t e d as a f u n c t i o n o f t e m p e r a t u r e a t c o n s t a n t p r e s s u r e and c o m p o s i t i o n ( t h e r a c e m i c c o m p o s i t i o n ) , then t h e s t a b l e ranges o f each c o u l d be d e t e r m i n e d . I n other organic s o l i d s , 83 84 f r e e energy c a l c u l a t i o n s have been used f o r j u s t t h i s purpose. ' S u f f i c i e n t information i n the m e l t i n g region of 1,1'-binaphthyl i s a v a i l a b l e t o a l l o w c a l c u l a t i o n o f t h e f r e e energy d i f f e r e n c e between the two c r y s t a l m o d i f i c a t i o n s a t 150°C (423°K). T h i s can be seen from the f r e e energy p l o t s ( F i g u r e 11 (a) and ( b ) ) and t h e s c h e m a t i c e n t h a l p y and e n t r o p y p l o t s o f F i g u r e 13. The e n t h a l p y d i f f e r e n c e i n g o i n g from the l o w - m e l t i n g (racemate) form t o t h e m e l t (L->M) can be c a l c u l a t e d t h e a r e a o f t h e d.s.c. endotherm a t 145°C (418°K). e n t h a l p y change h i g h - m e l t i n g ( e u t e c t i c ) form (431°K) can be d e t e r m i n e d . from S i m i l a r l y , the m e l t (H-*M) a t 158°C S i n c e t h e f r e e energy change a t t h e s e two p o i n t s i s z e r o , t h e e n t r o p y change on m e l t i n g can be c a l c u l a t e d f o r b o t h forms: [10] AS 418 L->M = 0 AG '418 ,L-*-M AH' 418 L->*i (418)AS 418 ,H->M = 0 AG '431 H->M AH 431 H--M (431)AS 431 and AS H->M 431 (431) I (a) 1 ]_ 145 158 TEMPERATURE (°C) I I 145 (b) F i g u r e 13. racemic 1 I 158 TEMPERATURE (°C) Schematic e n t h a l p y - and e n t r o p y - t e m p e r a t u r e 1,1'-binaphthyl. plots f o r (a) O r d e r i n g o f l o w - m e l t i n g form ( L ) , h i g h - m e l t i n g form (H) and m e l t e n t r o p i e s o f t h e same phases. (M) e n t h a l p i e s . (b) O r d e r i n g o f 75 where the subscript refers to the absolute temperature of the t r a n s i t i o n . Since 150°C i s close to the melting points of both forms (145°C and 158°C), we may assume to a good approximation that the enthalpy and entropy changes on melting are i d e n t i c a l to the corresponding changes at 150°C (423°K). AH That i s , 61 L->M AH 418 L->M H-*M 423 AH H-*M 431 = 423 fiH and [11] AS L-»M AS 418 L->M A<; 423 Ab H-»M 431 = H-*M A9 Ab 423 This approximation allows us to calculate the enthalpy, entropy, and free energy difference between the two c r y s t a l l i n e forms ( L and H ) at 150°C ( A H ^ j , AS^? 423 AH ~* [12] and AG^J, 423 L 4 2 3 423 A H 423 " A A S 4 2 3 " A = A H ^ 423 - H respectively). H->M _ 423 * L->M A H . H-^M " L-*M C [13] 418 A H 431 A S ^ 4 3 1 H A S 4 2 3 AG ^ 423 [14] L A H G " L A H S 4 2 3 = (423) A as a f u n c t i o n 4 1 8 " A B AS™ B e f o r e p r o c e e d i n g to show how determined S t h i s f r e e energy of temperature, we difference s h a l l p r e s e n t our can be results L-*-M thus f a r . The e n t h a l p y of m e l t i n g f o r the racemate ( A H ^ g ) was mined w i t h a sample which c o n t a i n e d n e g l i g i b l e e u t e c t i c not c r y s t a l l i z e any The endotherm was eutectic form the melt form and d i d above 1 4 5 ° C (418°K). a s i n g l e , sharp peak, from which an e n t h a l p y of 7 . 2 9 i 0 . 1 5 k c a l mole ^ ( 2 8 . 6 change, c a l c u l a t e d from deter- 0 . 6 c a l g "*") was obtained. The entropy from E q u a t i o n 1 0 , i s AS^'J = 1 7 . 4 8 t. 0 . 4 0 c a l deg ''"mole 76 Endotherms c o r r e s p o n d i n g t o t h e m e l t i n g o f t h e e u t e c t i c form H+M were s i m i l a r l y used t o c a l c u l a t e ^H^^^. However, t h e e u t e c t i c i s c a p a b l e o f h a v i n g any s p e c i f i c r o t a t i o n , depending on t h e r e l a t i v e amounts o f R and S c r y s t a l s i n t h e m i x t u r e . T h e r e f o r e , e n t h a l p i e s o f f u s i o n were determined f o r s e v e r a l samples o f e u t e c t i c form p o s s e s s i n g d i f f e r e n t activities (Table V I I ) . S e v e r a l d e t e r m i n a t i o n s were made f o r each sample, TABLE V I I E n t h a l p y o f F u s i o n o f t h e H i g h - M e l t i n g Form o f 1 , 1 ' - B i n a p h t h y l at Various Specific Rotations „H-»M . , , -1 AH,„,, k c a l mole , 431 * H-»M -1 AH,,..,, k c a l mole , 431 m u l t i p l e analyses mean v a l u e A , [ocj, degrees r n U -245 5.11, 4.70 4.91 -205 5.12, 5.28, 5.13, 5.36 5.22 -8 5.68, 5.61, 5.72, 5.65 5.67 +137 5.85, 5.43, 5.85, 5.43 5.64 +154 5.72, 5.68 +223 4.51, 4.95, +238 4.39, 4.60 5.70 4.68, 5.07 4.80 4.50 because a l l gave endotherms w i t h a s l i g h t l e a d i n g edge, which can produce 47 e r r o r s when the peaks a r e i n t e g r a t e d . samples h a v i n g h i g h r o t a t i o n s possess Comparing t h e mean v a l u e s , t h e H-*M somewhat lower v a l u e s o f A H ^ ^ . S i n c e t h e f i n a l s t a t e i n m e l t i n g e u t e c t i c form o f any a c t i v i t y i s t h e 77 r a c e m i c m e l t , the lower e n t h a l p i e s between r e s o l v e d and could r e f l e c t a d i f f e r e n c e i n enthalpy r a c e m i c e u t e c t i c form. However the d i f f e r e n c e s perhaps too c l o s e t o the s c a t t e r i n i n d i v i d u a l a n a l y s e s t o be seriously. For t h i s purpose the e n t h a l p y of f u s i o n of -1 used. The considered Moreover, our g o a l i s to d e t e r m i n e r e l a t i v e f r e e e n e r g i e s of the r a c e m i c system. [a] = -8° are sample (5.67 ± 0.08 i k c a l mole o r 22.3 H~*M c o r r e s p o n d i n g e n t r o p y change i s A S ^ . ^ I 0.3 13.15 = the - l cal g ) w i l l ± 0.22 cal be deg —1 , -1 mole The magnitudes o f the d e t e r m i n e d e n t h a l p y and f o r b o t h the low- and h i g h - m e l t i n g s c h e m a t i c e n t h a l p y and fusion forms j u s t i f i e s the o r d e r i n g entropy surfaces i n Figure A p p l i c a t i o n of E q u a t i o n s 12, 13 and and entropy of of the 13. 14 g i v e s the e n t h a l p y , e n t r o p y f r e e energy d i f f e r e n c e s between the racemate and the e u t e c t i c forms at 150°C (423°K): AH L->H 423 (7.29 AS L+H 423 (17.48 - 13.15) c a l d e g ^ m o l e " AG L-»H 423 [1620 The - 5.67) k c a l mole" 1 = 1.62 - (423)(4.33)] c a l m o l e ± 0.23 k c a l mole" 1 = 4.33 ± 0.62 - 1 = -212 ± 490 cal deg mole - 1 c a l mole" - 1 1 r a t h e r l a r g e e r r o r l i m i t s i n these v a l u e s i s d i s a p p o i n t i n g . A l t h o u g h the e n t h a l p i e s and entropies of f u s i o n f o r the racemate e u t e c t i c forms have been measured to l e s s than 2.3% L_*H d i f f e r e n c e s AH,__ 423 two 1 and measured v a l u e s , XJ->H A S . „ _ are r e l a t i v e l y s m a l l and 423 • r e s u l t i n g i n a 14% uncertainty, involve and the subtracting relative uncertainty. Finally, L-*H p e r f o r m i n g a second s u b t r a c t i o n to o b t a i n A G , _ 9 produces a v e r y large 78 uncertainty. Even the a l g e b r a i c s i g n o f the f r e e energy d i f f e r e n c e , the i m p o r t a n t c r i t e r i o n f o r r e l a t i v e s t a b i l i t y , i s i n some doubt. L~*H n u m e r i c a l r e s u l t AG^-j = -212 c a l mole —1 The r e p r e s e n t s t h e most p r o b a b l e v a l u e o f the f r e e energy d i f f e r e n c e a t 150°C. The f a c t t h a t this d i f f e r e n c e i s most p r o b a b l y n e g a t i v e i s i n a c c o r d w i t h our e x p e r i m e n t a l r e s u l t s - the e u t e c t i c form i s i n d e e d produced from the m e l t o f the racemate a t 150°C (see F i g u r e 11 (a) and Any f u r t h e r d i s c u s s i o n o f how ( b ) , p 67). the f r e e energy d i f f e r e n c e might change w i t h t e m p e r a t u r e t h e r e f o r e i n v o l v e s most p r o b a b l e v a l u e s . There i s s t i l l some advantage w i t h t h e hope t h a t i t may i n p r o c e e d i n g w i t h such a t r e a t m e n t , s u p p o r t the e x i s t e n c e of a s o l i d - s o l i d t r a n s i t i o n t e m p e r a t u r e x, even i f a p r e c i s e v a l u e i s not o b t a i n a b l e . Because o f the r a t h e r l e n g t h y development i s p r e s e n t e d i n Appendix B, p L e t us now necessary, t h i s treatment 184. summarize the e v i d e n c e f o r the e n a n t i o t r o p i c of racemic m o d i f i c a t i o n s . F i r s t of a l l , ordering slow and r a p i d c o o l i n g o f the m e l t on the d.s.c. g i v e s racemate and e u t e c t i c form, r e s p e c t i v e l y . Slow and r a p i d e v a p o r a t i o n o f s o l u t i o n s a t room t e m p e r a t u r e g i v e t h e same r e s u l t s . These o b s e r v a t i o n s a r e c o n s i s t e n t w i t h the b e i n g t h e more s t a b l e form a t room t e m p e r a t u r e . racemate S i n c e the l e s s stable o f two forms " r a r e l y , i f e v e r " can be produced above the t e m p e r a t u r e 81c at w h i c h b o t h have e q u a l f r e e e n e r g i e s , the f a c t t h a t b o t h can be o b t a i n e d at a l l by r e c r y s t a l l i z a t i o n a t room t e m p e r a t u r e i m p l i e s x i s above room t e m p e r a t u r e . S e c t i o n 3.5.1 that A n t i c i p a t i n g a r e s u l t presented i n ( p L L 2 ) , we have found t h a t the l o w e s t t e m p e r a t u r e a t w h i c h the racemate -*• e u t e c t i c form t r a n s f o r m a t i o n can be o b s e r v e d i s 76°C, 79 so that T must be lower than this temperature. The treatment i n Appendix B supports the enantiotropic r e l a t i o n s h i p , with a most probable t r a n s i t i o n temperature of 86°C. These independent observations together are consistent with the system R- and S-l,1'-binaphthyl possessing an enantiotropic phase r e l a t i o n ship at the racemic composition, and a phase diagram l i k e that i n Figure 11 (d), p 67, with the t r a n s i t i o n temperature x between 25 and 76°C. Because the higher temperature l i m i t i s closer to the calculated most probable t r a n s i t i o n temperature, the value of T w i l l be taken as ca. 70°C for the remainder of this t h e s i s . 3.3.3 The Stable and Metastable Phase Diagram The phase diagram for the R- and S-l,1'-binaphthyl system i s redrawn in Figure 14 (a). The s o l i d l i n e s represent phase boundaries r e f l e c t i n g the lowest free energy surfaces i n a temperature-composition-free energy plot (Section 2.3.2, p 32). This type of phase diagram (two racemic modifications, where a racemate i s the low temperature form and a eutectic mixture i s the high temperature form) has also been observed with (+)- rv> rum™ CH„CHCONH„ I o2 CH C O H ^ 2 f CO" 2 CH CHCONH 0H 34 3 2 NH. 4 + 35 |92~ CHOH C 0 R u + H CO " Ru 2 H 36 + TEMPERATURE: 130° >i pi 158 150 145 u o (b) w w w 130 - TEMPERATURE: 150° H Ed H ca. 70 (c) erf w w w 25 (a) 50 100 PERCENTAGE (-)-ENANTIOMER Figure 14. _L 50 PERCENTAGE (-)-ENANTIOMER (a) Phase diagram for the R- and S-l,1'-binaphthyl system, showing metastable ex- tensions (dotted lines) of the phase boundaries. (b) Schematic free energy-composition plot at 130°, showing the lowest (dashed line) and next-lowest (dotted lines) free energy surfaces, (c) As for (b), but at 150°. 100 81 and (-)-ammonium hydrogen m a l a t e ( 3 4 ) , where x = 73°; w i t h (+)- and 85 ( - ) - d i l a c t y l d i a m i d e ( 3 5 ) , where x = 35°; w i t h (+)- and ( - ) - r u b i d i u m 45d t a r t r a t e ( 3 6 ) , where x = 40°; and w i t h the complex s a l t (+)- and Q ( - ) - [ C o ( C 0 ) ] K - 3 . 5 H 0 , where x = 2 4 3 3 2 C 13°. The phase diagram ' r e p r e s e n t i n g the l o w e s t f r e e energy s u r f a c e s w i l l not show any s t r u c t u r e f o r the m e l t i n g of the 1 , 1 ' - b i n a p h t h y l racemate a t 145°, s i n c e t h i s t r a n s f o r m a t i o n i s m e t a s t a b l e and between phases which a r e a t h i g h e r f r e e e n e r g i e s a t t h i s occurs temperature. However the t r a n s f o r m a t i o n i s v e r y r e a l and f o r t h i s r e a s o n we have deduced the m e t a s t a b l e phase b o u n d a r i e s and superimposed F i g u r e 14 (a) ( d o t t e d l i n e s ) . them on The a r e a s e n c l o s e d by the d o t t e d l i n e s have no s i g n i f i c a n c e i n the phase r u l e sense; they m e r e l y r e p r e s e n t m e t a s t a b l e e x t r a p o l a t i o n s o f t h e s t a b l e a r e a s , and must be c o n s i d e r e d individually. The o r i g i n of the d o t t e d l i n e s can be seen i n the f r e e e n e r g y - c o m p o s i t i o n p l o t a t c o n s t a n t p r e s s u r e and a t 130° 14 ( b ) ) and a t 150° ( F i g u r e 14 ( c ) ) . The most s t a b l e f r e e arrangement at b o t h of t h e s e t e m p e r a t u r e s experimentally. (Figure energy i s shown by t h e dashed and i s seen to be a e u t e c t i c m i x t u r e o f R and S c r y s t a l s , schematic as line, determined The n e x t most s t a b l e arrangement i s shown by the d o t t e d l i n e s i n F i g u r e 14 (b) and ( c ) . At 130°, t h e s e connect s o l i d R w i t h racemate on one s i d e o f t h e diagram, and s o l i d S w i t h racemate on the o t h e r , i n the same manner as they do s t a b l y below c a . 70°. s i m i l a r d o t t e d l i n e s connect R and S c r y s t a l s individually At t o the m e l t phase, an arrangement which i s l o w e s t i n f r e e energy above 158°. g o i n g t o h i g h e r t e m p e r a t u r e s , the r a c e m i c m e l t d e c r e a s e s 150°, i n free In energy 82 r e l a t i v e t o t h e racemate and.the e u t e c t i c m i x t u r e , becoming l o w e r than the racemate a t 145° and lower than the e u t e c t i c m i x t u r e a t 158° ( s e e a l s o F i g u r e 11 ( b ) , p 6 7 ) . If a p a r t i a l l y resolved sample o f S - l , 1 ' - b i n a p h t h y l a t t a i n s i t s most s t a b l e s t a t e a t 25° ( p o i n t p, F i g u r e 14 ( a ) ) , i t w i l l c o n s i s t of S c r y s t a l s and racemate c r y s t a l s . only When t h e sample i s h e a t e d t o 150° ( o r , f o r t h a t m a t t e r , any t e m p e r a t u r e between 145° and 158°), t h e racemate w i l l melt i n t h e p r e s e n c e o f t h e more s t a b l e S c r y s t a l s . these c r y s t a l s exercise complete c o n t r o l o v e r t h e e n s u i n g If crystallization, then t h e e n t i r e sample w i l l become S - ( + ) - l , 1 ' - b i n a p h t h y l i n a d r i v e toward lower f r e e energy. (discussed i n Section Preparation 3.4, which f o l l o w s ) complete r e s o l u t i o n i n a s i n g l e Likewise, of the correct initial should therefore material result i n step. between c a . 70° and 145°, a d i r e c t racemate -*• e u t e c t i c t r a n s f o r m a t i o n would l o w e r t h e f r e e energy o f t h e system. Preliminary o b s e r v a t i o n s a t 120° ( T a b l e I I I , p 51) i n d i c a t e t h a t even w i t h o u t t h e i n t e r m e d i a c y o f t h e m e l t , enantiomer i n t e r c o n v e r s i o n i s possible, m i t t i n g a r e s o l u t i o n of 1,1'-binaphthyl completely i n the s o l i d Our extensive k i n e t i c investigations reported i n Section perstate. m i n t h i s t e m p e r a t u r e range a r e 3.5. We r e f e r t o t h i s g e n e r a l phenomenon as a s o l i d - s t a t e r e s o l u t i o n . At a l l t e m p e r a t u r e s , from 70° t o 158°, i t i s a r e s o l u t i o n by t h e s o l i d s t a t e - that i s , the r e s o l v i n g "agent" i s the d i s c r i m i n a t i n g s u r f a c e of t h e growing c r y s t a l s o f pure e n a n t i o m e r . Below 145°, the r e s o l u t i o n i s o c c u r r i n g t o t a l l y i n t h e s o l i d s t a t e , by means o f a s o l i d s o l i d phase transformation. 83 3.4 P e r f e c t i o n of t h e S o l i d - S t a t e R e s o l u t i o n Our i n i t i a l attempts to r e s o l v e neat, p o l y c r y s t a l l i n e 1,1 -binaphthyl 1 ( S e c t i o n 3.2, p 4 9 ) , a l t h o u g h s u c c e s s f u l , s u f f e r e d from a l a c k o f r e p r o ducibility. The b e s t method we d e v i s e d was a c y c l i n g p r o c e d u r e , which e v e n t u a l l y a c h i e v e d a h i g h r e s o l u t i o n , but d i d so i n an u n p r e d i c t a b l e fashion. Much o f our r e s e a r c h e f f o r t w i t h t h e 1 , 1 ' - b i n a p h t h y l was d i r e c t e d toward system t r y i n g t o a c h i e v e some c o n t r o l over t h e r e s o l u t i o n . The d e t e r m i n a t i o n o f t h e phase diagram was a major s t e p i n u n d e r s t a n d i n g what o r i g i n a l l y seemed a v e r y u n u s u a l r e a c t i o n . Perhaps now we c o u l d use t h i s knowledge t o p r e p a r e r e p r o d u c i b l y t h e e l u s i v e b a t c h o f s o l i d 1 , 1 ' - b i n a p h t h y l h a v i n g o r i g i n a l l y l i t t l e o r no o p t i c a l r o t a t i o n b u t p o s s e s s i n g t h e a b i l i t y t o r e s o l v e t o t a l l y s i m p l y on h e a t i n g t h e s o l i d material. Once t h i s i s a c c o m p l i s h e d , such a h i g h l y s t e r e o s p e c i f i c s o l i d c o u l d be used t o s t u d y t h e k i n e t i c s o f t h e r e s o l u t i o n e n a b l i n g , h o p e f u l l y , a more d e t a i l e d m e c h a n i s t i c process, description. Our s e v e r a l approaches t o t h e problem o f r e p r o d u c i b i l i t y a r e 79a treated i n this section. h i s attempted with h e t e r o h e l i c e n e r e s o l u t i o n s , "both e x c i t i n g and f r u s t r a t i n g , " and i n t h e end, v e r y 3.4.1 We found t h i s t a s k , as d i d Wynberg The B e h a v i o u r rewarding. o f S o l i d Racemic 1,1'-Binaphthyl B e f o r e t h e more e l a b o r a t e schemes a r e d i s c u s s e d , t h e b e h a v i o u r o f racemic 1 , 1 ' - b i n a p h t h y l , i s o l a t e d d i r e c t l y from t h e G r i g n a r d c o u p l i n g r e a c t i o n ( S e c t i o n 3.1.2, p 48) s h o u l d be e s t a b l i s h e d . 1,1'-binaphthyl was used as a c o n t r o l , and heated Initially, alongside a c t i v e samples w h i c h i n c r e a s e d i n r o t a t i o n a t 150°. racemic partially I n t h i s way, i t was 84 d i s c o v e r e d t h a t even r a c e m i c m a t e r i a l c o u l d d e v e l o p o p t i c a l a c t i v i t y on heating. Of t h e two b a t c h e s (A and B) o f r a c e m i c 1 , 1 ' - b i n a p h t h y l o r i g i n - a l l y s t u d i e d ( T a b l e I I I , p 5 1 ) , one (A) d i d n o t r e s o l v e a t a l l , b u t t h e o t h e r (B) gave s c a t t e r e d a c t i v i t i e s , w h i c h were a l l p o s i t i v e . Throughout t h e c o u r s e o f t h i s work, s e v e r a l G r i g n a r d p r e p a r a t i o n s were performed when s t o c k s o f r a c e m i c 1 , 1 ' - b i n a p h t h y l r a n l o w , and i t became r a t h e r r o u t i n e t o c h a r a c t e r i z e each b a t c h by h e a t i n g a few samples a t 150°and c h e c k i n g f o r any r e s o l u t i o n . Table V I I I compiles the r e s u l t s o f samples o f t h e r a c e m i c m a t e r i a l w h i c h were h e a t e d f o r v a r i o u s r e a s o n s . A d i f f e r e n t " b a t c h " i s p r e p a r e d each time a g i v e n p r e p a r a t i o n was r e c r y s t a l l i z e d , so t h a t a l l m a t e r i a l w i t h i n each b a t c h has t h e same phase c o n t e n t and average c r y s t a l s i z e and p e r f e c t i o n . A l t h o u g h some were r e c r y s t a l l i z e d i n the presence of racemic 1,1'-binaphthyl seeds, t h e r e was no d e l i b e r a t e a d d i t i o n o f any a c t i v e crystals. Racemic 1 , 1 ' - b i n a p h t h y l shows some v e r y i n t e r e s t i n g b e h a v i o u r on heating. Most o f t h e r a c e m i c b a t c h e s ( e x c e p t A, E, G, and 0) d e v e l o p e d o p t i c a l a c t i v i t y when heated a t t e m p e r a t u r e s from 100° t o 150°. The f a c t t h a t t h i s r e s o l u t i o n o c c u r s below 145° f i r m l y e s t a b l i s h e s t h a t t h e m e l t i s n o t n e c e s s a r y t o t h e r e s o l u t i o n p r o c e s s - t h e d i r e c t phase t r a n s f o r m a t i o n racemate -* e u t e c t i c form i s s u f f i c i e n t t o c r e a t e o p t i c a l activity. A l t h o u g h t h e b e h a v i o u r o f some b a t c h e s i s n o t w e l l d e f i n e d because o f t h e few samples h e a t e d , o t h e r s ( e . g . , B and L) were i n v e s t i g a t e d w i t h many samples and r e v e a l e d a v e r y s u r p r i s i n g tendency t o d e v e l o p o p t i c a l i n one d i r e c t i o n o n l y . F o r example, t h e 37 samples activity taken from Racemic B a t c h L a r e p l o t t e d i n F i g u r e 15 as a f u n c t i o n o f t i m e . A l l samples a r e p o s i t i v e and w i d e l y s c a t t e r e d i n o p t i c a l r o t a t i o n ; no k i n e t i c t r e n d s a r e 85 Table V I I I The Development o f O p t i c a l A c t i v i t y on H e a t i n g P o l y c r y s t a l l i n e , Racemic 1,1'-Binaphthyl Racemic B a t c h Time, hours [a] , degrees 1 +25 D 1 +65 E 1 0 F 1 G 1 I 15.5 -63 13 -77 C Temperature, °C 149.6 0 b -45 b 2 -78, - 1 4 0 b 16 -87, - 1 2 9 b 19 K +24, 0 -52, 5 -124 120 46 -108 100 120 L 135 0 t o 50 M 135 15 N 149.6 -5 see F i g u r e 15 -8, -9 1 -22 5 +3 2 0, o b b F o r Racemic Batches A and B, see T a b l e I I I , p 51. S p e c i f i c r o t a t i o n s o f two i n d i v i d u a l o f time a t t h e same t e m p e r a t u r e . samples h e a t e d f o r t h e same l e n g t h TEMPERATURE: 135° +250 on 3 o w p +200 o o o S3 O H < H O 1—I +150 o pi U o w 00 O oo o o o o +100 o o o +50 o o o &o-Q o o 1 — 10 J 30 20 TIME F i g u r e 15. S p e c i f i c r o t a t i o n as a f u n c t i o n b i n a p h t h y l (L Batch) a t 135°. L 40 50 (HOURS) o f time f o r t h e s o l i d - s t a t e r e s o l u t i o n o f racemic 1,1 87 discernible. An e q u a l l y r e m a r k a b l e r e s u l t , as a l r e a d y n o t e d , was o b t a i n e d w i t h Racemic B a t c h B, where a l l 11 samples r e s o l v e d i n a p o s i t i v e direction. Some b a t c h e s ( I and J , f o r example), a l t h o u g h i n v e s t i g a t e d l e s s e x t e n s i v e l y , develop only n e g a t i v e r o t a t i o n s . 