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Racemization and resolution in the organic solid state 1972

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RACEMIZATION AND RESOLUTION IN THE ORGANIC SOLID STATE by KEITH RAINIER WILSON B.Sc. (Hons.), U n i v e r s i t y of B r i t i s h Columbia, 1967 A THESIS SUBMITTED^IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY i n the Department of CHEMISTRY We accept t h i s t h e s i s as conforming to the re q u i r e d standard THE UNIVERSITY OF BRITISH January, 1972 COLUMBIA In presenting this thesis in partial fulfilment of the requirements for an advanced degree at the University of British Columbia, I agree that the Library shall make i t freely available for reference and study. I further agree that permission for extensive copying of this thesis for scholarly purposes may be granted by the Head of my Department or by his representatives. It is understood that copying or publication of this thesis for financial gain shall not be allowed without my written permission. Department of C H e ^ C S T ^ V The University of British Columbia Vancouver 8, Canada Date F£&G.Oflrg.-\ - 2 , 7 - . t^TT^ i i ABSTRACT Supervisor: Dr. R.E. Pincock Two examples of the s i m p l e s t type of organic s o l i d - s t a t e r e a c t i o n - the thermal i n t e r c o n v e r s i o n of o p t i c a l isomers - 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 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 . The 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 reverse D i e l s - A l d e r r e a c t i o n and recombination of the cyclopentadiene-fumaric a c i d adduct. P o l y c r y s t a l l i n e samples of (+)-enantiomer (m.p. 176°) racemize completely i n the s o l i d s t a t e * -1 + from 130° to 165°. F i r s t - o r d e r k i n e t i c s (AH = 40.0 k c a l mole , AS = 14 c a l deg "'"mole "*") are s t r i c t l y obeyed; the r a c e m i z a t i o n r a t e i s i n s e n - s i t i v e to v a r i a t i o n s i n c r y s t a l s i z e and o p t i c a l p u r i t y . The r e a c t i o n , which i s only f i v e times slower than the melt r a t e e x t r a p o l a t e d to these * -1 temperatures ( f o r the melt from 176° to 194°, AH' = 29.7 k c a l mole , AS* = -6.9 c a l deg "Snole "*") occurs 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 boundaries, d i s l o c a t i o n s , or other p r e f e r r e d s i t e s . Phase s t u d i e s show that the product separates as a racemic compound (m.p. 186°) which forms a e u t e c t i c (at 165°) w i t h the r e s o l v e d enantiomers. From 165° to 176°, the r a c e m i z a t i o n shows a u t o a c c e l e r a t i o n and sigmoid- shaped k i n e t i c curves c h a r a c t e r i s t i c of concurrent r e a c t i o n s i n the s o l i d and melt phases. The second system s t u d i e d was that formed between R - ( - ) - and S-(+)- 1,1'-binaphthyl, and 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 , was observed to occur from 76° to 158°. 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 racemic compound i i i (m.p. 145°) to a. e u t e c t i c mixture (m.p. 158°) of c r y s t a l s of pure e n a n t i o - mers, at temperatures where i n t e r c o n v e r s i o n occurs i n the reactant-product i n t e r f a c e . P o l y c r y s t a l l i n e 1 , 1 1-binaphthyl samples of very low o p t i c a l a c t i v i t y having the c o r r e c t phase content (racemate plus c r y s t a l s of only 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 r e p r o d u c i b l y prepared. These samples r e s o l v e from [ c t ] D = 2° to [ a ] D = .ca.. 210° ( i n e i t h e r (+) or (-) d i r e c t i o n s ) i n l e s s than one hour at 150°. The l i m i t of r e s o l u t i o n ( [ a j ^ = i245°) i s a t t a i n e d simply by r e c r y s t a l l i z a t i o n of the r e s o l v e d sample from acetone. 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 the con- v e r s i o n of a l l of a racemic m a t e r i a l to only one enantiomer. K i n e t i c s t u d i e s of the s o l i d - s t a t e r e s o l u t i o n show a smooth development of o p t i c a l a c t i v i t y w i t h time. A Prout-Tompkins a n a l y s i s i n d i c a t e s that c r y s t a l l i t e s of growing enantiomer spread throughout the racemic sample, r e q u i r i n g 62 k c a l mole 1 a c t i v a t i o n energy. C r y s t a l l i z a t i o n of completely racemic 1,1'-binaphthyl melt i n a c l o s e d system gives r i s e to 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 of 200 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 [ c t ] D = 0° and proves that o p t i c a l l y a c t i v e samples can be created under a b s o l u t e l y spontaneous c o n d i - t i o n s ( i . e . , i n the complete absence of e x t e r n a l dissymmetric i n f l u e n c e s ) . i v TABLE OF CONTENTS 1 I n t r o d u c t i o n 1 2 Racemization of (+) - B i c y c l o [ 2.2.1 ]hept-5-ene-trans_-2 ,3- d i c a r b o x y l i c A c i d i n the L i q u i d and S o l i d States 17 2.1 Racemization i n the L i q u i d State 18 2.2 Racemization i n the S o l i d State 23 2.3 The Phase Diagram 27 2.4 Mechanism i n the 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 of Racemic 1,1'-Binaphthyl i n the S o l i d State 45 3.1 The P r e p a r a t i o n of 1,1'-Binaphthyl 46 3.2 Discovery of 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 of the System R- and S-1,1'-Binaphthyl 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 of the 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 Generation of O p t i c a l l y A c t i v e 1,1'-Binaphthyl 139 3.7 Conclusion 147 4 Experimental 150 B i b l i o g r a p h y 172 Appendix A: The Phase L i m i t of R e s o l u t i o n 178 L~*H Appendix B: C a l c u l a t i o n of AG as a Function of Temperature 184 V LIST OF TABLES I F i r s t - O r d e r Rate Constants f o r Racemization of (+)-29 20 i n S o l i d , M e l t , and S o l u t i o n . I I A c t i v a t i o n Parameters f o r Racemization of (+)-29 i n 21 S o l i d , M e l t , and S o l u t i o n . I l l Summary of I n i t i a l I n v e s t i g a t i o n s of the Development of 51 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. IV Examples of the C y c l i n g of Racemic 1,1'-Binaphthyl to 54 High S p e c i f i c R o t a t i o n s . 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 Low-Melting (Racemate) 58 and High-Melting ( E u t e c t i c ) Forms of 1,1'-Binaphthyl. VI S p e c i f i c R otations of S i n g l e C r y s t a l s Obtained from the R e c r y s t a l l i z a t i o n of Racemic 1,1'-Binaphthyl. V I I Enthalpy of Fusion of the Hig h - M e l t i n g Form of 1,1'- B i n a p h t h y l at Various S p e c i f i c R o t a t i o n s . V I I I The Development of O p t i c a l A c t i v i t y on Heating P o l y - c r y s t a l l i n e , Racemic 1,1'-Binaphthyl. IX The Development of O p t i c a l A c t i v i t y on Heating P o l y - c r y s t a l l i n e , Racemic 1,1'-Binaphthyl Under a Solvent. X The I n f l u e n c e of Added Seed C r y s t a l s of O p t i c a l l y A c t i v e 1,1'-Binaphthyl on the S o l i d - S t a t e R e s o l u t i o n of P o l y c r y s t a l l i n e , Racemic 1,1'-Binaphthyl. XI The I n f l u e n c e of O p t i c a l l y A c t i v e 1,1'-Binaphthyl Seed C r y s t a l s on the 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 Supercooled, Racemic 1,1'-Binaphthyl M e l t . X I I F i n a l S p e c i f i c R otations 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). 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 of 1,1'-Binaphthyl. I l l XIV Avrami-Erofeev 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 131 of 1,1'-Binaphthyl. XV Prout-Tompkins Rate Constants ( k ? ) f o r the S o l i d - S t a t e 135 R e s o l u t i o n of 1,1'-Binaphthyl. XVI Low Temperature R e c r y s t a l l i z a t i o n of R- and S-1,1'- 179 B i n a p h t h y l . 61 76 85 90 92 93 109 v i LIST OF TABLES (continued) XVII Heat C a p a c i t i e s at Constant Pressure f o r Low-Melting (Racemate) and High-Melting ( E u t e c t i c ) Forms of 1,1'- B i n a p h t h y l . 190 v i i 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 of neat (+)- 19 d i a c i d 2_9 i n the melt phase. 2. R e l a t i o n of l o g ^ /T) to r e c i p r o c a l temperature f o r 22 ra c e m i z a t i o n of (+)-enantiomer 29. i n melt, s o l i d , and s o l u t i o n ( i n t e t r a l i n ) phases. 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 r a c e m i z a t i o n of neat, p o l y - 24 c r y s t a l l i n e (+)-29 i n the s o l i d phase. 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 - 25 c r y s t a l l i n e (+)-29 at 152° i n the s o l i d phase and at 161° where melt s o l i d . 5. K i n e t i c data f o r r a c e m i z a t i o n of neat samples of (+)-29 i n 26 the s o l i d (155°), i n the biphase melt + s o l i d system (166°), and i n a completely melted system (at 176°). 6. D i f f e r e n t i a l scanning c a l o r i m e t e r t r a c e s (programming r a t e : 29 10 deg min ^) f o r the d i a c i d 29_ at v a r i o u s compositions: (a) 0%, (b) 24.8%, (c) 45.2% and (d) 50% (-)-enantiomer. 7. Phase r e l a t i o n s h i p of mixtures of (+)- and (-)-enantiomer 31 of compound 29_. V e r t i c a l bars 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 temperatures (taken at the beginning of d.s.c. endotherms). Undetermined phase boundaries (dotted l i n e s ) are estimated f o r completeness. 8. (a) Schematic f r e e energy-composition p l o t i n the phase 39 system (+)- and (-)-29, at constant pressure (atmospheric) and temperature (150°). The dotted l i n e s show the lowest f r e e energy surfaces f o r the two-phase r e g i o n s . (b) Schematic f r e e e nergy-reaction coordinate 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)) at 150°. 9. I n f r a r e d spectrum of 1,1'-binaphthyl ( n u j o l m u l l ) . 56 (a) Low-melting form. (b) High-melting form. 10. Sketch of the h a b i t of a s i n g l e c r y s t a l of pure R- or S- 62 1,1'-binaphthyl, showing those faces which were apparent under the microscope, (a) View of a, b, and c f a c e s . (b) View normal to c f a c e , (c) View normal to d f a c e . v i i i LIST OF FIGURES (continued) 11. Schematic f r e e energy-temperature p l o t s f o r racemic 1,1'- 67 b i n a p h t h y l , showing low-melting form ( L ) , h i g h - m e l t i n g form (H) and melt (M) s u r f a c e s . (a) Monotropic r e l a t i o n - s h i p , (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 diagram which would r e s u l t from the monotropic r e l a t i o n s h i p , (d) Phase diagram which would r e s u l t from the enanti o - t r o p i c r e l a t i o n s h i p . 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 t r a c e s f o r racemic 69 1,1'-binaphthyl, as a f u n c t i o n of programming r a t e . (a) 2.5 deg min ^. (b) 10 deg min (c) 40 deg min ^. 13. Schematic enthalpy- and entropy-temperature p l o t s f o r 74 racemic 1,1'-binaphthyl. (a) Ordering of low-melting form ( L ) , h igh-melting form (H) and melt (M) e n t h a l p i e s . (b) Ordering of e n t r o p i e s of the same phases. 14. (a) Phase diagram f o r the R- and S - l , 1 ' - b i n a p h t h y l system, 80 showing metastable extensions (dotted l i n e s ) of the phase boundaries. (b) Schematic f r e e energy-composition p l o t at 130°, showing the lowest (dashed l i n e ) and the next-lowest (dotted 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 at 150°. 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 of time f o r the s o l i d - 86 s t a t e r e s o l u t i o n of racemic 1,1'-binaphthyl (L Batch) at 135°. 16. Schematic phase diagram between racemic 1,1'-binaphthyl 89 and a solvent w i t h b.p. > 160°. Dotted l i n e s are meta- s t a b l e e x t r a p o l a t i o n s of phase boundaries, and show the higher s o l u b i l i t y of the l e s s s t a b l e forms. 17. Schematic r e p r e s e n t a t i o n of the t e r n a r y system formed 102 between s o l v e n t , R- and S - l , 1 ' - b i n a p h t h y l . Metastable e x t r a p o l a t i o n s of phase boundaries ( s o l u b i l i t y curves) are shown as dotted l i n e s . (a) Temperature: -78°, (b) Temperature: +25°. 18. 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 b l y - 104 c r y s t a l l i n e 1,1'-binaphthyl, S - l K i n e t i c Batch at 135°. E f f e c t of g r i n d i n g and of storage at 25° f o r s i x weeks. 19. 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 - 105 c r y s t a l l i n e 1,1'-binaphthyl, S-2 K i n e t i c Batch at 125°. E f f e c t of storage of samples at 0° f o r four months. i x LIST OF FIGURES (continued) 20. K i n e t i c data f o r the s o l i d - s t a t e c r y s t a l l i n e 1,1'-binaphthyl, S-2 135°. 21. K i n e t i c data f o r the s o l i d - s t a t e c r y s t a l l i n e 1,1'-binaphthyl, S-2 115°. r e s o l u t i o n of neat, p o l y - 106 and R - l K i n e t i c Batches at r e s o l u t i o n of neat, p o l y - 107 and R - l K i n e t i c Batches at 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 - 108. c r y s t a l l i n e 1 , 1 1 - b i n a p h t h y l , S-3 K i n e t i c Batch at (a) 135 and (b) 115°. 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 phase a n a l y s i s by X-ray 121 powder photography. 24. Development of s p e c i f i c r o t a t i o n w i t h extent of phase 123 t r a n s f o r m a t i o n (Xy), S-2 K i n e t i c Batch at 125° ( a f t e r four months' storage at 0°). Diagonal represents the c o n d i t i o n [ a ] / [ o ] F = % . 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, 126 p o l y c r y s t a l l i n e 1,1'-binaphthyl, S - l K i n e t i c Batch at 135° and 105°. The sample s t o r e d s i x weeks at 25° i s p l o t t e d a g ainst l o g (time, seconds) + 1. 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, 127 p o l y c r y s t a l l i n e 1,1'-binaphthyl, S-2 K i n e t i c Batch at 135°, 125° ( o r i g i n a l r u n ) , 115°, and 105°. 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 of neat, 128 p o l y c r y s t a l l i n e 1,1'-binaphthyl, S - l K i n e t i c Batch at 135°. E f f e c t of g r i n d i n g and of storage at 25° f o r s i x weeks. 28. 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 of neat, 129 p o l y c r y s t a l l i n e 1,1'-binaphthyl, S-2, S-3 and R - l K i n e t i c Batches at 115°. 29. R e l a t i o n of l o g (ky) (from Prout-Tompkins p l o t s ) to 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 neat, 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 are l e a s t - s q u a r e s f i t s to data f o r each batch. 30. Percentage 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 - 141 t a t i o n s between +240°. The curve shows the Gaussian 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 of +0.14° and the standard d e v i a t i o n of 86.4°. X LIST OF FIGURES (continued) 31. R a t i o of samples having p o s i t i v e r o t a t i o n s to the t o t a l 142 number of samples of 1,1'-binaphthyl c r y s t a l l i z e d at 150°. The 200 samples are t r e a t e d as two sets of 100 each. The curves are confidence l i m i t s c a l c u l a t e d f o r a 0.99 degree of confidence and a p r o b a b i l i t y of 50% p o s i t i v e and 50% negative f o r each sample. 32. Schematic r e p r e s e n t a t i o n of the two p o s s i b l e t e r n a r y 181 systems formed between s o l v e n t , R- and S-1,1'-binaphthyl at -78°. (a) R- and S-enantiomers form a e u t e c t i c mixture, (b) R- and S-enantiomers form a racemate. Although (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 periods of time at -78°. 33. R e l a t i o n of the f r e e energy d i f f e r e n c e between racemate 187 and racemic e u t e c t i c forms of 1,1'-binaphthyl to temperature. L H F i r s t approximation, assuming C^ - = 0 (see t e x t ) . L~*ft Dotted l i n e s are 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 ^ 4 2 3 a n ^ ^ 4 2 3 ' t a ^ e n i n d i v i d u a l l y . 34. R e l a t i o n of the f r e e energy d i f f e r e n c e between racemate 189 and racemic e u t e c t i c forms of 1,1'-binaphthyl to temperature. L H Second approximation, assuming - = constant (see t e x t ) . L~*H Dotted l i n e s are 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 AH^ ^ AsV^?, and C^ - C^, taken i n d i v i d u a l l y . 423 423 p p x i ACKNOWLEDGEMENT I remain most g r a t e f u l to P r o f e s s o r Richard E. Pincock, who more than any other person was r e s p o n s i b l e f o r teaching me the methods and meaning of chemical research. I very much appreciate h i s guidance and continuous encouragement over the past four years. I would l i k e to thank my w i f e f o r her love and understanding, e s p e c i a l l y during the w r i t i n g of t h i s t h e s i s , f o r her help w i t h some of the t i n y , troublesome d e t a i l s during 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 ear to the words emanating from the author w h i l e bent over the t y p e w r i t e r . I would a l s o l i k e to thank P r o f e s s o r s H a r r i s o n , Stewart, T r o t t e r , Bree and Sche f f e r and t h e i r research groups f o r d i s c u s s i n g s e v e r a l aspects of 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 the l i b e r a l use of t h e i r instruments and equipment. Thanks are a l s o due to Mr. F. Slawson and Mr. G. Snider f o r help w i t h i l l u s t r a t i o n s and to Miss D. Johnson f o r p a r t i a l l y t y p i n g t h i s t h e s i s . I should a l s o l i k e to express my a p p r e c i a t i o n to the H.R. MacMillan Family Fund ( U n i v e r s i t y of B.C.) f o r a f e l l o w s h i p , and to the N a t i o n a l Research C o u n c i l and the Graduate Student F e l l o w s h i p Fund f o r f i n a n c i a l a s s i s t a n c e . 1 1 INTRODUCTION Modern knowledge of the organic s o l i d s t a t e l a r g e l y c o n s i s t s of in f o r m a t i o n on the 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 of a great v a r i e t y of m a t e r i a l s . Not n e a r l y so well-developed, however, i s our under- standing of chemical r e a c t i v i t y i n organic s o l i d s . U s u a l l y , systems which are che m i c a l l y unstable have been avoided. For example, many of the techniques used f o r the p h y s i c a l i n v e s t i g a t i o n s of organic s o l i d s - from u l t r a v i o l e t spectroscopy to semiconductor phy s i c s - r e q u i r e s t a b l e c r y s t a l s of high p u r i t y . Any chemical r e a c t i o n complicates the i n v e s t i g a t i o n , causing measured p r o p e r t i e s to change w i t h time, and e v e n t u a l l y causing the breakdown of 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 organic chemistry, where s o l i d reagents are encountered d a i l y , the s o l u t i o n phase has been the medium p r e f e r r e d f o r i n v e s t i g a t i o n s . Here, the view i s g e n e r a l l y h e l d that r e a c t i o n s i n organic s o l i d s are too s l u g g i s h to be of s y n t h e t i c u t i l i t y , or too complex to be amenable to common p h y s i c a l organic a n a l y s i s . There are, however, some w e l l - e s t a b l i s h e d areas of endeavour where the r e a c t i v i t y of the organic s o l i d s t a t e has been of great i n t e r e s t . The decomposition of s o l i d organic compounds, e s p e c i a l l y those r e l a t e d to organic 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 accounted f o r most of the research w i t h r e a c t i n g organic s o l i d s . 1 In s e v e r a l reviews from 1963-1966, Morawetz considered the reported examples of r e a c t i o n s i n organic s o l i d s , and drew a t t e n t i o n to the surge of 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 being w i d e l y explored. One f a s c i n a t i n g aspect of r e a c t i o n s i n organic s o l i d s , which has re c e i v e d the a t t e n t i o n of 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 - chemical c o n t r o l by the c r y s t a l l a t t i c e . The very elegant 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 of Schmidt and Cohen ' i n t o the pho t o d i m e r i z a t i o n s of c r y s t a l l i n e monomers are w e l l known. These workers demonstrated how the ge o m e t r i c a l o r i e n t a t i o n and spacing of r e a c t i n g molecules i n the l a t t i c e determines product stereochemistry. Such "topochemical c o n t r o l " e x p l a i n s the observed products i n most photoreactions of organic s o l i d s . More recent i n v e s t i g a t i o n s ^ have shown that even some of the exceptions may s t i l l be s u b j e c t to c o n t r o l s , but of a d i f f e r e n t nature. 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 gives a " h e a d - t o - t a i l " photodimer. This apparent f a i l u r e of l a t t i c e c o n t r o l was understood w i t h the discov 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 the c r y s t a l across which there are " h e a d - t o - t a i l " p a i r s of molecules. Reaction across the d i s l o c a t i o n then forms the observed stereoisomer. This r e s u l t underscores the i n f l u e n c e of c r y s t a l l i n e order, both i n the r e g u l a r l a t t i c e and at some d i s l o c a t i o n s , on the course of s o l i d - s t a t e r e a c t i o n s . Other accounts of the 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 product d i s t r i b u t i o n and stereochemistry have been given. Some recent r e p o r t s demonstrate the wide v a r i e t y of organic r e a c t i o n s which are s u s c e p t i b l e to s o l i d - s t a t e p e r t u r b a t i o n . A l l r e d and Smith*' have examined the thermal decomposition of the h e t e r o - s u b s t i t u t e d norbornene epimers 1_ and 2_: 3 1 3 4 CH„0 Thermolysis of the exo epimer 1_ i n the gas phase or p h o t o l y s i s i n s o l u t i o n gave the bicyclopentanes _3 and 4_, w i t h the trans isomer 3̂  i n s l i g h t excess; 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 almost t o t a l l y the c i s isomer 4_. 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 formation of h_ i n f l u i d media but an excess of _3 i n the c r y s t a l l i n e s t a t e . This r e v e r s a l of 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 formation of a s h o r t - l i v e d d i r a d i c a l which was i n v e r t e d i n f l u i d media but r e t a i n e d i t s conformation i n the r e s t r i c t e d environment of the s o l i d s t a t e . L i k e w i s e , S i t e , ^ i n a study of the decomposition of the quaternary ammonium s a l t 5_ i n the melted and s o l i d s t a t e s , n o t i c e d that 3 5 4 r e a c t i o n i n the s o l i d gives a higher p r o p o r t i o n of o r t h o - s u b s t i t u t i o n than r e a c t i o n i n the melt. 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 given by Penzien and Schmidt, who i n v e s t i g a t e d the r e a c t i o n of bromine vapor w i t h s i n g l e c r y s t a l s of 4,4'-dimethylchalcone ( 6 ) , an a c h i r a l compound which c r y s t a l l i z e s i n an enantiomorphic space group. The r e s u l t i n g dibromide was obtained w i t h one enantiomer i n 6 excess. Hence, t h i s process c o n s t i t u t e s an absolute asymmetric s y n t h e s i s . When the 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 develops. Another g a s - s o l i d r e a c t i o n , the a i r o x i d a t i o n of some 9 s t e r o i d s , was reported by Brenner e_t aJL. Reaction occurred on heati n g or on i r r a d i a t i o n , but depended s t r o n g l y on the polymorphic form of each compound. Some s t e r o i d s were very s u s c e p t i b l e to 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 ^ ' ^ or under i o n i z i n g r a d i a t i o n ^ i n organic m a t e r i a l s . Evidence of the expected greater cage e f f e c t has been presented both i n the form of increased r a t i o s of recombination r e a c t i o n s to hydrogen a b s t r a c t i o n outside the cage, 1^ and as inc r e a s e d s t e r e o - selectivity''"''" i n an organic g l a s s over t h a t i n s o l u t i o n . In f r e e r a d i c a l a d d i t i o n p o l y m e r i z a t i o n s i n the s o l i d s t a t e , which have r e c e n t l y 5 been reviewed, the polymer o f t e n bears 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 to the monomer l a t t i c e . ^ c > ^ j _ n f a c t , the very prospect of producing polymer chains which are more r e g u l a r l y o r i e n t e d than those produced i n s o l u t i o n has been a major reason f o r the renewed i n t e r e s t i n r e a c t i o n s i n organic s o l i d s . From reviewing the reported examples of 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 that most are e i t h e r chance observations or e l s e d e t a i l e d examinations of systems which tend to be r a t h e r complex. I f a good understanding of 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 to be achieved, then the very s i m p l e s t of r e a c t i o n s should be i n v e s t i g a t e d . These should provide i n s i g h t i n t o the most elementary processes o c c u r r i n g i n the r e a c t i n g organic s o l i d . In t h i s t h e s i s the "simple r e a c t i o n " w i l l be regarded as a thermal (organic) s o l i d - s t a t e r e a c t i o n which always c o n s i s t s of two components. The types 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 excludes can be considered as f o l l o w s . F i r s t of a l l , the organic s o l i d - s t a t e r e a c t i o n s which e i t h e r proceed under i r r a d i a t i o n or are r a d i a t i o n - i n d u c e d and then proceed t h e r m a l l y are r e l a t i v e l y complex processes. In 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 molecular s o l i d must be taken i n t o account, as w e l l as the mechanism of energy t r a n s f e r 13 1 w i t h i n the s o l i d . Relevant to 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 ' i n connection w i t h the photochemical r e a c t i o n s of 9 - s u b s t i t u t e d anthracenes. I f i o n i z i n g r a d i a t i o n i s used, r a t h e r i n d i s c r i m i n a n t bond breaking may r e s u l t , and there can be considerable damage to the c r y s t a l 2 s t r u c t u r e . The 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 of 6 two components. This l i m i t a t i o n f o l l o w s from the f a c t that systems of three or more components can possess exceedingly complex phase r e l a t i o n s h i p s . The task of i d e n t i f y i n g the r e a c t i v e phases could become very 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 to give at l e a s t two d i f f e r e n t products (such as thermal decompositions) are excluded, as are r e a c t i o n s of two (or more) d i f f e r e n t molecules to give one or s e v e r a l products. In the l a t t e r case, i f the two r e a c t a n t s are i n separate phases (two s o l i d s , s o l i d and l i q u i d , e t c . ) , any mechanistic d e s c r i p t i o n must a l s o i n c l u d e the process of 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 proceed beyond a monolayer of product molecules at the i n t e r f a c e between the r e a c t a n t s . The "simple r e a c t i o n s " are t h e r e f o r e those which have only a s i n g l e r e a c t a n t and a s i n g l e product. The r e a c t a n t must be e i t h e r neat or cont a i n only the product as an i m p u r i t y . Reactions performed i n i n e r t s o l i d media (e.g. g l a s s , host c r y s t a l or polymer matrix) are not "simple" 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 represented as: A ** nB where n i s a s m a l l i n t e g e r . When n equals 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, the r e a c t i o n i s a thermal monomer- dimer conversion. One 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 of a r y l isocyanates i n the s o l i d s t a t e . ^ The reverse process, the simple decomposition of a dimer i n t o i t s monomer fragments, i s e x e m p l i f i e d 14 by the thermal r e a c t i o n of 9-cyanoanthracene dimer. Processes where 7 n i s three or g r e a t e r are found i n the formation of oligomers, but the r e s t r i c t i o n s of " s i m p l i c i t y " makes examples r a r e . 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 , the t o t a l system becomes one of three components. Examples of thermal s o l i d - s t a t e i s o m e r i z a t i o n s are somewhat more common than those of thermal monomer-dimer r e a c t i o n s . Some of the reported examples are i n need of more experimental work, but a few have been i n v e s t i g a t e d i n considerable d e t a i l . There are a few i l l u s t r a t i o n s of thermal s o l i d - s t a t e tautomerism. 16 Pope and coworkers observed t h a t anthrone (7) r e a d i l y tautomerizes to a n thranol (8) i n the s o l i d - s t a t e from 84° to 158°. In f a c t , a n t h ranol i s e a s i l y prepared by h e a t i n g anthrone at 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 to room temperature. No k i n e t i c s were run, but the h a l f - l i f e at room temperature i n benzene s o l u t i o n i s about 2 hours. The n i t r o s o p h e n o l 9_, which 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 conversion at 129° to a "red form" (m.p. 154°) 17 which 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 to have the o_-quinone monoxime s t r u c t u r e 10. The same tautomerism e x i s t s i n s o l u t i o n , and both forms have i n t r a m o l e c u l a r hydrogen bonding. I f the pale y e l l o w 8 9 10 c r y s t a l s of 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 of o wavelength 4000 A, deep blue c r y s t a l s are produced. When the photo- product i s kept i n the dark, thermal reconversion to L l occurs i n a few H 11 12 hours. A c r y s t a l s t r u c t u r e determination of 11 l e d Seff and Trueblood to suggest tautomerisn ( v i a the oxygen of the o - n i t r o group) between s t r u c t u r e s 1_1 and 12. 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 revealed by a c r y s t a l l o g r a p h i c study of the photoisomer ( s t r u c t u r e 13) of bi(anthracene-9,10-dimethylene) (14). The photoisomer L3, which could be produced by s o l i d - s t a t e i r r a d i a t i o n of _14_ or simply by c r y s t a l l i z a t i o n from chloroform i n the l i g h t , undergoes a dark reconversion to i t s valence tautomer 14_ i n the s o l i d s t a t e . 9 An i n t e r e s t i n g case of stereoisomerism at 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 Byrn. The compound dimethy1-3,6-dichloro-2,5-dihydroxy- t e r e p h t h a l a t e e x i s t s i n both a y e l l o w form (m.p. 140°) and a white form (m.p. ca. 185°). Studies w i t h deuterated p h e n o l i c groups, and i n f r a r e d and n u c l e a r quadrupole resonance 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 white forms, 15a 15b r e s p e c t i v e l y . A thermal s o l i d - s t a t e conversion from the yellow to the white form occurs at 125°. A k i n e t i c study of the i s o m e r i z a t i o n of s o l i d cis-azobenzene (16) 21 has been performed by Tsuda and K u r a t a n i . The c i s - t r a n s conversion 10 was i n v e s t i g a t e d i n samples which were powdered and compressed i n KBr N=N 16 N=N^ d i s c s . The r e a c t i o n occurs i n the s o l i d s t a t e , g i v i n g r i s e to sigmoid- , shaped k i n e t i c curves, which were s e n s i t i v e to the method of sample preparation,and the extent of g r i n d i n g . One case of a s o l i d - s t a t e r e a c t i o n between conformational isomers 22 has been reported. Several years ago Brown and S u j i s h i observed what they p o s t u l a t e d as the conversion on h e a t i n g of an unsymmetrical isomer 17a to a symmetrical isomer 17b of a t r i - a - n a p h t h y l borine-ammonia adduct. The s o l i d - s t a t e conversion was discovered by n o t i n g that the • NH, 140°C NH, 17a 17b pressure 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 that the h i g h l y d i s s o c i a t e d adduct converted to the more s t a b l e adduct on h e a t i n g to 140°. Some i l l u s t r a t i o n s of thermal i s o m e r i z a t i o n v i a group migrations i n the s o l i d s t a t e e x i s t . Almost twenty years ago, Sluyterman and 23 coworkers examined the thermal r e a c t i o n s of t e t r a g l y d n e methyl e s t e r (18) i n the s o l i d s t a t e . Heating neat 1_8 at 100° produced s a r c o s y l 11 + H.N-CH.