1 , 1 ' - B i n a p h t h y l p r e p a r e d from o p t i c a l l y i n a c t i v e r e a g e n t s seems to are possess a b u i l t - i n s t e r e o s p e c i f i c i t y . Some d i s s y m m e t r i c i n f l u e n c e s p r e s e n t i n t h e b a t c h e s , w h i c h d e f i n i t e l y appear r a c e m i c when a n a l y z e d by p o l a r i m e t r y . As w i l l be proven i n S e c t i o n 3.6, r a c e m i c 1 , 1 ' - b i n a p h t h y l does n o t p o s s e s s any f o r e i g n d i s s y m m e t r i c i m p u r i t y w h i c h can i n f l u e n c e the d i r e c t i o n of r e s o l u t i o n . R a t h e r , t h e i n f l u e n c e s must a r i s e from t h e 1 , 1 ' - b i n a p h t h y l system i t s e l f , i n t h e form o f s m a l l , i m p e r c e p t i b l e 46 e x c e s s e s o f one enantiomer. I t i s generally recognized that racemic p r e p a r a t i o n s c o n t a i n t i n y e x c e s s e s o f one enantiomer due t o random s t a t i s t i c a l f l u c t u a t i o n s alone. However, o u r r a c e m i c p r e p a r a t i o n s were performed a f t e r t h e f i r s t o p t i c a l l y a c t i v e l , l ' - b i n a p h t h y l samples were obtained. I t i s p o s s i b l e t h e r e f o r e t h a t t h e s m a l l e x c e s s e s c o u l d have a r i s e n from r e s o l v e d 1 , 1 ' - b i n a p h t h y l d u s t i n o u r l a b o r a t o r y , which may overshadow any random f l u c t u a t i o n s . Whatever t h e r e a s o n f o r t h e i r e x i s t e n c e , t h e s e u n o b s e r v a b l e e x c e s s e s o f one enantiomer can be a m p l i f i e d t h r o u g h t h e phase i n t e r - a c t i o n s i n t h e R- and S - l , 1 ' - b i n a p h t h y l system. As r e v e a l e d by t h e q u a l i t a t i v e d.s.c. r e s u l t s i n S e c t i o n 3.3.2.2 (p 68), e v e r y r a c e m i c b a t c h c o n t a i n s some e u t e c t i c form, even i f t h i s i s p r e s e n t o n l y i n trace quantities. S i n c e any enantiomer excess must be c o n t a i n e d i n t h e e u t e c t i c form (as a g r e a t e r number o f , s a y , R than S c r y s t a l s ) , then i f t h i s form i s o n l y a s m a l l p a r t o f t h e t o t a l sample, the r a t i o of R to S c r y s t a l s w i l l be f a r g r e a t e r than t h e r a t i o o f R t o S m o l e c u l e s i n t h e 88 whole sample. On h e a t i n g , t h e enantiomer i n excess r e v e a l s i t s i d e n t i t y by c a u s i n g t h e c r y s t a l l i z a t i o n o f m o l e c u l e s o f i t s own c o n f i g u r a t i o n . The 1 , 1 ' - b i n a p h t h y l system i l l u s t r a t e s a n o v e l method o f c h e c k i n g f o r t r a c e enantiomer e x c e s s e s , f a r s i m p l e r than t h e hundreds of r e c r y s t a l - l i z a t i o n s on k i l o g r a m q u a n t i t i e s o f " r a c e m i c " m a t e r i a l w h i c h a r e sometimes n e c e s s a r y t o make such e x c e s s e s o b s e r v a b l e . ^ W h i l e t h e manner i n w h i c h r a c e m i c 1 , 1 ' - b i n a p h t h y l can produce o p t i c a l a c t i v i t y on h e a t i n g i s v e r y i n t e r e s t i n g i n i t s e l f , the s p e c i f i c r o t a t i o n s f a l l c o n s i d e r a b l y s h o r t o f complete r e s o l u t i o n ( [ a ] = ±245°). Perhaps c h a n g i n g t h e method o f r e s o l u t i o n might make some improvement. The phase changes accompanying the r e s o l u t i o n of racemic 1,1'-binaphthyl a r e racemate ->• melt -»• e u t e c t i c form a t 150° and racemate -*• e u t e c t i c below 145°. form An i n t e r e s t i n g a l t e r n a t i v e i s racemate ->- s o l u t i o n -*• e u t e c t i c form, w h i c h i s p o s s i b l e when t h e s o l i d r a c e m i c samples a r e h e a t e d i n t h e p r e s e n c e o f a s a t u r a t e d s o l u t i o n o f 1 , 1 ' - b i n a p h t h y l i n an o p t i c a l l y inactive solvent. Such a phase change i s c a l l e d a s o l u t i o n phase t r a n s - 8 ld formation, and o c c u r s because t h e more s t a b l e o f two c r y s t a l l i n e m o d i f i c a t i o n s i s always t h e l e s s s o l u b l e o f t h e two ( F i g u r e 1 6 ) . I n the t e m p e r a t u r e range 70-145° t h e racemate, b e i n g t h e more s o l u b l e (and l e s s s t a b l e ) form, m a i n t a i n s a s o l u t i o n o f 1 , 1 ' - b i n a p h t h y l w h i c h i s s u p e r s a t u r a t e d w i t h r e s p e c t t o the e u t e c t i c form, and t h e growth o f c r y s t a l s o f pure enantiomer can o c c u r from s o l u t i o n . Such a change i n growth environment may f a v o u r a b l y a f f e c t t h e r e s o l u t i o n . We t h e r e f o r e performed some s o l u t i o n phase t r a n s f o r m a t i o n s i n a tube s e a l e d a t b o t h ends and d i v i d e d i n t o two chambers by a f r i t t e d disc. The c r y s t a l s and s o l v e n t were l o c a t e d i n one end o f the tube which was 89 PERCENTAGE SOLVENT F i g u r e 16. Schematic phase diagram between racemic and a s o l v e n t w i t h b.p.> 160°. 1,1'-binaphthyl Dotted l i n e s are metastable e x t r a p o l a t i o n s o f phase b o u n d a r i e s , and show t h e h i g h e r s o l u b i l i t y o f t h e l e s s stable forms. 90 t o t a l l y immersed i n a b a t h h e l d a t the t e m p e r a t u r e o f i n t e r e s t . After a p e r i o d o f time the s o l u t i o n c o u l d be f i l t e r e d from the c r y s t a l s the s i n t e r e d g l a s s d i s c w i t h o u t removing bath. the sample from the through temperature The t r a n s f o r m e d c r y s t a l s c o u l d then be a n a l y z e d f o r o p t i c a l activity. The r e s u l t s of n i n e such e x p e r i m e n t s from 110° to 150° using 2 - p r o p a n o l and e t h y l e n e g l y c o l as s o l v e n t s a r e l i s t e d i n T a b l e IX. Racemic B a t c h I ( w h i c h , as shown i n T a b l e V I I I , r e s o l v e s p o o r l y i n the absence o f a s o l v e n t ) was used i n the e x p e r i m e n t s . A l t h o u g h somewhat h i g h e r r o t a t i o n s a r e were observed w i t h 2 - p r o p a n o l a t 120°, r o t a t i o n s c o u l d not be c o n s i s t e n t l y produced. the b e s t R a t h e r , the a c t i v i t i e s were s c a t t e r e d , but a l l were, c h a r a c t e r i s t i c a l l y , i n one direction (negative). Table IX The Development o f O p t i c a l A c t i v i t y on H e a t i n g P o l y c r y s t a l l i n e , Racemic 1,1'-Binaphthyl Solvent Temperature, Ethylene g l y c o l " " 2-Propanol 11 3 Under a S o l v e n t °C Time, hours [ a ] , degrees 110 17 0 130 24 -84 149.6 43 90 15 0 120 17 -158 " 43 -198 65 -186 19 -180 43 -144 A l l samples were t a k e n from Racemic Batch I . -2.5 91 3.4.2 P h y s i c a l A d d i t i o n o f Seed C r y s t a l s of A c t i v e 1 , 1 ' - B i n a p h t h y l I t appears t h a t the few c r y s t a l s o f R and/or S-l,l'-binaphthyl w h i c h happen to e x i s t i n the r a c e m i c samples, w h i l e e f f i c i e n t l y g o v e r n i n g the d i r e c t i o n of the development the magnitude of the r o t a t i o n . T h i s may o f a c t i v i t y , cannot o c c u r because control these c r y s t a l s a r e too few and too w i d e l y s c a t t e r e d t o be f u l l y e f f e c t i v e as seeds. At t h i s p o i n t we d e c i d e d t o abandon the r a c e m i c system and t o i n t r o d u c e m e c h a n i c a l l y some seed c r y s t a l s o f h i g h l y r e s o l v e d 1,1.'-binaphthyl t o the p o l y c r y s t a l l i n e m a t e r i a l , h o p i n g t o "swamp o u t " the e f f e c t of the o r i g i n a l seeds and t o c o n t r o l the r e s o l u t i o n a r t i f i c i a l l y . This physical s e e d i n g was done w i t h f i v e b a t c h e s o f r a c e m i c 1 , 1 ' - b i n a p h t h y l , w i t h t h e r e s u l t s i n T a b l e X. U s u a l l y , the added seed comprised l e s s t h a n 3% o f the t o t a l w e i g h t o f the sample, a c c o u n t i n g i t s e l f f o r l e s s than specific rotation. 6° The seed c r y s t a l s were added i n powdered form t o t h e r a c e m i c m a t e r i a l , c o n t a i n e d i n a g l a s s ampule. The ampule was then s e a l e d , shaken v i g o r o u s l y f o r f i v e minutes t o d i s t r i b u t e the added s e e d s , and then h e a t e d . I n two cases (F and G) the r e s o l v a b i l i t y o f the r a c e m i c m a t e r i a l ( T a b l e V I I I , p 85) was improved. However, r o t a t i o n s were n e v e r v e r y h i g h , and w i t h B a t c h I , seeds of b o t h p o s i t i v e and n e g a t i v e r o t a t i o n s s i m p l y d e c r e a s e d the n e g a t i v e a c t i v i t i e s d e v e l o p e d i n the racemic m a t e r i a l . unseeded, T h i s f a i l u r e o f the p h y s i c a l a d d i t i o n of seeds i s p r o b a b l y a r e f l e c t i o n of the d i f f i c u l t y i n m i x i n g two s o l i d s (i.e., seed c r y s t a l s and r a c e m i c m a t e r i a l ) m e c h a n i c a l l y . Perhaps the a d d i t i o n of seed c r y s t a l s t o the r a c e m i c , s u p e r c o o l e d 1 , 1 ' - b i n a p h t h y l melt might be more e f f e c t i v e than the m e c h a n i c a l m i x i n g of s o l i d s . A s e r i e s o f e x p e r i m e n t s were performed to t e s t t h i s s u g g e s t i o n , 92 Table X The I n f l u e n c e o f Added Seed C r y s t a l s o f O p t i c a l l y A c t i v e on the S o l i d - S t a t e R e s o l u t i o n o f P o l y c r y s t a l l i n e , Racemic [a] o f Seeds, Percent of T o t a l 1,1'-Binaphthyl 1,1'-Binaphthyl [a] P r o d u c e d , Racemic B a t c h degrees B +99 F +200 M a t e r i a l Due t o Seeds 10 3 degrees +55 +112 tt 0.9 +53 II ti 0.9 +91 II ti 0.7 +42 H II 0.05 +62 1.2 -20 1.6 -28 3.4 -15 G -212 I II II +204 II The t o t a l w e i g h t o f each sample ( e x c e p t H) was between 10 and 20 mg. The sample t a k e n from P.acemic B a t c h H weighed 2.0 g. I t s b e h a v i o u r i n the absence o f a r t i f i c i a l s e e d i n g was not checked. A f t e r h e a t i n g a t 150° f o r a t l e a s t one hour. and the r e s u l t s a r e l i s t e d i n T a b l e X I , i n the o r d e r i n which t h e y were obtained. E i g h t d i f f e r e n t samples o f h i g h l y a c t i v e 1,1'-binaphthyl were used as seeds. The s u p e r c o o l e d m e l t s were p r e p a r e d by h e a t i n g 0.2 g o f r a c e m i c 1,1'-binaphthyl i n a s t o p p e r e d t e s t tube a t 170-190° f o r t h r e e minutes t o d e s t r o y a l l s o l i d forms o f 1 , 1 ' - b i n a p h t h y l , then q u i c k l y 0 93 Table XI The I n f l u e n c e o f O p t i c a l l y A c t i v e l , l ' - B i n a p h t h y l Seed C r y s t a l s on t h e R e s o l u t i o n by C r y s t a l l i z a t i o n from a S u p e r c o o l e d , Racemic 1 , 1 ' - B i n a p h t h y l [a] o f Seeds, Number and Temperature o f degrees C o n d i t i o n o f Seeds S u p e r c o o l e d M e l t , °C ca. 1 mg c o a r s e powder 149.6 1 +200 2 ti II 3 0 3 -7 a few c o a r s e g r a n u l e s II 4 none 6 +200 7 +204 8 -212 tt II 14 -212 15 +204 II 16 -212 II 17 +204 18 -212 19 +204 20 it II it one granule it it II -7 +52 -6 +22 +172 135 it 11 +149 +176 +204 13 +126 it II a few c o a r s e g r a n u l e s +205 +203 +214 ti +204 B A -21Q 0 none degrees ti it 11 12 it it 9 10 a few c o a r s e g r a n u l e s II [a], Melt 0 0 +1 140 0 tt -9 145 +3 149.6 +144 155 -183 -10 -194 +76 +73 it -1 +51 it +81 +77 +25 +40 149.6 II 145 II +5 -18 b 94 (Table X I , continued) 149.6 cne g r a n u l e -73 -22 21 +194 22 +204 " " +139 23 +200 a few c o a r s e g r a n u l e s " +196 +158 24 -212 c a . 1 mg f i n e powder " -42 -35 25 +200 145 +95 26 -212 one g r a n u l e 0 D u p l i c a t e a n a l y s e s on t h e same sample a r e l i s t e d under A and B. immersing most o f t h e tube i n a t h e r m o s t a t t e d s i l i c o n e o i l b a t h h e l d a t 150°). (usually The s e e d i n g c r y s t a l s o f l , l ' - b i n a p h t h y l , which v a r i e d from a s i n g l e p a r t i c l e t o a f i n e powder, were then added t o t h e s u p e r c o o l e d melt. The tubes were s t o p p e r e d w h i l e t h e s o l i d l , l ' - b i n a p h t h y l grew ( u s u a l l y , o v e r n i g h t ) , to t r y to eliminate laboratory dust. Some e x p e r i m e n t s having [ a ] > 200°. experiments were v e r y s u c c e s s f u l i n p r o d u c i n g However, attempts usually failed. t o reproduce 1,1'-binaphthyl these s u c c e s s f u l The d u p l i c a t e a n a l y s e s show t h a t some i n d i v i d u a l samples were q u i t e inhomogeneous i n a c t i v i t y , i m p l y i n g t h a t the added seeds c o u l d n o t always e n t i r e melt. c o n t r o l the c r y s t a l l i z a t i o n of the U n i n t e n t i o n a l seeding probably accounts f o r the lack of r e p r o d u c e a b i l i t y , s i n c e even "unseeded" samples e v e n t u a l l y c r y s t a l l i z e d . I n a d v e r t e n t s e e d i n g can be e l i m i n a t e d by p e r f o r m i n g t h e c r y s t a l l i z a t i o n s i n s e a l e d ampules. I n f a c t , using a s p e c i a l procedure, a l l 1 , 1 ' - b i n a p h t h y l seeds can be e l i m i n a t e d , and t h e r e s o l u t i o n by c r y s t a l l i z a t i o n can be performed spontaneously. Because o f t h e i r special 95 i n t e r e s t , the r e s u l t s of these extensive experiments are reported i n S e c t i o n 3.6. F o r t h e p r e s e n t d i s c u s s i o n , we s h a l l s i m p l y s t a t e t h a t this method does n o t c o n s i s t e n t l y produce h i g h l y a c t i v e 1 , 1 ' - b i n a p h t h y l . Because s e v e r a l o t h e r systems have been s u c c e s s f u l l y r e s o l v e d by 85 seeding a supersaturated s o l u t i o n , t r i e d w i t h 1,1'-binaphthyl. t h i s a d d i t i o n a l method was a l s o By means o f a s p e c i a l e x p e r i m e n t a l p r o c e d u r e w h i c h we d e v e l o p e d , a s i n g l e seed h a v i n g [ a ] = -212° was p l a c e d i n c o n t a c t w i t h a f i l t e r e d , s u p e r s a t u r a t e d s o l u t i o n o f 1,1'-binaphthyl i n at 120° ( s e a l e d t u b e ) . i n d e e d a poor r e s u l t . 2-propanol C r y s t a l s d e v e l o p e d , b u t a n a l y s i s gave [ a ] = -2°, A second attempt was made, t h i s time u s i n g a h i g h - s p e e d s t i r r e r t o d i s p e r s e f i n e l y ground seed c r y s t a l s ( [ a ] = -194°) i n a supersaturated solution with ethylene g l y c o l . The r e s u l t i n g activity o f t h e p r e c i p i t a t e d m a t e r i a l was, however, o n l y [ a ] = -38°. No f u r t h e r a t t e m p t s t o seed out o p t i c a l l y a c t i v e 1,1'-binaphthyl from s o l u t i o n were made. 3.4.3 The B e h a v i o u r o f P a r t i a l l y A c t i v e S o l i d 1,1'-Binaphthyl E v i d e n t l y , t h e m e c h a n i c a l a d d i t i o n o f seed c r y s t a l s t o r a c e m i c 1,1 -binaphthyl 1 ( i n s o l i d , l i q u i d and s o l u t i o n phases) i s a poor method of r e p r o d u c i b l y p r e p a r i n g h i g h l y o p t i c a l l y a c t i v e m a t e r i a l . This i s p r o b a b l y due t o t h e f a c t t h a t i n t h e s e e x p e r i m e n t s , t h e e f f e c t o f t h e seeds i s n o t " f e l t " by t h e b u l k o f t h e sample, i n s p i t e o f e f f o r t s t o o b t a i n (manually) a good d i s t r i b u t i o n o f t h e seed c r y s t a l s . A f a r more i n t i m a t e mixture i s apparently required. The b e s t method o f m i x i n g o p t i c a l l y a c t i v e and r a c e m i c 1,1'- b i n a p h t h y l i s t o d i s s o l v e b o t h i n a s u i t a b l e s o l v e n t then r e c r y s t a l l i z e 96 the p a r t i a l l y a c t i v e m a t e r i a l . I n e f f e c t , t h i s was o r i g i n a l c y c l i n g e x p e r i m e n t s ( S e c t i o n 3.2, performed i n the p 4 9 ) , but not a l l o f r e c r y s t a l l i z e d b a t c h e s would r e s o l v e w e l l on h e a t i n g . have been due This f a i l u r e p l u s c r y s t a l s of o n l y one We now s t a t e , and may to the f a c t t h a t not a l l of the p a r t i a l l y a c t i v e samples were i n t h e i r most s t a b l e s t a t e at room t e m p e r a t u r e ( i . e . , (p 6 4 ) . the enantiomer), racemate as d i s c u s s e d i n S e c t i o n 3.3.2.1 t u r n our a t t e n t i o n t o the achievement o f t h i s most s t a b l e the p o s s i b i l i t y of r e p r o d u c i b l y p r e p a r i n g t h a t h i g h l y s t e r e o - s p e c i f i c batch of 1,1'-binaphthyl which w i l l r e s o l v e completely in a single heating. A sample w h i c h i s not i n i t s most s t a b l e s t a t e would be t o have too h i g h a e u t e c t i c phase c o n t e n t , and expected the approach t o t h i s s t a t e i s i d e n t i c a l w i t h the c o n v e r s i o n o f a l l r a c e m i c m a t e r i a l i n the sample t o the racemate, l e a v i n g o n l y racemate and enantiomer. c r y s t a l s o f the d e s i r e d Such a s o l i d - s t a t e c o n v e r s i o n , i f i t o c c u r s at a l l , i s c e r t a i n l y v e r y s l u g g i s h at room t e m p e r a t u r e . Slow s o l i d - s o l i d t r a n s f o r m a t i o n s can be speeded up t h r o u g h the use 8 ld o f s o l u t i o n phase t r a n s f o r m a t i o n s . t r a n s f o r m a t i o n racemate 70°, s o l u t i o n -*• e u t e c t i c form, w h i c h o c c u r s have a l r e a d y been r e p o r t e d periments, R e s u l t s of the s o l u t i o n phase ( S e c t i o n 3.4.1, p 8 3 ) . In these above ex- we had hoped t h a t the p r e s e n c e of a s o l u t i o n might improve the a c t u a l r e s o l u t i o n p r o c e s s . I f the r e v e r s e t r a n s f o r m a t i o n (racemic e u t e c t i c -> s o l u t i o n -* racemate) can be e f f e c t e d at room t e m p e r a t u r e (see F i g u r e 16, p 8 9 ) , i t might be p o s s i b l e t o p r e p a r e good s t a r t i n g m a t e r i a l f o r the s o l i d - s t a t e r e s o l u t i o n s . To t e s t the p o s s i b i l i t y of such a t r a n s f o r m a t i o n , we attempted t o 97 produce racemate from b o t h p a r t i a l l y a c t i v e and almost r a c e m i c e u t e c t i c form i n two s e p a r a t e e x p e r i m e n t s . However, even a f t e r v i g o r o u s s t i r r i n g of t h e p u l v e r i z e d e u t e c t i c samples i n c o n t a c t w i t h pentane a t room t e m p e r a t u r e f o r up t o t h r e e days, and a f t e r s e e d i n g t h e m i x t u r e w i t h c r y s t a l s o f racemate, no t r a n s f o r m a t i o n was o b s e r v e d . C o o l i n g the r a p i d l y - s t i r r i n g m i x t u r e t o -78° and changing s o l v e n t s t o methanol also has a b s o l u t e l y no e f f e c t . The f a i l u r e o f t h i s s o l u t i o n phase t r a n s f o r m a t i o n may c a s t some doubt on t h e c o n c l u s i o n from phase s t u d i e s t h a t the racemate i s the s t a b l e form o f r a c e m i c 1 , 1 ' - b i n a p h t h y l a t room t e m p e r a t u r e and below. However t h i s n e g a t i v e e v i d e n c e i s n o t e n l i g h t e n i n g , s i n c e even solution phase t r a n s f o r m a t i o n s may be s l o w , e s p e c i a l l y i f t h e d i f f e r e n c e i n 8 Id s o l u b i l i t i e s o f t h e two forms i s s l i g h t . The b e s t method o f p r o d u c i n g t h e racemate, i n s p i t e o f i t s unp r e d i c t a b l e r e s u l t s , i s r e c r y s t a l l i z a t i o n from s o l u t i o n . a l l y r e c r y s t a l l i z e d from b o i l i n g pentane at t h i s t e m p e r a t u r e were s l i g h t . We had o r i g i n - (36°), s i n c e l o s s e s i n r o t a t i o n Low t e m p e r t u r e r e c r y s t a l l i z a t i o n s (-78°) from a c e t o n e , used i n t h e l i m i t o f r e s o l u t i o n s t u d i e s (Appendix A, p 1 7 8 ) , can be c a r r i e d out w i t h v i r t u a l l y no l o s s e s i n a c t i v i t y by s o l u t i o n r a c e m i z a t i o n , and we n e x t e x p l o r e d t h i s as a method o f p r e p a r i n g 1,1'b i n a p h t h y l w h i c h might r e s o l v e w e l l on h e a t i n g . The p r o c e d u r e we f o l l o w e d i n v o l v e d making an almost saturated s o l u t i o n o f p a r t i a l l y a c t i v e ( [ a ] = ±10°) 1 , 1 ' - b i n a p h t h y l i n acetone a t room t e m p e r a t u r e . T h i s s o l u t i o n was c a r e f u l l y f i l t e r e d then p l a c e d i n a Dry I c e - a c e t o n e b a t h , where f i n e c r y s t a l s appeared i n about t e n m i n u t e s . A f t e r 30 minutes to one hour, c r y s t a l l i z a t i o n seemed c o m p l e t e , and r a p i d 98 f i l t r a t i o n w h i l e c o l d gave c a . 80% m a t e r i a l . The f i r s t such recrystalliz- a t i o n we t r i e d was p e r f e c t l y s u c c e s s f u l ; c r y s t a l s h a v i n g an a c t i v i t y o f [a] = +0.8° r e s o l v e d , on h e a t i n g a t 150° o v e r n i g h t , t o [a] = +209°. This r e p r e s e n t e d t h e l a r g e s t i n c r e m e n t i n o p t i c a l r o t a t i o n we had y e t o b s e r v e d . A second e x p e r i m e n t , r e p e a t i n g e x a c t l y t h e p r o c e d u r e o f t h e f i r s t , was a l s o s u c c e s s f u l ; m a t e r i a l o f a c t i v i t y [a] = +0.3° gave [a] = +205° on heating. The p r o c e d u r e seemed r e p r o d u c i b l e . A t h i r d experiment was performed on a l a r g e r amount (4 g) o f 1 , 1 ' - b i n a p h t h y l and i t , t o o , p r o duced 80% m a t e r i a l , [a] = +1.4°, w h i c h c o u l d i n c r e a s e t o [a] = +211° on h e a t i n g a t 150°. T h i s l a r g e b a t c h o f r e s o l v a b l e 1 , 1 ' - b i n a p h t h y l was used i n a k i n e t i c s t u d y (as K i n e t i c B a t c h S - l , S e c t i o n 3 . 5 ) , from w h i c h i t was l e a r n e d t h a t even a t 105°, r e s o l u t i o n t o [a] = +221° was possible. A f o u r t h low t e m p e r a t u r e r e c r y s t a l l i z a t i o n was an attempt t o o b t a i n 1 , 1 ' - b i n a p h t h y l w h i c h would g i v e h i g h n e g a t i v e r o t a t i o n s on h e a t i n g . Much to our d i s a p p o i n t m e n t , t h e attempt f a i l e d , and o n l y [a] = -31° was a t t a i n e d on h e a t i n g a t 135° o v e r n i g h t . A p p a r e n t l y we had unknowingly changed some parameter t o w h i c h t h e 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 i s r a t h e r sensitive. We then s e t out t o d e t e r m i n e t h e e x t e n t t o w h i c h our o r i g i n a l s u c c e s s f u l p r o c e d u r e c o u l d be a l t e r e d . S i x t e e n more r e c r y s t a l l i z a t i o n s were performed and s e v e r a l f a c t o r s were v a r i e d : the a c t i v i t y o f the s o l u t i o n o f 1 , 1 ' - b i n a p h t h y l from w h i c h r e c r y s t a l l i z a t i o n o c c u r r e d , from [a] = 0 t o [ a ] = 71°; the c o n c e n t r a t i o n o f 1 , 1 ' - b i n a p h t h y l i n t h i s solution, from 1.43 g / 100 ml acetone ( s a t u r a t e d ) t o 0.67 g / 100 ml a c e t o n e ; and the time a l l o w e d f o r r e c r y s t a l l i z a t i o n a t -78°, from 15 min t o 12 h. v a r i e d were such q u a l i t a t i v e f a c t o r s as a g i t a t i o n w h i l e Also recrystallization o c c u r r e d , methods o f f i l t r a t i o n , p u r i t y o f acetone s o l v e n t ( d i s t i l l e d o r 99 u n d i s t i l l e d ) , and s e e d i n g w i t h v a r i o u s forms o f 1 , 1 ' - b i n a p h t h y l ( b o t h a c t i v e and r a c e m i c ) . obtained. failed. I n a l l o f t h e s e e x p e r i m e n t s , poor r e s u l t s were Even v e r y c a r e f u l a t t e m p t s t o r e p r o d u c e t h e o r i g i n a l p r o c e d u r e We can o f f e r no e x p l a n a t i o n as t o why t h e f i r s t three r e c r y s t a l - l i z a t i o n s worked p e r f e c t l y , and t h e e n s u i n g s i x t e e n d i d not s u c c e e d . Perhaps t h e p r e p a r a t i o n o f r e s o l v a b l e 1 , 1 ' - b i n a p h t h y l by t h i s method i s governed by d e l i c a t e k i n e t i c f a c t o r s , w h i c h a r e d i f f i c u l t to control experimentally. At t h i s time we d i s c o v e r e d , somewhat by a c c i d e n t , a method w h i c h has produced h i g h l y r e s o l v a b l e 1 , 1 ' - b i n a p h t h y l e v e r y t i m e . of In the course c y c l i n g a q u a n t i t y o f 1 , 1 ' - b i n a p h t h y l t o h i g h r o t a t i o n s , we r e c r y s t a l - l i z e d an a c e t o n e s o l u t i o n o f [ a ] = +10° m a t e r i a l a t -78° ( h o p i n g t o o b t a i n c r y s t a l s w h i c h would produce a t l e a s t some a c t i v i t y on h e a t i n g ) , t h e n , to c o n s e r v e m a t e r i a l , we d i d n o t f i l t e r t h e c r y s t a l s from t h e s o l u t i o n , but i n s t e a d d i s t i l l e d o f f t h e acetone under reduced p r e s s u r e a t 25°. The m a t e r i a l o b t a i n e d ( [ a ] = -9.5°) r e s o l v e d t o [ a ] = -216° on h e a t i n g at 150° f o r 16 h. An e x t e n s i v e i n v e s t i g a t i o n o f t h i s e v a p o r a t i o n p r o c e d u r e was c o n d u c t e d . recrystallization- Twenty-seven e x p e r i m e n t s were p e r - formed, s i x t e e n o f w h i c h were r e p r o d u c i b i l i t y checks and p r e p a r a t i o n s o f h i g h l y r e s o l v a b l e 1 , 1 ' - b i n a p h t h y l , and e l e v e n o f w h i c h were v a r i a t i o n s on t h i s s u c c e s s f u l p r o c e d u r e . Of t h e s i x t e e n r e p e t i t i o n s , f i f t e e n gave m a t e r i a l which would r e s o l v e t o g r e a t e r than [ct] = 190° (78% r e s o l u t i o n ) on h e a t i n g a t 150°. The s