-C-(-N-CH.-C-)--OCH 2 2 |f | 2 || 3 O H 0 *• CH -NH -CH 0-C-(-N-CH 0-C).-0 3 2 2 || , 2 || 3 O H 0 t r i g l y c i n e (19), the r e s u l t of a methyl m i g r a t i o n , which i s perhaps most f e a s i b l y explained by an i n t e r m o l e c u l a r s h i f t from the e s t e r end of one molecule to the amino end of a neighbour. At higher tempera- tures (185°) and i n s o l u t i o n at 100° polycondensation i s the main r e a c t i o n . A k i n e t i c run at 100° showed S-shaped c h a r a c t e r ; the i n d u c t i o n p e r i o d was shortened somewhat by g r i n d i n g the sample. Another rearrangement i n the 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 a r y l a z o t r i b e n z o y l m e t h a n e s , 20 and 21, undergo m i g r a t i o n of a benzoyl group both to oxygen (forming the enol benzoate 22) and to n i t r o g e n (forming the hydrazone 23). The 0 22 N=N 20 X = H 21 X = Br 0 0 II (C H C-) C=N-N 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 of the bromo- d e r i v a t i v e 21_, by d i f f e r e n t i a l thermal a n a l y s i s , and by o b s e r v a t i o n of 12 the r e a c t i o n both i n s i n g l e c r y s t a l s on a microscope hot stage 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 . For example, when 20 i s heated at 5°/min, melt i n g occurs at ca. 124°, and i s f o l l o w e d immediately by rearrangement to an equimolar mixture of 22_ and 23, accompanied by the e v o l u t i o n of heat. F u r t h e r heating converts the isomer 22_ to 23_ over a temperature range of 40°, and f i n a l l y the pure hydrazone melts at 200°. Examination of mixtures of the three compounds 20_, 2_2_ and 2_3 suggested a e u t e c t i c temperature above 110°. 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 range 70-105°. Although the system i s v a s t l y s i m p l e r than most decompositions, i t u n f o r t u n a t e l y i n v o l v e s three components, and a more d e t a i l e d d e s c r i p t i o n of 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 r a t h e r d i f f i c u l t . 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 i s o m e r i z a t i o n of 2 , 2'-diiododibenzoyl peroxide (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 standpoint by Gougoutas. The r e a c t i o n occurs i n s e v e r a l weeks i n the c r y s t a l l i n e s t a t e at room temperature, and overnight at 110°. The product benziodoxole 25_ produced i n s i n g l e c r y s t a l s of _24 i s remarkably w e l l - o r d e r e d and bears 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 reactant l a t t i c e . This 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° during r e a c t i o n , a molecular movement which i s s u r p r i s i n g l y l a r g e i n terms of the spacing allowed i n the l a t t i c e . A study of the r e l a t e d peroxides 2_6̂  where X = hydrogen, 2-bromo, 2-chloro, 2 - f l u o r o , 3-chloro and 4 - n i t r o showed 0 — 0 26 2 7b 2 8 that a l l r e a c t i n the s o l i d s t a t e , and some undergo s i n g l e c r y s t a l - s i n g l e c r y s t a l t o p o t a c t i c transformations s i m i l a r to the d i i o d o compound 24. 29-33 Some simple i s o m e r i z a t i o n s , which occur e a s i l y on m e l t i n g , may a l s o proceed i n the s o l i d s t a t e . R e i n v e s t i g a t i o n of r e a c t i o n s i n these systems below 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 chemical r e a c t i o n s i n organic 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 the work of Pincock and Kiovsky ' on r e a c t i o n s i n frozen s o l u t i o n s . I t was discovered that common chemical r e a c t i o n s o c c u r r i n g i n organic 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 the f r e e z i n g p o i n t of the s o l v e n t . A d e t a i l e d k i n e t i c study proved that these observed changes i n k i n e t i c order and l a r g e r a t e a c c e l e r a t i o n s could be completely accounted f o r simply by the in c r e a s e d c o n c e n t r a t i o n of rea c t a n t s i n l i q u i d regions of the frozen s o l v e n t . I t was unnecessary to invoke any novel s o l i d - s t a t e e f f e c t s . These 14 l i q u i d regions 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 temperature of the 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 that i n a l l r a t e s t u d i e s i n f r o z e n systems, even those as f a r as 70° below the melting p o i n t s concerned, any r e a c t i o n i n a l i q u i d phase must be q u a n t i t a t i v e l y separated out before v a l i d c onclusions regarding s o l i d - s t a t e phenomena can be drawn. A l o g i c a l extension of the ideas developed during 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 from a k i n e t i c stand- 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 . In general the product w i l l lower the m e l t i n g p o i n t of the r e a c t a n t , and r e a c t i o n can p o t e n t i a l l y occur i n both the s o l i d and the l i q u i d phases at temperatures above the e u t e c t i c of the system. I f the system i s "simple", i . e . , has only two components, the important 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 reason, the f i r s t system s t u d i e d was the thermal muta- 3A 36 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-glucose. Isothermal k i n e t i c runs below the m e l t i n g p o i n t of pure a-D-glucose (146°) possessed an S-shaped charac t e r . Reaction began s l o w l y i n the i n i t i a l l y s o l i d sample, but as the product g-D-glucose developed, the r e a c t i o n a c c e l e r a t e d and the sample began to melt; maximum r a t e was observed on complete m e l t i n g , whereafter the r a t e decreased as e q u i l i b r i u m was approached. The sigmoid nature of the k i n e t i c curves could be e x p l a i n e d by n e g l e c t i n g any r e a c t i o n i n the s o l i d phase, and c o n s i d e r i n g only that i n the developing l i q u i d phase. The 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 incr e a s e s i n volume at the expense of the u n r e a c t i v e s o l i d phase. 37 A second study, that of the thermal 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 endo- and exo-5-norbornene-2,3-dicarboxylic anhydrides (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 of k i n e t i c s which can a r i s e from r e a c t i o n o c c u r r i n g simultaneously i n both s o l i d and l i q u i d phases. Chemical e q u i l i b r i u m i n the two- component systems occurs at an equimolar mixture of isomers, and can be approached from e i t h e r s i d e . S o l i d endo isomer, heated at 120-164°, e v e n t u a l l y melted, but u n l i k e a-D-glucose, the form of the k i n e t i c curves was not sigmoid, but f i r s t order. That i s , r e a c t i o n occurred as i f the system were t o t a l l y melted, even though the s o l i d phase was present. Phase s t u d i e s showed th a t s o l i d endo isomer was a " c r y s t a l l i n e 37 l i q u i d " above 94°, and that molecules i n t h i s phase possessed m o b i l i t y and could isomerize e q u a l l y as f a s t as those i n the l i q u i d phase. S o l i d exo anhydride could not isomerize as r e a d i l y as the endo adduct, and t h i s f a c t was r e f l e c t e d i n the shape of the k i n e t i c curves. Rate equations f o r both r e a c t i o n s were developed by assuming that 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 order. The r a t e equation could 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 values to the s o l i d - s t a t e r a t e constant, the form of both the endo and exo k i n e t i c curves could be generated. 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 both s o l i d and melt phase r e a c t i o n s was t h e r e f o r e accomplished. In view of the f a c i l i t y w i t h which r e a c t i o n proceeds i n s o l i d endo 16 and exo anhydrides, we decided to examine the p o s s i b i l i t y of 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. The f i r s t , a l s o a D i e l s - A l d e r adduct, 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). The second was a simple hydrocarbon, ( + ) - l , l ' - b i n a p h t h y l (30). Since the two components i n each of these systems are 29 30 enantiomers, 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 . Any t r u e s o l i d - s t a t e r e a c t i o n , i f i t occurs at a l l , should be e a s i l y recognized and, h o p e f u l l y , examined more c l o s e l y . The r e s u l t s of our study of the cyclopentadiene-fumaric a c i d adduct (29) are presented i n S e c t i o n 2 of the t h e s i s . Our i n v e s t i g a t i o n s (and unexpected f i n d i n g s ! ) w i t h the 1,1'-binaphthyl system are reported i n S e c t i o n 3. 17 2 RACEMIZATION OF (+)-BICYCLO[2.2.1]HEPT-5-ENE-TRANS-2,3-DICARBOXYLIC 38 ACID (29) IN THE LIQUID AND SOLID STATES This molecule, which owes i t s dissymmetry to two c h i r a l carbon atoms, can conceivably i n t e r c o n v e r t w i t h i t s enantiomer i n the melt 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 the s o l i d s t a t e . C ° 2 H A C0 2H C0 2H 29, (+)-enantiomer (m.p. 176°), (i)-racemate (m.p. 186°) 3. The racemic compound 29_ was prepared from the addends ( c y c l o - 39 pentadiene and fumaric acid) using the method of Koch. R e s o l u t i o n 40 to the (+)-enantiomer was e f f e c t e d v i a the br u c i n e s a l t , using 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 acetone-water. 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 of [ct]^ = +137° and +147° i n acetone) and possessed 40 a higher m e l t i n g p o i n t (177-179°) than that o r i g i n a l l y r e p o r t e d on ([a]p = +89°, m.p. 166-168°). Although the o p t i c a l p u r i t y of the re s o l v e d d i a c i d remains unknown, the k i n e t i c r e s u l t s presented below 3. The p r e p a r a t i o n and the r e s o l u t i o n of ( + ) - d i a c i d _29 was performed i n t h i s l a b o r a t o r y by M.M. Tong, before the work reported i n t h i s t h e s i s was begun. 18 d i d not depend, even i n the s o l i d s t a t e , on the extent of r e s o l u t i o n . 2.1 Racemization i n the L i q u i d State 2.1.1 The Melt Phase K i n e t i c runs i n the melt phase were performed from 176- 194°. The 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 p u r i f i e d C+)-29 i n a constant temperature bath. Racemization to [ c t j ^ = 0° occurred, and although there was a s l i g h t y e l l o w i n g of samples, t h i s was not s i g n i f i c a n t before the m a t e r i a l was e s s e n t i a l l y racemic. Product s t u d i e s showed that at long 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 occurred, but the i n i t i a l r e a c t i o n was simply an i n t e r c o n v e r s i o n of enantiomers. 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 vs. t i m e ) , s t r a i g h t l i n e s were obtained to over 90% r e a c t i o n (Figure 1 ) . The observed f i r s t - o r d e r r a t e constants are l i s t e d i n Table I. 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 at 194° to 12 min at 176°. The ease of r e a c t i o n at the m e l t i n g p o i n t of (+)-29 suggests that any s o l i d - s t a t e r e a c t i o n , even i f slower by one or two orders of magnitude, might s t i l l be measurable. 2.1.2 The S o l u t i o n Phase The r a c e m i z a t i o n of (+)-29 was a l s o s t u d i e d i n t e t r a l i n s o l u t i o n , at temperatures where the pure d i a c i d 2_9_ would be s o l i d (131-152°). 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 the observed r a t e constants are shown i n Table I. k 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 l i n e . 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 omitted f o r s i m p l i c i t y . 19 T I M E M I N U T E S Figure 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 of neat ( + ) - d i a c i d 29 i n the melt phase. 20 Table I F i r s t - O r d e r Rate Constants f o r Racemization of and S o l u t i o n (+)-29 i n S o l i d , Melt Temperature, °C k x 10"*, sec ̂  obs Phase 194.3 380 melt 189.1 248 I I 181.8 147 I I 176.6 103 I I 166.2 8.3 a melt + s o l i d 161.2 7.09 a I I ti 155.4 4.23 s o l i d 152.4 2.76 I I 140.2 0.654 I I 130.9 0.227 I I 152.4 6.98 s o l u t i o n 143.7 2.93 I I 131.3 0.834 I I I n i t i a l r a t e constant. The a c t i v a t i o n parameters f o r rac e m i z a t i o n i n the melt and i n s o l u t i o n were obtained from a p l o t of l o g k ^ /T v s * 1/1 a s r e q u i r e d by the E y r i n g equation: 21 where K and h are Boltzmann's and Planck's constants, r e s p e c t i v e l y , t f T i s the absolute temperature, and AS and AH are the entropy and enthalpy of a c t i v a t i o n . The f r e e energy of 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 are l i s t e d i n Table I I and p l o t t e d i n Figure 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 to be some 2.0-2.5 times Table I I A c t i v a t i o n Parameters f o r Racemization of (+)-29 i n S o l i d , M e l t , and S o l u t i o n k Q b g (150°), AG* (150°), AH* AS* sec 1 k c a l mole 1 k c a l mole 1 c a l mole "'"deg 1 melt 11.3 x I O - 5 a 32.6 29.7 -6.9 s o l i d 2.05 x 1 0 - 5 34.0 40.0 +14 s o l u t i o n 5.14 x 10~ 5 33.2 33.6 +0.8 E x t r a p o l a t e d from the temperature range 176-194' slower than that i n the melt ( e x t r a p o l a t e d ) . This s m a l l d i f f e r e n c e 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 her f r e e energy of a c t i v a t i o n i n t e t r a l i n s o l u t i o n . 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 of reverse D i e l s - A l d e r I90° 180° 170° 160° 150° i I 40 c • 2.20 2.30 '/ xlCT T ~2AO Figure 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 fo ra c e m i z a t i o n of (+)-enantiomer 2_9_ i n melt, s o l i d , and s o l u t i o n ( i n t e t r a l i n ) phases. 23 r e a c t i o n s and recombinations. A l s o , the magnitude of the absolute r a t e constants i n both l i q u i d media i s c l o s e to that of s i m i l a r reverse n- 1 A U 4 2 » 4 3 D i e l s - A l d e r r e a c t i o n s . 2.2 Racemization i n the S o l i d State The racemization of the ( + ) - d i a c i d .29 was explored 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 of r e s o l v e d 29 were sealed i n ampules and h e l d at v a r i o u s temperatures below 176°. I t was found that r a c e m i z a t i o n could indeed occur as low as 130°. Moreover, the k i n e t i c form of the r e a c t i o n from 130° to 155° was f i r s t - o r d e r . P l o t s of l o g [ a ] / [ a ] Q vs. time were again l i n e a r to at l e a s t 90% ra c e m i z a t i o n (see Fi g u r e s 3 and 4 ) . There were no i n h i b i t i o n p eriods as have been v i r t u a l l y always observed f o r s o l i d - s t a t e 1 44a organic 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 to g r i n d i n g , d i f f e r e n t batch p r e p a r a t i o n s or sample h i s t o r y . A l s o absent was any dependence on the extent of r e s o l u t i o n of the samples. The k i n e t i c s i m p l i c i t y of the r e a c t i o n from 130° to 155° permitted treatment of the observed r a t e constants (Table I) i n the same manner as those f o r r e a c t i o n i n the melt and i n s o l u t i o n . The p l o t of l o g k ^ /T aga i n s t r e c i p r o c a l temperature i s shown i n Figure 2. A c t i v a t i o n parameters (Table I I ) were obtained from the r e s u l t i n g s t r a i g h t l i n e . The r a t e constant a t 150° i s seen to be only about 5 times s m a l l e r than that obtained from the melt e x t r a p o l a t e d to 150°. In the temperature range 161°to 166°, a departure from simple f i r s t - o r d e r k i n e t i c s was observed (Figures 4 and 5 ) . A sigmoid shape 24 1 1 I i i I 2 0 0 0 4 0 0 0 6 0 0 0 8 0 0 0 IO.OOO TIME M I N U T E S Figure 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, p o l y - c r y s t a l l i n e (+)-29 i n the s o l i d phase. 25 < ' 1 1 i i i i O 2 0 0 4 0 0 6 0 0 8 0 0 IOOO 1200 1400 T IME M I N U T E S Figure 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 - c r y s t a l l i n e (+)-2_9 at 152° i n the s o l i d phase and at 161° where melt „ * i s o l i d . 26 2 0 4 0 6 0 8 0 IOO 120 TIME MINUTES Figure 5. K i n e t i c data f o r ra c e m i z a t i o n of neat samples of (+)-29 i n the s o l i d (155°), i n the biphase melt + s o l i d system (166°), and i n a completely melted system (at 176°) . 27 was q u i t e evident i n the f r a c t i o n unracemized vs. time p l o t s at these two temperatures (Fi g u r e 5 at 166°). The l o g p l o t s deviated from l i n e a r i t y ( F i g . 4 at 161°). Rate constants were, however, obtained from the i n i t i a l slopes of the l o g p l o t s (Table I) f o r comparison to the observed f i r s t - o r d e r constants from lower temperature runs. S i g n i f i c a n t y e l l o w i n g of the samples occurred, much more r a p i d l y than w i t h the melt r e a c t i o n at temperatures as high as 194°. Some s i n t e r i n g i n d i c a t e d p a r t i a l m e l t i n g . 2.3 The Phase Diagram 2.3.1 The Determination of the Phase Diagram In order to 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 necessary to a s c e r t a i n the temperature below which the system of enantiomers i s t o t a l l y s o l i d . To t h i s end, the b i n a r y phase diagram was 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 . In general there are only three types of b i n a r y phase diagrams 45a 46 formed between enantiomers. ' These are the simple e u t e c t i c , the formation of a "phase r u l e " compound, and formation of a s o l i d s o l u t i o n at a l l compositions. In the simple e u t e c t i c the c r y s t a l form of one enantiomer does not accommodate the other and the racemic m o d i f i c a t i o n i s a two-phase mixture of i n d i v i d u a l c r y s t a l s of pure enantiomers. The "phase r u l e " compound diagram 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 are i m m i s c i b l e , but the racemic m o d i f i c a t i o n i s a s i n g l e phase (the racemate) c o n t a i n i n g both enantiomers i n a 1:1 r a t i o . In the s o l i d c except at the extreme edges of the diagram. 28 s o l u t i o n type of diagram, the c r y s t a l l a t t i c e of one enantiomer can co n t a i n the other 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 compositions. The s i n g l e o b s e r v a t i o n that the racemic d i a c i d 29_ melts higher than the r e s o l v e d m a t e r i a l immediately r e s t r i c t s the choices of diagrams to two: (a) formation of a phase r u l e compound or (b) formation of a s o l i d s o l u t i o n m e l t i n g higher when racemic than when r e s o l v e d . The choice between these two i s e a s i l y made w i t h the d i f f e r e n t i a l 47 scanning 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, and can be used to measure phase changes which are r a p i d , such as me l t i n g or f a s t s o l i d - s o l i d t r a n s i t i o n s . The procedure i n v o l v e s heating a s m a l l amount of sample i n a pan and an empty reference pan at a constant r a t e . Any energy r e l e a s e or absor p t i o n i n the sample i s compensated by the c a l o r i m e t e r so that the area of the recorded peak 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 . T r a n s i t i o n temperatures are e a s i l y determined once the d.s.c. i s c a l i b r a t e d . Samples of the d i a c i d 29_ ranging i n s p e c i f i c r o t a t i o n from +137° to 0° were heated on the d s . c . and the temperatures and e n t h a l p i e s of t r a n s i t i o n were determined. Some r e p r e s e n t a t i v e d.s.c. tr a c e s are shown i n Figure 6. The re s o l v e d and racemic d i a c i d 29_ gave no peaks from room temperature up to the 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 recorded. The e n t h a l p i e s of f u s i o n (AH J ) were 5.38+ 0.16 k c a l mole" 1 (29.5 ± 0.9 c a l g _ 1 ) f u s i o n f o r the (+) enantiomer 29_ and 7.13 ± 0.24 k c a l mole" 1 (39 ±1.3 c a l g _ 1 ) f o r the racemic m a t e r i a l . The corresponding e n t r o p i e s of f u s i o n were c a l c u l a t e d from: 29 Figure 6. D i f f e r e n t i a l scanning c a l o r i m e t e r t r a c e s (programming r a t e : 10 deg min f o r the d i a c i d 2_9_ at various compositions: (a) 0%, (b) 24.8%, (c) 45.2%, and (d) 50% (-)-enantiomer. 30 A H . . [3] A S . . = ^ U S 1 ° n f u s i o n T m.p. which holds only at the melti n g p o i n t where the f r e e energies of s o l i d and melt are 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 f u s i o n — 12.0 ± 0.3 c a l deg "'"mole "*" and f o r the racemic d i a c i d , 15.5 ± 0.5 c a l deg "'"mole \ Samples intermediate i n a c t i v i t y , however, gave a s i n g l e endotherm at 165°, sometimes fo l l o w e d by a second endotherm at s l i g h t l y h i g h er temperatures. The endotherm at 165° i n samples having a range of 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. The endotherm i s l a r g e s t f o r a sample having a s p e c i f i c r o t a t i o n of +68°. These observations are those expected f o r a phase system w i t h racemic compound formation. A e u t e c t i c p o i n t (temperature: 165°, composition: h a l f resolved) e x i s t s between the r e s o l v e d and racemic d i a c i d 29. The temperatures at which the d.s.c. peaks appeared are p l o t t e d i n F i g ure 7. The appearance of a second endotherm f o r some samples i s 48 49a c o n s i s t e n t w i t h the phase system. ' At appropriate compositions, these samples w i l l p a r t l y melt at the i n v a r i a n t e u t e c t i c temperature, then f i n i s h m e l t i n g over a range of temperatures from the e u t e c t i c to the l i q u i d u s curve. The appearance of a second peak i n d i c a t e s the maximum rate of t h i s secondary m e l t i n g . The p o i n t at which the second peak returns to the base l i n e i s sometimes taken as the p o s i t i o n 48 of the l i q u i d u s curve, but i n our samples the melt was too v o l a t i l e to a l l o w a p r e c i s e determination of t h i s p o i n t . For completeness, the l i q u i d u s curves have been sketched i n the phase diagram (dotted l i n e s ) 31 u o w ai H 180 170 V —1 ^ - 160 150 140 MELT PHASE 1 / / / 1 SOLID SOLUTION (y) PHASE j I J L _L \ \ \ / x MELT PHASE \ \ \ \ / \ /\ * / '' \ / RACEMATE PHASE _L J L 20 40 60 PERCENTAGE (-)-ENANTIOMER 80 100 Figure 7. Phase relationship of mixtures of (+)- and (-)-enantiomers of compound 29_. Vertical bars indicate the uncertainties in transition temperatures (taken at the beginning of d.s.c. endotherms). Undetermined phase boundaries (dotted lines) are estimated for 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> which must e x i s t , ' but may have a composition range which i s s m a l l and d i f f i c u l t to determine w i t h the d.s.c. The second h a l f of 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 Figure 7 f o r completeness. The (-)-enantiomer 29 was not i s o l a t e d . The d.s.c. r e s u l t s were v e r i f i e d by X-ray powder photography. Photographs of 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 of the racemate. A sample which had been h a l f racemized showed both se t s of 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 . There are t h e r e f o r e two s o l i d phases at t h i s composition. No metastable i n t e r m e d i a t e phases are formed during 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 of Reactive Phases Knowing the phase diagram (Figure 7 ) , we are now able to consider the phases i n which r a c e m i z a t i o n occurs. From 130° to 155°, only s o l i d phases are 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 . As r a c e m i z a t i o n proceeds, an u n r e a c t i v e racemate separates from the r e a c t i v e s o l i d (+)-enantiomer. Between the e u t e c t i c temperature and the m e l t i n g p o i n t s concerned, the melt and s o l i d c o e x i s t , and r e a c t i o n occurs simultaneously i n both phases. S o l i d samples w i l l e v e n t u a l l y melt when held at tempera- tures i n t h i s range. As r a c e m i z a t i o n proceeds, the l i q u i d phase 37 grows i n volume at the expense of the s o l i d phase. I t can be shown that a f i r s t order r e a c t i o n i n a di 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 growing melted phase, w i l l give r i s e to 33 an S-shaped k i n e t i c curve. Such curves are observed i n runs at 161° and 166° (Figure 4,5). 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 and 37 melted phase r e a c t i o n s can, i n p r i n c i p l e , be separated. However, i n t h i s case the a v a i l a b i l i t y of k i n e t i c data at temperatures where the system i s t o t a l l y melted or 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 of the phase diagram to chart the course of a chemical r e a c t i o n should perhaps be e x p l a i n e d more f u l l y . The meaning of 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 described are not i n chemical e q u i l i b r i u m . Systems of dynamically i n t e r c o n v e r t i n g isomers such as the enantiomeric d i a c i d s 29_ are t r e a t e d i n standard t e x t s on phase e q u i l i b r i a as "pseudobinary s y s t e m s " . ' T h i s term means that 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 (such as w i t h a d.s.c.) i t i s p o s s i b l e to determine a b i n a r y phase diagram. The necessary c o n d i t i o n here i s that the composition of the sample should not change during the time taken f o r the experiment. In t h i s case, at the us u a l d.s.c. heating r a t e s (10°/min), the m e l t i n g r e g i o n i s covered i n l e s s than two minutes, during which time very 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 determining such " n o n e q u i l i b r i u m " phase diagrams 52 seem w e l l understood, but the meaning of such diagrams becomes c l e a r e r from the p o i n t of view of free energy. Consider f i r s t of a l l a Although 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 darkening of samples i n d i c a t e s that other components are formed. These can lower the b i n a r y e u t e c t i c temperature,53 causing the appearance of a l i q u i d phase. 34 two-component system of isomers, 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 r e a c t i o n . At constant pressure, the f r e e energy of each phase w i l l be a f u n c t i o n of temperature and composition. A three-dimensional p l o t of temperature - composition-free energy w i l l t h e r e f o r e c o n s i s t of i n d i v i d u a l f r e e energy surfaces - one f o r each phase - suspended over the temperature-composition plane ( i . e . the phase diagram). The s t a b l e phase (or phases) at each p o i n t on the diagram i s determined by the lowest f r e e energy su r f a c e (or combination of s u r f a c e s ) - ^ ' ^ above th a t p o i n t . Hence the e q u i l i b r i u m phase diagram i s generated. I f the phases at every p o i n t are always the most s t a b l e ones ( i . e . a l l phase changes are r a p i d ) , then a l l p o i n t s on the phase diagram are a t t a i n a b l e e x p e r i m e n t a l l y . 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 before. I t s t i l l , t h e r e f o r e , makes sense to 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 the phase diagram which these determine i s not an e q u i l i b r i u m diagram. For example, the e m e l t i n g p o i n t of a pure isomer can be d e f i n e d as the temperature at which the f r e e energies of the pure s o l i d and pure l i q u i d isomer are e q u a l , but such a p o i n t i s not i n e q u i l i b r i u m . The system can lower i t s f r e e energy f u r t h e r by changing i t s composition u n t i l f i n a l chemical e q u i l i b r i u m i s reached. I f the phases e x i s t i n g at any temperature and composition are always those having the lowest f r e e energies at that p o i n t , then the phase changes are f a s t . The diagram can then be determined e x p e r i m e n t a l l y , provided the i s o m e r i z a t i o n r e a c t i o n e Such a p o i n t has been c a l l e d an " i d e a l constant" and the pseudobinary system has been r e f e r r e d to as a system i n " f a l s e equilibrium"45b b ut. 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 , although i m p l i e d , should be e x p l i c i t l y s t a t e d . 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 too f a s t , some p o i n t s , such as the pure isomer m e l t i n g p o i n t s , may be imp o s s i b l e to a t t a i n (see S e c t i o n 3.3.2.1). In t h i s manner, by assuming that phase changes are more r a p i d than the i s o m e r i z a t i o n , the course of a r e a c t i o n may be mapped on a phase diagram. For example, when a r e a c t i o n i s "passing through" a two-phase s o l i d + melt r e g i o n at constant temperature and pr e s s u r e , the composition of the s o l i d and melt phases w i l l be constant and equal to the s o l i d u s and l i q u i d u s compositions. Such an approach i s b a s i c to our treatment of r e a c t i o n s i n neat organic m a t e r i a l s . 2.4 Mechanism i n the S o l i d State In view of the 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 the k i n e t i c s i m p l i c i t y of t h i s r a c e m i z a t i o n i s s u r p r i s i n g . Reactions i n organic 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 , " ^ or a dependence on aging and on p a r t i c l e s i z e . " ^ A l l of these f e a t u r e s are conspicuously absent below the e u t e c t i c of the system of enantiomers which 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 that the rate-determining 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 occur w i t h equal p r o b a b i l i t y at 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 , the l o c a t i o n of the d i a c i d molecules 2_9_ (whether they are at the edges of c r y s t a l l i t e s , at defects or d i s l o c a t i o n s , or deeply imbedded i n a re g i o n of 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 to t h e i r r e a c t i v i t y . C o nsistent 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 pub l i s h e d symposia on the R e a c t i v i t y of S o l i d s . 