u c c e s s f u l r e c r y s t a l l i z a t i o n - e v a p o r a t i o n p r o c e d u r e , summarized h e r e f o r d i s c u s s i o n and g i v e n i n d e t a i l i n S e c t i o n 4.3.2.3 ( b ) , p 1 5 8 ) , i s easy t o p e r f o r m . The method i n v o l v e s d i s s o l v i n g 1 , 1 ' - b i n a p h t h y l o f 100 [a] = 2° t o 15° i n d i s t i l l e d acetone (1.2 g / 100 m l ) , f i l t e r i n g t h e s o l u t i o n , then s w i r l i n g i t i n a Dry I c e - a c e t o n e b a t h u n t i l appear (about 15 m i n ) . crystals The c o l d f l a s k i s then p l a c e d on t h e r o t a r y e v a p o r a t o r and t h e vacuum (water a s p i r a t o r ) a p p l i e d . When t h e g r e a t e s t vacuum i s a t t a i n e d , t h e c o l d f l a s k i s l o w e r e d i n t o a b a t h a t 20-25°. As t h e f l a s k warms, t h e c r y s t a l s b e g i n t o d i s s o l v e and t h e acetone to d i s t i l l o f f . begins These two p r o c e s s e s (warming and l o s s o f s o l v e n t ) oppo- s i t e l y a f f e c t t h e amount o f 1 , 1 ' - b i n a p h t h y l i n s o l u t i o n , and most ( b u t not a l l ) o f t h e c r y s t a l s d i s s o l v e a t one p o i n t , w h e r e a f t e r they come back o u t o f s o l u t i o n as t h e l o s s o f s o l v e n t c o n t i n u e s . Eventually ( i n about 30 m i n ) , a l l t h e s o l v e n t d i s a p p e a r s , and t h e r e m a i n i n g crystals w i l l r e s o l v e w e l l on h e a t i n g . S t r a i g h t e v a p o r a t i o n o f a s o l u t i o n o f 1 , 1 ' - b i n a p h t h y l g i v e s poor results. A l s o , f o r t h e p r o c e d u r e t o s u c c e e d , t h e c r y s t a l s must n o t t o t a l l y d i s s o l v e during the evaporation. P a r t i a l evaporation of solvent f o l l o w e d by f i l t r a t i o n g i v e s u n p r e d i c t a b l e r e s u l t s . The s u c c e s s o f t h i s p r o c e d u r e e v i d e n t l y depends on t h e p r e s e n c e , during the evaporation of a s l i g h t l y a c t i v e s o l u t i o n of b i n a p h t h y l , of s u i t a b l e seed c r y s t a l s . These " c o r r e c t " seeds a r e g e n e r a t e d d u r i n g t h e warming o f a c o l d m i x t u r e o f s o l i d m a t e r i a l p l u s s o l u t i o n t o room temperature. The f a c t t h a t almost a l l c r y s t a l s d i s a p p e a r d u r i n g t h e e v a p o r a t i o n i m p l i e s t h a t those which d i s s o l v e a r e " u n d e s i r e d " seeds, t h e " c o r r e c t " seed c r y s t a l s r e m a i n i n g b e h i n d t o i n d u c e t h e f u r t h e r growth o f resolvable 1,1'-binaphthyl. A p o s s i b l e e x p l a n a t i o n f o r t h i s phenomenon l i e s i n a c o n s i d e r a t i o n o f t h e t e r n a r y system i n v o l v e d . racemate, When a p a i r o f enantiomers forms a t h e t e r n a r y phase diagram between R, S and o p t i c a l l y inactive 101 s o l v e n t appears as i n F i g u r e 17 a t any constant t e m p e r a t u r e which i s above t h e m e l t i n g p o i n t of t h e s o l v e n t and below t h a t of the mers. 5d,53,85 4 system a t -78°, F ig u r 11 e () a i s and F i g u r e 17 s c h e m a t i c r e p r e s e n t a t i o n of the a (b) r e p r e s e n t s l i n e s a r e t h e s t a b l e phase b o u n d a r i e s . and enantio- three-phase regions are l a b e l l e d . the same at 25°. I n F i g u r e 17 ternary The solid (b) the one- two- I n b o t h d i a g r a m s , the d o t t e d lines r e p r e s e n t m e t a s t a b l e e x t r a p o l a t i o n s of the s o l u b i l i t y c u r v e s of s o l i d racemate, and s o l i d S. Point y represents ( s c h e m a t i c a l l y ) the o v e r a l l c o m p o s i t i o n s l i g h t l y a c t i v e S - l , I - b i n a p h t h y l s o l u t i o n a t the b e g i n n i n g c r y s t a l l i z a t i o n - e v a p o r a t i o n procedure. At 25°, d i s s o l v e s at however, i t l i e s f o r m a l l y i n the S + racemate + s o l u t i o n r e g i o n , so t h a t t h e s e two a r a t e from t h e s o l u t i o n . the i t i s seen t o l i e i n the one-phase s o l u t i o n r e g i o n , s i n c e a l l s o l i d 1 , 1 ' b i n a p h t h y l At -78°, of of the r e - 1 t h i s temperature. R, three-phase s o l i d phases can In a d d i t i o n , i t probably l i e s behind sep- the s o l u b i l i t y c u r v e s o f a l l t h r e e s o l i d p h a s e s , and the m a t e r i a l w h i c h crystallizes t o 25° l i k e l y c o n t a i n s R, S, and (on the r o t a r y e v a p o r a t o r ) , racemate t o g e t h e r . (b). However, s i n c e l i e s f a r t h e s t from the R s o l u b i l i t y c u r v e , t h i s d i s s o l v e f i r s t and f a s t e s t , l e a v i n g b e h i n d o n l y S and out the 1 , 1 ' - b i n a p h t h y l i n s o l u t i o n as t h e e v a p o r a t i o n s o l i d m a t e r i a l thus obtained probably temperatures. form the can racemate t o seed proceeds. c o n s i s t s o n l y of racemate S c r y s t a l s , the l o n g - s o u g h t phase m i x t u r e which i s i d e a l l y r e s o l u t i o n at h i g h e r rewarming a l l t h r e e phases w i l l b e g i n t o d i s s o l v e as the system approaches t h a t i n F i g u r e 17 p o i n t y now On The and suited for 102 S SOLVENT F i g u r e 17. Schematic r e p r e s e n t a t i o n o f t h e t e r n a r y system formed between s o l v e n t , R- and S - l , 1 ' - b i n a p h t h y l . Metastable extrapolations of phase b o u n d a r i e s ( s o l u b i l i t y c u r v e s ) a r e shown as d o t t e d (a) Temperature: -78°, (b) Temperature: +25°. lines, 103 3.5 K i n e t i c Study of the S o l i d - S t a t e R e s o l u t i o n Once a method of p r e p a r i n g s o l i d 1 , 1 ' - b i n a p h t h y l which would r e s o l v e c o n s i s t e n t l y to a h i g h s p e c i f i c r o t a t i o n had been found, a k i n e t i c i n v e s t i g a t i o n of the r e s o l u t i o n p r o c e s s became p o s s i b l e . Four d i f f e r e n t b a t c h e s o f r e s o l v a b l e 1 , 1 - b i n a p h t h y l were used i n the k i n e t i c 1 s t u d y - t h r e e p r o d u c i n g S - ( + ) - 1 , 1 ' - b i n a p h t h y l and one g i v i n g R - ( - ) - l , l ' b i n a p h t h y l on h e a t i n g . The f i r s t k i n e t i c b a t c h , S - l , c o n s i s t e d o f g o f m a t e r i a l a c q u i r e d by a s i m p l e low temperature from acetone (p 98). The o t h e r s (S-2, 4.0 3.0 recrystallization g; S-3, 5.7 g; and R - l , 3.8 were p r e p a r e d from the s u c c e s s f u l r e c r y s t a l l i z a t i o n - e v a p o r a t i o n g) procedure (p 9 9 ) . 3.5.1 The Development of O p t i c a l A c t i v i t y w i t h Time The r e s o l u t i o n r e a c t i o n of each b a t c h was f o l l o w e d by h e a t i n g i n d i v i d u a l s e a l e d ampules c o n t a i n i n g a c a r e f u l l y weighed amount (15-20 of the p o l y c r y s t a l l i n e 1 , 1 ' - b i n a p h t h y l a t a g i v e n temperature f o r v a r i o u s l e n g t h s of t i m e . Some r e p r e s e n t a t i v e s p e c i f i c r o t a t i o n - t i m e p l o t s a r e shown i n F i g u r e s 18-22. - 135°, was of mg) 125°, 115°, K i n e t i c runs were performed a t f o u r and 105° e x p l o r e d o n l y a t 135° - f o r a l l k i n e t i c b a t c h e s except S - l , w h i c h and 105°. The f i n a l s p e c i f i c r o t a t i o n s , [a] , F each o f t h e s e runs a r e l i s t e d i n T a b l e X I I . A l l b a t c h e s r e s o l v e d to g r e a t e r than [a] = ±200° a t 150°, but w i t h a h a l f - l i f e accurate k i n e t i c temperatures too s h o r t f o r an description. S e v e r a l comments s h o u l d be made r e g a r d i n g the form of the k i n e t i c curves. What i s i m m e d i a t e l y o b v i o u s i s the smoothness to the k i n e t i c p o i n t s - much more s a t i s f a c t o r y f o r k i n e t i c a n a l y s i s than the s c a t t e r TEMPERATURE: 135° +250 CO w o w +200 53 O r-l H +150 Q < H O Pi O r-l U-i r-l O • O r i g i n a l k i n e t i c run Run performed a f t e r s i x weeks' s t o r a g e a t 25° +100 Li] CU CO A Run u s i n g ground +50 Run u s i n g more h i g h l y ground samples 20 40 E f f e c t of grinding 100 120 (MINUTES) K i n e t i c data f o r the s o l i d - s t a t e r e s o l u t i o n K i n e t i c Batch a t 135°. 80 60 TIME F i g u r e 18. samples of neat, p o l y c r y s t a l l i n e 1,1'-binaphthyl, S - l and o f s t o r a g e a t 25° f o r s i x weeks. o J 1 1 I I 1 I I I I 1 2 4 6 8 10 12 14 16 18 20 22 TIME F i g u r e 19. L 24 (HOURS) K i n e t i c d a t a f o r the s o l i d - s t a t e r e s o l u t i o n of n e a t , p o l y c r y s t a l l i n e 1 , 1 ' - b i n a p h t h y l , S K i n e t i c Batch at 125°. E f f e c t of s t o r a g e of samples a t 0° f o r f o u r months. 106 +150 TEMPERATURE: 135° +125 +100 +75 S-2 K i n e t i c Batch 00 +50 w Qi O W +25 a 53 o i—i 20 H <! H O Pi c_> M PK rH U W P-i -25 40 30 TIME 50 60 (MINUTES) -50 00 -75 -100 -125 G O -OR-l K i n e t i c Batch •150 Figure 20. K i n e t i c data for the s o l i d - s t a t e resolution of neat, p o l y c r y s t a l l i n e 1,1'-binaphthyl, S-2 and R-l K i n e t i c Batches at 135°. 107 F i g u r e 21. K i n e t i c d a t a f o r the s o l i d - s t a t e r e s o l u t i o n of n e a t , p o l y c r y s t a l l i n e 1 , 1 ' - b i n a p h t h y l , S-2 and R - l K i n e t i c Batches a t 115°. 108 +250 h 00 w w PS o O +200 z o M H <: H + 150 h u +100 h o r-l u W 00 +50 h 10 (a) 20 TIME 30 (MINUTES) +250 h oo w w Pi o w o +200 h z o l-l H < H O Pi +150 u +100 h 00 +50 h r-l CJ K 10 (b) F i g u r e 22. TIME 15 (HOURS) K i n e t i c data f o r the s o l i d - s t a t e r e s o l u t i o n of neat, p o l y c r y s t a l l i n e 1 , 1 ' - b i n a p h t h y l , S-3 K i n e t i c B a t c h a t (a) 135° and (b) 115°. 109 Table X I I F i n a l S p e c i f i c Rotations i n the S o l i d - S t a t e R e s o l u t i o n of 1,1'-Binaphthyl ( K i n e t i c Batches) K i n e t i c Batch Temperature, °C t S-l 149.6 +211 25 min 135.0 +201 37 min 0 ^ ' degrees Half-Life 135.0 b +201 53 min 135.0 d +182 13 min 135.0 e +61 3 min 105.1 +221 149.6 +226 <1 min 135.0 +84 14 min » 124.9 +67 » 124.9° +136 4 h 114.9 +110 17 h 105.1 +123 149.6 +200 <1 min 135.0 +201 5 min 124.9 +214 38 min 114.9 +223 5 105.1 +229 1.1 days 149.6 -233 <1 min 135.0 -123 13 min 124.9 -71 1.2 h 114.9 -69 6 105.1 -79 1.7 days S-2 S-3 » R-l 6.6 days 1.7 h 4.3 days h h 110 Time taken to a c h i e v e [a] /2. r Run performed a f t e r s i x weeks' s t o r a g e a t 25°. Run performed a f t e r f o u r months' s t o r a g e a t 0°. Run u s i n g ground samples. Run u s i n g more h i g h l y ground samples. o b t a i n e d when r a c e m i c 1 , 1 ' - b i n a p h t h y l Although the a c t i v i t y d e v e l o p s i s t i c shape to the c u r v e s . i s heated smoothly, ( F i g u r e 15, p 8 6 ) . t h e r e appears t o be no c h a r a c t e r - Some a r e s i g m o i d ( a l t h o u g h none have prolonged i n d u c t i o n p e r i o d s ) , and o t h e r s appear to i n c r e a s e l i n e a r l y w i t h time o r even show a r a t e maximum a t t h e s t a r t o f the r u n . lution also varies. 150°, t h e S-2 at lower The extent of r e s o - C o n t r a r y t o the v e r y h i g h r o t a t i o n s a c h i e v e d and R - l K i n e t i c Batches suffer a loss i n resolving at ability temperatures. The k i n e t i c runs a r e a l s o s e n s i t i v e to g r i n d i n g o r to s t o r a g e f o r any g r e a t l e n g t h o f t i m e . As demonstrated w i t h the S - l sample a t 135°, the a c t o f g r i n d i n g the s t a r t i n g m a t e r i a l causes a f a s t e r r e s o l u t i o n to a lower s p e c i f i c r o t a t i o n ( F i g u r e 18). A l s o , the S - l K i n e t i c B a t c h d i d not show the same k i n e t i c s b e f o r e and a f t e r s t o r a g e f o r s i x weeks a t room temperature (25°). I n s t e a d , the r e s o l u t i o n was a l t h o u g h t h e e x t e n t of r e s o l u t i o n was preserved. k i n e t i c s o f t h i s b a t c h ware not e x p l o r e d a t 115° slowed somewhat, For t h i s r e a s o n o r 125°. The others were s t o r e d a t 0° w h i l e the k i n e t i c runs were performed ( w i t h i n weeks). A r e p r o d u c e a b i l i t y check of the S-2 a f t e r f o u r months' s t o r a g e a t 0° K i n e t i c B a t c h was the five performed ( F i g u r e 1 9 ) , and showed an unchanged r a t e of r e s o l u t i o n but an enhanced e x t e n t of r e s o l u t i o n ( o r i g i n a l l y , to Ill [a] = +67°; a f t e r f o u r months, to [a] = 136°). T h e r e f o r e , the v a l u e of [a]_, w i l l have a l t e r e d t o some e x t e n t d u r i n g the f i v e weeks taken f o r the F k i n e t i c r u n s , but any changes i n the r a t e of r e s o l u t i o n a r e p r o b a b l y small. There i s some v a l u e i n n e g l e c t i n g t h e s e changes to a l l o w an a n a l y s i s i n terms o f known r a t e e q u a t i o n s f o r s o l i d - s t a t e reactions. T h i s w i l l be done i n S e c t i o n 3.5.2. Some samples o f t h e f a s t e s t - r e s o l v i n g b a t c h (S-3) were ground a c c e l e r a t e the r e a c t i o n even f u r t h e r ) and heated a t temperatures 105°, below to e s t a b l i s h the l o w e s t t e m p e r a t u r e a t which the r e s o l u t i o n proceed. The r e s u l t s a r e o r g a n i z e d i n T a b l e X I I I . Even a t 98°, (to can samples Table X I I I Low Temperature S o l i d - S t a t e R e s o l u t i o n o f Temperature, °C 97.7 93.0 87.6 Time, weeks [ot], degrees 0 +1.4 2.6 +9 11.2 +156 24.9 +227 0 +1.8 1.0 +67 3.7 +114 4.0 +125 0 +1.8 1.0 +33 3.7 +64 4.0 +77 1,1'-Binaphthyl Kinetic Batch S-l S-3, 'round 112 (Table X I I I , continued) 83.3 76.9 64.2 0 +1.8 1.0 +16 4.0 +26 0 +1.8 1.0 +5.8 4.0 +11 25.5 +22 0 +1.8 1.0 +1.9 4.0 +1.2 25.5 S-3, ground 0 are capable of r e s o l v i n g t o h i g h r o t a t i o n s , but c o n s i d e r a b l e l e n g t h s of time a r e r e q u i r e d . The l o w e s t t e m p e r a t u r e a t which an i n c r e a s e i n s p e c i f i c r o t a t i o n i s o b s e r v a b l e i s 76°, where [ a ] = +22° was a c h i e v e d a f t e r s i x months. No r e a c t i o n was d i s c e r n a b l e a t 64°, even a f t e r h a l f a year. The absence o f r e s o l u t i o n a t 64° c o u l d i m p l y t h a t t h i s temperature i s l o w e r than t h e s o l i d - s o l i d t r a n s i t i o n t e m p e r a t u r e T ( F i g u r e 11 ( d ) , p 67). However, c a u t i o n s h o u l d be used i n making such a c o n c l u s i o n , i n v i e w o f t h e slowness o f t h e r e s o l u t i o n a t 76°. I t i s best simply to s t a t e t h a t t h e low temperature k i n e t i c r e s u l t s i n d i c a t e t h a t x i s l o w e r than 76°. From t h e r e s u l t s g i v e n above i t i s o b v i o u s t h a t t h e k i n e t i c b e h a v i o u r o f t h e s o l i d - s t a t e r e s o l u t i o n of 1 , 1 ' - b i n a p h t h y l i s c o n s i d e r a b l y more 113 complex than the s i m p l e f i r s t - o r d e r s o l i d - s t a t e r a c e m i z a t i o n o f the d i a c i d _29_ r e p o r t e d i n S e c t i o n 2 o f t h i s t h e s i s . Such a k i n e t i c c o m p l e x i t y i s t o be e x p e c t e d , c o n s i d e r i n g the n a t u r e of t h e p r o c e s s e s i n v o l v e d i n the r e a c t i o n . The r e s o l u t i o n i s caused by the s t e r e o s p e c i f i c growth o f c r y s t a l s of one enantiomer a t the expense o f the racemate phase. p r o c e s s would be h i g h l y dependent Such a on the a r e a o f the i n t e r f a c e between t h e s o l i d r e a c t a n t phase and t h e s o l i d p r o d u c t phase. Any p r o c e d u r e w h i c h can change the a r e a of t h i s i n t e r f a c e i n the s t a r t i n g m a t e r i a l will 58 g r e a t l y a f f e c t the observed r a t e o f r e a c t i o n . The f a c t t h a t an e n t i r e sample o f a l m o s t - r a c e m i c 1 , 1 - b i n a p h t h y l 1 can c o n v e r t t o e s s e n t i a l l y o n l y one enantiomer means, o f c o u r s e , t h a t enantiomer i n t e r c o n v e r s i o n must o c c u r somewhere i n t h e sample. where the racemate m e l t s , l e a v i n g b e h i n d c r y s t a l s of o n l y one At enantiomer, r a c e m i z a t i o n o c c u r s v e r y r a p i d l y ( w i t h a h a l f - l i f e o f l e s s than sec i n the m e l t ) . 150°, 0.5 Growing S c r y s t a l s ( f o r example) can s e l e c t S m o l e c u l e s from a m e l t which i s e s s e n t i a l l y always r a c e m i c ( w h i l e i t l a s t s ) . t h e t e m p e r a t u r e range 76° t o 135°, where the sample i s e n t i r e l y In solid, enantiomer i n t e r c o n v e r s i o n (a s i m p l e c o n f o r m a t i o n a l change) can c o n c e i v a b l y o c c u r i n the i n t e r f a c e between growing S c r y s t a l s and the d i s a p p e a r i n g racemate c r y s t a l s . very extensive. I n a p o l y c r y s t a l l i n e sample, t h i s i n t e r f a c e w i l l be S i n c e the r e a c t a n t - p r o d u c t i n t e r f a c e r e p r e s e n t s an a r e a o f c o n t a c t between c e n t r o s y m m e t r i c (racemate) and n o n c e n t r o s y m m e t r i c (pure enantiomer) c r y s t a l s , i t w i l l be q u i t e d i s o r g a n i z e d ( " i n c o h e r e n t " ) ^ The h i g h e r ( s u r f a c e ) f r e e energy a s s o c i a t e d w i t h t h i s p a r t o f the s o l i d s t a t e c o u l d w e l l f a c i l i t a t e enantiomer i n t e r c o n v e r s i o n , making the s o l i d - s t a t e resolution. possible 3 114 If the i n t e r c o n v e r s i o n of enantiomers i n the r e a c t a n t - p r o d u c t inter- f a c e i s v e r y f a s t compared t o t h e r a t e o f growth o f c r y s t a l s o f pure e n a n t i o m e r , then t h e r e a c t i o n i s e s s e n t i a l l y o n l y a phase change. Phase 61 changes a r e almost always governed by n u c l e a t i o n - a n d - g r o w t h processes. That i s , n o t o n l y can a phase t r a n s f o r m a t i o n o c c u r v i a growth o f s m a l l c r y s t a l l i t e s of product which e x i s t i n i t i a l l y i n the r e a c t a n t phase, but new c r y s t a l l i t e s can form ( n u c l e a t e ) d u r i n g t h e phase change. t h i s p o i n t , we have c o n s i d e r e d enantiomer p r e s e n t Up t o o n l y t h e growth o f " s e e d " c r y s t a l s o f pure i n i t i a l l y i n t h e s o l i d sample o f 1,1'-binaphthyl. Indeed, t h e e l i m i n a t i o n o f c r y s t a l s o f "unwanted" enantiomer was t h e prime o b j e c t i v e i n t h e d e s i g n i n g o f e x p e r i m e n t s t o produce r e s o l v a b l e 1,1'binaphthyl. However, as w i l l be seen, t h e k i n e t i c r e s u l t s r e q u i r e a c o n s i d e r a t i o n o f t h e n u c l e a t i o n o f new e u t e c t i c c r y s t a l s from t h e r e a c t i n g racemate phase. The prospect o f n u c l e a t i o n i n t h e R , S - l , l ' - b i n a p h t h y l phase system c a r r i e s w i t h i t some i n t e r e s t i n g s t e r e o c h e m i c a l According consequences. t o t h e c l a s s i c a l t h e o r y o f n u c l e a t i o n , ^ ' ^ ^ new c r y s t a l s a r e formed from l o c a l s t a t i s t i c a l f l u c t u a t i o n s i n energy, c o n c e n t r a t i o n , and o r i e n t a t i o n o f m o l e c u l e s i n t h e r e a c t a n t phase. But i n t h e 1 , 1 ' - b i n a p h t h y l system, t h e r e a c t a n t phase i s a r a c e m i c c r y s t a l below 145° o r a r a c e m i c melt between 145° and 158°. j u s t as l i k e l y T h i s means t h a t t h e l o c a l f l u c t u a t i o n s a r e t o i n v o l v e R m o l e c u l e s as S m o l e c u l e s . I n o t h e r words, n u c l e a t i o n i n t h e r a c e m i c phase i s e x p e c t e d t o c r e a t e b o t h R and S c r y s t a l l i t e s with equal p r o b a b i l i t y . T h i s w i l l be t r u e r e g a r d l e s s o f t h e s i t e s o f n u c l e a t i o n i n the r e a c t a n t c r y s t a l . Whether n u c l e a t i o n i s homogeneous - o c c u r r i n g a t a l l p o i n t s i n t h e r e a c t a n t c r y s t a l w i t h equal 115 l i k e l i h o o d - o r whether i t o c c u r s o n l y a t d e f e c t s , d i s l o c a t i o n s o r boundaries between r e a c t a n t c r y s t a l l i t e s , t h e o v e r a l l p r o d u c t s o f n u c l e a t i o n s h o u l d be a r a c e m i c , e u t e c t i c m i x t u r e o f i n d i v i d u a l R and S crystallites. A racemic r e a c t a n t phase w i l l show no p r e f e r e n c e f o r the f o r m a t i o n o f any one The to reasons enantiomer. f o r t h e f a i l u r e o f some batches of 1,1'-binaphthyl r e s o l v e w e l l on h e a t i n g a r e t h e r e f o r e : (a) t h e presence lites o f b o t h enantiomers of c r y s t a l - i n the i n i t i a l m a t e r i a l before heating, (b) t h e n u c l e a t i o n o f racemic m a t e r i a l d u r i n g t h e r e a c t i o n , o r (c) b o t h . for The k i n e t i c r e s u l t s p r o v i d e an o p p o r t u n i t y t o t e s t t h e s e reasons f a i l u r e , s i n c e we know t h e c o n d i t i o n s under w h i c h t h e h i g h resolv- a b i l i t y of the batches S-l can be d e s t r o y e d . F o r example, g r i n d i n g t h e K i n e t i c B a t c h causes a f a s t e r r e s o l u t i o n , but t o a l o w e r rotation. C e r t a i n l y , g r i n d i n g w i l l break apart the S c r y s t a l l i t e s present initially i n t h e m a t e r i a l (and i m p a r t i n g a s m a l l s p e c i f i c r o t a t i o n o f [ a ] = +1.4°), c r e a t i n g a g r e a t e r r e a c t a n t - p r o d u c t i n t e r f a c e and c a u s i n g a more r a p i d reaction. I n a d d i t i o n , R c r y s t a l l i t e s a r e e i t h e r formed d u r i n g t h e g r i n d i n g p r o c e s s o r n u c l e a t e d ( a l o n g w i t h an e q u a l number o f S c r y s t a l l i t e s ) when t h e ground sample was h e a t e d . The f a c t t h a t t h e racemate has a l o w e r m o l a r volume (196.2 ml mole "*") than t h e e u t e c t i c form (214-216 ml n mole ^)° i m p l i e s t h a t t h e p r e s s u r e o f g r i n d i n g c o u l d n o t cause a phase n C a l c u l a t e d from t h e c r y s t a l l o g r a p h i c d a t a o f K e r r and R o b e r t s o n ^ f o r the l o w - m e l t i n g form o f l , l ' - b i n a p h t h y l , 82 E x t r a p o l a t e d t o 25° from t h e d i l a t o m e t r i c d a t a o f B i n n s and S q u i r e f o r t h e h i g h - m e l t i n g form o f l , l ' - b i n a p h t h y l between 120° and 158°. 