36 o b s e r v a t i o n that g r i n d i n g or use of d i f f e r e n t batch p r e p a r a t i o n s has no e f f e c t on the k i n e t i c r e s u l t s . In these d i f f e r e n t samples there 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 defect or 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 presence of the product (racemic compound). As the product phase grows, the reactant-product i n t e r f a c e w i l l i n c r e a s e , pass through a maximum, then decrease as the r e a c t a n t disappears. In some organic d e c o m p o s i t i o n s t h e developing product s u r f a c e causes a c c e l e r a t i o n of the r e a c t i o n and the p r o d u c t i o n of sigmoid-shaped k i n e t i c curves. In our system, maximum r a t e occurs at the beginning 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 due to a very short a c c e l e r a t i o n p e r i o d and the presence of product phase, because X-ray r e s u l t s c l e a r l y show only the pure enantiomer at the s t a r t of the r e a c t i o n . Therefore, the n e c e s s i t y of having to grow a product phase from a re 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 change of 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 to 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 be given to the nature of the rate-determining s t e p . In the melt, the r a c e m i z a t i o n w i l l c o n s i s t of a r e v e r s i b l e f i r s t - o r d e r r e a c t i o n : 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 decompositions show f i r s t - o r d e r behaviour because of a very 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 of 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 that our observed f i r s t - order k i n e t i c s are not due to t h i s e f f e c t . 37 k l A (melt) „ B (melt) k 2 where A and B are the enantiomeric adducts 29_- Since the r a c e m i z a t i o n proceeds to 0° s p e c i f i c r o t a t i o n , k^ = k^. The observed f i r s t - o r d e r r a t e constant w i l l , as i s usual i n such e q u i l i b r i a , c o n s i s t of the sum of the forward and reverse r a t e constants, o r : k (melt) = kn + k„ = 2k, obs 1 2 1 In the a c t i v a t i o n p l o t (Figure 2 ) , k k s (melt) was used. S u b s t i t u t i o n of k Q ^ s (melt) = 2k^ i n Equation 1 (p 20 ) w i l l make no d i f f e r e n c e to ± the enthalpy of a c t i v a t i o n , AH , but w i l l a f f e c t the i n t e r c e p t and hence As i n a s m a l l way. To c o r r e c t f o r t h i s , the entropy of a c t i v a t i o n should be augmented by 2.303R l o g 2 } or 1.4 c a l deg "'"mole "'". This c o r r e c t i o n i s s m a l l compared to the l a r g e entropy d i f f e r e n c e between r e a c t i o n i n the melt and i n the s o l i d (21 c a l deg "'"mole "'") . In the s o l i d , the mechanism cannot be t h i s s imple, i n view of the phase r e l a t i o n s h i p s between enantiomers. However, any mechanism must i n c o r p o r a t e the ob s e r v a t i o n of f i r s t - o r d e r k i n e t i c s . A reasonable sequence of events c o n s i s t s of the f o l l o w i n g : k 3 A(y) B ( Y ) k 4 k 5 A(y) + B ( Y ) C ( Y ) C ( Y ) • C(separate phase) 38 C represents the product compound, which i s considered as a hydrogen bonded p a i r of enantiomers. A l l species are f i r s t contained i n the Y phase (Figure 7). At low conversions, the f i r s t products formed from a f i r s t - o r d e r process i n a s i n g l e r e a c t a n t phase would 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 react a n t m a t r i x h could not form a separate phase. As r e a c t i o n proceeds, the react a n t phase would e v e n t u a l l y become supersaturated i n product, and unstable w i t h respect to a two-phase reactant-product system. The l a s t r e a c t i o n t h e r e f o r e shows the compound C se 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 discussed above) from the 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 of enantiomers w i l l not have equal r a t e constants ( i . e . , k^ ^ k^) i n the y phase as i s the case i n the melt phase. The y c r y s t a l s w i l l present a dissymmetric environment to the enantiomer B, causing a d i f f e r e n c e i n the f r e e energies of A and B i n the y phase. The a d d i t i o n of B enantiomer to pure A w i l l f i r s t lower^^'^''" then r a i s e the t o t a l f r e e energy of the y phase (see Figure 8 ( a ) ) . The f r e e energies of the species B and C r e l a t i v e to A are shown s c h e m a t i c a l l y i n Figure 8 (b). B and C are at a higher energy than A because they are not expected 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 constants w i l l t h e r e f o r e l i k e l y be ordered k. < k.. Once a B molecule i s formed, i t w i l l be surrounded 3 4 w i t h A molecules, and w i l l probably be e a s i l y able to move i n t o p o s i t i o n to form hydrogen bonds w i t h A, thereby c r e a t i n g compound C. I f t h i s k In some p h o t o d i m e r i z a t i o n s , the product i s c o n s i d e r a b l y s o l u b l e i n the reactant l a t t i c e . ' * TEMPERATURE: 150° o w •z w W W RACEMATE PHASE MIRROR IMAGE OF (y) PHASE' 50 PERCENTAGE (-)-ENANTIOMER 100 O W Z w w w Pi REACTION COORDINATE Figure 8. (a) Schematic f r e e energy-composition p l o t i n the phase system (+)- and (-)-29, at constant pressure (atmospheric) and temp- era t u r e (150°) . The dotted l i n e s show the lowest f r e e energy surfaces f o r the two-phase reg i o n s . (b) Schematic f r e e energy-reaction coordinate p l o t f o r the s o l i d - s t a t e r a c e mization of (+)-29 (shown as A (y)) at 150°. 40 r e a c t i o n i s f a s t , then perhaps 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 k^ << k,. A(y) throughout most of the r e a c t i o n . (A(y) i s the mole f r a c t i o n of t o t a l d i a c i d which i s A and i n y. This q u a n t i t y i s u n i t y at the beginning of the r a c e m i z a t i o n , and zero at the end.) The r a t e equation f o r the disappearance of A(y) i s : [ 4 ] _ dA£r)_ = k ^ A ( y ) _ k^B (y) + k 5 A ( y ) B ( y ) 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 ntermediate i n the y phase. A steady-state treatment on B(y) g i v e s : [5] = 0 = k 3 A ( y ) - k 4 B ( y ) - k 5 A ( y ) B ( y ) k A(y) k B(y) = J ~ J k 4 + k 5 A ( y ) k 5 S u b s t i t u t i o n of [5] i n t o [4] y i e l d s : [6] - = k 3A(y) - ^ + k 3 A ( y ) = 2k 3A(y) I n t e g r a t i o n w i l l give the r e s u l t k ^ g ( s o l i d ) = 2k^. Therefore, the above assumptions about the r e l a t i v e magnitudes of the r a t e constants l e a d to the c o n c l u s i o n that as soon as one A converts to B, another immediately disappears i n the formation of C. As w i t h the melt 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 Equation 1 (p 20 ) does not a l t e r AH' f o r the s o l i d , and ± -1 -1 changes the c a l c u l a t e d AS only by a s m a l l amount (1.4 c a l deg mole ) 41 The a c t i v a t i o n parameters d e s c r i b e the same process i n the melt as i n the s o l i d - the reverse D i e l s - A l d e r r e a c t i o n and recombination to form the enantiomer - and can be compared f o r the two phases. Although the f r e e energies of a c t i v a t i o n are c l o s e (Table I I ) , the c a l c u l a t e d J . 4. AH T and AS are markedly d i f f e r e n t . Passage of the adduct from the ground s t a t e to the t r a n s i t i o n s t a t e apparently i n v o l v e s an entropy i n c r e a s e (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 the cost of a higher energy of a c t i v a t i o n than i n the melt. The s i m i l a r i t y of r a t e constants i n the s o l i d and melt (k , (mel t ) / obs k Q k g ( s o l i d ) = 5 at 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 the few examples i n which 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 (ca. 10 -10 ). However, the endo cyclopentadiene-maleic anhydride 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 to a p l a s t i c c r y s t a l l i n e s o l i d 37 s t a t e . Such mobile s o l i d s are c h a r a c t e r i z e d by a low entropy of -1 -1 59a f u s i o n (ca. 5 c a l deg mole ), much sma l l e r than the entropy of f u s i o n observed (12 c a l deg "'"mole "'") f o r the (+)-cyclopentadiene- fumaric a c i d adduct 29_, reported here. U n l i k e the endo anhydride 27, there 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 the melt and i n the s o l i d s t a t e . S e v e r a l years ago H i n s h e l w o o d ^ considered t h i s energy d i f f e r e n c e i n r e l a t i o n to the r a t e constants i n both s t a t e s . Assuming that the t r a n s i t i o n s t a t e i s the same i n both s o l i d and melt, he suggested 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 to the enthalpy of f u s i o n : w A H . . f 7 i n k(melt) _ f u s i o n 1 J k ( s o l i d ) ~ RT However, s u b s t i t u t i o n of our determined AH^ . (5.38 k c a l mole ^) f u s i o n 2 leads to a r a t i o of k ( m e l t ) / k ( s o l i d ) of 6 x 10 at 150°, c o n s i d e r a b l y greater than the observed f a c t o r of 5. An improved r e l a t i o n s h i p 37 considers 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 . , accounts f o r both enthalpy and entropy d i f f e r e n c e s ) : r o , „ k(melt) G(melt) - G ( s o l i d ) [ 8 ] £ n k ( s o l i d ) = RT Near the m e l t i n g p o i n t , the f r e e energy d i f f e r e n c e between the phases can be approximated by the enthalpy and entropy of f u s i o n : ^ 1 w . . AH . AS. , roi o k(melt) _ f u s i o n f u s i o n 1 J l n k ( s o l i d ) RT ~ R f u s i o n ,1_ 1_ . R T̂ ~ T } m.p. where the r e l a t i o n A s . . = AH. . /T „ (Equation 3, p 30) has f u s i o n f u s i o n m.p, v ^ » ^ been taken i n t o the equation. S u b s t i t u t i n g . =5.38 k c a l mole n e f u s i o n y i e l d s k ( m e l t ) / k ( s o l i d ) = 1.5 at 150°, c o n s i d e r a b l y c l o s e r to the observed r a t i o of 5. In the 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 taken 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 energies o n l y . In g e n e r a l , however, both 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 those 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 molecule i n the 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 addends (cyclopentadiene and fumaric acid) produced as intermediates i n the reverse D i e l s - A l d e r r e a c t i o n w i l l be h e l d i n p o s i t i o n by the surrounding l a t t i c e r a t h e r than d i f f u s i n g apart. I f the r e s t r i c t i o n i s severe enough, such a cage e f f e c t could be s t e r e o s p e c i f i c ; i n t h i s case s t e r e o s p e c i f i c i t y would be revealed 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 , s i n c e 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 r a t e r e t a r d a t i o n i s only 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 are f r e e to r o t a t e q u i c k l y and recombine, forming the enantiomer 29. 2.5 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 r e o r g a n i z - t i o n r e a c t i o n s may not be a p p r e c i a b l y k i n e t i c a l l y hindered i n the s o l i d s t a t e . The higher energy needed to 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 favourable 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 . Reactions i n s o l i d s can be k i n e t i c a l l y simple even though a phase change occurs during r e a c t i o n . Examples of f i r s t - o r d e r r e a c t i o n s 37 62 i n neat organic s o l i d s ' are r a r e , but t h i s i s perhaps only a r e f l e c t i o n on the s m a l l number of systems that have been s t u d i e d from a k i n e t i c standpoint. Observation i n s i n g l e c r y s t a l s of a product phase appearing at 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 ' does not n e c e s s a r i l y i n d i c a t e that r e a c t i o n occurs at such s i t e s . Instead, i t may mean that the product has already been formed by a simple process i n s i d e the r e a c t a n t c r y s t a l , and i s only s e p a r a t i n g out at such i r r e g u l a r i t i e s . K i n e t i s t u d i e s w i t h p o l y c r y s t a l l i n e samples can be used to d i f f e r e n t i a t e between the two p o s s i b i l i t i e s . 3 RESOLUTION OF RACEMIC 1,1'-BINAPHTHYL IN THE SOLID STATE The compound 1,1'-binaphthyl i s one of the si m p l e s t c h i r a l hydro- carbons. I t s dissymmetry i s molecular i n nature, 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 simply by r o t a t i o n about the i n t e r a n n u l a r bond, r a t h e r than by any bond-breaking process. 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 to a l l o w i s o l a t i o n of e i t h e r enantiomer. F i r s t r e s o l v e d i n 1961, S-(+)-1,1'-binaphthyl has been used i n s o l u t i o n r a c e m i z a t i o n s t u d i e s . ^ ^ The h a l f - l i f e f o r rac e m i z a t i o n i n s e v e r a l s o l v e n t s i s ca, 15 min at 50°. Recently, R-(-)-1,1'-binaphthyl was 67 a l s o r e s o l v e d and st u d i e d i n s o l u t i o n . The absolute c o n f i g u r a t i o n 68 of 1,1'-binaphthyl was deduced from a c r y s t a l l o g r a p h i c study i n 1968. 46 3.1 The P r e p a r a t i o n of 1,1'-Binaphthyl 3.1.1 S-(+)-1,1'-Binaphthyl from the Diastereomeric R e s o l u t i o n of Racemic 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 of o p t i c a l l y a c t i v e 1,1'-binaphthyl by s y n t h e s i z i n g racemic naphthidine (31). The f i r s t p r e p a r a t i o n of naphthidine which we attempted was that 69 given by Sah and Yuin. 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 of 1-amino- naphthalene by f e r r i c oxide: NH 2 31 The reported y i e l d of p u r i f i e d naphthidine was 60%. However, i n our hands the method gave poor y i e l d s (<10%) of n a p h t h i d i n e , and the procedure was abandoned i n favour of another which seemed more promising. This second p r e p a r a t i v e route was developed by Cohen and O e s p e r . ^ 1-Aminonaphthalene was d i a z o t i z e d then r e d u c t i v e l y coupled to form azonaphthalene (32), which was i s o l a t e d i n a crude form. The azo- naphthalene was suspended i n b o i l i n g ethanol 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, which immediately rearranged to naphthidine h y d r o c h l o r i d e . Treatment w i t h sodium hydroxide regenerates the f r e e base. The y i e l d of r e c r y s t a l l i z e d 47 naphthidine was stated as 33.5%. The procedure worked well, and we were 32 able to prepare 45 g of pure naphthidine (m.p. 201-202°) by repeating the sequence eight times. Average yield of the last five preparations was 26%. Racemic naphthidine was then resolved by forming the salt with (+)-ammonium a-bromo-D-camphor—iT-sulfonate. Theilacker and Hopp^1 have performed this resolution. Use of two moles of resolving agent for each mole of naphthidine gave 65% material after recrystallization from ethanol-water. We carried this resolution as far as the salt 33, obtaining the material in somewhat lower yields but comparable specific rotations ([a] = +80°). 48 The (+)-naphthidine a-bromo-D-camphor-ir-sulf onate s a l t (33) can be d i r e c t l y deaminated to S - ( + ) - l , l ' - b i n a p h t h y l , without having to i s o l a t e 33 f r e e (+)-naphthidine. This procedure was devised by C o l t e r and Clemens, and gave (+)-1,1'-binaphthyl ([a] = +145-165°) i n 40-55% y i e l d . We adopted t h i s method, w i t h a s l i g h t l y m odified p u r i f i c a t i o n procedure, and were able to o b t a i n S-(+)-1,1'-binaphthyl ([a] = +97°) i n 55% y i e l d . 3.1.2 Racemic 1,1'-Binaphthvl from O p t i c a l l y I n a c t i v e Reagents In order to c h a r a c t e r i z e f u l l y the phase system formed between re 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 enantiomers), some racemic 1,1'-binaphthyl was prepared. 72 The p r e p a r a t i o n followed was that of S a k e l l a r i o s and K y r i m i s . The Grignard reagent from 1-bromonaphthalene was coupled 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 Resolution 1 1 1 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 will 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. It was learned that the figure should be correct to within ±2°. The increase therefore seemed genuine, but needed verification. 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 at 120°. A n a l y s i s showed that the l a t t e r had not changed at a l l from [a] = +79°, but the o r i g i n a l m a t e r i a l had increased from [a] = +99° to +114°. Even a f t e r such prolonged h e a t i n g the sample remained a white, c r y s t a l l i n e s o l i d and gave the s i n g l e 1,1'-binaphthyl peak when analyzed 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 racemizing, i n the s o l i d s t a t e . This 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 order to f i n d the range of temperatures i n which t h i s phenomenon might occur, the second temperature chosen was 150°, nearer the higher m e l t i n g p o i n t of 158°. Samples of both batches of o p t i c a l l y a c t i v e 1,1'-binaphthyl, along w i t h some c o n t r o l samples of racemic 1,1'-binaphthyl (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 pentane) were heated f o r v a r i o u s lengths of time (Table I I I ) . 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 of a c t i v e 1,1'-binaphthyl increased s t e a d i l y from [a] = +99° to +163° over a p e r i o d of 2.5 days. Samples from the s l o w l y r e c r y s t a l l i z e d batch, which had remained at [a] = +79° at 120°, increased to [a] = +205° w i t h i n two hours and remained at t h i s r o t a t i o n f o r 2.5 days. The racemic 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 at [a] = 0° throughout. However, the s l o w l y r e c r y s t a l - l i z e d racemic sample, s u r p r i s i n g l y , developed o p t i c a l a c t i v i t y . R o tations were somewhat s c a t t e r e d , but a l l eleven i n d i v i d u a l samples were p o s i t i v e . This s e l f - r e s o l u t i o n of l , l ' - b i n a p h t h y l can apparently occur even i n m a t e r i a l which i s racemic ([a] = 0.0 JT 0.5°). This unusual behaviour of s o l i d 1,1'-binaphthyl prompted a search f o r a method of preparing batches of b i n a p h t h y l which would r e s o l v e to a high 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 simply on he a t i n g . Since a l l 51 Table I I I Summary of I n i t i a l I n v e s t i g a t i o n s of the Development of 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 1,1'-Binaphthyl Used Temperature, °C Time, hours [ a ] , degrees M a t e r i a l of [a] = +99° 120 1 +108 I I i t 36 +114 i t 149.6 1 +126 I I tt 2 +130, +129° i t I I 5 +135, +133° i t I I 24 +157, +152 c " I I 63.5 +163 b M a t e r i a l of [a] = +79° 120 36 +79 I I 149.6 1 +105 " i t 2 +193, +205° I I i t 5 +208, +206° I I i t 24 +208, +210° I I I I 63.5 +207 Racemic Batch A 149.6 12.5 0, 0° I I I I 37.5 0, o c I I i t 63.5 0 ^Racemic Batch B 149.6 0.017 +4 I I it 0.083 +41, +47 C I I " 0.5 +98, +90 C I I it 1.0 +79 52 (Table I I I , continued) Racemic Batch B, continued 149.6 12.5 +119, +79 C I I I I 37.5 +93, +83 I I I I 63.5 +97 From a f a s t r e c r y s t a l l i z a t i o n (pentane). k From a slow r e c r y s t a l l i z a t i o n (pentane). S p e c i f i c r o t a t i o n s of two i n d i v i d u a l samples heated f o r the same leng t h of time at the same temperature. s o l i d samples of 1,1'-binaphthyl had been r e c r y s t a l l i z e d , the next s e v e r a l weeks were devoted to t r y i n g to develop a method of 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 " from pentane. V a r i a t i o n s were made i n the r a t e of r e c r y s t a l l i z a t i o n , the co n c e n t r a t i o n of 1,1'-binaphthyl i n the pentane s o l v e n t , and the method of seeding. No d e l i b e r a t e attempt was made to add seeds of f o r e i g n dissymmetric m a t e r i a l ; i t was d e s i r a b l e to r e s t r i c t the system e n t i r e l y to R- and S - l , 1 ' - b i n a p h t h y l . Once a r e s o l v a b l e batch ( i . e . , one which 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 heating) was obtained, however, c a r e f u l r e p e t i t i o n of the c r y s t a l l i z a t i o n procedure would not produce a second batch which was e q u a l l y as s u c c e s s f u l . From t h i s experimentation the f o l l o w i n g important f a c t was learned. A l l samples of 1 , 1 1 - b i n a p h t h y l , r e g a r d l e s s of the p a r t i c u l a r method of 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 or increased s p e c i f i c r o t a t i o n when heated i n the s o l i d s t a t e below 158°. No racemization ever occurred on heating pure, a c t i v e 1,1'-binaphthyl below i t s m e l t i n g p o i n t . A l s o , we observed that c o o l i n g a sample to room temperature or 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 increment 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 not cause a p p r e c i a b l e l o s s of a c t i v i t y . Combining these o b s e r v a t i o n s , we devised a c y c l i n g procedure which was capable 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 1,1'binaphthyl. 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 r e s o l v e d 1,1'-binaphthyl or a racemic m a t e r i a l which gained 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 at l e a s t as great as [a] = +190° could e v e n t u a l l y be obtained. (The l i m i t of r e s o l u t i o n , as we l a t e r discovered (Appendix A, p 178), i s [ct]p = i245°,) 1 F i r s t , the 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 conserve m a t e r i a l , the pentane was removed i n vacuo a f t e r the r e c r y s t a l l i z a t i o n was complete. The s o l i d was then heated at 150°, and an increment i n r o t a t i o n almost always occurred. A second r e c r y s t a l l i z a t i o n of t h i s more a c t i v e m a t e r i a l again produced c r y s t a l s which could 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, the o p t i c a l a c t i v i t y of any sample of 1,1'- bi n a p h t h y l could 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 which d i d not change on hea t i n g could be made to 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 at the r e c r y s t a l l i z a t i o n stage. An example of an experiment that produced a s p e c i f i c r o t a t i o n of [a] = +194° i n four c y c l e s , and one g i v i n g [a] = -194° a f t e r three c y c l e s are shown i n i ' Table IV. One shortcoming of t h i s procedure was that although some increment i n r o t a t i o n was assured, we were unable to p r e d i c t how l a r g e i t would be. Some samples would i n c r e a s e only a few degrees on h e a t i n g ; others i ° The highest s p e c i f i c r o t a t i o n at the sodium D l i n e , 5893 A, reported f o r samples of 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 obtained by the c l a s s i c a l r e s o l u t i o n procedure i s [O]D = +192°.65 Other values are [a] = +245° at 5791 X 6 4 and [a] = -250°at 4360 A. 6 7 This conversion of e s s e n t i a l l y a l l of a racemic m a t e r i a l to only one ^ enantiomer i s sometimes r e f e r r e d to 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 the more general term, " r e s o l u t i o n . " 54 Table IV Examples of the C y c l i n g of Racemic 1,1'-Binaphthyl to High S p e c i f i c R o t a t i o n s Cycle Number [a] A f t e r R e c r y s t a l l i z a t i o n , degrees [a] A f t e r Heating at 150° degrees 1 0 ( +41, +44) a 2 ( +42, +44) 3 (+109, +116) 3 3 (+110, +112) a (+186, +185) 3 4 (+175, +179) a (+197, +190) 3 1 0 ( -52, - 4 5 ) a 2 -34 -79 3 -49 b -194 D u p l i c a t e analyses of the batch being c y c l e d . This 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 occurred because de- c o l o u r i z i n g carbon was used i n the pentane s o l u t i o n . 1,1'-Binaphthyl ra 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 carbon b l a c k s . jumped some 150° i n r o t a t i o n . Therefore, the number of c y c l e s r e q u i r e d to achieve [a] = ±190-220° v a r i e d from one to g r e a t e r than four i n the experiments attempted. This remarkable a b i l i t y of l , l ' - b i n a p h t h y l to r e s o l v e simply on heating r e f l e c t s an unusual s t e r e o s p e c i f i c i t y i n the s o l i d s t a t e . A thorough knowledge of the phase r e l a t i o n s h i p s of the 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 part of any e x p l a n a t i o n of the 55 phenomenon. Our attempts to establish the nature and relative s t a b i l i t y of the phases are reported in the following section. 3.3 Phase Diagram of the System R- and S-l,1'-Binaphthyl 3.3.1 Nature of the Phases The low- and high-melting forms of l,l'-binaphthyl reported by 73 Badar ejt a l were also obtained in our recrystallizations of racemic and partially active material. Contrary to their observations with racemic 1,1'-binaphthyl, we found no good correlation between the rapidity of recrystallization and the form obtained."' Both low- and high-melting forms resulted from both slow and rapid recrystallizations. 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, recrystallization would yield 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 in a nujol mull (Figure 9). The striking difference at 769 cm ^ and also the smaller differences from 940-980 cm ^ reported by these investigators are quite apparent. When 73 either form is taken into solution, these differences disappear. The fact that the most marked difference was in the C-H out-of-plane vibration region of the spectrum led these authors to suggest that within each R or S configuration, a cis (30a) conformation might exist in one crystalline modification, and a trans (30b) conformation in the other. ^ or, as just presented, any relation to the speed of recrystallization and the a b i l i t y of the material to resolve on heating. Figure 9. I n f r a r e d spectrum of 1,1 1-binaphthyl ( n u j o l m u l l ) , (a) Low-melting form. (b) High-melting form. 57 30a R-C-)-1,1'-Binaphthyl, cis conformation 30b R-(-)-1,1'-Binaphthyl, trans conformation X-Ray powder diffraction also differentiates 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 is listed the intensity of the line relative to the most i n - tense line in the photograph.(designated 100). The three strongest lines are indicated. This format is that of the American Society for 76a Testing Materials and allows a comparison between our results (obtained with Cu Ka radiation, wavelength 1.54178 X) and those of Hofer (obtained with Fe Ka radiation, wavelength 1.93728 X). In spite of his reported melting point (159.5-160°), there is l i t t l e correspondence between our pattern for the high-melting form and the 1,1'-binaphthyl pattern of Hofer. Rather, the four strongest lines on his pattern and on ours for the low-melting form are in close agreement. Similarities among the weaker lines are d i f f i c u l t to find, but at these low inten- s i t i e s comparison is d i f f i c u l t because our figures represent integrated intensities whereas his are visual 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 Low-Melting (Racemate) and High- 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 Low-Melting Form High-Melting Form L i t e r a t u r e 75 d, A I/I, d, X uh d, £ 10.1 25 6.9 10 10.2 50 5.3 3rd 45 6.4 2nd 70 6.0 25 5.0 3 2nd 80 5.6 3rd 55 5.4 3rd 75 4.65 5 5.0 5 5.0 2nd 80 4.07 5 4.74 50 4.66 25 3.94 20 4.39 3 1st 100 4.39 10 3.67 1st 100 4.07 5 4.11 50 3.14 5 3.72 70 3.98 50 2.97 20 3.46 10 3.69 1st 100 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 Unresolved doublet. 59 The f a c t which i s most apparent from Table V i s that the patterns f o r the low- and high-melting forms are c o n s i d e r a b l y d i f f e r e n t . The t o t a l absence of the stronger l i n e s of one form of 1,1 1-binaphthyl i n the p a t t e r n of the other a t t e s t s to the high "phase p u r i t y " of our samples. The low-melting form analyzed was racemic, but the h i g h - m e l t i n g form, which we could 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 the same p a t t e r n r e g a r d l e s s of the s p e c i f i c r o t a t i o n of the sample analyzed. 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 study of 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 . ^ This c r y s t a l 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 space group (C2/c), w i t h l a t t i c e parameters a = 20.98 X, b = 6.35 X, c = 10.13 1 and 8 = 105.7°. There are four molecules to each u n i t c e l l , two of which have the R conformation, the others being S. The two naphthalene u n i t s i n both R and S molecules are c i s disposed, w i t h an angle of 68° between them, and are very c l o s e to the dimensions of naphthalene i t s e l f . The e x i s t e n c e of an ordered a r r a y of equal numbers of R and S molecules e s t a b l i s h e s the low-melting 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 . Let us now consider the nature of the h i g h - m e l t i n g form. The f a c t that the X-ray powder photographs of t h i s form are the same at 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 low-melting form) as a p o s s i b i l i t y . ^ ' ^ This leaves a choice of e i t h e r a e u t e c t i c mixture of i n d i v i d u a l R and S c r y s t a l s or a s o l i d s o l u t i o n capable of c o n t a i n i n g both enantiomers i n a l l p r o p o r t i o n s . 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 to i d e a l s i n c e the d spacings remain unchanged as a f u n c t i o n of composition. In a n o n i d e a l s o l u t i o n one would expect a molar volume change (and hence a change i n d spacings) as the composition i s v a r i e d . The choice between there two a l t e r n a t i v e s was e a s i l y made by means of a r a t h e r f o r t u i t o u s r e s u l t . One batch of racemic l , l ' - b i n a p h t h y l happened to c r y s t a l l i z e from acetone over a few days i n e s p e c i a l l y l a r g e c r y s t a l s (2-4 mm i n diameter) which were shown by i n f r a r e d a n a l y s i s to be the h i g h - m e l t i n g form. We were t h e r e f o r e given the o p p o r t u n i t y of hand-picking the well-formed c r y s t a l s f o r p o l a r i m e t r i c a n a l y s i s . 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 mixture 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 should possess a high o p t i c a l r o t a t i o n i n e i t h e r d i r e c t i o n . 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 antipode w i t h equal ease. The s i n g l e c r y s t a l s would then grow by s e l e c t i n g randomly e i t h e r R or S molecules from a racemic s o l u t i o n , and would t h e r e f o r e possess, most probably, a r o t a t i o n of zero. The c r y s t a l s were examined under the p o l a r i z i n g microscope. No hemihedral faces were d i s t i n g u i s h a b l e . Although such enantiomorphous faces are always present i n e u t e c t i c mixtures of enantiomers, they are 46 not always s u f f i c i e n t l y w e l l developed to be e a s i l y observed. How- ever, the s i n g l e c r y s t a l s were r e a d i l y recognized under the microscope The p i c k i n g apart of s i n g l e c r y s t a l s , the o l d e s t method of r e s o l v i n g racemic m a t e r i a l s , ^ has never been widely used and remains somewhat of a n o v e l t y . However t h i s procedure, which i s not s y n t h e t i c a l l y u s e f u l because of 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 give v a l u a b l e i n f o r m a t i o n about the nature of the racemic m o d i f i c a t i o n , or even the very 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 given 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 hetero- h e l i c e n e s . 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 of the microscope stage between crossed p o l a r s . A sketch of the h a b i t of these c r y s t a l s i s shown i n Figure 10. The c r y s t a l would e x t i n g u i s h when viewed i n any p o s i t i o n other than normal to the c and d face s . Such a f a i l u r e to e x t i n g u i s h 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 being viewed 80 along an o p t i c a x i s , a p r e l i m i n a r y i n d i c a t i o n that each c r y s t a l being examined contains molecules of only one enantiomer. 