116 change from t h e racemate t o an e q u i m o l a r m i x t u r e o f R and S c r y s t a l s . Hence t h e sample, b o t h b e f o r e and a f t e r g r i n d i n g , v e r y l i k e l y c o n t a i n e d e s s e n t i a l l y o n l y S c r y s t a l s and racemate c r y s t a l s , t h e R form b e i n g n u c l e a t e d ( a l o n g w i t h S) more r e a d i l y from t h e ground sample. The reason f o r t h e decreased e x t e n t o f r e s o l u t i o n i n ground samples may then be t h a t g r i n d i n g c r e a t e s s t r e s s e s , d i s l o c a t i o n s , and o t h e r i m p e r f e c t i o n s i n t h e r e a c t a n t l a t t i c e , and t h e s e can a c t as s i t e s f o r t h e n u c l e a t i o n of racemic m a t e r i a l . A l s o , t h e S-2 and R - l K i n e t i c Batches r e s o l v e d r a t h e r p o o r l y i n the t e m p e r a t u r e range 105-135° (where t h e r e a c t a n t phase i s t h e racemate) and e x c e l l e n t l y a t 150° (where t h e r e a c t a n t phase i s t h e m e l t ) . I f the poor r e s o l v a b i l i t y a t 105-135° i s due t o t h e i n i t i a l p r e s e n c e o f b o t h R and S c r y s t a l l i t e s , then one would a t 150°, which i s n o t t h e c a s e . expect t h e growth o f b o t h forms also A more t e n a b l e e x p l a n a t i o n i n v o l v e s t h e n u c l e a t i o n o f r a c e m i c m a t e r i a l from t h e racemate phase, b u t n o t from t h e m e l t phase. As mentioned e a r l i e r , t h e 1,1'-binaphthyl melt s u p e r c o o l s to a g r e a t e x t e n t , and c o m p l e t e l y m e l t e d samples w i l l remain a t 150° i n d e f i n i t e l y without c r y s t a l l i z a t i o n , unless c r y s t a l s are i n t e n t i o n a l l y added. A l t h o u g h growth on seed c r y s t a l s o c c u r s r e a d i l y a t 150°, n u c l e - a t i o n o f new c r y s t a l s does n o t . T h e r e f o r e a h i g h degree o f r e s o l u t i o n may o c c u r a t 150° b u t n o t a t 105-135°. The S - l and S-3 K i n e t i c B a t c h e s r e s o l v e t o g r e a t e r than 82% r e s o l u t i o n a t a l l temperatures s t u d i e d . The f a i l u r e t o a t t a i n total r e s o l u t i o n ( [ a ] = i245°) i n t h e s e b a t c h e s i s p r o b a b l y due t o c r y s t a l s o f unwanted R enantiomer p r e s e n t i n i t i a l l y , r a t h e r than t o n u c l e a t i o n , s i n c e t h e r e i s no improvement i n r e s o l u t i o n w i t h these samples a t 150°, where 117 n u c l e a t i o n i s absent. The changes on s t o r a g e o f the S-2 K i n e t i c B a t c h over s e v e r a l months i s c o n s i s t e n t both w i t h n u c l e a t i o n and w i t h the presence enantiomer. On one hand, the improved e x t e n t o f r e s o l u t i o n o f the m a t e r i a l on s t o r a g e c o u l d be due causing n u c l e a t i o n of A n n e a l i n g i s made p o s s i b l e racemic by the r e l i e f o f s u r f a c e and s t r a i n f r e e e n e r g i e s i n the p o l y c r y s t a l l i n e sample. the presence S-2 to the p a r t i a l a n n e a l i n g out of the c r y s t a l i m p e r f e c t i o n s and b o u n d a r i e s material. o f unwanted On t h e o t h e r hand, o f unwanted enantiomer c o u l d be d i m i n i s h e d by a v e r y phase t r a n s f o r m a t i o n a t 0°, c o n v e r t i n g r a c e m i c slow e u t e c t i c form back t o the racemate. The s e c r e t to preparing 1,1'-binaphthyl which w i l l r e s o l v e w e l l h e a t i n g a t a l l temperatures e v i d e n t l y i n v o l v e s m i n i m i z i n g not o n l y the c r y s t a l s o f unwanted enantiomer, but a l s o the tendency o f the racemate t o n u c l e a t e r a c e m i c , e u t e c t i c form. is d i f f i c u l t Although the l a t t e r requirement to c o n t r o l , i t can be a v o i d e d s i m p l y by p e r f o r m i n g r e s o l u t i o n a t 150°, on where t h e racemate m e l t s , and a l l b a t c h e s of b i n a p h t h y l p r e p a r e d by the s p e c i a l r e c r y s t a l l i z a t i o n - e v a p o r a t i o n the 1,1'pro- cedure (p 99) a t t a i n a v e r y h i g h degree o f r e s o l u t i o n . 3.5.2 Treatment o f R e s u l t s i n Terms of Rate Laws f o r S o l i d - S t a t e R e a c t i o n s Although some q u a l i t a t i v e c o n c l u s i o n s can be drawn from the k i n e t i c • r e s u l t s ( S e c t i o n 3.5.1), a more q u a n t i t a t i v e t r e a t m e n t can potentially p r o v i d e i n s i g h t i n t o the mechanism and e n e r g i e s i n v o l v e d i n the resolution. solid-state 118 As w i l l be seen, the r a t e e q u a t i o n s w h i c h have been developed s o l i d - s t a t e r e a c t i o n s i n v o l v e an e x p r e s s i o n o f y, the f r a c t i o n as a f u n c t i o n of t i m e . for transformed, I n t h i s r e s o l u t i o n r e a c t i o n , the f r a c t i o n t r a n s - formed i s c o n v e n i e n t l y t a k e n as the e x t e n t o f the phase t r a n s f o r m a t i o n racemate ->• e u t e c t i c form, r e g a r d l e s s of the f i n a l r o t a t i o n That i s , y = X^, where achieved. i s the mole f r a c t i o n o f 1 , 1 ' - b i n a p h t h y l the e u t e c t i c ( h i g h - m e l t i n g ) form. in A l t h o u g h X^ = 1 a t the end o f the t r a n s f o r m a t i o n , i t i s c l o s e t o but not e x a c t l y z e r o a t the b e g i n n i n g , s i n c e some s m a l l seed c r y s t a l s o f e u t e c t i c form e x i s t i n the material. initial Hence, b e f o r e the r e a c t i o n , the m a t e r i a l i s c o n s i d e r e d already s l i g h t l y as transformed. D u r i n g the r e s o l u t i o n , [a] was a f i n a l r o t a t i o n , [ a ] _ , was measured as a f u n c t i o n o f t i m e , attained. until I n t u i t i v e l y , i t would seem t h a t r [ a ] / [ a ] y = X^, but the c o n d i t i o n s under w h i c h t h i s e q u a l i t y w i l l h o l d s h o u l d be examined more c l o s e l y . I n any b a t c h of 1 , 1 - b i n a p h t h y l , 1 the o n l y phases p r e s e n t t h e racemate, c r y s t a l s o f R, and c r y s t a l s o f S. t h e e u t e c t i c form. (or \- -H •L *R- -F The [15] (or V W (or (or I t i s convenient The to d e f i n e the = mole f r a c t i o n o f R ( o r S) i n a l l are l a s t two c o n s t i t u t e following: phases = mole f r a c t i o n o f R ( o r S) i n e u t e c t i c ( h i g h - m e l t i n g ) form = mole f r a c t i o n of R ( o r S) i n racemate ( l o w - m e l t i n g ) X S-F> = mole f r a c t i o n o f R ( o r S) a t end of t r a n s f o r m a t i o n s p e c i f i c r o t a t i o n o f the sample a t a l l times i s : [ a ] = [ a ] S ( X S " V = C a ] R ( X R " V form 119 where [ct] = +245°, and [o]„ = -245°, the s p e c i f i c rotations of S R completely c resolved S and R-l,1'-binaphthyl, respectively. But since the racemate contains an equimolar , and since X quantity of S and R-l, 1'-binaphthyl, i . e . , = g + X_ g and X^ = X^ ^ + L = then the difference i n mole fractions of S- and R-l,1'-binaphthyl i n a l l phases i s i d e n t i c a l to that only i n the eutectic form (Xg - X^ = - ^) and so i t i s always true that: [16] [] = [a]g(X _ a s - H X^) At the end of the transformation, X = X b—ri [17] [ ] a F - [a] (X _ s s - p and X^ b-r Ul l»l Consider now perfectly. - " -" " "*S X F S , so that: K—r X_) R p Therefore, i n a l l batches of p o l y c r y s t a l l i n e [18) = X K—n 1,1'-binaphthyl, H - F " *R-F a hypothetical sample of 1,1'-binaphthyl which resolves I f the resolution i s to pure S-enantiomer, then [a] = [a] . r b In such a r e s o l u t i o n , no nucleation of racemic material would occur, and the eutectic form would always consist only of growing S c r y s t a l s . Therefore, X _ g rioi H = X^, M - Lsl = X_ R X F = 0, X _ S-H " g = 1, and Equation 18 becomes: F „ 120 T h e r e f o r e , i n t h e p e r f e c t r e s o l u t i o n , w h i c h i s approached by t h e S - l ' and S-3 K i n e t i c Batches a t a l l t e m p e r a t u r e s s t u d i e d , and by t h e S-2 and R - l K i n e t i c Batches a t 150°, the e x t e n t o f t r a n s f o r m a t i o n , y, e q u a l s [a]/[a] . p I n t h e k i n e t i c runs where [a]., i s f a r from [ a ] o r [a]„, i t may c not be a c c u r a t e t o equate and [ c t ] / [ a ] p . I n t h e s e samples, (S-2 and R - l from 105-135°) where n u c l e a t i o n o f r a c e m i c m a t e r i a l can o c c u r t o a c o n s i d e r a b l e e x t e n t , s i t u a t i o n s can c o n c e i v a b l y a r i s e where X^. advances more r a p i d l y than [a]/[a]„. F o r example, e x t e n s i v e n u c l e a t i o n o f r r a c e m i c e u t e c t i c form o c c u r r i n g a t t h e b e g i n n i n g o f t h e t r a n s f o r m a t i o n would n o t i n c r e a s e [ a ] / [ a ] p but would i n c r e a s e X^. I n k i n e t i c runs where [ctjj, << [ a ] g , t h e r e f o r e , t h e e x t e n t t o w h i c h X^ i s a p p r o x i m a t e d by measured r o t a t i o n s s h o u l d be i n d e p e n d e n t l y d e t e r m i n e d . An independent measurement o f X^ can be performed by f o l l o w i n g t h e r e s o l u t i o n r e a c t i o n by X-ray powder d i f f r a c t i o n . We t h e r e f o r e m o n i t o r e d t h e r e s o l u t i o n o f t h e S-2 K i n e t i c B a t c h a t 125° ( F i g u r e 19, p 105, k i n e t i c r u n a f t e r f o u r months a t 0°) u s i n g q u a n t i t a t i v e X-ray powder photography. The method we used was s i m i l a r t o t h e " d i r e c t comparison 76a method" d e s c r i b e d by C u l l i t y . By c h o o s i n g one l i n e i n t h e d i f f r a c t i o n o p a t t e r n o f t h e racemate (d = 10.1 A) and one i n t h e p a t t e r n o f t h e o e u t e c t i c form (d = 6.4 A) w h i c h would be d i s t i n c t i n a m i x t u r e o f t h e two forms, t h e d i s a p p e a r a n c e o f racemate and t h e appearance o f e u t e c t i c c o u l d be q u a n t i t a t i v e l y f o l l o w e d . A standard procedure f o r the develop- ment o f t h e powder photographs was d e v i s e d , so t h a t when the d e v e l o p e d photographs were a n a l y z e d on a m i c r o d e n s i t o m e t e r , t h e r e s u l t i n g peak a r e a s were r e p r o d u c i b l e . A c a l i b r a t i o n c u r v e ( F i g u r e 23) r e l a t i n g t h e 121 WEIGHT FRACTION F i g u r e 23. H (.. ... ) C a l i b r a t i o n c u r v e f o r q u a n t i t a t i v e phase a n a l y s i s by X - r a y powder photography. 122 peak "area fraction" of eutectic (high-melting) form (A^/A^tA^) to the weight fraction of eutectic form (W„/W„+W ) was constructed by analyzing T H known mixtures of the two forms. n L In several cases (e.g. at a weight fraction of 0.435) more than one sample was taken from the known phase mixture, to check the reproducability of the method. These multiple analyses agreed to within 2%. Samples of the S-2 Kinetic Batch were held at 125°for various lengths of time, then cooled to room temperature and analyzed for specific rotation as well as for phase content. Figure 24, which shows how The results are plotted in [ot]/[a]p depends on X^. The straight diagonal represents the case where [a]/[a]p = X^. As shown by the results given ±h the Figure, the development of optical activity, even in samples of 1,1'-binaphthyl which do not resolve well, is rather closely parallelled by the phase change racemate eutectic form. The i n i t i a l S-2 material contains some eutectic form, as expected from i t s i n i t i a l activity of [a] = +11.8°. However, the extent of phase transformation i s rather small considering the i n i t i a l rotation, implying that the eutectic form in the sample is pure S. For i f no R crystals were present, X^ = Xg_^ and from Equation 19, X^ = Xg_ [a]/[a] = 11.8/245 = 0.0482. c H = If R crystals existed in the i n i t i a l sample, X^ would be even larger. This result verifies the conclusion in Section 3.5.1 that the S-2 sample resolves poorly because of nu- cleation of racemic material rather than the presence of R crystals in the i n i t i a l sample. To a good approximation, then, the extent of transformation is given by [a]/[a]„. r One would expect that the approximation would improve F i g u r e 24. Development o f s p e c i f i c r o t a t i o n w i t h e x t e n t o f phase transformation at 0°). ( X ^ ) , S-2 K i n e t i c B a t c h a t 125° Diagonal represents the c o n d i t i o n ( a f t e r f o u r months' [a]/[ct] = storage 124 as [a] F approached [a] o (or [a] ) , u n t i l i n the perfect r e s o l u t i o n , as K discussed above, [ a ] / [ a ] ^ must equal X^. With this assurance, an analysis of the k i n e t i c r e s u l t s according to rate laws can now be conducted. The k i n e t i c s of reactions i n s o l i d s consisting i n i t i a l l y of a single component have been considered i n some d e t a i l i n two major f i e l d s of research. The k i n e t i c s of phase transformations have received con87 88 siderable i n t e r e s t i n metallurgy, ' and the k i n e t i c behaviour of 89 1 decomposition reactions (more inorganic explored rather widely i n chemistry. than organic ) has been However, from a l l of these i n - vestigations one must conclude that there exists no universal rate equation which describes the k i n e t i c s of a l l reactions i n s i n g l e s o l i d components. The t h e o r e t i c a l approaches to such s o l i d - s t a t e reactions find i l l u s t r a t i o n i n a l i m i t e d number of systems, and often describe 89 only the i n i t i a l or f i n a l part of a reaction. On the other hand, empirical rate equations known to apply to a larger number of systems 90 are d i f f i c u l t to interpret exactly i n terms of reaction mechanisms. The complexities of many s o l i d - s t a t e reactions have even led to the development of methods of treating k i n e t i c results i n the absence of A „. 88,91,92 any assumed rate equation. 88 Of the empirical rate equations that have been developed, two are most widely used. The f i r s t of these, usually called the Avrami- 90 93 Erofeev Equation i n inorganic chemistry ' or the Johnson-Mehl92 Avrami Equation i n metallurgy appears, i n d i f f e r e n t i a l form, as: [20] g = k" t " " 1 (1-y) 125 and i n i n t e g r a t e d form, as: [21] y = 1 - exp(- -f t ) n or: l o g logC^T") [22] = n log(t) + n log(k ) 6 Agreement w i t h t h i s r a t e e x p r e s s i o n w i l l - l o g ( 2 . 3 0 3 n) t h e r e f o r e be r e v e a l e d l i n e a r i t y o f a p l o t of l o g l o g ( ^ ') v s . l o g ( t ) . done f o r a l l f o u r k i n e t i c b a t c h e s , F i g u r e s 25 and by Such an a n a l y s i s was two o f w h i c h a r e i l l u s t r a t e d i n 26. 89 The second commonly used r a t e law i s the Prout-Tompkins E q u a t i o n , w h i c h i n d i f f e r e n t i a l form i s : & [23] = k 7 y (1-y) and w h i c h i n t e g r a t e s t o : logC^O [24] = k 7 t + constant The r e s o l u t i o n k i n e t i c s of a l l b a t c h e s were t r e a t e d a c c o r d i n g equation, to t h i s and some r e p r e s e n t a t i v e l o g ( j ^ - ) v s . time p l o t s a r e shown i n F i g u r e s 27 and 28. 58 90 93 I n t h e r e c e n t a c c o u n t s of s o l i d - s t a t e r e a c t i o n k i n e t i c s , ' ' i t has been emphasized t h a t c a u t i o n s h o u l d be used i n i n t e r p r e t i n g any apparent f i t of e m p i r i c a l r e s u l t s t o s o l i d - s t a t e r a t e e q u a t i o n s . Kinetic ' 2.5 3.0 3.5 4.0 LOG F i g u r e 25. binaphthyl, 4.5 5.0 5.5 6.0 6.5 (TIME, SECONDS) Avrami-Erofeev p l o t s f o r the s o l i d - s t a t e r e s o l u t i o n o f n e a t , p o l y c r y s t a l l i n e , 1,1'S - l K i n e t i c Batch at 135° and 105°. a g a i n s t l o g ( t i m e , seconds) + 1 . The sample s t o r e d s i x weeks a t 25° i s p l o t t e d ^ 2.5 3.0 3.5 4.0 LOG 26. 4.5 5.0 5.5 6.0 6.5 (TIME, SECONDS) Avrami-Erofeev p l o t s f o r the s o l i d - s t a t e r e s o l u t i o n of n e a t , p o l y c r y s t a l l i n e 1, b i n a p h t h y l , S-2 K i n e t i c Batch a t 135°, 125° ( o r i g i n a l r u n ) , 115°, and 105°. + 1.5 +1.0 +0.5 4 u o 0.0 -0.5 -1.0 O A O O r i g i n a l k i n e t i c run A Run performed a f t e r s i x weeks' s t o r a g e a t 25 c O Run u s i n g ground samples -1.5 A 10 20 _L 30 J_ 40 50 60 70 80 90 100 110 120 TIME (MINUTES) F i g u r e 27. Prout-Tompkins p l o t s f o r the s o l i d - s t a t e r e s o l u t i o n o f n e a t , p o l y c r y s t a l l i n e 1,1'- b i n a p h t h y l , S - l K i n e t i c Batch a t 135°. E f f e c t of g r i n d i n g and o f s t o r a g e a t 25° f o r s i x weeks. +1.0 S-2 K i n e t i c B a t c h 10 15 20 25 TIME F i g u r e 28. Prout-Tompkins 30 35 40 (HOURS) p l o t s f o r the s o l i d - s t a t e r e s o l u t i o n of n e a t , p l o y c r y s t a l l i n e b i n a p h t h y l , S-2, S-3 and R - l K i n e t i c Batches at 115°. 50 45 1,1'- 130 r e s u l t s s h o u l d , wherever p o s s i b l e , be supplemented by a d d i t i o n a l i n f o r m a t i o n , such as the d i r e c t o b s e r v a t i o n of the n u c l e a t i o n and growth under the m i c r o s c o p e . processes Indeed, t h e r e a r e even cases o f agreement w i t h 58 b o t h the A v r a m i - E r o f e e v and Prout-Tompkins E q u a t i o n s , 89 ' and i n such cases r e c o u r s e must be made t o n o n - k i n e t i c o b s e r v a t i o n s b e f o r e any mechanism can be proposed. Even when the f i t i s poor when the e n t i r e r e a c t i o n i s c o n s i d e r e d t h e r e has been a tendency to l o o k f o r s t r a i g h t p o r t i o n s 21 89 over o n l y p a r t of the r e a c t i o n ' ( e . g . , y = 0.2 to y = 0.5), the j u s t i f i c a t i o n f o r t h i s b e i n g t h a t d i f f e r e n t mechanisms a p p l y to d i f f e r e n t p a r t s o f the r e a c t i o n . However, any m e a n i n g f u l a n a l y s i s from such p a r t i a l f i t s s h o u l d be backed by many k i n e t i c p o i n t s known v e r y p r e c i s e l y , as w e l l as by a d d i t i o n a l o b s e r v a t i o n s . No m i c r o s c o p i c o b s e r v a t i o n s of the s o l i d - s t a t e r e s o l u t i o n of b i n a p h t h y l were made, so t h a t any 1,1'- i n t e r p r e t a t i o n o f the e m p i r i c a l p l o t s must be c o n s i d e r e d as s u b j e c t to v e r i f i c a t i o n by independent methods. L e t us c o n s i d e r f i r s t The s l o p e of Equation the A v r a m i - E r o f e e v p l o t s ( F i g u r e s 25 and 22 g i v e s the exponent n ( T a b l e X I V ) . W i t h the S - l K i n e t i c B a t c h the r e s u l t s f i t a s t r a i g h t l i n e ( w i t h n n e a r two) well. L e s s p e r f e c t f i t s a r e found w i t h the S-3 rather and R - l m a t e r i a l (not shown), where the p l o t i s b e t t e r d e s c r i b e d a t some t e m p e r a t u r e s by s t r a i g h t l i n e s (both s l o p e s a r e l i s t e d i n T a b l e X I V ) . bend o c c u r s w i t h the S-2 s l o p e s o f c a . 0.65 The and K i n e t i c Batch 1.7 at a l l four 26). The most ( F i g u r e 2 6 ) , which g i v e s two obvious limiting temperatures. s t r a i g h t l i n e o b t a i n e d w i t h the S - l m a t e r i a l m e r i t s some discussion. The exact m e c h a n i s t i c i m p l i c a t i o n o f t h i s f i t i s not gether c e r t a i n , c o n s i d e r i n g that Equation alto- 21 has been d e r i v e d i n a number 131 T a b l e XIV A v r a m i - E r o f e e v Exponents f o r the S o l i d - S t a t e R e s o l u t i o n of 1 , 1 ' - B i n a p h t h y l K i n e t i c Batch Temperature, °C S-l Exponent 135.0 1.8 II 135.0 II 105.1 S-2 135.0 0.7 to 1.6 b 124.9 0,7 to 1.9 b 114.9 0.6 to 1.6 b 105.1 0.6 to 1.6 b it it it S-3 tt 2.0 a 1.8 135.0 1.6 124.9 1.7 II 114.9 1.2 to 1.7 b II 105.1 0.8 t o 1.3 b R-l 135.0 1.0 t o 2.0 tt it it 124.9 1.0 114.9 0.7 105.1 0.8 Run performed a f t e r s i x weeks' s t o r a g e a t 25°. Minimum and maximum v a l u e s . 132 of d i f f e r e n t w a y s . ^ ' ^ One D common i n t e r p r e t a t i o n " ^ ' ^ of t h e exponent n i s t h a t i t i s composed o f two q u a n t i t i e s , namely, n = 3 + X. The exponent B r e f e r s t o the number of s t e p s r e q u i r e d t o form a n u c l e u s , and i s r e v e a l e d i n a power law o f t h e type N = k t , where N i s the number o f n u c l e i formed i n time t . The number B i s u s u a l l y determined from the i n i t i a l k i n e t i c s o f a s o l i d r e a c t i o n o r from c o u n t i n g the n u c l e i under a m i c r o s c o p e 3.5.1 as a f u n c t i o n o f t i m e . However, as shown i n S e c t i o n (p 103), the S - l and S-3 K i n e t i c Batches o f new m a t e r i a l , so t h a t S = 0. The visible do not undergo n u c l e a t i o n exponent X i s the number o f dimen- s i o n s i n w h i c h growth of e x i s t i n g p r o d u c t c r y s t a l l i t e s occurs. Hence our o b s e r v a t i o n of n = X = 2 w i t h the S - l m a t e r i a l can be t a k e n as p l y i n g t h a t the growing S crystallites spread i n two dimensions f o r example, p r e f e r r e d l a t t i c e p l a n e s o r b o u n d a r i e s im- along, between racemate crystallites. Although lower v a l u e s o f n r e s u l t from p l o t s of t h e o t h e r k i n e t i c b a t c h e s , t h e s e have l i t t l e s i g n i f i c a n c e i n v i e w of the r a t h e r poor f i t . The S-2 K i n e t i c Batch partway through the r e a c t i o n , but the k i n e t i c p o i n t s a r e too i m p r e c i s e to j u s t i f y such an The ( F i g u r e 26) might s u f f e r a change i n mechanism interpretation. r a t e c o n s t a n t k^ ( E q u a t i o n s 20-22) has a t e d from a p l o t o f [ l o g ( ^ •) ] " ^ n sometimes been e v a l u - a g a i n s t t i m e , once n has been d e t e r - 58 mined. T h i s procedure a l l o w s the d e t e r m i n a t i o n o f an 88 energy, but t h e r e have been o b j e c t i o n s activation to the comparison of a c t i v a t i o n energies to those f o r other molecular processes. such This o b j e c t i o n i s based on the f a c t t h a t k^ a r i s e s i n a r a t e e q u a t i o n e x p r e s s i n g dy/dt i n terms of time as w e l l as y ( E q u a t i o n 2 0 ) , whereas 133 the most commonly encountered r a t e c o n s t a n t r e s u l t s from an e x p r e s s i o n 88 of dy/dt as a f u n c t i o n o f y o n l y . The Prout-Tompkins y = 0.3 ( l o g ( j ~ ) - 0.37) p l o t s ( F i g u r e 27-28) show l i n e a r i t y beyond f o r a l l k i n e t i c batches. Prout-Tompkins o f t e n show two s t r a i g h t l i n e s , y i e l d i n g r a t e c o n s t a n t s which may 44b 58 may not have t h e same a c t i v a t i o n e n e r g i e s . c a s e , t h e r e may be a second ' l i n e o f g r e a t e r s l o p e below y = 0.3, The r a t e c o n s t a n t s d e r i v e d from the Prout-Tompkins has been done i n F i g u r e 29. possibility. p l o t s are f o r the S - l , S-2, S-3, Such a p l o t The A r r h e n i u s a c t i v a t i o n e n e r g i e s , c a l c u - l a t e d from 2.303 R ( s l o p e o f l i n e ) , a r e 57.7, 1 62.5, 59.4 and R - l K i n e t i c B a t c h e s , The t h e o r e t i c a l b a s i s f o r the Prout-Tompkins and 67.0 the p o l y c r y s t a l l i n e s o l i d . kcal respectively. Equation l i e s i n c o n s i d e r i n g t h e r e a c t i o n as p r o c e e d i n g by a b r a n c h i n g p r o c e s s 90 spreads throughout but S i n c e the c o n s t a n t k^ i s d e f i n e d i n terms o f y o n l y ( E q u a t i o n 2 3 ) , an a c t i v a t i o n p l o t i s w o r t h w h i l e . mole or I n the 1 , 1 ' - b i n a p h t h y l t h e r e a r e f a r too few p o i n t s i n t h i s r e g i o n t o v e r i f y t h i s l i s t e d i n T a b l e XV. plots which While the exact nature o f the b r a n c h i n g s p e c i e s i s u n c e r t a i n , one l i k e l y mechanism i n v o l v e s the s p r e a d o f r e a c t i o n p r o d u c t a l o n g g r a i n b o u n d a r i e s , dislocations, and t h e l i k e , c a u s i n g t h e b r e a k i n g a p a r t o f r e a c t a n t c r y s t a l l i t e s 58 t h e c r e a t i o n o f new avenues f o r the advance of the p r o d u c t . and Since i n the case o f the S - l and S-3 K i n e t i c B a t c h e s , h i g h r e s o l u t i o n s were o b t a i n e d , the c h a i n b r a n c h i n g p r o c e s s i s most l i k e l y a growth o n l y and does not i n v o l v e the n u c l e a t i o n of new That growth from E q u a t i o n 23. process material. i s a b r a n c h i n g p r o c e s s can be seen qualitatively The r a t e of t r a n s f o r m a t i o n depends both on the amount 134 2.20 2.30 2.40 1 TEMPERATURE Figure 29. 3 X 1 0 (DEGREES 2.50 -1 ) Relation of log (k^) (from Prout-Tompkins plots) temperature for the s o l i d - s t a t e resolution 1,1'-binaphthyl, a l l four k i n e t i c batches. squares f i t s to data for each batch. to r e c i p r o c a l of neat, p o l y c r y s t a l l i n e Straight l i n e s are least 135 T a b l e XV Prout-Tompkins Rate C o n s t a n t s ( k ^ ) f o r t h eS o l i d - S t a t e R e s o l u t i o n o f 1,1'-Binaphthyl i i n k^ x 10 K i n e t i c Batch Temperature, °C S-l 135.0 II 135.0 a 103.6 II 135.0 b 377.1 II 105.1 S-2 135.0 it 124.9 ti 114.9 2.766 II 105.1 0.4638 S-3 135.0 514.3 It 124.9 100.8 II 114.9 If 105.1 R-l 135.0 II 124.9 II 114.9 4.782 II 105.1 0.4216 sec 107.6 Run performed a f t e r s i x weeks' s t o r a g e a t 25°. Run performed w i t h ground samples. 