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 separated from the mixture, d i s s o l v e d i n benzene, and analyzed f o r a c t i v i t y . The r e s u l t s (Table VI) show that each c r y s t a l was h i g h l y r e s o l v e d (nine out of ten Table VI S p e c i f i c R o t a t i o n s of S i n g l e C r y s t a l s Obtained from the R e c r y s t a l l i z a t i o n of Racemic 1,1'-Binaphthyl C r y s t a l Number Weight, 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 10 9.55 +197 62 Figure 10. Sketch of the habit of a s i n g l e c r y s t a l of pure R- or S-l,1'binaphthyl, showing those faces which were apparent under the microscope. (a) View of a, b, and c faces. (b) View normal to c face. (c) View normal to d face. 63 were at l e a s t 80% r e s o l v e d ) , and'that both R and S c r y s t a l s were present i n the mixture. The high-melting form i s t h e r e f o r e a e u t e c t i c mixture of i n d i v i d u a l R and S c r y s t a l s . In 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 "high-melting form," and w i l l apply to mixtures 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 composition (where an equimolar mixture of R and S c r y s t a l s e x i s t ) , to 100% S. The e u t e c t i c form i s not a s i n g l e s o l i d phase l i k e the racemate (low-melting form), but c o n s i s t s i n s t e a d of two s o l i d phases, an R phase and as S phase. The hi g h - m e l t i n g form i s not considered a polymorph^* 3 of the low- m e l t i n g form. Although the nature of both 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 of c r y s t a l l i n e 1,1'-binaphthyl are now known, the phase diagram cannot yet be c o n s t r u c t e d . Some i n f o r m a t i o n as to the temp- era t u r e ranges over which each form i s s t a b l e , must be obtained. This problem and i t s connection 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 be considered next. 3.3.2 R e l a t i v e S t a b i l i t y of the Phases The s i m p l e s t way to determine which of two phases l i e s lowest i n f r e e energy at a given temperature and composition ( i . e . , at a given p o i n t on the phase diagram) i s to observe the conversion of one to another at the p o i n t i n q u e s t i o n . With f a s t transformations (such as melting) t h i s o b s e r v a t i o n i s e a s i l y made. I f the phase changes are slow the problem becomes more d i f f i c u l t . In the course of t h i s work, s e v e r a l approaches were necessary i n determining the r e l a t i v e s t a b i l i t y 64 of a l l 1,1'-binaphthyl phases. 3.3.2.1 M e l t i n g 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'-binaphthyl was based on m e l t i n g p o i n t s . We confirmed that the low-melting form (a racemate) melts at 144-145°, and that the h i g h - m e l t i n g form (a e u t e c t i c mixture) melts at 157-158°. In f a c t , a l l samples of high-melting form, from [a] = 0 to ±245°, melted at 157-158°. This observation at f i r s t appears to c o n t r a d i c t our e a r l i e r f i n d i n g s , s i n c e e u t e c t i c mixtures of enantiomers c h a r a c t e r i s t i c a l l y melt lower at the racemic than at the r e s o l v e d composition. 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 of enantiomers, the system R- and S - l , 1 ' - b i n a p h t h y l i s a pseudobinary system ( S e c t i o n 2.3.2, p 32). 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 occur f a r below the i d e a l v a l u e s . The presence of f a c i l e r a c e m i z a t i o n i n the melt was e a s i l y v e r i f i e d . A 20 mg sample of 1,1'-binaphthyl ([a] = +234°) was sealed i n an ampule and immersed i n a bath thermostatted at 160.3°. In three minutes the sample a t t a i n e d t h i s temperature and completely melted, and a f t e r a t o t a l of f i v e minutes i t was quenched to room temperature. A n a l y s i s gave [cx]= 0.0 ± 0.5°. I f s o l u t i o n r a t e s of racemization of 1 , 1 ' - b i n a p h t h y l ^ ^ are e x t r a p o l a t e d to t h i s temper- a t u r e , the h a l f - l i f e i s l e s s than 0.5 sec. Racemization i s v i r t u a l l y instantaneous, and a r e l a t i v e l y slow r a t e of heating (1 deg min 1 i n a c a p i l l a r y m e l t i n g p o i n t apparatus, or even 40 deg min 1 w i t h a d i f f e r e n t i a l scanning c a l o r i m e t e r , as mentioned 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 of a m e l t i n g p o i n t which i s in 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- or S- 1,1'-binaphthyl i s t h e r e f o r e i m p o s s i b l e to determine."'" 1,1'-Binaphthyl which has been melted above 158° supercools to a great extent. Some melted samples can be h e l d at 125° 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 . However, the a d d i t i o n of seed c r y s t a l s of h i g h - m e l t i n g form to the melt j u s t below 158° r e a d i l y causes c r y s t a l - l i z a t i o n . S i m i l a r observations of the m e t a s t a b i l i t y of the 1,1'- 82 b i n a p h t h y l melt have been made by Binns and Squire, who reported that samples could be cooled as low as 120° without c r y s t a l l i z a t i o n . Samples of low-melting form c o n t a i n i n g very l i t t l e of the e u t e c t i c m o d i f i c a t i o n melted e s s e n t i a l l y completely at 144-145°. However, i f the samples cantained l a r g e r q u a n t i t i e s of the higher m e l t i n g e u t e c t i c , the 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 the melt of the former i n the temperature 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 to melt at a l l at 145°. In such cases, some m e l t i n g could be observed i f the sample was r a p i d l y immersed i n a temperature bath between 145-158°. From these observed t r a n s i t i o n s ( e u t e c t i c form ->- melt at 157-158°, racemate -*• melt -*• e u t e c t i c form from 145° to 158°, and melt -*-eutectic form below 158°), some or d e r i n g of the f r e e energy surfaces a s s o c i a t e d w i t h each phase can be deduced. The two p o s s i b l e f r e e energy s i t u a t i o n s 1 The behaviour of 1,1 1-binaphthyl on m e l t i n g emphasizes the dangers i n using m e l t i n g point as a means of deducing phase systems between o p t i c a l isomers. Although commonly used,^6 the m e l t i n g p o i n t diagram can lea d to erroneous conclusions i f the enantiomers are o p t i c a l l y u n s table. 66 are 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 Figure 11 (a) and ( b ) . The f r e e energy- temperature diagrams are taken at the racemic composition and at constant pressure (atmospheric). These curves resemble those f o r the two ways i n which 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 : the monotropic (Figure 11 (a)) and the e n a n t i o t r o p i c ( F i g u r e 11 (b)) r e l a t i o n s h i p . ^ * 3 ' ^ ' ^ k i n t h e f i r s t , the low-melting form (L) i s unstable r e l a t i v e to the h i g h - m e l t i n g form (H) at a l l temperatures below 158°. At 145°, L i n t e r s e c t s the melt s u r f a c e (M) and melts 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 of t h i s melt and a lowering of the f r e e energy of the system. At 158°, 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 e q u i l - i b r i u m w i t h the melt. In the second r e l a t i o n s h i p ( F i g u r e 11 ( b ) ) , the low-melting form i s s t a b l e below a t r a n s i t i o n temperature ( x ) , but e x h i b i t s the same m e l t i n g behaviour as i n the monotropic case. The choice 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 presence or absence of the 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 to p o s t u l a t e a mechanism f o r the r e s o l u t i o n r e a c t i o n . 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 e v i - d e n t l y occurs because the racemate phase melts, l e a v i n g c r y s t a l s of R- and S - l , l ' b i n a p h t h y l ( e u t e c t i c form) behind to act as seeds f o r the ensuing melt -* 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 the 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 only 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 only of S - l , 1 ' - b i n a p h t h y l can occur, the supply of S molecules being maintained 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 melt phase. Conversion of the e n t i r e sample to 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 , provided the unwanted R c r y s t a l s have been 67 Pi w w w (a) 145 158 TEMPERATURE (°C) PS W W w (b) T 145 158 TEMPERATURE (°C) u o (c) 0 50 100 PERCENTAGE S-ENANTIOMER o H 158 145 (d) 0 50 100 PERCENTAGE S-ENANTIOMER Figure 11. Schematic f r e e energy-temperature p l o t s f o r racemic 1,1'-binaphthyl, showing low-melting form ( L ) , high - m e l t i n g form (H) and melt (M) s u r f a c e s . (a) Monotropic r e l a t i o n s h i p , (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 diagram which would r e s u l t from the monotropic r e l a t i o n s h i p . (d) Phase diagram which would r e s u l t from the 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 . 68 e l i m i n a t e d . From studying the p o s s i b l e phase diagrams a r i s i n g from the mono- t r o p i c and 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 (Figure 11 (c) and (d).) , an important c o n c l u s i o n can be drawn. 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'-binaphthyl h e l d at p o i n t p contains only S c r y s t a l s and racemate c r y s t a l s when i n i t s most s t a b l e s t a t e . Such a sample, on heating to 150°, should t h e r e f o r e t o t a l l y r e s o l v e to S - l , 1 ' - b i n a p h t h y l because of the absence of R c r y s t a l s . Thermodynamics would t h e r e f o r e be o p e r a t i n g so as to favour the pro- d u c 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 sample of s o l i d 1,1'-binaphthyl. I t i s very d e s i r a b l e , then, to know which phase diagram describes the R- and S - l , 1 ' - b i n a p h t h y l system. 3.3.2.2 D i f f e r e n t i a l Scanning Ca l o r i m e t r y - Q u a l i t a t i v e The d i f f e r e n t i a l scanning c a l o r i m e t e r i s very h e l p f u l i n d e t e r - mining phase diagrams ( S e c t i o n 2.3.1, p 27). In the course of our s t u d i e s , many hundreds of samples of 1,1'-binaphthyl were run on the d.s.c. In none of the samples was any s i g n of a s o l i d - s o l i d t r a n s i t i o n apparent. The only peaks occurred from 145° to 158°. A t y p i c a l d.s.c. t r a c e of a sample c o n t a i n i n g both the low-melting (racemate) and h i g h - m e l t i n g ( e u t e c t i c ) forms i s shown i n Figure 12 as a f u n c t i o n of pro- gramming (heating) r a t e . Two endotherms and an exotherm are d i s c e r n i b l e . The f i r s t endotherm, at 144-145°, corresponds to the metastable m e l t i n g of the racemate. This i s f o l l o w e d immediately by the exothermic c r y s t a l l i z a t i o n of the e u t e c t i c form from the melt, then f i n a l l y by the (endothermic) m e l t i n g of the e u t e c t i c form. The f i n a l endotherm t h e r e - 69 w sa H o X w w H o Q z w (a) (b) (c) 144-145 157-158 144-145 157-158 TEMPERATURE (°C) Figure 12. Differential scanning calorimeter traces for racemic 1,1'-binaphthyl, as a function of programming rate. (a) 2.5 deg min (b) 10 deg min * (c) 40 deg min * -1 70 f o r e comprises both the e u t e c t i c form o r i g i n a l l y present i n the sample plus that which c r y s t a l l i z e d from the melt of the racemate. At f a s t e r programming r a t e s , the diminished s i z e of the f i n a l endotherm and of the exotherm mean that the o r i g i n a l sample d i d not co n t a i n much e u t e c t i c form. Rather, most of i t c r y s t a l l i z e d from the melt at slower h e a t i n g r a t e s . Pure h i g h - m e l t i n g form (obtained by h o l d i n g any sample of 1,1'- b i n a p h t h y l at 150°) shows a s i n g l e endotherm at 157-158° reg a r d l e s s of the s p e c i f i c r o t a t i o n of the sample. Even at 40 deg min \ the temp- erature of the endotherm (apparently s l i g h t l y higher because of the thermal r e s i s t a n c e of the instrument) i s the same whether the sample i s r e s o l v e d 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), constancy of m e l t i n g p o i n t w i t h composition w i l l occur when extremely r a p i d enantiomer i n t e r c o n v e r s i o n takes place on m e l t i n g . Since i t i s impossible to c r y s t a l l i z e the hi g h - m e l t i n g form from the melt at 150° without the use of seed c r y s t a l s , the appearance of the higher temperature endotherm on d.s.c. a n a l y s i s of 1,1'-binaphthyl i m p l i e s that t h i s form must have been present i n the o r i g i n a l sample i n at l e a s t t r a c e ("seed") q u a n t i t i e s . Thermal analyses of dozens of d i f f e r e n t samples of 1,1'-binaphthyl prepared i n va r i o u s ways showed that i t was impossible to produce workable q u a n t i t i e s of low-melting 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 of the hi g h - m e l t i n g form. A l l showed endotherms at 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 content, s i n c e no high-melting endotherm was observed at the usual heating r a t e of 10 deg min ^. However, on reducing the r a t e to 2.5 deg rain \ some e u t e c t i c form c r y s t a l l i z e d then melted, i n d i c a t i n g 71 traces of this form in the sample- This method is therefore a sensitive check of the "phase purity" of low-melting samples. One single procedure did, however, produce absolutely pure low- melting form in small quantities. When pure 1,1'-binaphthyl, regardless of its 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 is 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 is replaced in 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 is 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. is revealing. In the experience of McCrone, i f two polymorphs are obtained by cooling the melt in different ways, the least stable form is that which crystallizes -from the most highly supercooled melt. Melts can be highly supercooled when a small amount is cooled very 72 r a p i d l y , l i k e the way i n which the h i g h - m e l t i n g form was produced i n the d.s.c. p l a n c h e t t e . The suggestion i s t h e r e f o r e that at lower temper- atures the low-melting form i s the more s t a b l e m o d i f i c a t i o n . These observations w i t h a supercooled melt should a l s o o b t a i n 81c w i t h a supersaturated s o l u t i o n . That i s , the more h i g h l y super- satura t e d s o l u t i o n should y i e l d the l e s s s t a b l e of the two forms. A c c o r d i n g l y , we prepared f i l t e r e d s o l u t i o n s of racemic 1,1'-binaphthyl i n e t h e r , acetone, and benzene. These were allowed to. evaporate'slowly at room temperature over s e v e r a l days. In each case the r e s u l t i n g c r y s t a l s were racemate form w i t h very few seeds of e u t e c t i c form, as revealed by d.s.c. a n a l y s i s . S i m i l a r l y prepared s o l u t i o n s were evap- orated q u i c k l y ( i n l e s s than f i v e minutes) i n a stream of dry a i r at room temperature. The e u t e c t i c form was obtained i n high phase p u r i t y (X-ray a n a l y s i s ) . I f i t i s true that the more supersaturated c o n d i t i o n s produce the l e s s s t a b l e form, then again the i m p l i c a t i o n i s that the racemate i s s t a b l e at room temperature. 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 decided to search f o r any other 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 low- and h i g h - m e l t i n g forms) by c r e a t i n g an extremely supercooled melt. To t h i s end, some racemic 1,1'-binaphthyl was packed i n an X-ray powder c a p i l l a r y then melted i n a 175° bath. The c a p i l l a r y was then immediately immersed i n t o a bath of l i q u i d n i t r o g e n . A g l a s s y substance formed i n the tube. The c a p i l l a r y was then mounted i n the powder camera and ex- posed to X-rays f o r 20 h. W i t h i n four hours the sample s o l i d i f i e d . The 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 only to the racemate and the e u t e c t i c form, and no other c r y s t a l m o d i f i c a t i o n . 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 Although the above observations suggest an 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 , a more q u a n t i t a t i v e approach would be very h e l p f u l . S p e c i f i c a l l y , i f the a c t u a l f r e e energy d i f f e r e n c e between the racemate and the e u t e c t i c forms could be c a l c u l a t e d as a f u n c t i o n of temperature at constant pressure and composition (the racemic composition), then the s t a b l e ranges of each could be determined. In 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 i n f o r m a t i o n 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 to al l o w c a l c u l a t i o n of the 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 at 150°C (423°K). This can be seen from the f r e e energy p l o t s (Figure 11 (a) and (b)) and the schematic enthalpy and entropy p l o t s of F i g u r e 13. The enthalpy d i f f e r e n c e i n going from the low-melting (racemate) form to the melt (L->M) can be c a l c u l a t e d from the area of the d.s.c. endotherm at 145°C (418°K). S i m i l a r l y , the enthalpy change high-melting ( e u t e c t i c ) form melt (H-*M) at 158°C (431°K) can be determined. Since the f r e e energy change at these two po i n t s i s zero, the entropy change on m e l t i n g can be c a l c u l a t e d f o r both forms: AG L->M '418 = 0 AH' ,L-*-M 418 - (418)AS L->*i 418 AG ,H->M '431 = 0 AH H->M 431 - (431)AS H--M 431 [10] AS 418 and AS H->M 431 (431) I 1 ]_ 145 158 (a) TEMPERATURE (°C) I I 1 I 145 158 (b) TEMPERATURE (°C) Figure 13. Schematic enthalpy- and entropy-temperature p l o t s f o r racemic 1,1'-binaphthyl. (a) Ordering of low-melting form ( L ) , high-melting form (H) and melt (M) e n t h a l p i e s . (b) Ordering of entropies of the same phases. 7 5 where the subscript refers to the absolute temperature of the transition. Since 150°C is 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 identical to the corresponding changes at 150°C (423°K). 6 1 That i s , A H L->M 418 A H L->M 423 [11] A S L - » M 418 A S L->M 423 and H - * M H - * M A H431 = fiH423 H-»M H - * M A<; = A9 A b431 A b423 This approximation allows us to calculate the enthalpy, entropy, and free energy difference between the two crystalline forms ( L and H ) at 150°C (AH^j, AS^? and AG^J, respectively). 423 423 423 [ 1 2 ] A H L ~ * -4 2 3 A H 4 2 3 " H->M _ L->M A H 4 2 3 * A H 4 1 8 " A H 4 3 1 [ 1 3 ] A S 4 2 3 " A S 4 2 3 " . C H - ^ M L - * M A S 4 2 3 = A S 4 1 8 " A S H ^ A B 4 3 1 [ 1 4 ] A G L ^ H = A G 4 2 3 A H L ^ - A H 4 2 3 (423) A S ™ Before proceeding to show how t h i s free energy d i f f e r e n c e can be determined as a function of temperature, we s h a l l present our r e s u l t s L-*-M thus f a r . The enthalpy of melting for the racemate (AH^g) was deter- mined with a sample which contained n e g l i g i b l e e u t e c t i c form and did not c r y s t a l l i z e any e u t e c t i c form from the melt above 1 4 5 ° C ( 4 1 8 ° K ) . The endotherm was a s i n g l e , sharp peak, from which an enthalpy of 7 . 2 9 i 0 . 1 5 k c a l mole ^ ( 2 8 . 6 - 0 . 6 c a l g "*") was obtained. The entropy change, ca l c u l a t e d from Equation 1 0 , i s AS^'J = 1 7 . 4 8 t. 0 . 4 0 c a l deg ''"mole 76 Endotherms corresponding to the me l t i n g of the e u t e c t i c form H+M were s i m i l a r l y used to c a l c u l a t e ^H^^^. However, the e u t e c t i c i s capable of having any s p e c i f i c r o t a t i o n , depending on the r e l a t i v e amounts of R and S c r y s t a l s i n the mixture. Therefore, e n t h a l p i e s of f u s i o n were determined f o r s e v e r a l samples of e u t e c t i c form possessing d i f f e r e n t a c t i v i t i e s (Table V I I ) . S e v e r a l determinations were made f o r each sample, TABLE V I I Enthalpy of Fusion of the High-Melting Form of 1,1'-Binaphthyl at Various S p e c i f i c R o t a t i o n s A„H-»M . , , -1 *UH-»M -1 AH,„,, k c a l mole , AH,,..,, k c a l mole , r n , 431 431 [ocj, degrees m u l t i p l e analyses mean value -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 5.70 +223 4.51, 4.95, 4.68, 5.07 4.80 +238 4.39, 4.60 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 are i n t e g r a t e d . Comparing the mean v a l u e s , the H-*M samples having high r o t a t i o n s possess somewhat lower values of AH^^. Since the 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 of any a c t i v i t y i s the 77 racemic melt, the lower e n t h a l p i e s could r e f l e c t a d i f f e r e n c e i n enthalpy between re s o l v e d and racemic e u t e c t i c form. However the d i f f e r e n c e s are perhaps too c l o s e to the s c a t t e r i n i n d i v i d u a l analyses to be considered s e r i o u s l y . Moreover, our goal i s to determine r e l a t i v e f r e e energies of the racemic system. For t h i s purpose the enthalpy of f u s i o n of the -1 i - l [a] = -8° sample (5.67 ± 0.08 k c a l mole or 22.3 I 0.3 c a l g ) w i l l be H~*M —1 used. The corresponding entropy change i s AS^.^ = 13.15 ± 0.22 c a l deg , -1 mole The magnitudes of the determined enthalpy and entropy of f u s i o n f o r both the low- and high-melting forms j u s t i f i e s the o r d e r i n g of the schematic enthalpy and entropy surfaces i n F i g u r e 13. A p p l i c a t i o n of Equations 12, 13 and 14 gives the enthalpy, entropy and 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): (7.29 - 5.67) k c a l mole" 1 = 1.62 ± 0.23 k c a l mole" 1 (17.48 - 13.15) c a l d e g ^ m o l e " 1 = 4.33 ± 0.62 c a l d e g - 1 m o l e - 1 [1620 - (423)(4.33)] c a l m o l e - 1 = -212 ± 490 c a l mole" 1 AH AS AG L->H 423 L+H 423 L-»H 423 The 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 values i s d i s a p p o i n t i n g . Although the e n t h a l p i e s and e n t r o p i e s of f u s i o n f o r the racemate and e u t e c t i c forms have been measured to l e s s than 2.3% u n c e r t a i n t y , the L_*H XJ->H d i f f e r e n c e s AH,__ and AS.„_ are r e l a t i v e l y small and i n v o l v e s u b t r a c t i n g 423 423 • two measured v a l u e s , r e s u l t i n g i n a 14% r e l a t i v e u n c e r t a i n t y . F i n a l l y , L-*H performing a second s u b t r a c t i o n to o b t a i n AG, 9_ produces a very l a r g e 78 u n c e r t a i n t y . Even the a l g e b r a i c s i g n of the f r e e energy d i f f e r e n c e , the important 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. The L~*H —1 numerical r e s u l t AG^-j = -212 c a l mole represents the most probable value of the f r e e energy d i f f e r e n c e at 150°C. The f a c t that t h i s d i f f e r e n c e i s most probably negative i s i n accord w i t h our experimental r e s u l t s - the e u t e c t i c form i s indeed produced from the melt of the racemate at 150°C (see Figure 11 (a) and ( b ) , p 67). Any f u r t h e r d i s c u s s i o n of how the f r e e energy d i f f e r e n c e might change w i t h temperature t h e r e f o r e i n v o l v e s most probable v a l u e s . There i s s t i l l some advantage i n proceeding w i t h such a treatment, w i t h the hope that i t may support 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 temperature x, even i f a p r e c i s e value i s not o b t a i n a b l e . Because of the r a t h e r lengthy development necessary, t h i s treatment i s presented i n Appendix B, p 184. Let us now summarize the evidence f o r the e n a n t i o t r o p i c o r d e r i n g of racemic m o d i f i c a t i o n s . F i r s t of a l l , slow and r a p i d c o o l i n g of the melt on the d.s.c. gives 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 evaporation of s o l u t i o n s at room temperature give the same r e s u l t s . These observations are c o n s i s t e n t w i t h the racemate being the more s t a b l e form at room temperature. Since the l e s s s t a b l e of two forms " r a r e l y , i f ever" can be produced above the temperature 81c at which both have equal f r e e e n e r g i e s , the f a c t that both can be obtained at a l l by r e c r y s t a l l i z a t i o n at room temperature i m p l i e s that x i s above room temperature. A n t i c i p a t i n g a r e s u l t presented i n S e c t i o n 3.5.1 (pLL2), we have found that the lowest temperature at which 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 observed i s 76°C, 79 so that T must be lower than this temperature. The treatment in Appendix B supports the enantiotropic relationship, with a most probable transition temperature of 86°C. These independent observations together are consistent with the system R- and S-l,1'-binaphthyl possessing an enantiotropic phase relation- ship at the racemic composition, and a phase diagram lik e that in Figure 11 (d), p 67, with the transition temperature x between 25 and 76°C. Because the higher temperature limit i s closer to the calculated most probable transition temperature, the value of T w i l l be taken as ca. 70°C for the remainder of this thesis. 3.3.3 The Stable and Metastable Phase Diagram The phase diagram for the R- and S-l,1'-binaphthyl system is redrawn in Figure 14 (a). The solid lines represent phase boundaries reflecting the lowest free energy surfaces in 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 is the high temperature form) has also been observed with (+)- C O o H rv> r u m ™ C 0 9 ~ R u + I 2 CH„CHCONH„ | 2 CH2 ^ CHOH f0H CH3CHCONH2 H H CO" NH.+ CO " Ru + 2 4 2 34 35 36 u o H Ed H (a) 158 150 145 130 - ca. 70 25 50 100 PERCENTAGE (-)-ENANTIOMER ( b ) (c) >i pi w w w erf w w w TEMPERATURE: 130° TEMPERATURE: 150° _L Figure 14. (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°. 50 100 PERCENTAGE (-)-ENANTIOMER 81 and (-)-ammonium hydrogen malate (34), where x = 73°; w i t h (+)- and 85 ( - ) - d i l a c t y l d i a m i d e (35), where x = 35°; w i t h (+)- and (-)-rubidium 45d t a r t r a t e (36), where x = 40°; and w i t h the complex s a l t (+)- and Q C ( - ) - [ C o ( C 2 0 4 ) 3 ] K 3 - 3 . 5 H 2 0 , where x = 13°. The phase diagram 'representing the lowest f r e e energy surfaces 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'-binaphthyl racemate at 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 metastable and occurs between phases which are at higher f r e e energies at t h i s temperature. However the t r a n s f o r m a t i o n i s very r e a l and f o r t h i s reason we have deduced the metastable phase boundaries and superimposed them on Figure 14 (a) (dotted l i n e s ) . The areas enclosed by the dotted 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 merely represent metastable e x t r a p o l a t i o n s of the s t a b l e areas, and must be considered i n d i v i d u a l l y . The o r i g i n of the dotted l i n e s can be seen i n the schematic f r e e energy-composition p l o t at constant pressure and at 130° ( F i g u r e 14 (b)) and at 150° (Figure 14 ( c ) ) . The most s t a b l e f r e e energy arrangement at both of these temperatures i s shown by the dashed l i n e , and i s seen to be a e u t e c t i c mixture of R and S c r y s t a l s , as determined e x p e r i m e n t a l l y . The next most s t a b l e arrangement i s shown by the dotted l i n e s i n Figure 14 (b) and ( c ) . At 130°, these connect s o l i d R w i t h racemate on one s i d e of the 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 ca. 70°. At 150°, s i m i l a r dotted l i n e s connect R and S c r y s t a l s i n d i v i d u a l l y to the melt phase, an arrangement which i s lowest i n f r e e energy above 158°. In going to higher temperatures, the racemic melt decreases i n f r e e energy 82 r e l a t i v e to the racemate and.the e u t e c t i c mixture, becoming lower than the racemate at 145° and lower than the e u t e c t i c mixture at 158° (see al s o Figure 11 ( b ) , p 67). I f a p a r t i a l l y r e s o l v e d sample of 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 at 25° (point p, Figure 14 ( a ) ) , i t w i l l c o n s i s t only of S c r y s t a l s and racemate c r y s t a l s . When the sample i s heated to 150° ( o r , f o r that matter, any temperature between 145° and 158°), the racemate w i l l melt i n the presence of the more s t a b l e S c r y s t a l s . I f these c r y s t a l s e x e r c i s e complete c o n t r o l over the ensuing c r y s t a l l i z a t i o n , then the e n t i r e sample w i l l become S-(+)-l,1'-binaphthyl i n a d r i v e toward lower f r e e energy. P r e p a r a t i o n of the c o r r e c t i n i t i a l m a t e r i a l (discussed i n Se c t i o n 3.4, which f o l l o w s ) should t h e r e f o r e r e s u l t i n complete r e s o l u t i o n i n a s i n g l e step. L i k e w i s e , between ca. 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 lower the f r e e energy of the system. P r e l i m i n a r y observations at 120° (Table I I I , p 51) i n d i c a t e that even without the intermediacy of the melt, 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 , per- 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 s t a t e . m Our e xtensive k i n e t i c i n v e s t i g a t i o n s i n t h i s temperature range are reported i n S e c t i o n 3.5. We r e f e r to t h i s general 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 temperatures, from 70° to 158°, i t i s a r e s o l u t i o n by the 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 urface of the growing c r y s t a l s of pure enantiomer. Below 145°, the reso- 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 the s o l i d s t a t e , by means of a s o l i d - s o l i d phase tra n s f o r m a t i o n . 83 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 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 1-binaphthyl ( S e c t i o n 3.2, p 49), although s u c c e s s f u l , s u f f e r e d from a l a c k of repro- d u c i b i l i t y . The best method we devised was a c y c l i n g procedure, which e v e n t u a l l y achieved a high 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 f a s h i o n . Much of our research e f f o r t w i t h the 1,1'-binaphthyl system was d i r e c t e d toward t r y i n g to achieve some c o n t r o l over the r e s o l u t i o n . The determination of the phase diagram was a major step i n understanding what o r i g i n a l l y seemed a very unusual r e a c t i o n . Perhaps now we could use t h i s knowledge to prepare r e p r o d u c i b l y the e l u s i v e batch of s o l i d 1,1'-binaphthyl having o r i g i n a l l y l i t t l e or no o p t i c a l r o t a t i o n but possessing the a b i l i t y to r e s o l v e t o t a l l y simply on hea t i n g the s o l i d m a t e r i a l . Once t h i s i s accomplished, 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 could be used to study the k i n e t i c s of the r e s o l u t i o n process, 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 mechanistic d e s c r i p t i o n . Our s e v e r a l approaches to the problem of r e p r o d u c i b i l i t y are 79a t r e a t e d i n t h i s s e c t i o n . We found t h i s task, as d i d Wynberg w i t h h i s attempted 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 the end, very rewarding. 