5 0.4036 194.8 22.71 11.45 1.733 340.7 25.11 - 1 136 of m a t e r i a l t r a n s f o r m e d (y) and t h a t which has n o t y e t r e a c t e d (1-y). 44b 88 The r a t e e q u a t i o n i s t h a t o f an a u t o c a t a l y t i c r e a c t i o n . ' In order f o r a dependence on y, t h e p r o d u c t ( c r y s t a l s o f pure enantiomer) must be a v a i l a b l e t o t h e r e a c t a n t ( t h e r a c e m a t e ) , a s i t u a t i o n w h i c h i s approached i f the product i s h i g h l y dispersed. This i s i n contrast to i n d i v i d u a l , compact spheres o f growing p r o d u c t , w h i c h would i s o l a t e t h e r e a c t a n t phase from much o f t h e p r o d u c t . Some a t t e n t i o n s h o u l d now be g i v e n t o t h e r a t h e r l a r g e a c t i v a t i o n energy f o r t h e growth o f c r y s t a l s o f pure enantiomer t h r o u g h o u t t h e p o l y c r y s t a l l i n e racemate. For the r e s o l u t i o n to occur, 1,1'-binaphthyl m o l e c u l e s must be r e l e a s e d from t h e racemate c r y s t a l l i t e s , interconvert i n t h e r e a c t a n t - p r o d u c t i n t e r f a c e , then add t o t h e g r o w i n g p r o d u c t crystallites. The r a t e - d e t e r m i n i n g s t e p f o r t h e p r o c e s s cannot be s i m p l y t h e r e l e a s e o f m o l e c u l e s from t h e racemate t o an i n t e r f a c e r e s e m b l i n g t h e m e l t , s i n c e o n l y some 7 k c a l mole ^ a r e r e q u i r e d t o m e l t the racemate ( S e c t i o n 3.3.2, p 7 5 ) . More p r o b a b l y , t h e s l o w e s t s t e p i n v o l v e s n o t o n l y t h e r e l e a s e o f 1 , 1 ' - b i n a p h t h y l from t h e racemate, b u t a l s o the simultaneous i n t e r c o n v e r s i o n of enantiomers. But t h e r a c e m i z - a t i o n o f 1 , 1 ' - b i n a p h t h y l i n n-heptane s o l u t i o n r e q u i r e s o n l y 21.7 —1 66 k c a l mole a c t i v a t i o n energy, a f i g u r e w h i c h , when added t o 7 k c a l mole \ i s s t i l l f a r from t h e o b s e r v e d 62 k c a l mole ^. The l a r g e s t p o s s i b l e energy increment a s s o c i a t e d w i t h t h e removal of m o l e c u l e s from a m o l e c u l a r c r y s t a l i s the h e a t o f s u b l i m a t i o n , a l s o c a l l e d t h e b i n d i n g energy, o f t h e c r y s t a l . Binding energies f o r aromatic h y d r o c a r b o n s a r e u s u a l l y o f t h e o r d e r o f 20 k c a l mole ^ ( a n t h r a c e n e i s -1 94 " f a i r l y t y p i c a l " a t 22 k c a l mole ). However, t h e energy (per m o l e c u l e ) r e q u i r e d t o remove a s i n g l e m o l e c u l e from i n s i d e a c r y s t a l t o t h e vapour 137 i s twice the energy (per molecule) needed to vaporize the entire c r y s t a l , since twice as many Van der Waals bonds are broken in the former case.'' Doubling the binding energy and adding the 21.7 kcal mole 1 required for enantiomer interconversion i s much closer to the a c t i v a t i o n energy of 62 kcal mole . 1 For 1,1'-binaphthyl, the heat of sublimation of the c r y s t a l can be estimated as follows. With nonpolar molecules, the heat of vaporization of the melt i s related empirically to the normal b o i l i n g point through , _ Trouton s r u l e : 95 AH • • vaporization — b.p. i = i „, , , - 1 , - 1 21 c a l deg mole 96 The b o i l i n g point of 1,1'-binaphthyl has been determined as 240° at a pressure of 13 t o r r , which converts to a b o i l i n g point of 410°C (638°K) at atmospheric pressure, using a common vapour pressure-temperature 97 -1 The heat of vaporization i s therefore 14.3 kcal mole nomograph. If AH . i s the same at 105-135°C as i t i s at 410°C (probably vaporization a crude approximation), and i f AH. . i s the same i n this * ' fusion r temperature r range as at 145°C, then; AH ^ , sublimation = AH^ . fusion + AH . _ . vaporization If the coordination number of the c r y s t a l i s n, then there are n/2 bonds per molecule i n the c r y s t a l , i . e . , vaporizing the entire c r y s t a l breaks n/2 bonds per molecule. However, i f a single molecule i s removed, a l l n bonds to i t must be broken. Therefore, twice the energy per molecule i s required. 138 from 105-135°C and a t a t m o s p h e r i c * f o r the l o w - m e l t i n g The pressure. T h e r e f o r e , AH (racemate) form i s 14.3 + 7.3 energy r e q u i r e d t o remove one = 21.6 , sublimation k c a l mole ^. 1,1'-binaphthyl molecule ( e f f e c t i v e l y , 2 &) i s t h e r e f o r e 43.2 k c a l mole to i n f i n i t y and i f the molecule must s i m u l t a n e o u s l y i n t e r c o n v e r t , the a c t i v a t i o n energy c o u l d be h i g h as 43.2 + 21.7 = 64.9 as kcal mole" . 1 Such a h i g h a c t i v a t i o n energy r e p r e s e n t s an upper l i m i t t o the s i m p l e b r e a k i n g of Van der Waals f o r c e s i n the racemate c r y s t a l a c companied by t h e c o n f o r m a t i o n a l f l i p w h i c h i n t e r c o n v e r t s e n a n t i o m e r s . The fact that 1,1'-binaphthyl seems t o r e q u i r e almost a l l o f t h i s energy to r e a c h the t r a n s i t i o n s t a t e means t h a t the m o l e c u l e needs c o n s i d e r a b l e freedom t o i n t e r c o n v e r t i n the r e a c t a n t - p r o d u c t i n t e r f a c e . o f a c t i v a t i o n would have t o be q u i t e f a v o u r a b l e i n r e a c t i o n t o be o b s e r v a b l e a t a l l . of 1 , 1 ' - b i n a p h t h y l solid The entropy o r d e r f o r the T h e r e f o r e , b o t h w i t h the resolution and the r a c e m i z a t i o n o f the ( + ) - d i a c i d 29_ i n the phase, a h i g h a c t i v a t i o n energy i s observed and i s compensated by a h i g h a c t i v a t i o n e n t r o p y , f a c i l i t a t i n g the s o l i d - s t a t e r e a c t i o n s . In summary, we s h o u l d emphasize t h a t a l t h o u g h some h i g h degree o f c o n t r o l can be e x e r c i s e d over the s o l i d - s t a t e r e s o l u t i o n each p r e p a r e d b a t c h remains an i n d i v i d u a l . such i n t e r f a c e - c o n t r o l l e d of 1,1'-binaphthyl, The k i n e t i c c o m p l e x i t i e s o f s o l i d - s t a t e r e a c t i o n s s h o u l d n o t , however, overshadow the s i g n i f i c a n t f a c t t h a t r e a c t i o n s i n o r g a n i c s o l i d s can o c c u r w i t h f a c i l i t y and w i t h f a s c i n a t i n g s t e r e o c h e m i c a l consequences. 139 3^6 The Spontaneous Generation of Optically Active 1,1'-Binaphthyl ' In this section are described some experiments involving the crystallization of 1,1'-binaphthyl from the melt in a closed system. These experiments grew out of our earlier attempts (Section 3 . 4 . 2 , p 9 1 ) to obtain, reproducibly, 1,1'-binaphthyl of high specific rotation by seeding the supercooled melt in open test tubes. A few preliminary crystallizations in sealed ampules in which optically active seeds were purposefully excluded had shown that optical activity could develop even in a closed system consisting i n i t i a l l y of a racemic 1,1'-binaphthyl meltc Both enantiomers could be obtained. It then became of interest, as a separate problem, to examine the behaviour of a large number of individual sealed samples, keeping a tally of the direction and magnitude of the specific rotations obtained. Accordingly, two hundred individual ampules containing about 20 mg of carefully weighed 1,1'-binaphthyl crystals (from various racemic batch preparations) were sealed and then held, in groups of twelve, at temperatures of 170 to 185° for five minutes to melt and destroy a l l forms of solid 1,1'-binaphthyl,, The totally melted samples were then quickly transferred to a bath maintained at 1 5 0 ° . At this temperature the melt w i l l remain supercooled almost indefinitely. Crystallization was induced, however, by removing each sample, holding i t against a piece of Dry Ice for a few seconds, then quickly replacing i t in the 150° bath. In this manner, a small area of the bulk of the melt was cooled drastically, forming some seed crystals on which the remaining melt could crystallize at 1 5 0 ° . three hours. Crystallization was complete within The solid samples were then cooled to room temperature, 140 opened, and a n a l y z e d f o r o p t i c a l a c t i v i t y . The m a t e r i a l o b t a i n e d was almost always o p t i c a l l y a c t i v e , a l t h o u g h e x c e s s i v e a p p l i c a t i o n o f the c o o l i n g Dry I c e r e s u l t e d i n no a c t i v i t y . These few cases of s p e c i f i c r o t a t i o n s l e s s than -2° were not c o n s i d e r e d i n the f o l l o w i n g statistical analysis. The d i s t r i b u t i o n of the 200 s p e c i f i c r o t a t i o n s i s shown i n F i g u r e 30, w h i c h i s a p r e s e n t a t i o n o f p e r c e n t a g e of o b s e r v a t i o n s f a l l i n g various rotations. [a] is = -218° within The l a r g e s t o b s e r v e d r o t a t i o n s o f the 200 were and +206° ( o p t i c a l l y pure l , l ' - b i n a p h t h y l (Appendix A, p 178) [a] = ^245°) ; however, as shown, samples o f low r o t a t i o n ("±2° t o ±48°) were most common. The o b s e r v e d r o t a t i o n s f i t a G a u s s i a n d i s t r i b u t i o n w i t h a mean o f [a] = +0.14°and a s t a n d a r d d e v i a t i o n of 86.4°.^ From t h i s d i s t r i b u t i o n i t i s apparent t h a t o b t a i n i n g 1 , 1 ' - b i n a p h t h y l w i t h an o p t i c a l p u r i t y above 90% by t h i s method would be a v e r y e x c e p t i o n a l event ( o b s e r v a b l e about once i n 150 trys). The symmetry of the d i s t r i b u t i o n i s r e f l e c t e d i n F i g u r e 31 by the r a t i o o f t h e number o f S-(+) samples t o t h e t o t a l number of samples p l o t t e d f o r two runs of 100 samples each. i n c r e a s e s , the r a t i o tends toward 0.5 As the t o t a l number o f samples and i t f a l l s a t a l l p o i n t s w e l l w i t h i n the 99% c o n f i d e n c e l i m i t s c a l c u l a t e d f o r a p r o b a b i l i t y of 50% and 50% (-) of samples. (+) A f t e r 200 independent c r y s t a l l i z a t i o n s , the number d e x t r o r o t a t o r y samples o b t a i n e d (95) i s i n s i g n i f i c a n t l y different from the number of l e v o r o t a t o r y samples o b t a i n e d (105) . ^ I f the cases of [a] = 0° o b t a i n e d from o v e r c o o l i n g the samples were i n c l u d e d i n t h i s t r e a t m e n t , the symmetry o f the d i s t r i b u t i o n would, of c o u r s e , be p r e s e r v e d , but the s t a n d a r d d e v i a t i o n would be reduced. 141 F i g u r e 30, P e r c e n t a g e o f 1 , 1 ' - b i n a p h t h y l samples g i v i n g s p e c i f i c between ±240°. calculated The c u r v e shows t h e G a u s s i a n normal distribution f o r t h e mean o f +0.14° and s t a n d a r d d e v i a t i o n o f 86.4°. rotations 142 j~ 5 F i g u r e 31. r~ IO 1 ~r~' 20 i " 30 1 1 AO 1 50 1 eO 1 1 TO R a t i o o f samples h a v i n g p o s i t i v e r o t a t i o n s as two s e t s o f 100 each. calculated 1 Number of Samples of samples o f 1 , 1 ' - b i n a p h t h y l c r y s t a l l i z e d treated 1 a t 150°. 1 1 80 1 90 r— 1 lOO t o t h e t o t a l number The 200 samples a r e The c u r v e s a r e c o n f i d e n c e limits f o r a 0.99 degree o f c o n f i d e n c e and a p r o b a b i l i t y o f 50% p o s i t i v e and 50% n e g a t i v e f o r each sample. 1 143 An i m p o r t a n t c o n c l u s i o n can be drawn from the symmetric distribution. probability The development o f o p t i c a l a c t i v i t y i n each sample was d e t e r m i n e d by o n l y t h e chance f o r m a t i o n of R o r S c r y s t a l s from t h e r a c e m i c melt. The g e n e r a t i o n of o p t i c a l a c t i v i t y i n the 1 , 1 ' - b i n a p h t h y l system i s t r u l y spontaneous. H e r e , "spontaneous" i s t a k e n as meaning " p e r t a i n i n g o n l y t o t h e system i t s e l f . " A spontaneous r e s o l u t i o n , t h e r e f o r e , o c c u r s when measurable o p t i c a l a c t i v i t y i s produced from a t o t a l l y r a c e m i c system i n the complete absence o f e x t e r n a l d i s s y m m e t r i c i n f l u e n c e s o f any t y p e - p h y s i c a l , c h e m i c a l , o r human. The p r o b a b i l i t y d i s t r i b u t i o n o f a l a r g e number o f i n d i v i d u a l r e s o l u t i o n s i s a s e n s i t i v e check f o r the p r e sence o f any such e x t e r n a l i n f l u e n c e , w h i c h w i l l be r e v e a l e d as a mean s p e c i f i c r o t a t i o n s i g n i f i c a n t l y d i f f e r e n t from z e r o , and as a g r e a t e r number of samples of one handedness t h a n the o t h e r , as shown by an approach to t h e 99% l i m i t s o f c o n f i d e n c e c a l c u l a t e d f o r t h e t o t a l l y random s i t u a t i o n . A l t h o u g h the spontaneous g e n e r a t i o n o f o p t i c a l i s o m e r s i n a t o t a l l y symmetric environment seems i n t u i t i v e l y r e a s o n a b l e , i t has n e v e r b e f o r e 98 been c a r e f u l l y d e m o n s t r a t e d . served. I n f a c t , q u i t e t h e o p p o s i t e has been ob- The r e p o r t e d examples of a t t e m p t s t o e l i m i n a t e a l l d i s s y m m e t r i c 98 99 i n f l u e n c e s from s e v e r a l systems, w h i c h a r e r e c e n t l y r e v i e w e d shown a tendency f o r p r e f e r e n t i a l c r y s t a l l i z a t i o n of one T h i s may ' have enantiomorph. s i m p l y be a r e f l e c t i o n on the s m a l l number of i n d i v i d u a l trials i n some i n v e s t i g a t i o n s ( a f t e r 10 samples, even 1 , 1 ' - b i n a p h t h y l showed e i g h t n e g a t i v e and two p o s i t i v e r o t a t i o n s ) , but n e v e r t h e l e s s , such apparent b i a s has engendered the f e e l i n g t h a t the t o t a l l y symmetric experiment i s e i t h e r e x t r e m e l y d i f f i c u l t because of omnipresent o p t i c a l l y active impurities o r c o m p l e t e l y i m p o s s i b l e because o f a weak d i s s v m - 144 m e t r i c b i a s i n the u n i v e r s e . of 101 The f a c t t h a t 1 , 1 ' - b i n a p h t h y l i s c a p a b l e t r u l y spontaneous r e s o l u t i o n not o n l y proves t h a t such a phenomenon i s p o s s i b l e , but a l s o t h a t d i s s y m m e t r i c m a t e r i a l s w h i c h were almost certain p r e s e n t as d u s t p a r t i c l e s or l e s s w e l l d e f i n e d d i s s y m m e t r i c f o r c e s , do n o t always i n f l u e n c e the development o f o p t i c a l a c t i v i t y . Perhaps one c o u l d say t h a t because 1 , 1 ' - b i n a p h t h y l i s a r e l a t i v e l y u n n a t u r a l compound, its n u c l e a t i o n and c r y s t a l l i z a t i o n i s i n s e n s i t i v e t o d i s s y m m e t r i c p u r i t i e s d e r i v e d from life. The q u e s t i o n t h e r e f o r e a r i s e s as t o w h i c h , i f any, m a t e r i a l s can i n f l u e n c e t h e 1 , 1 ' - b i n a p h t h y l r e s o l u t i o n . performed im- dissymmetric We t h e r e f o r e s e v e r a l i n d i v i d u a l c r y s t a l l i z a t i o n s i n the p r e s e n c e o f b o t h d- and 1-mandelic acid (37) . The a d d i t i o n of 5% by w e i g h t o f d-mandelic OH 37 a c i d i n experiments at 130° s i m i l a r to t h o s e d e s c r i b e d above produced 1 , 1 ' - b i n a p h t h y l w i t h an excess (+) r o t a t i o n ( a f t e r c o r r e c t i n g f o r the s m a l l r o t a t i o n a r i s i n g from m a n d e l i c a c i d ) i n 18 out o f 19 samples. the o t h e r hand, 5% 1-mandelic (-) On a c i d i n 1 , 1 ' - b i n a p h t h y l gave samples w i t h r o t a t i o n s i n 17 t r i e s out o f 17. These d i s t r i b u t i o n s f a l l well o u t s i d e those c a l c u l a t e d f o r a 50-50 p r o b a b i l i t y and they i n d i c a t e t h a t the c o n f i g u r a t i o n o f m a n d e l i c a c i d e s s e n t i a l l y c o m p l e t e l y c o n t r o l s c o n f i g u r a t i o n of 1 , 1 ' - b i n a p h t h y l o b t a i n e d . the 145 It i s possible t o d i s t i n g u i s h t h r e e t y p e s o f systems i n w h i c h spontaneous r e s o l u t i o n i s p o s s i b l e . The f i r s t , e x e m p l i f i e d by R- and S- 1 , 1 ' - b i n a p h t h y l , i s a system i n w h i c h c r y s t a l l i z a t i o n can o c c u r from a racemic l i q u i d c o n t a i n i n g rapidly interconverting p r e s e n c e o f a mechanism f o r i n t e r c o n v e r s i o n enantiomers. means t h a t t h e system f i n i s h e s c r y s t a l l i z i n g i n a thermodynamically s t a b l e s t a t e . f i n a l p r o d u c t can t h e r e f o r e activity The The be a n a l y z e d a t l e i s u r e f o r any o p t i c a l (provided, of course, that interconversion room t e m p e r a t u r e t o p e r m i t a n a l y s i s ) . c r y s t a l l i z a t i o n from s o l u t i o n r a t h e r i s s l o w enough a t Other examples, involving than from t h e m e l t , a r e t h e systems 102 and ( - ) - m e t h y l e t h y l a l l y l a n i l i n i u m i o d i d e (38) and ( + ) - and ( - ) 103 t r i - o - t h y m o t i d e (39) . A l t h o u g h t h e s e systems d e v e l o p o p t i c a l a c t i v i t y (+)- CH 3 38 39 from a r a c e m i c s o l u t i o n , t h e number o f samples t a k e n i n each i s too few to d e c i d e whether d i s s y m m e t r i c i m p u r i t i e s are i n f l u e n c i n g i . e . , whether o r n o t t h e r e s o l u t i o n i s t r u l y the r e s o l u t i o n , spontaneous. The second t y p e o f system i n which i t might be p o s s i b l e s t r a t e spontaneous t o demon- r e s o l u t i o n i s one i n w h i c h enantiomers a r e o p t i c a l l y s t a b l e , but a s o l u t i o n ( o r melt) i s only p a r t i a l l y c r y s t a l l i z e d . In 146 such a system, t o t a l c r y s t a l l i z a t i o n would, o f c o u r s e , l e a d t o a racemic batch of c r y s t a l s . In a p a r t i a l c r y s t a l l i z a t i o n , the c r y s t a l s c o u l d w e l l have an excess o f one enantiomer w h i l e t h e l i q u i d phase cont a i n s an excess o f t h e o t h e r . However, t h i s r e p r e s e n t s an u n s t a b l e s t a t e , s i n c e t h e l i q u i d phase w i l l always be s u p e r s a t u r a t e d i n one e n a n t i o m e r , and t h e two phases must be s u c c e s s f u l l y s e p a r a t e d (by f i l t r a t i o n ) without d i s t u r b i n g the metastable l i q u i d . I n s p i t e of the 85 s e e m i n g l y p r e c a r i o u s p r o c e d u r e , t h i s method i s r a t h e r w i d e l y u s e d , t o r e s o l v e enantiomers under non-spontaneous p u r p o s e f u l a d d i t i o n o f seed c o n d i t i o n s (e.g. the crystals). The t h i r d system w h i c h can i n p r i n c i p l e show spontaneous resolution i s one w h i c h c o n t a i n s an a c h i r a l m o l e c u l e i n s o l u t i o n ( o r i n t h e m e l t ) . I f such a compound c r y s t a l l i z e s i n an enantiomorphous an excess o f m o l e c u l e s i n one enantiomorphous space g r o u p , then crystal constitutes, i n a sense, a r e s o l u t i o n of o p t i c a l l y a c t i v e c r y s t a l s . As w i t h t h e f i r s t t y p e o f system, t h e f i n a l s t a t e i s t h e r m o d y n a m i c a l l y s t a b l e . However, a n a l y s i s p r e s e n t s some p r o b l e m s , s i n c e i n an i n d i v i d u a l crop o f c r y s t a l s each must be weighed and examined f o r h e m i h e d r a l f a c e s o r o p t i c a l r o t a t i o n , b e f o r e i t can be c o n c l u d e d t h a t t h e g i v e n crop c o n t a i n e d an excess o f m o l e c u l e s i n one enantiomorphous crystal. S u f f i c i e n t crops must a l s o be examined b e f o r e any c o n c l u s i o n s as t o s p o n t a n e i t y can be 104 drawn. I n s p i t e o f t h i s time-consuming requirement, Soret examined 844 c r y s t a l l i z a t i o n s o f sodium c h l o r a t e from s o l u t i o n i n s e a l e d .ampules, and o b s e r v e d an excess o f r i g h t - h a n d e d c r y s t a l s i n 51.3% o f t h e samples, w h i l e 48.7% o f the samples had l e f t - h a n d e d c r y s t a l s i n e x c e s s . Other 105 results r e c o r d a w e i g h t e d average o f 50.08 d e x t r o r o t a t o r y crystals 147 from 46 independent c r o p s . As f a r as we know, t h i s i s the o n l y o t h e r c a r e f u l l y demonstrated case o f the spontaneous g e n e r a t i o n of o p t i c a l l y active material. U n l i k e t h e enantiomorphous sodium c h l o r a t e c r y s t a l , w h i c h loses a l l o p t i c a l a c t i v i t y i m m e d i a t e l y on d i s s o l u t i o n , the 1 , 1 ' - b i n a p h t h y l system i n v o l v e s t h e spontaneous c r e a t i o n of o p t i c a l l y a c t i v e molecules which r e t a i n t h e i r c o n f i g u r a t i o n f o r a c o n s i d e r a b l e l e n g t h of t i m e i n s o l u t i o n (at 0°). The r e s o l u t i o n o f 1 , 1 ' - b i n a p h t h y l i s t h e r e f o r e a s i m p l e i l l u s t r a t i o n o f C a l v i n ' s h y p o t h e t i c a l scheme"'"^ f o r t h e a u t o c a t a l y t i c s e l e c t i o n o f one enantiomer i n the g e n e s i s o f o p t i c a l l y a c t i v e m o l e c u l e s . 3.7 Conclusion The development o f o p t i c a l a c t i v i t y s i m p l y by h e a t i n g and a r a c e m i c m a t e r i a l l i k e 1 , 1 ' - b i n a p h t h y l seems, a t f i r s t impossible process. cooling t h o u g h t , t o be an The thought a r i s e s because t h e i n t e r c o n v e r s i o n o f enantiomers i n s o l u t i o n always l e a d s t o r a c e m i z a t i o n , n o t because o f an i n c r e a s e i n e n t r o p y due t o g r e a t e r d i s o r d e r . resolution, But i n g o i n g from such a homogeneous system t o a heterogeneous system such as the phases formed between two e n a n t i o m e r s , r e s o l u t i o n can become a p o s s i b l e , even p r o b a b l e , p r o c e s s . R e s o l u t i o n i s c o m p a t i b l e w i t h the achievement o f l o w e r f r e e energy because e n t h a l p y and e n t r o p y changes accompanying phase t r a n s f o r m a t i o n s can more than compensate f o r any l o s s e s i n f r e e energy due t o f o r m a t i o n of m o l e c u l e s of o n l y one k i n d . These l o s s e s a r e , i n f a c t , v e r y s m a l l . F o r example, even the most i n t i m a t e o f m i x t u r e s o f enantiomers - the l i q u i d s o l u t i o n of one i n the o t h e r - would l o s e o n l y 1.37 c a l deg ''"mole 148 o f e n t r o p y and no e n t h a l p y ( i n t h e case o f i d e a l s o l u t i o n s ) i n hypo46 t h e t i c a l l y c h a n g i n g from a r a c e m i c t o a f u l l y r e s o l v e d s t a t e . 150°, t h i s e n t r o p y change amounts t o 580 c a l mole 1 of free At energy. The e n t r o p y d i f f e r e n c e between t h e f a r l e s s i n t i m a t e m i x t u r e found i n a e u t e c t i c c o n g l o m e r a t i o n o f l a r g e a g g r e g a t e s ( c r y s t a l l i t e s ) o f pure e n a n t i o m e r s and t h e p o l y c r y s t a l l i n e s i n g l e enantiomer i s even smaller. I n f a c t , t h e e n t r o p y , e n t h a l p y and f r e e energy o f m i x i n g a r e i m p l i c i t l y t a k e n as z e r o when two pure s o l i d s form a m e c h a n i c a l m i x t u r e and t h e f r e e energy o f t h e m i x t u r e i s l i n e a r l y r e l a t e d t o i t s c o m p o s i t i o n . " ' Therefore, there i s l i t t l e , 1 i f any, thermodynamic p r e f e r e n c e f o r t h e formation of a racemic e u t e c t i c m i x t u r e over that of a p o l y c r y s t a l l i n e single enantiomer. The c h o i c e o f w h i c h i s formed i s governed e n t i r e l y by k i n e t i c s . I n t h e spontaneous c r y s t a l l i z a t i o n o f 1 , 1 ' - b i n a p h t h y l from t h e m e l t , t h e chance f o r m a t i o n o f one enantiomer l o w e r s t h e f r e e energy o f a c t i v a t i o n towards t h e f u r t h e r c r y s t a l l i z a t i o n o f t h a t enantiomer by p r e s e n t i n g a s u r f a c e on w h i c h m o l e c u l e s o f o n l y one c o n f i g u r a t i o n may be d e p o s i t e d . The element o f chance can be c o m p l e t e l y e l i m i n a t e d by p e r f o r m i n g a c o n t r o l l e d s o l i d - s t a t e r e s o l u t i o n through the p r e p a r a t i o n of a h i g h l y s t e r e o s p e c i f i c s o l i d c o n s i s t i n g o f a racemate and seed c r y s t a l s o f t h e desired enantiomer. The R- and S - l , 1 ' - b i n a p h t h y l system i l l u s t r a t e s t h e n o v e l t y o f w o r k i n g w i t h t h e phase t r a n s f o r m a t i o n s o f o p t i c a l l y l a b i l e enantiomers. A sample o f neat 1 , 1 - b i n a p h t h y l ( [ a ] = +234°) h e l d a t 160° r a c e m i z e s 1 c o m p l e t e l y i n l e s s than f i v e m i n u t e s . activity A n o t h e r sample o f low o p t i c a l ([«] = +11°) can be p r e p a r e d so t h a t i s w i l l r e s o l v e t o 149 [a] = +214° i n l e s s than f i v e minutes a t 150°, o n l y 10° l o w e r i n t e m p e r a t u r e . How g e n e r a l i s t h i s phenomenon? The development o f o p t i c a l by c r y s t a l l i z a t i o n o f t h e melt r e q u i r e s t h a t the enantiomers activity interconvert r e l a t i v e l y q u i c k l y i n t h e m e l t and y e t be o p t i c a l l y s t a b l e ( u n l i k e t h e ( + ) - d i a c i d 2_9, S e c t i o n 2) as a e u t e c t i c m i x t u r e . The c o n t r o l l e d s o l i d - s t a t e r e s o l u t i o n r e q u i r e s t h e e x i s t e n c e o f two r a c e m i c m o d i f i c a t i o n s , e i t h e r a racemate o r a s o l i d s o l u t i o n w h i c h decomposes to a e u t e c t i c m i x t u r e a t t e m p e r a t u r e s where i n t e r c o n v e r s i o n i s r e l a t i v e l y rapid. The e x i s t e n c e o f more than one c r y s t a l l i n e m o d i f i c a t i o n o f a s i n g l e compound i s more w i d e s p r e a d than commonly supposed. a l l organic Over o n e - t h i r d o f compounds s t u d i e d t h e r m o d y n a m i c a l l y up t o 1969 e x h i b i t p o l y - , . 107a „ . . . , 81a _ morphism. I t i s the opinion of s e v e r a l authors that every T organic compound p o s s e s s e s more than one s o l i d s t a t e , w h i c h have o n l y t o be discovered through s u i t a b l y o r i e n t e d research. The unprecedented s o l i d - s t a t e r e s o l u t i o n o f 1,1'-binaphthyl, a l t h o u g h s u r p r i s i n g when f i r s t e n c o u n t e r e d , i s a c t u a l l y e a s i l y e x p l a i n e d and should isomers. be a n t i c i p a t e d i n f u t u r e s t u d i e s w i t h phase systems o f o p t i c a l 150 4. 4.1 EXPERIMENTAL General Reagents and s o l v e n t s used were r e a g e n t grade and were employed without f u r t h e r p u r i f i c a t i o n , unless otherwise noted. Melting points, d e t e r m i n e d on a Thomas Hoover C a p i l l a r y M e l t i n g P o i n t a p p a r a t u s i n u n s e a l e d c a p i l l a r i e s , were c o r r e c t e d . Infrared spectra ( a l l m u l l s ) were r u n on a P e r k i n - E l m e r 137 sodium c h l o r i d e A n a l y t i c a l p r o c e d u r e s r e q u i r i n g a more d e t a i l e d (polarimet'ry, d i f f e r e n t i a l scanning nujol spectrophotometer. description c a l o r i m e t r y , and X-ray powder d i f f r a c t i o n ) a r e d e s c r i b e d i n S e c t i o n 4.6. 4.2 Preparations 4.2.1 P r e p a r a t i o n o f Racemic N a p h t h i d i n e (31) The p r o c e d u r e f o l l o w e d f o r t h e p r e p a r a t i o n o f r a c e m i c n a p h t h i d i n e was s i m i l a r t o t h a t of Cohen and O e s p e r . ^ of p u l v e r i z e d a-napthylamine I n a 1 i b e a k e r , 27.9 g were s t i r r e d i n t o 500 ml w a t e r , 33.8 ml o f c o n c e n t r a t e d h y d r o c h l o r i c a c i d was added, and the m i x t u r e warmed on a steam b a t h t o g i v e a l i g h t p u r p l e p r e c i p i t a t e of cc-nap thy lamine hydrochloride. The m i x t u r e was then c o o l e d i n an i c e b a t h t o 0-3° and c o l d , d i l u t e d s u l f u r i c a c i d (21 ml o f the c o n c e n t r a t e d a c i d p l u s 200 ml w a t e r ) was s t i r r e d i n . The suspended amine s a l t was then d i a z o t i z e d ( w i t h v i g o r o u s s t i r r i n g , k e e p i n g the temperature n e a r 0°) by 151 s l o w l y a d d i n g a c o l d s o l u t i o n o f 14 g sodium n i t r i t e d i s s o l v e d i n 90 ml water. The r e d d i s h brown s o l u t i o n o f the d i a z o n i u m s a l t was a l l o w e d to s t a n d f o r 5 min i n t h e i c e b a t h then s u c t i o n f i l t e r e d , the f i l t r a t e b e i n g r e c e i v e d i n a p r e c o o l e d f i l t e r f l a s k s u r r o u n d e d by an i c e b a t h . The c o l d f i l t r a t e was t r a n s f e r r e d to a 2 £ b e a k e r c o l d s o l u t i o n o f 79.9 g anhydrous ( i c e b a t h ) and a p o t a s s i u m a c e t a t e i n 300 ml w a t e r was s l o w l y s t i r r e d i n , t h e temperature b e i n g k e p t below 4°. A cooled s o l u t i o n o f 31 g sodium s u l f i t e i n 200 ml water was then s l o w l y added, c a u s i n g a v i g o r o u s e v o l u t i o n o f n i t r o g e n and the appearance azonaphthalene was completed min. crystals. of 1,1'- A f t e r the a d d i t i o n o f sodium s u l f i t e solution the s o l u t i o n was a l l o w e d t o s t i r f o r an a d d i t i o n a l 5 The s u s p e n s i o n was then t a k e n o u t of the i c e b a t h , warmed on a steam b a t h t o ~60°, and the orange p r e c i p i t a t e was f i l t e r e d o f f , washed w i t h w a t e r , and d r i e d i n a i r . W i t h o u t f u r t h e r p u r i f i c a t i o n the crude a z o n a p h t h a l e n e was p u l v e r i z e d and suspended weak b o i l . ( c a . 18 g) i n 200 ml 95% e t h a n o l , and b r o u g h t t o a A s o l u t i o n o f 48 g stannous c h l o r i d e d i h y d r a t e i n 100 m l c o n c e n t r a t e d h y d r o c h l o r i c a c i d was s l o w l y added over c a . 5 min ( w i t h occasional swirling). A c o l o u r change (from y e l l o w t o reddish-brown) o c c u r r e d , and t h e m i x t u r e was i m m e d i a t e l y c o o l e d t o room t e m p e r a t u r e . C o n c e n t r a t e d h y d r o c h l o r i c a c i d (100 ml) was then added t o p r e c i p i t a t e any r e m a i n i n g n a p h t h i d i n e h y d r o c h l o r i d e . The p r e c i p i t a t e was washed w i t h w a t e r , then suspended i n 200 m l w a t e r . Twenty ml o f 20% sodium h y d r o x i d e was then added, and the m i x t u r e a l l o w e d to s t i r a t 40° f o r 10 min. The s l u r r y was c o o l e d i n an i c e b a t h , f i l t e r e d , washed w i t h w a t e r and d r i e d i n a i r . The crude n a p h t h i d i n e was d i s s o l v e d i n 160 m l 152 o f a hot 3:1 ethanol-pyridine solvent pair. f i l t e r e d and a l l o w e d to c o o l s l o w l y . The The h o t s o l u t i o n was p u r i f i e d naphthidine 26% from a-naphthylamine) was o b t a i n e d as w e l l - f o r m e d , plates 198-199°). (m.p. 4.2.2 201-202°, l i t . 7 0 (7.1 g, l i g h t brown P r e p a r a t i o n o f (+)-Naphthidine-a-bromo-D-camphor-~-sulfonate T h i s s a l t was Hopp. 71 u s i n g the p r o c e d u r e of T h e i l a c k e r To 400 ml w a t e r and 40 ml 1 N h y d r o c h l o r i c a c i d was s o l u t i o n of 2.84 T h i s was prepared g (10 mmoles) r a c e m i c n a p h t h i d i n e followed immediately bromo-D-camphor-ir-sulfonate. w i t h 6.54 and added a i n 50 ml hot acetone. g (20 mmoles) (+)-ammonium-a- A l i g h t - b r o w n p r e c i p i t a t e soon formed the m i x t u r e was a l l o w e d t o s t a n d a t room temperature o v e r n i g h t . p r e c i p i t a t e was f i l t e r e d and r e c r y s t a l l i z e d from 70 ml 60% ethanol-water. Two crops (4.27 g, 46%) were o b t a i n e d . 25 71 gave a s p e c i f i c r o t a t i o n of [ c t ] = +80° ( l i t . 20 4.2.3 33 P r e p a r a t i o n of S - ( + ) - l , l ' - B i n a p h t h y l from s a l t 33 was d i r e c t l y deaminated to of 150 ml w a t e r , 3.45 The (by volume) = +99°). S-(+)-1,1'-binaphthyl u s i n g a p r o c e d u r e s i m i l a r t o t h a t o f C o l t e r and i c e - c o l d suspension and This m a t e r i a l D The (33) Clemens.^ g of s a l t J3J3, 2.3 To an ml concen- t r a t e d h y d r o c h l o r i c a c i d , and 50 ml 50% hypophorphorous a c i d i n a 3-necked f l a s k f i t t e d w i t h an overhead s t i r r e r was nitrite. A f t e r 2 h an a d d i t i o n a l 1 g sodium n i t r i t e was cold mixture was added 1.2 and s t i r r i n g was then s t o p p e r e d continued f o r a n o t h e r 3 h. g sodium added t o the The flask l i g h t l y and p l a c e d i n the r e f r i g e r a t o r o v e r n i g h t (0°). 153 F o r two days the f l a s k was s t i r r e d and k e p t c o l d d u r i n g the daytime and s t o r e d i n the r e f r i g e r a t o r o v e r n i g h t , d u r i n g w h i c h time a total o f 6 g sodium n i t r i t e were added i n 1 g p o r t i o n s . The c o l d m i x t u r e was f i l t e r e d and the s o l i d m a t e r i a l suspended i n 200 ml c o l d (8°) benzene. The s u s p e n s i o n was f i l t e r e d and the s o l u t i o n e x t r a c t e d s u c c e s s i v e l y w i t h 10% sodium h y d r o x i d e , w a t e r , 10% h y d r o c h l o r i c a c i d , and w a t e r MgSO^. After f i l t r a t i o n ( a l l a t ^ 8°), and d r i e d o v e r ( c o l d a p p a r a t u s ) , the benzene was anhydrous removed on the r o t a r y e v a p o r a t o r (25-30°), and the s o l i d p l a c e d on a column ( w i t h a w a t e r j a c k e t ) packed w i t h 25 g a l u m i n a (Woelm, n e u t r a l , grade 1) i n p e t r o l e u m e t h e r (30-60°). through the j a c k e t . C o l d w a t e r was The f r a c t i o n s , e l u t e d w i t h 4% p e t r o l e u m e t h e r (30-60°) a f f o r d e d w h i t e c r y s t a l s D [a] = +145-192°, m.p. 156-159°; l i t . 6 4 [a] 5 7 9 1 circulated (by volume) (0.536 g, 55%) 25 o p t i c a l l y a c t i v e 1 , 1 ' - b i n a p h t h y l ( [ a ] = +97°; m.p. activity benzeneof 156-157°; l i t . = +245°, m.p. 65 157- 159°) . 4.2.4 P r e p a r a t i o n o f Racemic 1 , 1 ' - B i n a p h t h y l The p r o c e d u r e used was analogous t o t h a t of S a k e l l a r i o s and K r y i m i s . To a d r y 3-necked f l a s k f i t t e d w i t h an overhead s t i r r e r and was added (under d r y n i t r o g e n ) 9.6 e t h e r , 56 ml a-bromonaphthalene condenser g magnesium t u r n i n g s , 72 ml anhydrous and a s i n g l e c r y s t a l o f i o d i n e . The s t i r r e d m i x t u r e was h e a t e d t o r e f l u x t o s t a r t the r e a c t i o n , w h i c h proceeded w i t h o u t f u r t h e r h e a t i n g f o r 20 min. was The r e a c t i o n m i x t u r e then h e a t e d to r e f l ux f o r 6 h, w i t h the a d d i t i o n of up to 200 ml d r y benzene t o t h i n the s l u r r y when n e c e s s a r y . The r e a c t i o n was cooled t o room temperature and added s l o w l y t o a s t i r r e d s u s p e n s i o n of 54 g 154 anhydrous c u p r i c c h l o r i d e ( p r e p a r e d by d r y i n g f o r 4 h a t 100°) i n 200 ml anhydrous e t h e r . the d i h y d r a t e The e n s u i n g r e a c t i o n was c o n t r o l l e d w i t h an i c e - w a t e r b a t h . salt vigorous The s u s p e n s i o n was then s t i r r e d o v e r n i g h t a t room temperature under d r y n i t r o g e n . The r e a c t i o n m i x t u r e was quenched by slow a d d i t i o n t o 100 ml 10% h y d r o c h l o r i c a c i d and i c e . The e t h e r - b e n z e n e l a y e r was e x t r a c t e d s u c c e s s i v e l y w i t h s e v e r a l p o r t i o n s o f 10% h y d r o c h l o r i c a c i d , w a t e r , s a t u r a t e d sodium b i c a r b o n a t e anhydrous magnesium s u l f a t e . s o l u t i o n and w a t e r , and d r i e d o v e r The s o l v e n t s were removed in_ vacuo t o a f f o r d an o i l , w h i c h c r y s t a l l i z e d on c o o l i n g t o 0°. The brown m a t e r i a l was t r a n s f e r r e d t o a Buchner f u n n e l , washed w i t h a s m a l l amount o f cold petroleum ether ether (65-110°). (30-60°), and r e c r y s t a l l i z e d once from p e t r o l e u m The crude 1 , 1 ' - b i n a p h t h y l (^ 12 g) was then mixed w i t h an e q u a l w e i g h t o f a l u m i n a ( S h a w i n i g a n r e a g e n t ) and p l a c e d on a column o f 300 g a l u m i n a packed i n p e t r o l e u m e t h e r (30-60°). After 1 I had been e l u t e d w i t h 10% b e n z e n e - p e t r o l e u m e t h e r (30-60°), the f i r s t appearance o f 1 , 1 ' - b i n a p h t h y l white was r e v e a l e d by the p r e s e n c e o f c r y s t a l s a t the t i p o f t h e column. r e q u i r e d 3 I f o r complete e l u t i o n . The e n t i r e b i n a p h t h y l Evaporation fraction o f the s o l v e n t i n vacuo and r e c r y s t a l l i z a t i o n o f the b i n a p h t h y l from acetone a f f o r d e d 10 g (20%) o f w h i t e c r y s t a l s , m.p.'s 144-145° ( l o w - m e l t i n g form) and 73 157-158° ( h i g h - m e l t i n g f o r m ) . (low-melting Badar, e t a l . form) and 157-159° ( h i g h - m e l t i n g r e p o r t m.p. form). 144.5-145° 155 4.3 P r o c e d u r e s f o r the R e s o l u t i o n of Racemic 1 , 1 ' - B i n a p h t h y l 4.3.1 R e s o l u t i o n i n C o m p l e t e l y M e l t e d Samples 4.3.1.1 Spontaneous R e s o l u t i o n To observe r e s o l u t i o n from a m e l t w h i c h i s t o t a l l y racemic, c a r e f u l l y weighed samples of 1 , 1 ' - b i n a p h t h y l (from s e v e r a l d i f f e r e n t b a t c h p r e p a r a t i o n s ) r a n g i n g from 10-30 g l a s s ampules. mg i n w e i g h t were s e a l e d i n 1 ml I n groups of 12, the s e a l e d ampules were h e l d i n a s i l i c o n e - o i l a t 170-185° t o d e s t r o y a l l forms o f s o l i d 1 , 1 ' - b i n a p h t h y l . The c o m p l e t e l y m e l t e d samples were t h e n q u i c k l y t r a n s f e r r e d t o a second s i l i c o n e o i l b a t h m a i n t a i n e d a t p r e c i s e l y 149.6°, where they would have remained was as a s u p e r c o o l e d m e l t i n d e f i n i t e l y . i n d u c e d by removing Crystallization the ampules i n d i v i d u a l l y from the b a t h , h o l d i n g each one a g a i n s t a p i e c e o f Dry I c e f o r ca. 5 s e c , then i m m e d i a t e l y r e p l a c i n g i t i n the 149.6° b a t h . was p e r f o r m e d q u i c k l y , so t h a t no sample was f o r more than 10 s e c . The cooling operation o u t s i d e o f the b a t h The samples r e q u i r e d about 2 h to c r y s t a l l i z e c o m p l e t e l y , a f t e r w h i c h time they were c o o l e d t o room t e m p e r a t u r e , opened, and a n a l y z e d f o r o p t i c a l activity. P o l y c r y s t a l l i n e 1 , 1 ' - b i n a p h t h y l c o n t a i n i n g a known amount o f a d i s s y m m e t r i c " i m p u r i t y " ( d - and £-mandelic a c i d ) was follows. I n 50 ml acetone p r e p a r e d as ( d i s t i l l e d from p o t a s s i u m permanganate) 0.49252 g r a c e m i c 1 , 1 ' - b i n a p h t h y l and 0.02639 g d-mandelic dissolved. The s o l u t i o n was a c i d were f i l t e r e d and the s o l v e n t removed i r i The r e s u l t i n g m i x t u r e , which c o n t a i n e d 5.08% (by w e i g h t ) d-mandelic a c i d , was s e a l e d i n ampules, m e l t e d , and c r y s t a l l i z e d i n a manner analogous t o the above p r o c e d u r e w i t h the c o m p l e t e l y r a c e m i c binaphthyl. A s i m i l a r p r o c e d u r e was vacuo. used f o r the m i x i n g of 1,1'£-mandelic 156 a c i d w i t h racemic 4.3.1.2 1,1'-binaphthyl. Deliberate Addition of Crystals of Active 1,1'-Binaphthyl To t e s t t h e e f f e c t o f o p t i c a l l y a c t i v e l , l ' - b i n a p h t h y l seed c r y s t a l s on c r y s t a l l i z a t i o n from c o m p l e t e l y m e l t e d samples ( T a b l e XI, p 93), ca_. 200 mg o f s o l i d r a c e m i c 1,1'-binaphthyl (from v a r i o u s b a t c h p r e p a r a t i o n s ) were p l a c e d i n t h e bottom o f a t e s t tube 15 cm i n l e n g t h and f i t t e d w i t h a ground g l a s s s t o p p e r . The s o l i d was i n t r o d u c e d t h r o u g h a long-stemmed f u n n e l t o a v o i d c o a t i n g the upper p a r t o f t h e t e s t tube w i t h c r y s t a l s . The e n t i r e tube ( e x c e p t f o r t h e top 2 cm) was then immersed i n a b a t h a t 170-180°, where a l l 1,1'-binaphthyl m e l t e d , and i m m e d i a t e l y t r a n s f e r r e d t o a 149.6° b a t h and immersed t o t h e same l e v e l . The s t o p p e r was removed f o r ca. 10 s e c w h i l e t h e a c t i v e 1,1'-binaphthyl seeds were dropped of a spatula. complete. i n from t h e t i p C r y s t a l l i z a t i o n r e q u i r e d o v e r n i g h t (16 h) t o become The sample was then c o o l e d t o room t e m p e r a t u r e , t h e cake o f s o l i d b r o k e n up w i t h a s p a t u l a , and d u p l i c a t e a n a l y s e s f o r o p t i c a l activity performed. 4.3.2 Resolution i n the S o l i d State 4.3.2.1 The H e a t i n g o f Racemic 1,1'-Binaphthyl As a s t a n d a r d c h a r a c t e r i z a t i o n o f f e s h l y p r e p a r e d r a c e m i c 1,1'b i n a p h t h y l , a few i n d i v i d u a l samples form a g i v e n b a t c h o f r a c e m i c m a t e r i a l were h e a t e d a t 149.6°. Samples were c o o l e d t o room temperature and a n a l y z e d f o r o p t i c a l a c t i v i t y T a b l e VIII, p 85 ). ( T a b l e III, p 51 and 157 I n some e x p e r i m e n t s ( T a b l e X, p 92) c a r e f u l l y weighed optically a c t i v e b i n a p h t h y l was added t o the weighed r a c e m i c m a t e r i a l b e f o r e the ampules were s e a l e d . The s e a l e d samples were then mixed t h o r o u g h l y by h o l d i n g them i n c o n t a c t w i t h a L a b - L i n e "Super-Mixer" f o r 5 m i n , h e a t e d a t 149.6° and a n a l y z e d f o r s p e c i f i c rotation. 4.3.2.2 C y c l i n g S o l i d 1,1'-Binaphthyl t o High S p e c i f i c R o t a t i o n A t t h e bottom o f a 15 cm t e s t tube was p l a c e d 2.00 g o f r a c e m i c 1 , 1 ' - b i n a p h t h y l (Racemic B a t c h G). The t e s t tube was s e a l e d , p l a c e d i n a 149.6° b a t h f o r 2 h ( t h e sample appeared t o remain s o l i d out) , then c o o l e d t o room temperature and opened. a n a l y s i s gave [ a l = +42°. through- Polarimetric The s o l i d was d i s s o l v e d i n 400 ml pentane, D and the s o l u t i o n was f i l t e r e d , b o i l e d down t o 150 ml a l l o w e d t o c o o l to room temperature ( t o t a l time a t the b.p. o f pentane m i n ) , and p l a c e d i n t h e r e f r i g e r a t o r (0°) f o r 1 h. (36°) was 15-20 The pentane was removed on the r o t a r y e v a p o r a t o r t o a f f o r d 94% m a t e r i a l h a v i n g the same s p e c i f i c r o t a t i o n ( [ a l D = +43°). The 1 , 1 ' - b i n a p h t h y l was then s e a l e d i n a second t e s t tube and h e a t e d , as b e f o r e , a t 149.6° f o r 2 h. The r e c r y s c a l l i z a t i o n from pentane was r e p e a t e d i n e x a c t l y the same manner as b e f o r e , p r e p a r i n g t h e m a t e r i a l f o r t h e t h i r d h e a t i n g a t 149.6°. The c y c l e was r e p e a t e d a f o u r t h time t o o b t a i n 1.10 g ( t h e w e i g h t l o s s e s due m a i n l y t o samples t a k e n f o r p o l a r i m e t r i c and d i f f e r e n t i a l s c a n n i n g a n a l y s e s ) of S - ( + ) - l , l ' - b i n a p h t h y l , Other c y c l i n g e x p e r i m e n t s above p r o c e d u r e . (Table I V , p [-l^ = +194°. 54 ) were p a t t e r n e d a f t e r t h e 158 4.3.2.3 (a) The Heating of S l i g h t l y Active 1,1'-Binaphthyl The Preparation of S - l K i n e t i c Batch A solution of 0.181 3.819 g of active 1,1*-binaphthyl ( M D = +208°) and g of racemic 1,1'-binaphthyl (comprising together 4.000 g of material with t a ] = +9.4°) i n 280 ml acetone (Fisher reagent) was Q prepared and f i l t e r e d into a 500 ml Erlenmeyer f l a s k . was The s o l u t i o n then placed i n a Dry-Ice-acetone bath, with occasional s w i r l i n g . P r e c i p i t a t i o n , which began i n ~10 min, appeared to be complete i n 1 h. The crystals were suction f i l t e r e d immediately on removal from the cold bath. The 1,1'-binaphthyl obtained (2.97 g, 74% recovery) possessed a s p e c i f i c rotation of [a]^ = +1.4°. Samples taken from this batch resolved to [ a ] = +211° within 16 h at 149.6°. D Other batches prepared by this procedure did not always resolve w e l l on heating. (b) The Recrystallization-Evaporation Procedure - The Preparation of S-3 K i n e t i c Batch A solution of 0.133 g of active 1,1'-binaphthyl and 5.57 g of racemic 1,1'-binaphthyl (comprising together 5.70 [a] = +2.2°) i n 400 ml acetone (freshly d i s t i l l e d from potassium permanganate) was was g of material with f i l t e r e d into a 1 £ round-bottom f l a s k . The solution then cooled i n a Dry Ice-acetone bath (-78°) for 10 min with s w i r l i n g , during which time c r y s t a l l i z a t i o n began. Without completing the c r y s t a l l i z a t i o n , the f l a s k was removed and immediately placed on a rotary evaporator (Buchi Rotavapor <R> ) . The flask was rotated i n a i r while f u l l vacuum (water aspirator) was being established (5 min), then was lowered into the rater bath, maintained between 20 and 25°. As the 159 f l a s k warmed, some (but not a l l ) o f the c r y s t a l s d i s s o l v e d , reprecipitated w i t h the l o s s o f s o l v e n t . then The e v a p o r a t i o n was taken to d r y n e s s , and any r e s i d u a l acetone was removed on the h i g h vacuum pump. activity The m a t e r i a l , w h i c h was 100% r e c o v e r e d , p o s s e s s e d an of (a) = +2.0°, and r e s o l v e d t o (a) > +200° on h e a t i n g a t any temperature between 105° and 150°. K i n e t i c b a t c h e s S-2 and R - l were p r e p a r e d by an procedure. analogous The s o l i d 1 , 1 ' - b i n a p h t h y l ( [ a ] = -2° t o ±15°) o b t a i n e d n by t h i s method almost always r e s o l v e d t o a t l e a s t [ a ] = ±190° on Q h e a t i n g t o 150° f o r 2 h. 4.3.3 Resolution Involving O p t i c a l l y Inactive Solvents 4.3.3.1 H e a t i n g o f Racemic 1 , 1 ' - B i n a p h t h y l Under a S o l v e n t A g l a s s tube 20 cm i n l e n g t h and c o n t a i n i n g a c o a r s e fritted d i s c 10 cm from e i t h e r end was h e l d i n a v e r t i c a l p o s i t i o n w h i l e 200 mg r a c e m i c 1 , 1 ' - b i n a p h t h y l was p l a c e d on the d i s c . s e a l e d , the tube i n v e r t e d , and 0.5 ml 2-propanol from stannous c h l o r i d e ) p l a c e d t h r o u g h The top end was (freshly then distilled the r e m a i n i n g open end. The s e a l e d end was immersed i n a d r y i c e - a c e t o n e b a t h to p u l l the 2-propanol through t h e d i s c and i n t o the b i n a p h t h y l chamber. The open end was then s e a l e d , and t h e e n t i r e tube submerged i n a b a t h m a i n t a i n e d a t 120°, and o r i e n t e d so t h a t the b i n a p h t h y l / 2 - p r o p a n o l m i x t u r e remained a t the bottom end. About h a l f the s o l i d b i n a p h t h y l dissolved. A f t e r 43 h the tube was i n v e r t e d i n the b a t h , a l l o w i n g the 2-propanol t o d r a i n from the disc. Residual 1 , 1 ' - b i n a p h t h y l t h r o u g h the f r i t t e d 2 - p r o p a n o l was removed by t a k i n g the tube from the b a t h and q u i c k l y immersing the 2 - p r o p a n o l chamber i n Dry I c e - a c e t o n e . 