3.4.1 The Behaviour of S o l i d Racemic 1,1'-Binaphthyl Before the more ela b o r a t e schemes are di s c u s s e d , the behaviour of racemic 1,1'-binaphthyl, i s o l a t e d d i r e c t l y from the Grignard 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) should be e s t a b l i s h e d . I n i t i a l l y , racemic 1,1'-binaphthyl was used as a c o n t r o l , and heated alongside p a r t i a l l y a c t i v e samples which increased i n r o t a t i o n at 150°. In t h i s way, i t was 84 discovered that even racemic m a t e r i a l could develop o p t i c a l a c t i v i t y on hea t i n g . Of the two batches (A and B) of racemic 1,1'-binaphthyl o r i g i n - a l l y s t u d i e d (Table I I I , p 51), one (A) d i d not r e s o l v e at a l l , but the other (B) gave s c a t t e r e d a c t i v i t i e s , which were a l l p o s i t i v e . Throughout the course of t h i s work, s e v e r a l Grignard p r e p a r a t i o n s were performed when stocks of racemic 1,1'-binaphthyl ran low, and i t became r a t h e r r o u t i n e to c h a r a c t e r i z e each batch by heating a few samples at 150°and checking 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 of samples of the racemic m a t e r i a l which were heated f o r v a r i o u s reasons. A d i f f e r e n t "batch" i s prepared each time a given 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 that a l l m a t e r i a l w i t h i n each batch has the same phase content and average c r y s t a l s i z e and p e r f e c t i o n . Although 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, there was no d e l i b e r a t e a d d i t i o n of any a c t i v e c r y s t a l s . Racemic 1,1'-binaphthyl shows some very i n t e r e s t i n g behaviour on heating. Most of the racemic batches (except A, E, G, and 0) developed o p t i c a l a c t i v i t y when heated at temperatures from 100° to 150°. The f a c t that t h i s r e s o l u t i o n occurs below 145° f i r m l y e s t a b l i s h e s that the melt i s not necessary to the r e s o l u t i o n process - the 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 to create o p t i c a l a c t i v i t y . Although the behaviour of some batches i s not w e l l defined because of the few samples heated, others (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 revealed a very s u r p r i s i n g tendency to develop o p t i c a l a c t i v i t y i n one d i r e c t i o n o n l y . For example, the 37 samples taken from Racemic Batch L are p l o t t e d i n Figure 15 as a f u n c t i o n of time. A l l samples are p o s i t i v e and wi 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 trends are 85 Table V I I I The Development of O p t i c a l A c t i v i t y on Heating P o l y c r y s t a l l i n e , Racemic 1,1'-Binaphthyl Racemic Batch Temperature, °C Time, hours [a] , degrees C D E F G I 149.6 K L M N 120 100 135 135 149.6 1 1 1 1 1 15.5 13 19 2 16 5 46 120 0 to 50 15 1 5 2 +25 +65 0 +24, 0 b 0 -63 -77 -52, -45 b -78, -140 b -87, -129 b -124 -108 -5 see Figure 15 -8, - 9 b -22 +3 0, o b For Racemic Batches A and B, see Table I I I , p 51. S p e c i f i c r o t a t i o n s of two i n d i v i d u a l samples heated f o r the same l e n g t h of time at the same temperature. on 3 o w p S3 O 1—I H < H O pi U o w 00 +250 +200 +150 +100 +50 TEMPERATURE: 135° O o o oo o o o o &o-Q 1 — o o o o o o o o J L o o 10 20 30 TIME (HOURS) 40 50 Figure 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 of time 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 racemic 1,1 binaphthyl (L Batch) at 135°. 87 d i s c e r n i b l e . An e q u a l l y remarkable r e s u l t , as already noted, was obtained w i t h Racemic Batch 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 d i r e c t i o n . Some batches (I and J , f o r example), although 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 negative r o t a t i o n s . 1,1'-Binaphthyl prepared from o p t i c a l l y i n a c t i v e reagents seems to 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 dissymmetric i n f l u e n c e s are present i n the batches, which d e f i n i t e l y appear racemic when analyzed 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, racemic 1,1'-binaphthyl does not possess any f o r e i g n dissymmetric i m p u r i t y which 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 . Rather, the i n f l u e n c e s must a r i s e from the 1,1'-binaphthyl system i t s e l f , i n the form of s m a l l , i m p e r c e p t i b l e 46 excesses of one enantiomer. I t i s g e n e r a l l y 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 excesses of one enantiomer due to 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, our racemic p r e p a r a t i o n s were performed a f t e r the 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 that the small excesses could have a r i s e n from r e s o l v e d 1,1'-binaphthyl dust i n our 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 the reason f o r t h e i r e x i s t e n c e , these unobservable excesses of one enantiomer can be a m p l i f i e d through the phase i n t e r - a c t i o n s i n the R- and S- l , 1 ' - b i n a p h t h y l system. As revealed by the 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), every racemic batch contains some e u t e c t i c form, even i f t h i s i s present only i n tra c e q u a n t i t i e s . Since any enantiomer excess must be contained i n the e u t e c t i c form (as a grea t e r number o f , say, R than S c r y s t a l s ) , then i f t h i s form i s only a small part of the 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 the r a t i o of R to S molecules i n the 88 whole sample. On h e a t i n g , the enantiomer i n excess r e v e a l s i t s i d e n t i t y by causing the c r y s t a l l i z a t i o n of molecules of i t s own c o n f i g u r a t i o n . The 1,1'-binaphthyl system i l l u s t r a t e s a novel method of checking f o r t r a c e enantiomer excesses, f a r simpler than the hundreds of r e c r y s t a l - l i z a t i o n s on kilogram q u a n t i t i e s of "racemic" m a t e r i a l which are sometimes necessary to make such excesses o b s e r v a b l e . ^ While the manner i n which racemic 1,1'-binaphthyl can produce o p t i c a l a c t i v i t y on heating i s very 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 short of complete r e s o l u t i o n ([a] = ±245°). Perhaps changing the method of 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 are racemate ->• melt -»• e u t e c t i c form at 150° and racemate -*• e u t e c t i c form below 145°. 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, which i s p o s s i b l e when the s o l i d racemic samples are heated i n the presence of a saturate d s o l u t i o n of 1,1'-binaphthyl i n 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 . 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 l d f ormation, and occurs because the more s t a b l e of 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 the l e s s s o l u b l e of the two (Figu r e 16). In the temperature range 70-145° the racemate, being the more s o l u b l e (and l e s s s t a b l e ) form, maintains a s o l u t i o n of 1,1'-binaphthyl which i s super- s a t u r a t e d w i t h respect to the e u t e c t i c form, and the growth of c r y s t a l s of pure enantiomer can occur from s o l u t i o n . Such a change i n growth environment may favourably a f f e c t the 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 transformations i n a tube sealed at both ends and d i v i d e d i n t o two chambers by a f r i t t e d d i s c . The c r y s t a l s and solvent were l o c a t e d i n one end of the tube which was 89 PERCENTAGE SOLVENT Figure 16. Schematic phase diagram between racemic 1,1'-binaphthyl and a solvent w i t h b.p.> 160°. Dotted l i n e s are metastable e x t r a p o l a t i o n s of phase boundaries, and show the higher s o l u b i l i t y of the l e s s s t a b l e forms. 90 t o t a l l y immersed i n a bath held at the temperature of i n t e r e s t . A f t e r a p e r i o d of time the s o l u t i o n could be f i l t e r e d from the c r y s t a l s through the s i n t e r e d g l a s s d i s c without removing the sample from the temperature bath. The transformed c r y s t a l s could then be analyzed f o r o p t i c a l a c t i v i t y . The r e s u l t s of nine such experiments from 110° to 150° using 2 - p r o p a n o l and ethylene g l y c o l as s o l v e n t s are l i s t e d i n Table IX. Racemic Batch I (which, as shown i n Table V I I I , r e s o l v e s poorly i n the absence of a s o l v e n t ) was used i n the experiments. Although somewhat higher r o t a t i o n s are were observed w i t h 2-propanol at 120°, the best r o t a t i o n s could not be c o n s i s t e n t l y produced. Rather, 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 d i r e c t i o n ( n e g a t i v e ) . Table IX The Development of O p t i c a l A c t i v i t y on Heating P o l y c r y s t a l l i n e , Racemic 1,1'-Binaphthyl Under a Solvent Solvent Temperature, °C Time, hours [ a ] , degrees Ethylene g l y c o l 110 17 0 " " 130 24 -84 149.6 43 -2.5 2-Propanol 90 15 0 11 120 17 -158 " 43 -198 65 -186 19 -180 43 -144 3 A l l samples were taken from Racemic Batch I . 91 3.4.2 P h y s i c a l A d d i t i o n of Seed C r y s t a l s of A c t i v e 1,1'-Binaphthyl I t appears that the few c r y s t a l s of R and/or S - l , l ' - b i n a p h t h y l which happen to e x i s t i n the racemic samples, w h i l e e f f i c i e n t l y governing the d i r e c t i o n of the development of a c t i v i t y , cannot c o n t r o l the magnitude of the r o t a t i o n . This may occur because these c r y s t a l s are too few and too widely s c a t t e r e d to 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 decided to abandon the racemic system and to i n t r o d u c e mechanically some seed c r y s t a l s of h i g h l y r e s o l v e d 1,1.'-binaphthyl to the p o l y c r y s t a l l i n e m a t e r i a l , hoping to "swamp out" the e f f e c t of the o r i g i n a l seeds and to 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 p h y s i c a l seeding was done w i t h f i v e batches of racemic 1,1'-binaphthyl, w i t h the r e s u l t s i n Table X. U s u a l l y , the added seed comprised l e s s than 3% of the t o t a l weight of the sample, accounting i t s e l f f o r l e s s than 6° s p e c i f i c r o t a t i o n . The seed c r y s t a l s were added i n powdered form to the racemic m a t e r i a l , contained 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 to d i s t r i b u t e the added seeds, and then heated. In two cases (F and G) the r e s o l v a b i l i t y of the racemic m a t e r i a l (Table V I I I , p 85) was improved. However, r o t a t i o n s were never very h i g h , and w i t h Batch I , seeds of both p o s i t i v e and negative r o t a t i o n s simply decreased the negative a c t i v i t i e s developed i n the unseeded, racemic m a t e r i a l . This f a i l u r e of the p h y s i c a l a d d i t i o n of seeds i s probably 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 mixing two s o l i d s ( i . e . , seed c r y s t a l s and racemic m a t e r i a l ) mechanically. Perhaps the a d d i t i o n of seed c r y s t a l s to the racemic, supercooled 1,1'-binaphthyl melt might be more e f f e c t i v e than the mechanical mixing of s o l i d s . A s e r i e s of experiments were performed to t e s t t h i s suggestion, 92 Table X The I n f l u e n c e of Added Seed C r y s t a l s of O p t i c a l l y A c t i v e 1,1'-Binaphthyl on the S o l i d - S t a t e R e s o l u t i o n of P o l y c r y s t a l l i n e , Racemic 1,1'-Binaphthyl Racemic Batch [a] of Seeds, degrees Percent of T o t a l M a t e r i a l Due to Seeds [a] Produced, 0 degrees B +99 10 +55 F +200 3 +112 G tt 0.9 +53 I I ti 0.9 +91 I I ti 0.7 +42 H I I 0.05 +62 I -212 1.2 -20 I I I I 1.6 -28 I I +204 3.4 -15 The t o t a l weight of each sample (except H) was between 10 and 20 mg. The sample taken from P.acemic Batch H weighed 2.0 g. I t s behaviour i n the absence of a r t i f i c i a l seeding was not checked. A f t e r heating at 150° f o r at l e a s t one hour. and the r e s u l t s are l i s t e d i n Table X I , i n the order i n which they were obtained. Eight d i f f e r e n t samples of h i g h l y a c t i v e 1,1'-binaphthyl were used as seeds. The supercooled melts were prepared by heat i n g 0.2 g of racemic 1,1'-binaphthyl i n a stoppered t e s t tube at 170-190° f o r three minutes to destroy a l l s o l i d forms of 1,1'-binaphthyl, then q u i c k l y 93 Table XI The I n f l u e n c e of 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 the Re 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 Supercooled, Racemic 1,1'-Binaphthyl Melt [a] of Seeds, Number and Temperature of [ a ] , degrees degrees C o n d i t i o n of Seeds Supercooled M e l t , °C A B 1 +200 ca. 1 mg coarse powder 149.6 +205 +203 2 ti I I I I +126 +149 3 0 a few coarse granules it -7 -6 3 -7 I I I I +52 +22 4 none ti -21Q +214 6 +200 a few coarse granules it +176 +172 7 +204 tt 135 0 8 -212 it it 0 9 0 ti I I +1 10 +204 it 140 0 11 none tt -9 -10 12 +204 a few coarse granules 145 +3 13 11 I I 149.6 +144 14 -212 it 155 -183 -194 15 +204 I I 149.6 +76 +73 16 -212 I I it -1 +51 17 +204 one granule it +81 +77 18 -212 it I I +25 +40 19 +204 it 145 +5 20 it I I I I -18 b 94 (Table X I , continued) 21 +194 cne granule 22 +204 " 23 +200 a few coarse granules 24 -212 ca. 1 mg f i n e powder 25 +200 one granule 26 -212 149.6 -73 -22 " +139 " +196 +158 " -42 -35 145 +95 0 D u p l i c a t e analyses on the same sample are l i s t e d under A and B. immersing most of the tube i n a thermostatted s i l i c o n e o i l bath ( u s u a l l y h e l d at 150°). The seeding c r y s t a l s of 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 to a f i n e powder, were then added to the supercooled melt. The tubes were stoppered w h i l e the 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 e l i m i n a t e l a b o r a t o r y dust. Some experiments were very s u c c e s s f u l i n producing 1,1'-binaphthyl having [a] > 200°. However, attempts to reproduce these s u c c e s s f u l experiments u s u a l l y f a i l e d . The d u p l i c a t e analyses show that 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 mplying that the added seeds could not always 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 e n t i r e melt. U n i n t e n t i o n a l seeding probably accounts f o r the l a c k 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 . Inadvertent seeding can be e l i m i n a t e d by performing the c r y s t a l - l i z a t i o n s i n sealed ampules. In f a c t , using a s p e c i a l procedure, a l l 1,1'-binaphthyl seeds can be e l i m i n a t e d , and the 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 of t h e i r s p e c i a l 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 Se c t i o n 3.6. For the present d i s c u s s i o n , we s h a l l simply s t a t e that t h i s method does not 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'-binaphthyl. Because s e v e r a l other 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 h i s a d d i t i o n a l method was a l s o t r i e d w i t h 1,1'-binaphthyl. By means of a s p e c i a l experimental procedure which we developed, a s i n g l e seed having [a] = -212° was placed i n contact w i t h a f i l t e r e d , supersaturated s o l u t i o n of 1,1'-binaphthyl i n 2-propanol at 120° (sealed tube). C r y s t a l s developed, but a n a l y s i s gave [a] = -2°, indeed a poor r e s u l t . A second attempt was made, t h i s time using a high-speed s t i r r e r to 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 s o l u t i o n w i t h ethylene g l y c o l . The r e s u l t i n g a c t i v i t y of the p r e c i p i t a t e d m a t e r i a l was, however, only [a] = -38°. No f u r t h e r attempts to 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 Behaviour of 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 , the mechanical a d d i t i o n of seed c r y s t a l s to racemic 1,1 1-binaphthyl ( 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 preparing 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 probably due to the f a c t that i n these experiments, the e f f e c t of the seeds i s not " f e l t " by the bulk of the sample, i n s p i t e of e f f o r t s to o b t a i n (manually) a good d i s t r i b u t i o n of the 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 r e q u i r e d . The best method of mixing o p t i c a l l y a c t i v e and racemic 1,1'- b i n a p h t h y l i s to d i s s o l v e both i n a s u i t a b l e solvent 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 . In e f f e c t , t h i s was performed i n the o r i g i n a l c y c l i n g experiments ( S e c t i o n 3.2, p 49), but not a l l of the r e c r y s t a l l i z e d batches would r e s o l v e w e l l on h e a t i n g . This f a i l u r e may have been due to the f a c t that 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 temperature ( i . e . , racemate plus c r y s t a l s of only one enantiomer), as discussed i n S e c t i o n 3.3.2.1 (p 64). We now turn our a t t e n t i o n to the achievement of t h i s most s t a b l e s t a t e , and 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 preparing that 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 i n a s i n g l e h e a t i n g . A sample which i s not i n i t s most s t a b l e s t a t e would be expected to have too high a e u t e c t i c phase content, and the approach to 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 conversion of a l l racemic m a t e r i a l i n the sample to the racemate, l e a v i n g only racemate and c r y s t a l s of the d e s i r e d enantiomer. Such a s o l i d - s t a t e conversion, i f i t occurs at a l l , i s c e r t a i n l y very s l u g g i s h at room temperature. Slow s o l i d - s o l i d t r ansformations can be speeded up through the use 8 l d of s o l u t i o n phase tr a n s f o r m a t i o n s . R e s u l t s of the s o l u t i o n phase tr a n s f o r m a t i o n racemate s o l u t i o n -*• e u t e c t i c form, which occurs above 70°, have already been reported ( S e c t i o n 3.4.1, p 83). In these ex- periments, we had hoped that the presence 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 process. I f the reverse 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 temperature (see Figure 16, p 8 9 ) , i t might be p o s s i b l e to prepare 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 to 97 produce racemate from both p a r t i a l l y a c t i v e and almost racemic e u t e c t i c form i n two separate experiments. However, even a f t e r vigorous s t i r r i n g of the p u l v e r i z e d e u t e c t i c samples i n contact w i t h pentane at room temperature f o r up to three days, and a f t e r seeding the mixture w i t h c r y s t a l s of racemate, no t r a n s f o r m a t i o n was observed. Cooling the r a p i d l y - s t i r r i n g mixture to -78° and changing s o l v e n t s to methanol a l s o 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 of 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 cast some doubt on the co n c l u s i o n from phase s t u d i e s that the racemate i s the s t a b l e form of racemic 1,1'-binaphthyl at room temperature and below. However t h i s negative evidence i s not e n l i g h t e n i n g , s i n c e even s o l u t i o n phase transformations may be slow, e s p e c i a l l y i f the 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 of the two forms i s s l i g h t . The best method of producing the racemate, i n s p i t e of i t s un- p 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 . We had o r i g i 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 (36°), s i n c e l o s s e s i n r o t a t i o n at t h i s temperature were s l i g h t . Low temperture r e c r y s t a l l i z a t i o n s (-78°) from acetone, used i n the l i m i t of r e s o l u t i o n s t u d i e s (Appendix A, p 178), can be c a r r i e d out with 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 next explored t h i s as a method of preparing 1,1'- b i n a p h t h y l which might r e s o l v e w e l l on h e a t i n g . The procedure we followed i n v o l v e d making an almost s a t u r a t e d s o l u t i o n of p a r t i a l l y a c t i v e ([a] = ±10°) 1,1'-binaphthyl i n acetone at room temperature. This 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 placed i n a Dry Ice-acetone bath, where f i n e c r y s t a l s appeared i n about ten minutes. 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 complete, 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 ca. 80% m a t e r i a l . The f i r s t such r e c r y s t a l l i z - 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 having an a c t i v i t y of [a] = +0.8° r e s o l v e d , on heating at 150° o v e r n i g h t , to [a] = +209°. This represented the l a r g e s t increment i n o p t i c a l r o t a t i o n we had yet observed. A second experiment, repeating e x a c t l y the procedure of the 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 of a c t i v i t y [a] = +0.3° gave [a] = +205° on h e a t i n g . The procedure 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) of 1,1'-binaphthyl and i t , too, pro- duced 80% m a t e r i a l , [a] = +1.4°, which could i n c r e a s e to [a] = +211° on heating at 150°. This l a r g e batch of r e s o l v a b l e 1,1'-binaphthyl was used i n a k i n e t i c study (as K i n e t i c Batch S - l , S e c t i o n 3.5), from which i t was learned that even at 105°, r e s o l u t i o n to [a] = +221° was p o s s i b l e . A f o u r t h low temperature r e c r y s t a l l i z a t i o n was an attempt to o b t a i n 1,1'-binaphthyl which would give high negative r o t a t i o n s on h e a t i n g . Much to our disappointment, the attempt f a i l e d , and only [a] = -31° was a t t a i n e d on heating at 135° overnight. Apparently we had unknowingly changed some parameter to which the r e c r y s t a l l i z a t i o n procedure i s r a t h e r s e n s i t i v e . We then set out to determine the extent to which our o r i g i n a l s u c c e s s f u l procedure could 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 of the s o l u - t i o n of 1,1'-binaphthyl from which r e c r y s t a l l i z a t i o n occurred, from [a] = 0 to [a] = 71°; the c o n c e n t r a t i o n of 1,1'-binaphthyl i n t h i s s o l u t i o n , from 1.43 g / 100 ml acetone (saturated) to 0.67 g / 100 ml acetone; and the time allowed f o r r e c r y s t a l l i z a t i o n at -78°, from 15 min to 12 h. Al s o 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 r e c r y s t a l l i z a t i o n occurred, methods of f i l t r a t i o n , p u r i t y of acetone s o l v e n t ( d i s t i l l e d or 99 u n d i s t i l l e d ) , and seeding w i t h various forms of 1,1'-binaphthyl (both a c t i v e and racemic). In a l l of these experiments, poor r e s u l t s were obtained. Even very c a r e f u l attempts to reproduce the o r i g i n a l procedure f a i l e d . We can o f f e r no e x p l a n a t i o n as to why the 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 the ensuing s i x t e e n d i d not succeed. Perhaps the p r e p a r a t i o n of r e s o l v a b l e 1,1'-binaphthyl 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 , which are d i f f i c u l t to c o n t r o l e x p e r i m e n t a l l y . At t h i s time we di s c o v e r e d , somewhat by a c c i d e n t , a method which has produced h i g h l y r e s o l v a b l e 1,1'-binaphthyl every time. In the course of c y c l i n g a q u a n t i t y of 1,1'-binaphthyl to high 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 acetone s o l u t i o n of [a] = +10° m a t e r i a l at -78° (hoping to o b t a i n c r y s t a l s which would produce at l e a s t some a c t i v i t y on h e a t i n g ) , then, to conserve m a t e r i a l , we d i d not f i l t e r the c r y s t a l s from the 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 the acetone under reduced pressure at 25°. The m a t e r i a l obtained ( [ a ] = -9.5°) re s o l v e d to [a] = -216° on hea t i n g at 150° f o r 16 h. An extensive i n v e s t i g a t i o n of t h i s r e c r y s t a l l i z a t i o n - evaporation procedure was conducted. Twenty-seven experiments were per- formed, s i x t e e n of which were r e p r o d u c i b i l i t y checks and preparations of h i g h l y r e s o l v a b l e 1,1'-binaphthyl, and eleven of which 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 procedure. Of the 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 to grea 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 at 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 procedure, summarized here f o r d i s c u s s i o n and given i n d e t a i l i n Se c t i o n 4.3.2.3 ( b ) , p 158), i s easy to perform. The method i n v o l v e s d i s s o l v i n g 1,1'-binaphthyl of 100 [a] = 2° to 15° i n d i s t i l l e d acetone (1.2 g / 100 ml), f i l t e r i n g the s o l u t i o n , then s w i r l i n g i t i n a Dry Ice-acetone bath u n t i l c r y s t a l s appear (about 15 min). The c o l d f l a s k i s then placed on the r o t a r y evaporator and the vacuum (water a s p i r a t o r ) a p p l i e d . When the great e s t vacuum i s a t t a i n e d , the c o l d f l a s k i s lowered i n t o a bath at 20-25°. As the f l a s k warms, the c r y s t a l s begin to d i s s o l v e and the acetone begins to d i s t i l l o f f . These two processes (warming and l o s s of sol v e n t ) oppo- s i t e l y a f f e c t the amount of 1,1'-binaphthyl i n s o l u t i o n , and most (but not a l l ) of the c r y s t a l s d i s s o l v e at one p o i n t , whereafter they come back out of s o l u t i o n as the l o s s of sol v e n t continues. E v e n t u a l l y ( i n about 30 min), a l l the sol v e n t disappears, and the remaining c r y s t a l s 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 evaporation of a s o l u t i o n of 1,1'-binaphthyl gives poor r e s u l t s . A l s o , f o r the procedure to succeed, the c r y s t a l s must not 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 s o l v e n t followed 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 success of t h i s procedure e v i d e n t l y depends on the presence, 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 are generated during the warming of a co l d mixture of s o l i d m a t e r i a l plus s o l u t i o n to room temperature. The f a c t that almost a l l c r y s t a l s disappear during the evaporation i m p l i e s that those which d i s s o l v e are "undesired" seeds, the " c o r r e c t " seed c r y s t a l s remaining behind to induce the f u r t h e r growth of r e s o l v a b l e 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 of the ter n a r y system i n v o l v e d . When a p a i r of enantiomers forms a racemate, the ternary phase diagram between R, S and o p t i c a l l y i n a c t i v e 101 s o l v e n t appears as i n Figure 17 at any constant temperature which i s above the m e l t i n g p o i n t of the s o l v e n t and below that of the enantio- mers. 45d,53,85 F i g u r e 11 ( a) i s a schematic r e p r e s e n t a t i o n of the t e r n a r y system at -78°, and Figure 17 (b) represents the same at 25°. The s o l i d l i n e s are the s t a b l e phase boundaries. In F i g u r e 17 (b) the one- two- and three-phase regions are l a b e l l e d . In both diagrams, the dotted l i n e s represent metastable 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 curves of s o l i d R, racemate, and s o l i d S. P o i n t y represents ( s c h e m a t i c a l l y ) the o v e r a l l composition of the s l i g h t l y a c t i v e S - l , I 1 - b i n a p h t h y l s o l u t i o n at the beginning of the 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 procedure. At 25°, i t i s seen to 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'binaphthyl d i s s o l v e s at t h i s temperature. At -78°, however, i t l i e s f o r m a l l y i n the three-phase S + racemate + s o l u t i o n r e g i o n , so that these two s o l i d phases can sep- a r a t e from the s o l u t i o n . In a d d i t i o n , i t probably l i e s behind the s o l u b i l i t y curves of a l l three s o l i d phases, and the m a t e r i a l which c r y s t a l l i z e s l i k e l y contains R, S, and racemate together. On rewarming to 25° (on the r o t a r y evaporator), a l l three phases w i l l begin to d i s s o l v e as the system approaches that i n F i g u r e 17 ( b ) . However, s i n c e the p o i n t y now 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 curve, t h i s form can 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 behind only S and racemate to seed out the 1,1'-binaphthyl i n s o l u t i o n as the evaporation proceeds. The s o l i d m a t e r i a l thus obtained probably c o n s i s t s only of racemate and S c r y s t a l s , the long-sought phase mixture which i s i d e a l l y s u i t e d f o r r e s o l u t i o n at higher temperatures. 102 S SOLVENT Figure 17. Schematic r e p r e s e n t a t i o n of the te 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 e x t r a p o l a t i o n s of phase boundaries ( s o l u b i l i t y curves) are shown as dotted l i n e s , (a) Temperature: -78°, (b) Temperature: +25°. 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 preparing s o l i d 1,1'-binaphthyl which would r e s o l v e c o n s i s t e n t l y to a high 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 process became p o s s i b l e . Four d i f f e r e n t batches of r e s o l v a b l e 1,1 1-binaphthyl were used i n the k i n e t i c study - three producing S-(+)-1,1'-binaphthyl 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 batch, S - l , c o n s i s t e d of 3.0 g of m a t e r i a l acquired by a simple low temperature r e c r y s t a l l i z a t i o n from acetone (p 98). The others (S-2, 4.0 g; S-3, 5.7 g; and R - l , 3.8 g) were prepared 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 procedure (p 99). 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 batch was followed by h e a t i n g i n d i v i d u a l sealed 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 mg) of the p o l y c r y s t a l l i n e 1,1'-binaphthyl at a given temperature f o r v a r i o u s lengths of time. 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 are shown i n Figures 18-22. K i n e t i c runs were performed at four temperatures - 135°, 125°, 115°, and 105° - f o r a l l k i n e t i c batches except S - l , which was explored only at 135° 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 of each of these runs are l i s t e d i n Table X I I . A l l batches r e s o l v e d to greater than [a] = ±200° at 150°, but w i t h a h a l f - l i f e too short f o r an accurate k i n e t i c d e s c r i p t i o n . S e v e r a l comments should be made regarding the form of the k i n e t i c curves. What i s immediately obvious 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 CO w o w Q 53 O r-l H < H O Pi O r-l U-i r-l O Li] CU CO +250 +200 +150 +100 +50 TEMPERATURE: 135° • 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' storage at 25° A Run using ground samples Run using more h i g h l y ground samples 20 40 60 TIME (MINUTES) 80 100 120 Figure 18. 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'-binaphthyl, S - l K i n e t i c Batch at 135°. E f f e c t of gr i n d i n g and of storage at 25° f o r s i x weeks. o J 1 1 I I 1 I I I I 1 L 2 4 6 8 10 12 14 16 18 20 22 24 TIME (HOURS) Figure 19. 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'-binaphthyl, S K i n e t i c Batch at 125°. E f f e c t of storage of samples at 0° f o r four months. 106 +150 TEMPERATURE: 135° 00 w Qi O W a 53 o i—i H <! H O Pi c_> M PK rH U W P-i 00 +125 +100 +75 +50 +25 S-2 Kinetic Batch -25 -50 -75 -100 -125 20 30 TIME (MINUTES) 40 50 60 G O -O- R-l Kinetic Batch •150 Figure 20. Kinetic data for the solid-state resolution of neat, polycrystalline 1,1'-binaphthyl, S-2 and R-l Kinetic Batches at 135°. 107 Figure 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'-binaphthyl, S-2 and R - l K i n e t i c Batches at 115°. 108 00 w w PS o O z o M H <: H o r-l u W 00 +250 h +200 + 150 h u +100 h +50 h 10 (a) 20 30 TIME (MINUTES) oo w w Pi o w o z o l-l H < H O Pi r-l CJ K 00 +250 h +200 h +150 u +100 h +50 h (b) 10 15 TIME (HOURS) Figure 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'-binaphthyl, S-3 K i n e t i c Batch at (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 0 ^ ' degrees H a l f - L i f e S - l 149.6 +211 25 min 135.0 +201 37 min 135.0 b +201 53 min 135.0 d +182 13 min 135.0 e +61 3 min 105.1 +221 6.6 days S-2 149.6 +226 <1 min 135.0 +84 14 min » 124.9 +67 1.7 h » 124.9° +136 4 h 114.9 +110 17 h 105.1 +123 4.3 days S-3 149.6 +200 <1 min 135.0 +201 5 min » 124.9 +214 38 min 114.9 +223 5 h 105.1 +229 1.1 days R - l 149.6 -233 <1 min 135.0 -123 13 min 124.9 -71 1.2 h 114.9 -69 6 h 105.1 -79 1.7 days 110 Time taken to achieve [a] /2. r Run performed a f t e r s i x weeks' storage at 25°. Run performed a f t e r four months' storage at 0°. Run using ground samples. Run using more h i g h l y ground samples. obtained when racemic 1,1'-binaphthyl i s heated ( F i g u r e 15, p 86). Although the a c t i v i t y develops smoothly, there appears to be no c h a r a c t e r - i s t i c shape to the curves. Some are sigmoid (although none have prolonged i n d u c t i o n p e r i o d s ) , and others appear to i n c r e a s e l i n e a r l y w i t h time or even show a r a t e maximum at the s t a r t of the run. The extent of reso- l u t i o n a l s o v a r i e s . Contrary to the very high r o t a t i o n s achieved at 150°, the S-2 and R - l K i n e t i c Batches s u f f e r a l o s s i n r e s o l v i n g a b i l i t y at lower temperatures. The k i n e t i c runs are a l s o s e n s i t i v e to g r i n d i n g or to storage f o r any great length of time. As demonstrated with the S - l sample at 135°, the act of 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 (Figure 18). A l s o , the S - l K i n e t i c Batch d i d not show the same k i n e t i c s before and a f t e r storage f o r s i x weeks at room temperature (25°). Instead, the r e s o l u t i o n was slowed somewhat, although the extent of r e s o l u t i o n was preserved. For t h i s reason the k i n e t i c s of t h i s batch ware not explored at 115° or 125°. The others were stored at 0° w h i l e the k i n e t i c runs were performed ( w i t h i n f i v e weeks). A r e p r o d u c e a b i l i t y check of the S-2 K i n e t i c Batch was performed a f t e r four months' storage at 0° (Figure 19), and showed an unchanged r a t e of r e s o l u t i o n but an enhanced extent of r e s o l u t i o n ( o r i g i n a l l y , to I l l [a] = +67°; a f t e r four months, to [a] = 136°). Therefore, the value of [a]_, w i l l have a l t e r e d to some extent during the f i v e weeks taken f o r the F k i n e t i c runs, but any changes i n the r a t e of r e s o l u t i o n are probably s m a l l . There i s some value i n n e g l e c t i n g these changes to a l l o w an a n a l y s i s i n terms of known r a t e equations f o r s o l i d - s t a t e r e a c t i o n s . This w i l l be done i n Se c t i o n 3.5.2. Some samples of the f a s t e s t - r e s o l v i n g batch (S-3) were ground (to 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 at temperatures below 105°, to e s t a b l i s h the lowest temperature at which the r e s o l u t i o n can proceed. The r e s u l t s are organized i n Table X I I I . Even at 98°, 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 of 1,1'-Binaphthyl Temperature, °C Time, weeks [ot], degrees K i n e t i c Batch 97.7 93.0 87.6 0 2.6 11.2 24.9 0 1.0 3.7 4.0 0 1.0 3.7 4.0 +1.4 +9 +156 +227 +1.8 +67 +114 +125 +1.8 +33 +64 +77 S - l S-3, 'round 112 (Table X I I I , continued) 83.3 76.9 64.2 0 1.0 4.0 0 1.0 4.0 25.5 0 1.0 4.0 25.5 +1.8 +16 +26 +1.8 +5.8 +11 +22 +1.8 +1.9 +1.2 0 S-3, ground are capable of r e s o l v i n g to high r o t a t i o n s , but c o n s i d e r a b l e lengths of time are r e q u i r e d . The lowest temperature at 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 observable i s 76°, where [a] = +22° was achieved 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 at 64°, even a f t e r h a l f a year. The absence of r e s o l u t i o n at 64° could imply that t h i s temperature i s lower than the s o l i d - s o l i d t r a n s i t i o n temperature T (Figure 11 ( d ) , p 67). However, c a u t i o n should be used i n making such a c o n c l u s i o n , i n view of the slowness of the r e s o l u t i o n at 76°. I t i s best simply to s t a t e that the low temperature k i n e t i c r e s u l t s i n d i c a t e that x i s lower than 76°. From the r e s u l t s given above i t i s obvious that the k i n e t i c behaviour of 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 i s c o n s i d e r a b l y more 113 complex than the simple 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 of the d i a c i d _29_ reported i n S e c t i o n 2 of t h i s t h e s i s . Such a k i n e t i c complexity i s to be expected, c o n s i d e r i n g the nature of the processes 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 of c r y s t a l s of one enantiomer at the expense of the racemate phase. Such a process would be h i g h l y dependent on the area of the i n t e r f a c e between the s o l i d reactant phase and the s o l i d product phase. Any procedure which can change the area 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 w i l l 58 g r e a t l y a f f e c t the observed r a t e of r e a c t i o n . The f a c t that an e n t i r e sample of almost-racemic 1 , 1 1 - b i n a p h t h y l can convert to e s s e n t i a l l y only one enantiomer means, of course, that enantiomer i n t e r c o n v e r s i o n must occur somewhere i n the sample. At 150°, where the racemate melts, l e a v i n g behind c r y s t a l s of only one enantiomer, ra c e m i z a t i o n occurs very r a p i d l y (with a h a l f - l i f e of l e s s than 0.5 sec i n the m e l t ) . Growing S c r y s t a l s ( f o r example) can s e l e c t S molecules from a melt which i s e s s e n t i a l l y always racemic (while i t l a s t s ) . In the temperature range 76° to 135°, where the sample i s e n t i r e l y s o l i d , enantiomer i n t e r c o n v e r s i o n (a simple conformational change) can conceivably occur 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 disappearing racemate c r y s t a l s . In 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 very e x t e n s i v e . Since the reactant-product i n t e r f a c e represents an area of contact between centrosymmetric (racemate) and noncentrosymmetric (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 " ) ^ 3 The higher (surface) f r e e energy a s s o c i a t e d w i t h t h i s part of the s o l i d s t a t e could 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 p o s s i b l e the s o l i d - s t a t e r e s o l u t i o n . 114 I f the i n t e r c o n v e r s i o n of enantiomers i n the reactant-product i n t e r - face i s very f a s t compared to the r a t e of growth of c r y s t a l s of pure enantiomer, then the r e a c t i o n i s e s s e n t i a l l y only a phase change. Phase 61 changes are almost always governed by nucleation-and-growth processes. That i s , not only can a phase t r a n s f o r m a t i o n occur v i a growth of sm 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 reactant phase, but new c r y s t a l l i t e s can form (nucleate) during the phase change. Up to t h i s p o i n t , we have considered only the growth of "seed" c r y s t a l s of pure enantiomer present i n i t i a l l y i n the s o l i d sample of 1,1'-binaphthyl. Indeed, the e l i m i n a t i o n of c r y s t a l s of "unwanted" enantiomer was the prime o b j e c t i v e i n the designing of experiments to produce r e s o l v a b l e 1,1'- b i n a p h t h y l . However, as w i l l be seen, the 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 of the n u c l e a t i o n of new e u t e c t i c c r y s t a l s from the r e a c t i n g racemate phase. The prospect of n u c l e a t i o n i n the 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 stereochemical consequences. According to the c l a s s i c a l theory of n u c l e a t i o n , ^ ' ^ ^ new c r y s t a l s are 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 of molecules i n the reactant phase. But i n the 1,1'-binaphthyl system, the reactant phase i s a racemic c r y s t a l below 145° or a racemic melt between 145° and 158°. This means that the l o c a l f l u c t u a t i o n s are j u s t as l i k e l y to i n v o l v e R molecules as S molecules. In other words, n u c l e a t i o n i n the racemic phase i s expected to create both R and S c r y s t a l l i t e s w i t h equal p r o b a b i l i t y . This w i l l be true r e g a r d l e s s of the s i t e s of n u c l e a t i o n i n the reactant 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 at a l l p o i n t s i n the reactant c r y s t a l w i t h equal 115 l i k e l i h o o d - or whether i t occurs only at d e f e c t s , d i s l o c a t i o n s or boundaries between reactant c r y s t a l l i t e s , the o v e r a l l products of n u c l e a t i o n should be a racemic, e u t e c t i c mixture of i n d i v i d u a l R and S c r y s t a l l i t e s . A racemic r e a c t a n t phase w i l l show no preference f o r the formation of any one enantiomer. The reasons f o r the f a i l u r e of some batches of 1,1'-binaphthyl to r e s o l v e w e l l on heating are t h e r e f o r e : (a) the presence of c r y s t a l - l i t e s of both enantiomers i n the i n i t i a l m a t e r i a l before h e a t i n g , (b) the n u c l e a t i o n of racemic m a t e r i a l during the r e a c t i o n , or (c) both. The k i n e t i c r e s u l t s provide an opportunity to t e s t these reasons f o r f a i l u r e , s i n c e we know the c o n d i t i o n s under which the high r e s o l v - a b i l i t y of the batches can be destroyed. For example, g r i n d i n g the S - l K i n e t i c Batch causes a f a s t e r r e s o l u t i o n , but to a lower r o t a t i o n . 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 i n i t i a l l y i n the m a t e r i a l (and imparting a s m a l l s p e c i f i c r o t a t i o n of [a] = +1.4°), c r e a t i n g a gre a t e r reactant-product i n t e r f a c e and causing a more r a p i d r e a c t i o n . In a d d i t i o n , R c r y s t a l l i t e s are e i t h e r formed during the g r i n d i n g process or nucleated (along w i t h an equal number of S c r y s t a l l i t e s ) when the ground sample was heated. The f a c t that the racemate has a lower molar volume (196.2 ml mole "*") n than the e u t e c t i c form (214-216 ml mole ^)° i m p l i e s that the pressure of g r i n d i n g could not cause a phase n C a l c u l a t e d from the c r y s t a l l o g r a p h i c data of Kerr and R o b e r t s o n ^ f o r the low-melting form of l , l ' - b i n a p h t h y l , 82 Ex t r a p o l a t e d to 25° from the d i l a t o m e t r i c data of Binns and Squire f o r the high-melting form of l , l ' - b i n a p h t h y l between 120° and 158°. 116 change from the racemate to an equimolar mixture of R and S c r y s t a l s . Hence the sample, both before and a f t e r g r i n d i n g , very l i k e l y contained e s s e n t i a l l y only S c r y s t a l s and racemate c r y s t a l s , the R form being nucleated (along w i t h S) more r e a d i l y from the ground sample. The reason f o r the decreased extent of r e s o l u t i o n i n ground samples may then be that g r i n d i n g creates s t r e s s e s , d i s l o c a t i o n s , and other i m p e r f e c t i o n s i n the reactant l a t t i c e , and these can act as s i t e s f o r the n u c l e a t i o n of racemic m a t e r i a l . A l s o , the 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 poorly i n the temperature range 105-135° (where the reactant phase i s the racemate) and e x c e l l e n t l y at 150° (where the react a n t phase i s the m e l t ) . I f the poor r e s o l v a b i l i t y at 105-135° i s due to the i n i t i a l presence of both R and S c r y s t a l l i t e s , then one would expect the growth of both forms a l s o at 150°, which i s not the case. A more tenable e x p l a n a t i o n i n v o l v e s the n u c l e a t i o n of racemic m a t e r i a l from the racemate phase, but not from the melt phase. As mentioned e a r l i e r , the 1,1'-binaphthyl melt supercools to a great extent, and completely melted samples w i l l remain at 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. Although growth on seed c r y s t a l s occurs r e a d i l y at 150°, n u c l e - a t i o n of new c r y s t a l s does not. Therefore a high degree of r e s o l u t i o n may occur at 150° but not at 105-135°. The S - l and S-3 K i n e t i c Batches r e s o l v e to grea t e r than 82% r e s o l u t i o n at a l l temperatures s t u d i e d . The f a i l u r e to a t t a i n t o t a l r e s o l u t i o n ([a] = i245°) i n these batches i s probably due to c r y s t a l s of unwanted R enantiomer present i n i t i a l l y , r a t h e r than to n u c l e a t i o n , s i n c e there i s no improvement i n r e s o l u t i o n w i t h these samples at 150°, where 117 n u c l e a t i o n i s absent. The changes on storage of the S-2 K i n e t i c Batch 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 of unwanted enantiomer. On one hand, the improved extent of r e s o l u t i o n of the S-2 m a t e r i a l on storage could be due to the p a r t i a l annealing out of the c r y s t a l i m p e r f e c t i o n s and boundaries causing n u c l e a t i o n of racemic m a t e r i a l . Annealing i s made p o s s i b l e by the r e l i e f of surface and s t r a i n f r e e energies i n the p o l y c r y s t a l l i n e sample. On the other hand, the presence of unwanted enantiomer could be diminished by a very slow phase t r a n s f o r m a t i o n at 0°, c o n v e r t i n g racemic e u t e c t i c form back to 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 on heating at 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 only the c r y s t a l s of unwanted enantiomer, but a l s o the tendency of the racemate to n u c l e a t e racemic, e u t e c t i c form. Although the l a t t e r requirement i s d i f f i c u l t to c o n t r o l , i t can be avoided simply by performing the r e s o l u t i o n at 150°, where the racemate melts, and a l l batches of 1,1'- b i n a p h t h y l prepared 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 pro- cedure (p 99) a t t a i n a very high degree of r e s o l u t i o n . 3.5.2 Treatment of Results i n Terms of Rate Laws f o r S o l i d - S t a t e Reactions Although some q u a l i t a t i v e c onclusions 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 treatment can p o t e n t i a l l y provide i n s i g h t i n t o the mechanism and energies i n v o l v e d i n the s o l i d - s t a t e r e s o l u t i o n . 118 As w i l l be seen, the r a t e equations which have been developed f o r 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 expression of y, the f r a c t i o n transformed, as a f u n c t i o n of time. In 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 con v e n i e n t l y taken as the extent of 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 achieved. That i s , y = X^, where i s the mole f r a c t i o n of 1,1'-binaphthyl i n the e u t e c t i c (high-melting) form. Although X^ = 1 at the end of the t r a n s f o r m a t i o n , i t i s c l o s e to but not e x a c t l y zero at the beginning, s i n c e some sm a l l seed c r y s t a l s of e u t e c t i c form e x i s t i n the i n i t i a l m a t e r i a l . Hence, before the r e a c t i o n , the m a t e r i a l i s considered as already s l i g h t l y transformed. During the r e s o l u t i o n , [a] was measured as a f u n c t i o n of time, u n t i l a f i n a l r o t a t i o n , [ a ] _ , was a t t a i n e d . I n t u i t i v e l y , i t would seem that r [ a ] / [ a ] y = X^, but the c o n d i t i o n s under which t h i s e q u a l i t y w i l l h o l d should be examined more c l o s e l y . I n any batch of 1 , 1 1 - b i n a p h t h y l , the only phases present are the racemate, c r y s t a l s of R, and c r y s t a l s of S. The l a s t two c o n s t i t u t e the e u t e c t i c form. I t i s convenient to d e f i n e the f o l l o w i n g : a l l phases e u t e c t i c (high-melting) form racemate (low-melting) form end of t r a n s f o r m a t i o n The s p e c i f i c r o t a t i o n of the sample at a l l times i s : (or V = mole \- -H (or W = mole •L (or = mole *R- -F (or XS-F> = mole f r a c t i o n of R (or S) i n f r a c t i o n of R (or S) i n f r a c t i o n of R (or S) i n f r a c t i o n of R (or S) at [15] [ a ] = [ a ] S ( X S " V = C a ] R ( X R " V 119 where [ct]c = +245°, and [o]„ = -245°, the specific rotations of completely S R resolved S and R-l,1'-binaphthyl, respectively. But since the racemate contains an equimolar quantity of S and R-l, 1'-binaphthyl, i.e., = , and since Xg = + X g_ L and X^ = X^ ^ + then the difference in mole fractions of S- and R-l,1'-binaphthyl in a l l phases is identical to that only in the eutectic form (Xg - X^ = - ^) and so i t is always true that: [16] [ a] = [a]g(X s_ H - X ^ ) At the end of the transformation, X = X and X^ = X , so that: b—ri b - r K—n K—r [17] [ a ] F - [ a ] s ( X s _ p - X R_ p) Therefore, in a l l batches of polycrystalline 1,1'-binaphthyl, [18) Ul - "S-" " "*-H l»l F X S - F " *R-F Consider now a hypothetical sample of 1,1'-binaphthyl which resolves perfectly. If the resolution is to pure S-enantiomer, then [a] = [a] . r b In such a resolution, no nucleation of racemic material would occur, and the eutectic form would always consist only of growing S crystals. Therefore, X g_ H = X^, = X R_ F = 0, X g_ F = 1, and Equation 18 becomes: rioi M - Lsl X S - H " „ 120 Therefore, i n the p e r f e c t r e s o l u t i o n , which i s approached by the S - l ' and S-3 K i n e t i c Batches at a l l temperatures s t u d i e d , and by the S-2 and R - l K i n e t i c Batches at 150°, the extent of t r a n s f o r m a t i o n , y, equals [a]/[a] p . In the k i n e t i c runs where [a]., i s f a r from [ a ] c or [a]„, i t may not be accurate to equate and [ct]/[a]p. In these samples, (S-2 and R - l from 105-135°) where n u c l e a t i o n of racemic m a t e r i a l can occur to a c o n s i d e r a b l e extent, s i t u a t i o n s can conceivably a r i s e where X̂ . advances more r a p i d l y than [a]/[a]„. For example, extensive n u c l e a t i o n of r racemic e u t e c t i c form o c c u r r i n g at the beginning of the t r a n s f o r m a t i o n would not in c r e a s e [ a ] / [ a ] p but would i n c r e a s e X^. In k i n e t i c runs where [ctjj, << [a]g, t h e r e f o r e , the extent to which X^ i s approximated by measured r o t a t i o n s should be independently determined. An independent measurement of X^ can be performed by f o l l o w i n g the 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 monitored the r e s o l u t i o n of the S-2 K i n e t i c Batch at 125° (Figure 19, p 105, k i n e t i c run a f t e r four months at 0°) using 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 to the " d i r e c t comparison 76a method" described by C u l l i t y . By choosing one l i n e i n the d i f f r a c t i o n o p a t t e r n of the racemate (d = 10.1 A) and one i n the p a t t e r n of the o e u t e c t i c form (d = 6.4 A) which would be d i s t i n c t i n a mixture of the two forms, the disappearance of racemate and the appearance of e u t e c t i c could 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 of the powder photographs was devised, so that when the developed photographs were analyzed on a microdensitometer, the r e s u l t i n g peak areas 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 curve (Figure 23) r e l a t i n g the 121 H WEIGHT FRACTION (.. ... ) F i g u r e 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 phase a n a l y s i s by X-ray powder photography. 122 peak "area fraction" of eutectic (high-melting) form (A^/A^tA^) to the weight fraction of eutectic form (W„/W„+WT) was constructed by analyzing H n L known mixtures of the two forms. 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. The results are plotted in Figure 24, which shows how [ot]/[a]p depends on X̂ . The straight diagonal represents the case where [a]/[a]p = X̂ . 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 its i n i t i a l activity of [a] = +11.8°. However, the extent of phase transformation is 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_H = [a]/[a] c = 11.8/245 = 0.0482. If R crystals existed in the i n i t i a l sample, X̂  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]„. One would expect that the approximation would improve r Figure 24. Development of s p e c i f i c r o t a t i o n w i t h extent of phase t r a n s f o r m a t i o n ( X ^ ) , S-2 K i n e t i c Batch at 125° ( a f t e r four months' storage at 0°). Diagonal represents the c o n d i t i o n [a]/[ct] = 124 as [a] approached [a] (or [a] ) , unt i l in the perfect resolution, as F o K discussed above, [a]/[a]^ must equal X^. With this assurance, an analysis of the kinetic results according to rate laws can now be conducted. The kinetics of reactions in solids consisting i n i t i a l l y of a single component have been considered in some detail in two major fields of research. The kinetics of phase transformations have received con- 87 88 siderable interest in metallurgy, ' and the kinetic behaviour of 89 1 decomposition reactions (more inorganic than organic ) has been explored rather widely in chemistry. However, from a l l of these i n - vestigations one must conclude that there exists no universal rate equation which describes the kinetics of a l l reactions in single solid components. The theoretical approaches to such solid-state reactions find i l l u s t r a t i o n in a limited 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 in terms of reaction mechanisms. The complexities of many solid-state reactions have even led to the development of methods of treating kinetic results in 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 in inorganic chemistry ' or the Johnson-Mehl- 92 Avrami Equation in metallurgy appears, in differential 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: [22] l o g l ogC^T" ) = n l o g ( t ) + n l o g ( k 6 ) - l og(2.303 n) Agreement w i t h t h i s r a t e expression w i l l t h e r e f o r e be revealed by l i n e a r i t y of a p l o t of l o g l o g ( ^ ') vs. l o g ( t ) . Such an a n a l y s i s was done f o r a l l four k i n e t i c batches, two of which are i l l u s t r a t e d i n Figures 25 and 26. 89 The second commonly used r a t e law i s the Prout-Tompkins Equation, ' which i n d i f f e r e n t i a l form i s : [23] & = k 7 y (1-y) and which i n t e g r a t e s to: [24] l o g C ^ O = k 7 t + c o n s t a n t The r e s o l u t i o n k i n e t i c s of a l l batches were t r e a t e d according to t h i s equation, and some r e p r e s e n t a t i v e l o g ( j ^ - ) vs. time p l o t s are shown i n Figures 27 and 28. 58 90 93 In the recent accounts 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 that c a u t i o n should 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 to s o l i d - s t a t e r a t e equations. K i n e t i c 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 LOG (TIME, SECONDS) Figure 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 Batch at 135° and 105°. The sample stored s i x weeks at 25° i s p l o t t e d against l o g (time, seconds) + 1 . ^ 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 LOG (TIME, SECONDS) 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, b i n a p h t h y l , S-2 K i n e t i c Batch at 135°, 125° ( o r i g i n a l r un), 115°, and 105°. 4 u o + 1.5 +1.0 +0.5 0.0 -0.5 -1.0 -1.5 O A O A _L 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' storage at 25 c Run using ground samples J_ 10 20 30 40 50 60 70 80 90 100 110 120 TIME (MINUTES) Figure 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 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 Batch at 135°. E f f e c t of g r i n d i n g and of storage at 25° f o r s i x weeks. +1.0 S-2 K i n e t i c Batch 10 15 20 25 30 TIME (HOURS) 35 40 45 50 Figure 28. 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 of neat, p l o 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 at 115°. 130 r e s u l t s should, 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 processes under the microscope. Indeed, there are even cases of agreement w i t h 58 89 both the Avrami-Erofeev and Prout-Tompkins Equations, ' and i n such cases recourse must be made to n o n - k i n e t i c observations before any mech- anism 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 considered there has been a tendency to look f o r s t r a i g h t p o r t i o n s 21 89 over only part 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 being that d i f f e r e n t mechanisms apply to d i f f e r e n t p a r t s of the r e a c t i o n . However, any meaningful a n a l y s i s from such p a r t i a l f i t s should be backed by many k i n e t i c p o i n t s known very 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 microscopic observations of 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 were made, so that any i n t e r p r e t a t i o n of the e m p i r i c a l p l o t s must be considered as subject to v e r i f i c a t i o n by independent methods. Let us consider f i r s t the Avrami-Erofeev p l o t s (Figures 25 and 26). The slope of Equation 22 gives the exponent n (Table XIV). With the S - l K i n e t i c Batch the r e s u l t s f i t a s t r a i g h t l i n e (with n near two) r a t h e r w e l l . Less p e r f e c t f i t s are found w i t h the S-3 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 described at some temperatures by two s t r a i g h t l i n e s (both slopes are l i s t e d i n Table XIV). The most obvious bend occurs w i t h the S-2 K i n e t i c Batch (Figure 26), which gives l i m i t i n g slopes of ca. 0.65 and 1.7 at a l l four temperatures. The s t r a i g h t l i n e obtained w i t h the S - l m a t e r i a l merits some d i s c u s s i o n . The exact mechanistic i m p l i c a t i o n of t h i s f i t i s not a l t o - gether c e r t a i n , c o n s i d e r i n g that Equation 21 has been de r i v e d i n a number 131 Table XIV Avrami-Erofeev 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 K i n e t i c Batch Temperature, °C Exponent S - l 135.0 1.8 II 135.0 a 2.0 II 105.1 1.8 S-2 135.0 0.7 to 1.6 b it 124.9 0,7 to 1.9 b it 114.9 0.6 to 1.6 b it 105.1 0.6 to 1.6 b S-3 135.0 1.6 tt 124.9 1.7 II 114.9 1.2 to 1.7 b II 105.1 0.8 to 1.3 b R - l 135.0 1.0 to 2.0 tt 124.9 1.0 it 114.9 0.7 it 105.1 0.8 Run performed a f t e r s i x weeks' storage at 25°. Minimum and maximum val u e s . 132 of d i f f e r e n t w a y s . ^ D ' ^ One common i n t e r p r e t a t i o n " ^ ' ^ of the exponent n i s that i t i s composed of two q u a n t i t i e s , namely, n = 3 + X. The exponent B r e f e r s to the number of steps r e q u i r e d to form a nucleus, and i s revealed i n a power law of the type N = k t , where N i s the number of 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 of a s o l i d r e a c t i o n or from counting the n u c l e i v i s i b l e under a microscope as a f u n c t i o n of time. However, as shown i n S e c t i o n 3.5.1 (p 103), the S - l and S-3 K i n e t i c Batches do not undergo n u c l e a t i o n of new m a t e r i a l , so that S = 0. The exponent X i s the number of dimen- sions i n which growth of e x i s t i n g product 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 taken as im- p l y i n g that the growing S c r y s t a l l i t e s spread i n two dimensions along, f o r example, p r e f e r r e d l a t t i c e planes or boundaries between racemate c r y s t a l l i t e s . Although lower values of n r e s u l t from p l o t s of the other k i n e t i c batches, these have l i t t l e s i g n i f i c a n c e i n view of the r a t h e r poor f i t . The S-2 K i n e t i c Batch ( F i g u r e 26) might s u f f e r a change i n mechanism 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 are too imprecise to j u s t i f y such an i n t e r p r e t a t i o n . The r a t e constant k^ (Equations 20-22) has sometimes been e v a l u - ated from a p l o t of [ l o g ( ^ •) ] " ^ n against time, once n has been d e t e r - 58 mined. This procedure allows the determination of an a c t i v a t i o n 88 energy, but there have been o b j e c t i o n s to the comparison of such a c t i v a t i o n energies to those f o r other molecular processes. This o b j e c t i o n i s based on the f a c t that k^ a r i s e s i n a r a t e equation expressing dy/dt i n terms of time as w e l l as y (Equation 20), whereas 133 the most commonly encountered r a t e constant r e s u l t s from an expression 88 of dy/dt as a f u n c t i o n of y o n l y . The Prout-Tompkins p l o t s ( F i g u r e 27-28) show l i n e a r i t y beyond y = 0.3 ( l o g ( j ~ ) - 0.37) f o r a l l k i n e t i c batches. Prout-Tompkins p l o t s 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 constants which may or 44b 58 may not have the same a c t i v a t i o n energies. ' In the 1,1'-binaphthyl case, there may be a second l i n e of g r e a t e r slope below y = 0.3, but there are f a r too few p o i n t s i n t h i s r e g ion to v e r i f y t h i s p o s s i b i l i t y . The r a t e constants d e r i v e d from the Prout-Tompkins p l o t s are l i s t e d i n Table XV. Since the constant k^ i s defined i n terms of y only (Equation 23), an a c t i v a t i o n p l o t i s worthwhile. Such a p l o t has been done i n Figure 29. The Arrhenius 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 (slope of l i n e ) , are 57.7, 62.5, 59.4 and 67.0 k c a l mole 1 f o r the S - l , S-2, S-3, and R - l K i n e t i c Batches, r e s p e c t i v e l y . The t h e o r e t i c a l b a s i s f o r the Prout-Tompkins Equation l i e s i n c o n s i d e r i n g the r e a c t i o n as proceeding by a branching process which 90 spreads throughout the p o l y c r y s t a l l i n e s o l i d . While the exact nature of the branching species 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 spread of r e a c t i o n product along g r a i n boundaries, d i s l o c a t i o n s , and the l i k e , causing the breaking apart of reactant c r y s t a l l i t e s and 58 the c r e a t i o n of new avenues f o r the advance of the product. Since i n the case of the S - l and S-3 K i n e t i c Batches, high r e s o l u t i o n s were obtained, the chain branching process i s most l i k e l y a growth process only and does not i n v o l v e the n u c l e a t i o n of new m a t e r i a l . That growth i s a branching process can be seen q u a l i t a t i v e l y from Equation 23. 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 2.50 1 3 -1 TEMPERATURE X 1 0 (DEGREES ) Figure 29. Relation of log (k^) (from Prout-Tompkins plots) to reciprocal temperature for the solid-state resolution of neat, polycrystalline 1,1'-binaphthyl, a l l four kinetic batches. Straight lines are least squares f i t s to data for each batch. 