160 This procedure allows complete removal of the solution from the crystals at 120°. Then binaphthyl end was then opened and the crystals were analyzed for optical activity. In this example, [a]^ = +198°, but such a high rotation was not consistently obtained (see Table IX, p 90). 4.3.3.2 Seeding of a Racemic, Supersaturated Solution Using a procedure identical to the above (Section 4.3.3.1), 200 mg racemic 1,1*-binaphthyl and 0.5 ml isopropanol (freshly distilled) were placed i n the sealed end of the fritted disc tube. In the open end was placed a glass capillary containing some seed crystals of active binaphthyl ([a] = -212°) at the tip remote from the fritted disc. The open end was then sealed and the tube immersed i n a 135° bath. A l l of the binaphthyl i n contact with the isopropanol dissolved. The tube was transferred to a 120° bath and inverted. The isopropanol solution of binaphthyl drained through the fritted disc and came i n contact with the active seed crystals. After 20 h at 120°, some crystals had grown from the supersaturated solution, and the tube was again inverted to drain the solution from the crystals. The crystals were recovered as before, and analysis gave la]^ = -2.3°. Seeding from solution, even with considerable care, did not consistently give highly-resolved 4.4 1,1'-binaphthyl. Characterization of the R- and S-l,1'-Binaphthyl Phase System 4.4.1 The Crystal Picking Experiment The batch of large (2-4 mm) crystals obtained by slow recrystallization (2 days) from actone solution was examined under a microscope w i t h permanently c r o s s e d p o l a r i z e r and a n a l y s e r and r o t a t a b l e s t a g e . C r y s t a l s w h i c h were n o t members of clumps were examined c l o s e l y . Any s m a l l c r y s t a l s a d h e r i n g t o the s u r f a c e were removed, and i f the e n t i r e c r y s t a l , viewed a t any a n g l e e x c e p t normal t o t h e c o r d f a c e s ( F i g u r e 10, p 62 ) e x t i n g u i s h e d s h a r p l y as t h e s t a g e was r o t a t e d , i t was s e t a s i d e f o r p o l a r i m e t r i c a n a l y s i s . No attempt was made t o p o l i s h the c r y s t a l f a c e s , a few o f w h i c h were rough i n appearance. 4.4.2 C r y s t a l l i z a t i o n o f Low and H i g h - M e l t i n g Forms In a t y p i c a l r e c r y s t a l l i z a t i o n from p e n t a n e , 0.50 g o f r a c e m i c 1 , 1 ' - b i n a p h t h y l was d i s s o l v e d i n 100 ml b o i l i n g pentane. The warm s o l u t i o n was f i l t e r e d and t h e f i l t r a t e r e d u c e d t o 40 ml by b o i l i n g o f f the pentane. The s o l u t i o n was e i t h e r a l l o w e d t o c o o l s l o w l y t o 0° c o o l e d r a p i d l y i n an i c e b a t h , o r seeded w i t h v a r i o u s samples o f racemic b i n a p h t h y l . Racemic Batches A t o J were p r e p a r e d by v a r i o u s r e c r y s t a l l i z a t i o n s from pentane ( e x c e p t D, w h i c h was p r e p a r e d by r e c r y t a l l i z i n g 0.50 g r a c e m i c 1 , 1 ' - b i n a p h t h y l from 10 ml g l a c i a l acetic acid). Racemic B a t c h e s K, L, and N were p r e p a r e d by r e c r y s t a l - l i z a t i o n from p e t r o l e u m e t h e r (65-110°), u s i n g 25 ml s o l v e n t f o r each gram t o be r e c r y s t a l l i z e d . Racemic B a t c h M was r e c r y s t a l l i z e d from acetone a t -78° (see S e c t i o n 4.4.3 f o r a s i m i l a r p r o c e d u r e ) , and Racemic B a t c h 0 was a commercial sample o f 1 , 1 ' - b i n a p h t h y l (K and K Laboratories, Inc.). To check f o r the c r y s t a l m o d i f i c a t i o n s o f 1 , 1 ' - b i n a p h t h y l produce by s l o w and f a s t removal o f s o l v e n t , 100 mg p o r t i o n s o f r a c e m i c m a t e r i a l were d i s s o l v e d i n 15 ml s o l v e n t ( e t h e r , a c e t o n e , o r benzene). 162 Slow e v a p o r a t i o n : The s o l u t i o n s were f i l t e r e d i n t o t h r e e 25 ml E r l e m e y e r f l a s k s and p l a c e d under an u p t u r n e d b e a k e r f o r s e v e r a l days. The e t h e r s o l v e n t d i s a p p e a r e d w i t h i n one day, the acetone i n two days, and t h e benzene i n f o u r days. Fast evaporation: The t h r e e s o l u t i o n s ( p r e p a r e d as above) were n o t f i l t e r e d , b u t were s u b j e c t e d t o a stream of d r y a i r w h i l e b e i n g h e l d i n a w a t e r b a t h a t room t e m p e r a t u r e . S o l v e n t s were removed w i t h i n 5 m i n . The c r y s t a l s from a l l s i x samples were a n a l y z e d on the d.s.c. Slow and f a s t s o l i d i f i c a t i o n o f t h e r a c e m i c m e l t was s t u d i e d on t h e d.s.c. ( S e c t i o n 4.6.2). S o l i d r a c e m i c 1 , 1 ' - b i n a p h t h y l was m e l t e d i n a d.s.c. sample p l a n c h e t t e a t 160°, then c o o l e d a t a r a t e o f 20 deg min 1 t o o b t a i n pure l o w - m e l t i n g form. A f e s h sample ( o r the same one) was m e l t e d a t 160° and c o o l e d r a p i d l y by removing and p l a c i n g i t on a m e t a l s u r f a c e . t h e sample p l a n c h e t t e R e p l a c i n g t h e sample i n t h e d.s.c. and warming t o 90-100° gave pure h i g h - m e l t i n g form. The most sudden c o o l i n g o f t h e m e l t was o b t a i n e d by p a c k i n g a c a p i l l a r y f o r X-ray powder d i f f r a c t i o n ( S e c t i o n 4.6.3) w i t h r a c e m i c l , l ' - b i n a t > h t h y l m e l t i n g the sample a t 175°, and i m m e d i a t e l y immersing t h e ( u n s e a l e d ) c a p i l l a r y i n a l i q u i d nitrogen bath. The c a p i l l a r y was r e t r i e v e d and mounted i n a D e b y e - S c h e r r e r camera f o r a n a l y s i s . 4.4.3 Phase L i m i t o f R e s o l u t i o n The f o l l o w i n g p r o c e d u r e used f o r R - ( - ) - 1 , 1 ' - b i n a p h t h y l was s i m i l a r l y applied to S-(+)-1,1'-binaphthyl. I n 180 m l acetone ( d i s t i l l e d from p o t a s s i u m permanganate) was d i s s o l v e d 1.53 g o f R-l,l'-binaphthyl ([ct] n = -216°). The s o l u t i o n was f i l t e r e d and immersed 163 i n a Dry I c e - a c e t o n e b a t h (-78°). t u r e was 15 min. The l e n g t h o f time a t room tempera- C r y s t a l l i z a t i o n was complete a f t e r 30 min a t -78° (occasional swirling). The c r y s t a l s were then r a p i d l y through a s i n t e r e d g l a s s f u n n e l . Both c r y s t a l s suction-filtered (1.26 g, 82%) and m a t e r i a l from s o l u t i o n were a n a l y z e d f o r o p t i c a l a c t i v i t y , t h e l a t t e r made p o s s i b l e by removal o f acetone s o l v e n t i n vacuo 15 min. a t 25° w i t h i n The r e c r y s t a l l i z e d R - l , 1 ' - b i n a p h t h y l p o s s e s s e d the m a t e r i a l from s o l u t i o n h a v i n g [ a ] ^ = -111°. Three [ a ] = +228°, Q further r e c r y s t a l l i z a t i o n s were p e r f o r m e d , w i t h the r e s u l t s l i s t e d i n T a b l e X V I , p 179. 4.5 K i n e t i c Methods 4.5.1 Standard Procedure The p r o c e d u r e f o r t h e k i n e t i c s t u d y o f t h e r a c e m i z a t i o n o f the d i a c i d 29_ i n t h e s o l i d and t h e m e l t e d s t a t e s , was i d e n t i c a l w i t h t h a t o f the s o l i d - s t a t e r e s o l u t i o n o f 1 , 1 ' - b i n a p h t h y l . 10-30 I n both cases, mg o f t h e n e a t , p o l y c r y s t a l l i n e m a t e r i a l was c a r e f u l l y weighed i n 1 ml ampules. The ampules were s e a l e d i n a i r , and c o m p l e t e l y immersed i n a c o n s t a n t - t e m p e r a t u r e s i l i c o n e o i l b a t h . times i n d i v i d u a l samples were w i t h d r a w n , opened, and a n a l y z e d f o r o p t i c a l At appropriate c o o l e d t o room t e m p e r a t u r e , activity. F o r the s o l u t i o n phase r a c e m i z a t i o n o f (+)-29, s e a l e d ampules c o n t a i n e d ^ 10 mg o f c a r e f u l l y weighed (+)-29 and 0.2 ml p u r i f i e d tetralin. The d i a c i d 29_ d i s s o l v e d o n l y when the samples were h e a t e d f o r the r u n ; c o n c e n t r a t e d s o l u t i o n s possible. ( c a . 0.27 M) were t h e r e f o r e 164 First-order rate constants (^ ^ ) were obtained by plotting log 0 g ( [ a ] / [ a ] ) +2 against time, where [al i s t^- specific rotation (sodium e Q D line) at time zero. The rate constant was calculated from k , = 2.303 x (slope of line), obs r 4.5.2 Kinetic Runs with 1,1'-Binaphthyl from 64° to 98° Samples of 1,1'-binaphthyl were sealed in the standard way and placed in a drying pistol with a jacket for refluxing solvents. Temperatures were maintained by the following solvents: 64.2°, methanol; 76.9°, carbon tetrachloride; 83.3°, 1,2-dichloroethane; 87.6°, 1:3 tetrachloroethylene-water; 93.0°, 1:3 1-butanol-water; and 97.7°, n-heptane. Activities obtained at these temperatures are listed in Table XIII, p 111. 4.5.3 Kinetic Runs with Ground Samples Samples of 1,1'-binaphthyl were ground i n a small (1 cm o.d.) test tube using a glass stirring rod which had been molded the bottom of the test tube. to f i t This method was more satisfactory than pulverization in a mortar and pestle, which caused the buildup of a static charge on the crystals and made the handling of large (100 mg) quantities d i f f i c u l t . 4.5.4 Product Studies In the racemization of (+)-29, samples remained colourless and crystalline throughout the runs at 130-155°. In the melt (176-194°) some yellowing occurred, but did not become significant before 165 r a c e m i z a t i o n was complete. A t 161 and 166°, y e l l o w i n g was more apparent than i n t h e m e l t , and t h e samples p a r t i a l l y melted. Racemic d i a c i d 29_ was h e a t e d i n t e t r a l i n a t 140° f o r 96 h ( g r e a t e r t h a n 15 h a l f - l i v e s f o r r a c e m i z a t i o n o f (+)-29). Extraction of the d i a c i d i n t o 10% sodium h y d r o x i d e and a c i d i f i c a t i o n g i v e r a c e m i c 29_, whose n u c l e a r m a g n e t i c resonance spectrum was i d e n t i c a l w i t h that of the o r i g i n a l d i a c i d . No f u m a r i c a c i d s i g n a l was p r e s e n t i n t h e spectrum. I n a n o t h e r r u n , 0.45 g o f t h e r a c e m i c d i a c i d 29_ was h e a t e d w i t h 10 ml o f t e t r a l i n a t 140° f o r 52 h ( c a . 9 h a l f - l i v e s ) . On c o o l i n g , 0.32 g (71%) o f r a c e m i c 29, m.p. 180-184° was r e c o v e r e d . E x t r a c t i o n o f mether l i q u o r s w i t h d i l u t e base gave 0.094 g (21%) o f s t i c k y , probably polymeric, s o l i d . E s s e n t i a l l y complete interconversion o f enantiomers o c c u r s b e f o r e s i d e r e a c t i o n s become i m p o r t a n t a t l o n g reaction times. The k i n e t i c b a t c h e s o f 1 , 1 ' - b i n a p h t h y l remained w h i t e , c r y s t a l l i n e s o l i d s from 105-150° u n t i l w e l l beyond c o m p l e t i o n o f the r e s o l u t i o n . At 98°, some y e l l o w i n g o c c u r r e d a t l o n g r e a c t i o n times (3-6 months). The p r o d u c t o f the r e s o l u t i o n g i v e s the d . s . c , i n f r a r e d , and X-ray a n a l y s e s o f t h e h i g h - m e l t i n g form o f 1 , 1 ' - b i n a p h t h y l ( i n f r a r e d s p e c t r a 73 r e p o r t e d by Badar, e t a l . ). C o - i n j e c t i o n of the s t a r t i n g and r e s o l v e d p r o d u c t i n t o a g a s - l i q u i d chromatograph material [ u s i n g an 8% SE-30 on Chromosorb W (80/100) (6 f e e t x 1/8 i n c h ) column; c a r r i e r gas: h e l i u m ; f l o w r a t e : 110 ml min "*"; t e m p e r a t u r e : 150° f o r 3 m i n , the h e a t i n g a t 32 deg min ^ t o 270°, m a i n t a i n e d f o r 10 m i n ; i n s t r u m e n t : P e r k i n - E l m e r 900 Gas Chromatograph] gave a s i n g l e peak. 166 4.6 A n a l y t i c a l Procedures 4.6.1 Polarimetry A B e n d i x type 143 A a u t o m a t i c sample c e l l . p o l a r i m e t e r was used w i t h a m o d i f i e d The s u p p l i e d c e l l h o l d e r assembly was used t o c o n t a i n a c e l l composed o f a round m e t a l s p a c e r h a v i n g a t h i c k n e s s o f 1 cm. separated a c o n c e n t r i c h o l e and C e l l windows were composed o f round g l a s s slides from t h e s p a c e r and t h e r e s t o f t h e assembly by round T e f l o n wafers w i t h h o l e s punched i n t h e c e n t e r . The p i e c e s o f t h e c e l l were sandwiched t o g e t h e r i n t h e c e l l h o l d e r assembly i n t h e i n t e n d e d fashion. Sample s o l u t i o n s were i n t r o d u c e d t h r o u g h a h o l e d r i l l e d i n t h e s i d e of t h e m e t a l s p a c e r w h i c h formed t h e c e l l . Each sample ampule (1 ml) from t h e k i n e t i c runs was opened and t h e s o l i d m a t e r i a l completely d i s s o l v e d i n acetone ( f o r the ( + ) - d i a c i d 29, w h i c h does n o t r a c e m i z e a p p r e c i a b l y i n acetone a t 25°) o r i n benzene ( f o r o p t i c a l l y a c t i v e 1 , 1 ' - b i n a p h t h y l , which possesses a h a l f 74 l i f e o f 11.4 h f o r r a c e m i z a t i o n i n benzene a t 25° was ). The s o l u t i o n t r a n s f e r r e d t o a 3 ml v o l u m e t r i c f l a s k and d i l u t e d t o t h e mark w i t h washings from t h e opened ampule. filling Three r e a d i n g s were made by the p o l a r i m e t e r c e l l s u c c e s s i v e l y w i t h three samplings ( c a . 0.8 ml each) o f t h e s o l u t i o n . solvent. Zero r e a d i n g s were taken u s i n g t h e pure o A l l measurements were made a t t h e sodium D l i n e s p e c i f i c r o t a t i o n s were c a l c u l a t e d from [ct]p = 3 x 10^ x a (5890 A ) , and x c/ (sample wt. i n mg) where a i s t h e o b s e r v e d r o t a t i o n and c = 0.80 i s a c e l l constant solutions. o b t a i n e d by c a l i b r a t i o n w i t h known s t a n d a r d sucrose 167 4.6.2 D i f f e r e n t i a l Scanning The Calorimetry 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 e r ( d . s . c . ) used was Elmer DSC-1B. For q u a l i t a t i v e r u n s , c a . 5 mg a Perkin- c r y s t a l s were p l a c e d i n an aluminum sample p l a n c h e t t e and covered w i t h an aluminum l i d . l i d was p r e s s e d f i r m l y a g a i n s t the p l a n c h e t t e , p a r t i a l l y c r u s h i n g the c r y s t a l s , but t h e p l a n c h e t t e and l i d were not crimped s t a n d a r d programming r a t e o f 10 deg min ^ was noted. The The temperature readout was together. used u n l e s s A otherwise c a r e f u l l y c a l i b r a t e d f o r 10 deg min heating r a t e w i t h m e l t i n g p o i n t standards, u s i n g slope s e t t i n g s of 545-585, and d i f f e r e n t i a l and average temperature and 522, r e s p e c t i v e l y . beginning T r a n s i t i o n temperatures s e t t i n g s of were measured a t the ( i . e . , a t f i r s t d e p a r t u r e from b a s e l i n e ) o f r e c o r d e d p e a k s . F o r q u a n t i t a t i v e e n t h a l p y d e t e r m i n a t i o n s , the sample was on a Cahn 485 E l e c t r o b a l a n c e (Model M-10) on the d.s.c. and run through a t a programming r a t e of 10 deg min \ a c h a r t speed of 4 i n min ^ (Leeds N o r t h r u p the weighed transition a range o f 16x Speedomax W c h a r t r e c o r d e r ) . A c a l i b r a t i o n run u s i n g the weighed h i g h - p u r i t y i n d i u m s t a n d a r d was and performed under i d e n t i c a l c o n d i t i o n s , from w h i c h i t was provided learned t h a t a t the s e t t i n g s used, each square i n c h of c h a r t paper r e p r e s e n t e d a heat f l o w of 27.3 m i l l i c a l o r i e s . Peak areas were i n t e g r a t e d by t a k i n g the average o f s i x d e t e r m i n a t i o n s w i t h a p l a n i m e t e r Instrument r Co.). The (Gelman e n t h a l p y of the t r a n s i t i o n i n k c a l mole was 47 The c a l i b r a t i o n f a c t o r changes somewhat w i t h t e m p e r a t u r e , but v a l u e of 27.3 meal i n ^ w i l l not change s i g n i f i c a n t l y i n the temperature range 140-190°. - the 168 calculated from: 2 AH = ( a r e—a of sample — ; t r a n s ir t i o n ,- i n ) (weight of sample, mg) x (,., m o l e c u l.,a r w e i•g h t ; 27.3 The heat x 10~ c a p c i t y (Cp) measurements ( T a b l e X V I I , p i \ x of sample) c 3 190 ) were p e r f o r m e d u s i n g the S p e c i f i c Heat K i t , an a c c e s s o r y to the DSC-1B. method i n v o l v e d comparison t o a s t a n d a r d , w h i c h was p u r i t y sapphire. The The a d i s c of h i g h - s a p p h i r e s t a n d a r d was w e i g h e d , p l a c e d i n a sample 47 p l a n c h e t t e , and c o v e r e d i n the recommended manner. i s o t h e r m a l l y t o e s t a b l i s h a b a s e l i n e , then i t was min The d.s.c. was programmed a t 10 ^ (range: 4 x ) , c a u s i n g a pen d e f l e c t i o n p r o p o r t i o n a l t o c a p a c i t y o f the s a p p h i r e . The programming was the run deg heat discontinued after h e a t i n g f o r t e n d e g r e e s , and the b a s e l i n e r e - e s t a b l i s h e d . I n t h i s manner, the s a p p h i r e was heated from 50° to 150° i n t e n degree' i n t e r v a l s w h i c h o v e r l a p p e d so t h a t two measurements of the o f t h e d e f l e c t i o n c o u l d be made a t 60°, was removed and a b l a n k run was i d e n t i c a l fashion. repeated. ... 140°. The then f i l l e d w i t h a weighed (pure h i g h - m e l t i n g form) and the A l l t h r e e ( s a p p h i r e , b l a n k and sample) runs were w i t h pure l o w - m e l t i n g b i n a p h t h y l , from 50° d i d any w e i g h t the a m p l i t u d e t o 140°. l o s s o r phase t r a n s f o r m a t i o n o c c u r . of the b l a n k was and b i n a p h t h y l samples, and Cp sapphire performed w i t h the same p l a n c h e t t e i n an The p l a n c h e t t e was amount of 1 , 1 ' - b i n a p h t h y l 70°, amplitude procedure repeated I n n e i t h e r sample At each s u b t r a c t e d from t h a t of the temperature sapphire ( i n c a l deg ''"mole ''") c a l c u l a t e d from: 169 = r ( a m p l i t u d e sample) (amplitude sapphire) (weight s a p p h i r e ) (weight sample) x % Q f (molecular weight of The two s a p p h i r e runs agreed g h ± ( i n amplitude) t o w i t h i n 1% a t a l l a c c u r a c y o f the method was t e s t e d by measuring n a p h t h a l e n e a t 51° as 43.7 (lit."'" 0 8 44.0 and 45.9 was b e t t e r than 4.6.3 x 1,1'-binaphthyl) t e m p e r a t u r e s , good e v i d e n c e of the p r e c i s i o n of the method. and 61° -1, c a l and 46.0 c a l mole "*"deg \ The the h e a t c a p a c i t y o f c a l mole "'"deg \ respectively). The respectively accuracy 1%. X-Ray Powder D i f f r a c t i o n The f o l l o w i n g p r o c e d u r e f o r q u a n t i t a t i v e phase a n a l y s i s was The sample to be a n a l y z e d was adopted. t h o r o u g h l y p u l v e r i z e d i n a s m a l l agate m o r t a r , and packed f i r m l y i n a 0.3 mm g l a s s c a p i l l a r y by p l a c i n g the c a p i l l a r y i n a t e s t tube and h o l d i n g the assembly a g a i n s t a L a b - L i n e "Super M i x e r " . The bottom 1.5 and a l i g n e d i n a Debye-Scherrer cm of the c a p i l l a r y was b r o k e n o f f , powder camera ( P h i l i p s PW equipped w i t h the s m a l l e r (0.5 mm) camera was 1024/10) c o l l i m a t o r and beam s t o p . then l o a d e d w i t h Kodak No-Screen NS-392 T 35 mm The X-ray film and mounted on the n o n - d i v e r g e n t q u a r t e r o f the P h i l i p s PW 1008/85 X-ray g e n e r a t o r (CuK^ r a d i a t i o n , N i f i l t e r ) . and 15 mA, and the f i l m exposed The f i l m was The s o u r c e was a c t i v a t e d (40 kV f o r e x a c t l y 20 h. developed w i t h Kodak D-19 d e v e l o p e r (a s t o c k s o l u t i o n p r e p a r e d as recommended, but u s i n g d i s t i l l e d w a t e r and b u b b l i n g n i t r o g e n through the s o l u t i o n ) d i l u t e d t e n times w i t h w a t e r at 20°C (68°F). 170 Development, performed i n an Anscomatic 4 min w i t h s w i r l i n g e v e r y 30 s e c . stop bath (stock s o l u t i o n : rinsed, After and f i x e d rinsing d e v e l o p i n g t a n k , took f i l m was 13 ml g l a c i a l a c e t i c then immersed i n a acid i n 1 £ water), (Kodak R a p i d F i x , f r e s h l y p r e p a r e d ) f o r 30 min, the f i l m was to d r y f o r 3-4 The The 35 mm immersed i n P h o t o f l o w and hung h. d e n s i t y of the d i f f r a c t i o n l i n e s on the photograph on a J o y c e double beam r e c o r d i n g m i c r o d e n s i t o m e t e r following control: slit: f o r four minutes. s e t t i n g s were used. Mode: Forward 5; pen damping: 5; i r i s : o p t i c a l d e n s i t y was units background (mk I I I C ) . o p t i c a l d e n s i t y (O.D.) u n i t s (B 335); r a t i o arm: The 10 t i m e s . The O.D. d e n s i t y wedge. between 0.40 and 1.20 O.D. units zero of undeveloped range o f o p t i c a l d e n s i t y (from the fog l e v e l t o the most dense measured peak) was w i t h the 0-2 The Integrate; d i f f e r e n t i a l taken as the d e n s i t y o f unexposed, f i l m w h i c h had been f i x e d . measured f u l l y open; s l i t h e i g h t : f u l l h e i g h t ; 25; a p e r t u r e : 25; d e n s i t y wedges: 0-2 (D 453) and 0-1 O.D. was measured I n a l l f i l m s t a k e n , t h i s range ( t h e l i n e a r range (where O.D. was is 109 p r o p o r t i o n a l to exposure) o f Kodak No-Screen f i l m i s 0.2 to 1.5 ). The d i f f r a c t i o n l i n e s t o be measured were t r a c e d as peaks u s i n g the (more p r e c i s e ) 0-1 O.D. The d e n s i t y wedge. d i f f r a c t i o n l i n e s chosen f o r i n t e n s i t y measurement were the o 10.1 A l i n e o o f the racemate and the 6.4 A l i n e of the e u t e c t i c I n t e g r a t e d i n t e n s i t i e s were measured from the d e n s i t o m e t e r u s i n g the average o f s i x a r e a d e t e r m i n a t i o n s w i t h form. tracings the p l a n i m e t e r . f r a c ta ir oe na of the et uo tteaclt iacr e a( hof The i g h the - m e l two t i n g )peaks: form (A^) was e x p r e s s e d as a 171 a r e a f r a c t i o n ( h i g h - m e l t i n g form) = C a l i b r a t i o n samples c o n s i s t i n g of known w e i g h t s of low- and forms were p r e p a r e d by grinding and t h o r o u g h l y m i x i n g the two high-melting forms t o g e t h e r , then a n a l y z i n g t h e s e samples u s i n g the d e s c r i b e d X - r a y procedure. The r e s u l t i n g weight fractions: W weight f r a c t i o n ( h i g h - m e l t i n g form) = W H H L + W were p l o t t e d a g a i n s t t h e i r c o r r e s p o n d i n g a r e a f r a c t i o n s ( F i g u r e 23, p and t h e r e s u l t i n g c a l i b r a t i o n curve used t o determine o f samples of the S-2 ( F i g u r e 24, p The the phase K i n e t i c Batch at v a r i o u s stages of 121) content resolution 123) . d s p a c i n g s o f the low- and h i g h - m e l t i n g forms ( T a b l e V, p 58) were c a l c u l a t e d by measuring the d i f f r a c t i o n l i n e s on the p h o t o g r a p h w i t h an a c c u r a t e m i l l i m e t e r s c a l e , and c o n v e r t i n g t o 28. c o n v e r s i o n was 1 mm c o n s t r u c t e d so t h a t r e p r e s e n t e d 2° 2 9 , a l l o w i n g f o r "normal f i l m s h r i n k a g e " development. and easy s i n c e the P h i l i p s camera was This the The d s p a c i n g s were then o b t a i n e d from the 28 on values relation: d = where X i s the w a v e l e n g t h o f CuK^ 2sin8 r a d i a t i o n (1.5418 A ) . 