135 Table XV Prout-Tompkins Rate Constants (k^) f o r the 1,1'-Binaphthyl S o l i d - S t a t e R e s o l u t i o n of K i n e t i c Batch Temperature, °C i i n 5 - 1 k^ x 10 sec S - l 135.0 107.6 II 135.0 a 103.6 II 135.0 b 377.1 II 105.1 0.4036 S-2 135.0 194.8 it 124.9 22.71 ti 114.9 2.766 II 105.1 0.4638 S-3 135.0 514.3 It 124.9 100.8 II 114.9 11.45 If 105.1 1.733 R - l 135.0 340.7 II 124.9 25.11 II 114.9 4.782 II 105.1 0.4216 Run performed a f t e r s i x weeks' storage at 25°. Run performed w i t h ground samples. 136 of m a t e r i a l transformed (y) and that which has not yet reacted ( 1 - y ) . 44b 88 The r a t e equation i s that of 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, the product ( c r y s t a l s of pure enantiomer) must be a v a i l a b l e to the reactant (the racemate), a s i t u a t i o n which i s approached i f the product i s h i g h l y d i s p e r s e d . This i s i n c o n t r a s t to i n d i v i d u a l , compact spheres of growing product, which would i s o l a t e the reactant phase from much of the product. Some a t t e n t i o n should now be given to the 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 the growth of c r y s t a l s of pure enantiomer throughout the 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 molecules must be rel e a s e d from the racemate c r y s t a l l i t e s , i n t e r c o n v e r t i n the reactant-product i n t e r f a c e , then add to the growing product c r y s t a l l i t e s . The rate-determining step f o r the process cannot be simply the r e l e a s e of molecules from the racemate to an i n t e r f a c e r e - sembling the melt, s i n c e only some 7 k c a l mole ^ are r e q u i r e d to melt the racemate ( S e c t i o n 3.3.2, p 75). More probably, the slowest step i n v o l v e s not only the r e l e a s e of 1,1'-binaphthyl from the racemate, but al s o the simultaneous i n t e r c o n v e r s i o n of enantiomers. But the racemiz- a t i o n of 1,1'-binaphthyl i n n-heptane s o l u t i o n r e q u i r e s only 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 which, when added to 7 k c a l mole \ i s s t i l l f a r from the observed 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 the removal of molecules from a molecular c r y s t a l i s the heat of s u b l i m a t i o n , a l s o c a l l e d the bindi n g energy, of the c r y s t a l . B i n d i n g energies f o r aromatic hydrocarbons are u s u a l l y of the order of 20 k c a l mole ^ (anthracene i s -1 94 " f a i r l y t y p i c a l " at 22 k c a l mole ). However, the energy (per molecule) r e q u i r e d to remove a s i n g l e molecule from i n s i d e a c r y s t a l to the vapour 137 is twice the energy (per molecule) needed to vaporize the entire crystal, 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 is much closer to the activation energy of 62 kcal mole 1 . For 1,1'-binaphthyl, the heat of sublimation of the crystal can be estimated as follows. With nonpolar molecules, the heat of vaporization of the melt is related empirically to the normal boiling point through , _ 95 Trouton s rule: AH • • i i vaporization „, , , - 1 , - 1 — = 21 cal deg mole b.p. 96 The boiling point of 1,1'-binaphthyl has been determined as 240° at a pressure of 13 torr, which converts to a boiling point of 410°C (638°K) at atmospheric pressure, using a common vapour pressure-temperature 97 -1 nomograph. The heat of vaporization is therefore 14.3 kcal mole If AH . is the same at 105-135°C as i t is at 410°C (probably vaporization a crude approximation), and i f AH. . is the same in this temperature r* ' fusion r range as at 145°C, then; AH , = AH^ . + AH . _ . sublimation fusion vaporization ^ If the coordination number of the crystal is n, then there are n/2 bonds per molecule in the crystal, i.e., vaporizing the entire crystal breaks n/2 bonds per molecule. However, i f a single molecule is removed, a l l n bonds to i t must be broken. Therefore, twice the energy per molecule is required. 138 from 105-135°C and at atmospheric pressure. Therefore, AH , * s u b l i m a t i o n f o r the low-melting (racemate) form i s 14.3 + 7.3 = 21.6 k c a l mole ^. The energy r e q u i r e d to remove one 1,1'-binaphthyl molecule to i n f i n i t y ( 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 and i f the molecule must simultaneously i n t e r c o n v e r t , the a c t i v a t i o n energy could be as high as 43.2 + 21.7 = 64.9 k c a l mole" 1. Such a high a c t i v a t i o n energy represents an upper l i m i t to the simple breaking of Van der Waals f o r c e s i n the racemate c r y s t a l ac- companied by the conformational f l i p which i n t e r c o n v e r t s enantiomers. The f a c t that 1,1'-binaphthyl seems to r e q u i r e almost a l l of t h i s energy to reach the t r a n s i t i o n s t a t e means that the molecule needs c o n s i d e r a b l e freedom to i n t e r c o n v e r t i n the reactant-product i n t e r f a c e . The entropy of a c t i v a t i o n would have to be q u i t e favourable i n order f o r the r e a c t i o n to be observable at a l l . Therefore, both w i t h the r e s o l u t i o n of 1,1'-binaphthyl and the racemization of the ( + ) - d i a c i d 29_ i n the s o l i d phase, a high a c t i v a t i o n energy i s observed and i s compensated by a high a c t i v a t i o n entropy, 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 should emphasize that although some high degree of 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 of 1,1'-binaphthyl, each prepared batch remains an i n d i v i d u a l . The k i n e t i c c o m p l e x i t i e s of such i n t e r f a c e - c o n t r o l l e d s o l i d - s t a t e r e a c t i o n s should not, however, overshadow the s i g n i f i c a n t f a c t that r e a c t i o n s i n organic s o l i d s can occur 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 stereochemical 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 in i t i a l l y of a racemic 1,1'-binaphthyl m e l t c Both enantiomers could be obtained. I t 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 will 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 °. Crystallization was complete within three hours. The solid samples were then cooled to room temperature, 140 opened, and analyzed 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 obtained was almost always o p t i c a l l y a c t i v e , although excessive a p p l i c a t i o n of the c o o l i n g Dry Ice 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 considered i n the f o l l o w i n g s t a t i s t i c a l a n a l y s i s . 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, which i s a p r e s e n t a t i o n of percentage of observations f a l l i n g w i t h i n v a r i ous r o t a t i o n s . The l a r g e s t observed r o t a t i o n s of the 200 were [a] = -218° 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) i s [a] = ^245°) ; however, as shown, samples of low r o t a t i o n ("±2° to ±48°) were most common. The observed r o t a t i o n s f i t a Gaussian d i s t r i b u t i o n w i t h a mean of [a] = +0.14°and a standard 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 that o b t a i n i n g 1,1'-binaphthyl 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 very e x c e p t i o n a l event (obser- vable about once i n 150 t r y s ) . 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 Figure 31 by the r a t i o of the number of S-(+) samples to the t o t a l number of samples p l o t t e d f o r two runs of 100 samples each. As the t o t a l number of samples i n c r e a s e s , the r a t i o tends toward 0.5 and i t f a l l s at a l l p o i n t s w e l l w i t h i n the 99% confidence 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% (-) 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 of d e x t r o r o t a t o r y samples obtained (95) i s i n s i g n i f i c a n t l y d i f f e r e n t from the number of l e v o r o t a t o r y samples obtained (105) . ^ I f the cases of [a] = 0° obtained from o v e r c o o l i n g the samples were included i n t h i s treatment, the symmetry of the d i s t r i b u t i o n would, of course, be preserved, but the standard d e v i a t i o n would be reduced. 141 Figure 30, Percentage of 1,1'-binaphthyl 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 curve shows the Gaussian 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 of +0.14° and standard d e v i a t i o n of 86.4°. 142 j~ r~ 1 ~ r ~ ' i " 1 1 1 1 1 1 1 1 1 1 1 1 r—1 5 IO 2 0 3 0 AO 5 0 eO TO 8 0 9 0 lOO Number of Samples Figure 31. Ratio of samples having p o s i t i v e r o t a t i o n s to the t o t a l number of samples of 1,1'-binaphthyl c r y s t a l l i z e d at 150°. The 200 samples are t r e a t e d as two sets of 100 each. The curves are confidence l i m i t s c a l c u l a t e d f o r a 0.99 degree of confidence and a p r o b a b i l i t y of 50% p o s i t i v e and 50% negative f o r each sample. 143 An important c o n c l u s i o n can be drawn from the symmetric p r o b a b i l i t y d i s t r i b u t i o n . The development of o p t i c a l a c t i v i t y i n each sample was determined by only the chance formation of R or S c r y s t a l s from the racemic melt. The generation of o p t i c a l a c t i v i t y i n the 1,1'-binaphthyl system i s t r u l y spontaneous. Here, "spontaneous" i s taken as meaning " p e r t a i n i n g only to the 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 , occurs 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 racemic system i n the complete absence of e x t e r n a l dissymmetric i n f l u e n c e s of any type - p h y s i c a l , chemical, or 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 of a l a r g e number of 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 pre- sence of any such e x t e r n a l i n f l u e n c e , which w i l l be revealed 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 zero, and as a g r e a t e r number of samples of one handedness than the other, as shown by an approach to the 99% l i m i t s of confidence c a l c u l a t e d f o r the t o t a l l y random s i t u a t i o n . Although the spontaneous generation of o p t i c a l isomers i n a t o t a l l y symmetric environment seems i n t u i t i v e l y reasonable, i t has never before 98 been c a r e f u l l y demonstrated. In f a c t , q u i t e the opposite has been ob- served. The reported examples of attempts to e l i m i n a t e a l l dissymmetric 98 99 i n f l u e n c e s from s e v e r a l systems, which are r e c e n t l y reviewed ' have 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 enantiomorph. This may simply be a r e f l e c t i o n on the small number of i n d i v i d u a l t r i a l s 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'-binaphthyl showed eight negative 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 that the t o t a l l y symmetric experiment i s e i t h e r extremely d i f f i c u l t because of omnipresent o p t i c a l l y a c t i v e i m p u r i t i e s or completely impossible because of a weak dissvm- 144 m e t r i c b i a s i n the u n i v e r s e . 101 The f a c t that 1,1'-binaphthyl i s capable of t r u l y spontaneous r e s o l u t i o n not only proves that such a phenomenon i s p o s s i b l e , but a l s o that dissymmetric m a t e r i a l s which were almost c e r t a i n present as dust p a r t i c l e s or l e s s w e l l d efined dissymmetric f o r c e s , do not always i n f l u e n c e the development of o p t i c a l a c t i v i t y . Perhaps one could say that because 1,1'-binaphthyl i s a r e l a t i v e l y u n n a t u r a l compound, i t s 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 to dissymmetric im- p u r i t i e s d e r i v e d from l i f e . The question t h e r e f o r e a r i s e s as to which, i f any, dissymmetric m a t e r i a l s can i n f l u e n c e the 1,1'-binaphthyl r e s o l u t i o n . We t h e r e f o r e performed 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 presence of both d- and 1-mandelic a c i d (37) . The a d d i t i o n of 5% by weight of d-mandelic a c i d i n experiments at 130° s i m i l a r to those described above produced 1,1'-binaphthyl 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 small r o t a t i o n a r i s i n g from mandelic acid) i n 18 out of 19 samples. On the other hand, 5% 1-mandelic a c i d i n 1,1'-binaphthyl gave samples w i t h (-) r o t a t i o n s i n 17 t r i e s out of 17. These d i s t r i b u t i o n s f a l l w e l l 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 that the c o n f i g u r a t i o n of mandelic a c i d e s s e n t i a l l y completely c o n t r o l s the c o n f i g u r a t i o n of 1,1'-binaphthyl obtained. OH 37 145 I t i s p o s s i b l e to d i s t i n g u i s h three types of systems i n which 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'-binaphthyl, i s a system i n which c r y s t a l l i z a t i o n can occur from a racemic l i q u i d c o n t a i n i n g r a p i d l y i n t e r c o n v e r t i n g enantiomers. The presence of a mechanism f o r i n t e r c o n v e r s i o n means that the 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 . The f i n a l product can t h e r e f o r e be analyzed at l e i s u r e f o r any o p t i c a l a c t i v i t y (provided, of course, that i n t e r c o n v e r s i o n i s slow enough at room temperature to permit a n a l y s i s ) . Other examples, i n v o l v i n g 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 than from the melt, are the 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 tr i - o - t h y m o t i d e (39) . Although these systems develop o p t i c a l a c t i v i t y from a racemic s o l u t i o n , the number of samples taken i n each i s too few to decide whether dissymmetric i m p u r i t i e s are i n f l u e n c i n g the r e s o l u t i o n , i . e . , whether or not the r e s o l u t i o n i s t r u l y spontaneous. The second type of system i n which i t might be p o s s i b l e to demon- s t r a t e spontaneous r e s o l u t i o n i s one i n which enantiomers are 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 (or 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 CH3 38 39 146 such a system, t o t a l c r y s t a l l i z a t i o n would, of course, lea d to 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 could w e l l have an excess of one enantiomer w h i l e the l i q u i d phase con- t a i n s an excess of the other. However, t h i s represents an unstable s t a t e , s i n c e the l i q u i d phase w i l l always be supersaturated i n one enantiomer, and the two phases must be s u c c e s s f u l l y separated (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 . In s p i t e of the 85 seemingly p r e c a r i o u s procedure, t h i s method i s r a t h e r w i d e l y used, to r e s o l v e enantiomers under non-spontaneous c o n d i t i o n s (e.g. the purpo s e f u l a d d i t i o n of seed c r y s t a l s ) . The t h i r d system which can i n p r i n c i p l e show spontaneous r e s o l u t i o n i s one which contains an a c h i r a l molecule i n s o l u t i o n (or i n the 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 space group, then an excess of molecules i n one enantiomorphous c r y s t a l c o n s t i t u t e s , 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 the f i r s t type of system, the f i n a l s t a t e i s thermodynamically s t a b l e . However, a n a l y s i s presents some problems, s i n c e i n an i n d i v i d u a l crop of c r y s t a l s each must be weighed and examined f o r hemihedral faces or o p t i c a l r o t a t i o n , before i t can be concluded that the given crop contained an excess of molecules i n one enantiomorphous c r y s t a l . S u f f i c i e n t crops must a l s o be examined before any conclusions as to spontaneity can be 104 drawn. In s p i t e of 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 of sodium c h l o r a t e from s o l u t i o n i n sealed .ampules, and observed an excess of right-handed c r y s t a l s i n 51.3% of the samples, w h i l e 48.7% of the samples had left-handed c r y s t a l s i n excess. Other 105 r e s u l t s record a weighted average of 50.08 d e x t r o r o t a t o r y c r y s t a l s 147 from 46 independent crops. As f a r as we know, t h i s i s the only other c a r e f u l l y demonstrated case of the spontaneous generation of o p t i c a l l y a c t i v e m a t e r i a l . U n l i k e the enantiomorphous sodium c h l o r a t e c r y s t a l , which loses a l l o p t i c a l a c t i v i t y immediately on d i s s o l u t i o n , the 1,1'-binaphthyl system i n v o l v e s the 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 time i n s o l u t i o n (at 0°). The r e s o l u t i o n of 1,1'-binaphthyl i s t h e r e f o r e a simple i l l u s t r a t i o n of C a l v i n ' s h y p o t h e t i c a l scheme"'"^ f o r the a u t o c a t a l y t i c s e l e c t i o n of one enantiomer i n the genesis of o p t i c a l l y a c t i v e molecules. 3.7 Conclusion The development of o p t i c a l a c t i v i t y simply by h e a t i n g and c o o l i n g a racemic m a t e r i a l l i k e 1,1'-binaphthyl seems, at f i r s t thought, to be an im p o s s i b l e process. The thought a r i s e s because the i n t e r c o n v e r s i o n of enantiomers i n s o l u t i o n always leads to r a c e m i z a t i o n , not r e s o l u t i o n , because of an increase i n entropy due to gr e a t e r d i s o r d e r . But i n going from such a homogeneous system to a heterogeneous system such as the phases formed between two enantiomers, r e s o l u t i o n can become a p o s s i b l e , even probable, process. R e s o l u t i o n i s compatible w i t h the achievement of lower f r e e energy because enthalpy and entropy changes accompanying phase transformations can more than compensate f o r any l o s s e s i n f r e e energy due to formation of molecules of only one k i n d . These l o s s e s are, i n f a c t , very s m a l l . For example, even the most i n t i m a t e of mixtures of enantiomers - the l i q u i d s o l u t i o n of one i n the other - would l o s e only 1.37 c a l deg ''"mole 148 of entropy and no enthalpy ( i n the case of i d e a l s o l u t i o n s ) i n hypo- 46 t h e t i c a l l y changing from a racemic to a f u l l y r e s o l v e d s t a t e . At 150°, t h i s entropy change amounts to 580 c a l mole 1 of f r e e energy. The entropy d i f f e r e n c e between the f a r l e s s i n t i m a t e mixture found i n a e u t e c t i c conglomeration of l a r g e aggregates ( c r y s t a l l i t e s ) of pure enantiomers and the 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 s m a l l e r . In f a c t , the entropy, enthalpy and f r e e energy of mixing are i m p l i c i t l y taken as zero when two pure s o l i d s form a mechanical mixture and the f r e e energy of the mixture i s l i n e a r l y r e l a t e d to i t s composition."' 1 Therefore, there i s l i t t l e , i f any, thermodynamic preference f o r the formation of a racemic e u t e c t i c mixture over that of a p o l y c r y s t a l l i n e s i n g l e enantiomer. The choice of which i s formed i s governed e n t i r e l y by k i n e t i c s . In the spontaneous c r y s t a l l i z a t i o n of 1,1'-binaphthyl from the melt, the chance formation of one enantiomer lowers the f r e e energy of a c t i v a t i o n towards the f u r t h e r c r y s t a l l i z a t i o n of that enantiomer by p r e s e n t i n g a surf a c e on which molecules of only one c o n f i g u r a t i o n may be deposited. The element of chance can be completely e l i m i n a t e d by performing 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 of a racemate and seed c r y s t a l s of the d e s i r e d 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 the n o v e l t y of working w i t h the phase transformations of o p t i c a l l y l a b i l e enantiomers. A sample of neat 1,1 1-binaphthyl ([a] = +234°) held at 160° racemizes completely i n l e s s than f i v e minutes. Another sample of low o p t i c a l a c t i v i t y ([«] = +11°) can be prepared so that i s w i l l r e s o l v e to 149 [a] = +214° i n l e s s than f i v e minutes at 150°, only 10° lower i n temperature. How general i s t h i s phenomenon? The development of o p t i c a l a c t i v i t y by c r y s t a l l i z a t i o n of the melt r e q u i r e s that the enantiomers i n t e r c o n v e r t r e l a t i v e l y q u i c k l y i n the melt and yet be o p t i c a l l y s t a b l e ( u n l i k e the (+ ) - 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 mixture. 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 the ex i s t e n c e of two racemic m o d i f i c a t i o n s , e i t h e r a racemate or a s o l i d s o l u t i o n which decomposes to a e u t e c t i c mixture at temperatures 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 r a p i d . The e x i s t e n c e of 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 of a s i n g l e compound i s more widespread than commonly supposed. Over o n e - t h i r d of a l l organic compounds s t u d i e d thermodynamically up to 1969 e x h i b i t p o l y - , . 107a T„ . . . , 81a _ morphism. I t i s the o p i n i o n of s e v e r a l authors that every organic compound possesses more than one s o l i d s t a t e , which have only to 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 of 1,1'-binaphthyl, although s u r p r i s i n g when f i r s t encountered, i s a c t u a l l y e a s i l y explained and should 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 of o p t i c a l isomers. 150 4. EXPERIMENTAL 4.1 General Reagents and s o l v e n t s used were reagent 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. M e l t i n g p o i n t s , determined 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 apparatus i n unsealed c a p i l l a r i e s , were c o r r e c t e d . I n f r a r e d s p e c t r a ( a l l n u j o l mulls) were run on a Perkin-Elmer 137 sodium c h l o r i d e spectrophotometer. A n a l y t i c a l procedures r e q u i r i n g a more d e t a i l e d d e s c r i p t i o n (polarimet'ry, 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 ) are described i n S e c t i o n 4.6. 4.2 Pre p a r a t i o n s 4.2.1 P r e p a r a t i o n of Racemic Naphthidine (31) The procedure f o l l o w e d f o r the p r e p a r a t i o n of racemic naphthidine was s i m i l a r to that of Cohen and O e s p e r . ^ In a 1 i beaker, 27.9 g of p u l v e r i z e d a-napthylamine were s t i r r e d i n t o 500 ml water, 33.8 ml of concentrated h y d r o c h l o r i c a c i d was added, and the mixture warmed on a steam bath to give a l i g h t purple p r e c i p i t a t e of cc-nap thy lamine h y d r o c h l o r i d e . The mixture was then cooled i n an i c e bath to 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 of the concentrated a c i d plus 200 ml water) 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 (with vigorous s t i r r i n g , keeping the temperature near 0°) by 151 sl o w l y adding a c o l d s o l u t i o n of 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 red d i s h brown s o l u t i o n of the diazonium s a l t was allowed to stand f o r 5 min i n the i c e bath 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 being r e c e i v e d i n a precooled f i l t e r f l a s k surrounded by an i c e bath. 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 £ beaker ( i c e bath) and a co l d s o l u t i o n of 79.9 g anhydrous potassium acetate i n 300 ml water was s l o w l y s t i r r e d i n , the temperature being kept below 4°. A cooled s o l u t i o n of 31 g sodium s u l f i t e i n 200 ml water was then s l o w l y added, causing a vigorous e v o l u t i o n of n i t r o g e n and the appearance of 1,1'- azonaphthalene c r y s t a l s . A f t e r the a d d i t i o n of sodium s u l f i t e s o l u t i o n was completed the s o l u t i o n was allowed to s t i r f o r an a d d i t i o n a l 5 min. The suspension was then taken out of the i c e bath, warmed on a steam bath to ~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 water, and d r i e d i n a i r . Without f u r t h e r p u r i f i c a t i o n the crude azonaphthalene (ca. 18 g) was p u l v e r i z e d and suspended i n 200 ml 95% e t h a n o l , and brought to a weak b o i l . A s o l u t i o n of 48 g stannous c h l o r i d e dihydrate i n 100 ml concentrated 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 ca. 5 min (with o c c a s i o n a l s w i r l i n g ) . A colour change (from y e l l o w to reddish-brown) occurred, and the mixture was immediately cooled to room temperature. Concentrated h y d r o c h l o r i c a c i d (100 ml) was then added to p r e c i p i t a t e any remaining naphthidine 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 water, then suspended i n 200 ml water. Twenty ml of 20% sodium hydroxide was then added, and the mixture allowed to s t i r at 40° f o r 10 min. The s l u r r y was cooled i n an i c e bath, f i l t e r e d , washed w i t h water and d r i e d i n a i r . The crude naphthidine was d i s s o l v e d i n 160 ml 152 of a hot 3:1 e t h a n o l - p y r i d i n e s o l v e n t p a i r . The hot s o l u t i o n was f i l t e r e d and allowed to c o o l s l o w l y . The p u r i f i e d naphthidine (7.1 g, 26% from a-naphthylamine) was obtained as well-formed, l i g h t brown p l a t e s (m.p. 201-202°, l i t . 7 0 198-199°). 4.2.2 P r e p a r a t i o n of (+)-Naphthidine-a-bromo-D-camphor-~-sulfonate (33) This s a l t was prepared using the procedure of T h e i l a c k e r and Hopp. 7 1 To 400 ml water and 40 ml 1 N h y d r o c h l o r i c a c i d was added a s o l u t i o n of 2.84 g (10 mmoles) racemic naphthidine i n 50 ml hot acetone. This was f o l l o w e d immediately w i t h 6.54 g (20 mmoles) (+)-ammonium-a- bromo-D-camphor-ir-sulfonate. A l i g h t - b r o w n p r e c i p i t a t e soon formed and the mixture was allowed to stand at room temperature overnight. The 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% (by volume) ethanol-water. Two crops (4.27 g, 46%) were obtained. This m a t e r i a l 25 71 20 gave a s p e c i f i c r o t a t i o n of [ c t ] D = +80° ( l i t . = +99°). 4.2.3 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 33 The s a l t 33 was d i r e c t l y deaminated to S-(+)-1,1'-binaphthyl u s i n g a procedure s i m i l a r to t h a t of C o l t e r and Clemens.^ To an i c e - c o l d suspension of 150 ml water, 3.45 g of s a l t J3J3, 2.3 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 added 1.2 g sodium n i t r i t e . 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 added to the c o l d mixture and s t i r r i n g was continued f o r another 3 h. The f l a s k was then stoppered l i g h t l y and placed i n the r e f r i g e r a t o r overnight (0°). 153 For two days the f l a s k was s t i r r e d and kept c o l d during 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 rnight, during which time a t o t a l of 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 mixture 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 suspension 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 hydroxide, water, 10% h y d r o c h l o r i c a c i d , and water ( a l l at ^ 8°), and d r i e d over anhydrous MgSO^. A f t e r f i l t r a t i o n ( c o l d apparatus), the benzene was removed on the r o t a r y evaporator (25-30°), and the s o l i d p laced on a column (with a water j a c k e t ) packed w i t h 25 g alumina (Woelm, n e u t r a l , a c t i v i t y grade 1) i n petroleum ether (30-60°). Cold water was c i r c u l a t e d through the j a c k e t . The f r a c t i o n s , e l u t e d w i t h 4% (by volume) benzene- petroleum ether (30-60°) a f f o r d e d white c r y s t a l s (0.536 g, 55%) of 25 65 o p t i c a l l y a c t i v e 1,1'-binaphthyl ( [ a ] D = +97°; m.p. 156-157°; l i t . [a] = +145-192°, m.p. 156-159°; l i t . 6 4 [ a ] 5 7 9 1 = +245°, m.p. 157- 159°) . 4.2.4 P r e p a r a t i o n of Racemic 1,1'-Binaphthyl The procedure used was analogous to that of S a k e l l a r i o s and K r y i m i s . To a dry 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 condenser was added (under dry n i t r o g e n ) 9.6 g magnesium t u r n i n g s , 72 ml anhydrous e t h e r , 56 ml a-bromonaphthalene and a s i n g l e c r y s t a l of i o d i n e . The s t i r r e d mixture was heated to r e f l u x to s t a r t the r e a c t i o n , which proceeded without f u r t h e r h e a t i n g f o r 20 min. The r e a c t i o n mixture was then heated 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 dry benzene to t h i n the s l u r r y when necessary. The r e a c t i o n was cooled to room temperature and added s l o w l y to a s t i r r e d suspension of 54 g 154 anhydrous c u p r i c c h l o r i d e (prepared by d r y i n g the dihydrate s a l t f o r 4 h at 100°) i n 200 ml anhydrous ether. The ensuing vigorous r e a c t i o n was c o n t r o l l e d w i t h an ice-water bath. The suspension was then s t i r r e d overnight at room temperature under dry n i t r o g e n . The r e a c t i o n mixture was quenched by slow a d d i t i o n to 100 ml 10% h y d r o c h l o r i c a c i d and i c e . The ether-benzene 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 of 10% h y d r o c h l o r i c a c i d , water, s a t u r a t e d sodium bicarbonate s o l u t i o n and water, and d r i e d over anhydrous magnesium s u l f a t e . The so l v e n t s were removed in_ vacuo to a f f o r d an o i l , which c r y s t a l l i z e d on c o o l i n g to 0°. The brown m a t e r i a l was t r a n s f e r r e d to a Buchner f u n n e l , washed w i t h a s m a l l amount of c o l d petroleum ether (30-60°), and r e c r y s t a l l i z e d once from petroleum ether (65-110°). The crude 1,1'-binaphthyl (̂  12 g) was then mixed w i t h an equal weight of alumina (Shawinigan reagent) and plac e d on a column of 300 g alumina packed i n petroleum ether (30-60°). A f t e r 1 I had been e l u t e d w i t h 10% benzene-petroleum ether (30-60°), the f i r s t appearance of 1,1'-binaphthyl was revealed by the presence of white c r y s t a l s at the t i p of the column. The e n t i r e b i n a p h t h y l f r a c t i o n r e q u i r e d 3 I f o r complete e l u t i o n . Evaporation of 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 of the b i n a p h t h y l from acetone a f f o r d e d 10 g (20%) of white c r y s t a l s , m.p.'s 144-145° (low-melting form) and 73 157-158° (high-melting form). Badar, et a l . r e p o r t m.p. 144.5-145° (low-melting form) and 157-159° (high-melting form). 155 4.3 Procedures f o r the R e s o l u t i o n of Racemic 1,1'-Binaphthyl 4.3.1 R e s o l u t i o n i n Completely Melted 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 melt which i s t o t a l l y racemic, c a r e f u l l y weighed samples of 1,1'-binaphthyl (from s e v e r a l d i f f e r e n t batch p r e p a r a t i o n s ) ranging from 10-30 mg i n weight were sealed i n 1 ml g l a s s ampules. In groups of 12, the sealed ampules were h e l d i n a s i l i c o n e - o i l at 170-185° to destroy a l l forms of s o l i d 1,1'-binaphthyl. The completely melted samples were then q u i c k l y t r a n s f e r r e d to a second s i l i c o n e o i l bath maintained at p r e c i s e l y 149.6°, where they would have remained as a supercooled melt i n d e f i n i t e l y . C r y s t a l l i z a t i o n was induced by removing 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 piece of Dry I c e f o r ca. 5 sec, then immediately r e p l a c i n g i t i n the 149.6° bath. The c o o l i n g o p e r a t i o n was performed q u i c k l y , so t h a t no sample was outside of the bath f o r more than 10 sec. 