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Soc., 93, 1291 (1971) c 178 APPENDIX A THE PHASE LIMIT OF RESOLUTION S i n c e a l l o f our e x p e r i m e n t s w i t h 1 , 1 ' - b i n a p h t h y l produced samples h a v i n g v a r i o u s s p e c i f i c r o t a t i o n s , i t was v e r y d e s i r a b l e t o know t h e h i g h e s t p o s s i b l e r o t a t i o n ( a t t h e sodium D l i n e , where a l l o f our s p e c i f i c r o t a t i o n s were measured) o b s e r v a b l e i n t h e R- and S - l , 1 ' - b i n a p h t h y l system. An i n d i c a t i o n as t o how t h i s might be a c c o m p l i s h e d was o b t a i n e d when s e v e r a l samples o f h i g h l y a c t i v e 1 , 1 ' - b i n a p h t h y l were r e c r y s t a l l i z e d from a c e t o n e a t -78°, as a f i n a l p u r i f i c a t i o n measure b e f o r e t h e f u r t h e r s t u d y o f samples w i t h h i g h a c t i v i t y . The m a t e r i a l o b t a i n e d from t h e r e c r y s t a l - l i z a t i o n p o s s e s s e d a s p e c i f i c r o t a t i o n h i g h e r than t h a t o f t h e o r i g i n a l solid. A s t u d y o f t h e t e r n a r y system formed between R and S - l , 1 ' - b i n a p h t h y l and an o p t i c a l l y i n a c t i v e s o l v e n t r e v e a l e d t h a t s i m p l y from phase e q u i l i brium c o n s i d e r a t i o n s alone, a h i g h l y r e s o l v e d m a t e r i a l should s p e c i f i c r o t a t i o n u n t i l a constant f i g u r e i s obtained increase i n (see below). We t h e r e f o r e performed m u l t i p l e r e c r y s t a l l i z a t i o n s on a sample o f w e l l - r e s o l v e R-l,1'-binaphthyl t o see how h i g h an a c t i v i t y c o u l d be o b t a i n e d . w i t h 1.53 g o f m a t e r i a l h a v i n g Starting [ a ] = -216°, we o b t a i n e d , a f t e r f o u r r e - c r y s t a l l i z a t i o n s from a c e t o n e a t -78°, 0.56 g o f 1 , 1 ' - b i n a p h t h y l a s p e c i f i c r o t a t i o n o f [ a ] = -245° ± l°(Table X V I ) . having We proceeded no f u r t h e r because t h e r o t a t i o n d i d not i n c r e a s e i n t h e l a s t recrystallization 179 T a b l e XVI Low Temperature R e c r y s t a l l i z a t i o n o f R- and S - l , 1 ' - B i n a p h t h y l Weight a f t e r [a] a f t e r [a] of Recrystallization, Recrystallization, Solution, g degrees degrees Recrystallization Number R- ( - ) - 1 , 1 ' - B i n a p h t h y l : 0 1.53 -216 1 1.26 -228 -110 2 0.94 -244 -151 3 0.74 -247 -219 4 0.56 -245 -230 3 a S-(+)-1,1'-Binaphthyl: 0 1.41 1 1.19 +234 +202 2 0.95 +236 +220 3 0.70 +238 +225 Weight and s p e c i f i c r o t a t i o n The +226 a of i n i t i a l a material. a c t i v i t y o f t h e m a t e r i a l i n s o l u t i o n was a l s o m o n i t o r e d . s o l i d i s completely r e s o l v e d , the m a t e r i a l i n s o l u t i o n same a c t i v i t y as t h e r e c r y s t a l l i z e d s o l i d . When t h e s h o u l d have t h e However, our method o f i s o l a t i n g t h e s o l u t e (by removal o f s o l v e n t _in_ vacuo a t 25°) caused some 180 r a c e m i z a t i o n , and t h e h i g h e s t s o l u t e a c t i v i t y was t h e r e f o r e [a] = -230°. Assuming that a f t e r the f o u r t h r e c r y s t a l l i z a t i o n the s o l u t i o n possessed [a] = -245° a t -78°, we e s t i m a t e d the l o s s i n a c t i v i t y i n recovering the s o l u t e from s o l u t i o n (based on a h a l f - l i f e o f r a c e m i z a t i o n o f 11.4 h i n 74 benzene a t 25° ) as 14°. I t would n o t be p o s s i b l e , t h e r e f o r e , t o o b s e r v e a s o l u t e a c t i v i t y above 231°, c l o s e t o t h e f i n a l o b s e r v e d v a l u e . A sample o f S - l , 1 ' - b i n a p h t h y l was a l s o r e c r y s t a l l i z e d t o see i f the same s p e c i f i c r o t a t i o n o f t h e c r y s t a l s ( [ a ] = |245[°) c o u l d be o b t a i n e d . The i n i t i a l a c t i v i t y o f t h e 1.41 g sample o f S - l , 1 ' - b i n a p h t h y l was [a] = +226°. A f t e r t h r e e r e c r y s t a l l i z a t i o n s , an a c t i v i t y o f [ a ] = +238 ± 1° (0.70 g) r e s u l t e d ( T a b l e X V I ) . The t h i r d r e c r y s t a l l i z a t i o n d i d n o t r e p r e s e n t much o f an i n c r e a s e over t h e second. The s p e c i f i c r o t a t i o n o f t h e r e c o v e r e d s o l u t e was 13° l o w e r than t h a t o f t h e c r y s t a l s , to the estimated l o s s e s by r a c e m i z a t i o n d u r i n g s o l v e n t close evaporation. F u r t h e r r e c r y s t a l l i z a t i o n s were t h e r e f o r e n o t performed. The increment i n s p e c i f i c r o t a t i o n on r e c r y s t a l l i z a t i o n o f t h e s o l i d can be seen from t h e t e r n a r y phase diagrams w h i c h d e s c r i b e t h e r e c r y s t a l l i z i n g system a t -78° ( F i g u r e 3 2 ) . The phase r e l a t i o n s h i p s between s o l v e n t and R- and S-enantiomers when t h e l a t t e r form a racemate ( F i g u r e 32 ( b ) ) have a l r e a d y been e x p l a i n e d i n S e c t i o n 3.4.3 (p 95) and F i g u r e 17 (p 102). system a t -78 . T h i s diagram r e p r e s e n t s t h e most s t a b l e t e r n a r y The phase system formed between the e u t e c t i c form and the s o l v e n t i s a l s o shown ( F i g u r e 32 ( a ) ) . Because o f t h e i m p e r c e p t a b l e slowness o f t h e s o l u t i o n phase t r a n s f o r m a t i o n e u t e c t i c -> s o l u t i o n ->• racemate a t -78° ( S e c t i o n 3.4.1, p 8 3 ) , t h e e u t e c t i c form can e x i s t f o r indeterminable l e n g t h s o f time a t t h i s temperature i n c o n t a c t w i t h s o l v e n t . 181 SOLVENT F i g u r e 32. Schematic r e p r e s e n t a t i o n of t h e two p o s s i b l e t e r n a r y systems formed between s o l v e n t , R- and S - l , 1 ' - b i n a p h t h y l (a) R- and S-enantiomers S-enantiomers form a e u t e c t i c m i x t u r e . form a racemate. (b) at -78°. R- A l t h o u g h (b) i s more s t a b l e , (a) can e x i s t f o r i n d e f i n i t e p e r i o d s of time at -78°. and 182 Although the original samples in both of the above recrystallization sequences were the eutectic form (having been produced at 150°), the f i r s t batch of crystals could have been either form, or even both. That i s , the "racemic part" of the less-than-fully-resolved samples could have been either a racemate or a eutectic mixture of R and S crystals, or both, after the f i r s t recrystallization. Consider point y on the eutectic isotherm (Figure 32 (a)), which represents a possible allover composition of the solvent, R- and S-l,I'll inaph thy 1 mixture. At room temperature, the solubility curve abc w i l l be found closer to the 1,1'-binaphthyl edge of the diagram, and y w i l l be in the (single phase) solution region. At -78°, y w i l l be in the (threephase) R + S + solution region, so that precipitation can occur. If equilibrium in this eutectic ternary system i s attained, then the solution w i l l have composition b (racemic). The solid, however, w i l l have a higher activity x' than i t originally had (x). When x' i s filtered from the solution and redissolved in acetone, the allover composition w i l l now be y f (which, in this example, is in the two-phase R + solution region) at -78°. On attainment of equilibrium, the solid w i l l be fully resolved R and the solution composition w i l l be d, as determined by the tie-line Rd. Therefore, by such an equilibrium process, the excess of one enantiomer can be separated from a non-racemic material. If attainment of equilibrium at -78° i s particularly slow, a solid material having a rotation greater than x may separate, leaving a meta1 stable solution having an excess of the other enantiomer (R). When crystals Similar considerations hold for the racemate isotherm (Figure 32 (b)). By a similar process, the very small excess of one enantiomer in a "racemic" preparation can be made observable, as discussed on p 88. 183 and s o l u t i o n a r e s e p a r a t e d , n e t r e s o l u t i o n has been performed. n o n e q u i l i b r i u m methods o f r e s o l u t i o n , u s u a l l y Such a c c o m p l i s h e d be s e e d i n g r a c e m i c s o l u t i o n s , have been t r i e d w i t h a number o f p a i r s o f e n a n t i o 85 mers. I n o u r c r y s t a l l i z a t i o n s , the n o n e q u i l i b r i u m p r o c e s s i s probably o p e r a t i n g t o some e x t e n t , s i n c e d u p l i c a t e c r y s t a l l i z a t i o n s do n o t g i v e m a t e r i a l w i t h t h e same r o t a t i o n . The l i m i t o f r e s o l u t i o n w h i c h we have d e t e r m i n e d (+238°, -245°) s h o u l d perhaps be r e f e r r e d t o as a "phase l i m i t " o f r e s o l u t i o n , the t e r m i n a l s o l i d s o l u t i o n s ^ ' e x i s t i n g 0 since a t t h e edges o f t h e b i n a r y R- and S - l , 1 ' - b i n a p h t h y l phase diagram ( F i g u r e 14 ( a ) , p 80) may have a composition range o f a few p e r c e n t . thus be s l i g h t l y o p t i c a l l y impure. The R and S c r y s t a l s o b t a i n e d may In t h i s t h e s i s , the value [ a ] = ±245° i s however t a k e n as t h e f u l l y r e s o l v e d s p e c i f i c r o t a t i o n , and where i t i s used, " p e r c e n t r e s o l u t i o n " has been c a l c u l a t e d from t h i s figure. 184 APPENDIX B T )H CALCULATION OF AG AS A FUNCTION OF TEMPERATURE I n S e c t i o n 3.3.2.3 (p 7 3 ) , t h e s t a t e m e n t was made t h a t t h e e n a n t i o t r o p i c o r d e r i n g o f r a c e m i c 1 , 1 ' - b i n a p h t h y l m o d i f i c a t i o n s ( F i g u r e 11 ( b ) , p 67) c o u l d be proven by c a l c u l a t i n g t h e f r e e energy d i f f e r e n c e between the racemate ( l o w - m e l t i n g ) form and t h e r a c e m i c e u t e c t i c ( h i g h - m e l t i n g ) L->H form, AG , as a f u n c t i o n o f t e m p e r a t u r e . However, a c a l c u l a t i o n o f t h i s d i f f e r e n c e a t 150°C (423°K) u s i n g m e l t i n g e n t h a l p i e s and e n t r o p i e s o f t h e two m o d i f i c a t i o n s gave a n u m e r i c a l r e s u l t , 212 + 490 c a l mole \ w h i c h was v e r y i m p r e c i s e when t h e l i m i t s o f e r r o r were a d d i t i v e l y propagated through the c a l c u l a t i o n . Any s o l i d - s o l i d t r a n s i t i o n L->H T r e s u l t i n g from an e x p r e s s i o n o f AG temperature as a f u n c t i o n o f t e m p e r a t u r e would a l s o be i m p r e c i s e . However i f o u r o r i g i n a l g o a l o f d e t e r m i n i n g x e x a c t l y i s abandoned, some u s e f u l i n f o r m a t i o n can s t i l l be o b t a i n e d L~*H from t h e c a l c u l a t i o n o f t h e t e m p e r a t u r e dependence o f AG see i f i t i n c r e a s e s o r d e c r e a s e s w i t h t e m p e r a t u r e . , i f only to Referring again to F i g u r e 11, t h e monotropic system p o s s e s s e s an i m a g i n a r y s o l i d - s o l i d t r a n s i t i o n p o i n t i n t h e r e g i o n where t h e m e l t i s s t a b l e ^ ' 1 8 1 b whereas i n an e n a n t i o t r o p i c system, t h e t r a n s i t i o n p o i n t i s a t l o w e r t e m p e r a t u r e s . T h e r e f o r e , some d i s t i n c t i o n between t h e two can be made by n o t i n g whether o r n o t t h e f r e e energy s u r f a c e s f o r racemate o r e u t e c t i c converge o r d i v e r g e i n g o i n g t o l o w e r t e m p e r a t u r e s from 150°C. 185 The f r e e energy d i f f e r e n c e a t any t e m p e r a t u r e can be c a l c u l a t e d i f the e n t h a l p y and e n t r o p y d i f f e r e n c e s a r e known as a f u n c t i o n o f t e m p e r a t u r e . These, i n t u r n , can be c a l c u l a t e d from t h e heat c a p a c i t y d i f f e r e n c e as a f u n c t i o n o f t e m p e r a t u r e , as f o l l o w s . E n t h a l p y and e n t r o p y a r e f u n c t i o n s o f s t a t e . change i n g o i n g from t h e racemate Therefore, the enthalpy t o t h e r a c e m i c e u t e c t i c ( i . e . , L->H) a t any t e m p e r a t u r e T i s e q u a l t o t h e e n t h a l p y change i n t a k i n g t h e racemate from T t o 150°C (423°K), p l u s t h e change on g o i n g t o t h e e u t e c t i c form at 150°C (which i s known), p l u s t h e change on b r i n g i n g t h e e u t e c t i c back t o T. That i s : AH L->H 423 C dT L p + AH™ 423 + C 423 H dT P L H where C and C a r e heat c a p a c i t i e s a t c o n s t a n t p r e s s u r e o f t h e l o w P P (racemate) and h i g h - m e l t i n g ( e u t e c t i c ) forms, r e s p e c t i v e l y . simplifies to: [25] AH L->H 423 (C - C ) dT P P L H E n t r o p y can be t r e a t e d i n a s i m i l a r [26] The AS L->H 423 (C - c ) P P L H + L->H AH 423 fashion: 4?T + AS L->H 423 f r e e energy d i f f e r e n c e a t t e m p e r a t u r e T i s t h e r e f o r e : This expression 186 A £* [27] = G AH™ - T A s f L~*H We a r e i n t e r e s t e d i n f i n d i n g whether A G w i t h temperature T i n c r e a s e s or decreases from 150°C t o , s a y , room t e m p e r a t u r e . As a f i r s t (and r a t h e r crude) a p p r o x i m a t i o n , we can assume t h a t t h e e n t h a l p y and e n t r o p y L^H L-*H d i f f e r e n c e s AH^ and AS^ Thus, AH^ of i n t e r e s t . a r e independent = AH^^-j a n u AS^, o f temperature = AS423 > a n ° l t ; i n t h e range c a ° n e s e e n from E q u a t i o n s 25 and 26 t h a t t h i s a p p r o x i m a t i o n amounts t o assuming t h a t the heat c a p a c i t i e s o f b o t h m o d i f i c a t i o n s a r e i d e n t i c a l i n t h i s L range, i . e . , C temperature H = C . The a p p r o x i m a t i o n g r e a t l y s i m p l i f i e s E q u a t i o n 27, Lr*"H and s u b s t i t u t i o n o f o u r e n t h a l p y and e n t r o p y v a l u e s a t 150 C g i v e s AG^, as a f u n c t i o n o f t e m p e r a t u r e : _L+H AG [28] r 9 8 1 A T _ = .„Lr>H AH = (1620 - 4.33T) c a l m o l e 4 2 3 - Lr>H T A S ^ - 1 L-*H The e q u a t i o n becomes t h a t o f a s t r a i g h t l i n e , h a v i n g a n e g a t i v e AG^ v a l u e a t 150°C, a z e r o v a l u e a t 102°C, and becoming more p o s i t i v e a t Lr^H lower temperatures (Figure 33). Taking the u n c e r t a i n t i e s i n A H a n 4 2 3 ^ Lr*"H AS 4 2 3 individually 102° i 52°C. (dotted l i n e s , F i g u r e 3 3 ) , the u n c e r t a i n t y i n x i s T h i s a p p r o x i m a t i o n t h e r e f o r e i n d i c a t e s t h a t t h e system i s e n a n t i o t r o p i c w i t h t h e racemate s t a b l e below about 102°C. we have o b s e r v e d However, the L,-*H t r a n s i t i o n as low as 76°C ( S e c t i o n 3.5.1, p 1 0 3 ) . T a k i n g t h e s e two o b s e r v a t i o n s t o g e t h e r , we s h o u l d more c o r r e c t l y con- c l u d e t h a t t h e e u t e c t i c i s s t a b l e a t l e a s t from 150°C t o 76°C, w i t h t h e racemate becoming s t a b l e a t l o w e r temperatures. 187 F i g u r e 33. R e l a t i o n o f the f r e e energy d i f f e r e n c e between racemate racemic e u t e c t i c form of 1 , 1 - b i n a p h t h y l 1 L mation, assuming i n AG C T First approxi- H - C P to temperature. and = 0 (see t e x t ) . P caused by e r r o r s i n A H ^ ^ Dotted l i n e s are u n c e r t a i n t i e s and A S ^ ^ , taken i n d i v i d u a l l y . 188 As a second a p p r o x i m a t i o n , the q u a n t i t y C L - C P c o n s t a n t from room t e m p e r a t u r e to 150°C. H can be assumed P E q u a t i o n s 25 and 26 can be i n t e g r a t e d to give: [29] AH™ T = (C - C ) p p [30] AS™ T = 2.303 ( C - C ) p p The q u a n t i t y L (423 - T) H L (C^ - C^) was H + 1620 c a l mole l o g (~) T + 4.33 d e t e r m i n e d on the d.s.c. i n v o l v e d u s i n g a sapphire standard ( f o r which a f u n c t i o n o f t e m p e r a t u r e ) and measuring L Although the C c a l deg "'mole The 4 f o r b o t h the racemate v a l u e s a t each A - deg 1 1 temperature P i n d i v i d u a l u n c e r t a i n t i e s a r e reduced by a f a c t o r o f /To - C P and The r e s u l t s a r e i n v o l v e s u b t r a c t i o n of two measured q u a n t i t i e s , the r a t h e r The d i f f e r e n c e as H - C P mean o f t e n v a l u e s . 1 procedure ^ i s known a c c u r a t e l y the e u t e c t i c ( [ a ] = -8°, i . e . , almost r a c e m i c ) form. l i s t e d i n Table XVII. 1 H large by t a k i n g the I s t h e r e f o r e -13 ± 4 c a l P "I mole When the r e s u l t i n g f r e e energy d i f f e r e n c e ( E q u a t i o n 27) i s p l o t t e d a g a i n s t t e m p e r a t u r e , the s o l i d l i n e i n F i g u r e 34 r e s u l t s . The e r r o r i n L~*H L-*-H L-*-H AG i n t r o d u c e d by the i n d i v i d u a l u n c e r t a i n t i e s i n AH,„„, A S , , and T 423 423 L H L H C - C i s a l s o shown ( d o t t e d l i n e s ) . The u n c e r t a i n t y i n C - C does P P P P L~**H L-^H L~**H not cause n e a r l y so l a r g e an e r r o r i n AG^ " as do t h o s e i n A H ^ ^ d ^423' m 0 0 a n As i n the f i r s t a p p r o x i m a t i o n , the most p r o b a b l e v a l u e o f the f r e e A energy d i f f e r e n c e becomes l e s s n e g a t i v e as the temperature i s lowered from 150°C, becoming z e r o at about 86°C. T h i s most p r o b a b l e t r a n s i t i o n temper- a t u r e T i s c l o s e t o the l o w e s t o b s e r v e d t r a n s i t i o n L+H (76°C). The second 189 500 - Figure 34. Relation of the free energy difference between racemate and racemic eutectic form of 1,1'-binaphthyl to temperature. L mation, assuming C certainties in AG T H - C P 1_>H individually. Second approxi- = constant (see t e x t ) . Dotted l i n e s are unP caused by errors i n A H ^ , AS ^ and C - C , taken 423 423 p p 1 1 L 190 T a b l e XVII Heat C a p a c i t i e s at Constant P r e s s u r e f o r Melting Temperature ( E u t e c t i c ) Forms of Low-Melting (Racemate) and High l,l'-Binaphthyl c <v. H -c , L P P -1 -1 c a l deg mole C K , -1mole , -1 • c a l deg 50 323.16 85.7 71.7 14.0 60 333.16 87.6 73.8 13.8 70 343.16 90.4 76.3 14.1 80 353.16 94.3 82.1 12.2 90 363.16 96.2 85.4 10.8 100 373.16 98.2 85.5 12.7 110 383.16 99.7 87.1 12.6 120 393.16 101.6 90.1 11.5 130 403.16 105.8 92.8 13.0 140 413.16 112.9 96.9 16.0 150 423.16 117.9 c a l deg approximation t h e r e f o r e also implies that system -1 , -1 mole Mean: the racemic 13.07 1,1'-binaphthyl i s e n a n t i o t r o p i c , w i t h t h e • t r a n s i t i o n temperature probably only s l i g h t l y below 76 C. L H A t h i r d a p p r o x i m a t i o n i n v o l v e s the d e t e r m i n a t i o n o f C - C as a P P f u n c t i o n o f temperature. The i n d i v i d u a l heat c a p a c i t y d i f f e r e n c e s i n L T a b l e XVII were f i t t e d t o a p o l y n o m i a l o f the type -2 a + bT + cT to o b t a i n : C H - C = 191 • 180.5 c = T h i s polynomial"'' ' 08 Equations 3 58.6 + + 0.3511 i + 8.528 x 10 + + 6 0.1066 2.589 x 1 0 was s u b s t i t u t e d i n E q u a t i o n s + 6 25 and 26, and t h e t h r e e 25, 26 and 27 were s o l v e d s i m u l t a n e o u s l y f o r AH , AS and x. x x was 84°C, not much d i f f e r e n t from the v a l u e x The t r a n s i t i o n temperature E~*"H o b t a i n e d from t h e second a p p r o x i m a t i o n . mole 1 and 2.16 c a l deg "'"mole \ AH x respectively. L"*"H and AS x were 772 c a l These thermodynamic c a l c u l a t i o n s , performed w i t h t h e measurements made w i t h t h e 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 e r , y i e l d an i m p r e c i s e v a l u e o f x but s u p p o r t an e n a n t i o t r o p i c o r d e r i n g o f racemic modifications. 1,1'-binaphthyl A more e x a c t v a l u e o f t h e t r a n s i t i o n temperature could 59b be o b t a i n e d w i t h t h e v e r y p r e c i s e methods o f a d i a b a t i c c a l o r i m e t r y .
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Racemization and resolution in the organic solid state Wilson, Keith Rainier 1972
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Title | Racemization and resolution in the organic solid state |
Creator |
Wilson, Keith Rainier |
Publisher | University of British Columbia |
Date Issued | 1972 |
Description | Two examples of the simplest type of organic solid-state reaction - the thermal interconversion of optical isomers - have been extensively studied by means of polarimetry, differential scanning calorimetry, and X-ray powder diffraction. The first reaction investigated was the reverse Diels-Alder reaction and recombination of the cyclopentadiene-fumaric acid adduct. Polycrystalline samples of (+)-enantiomer (m.p. 176°) racemize completely in the solid state from 130° to 165°. First-order kinetics (ΔH = 40.0 kcal mole⁻¹, ΔS = 14 cal deg⁻¹mole⁻¹) are strictly obeyed; the racemization rate is insensitive to variations in crystal size and optical purity. The reaction, which is only five times slower than the melt rate extrapolated to these temperatures (for the melt from 176° to 194°, ΔH = 29.7 kcal mole⁻¹, ΔS = -6.9 cal deg⁻¹mole⁻¹) occurs throughout the polycrystalline sample rather than at crystallite boundaries, dislocations, or other preferred sites. Phase studies show that the product separates as a racemic compound (m.p. 186°) which forms a eutectic (at 165°) with the resolved enantiomers. From 165° to 176°, the racemization shows autoacceleration and sigmoid-shaped kinetic curves characteristic of concurrent reactions in the solid and melt phases. The second system studied was that formed between R-(-)- and S-(+)-1,1'-binaphthyl, and surprisingly, resolution, rather than racemization, was observed to occur from 76° to 158°. This unprecedented solid-state resolution is made possible by a solid-solid phase change from a racemic compound (m.p. 145°) to a. eutectic mixture (m.p. 158°) of crystals of pure enantiomers, at temperatures where interconversion occurs in the reactant-product interface. Polycrystalline 1,1’-binaphthyl samples of very low optical activity having the correct phase content (racemate plus crystals of only one enantiomer) for a controlled resolution can be easily and reproducibly prepared. These samples resolve from [α][sub D] = 2° to [α][sub D] = ca. 210° (in either (+) or (-) directions) in less than one hour at 150°. The limit of resolution ([α][sub D] = ±245°) is attained simply by recrystallization of the resolved sample from acetone. The resolution therefore involves the conversion of all of a racemic material to only one enantiomer. Kinetic studies of the solid-state resolution show a smooth development of optical activity with time. A Prout-Tompkins analysis indicates that crystallites of growing enantiomer spread throughout the racemic sample, requiring 62 kcal mole⁻¹ activation energy. Crystallization of completely racemic 1,1'-binaphthyl melt in a closed system gives rise to optical activity. The probability distribution of 200 individual crystallizations is symmetric about [α][sub D] = 0° and proves that optically active samples can be created under absolutely spontaneous conditions (i.e., in the complete absence of external dissymmetric influences). |
Genre |
Thesis/Dissertation |
Type |
Text |
Language | eng |
Date Available | 2011-03-29 |
Provider | Vancouver : University of British Columbia Library |
Rights | For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use. |
DOI | 10.14288/1.0060105 |
URI | http://hdl.handle.net/2429/33027 |
Degree |
Doctor of Philosophy - PhD |
Program |
Chemistry |
Affiliation |
Science, Faculty of Chemistry, Department of |
Degree Grantor | University of British Columbia |
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UBCV |
Scholarly Level | Graduate |
Aggregated Source Repository | DSpace |
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