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 completely, a f t e r which time they were cooled to room temperature, opened, and analyzed f o r o p t i c a l a c t i v i t y . P o l y c r y s t a l l i n e 1,1'-binaphthyl c o n t a i n i n g a known amount of a dissymmetric " i m p u r i t y " (d- and £-mandelic acid) was prepared as f o l l o w s . In 50 ml acetone ( d i s t i l l e d from potassium permanganate) 0.49252 g racemic 1,1'-binaphthyl and 0.02639 g d-mandelic a c i d were d i s s o l v e d . The s o l u t i o n was f i l t e r e d and the s o l v e n t removed i r i vacuo. The r e s u l t i n g mixture, which contained 5.08% (by weight) d-mandelic a c i d , was sealed i n ampules, melted, and c r y s t a l l i z e d i n a manner analogous to the above procedure w i t h the completely racemic 1,1'- b i n a p h t h y l . A s i m i l a r procedure was used f o r the mixing of £-mandelic 156 a c i d w i t h racemic 1,1'-binaphthyl. 4.3.1.2 D e l i b e r a t e A d d i t i o n of C r y s t a l s of A c t i v e 1,1'-Binaphthyl To t e s t the e f f e c t of 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 completely melted samples (Table XI, p 93), ca_. 200 mg of s o l i d racemic 1,1'-binaphthyl (from v a r i o u s batch preparations) were pla c e d i n the bottom of a t e s t tube 15 cm i n length and f i t t e d w i t h a ground g l a s s stopper. The s o l i d was introduced through a long-stemmed f u n n e l to avoid c o a t i n g the upper par t of the 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 (except f o r the top 2 cm) was then immersed i n a bath at 170-180°, where a l l 1,1'-binaphthyl melted, and immediately t r a n s f e r r e d to a 149.6° bath and immersed to the same l e v e l . The stopper was removed f o r ca. 10 sec w h i l e the a c t i v e 1,1'-binaphthyl seeds were dropped i n from the t i p of a s p a t u l a . C r y s t a l l i z a t i o n r e q u i r e d overnight (16 h) to become complete. The sample was then cooled to room temperature, the cake of s o l i d broken up w i t h a s p a t u l a , and d u p l i c a t e analyses f o r o p t i c a l a c t i v i t y performed. 4.3.2 R e s o l u t i o n i n the S o l i d State 4.3.2.1 The Heating of Racemic 1,1'-Binaphthyl As a standard c h a r a c t e r i z a t i o n of f e s h l y prepared racemic 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 given batch of racemic m a t e r i a l were heated at 149.6°. Samples were cooled to room temperature and analyzed f o r o p t i c a l a c t i v i t y (Table III, p 51 and Table VIII, p 85 ). 157 In some experiments (Table X, p 92) c a r e f u l l y weighed o p t i c a l l y a c t i v e b i n a p h t h y l was added to the weighed racemic m a t e r i a l before the ampules were sealed. The sealed samples were then mixed thoroughly by h o l d i n g them i n contact w i t h a Lab-Line "Super-Mixer" f o r 5 min, heated at 149.6° and analyzed f o r s p e c i f i c r o t a t i o n . 4.3.2.2 C y c l i n g S o l i d 1,1'-Binaphthyl to High S p e c i f i c R o t a t i o n At the bottom of a 15 cm t e s t tube was placed 2.00 g of racemic 1,1'-binaphthyl (Racemic Batch G). The t e s t tube was s e a l e d , placed i n a 149.6° bath f o r 2 h (the sample appeared to remain s o l i d through- out) , then cooled to room temperature and opened. P o l a r i m e t r i c a n a l y s i s gave [ a l D = +42°. The s o l i d was d i s s o l v e d i n 400 ml pentane, 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 allowed to c o o l to room temperature ( t o t a l time at the b.p. of pentane (36°) was 15-20 min), and placed i n the r e f r i g e r a t o r (0°) f o r 1 h. The pentane was removed on the r o t a r y evaporator to a f f o r d 94% m a t e r i a l having 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'-binaphthyl was then sealed i n a second t e s t tube and heated, as b e f o r e , at 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 repeated i n e x a c t l y the same manner as befor e , preparing the m a t e r i a l f o r the t h i r d h e a t i n g at 149.6°. The c y c l e was repeated a f o u r t h time to o b t a i n 1.10 g (the weight l o s s e s due mainly to samples taken 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 scanning analyses) of S - ( + ) - l , l ' - b i n a p h t h y l , [ - l ^ = +194°. Other c y c l i n g experiments (Table IV, p 54 ) were patterned a f t e r the above procedure. 158 4.3.2.3 The Heating of Slightly Active 1,1'-Binaphthyl (a) The Preparation of S-l Kinetic Batch A solution of 0.181 g of active 1,1*-binaphthyl ( M D = +208°) and 3.819 g of racemic 1,1'-binaphthyl (comprising together 4.000 g of material with ta] Q = +9.4°) in 280 ml acetone (Fisher reagent) was prepared and f i l t e r e d into a 500 ml Erlenmeyer flask. The solution was then placed in a Dry-Ice-acetone bath, with occasional swirling. Precipitation, which began in ~10 min, appeared to be complete in 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 specific rotation of [a]^ = +1.4°. Samples taken from this batch resolved to [ a ] D = +211° within 16 h at 149.6°. Other batches prepared by this procedure did not always resolve well on heating. (b) The Recrystallization-Evaporation Procedure - The Preparation of S-3 Kinetic 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 g of material with [a] = +2.2°) in 400 ml acetone (freshly d i s t i l l e d from potassium permanganate) was f i l t e r e d into a 1 £ round-bottom flask. The solution was then cooled in a Dry Ice-acetone bath (-78°) for 10 min with swirling, during which time crystallization began. Without completing the crystallization, the flask was removed and immediately placed on a rotary evaporator (Buchi Rotavapor <R> ) . The flask was rotated in air 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 ) of the c r y s t a l s d i s s o l v e d , then r e p r e c i p i t a t e d w i t h the l o s s of s o l v e n t . The evaporation was taken to dryness, and any r e s i d u a l acetone was removed on the high vacuum pump. The m a t e r i a l , which was 100% recovered, possessed an a c t i v i t y of (a) = +2.0°, and r e s o l v e d to (a) > +200° on h e a t i n g at any temperature between 105° and 150°. K i n e t i c batches S-2 and R - l were prepared by an analogous procedure. The s o l i d 1,1'-binaphthyl ( [ a ] n = -2° to ±15°) obtained by t h i s method almost always r e s o l v e d to at l e a s t [ a ] Q = ±190° on heating to 150° f o r 2 h. 4.3.3 R e s o l u t i o n I n v o l v i n g O p t i c a l l y I n a c t i v e Solvents 4.3.3.1 Heating of Racemic 1,1'-Binaphthyl Under a Solvent A g l a s s tube 20 cm i n length and c o n t a i n i n g a coarse f r i t t e d 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 racemic 1,1'-binaphthyl was placed on the d i s c . The top end was then s e a l e d , the tube i n v e r t e d , and 0.5 ml 2-propanol ( f r e s h l y d i s t i l l e d from stannous c h l o r i d e ) placed through the remaining open end. The sealed end was immersed i n a dry ice-acetone bath to p u l l the 2 - p r o p a n o l through the 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 the e n t i r e tube submerged i n a bath maintained at 120°, and o r i e n t e d so that the b i n a p h t h y l / 2 - propanol mixture remained at the bottom end. About h a l f the s o l i d b i n a p h t h y l d i s s o l v e d . A f t e r 43 h the tube was i n v e r t e d i n the bath, a l l o w i n g the 2- p r o p a n o l to d r a i n from the 1,1'-binaphthyl through the f r i t t e d d i s c . R e s i d u a l 2-propanol was removed by t a k i n g the tube from the bath and q u i c k l y immersing the 2 - p r o p a n o l chamber i n Dry Ice-acetone. 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 in 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 in a 135° bath. A l l of the binaphthyl in 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 in 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 1,1'-binaphthyl. 4.4 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 recrystalliza- tion (2 days) from actone solution was examined under a microscope w i t h permanently crossed p o l a r i z e r and analy s e r and r o t a t a b l e stage. C r y s t a l s which were not 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 adhering to the surface were removed, and i f the e n t i r e c r y s t a l , viewed at any angle except normal to the c or d faces (Figure 10, p 62 ) e x t i n g u i s h e d s h a r p l y as the stage was r o t a t e d , i t was set aside 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 to p o l i s h the c r y s t a l f a c e s , a few of which were rough i n appearance. 4.4.2 C r y s t a l l i z a t i o n of Low and High-Melting 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 pentane, 0.50 g of racemic 1,1'-binaphthyl 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 the f i l t r a t e reduced to 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 allowed to c o o l s l o w l y to 0° cooled r a p i d l y i n an i c e bath, or seeded w i t h v a r i o u s samples of racemic b i n a p h t h y l . Racemic Batches A to J were prepared 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 (except D, which was prepared by r e c r y t a l l i z i n g 0.50 g racemic 1,1'-binaphthyl from 10 ml g l a c i a l a c e t i c a c i d ) . Racemic Batches K, L, and N were prepared by r e c r y s t a l - l i z a t i o n from petroleum ether (65-110°), using 25 ml s o l v e n t f o r each gram to be r e c r y s t a l l i z e d . Racemic Batch M was r e c r y s t a l l i z e d from acetone at -78° (see Se c t i o n 4.4.3 f o r a s i m i l a r procedure), and Racemic Batch 0 was a commercial sample of 1,1'-binaphthyl (K and K L a b o r a t o r i e s , I n c . ) . 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 of 1,1'-binaphthyl produce by slow and f a s t removal of s o l v e n t , 100 mg p o r t i o n s of racemic 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 (ether, acetone, or benzene). 162 Slow evaporation: The s o l u t i o n s were f i l t e r e d i n t o three 25 ml Erlemeyer f l a s k s and placed under an upturned beaker f o r s e v e r a l days. The ether s o l v e n t disappeared w i t h i n one day, the acetone i n two days, and the benzene i n fou r days. Fast evaporation: The three s o l u t i o n s (prepared as above) were not f i l t e r e d , but were subjected to a stream of dry a i r w h i l e being h e l d i n a water bath at room temperature. Solvents were removed w i t h i n 5 min. The c r y s t a l s from a l l s i x samples were analyzed 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 of the racemic melt was s t u d i e d on the d.s.c. ( S e c t i o n 4.6.2). S o l i d racemic 1,1'-binaphthyl was melted i n a d.s.c. sample p l a n c h e t t e at 160°, then cooled at a r a t e of 20 deg min 1 to o b t a i n pure low-melting form. A fesh sample (or the same one) was melted a t 160° and cooled r a p i d l y by removing the sample p l a n c h e t t e and p l a c i n g i t on a metal surface. Replacing the sample i n the d.s.c. and warming to 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 of the melt was obtained by packing 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 racemic l , l ' - b i n a t > h t h y l m e l t i n g the sample at 175°, and immediately immersing the (unsealed) c a p i l l a r y i n a l i q u i d n i t r o g e n 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 Debye-Scherrer camera f o r a n a l y s i s . 4.4.3 Phase L i m i t of R e s o l u t i o n The f o l l o w i n g procedure used f o r R-(-)-1,1'-binaphthyl was s i m i l a r l y a p p l i e d to S-(+)-1,1'-binaphthyl. In 180 ml acetone ( d i s t i l l e d from potassium permanganate) was d i s s o l v e d 1.53 g of R - l , l ' - b i n a p h t h y l ( [ c t ] 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 Ice-acetone bath (-78°). The le n g t h of time at room tempera- ture was 15 min. C r y s t a l l i z a t i o n was complete a f t e r 30 min at -78° ( o c c a s i o n a l s w i r l i n g ) . The c r y s t a l s were then r a p i d l y s u c t i o n - f i l t e r e d 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 (1.26 g, 82%) and m a t e r i a l from s o l u t i o n were analyzed f o r o p t i c a l a c t i v i t y , the l a t t e r made p o s s i b l e by removal of acetone s o l v e n t i n vacuo at 25° w i t h i n 15 min. 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 possessed [ a ] Q = +228°, the m a t e r i a l from s o l u t i o n having [ a ] ^ = -111°. Three 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 performed, w i t h the r e s u l t s l i s t e d i n Table XVI, p 179. 4.5 K i n e t i c Methods 4.5.1 Standard Procedure The procedure f o r the k i n e t i c study of the r a c e m i z a t i o n of the d i a c i d 29_ i n the s o l i d and the melted s t a t e s , was i d e n t i c a l w i t h that of 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. In both cases, 10-30 mg of the neat, 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 sealed i n a i r , and completely immersed i n a constant-temperature s i l i c o n e o i l bath. At ap p r o p r i a t e times i n d i v i d u a l samples were withdrawn, cooled to room temperature, opened, and analyzed f o r o p t i c a l a c t i v i t y . For the s o l u t i o n phase r a c e m i z a t i o n of (+)-29, s e a l e d ampules contained ^ 10 mg of c a r e f u l l y weighed (+)-29 and 0.2 ml p u r i f i e d t e t r a l i n . The d i a c i d 29_ d i s s o l v e d only when the samples were heated f o r the run; concentrated s o l u t i o n s (ca. 0.27 M) were t h e r e f o r e p o s s i b l e . 164 First-order rate constants ( 0̂̂ g) were obtained by plotting log ( [ a ] / [ a ] Q ) +2 against time, where [al is t^-e specific rotation (sodium 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 in a small (1 cm o.d.) test tube using a glass stirring rod which had been molded to f i t the bottom of the test tube. 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 difficult. 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 racemization was complete. At 161 and 166°, y e l l o w i n g was more apparent than i n the melt, and the samples p a r t i a l l y melted. Racemic d i a c i d 29_ was heated i n t e t r a l i n at 140° f o r 96 h (greater than 15 h a l f - l i v e s f o r ra c e m i z a t i o n of (+)-29). E x t r a c t i o n of the d i a c i d i n t o 10% sodium hydroxide and a c i d i f i c a t i o n give racemic 29_, whose n u c l e a r magnetic 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 fumaric a c i d s i g n a l was present i n the spectrum. In another run, 0.45 g of the racemic d i a c i d 29_ was heated w i t h 10 ml of t e t r a l i n at 140° f o r 52 h (ca. 9 h a l f - l i v e s ) . On c o o l i n g , 0.32 g (71%) of racemic 29, m.p. 180-184° was recovered. E x t r a c t i o n of mether l i q u o r s w i t h d i l u t e base gave 0.094 g (21%) of s t i c k y , probably p o lymeric, s o l i d . E s s e n t i a l l y complete i n t e r c o n v e r s i o n of enantiomers occurs before s i d e r e a c t i o n s become important at long r e a c t i o n times. The k i n e t i c batches of 1,1'-binaphthyl 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 completion of the r e s o l u t i o n . At 98°, some y e l l o w i n g occurred at long r e a c t i o n times (3-6 months). The product of the r e s o l u t i o n gives the d . s . c , i n f r a r e d , and X-ray analyses of the high-melting form of 1,1'-binaphthyl ( i n f r a r e d s p e c t r a 73 reported by Badar, et a l . ). C o - i n j e c t i o n of the s t a r t i n g m a t e r i a l and r e s o l v e d product i n t o a g a s - l i q u i d chromatograph [using an 8% SE-30 on Chromosorb W (80/100) (6 f e e t x 1/8 inch) column; c a r r i e r gas: helium; flow r a t e : 110 ml min "*"; temperature: 150° f o r 3 min, the heating at 32 deg min ^ to 270°, maintained f o r 10 min; instrument: Perkin-Elmer 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 P o l a r i m e t r y A Bendix type 143 A automatic p o l a r i m e t e r was used w i t h a modified sample c e l l . The s u p p l i e d c e l l holder assembly was used to c o n t a i n a c e l l composed of a round metal spacer having a c o n c e n t r i c hole and a thi c k n e s s of 1 cm. C e l l windows were composed of round glass s l i d e s separated from the spacer and the r e s t of the assembly by round T e f l o n wafers w i t h holes punched i n the center. The pieces of the c e l l were sandwiched together i n the c e l l h o l d e r assembly i n the intended f a s h i o n . Sample s o l u t i o n s were introduced through a hole d r i l l e d i n the s i d e of the metal spacer which formed the c e l l . Each sample ampule (1 ml) from the k i n e t i c runs was opened and the 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, which does not racemize a p p r e c i a b l y i n acetone at 25°) or i n benzene ( f o r o p t i c a l l y a c t i v e 1,1'-binaphthyl, which possesses a h a l f - 74 l i f e of 11.4 h f o r racemization i n benzene at 25° ). The s o l u t i o n was t r a n s f e r r e d to 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 to the mark w i t h washings from the opened ampule. Three readings were made by f i l l i n g 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 (ca. 0.8 ml each) of the s o l u t i o n . Zero readings were taken using the pure o s o l v e n t . A l l measurements were made at the sodium D l i n e (5890 A ) , and 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 x c/ (sample wt. i n mg) where a i s the observed r o t a t i o n and c = 0.80 i s a c e l l constant obtained by c a l i b r a t i o n w i t h known standard sucrose s o l u t i o n s . 167 4.6.2 D i f f e r e n t i a l Scanning C a l o r i m e t r y The d i f f e r e n t i a l scanning c a l o r i m e t e r (d.s.c.) used was a P e r k i n - Elmer DSC-1B. For q u a l i t a t i v e runs, ca. 5 mg c r y s t a l s were placed 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 . The l i d was pressed f i r m l y against the p l a n c h e t t e , p a r t i a l l y crushing the c r y s t a l s , but the p l a n c h e t t e and l i d were not crimped together. A standard programming r a t e of 10 deg min ^ was used unless otherwise noted. The temperature readout was 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, using 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 s e t t i n g s of 485 and 522, r e s p e c t i v e l y . T r a n s i t i o n temperatures were measured at the beginning ( i . e . , at f i r s t departure from b a s e l i n e ) of recorded peaks. For q u a n t i t a t i v e enthalpy d e t e r m i n a t i o n s , the sample was weighed on a Cahn E l e c t r o b a l a n c e (Model M-10) and run through the t r a n s i t i o n on the d.s.c. at a programming r a t e of 10 deg min \ a range of 16x and a chart speed of 4 i n min ^ (Leeds Northrup Speedomax W chart r e c o r d e r ) . A c a l i b r a t i o n run using the weighed h i g h - p u r i t y indium standard provided was performed under i d e n t i c a l c o n d i t i o n s , from which i t was learned that at the s e t t i n g s used, each square i n c h of chart paper represented a heat flow 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 of s i x determinations w i t h a planimeter (Gelman Instrument Co.). The enthalpy of the t r a n s i t i o n i n k c a l mole was r 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 temperature, but the value 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°. 168 c a l c u l a t e d from: 2 (area of sample t r a n s i t i o n , i n ) ,., ., • c i \ AH = — ; — ; r - x(molecular weight of sample) x (weight of sample, mg) 27.3 x 10~ 3 The heat c a p c i t y (Cp) measurements (Table X V I I , p 190 ) were performed using the S p e c i f i c Heat K i t , an accessory to the DSC-1B. The method i n v o l v e d comparison to a standard, which was a d i s c of h i g h - p u r i t y sapphire. The sapphire standard was weighed, placed i n a sample 47 p l a n c h e t t e , and covered i n the recommended manner. The d.s.c. was run i s o t h e r m a l l y to e s t a b l i s h a b a s e l i n e , then i t was programmed at 10 deg min ^ (range: 4x), causing a pen d e f l e c t i o n p r o p o r t i o n a l to the heat c a p a c i t y of the sapphire. The programming was d i s c o n t i n u e d a f t e r heating f o r ten degrees, and the b a s e l i n e r e - e s t a b l i s h e d . In t h i s manner, the sapphire was heated from 50° to 150° i n ten degree' i n t e r v a l s which overlapped so t h a t two measurements of the amplitude of the d e f l e c t i o n could be made at 60°, 70°, ... 140°. The sapphire was removed and a blank run was performed w i t h the same pl a n c h e t t e i n an i d e n t i c a l f a s h i o n . The p l a n c h e t t e was then f i l l e d w i t h a weighed amount of 1,1'-binaphthyl (pure h i g h - m e l t i n g form) and the procedure repeated. A l l three (sapphire, blank and sample) runs were repeated w i t h pure low-melting b i n a p h t h y l , from 50° to 140°. In n e i t h e r sample d i d any weight l o s s or phase t r a n s f o r m a t i o n occur. At each temperature the amplitude of the blank was s u b t r a c t e d from that of the sapphire and b i n a p h t h y l samples, and Cp ( i n c a l deg ''"mole ''") c a l c u l a t e d from: 169 = (amplitude sample) x (weight sapphire) % Q f g h ± c a l -1, x r (amplitude sapphire) (weight sample) (molecular weight of 1,1'-binaphthyl) The two sapphire runs agreed ( i n amplitude) to w i t h i n 1% at a l l temperatures, good evidence of the p r e c i s i o n of the method. The accuracy of the method was t e s t e d by measuring the heat c a p a c i t y of naphthalene at 51° and 61° as 43.7 and 46.0 c a l mole "'"deg \ r e s p e c t i v e l y ( l i t . " ' " 0 8 44.0 and 45.9 c a l mole "*"deg \ r e s p e c t i v e l y ) . The accuracy was b e t t e r than 1%. 4.6.3 X-Ray Powder D i f f r a c t i o n The f o l l o w i n g procedure 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 adopted. The sample to be analyzed was thoroughly p u l v e r i z e d i n a s m a l l agate mortar, 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 Lab-Line "Super Mixer". The bottom 1.5 cm of the c a p i l l a r y was broken o f f , and a l i g n e d i n a Debye-Scherrer powder camera ( P h i l i p s PW 1024/10) equipped w i t h the smaller (0.5 mm) c o l l i m a t o r and beam stop. The camera was then loaded w i t h Kodak No-Screen NS-392 T 35 mm X-ray f i l m and mounted on the non-divergent quarter of the P h i l i p s PW 1008/85 X-ray generator (CuK^ r a d i a t i o n , N i f i l t e r ) . The source was a c t i v a t e d (40 kV and 15 mA, and the f i l m exposed f o r e x a c t l y 20 h. The f i l m was developed w i t h Kodak D-19 developer (a stock s o l u t i o n prepared as recommended, but using d i s t i l l e d water and bubbling 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 ten times w i t h water at 20°C (68°F). 170 Development, performed i n an Anscomatic 35 mm developing tank, took 4 min w i t h s w i r l i n g every 30 sec. The f i l m was then immersed i n a stop bath (stock s o l u t i o n : 13 ml g l a c i a l a c e t i c a c i d i n 1 £ w a t e r ) , r i n s e d , and f i x e d (Kodak Rapid F i x , f r e s h l y prepared) f o r four minutes. A f t e r r i n s i n g f o r 30 min, the f i l m was immersed i n Photoflow and hung to dry f o r 3-4 h. The 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 was measured on a Joyce double beam r e c o r d i n g microdensitometer (mk I I I C). The f o l l o w i n g s e t t i n g s were used. Mode: Forward I n t e g r a t e ; d i f f e r e n t i a l c o n t r o l : 5; pen damping: 5; i r i s : 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 ; s l i t : 25; aperture: 25; d e n s i t y wedges: 0-2 o p t i c a l d e n s i t y (O.D.) u n i t s (D 453) and 0-1 O.D. u n i t s (B 335); r a t i o arm: 10 times. The zero of o p t i c a l d e n s i t y was taken as the d e n s i t y of unexposed, undeveloped f i l m which had been f i x e d . The range of o p t i c a l d e n s i t y (from the background fog l e v e l to the most dense measured peak) was measured w i t h the 0-2 O.D. d e n s i t y wedge. In a l l f i l m s taken, t h i s range was between 0.40 and 1.20 O.D. u n i t s (the l i n e a r range (where O.D. i s 109 p r o p o r t i o n a l to exposure) of 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 to be measured were t r a c e d as peaks using the (more p r e c i s e ) 0-1 O.D. d e n s i t y wedge. The 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 o 10.1 A l i n e of the racemate and the 6.4 A l i n e of the e u t e c t i c form. 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 densitometer t r a c i n g s using the average of s i x area determinations w i t h the planimeter. The area of the e u t e c t i c (high-melting) form (A^) was expressed as a f r a c t i o n t o t a l area of th  wo peaks: 171 area f r a c t i o n (high-melting 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 weights of low- and high-melting forms were prepared by grinding and thoroughly mixing the two forms together, then a n a l y z i n g these samples using the described X-ray procedure. The r e s u l t i n g weight f r a c t i o n s : WH weight f r a c t i o n (high-melting form) = WH + WL were p l o t t e d against t h e i r corresponding area f r a c t i o n s (Figure 23, p 121) and the r e s u l t i n g c a l i b r a t i o n curve used to determine the phase content of samples of the S-2 K i n e t i c Batch at v a r i o u s stages of r e s o l u t i o n (Figure 24, p 123) . The d spacings of the low- and h i g h - m e l t i n g forms (Table 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 photograph w i t h an accurate m i l l i m e t e r s c a l e , and converting to 28. This conversion was easy s i n c e the P h i l i p s camera was constructed so that 1 mm represented 2° 29,allowing f o r "normal f i l m shrinkage" on development. The d spacings were then obtained from the 28 values and the r e l a t i o n : d = 2sin8 where X i s the wavelength of CuK^ r a d i a t i o n (1.5418 A). The i n t e n s i t i e s of the l i n e s were obtained by i n t e g r a t i n g the peaks obtained from the microdensitometer. 172 BIBLIOGRAPHY 1. C.E.H. Bavn i n "Chemistry of the S o l i d S t a t e , " W.E. Garner, Ed., Butterworth, London, 1955, Chapter 10. 2. (a) H. Morawetz i n "Physics and Chemistry of the Organic S o l i d S t a t e , " V o l . I , D. Fox, M.M. Labes, and A. Weissberger, Ed., I n t e r s c i e n c e , New York, 1963, Chapter 4 (and Addendum, V o l . I I , 1965, p 853). (b) H. Morawetz, Science, 152, 705 (1966). (c) H. Morawetz, S.Z. Jakabhazy, J.B. Lando, and J . Shafer, Proc. Nat. Acad. S c i . U.S., 49., 789 (1963) (d) H. Morawetz i n " R e a c t i v i t y of S o l i d s , " G.-M. Schwab, Ed., E l s e v i e r , Amsterdam, 1965, p 140. 3. G.M.J. Schmidt i n " R e a c t i v i t y of the Photoexcited Organic Molecule," I n t e r s c i e n c e , New York, 1967, p 227. 4. M;D. Cohen i n "Organic S o l i d State Chemistry," G. 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Soc., 93, 1291 (1971) 178 APPENDIX A THE PHASE LIMIT OF RESOLUTION Since a l l of our experiments w i t h 1,1'-binaphthyl produced samples having 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 very d e s i r a b l e to know the highest p o s s i b l e r o t a t i o n (at the sodium D l i n e , where a l l of our s p e c i f i c r o t a t i o n s were measured) observable i n the 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 to how t h i s might be accomplished was obtained when s e v e r a l samples of h i g h l y a c t i v e 1,1'-binaphthyl were r e c r y s t a l l i z e d from acetone at -78°, as a f i n a l p u r i f i c a t i o n measure before the f u r t h e r study of samples w i t h high a c t i v i t y . The m a t e r i a l obtained from the r e c r y s t a l - l i z a t i o n possessed a s p e c i f i c r o t a t i o n higher than that of the o r i g i n a l s o l i d . A study of the 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 solvent revealed that simply 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 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 u n t i l a constant f i g u r e i s obtained (see below). We th 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 of w e l l - r e s o l v e R - l , 1 ' - b i n a p h t h y l to see how high an a c t i v i t y could be obtained. S t a r t i n g w i t h 1.53 g of m a t e r i a l having [a] = -216°, we obtained, a f t e r four r e - c r y s t a l l i z a t i o n s from acetone at -78°, 0.56 g of 1,1'-binaphthyl having a s p e c i f i c r o t a t i o n of [a] = -245° ± l°(Table XVI). We proceeded no f u r t h e r because the r o t a t i o n d i d not increase i n the l a s t r e c r y s t a l l i z a t i o n 179 Table XVI Low Temperature R e c r y s t a l l i z a t i o n of 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 R e c r y s t a l l i z a t i o n R e c r y s t a l l i z a t i o n , R e c r y s t a l l i z a t i o n , S o l u t i o n , Number g degrees degrees R- (-)-1,1'-Binaphthyl: 0 1.53 3 -216 a 1 1.26 -228 -110 2 0.94 -244 -151 3 0.74 -247 -219 4 0.56 -245 -230 S-(+)-1,1'-Binaphthyl: 0 1.41 a +226 a 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 of i n i t i a l m a t e r i a l . The a c t i v i t y of the m a t e r i a l i n s o l u t i o n was a l s o monitored. When the 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 should have the same a c t i v i t y as the r e c r y s t a l l i z e d s o l i d . However, our method of i s o l a t i n g the s o l u t e (by removal of solvent _in_ vacuo at 25°) caused some 180 r a c e m i z a t i o n , and the highest 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° at -78°, we estimated the l o s s i n a c t i v i t y i n re c o v e r i n g 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 of rac e m i z a t i o n of 11.4 h i n 74 benzene at 25° ) as 14°. I t would not be p o s s i b l e , t h e r e f o r e , to observe a s o l u t e a c t i v i t y above 231°, c l o s e to the f i n a l observed valu e . A sample of 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 to see i f the same s p e c i f i c r o t a t i o n of the c r y s t a l s ([a] = |245[°) could be obtained. The i n i t i a l a c t i v i t y of the 1.41 g sample of S - l , 1 ' - b i n a p h t h y l was [a] = +226°. A f t e r three 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 of [a] = +238 ± 1° (0.70 g) r e s u l t e d (Table XVI). 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 not represent much of an in c r e a s e over the second. The s p e c i f i c r o t a t i o n of the recovered s o l u t e was 13° lower than that of the c r y s t a l s , c l o s e to the estimated l o s s e s by rac e m i z a t i o n during s o l v e n t evaporation. Further 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 not 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 of the s o l i d can be seen from the t e r n a r y phase diagrams which d e s c r i b e the r e c r y s t a l l i z i n g system at -78° (Figu r e 32). The phase r e l a t i o n s h i p s between solvent and R- and S-enantiomers when the l a t t e r form a racemate (Figure 32 (b)) have already been explained i n S e c t i o n 3.4.3 (p 95) and Figure 17 (p 102). This diagram represents the most s t a b l e t e r n a r y system at -78 . The phase system formed between the e u t e c t i c form and the solvent i s a l s o shown (Figure 32 ( a ) ) . Because of the imperceptable slowness of the 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 at -78° (S e c t i o n 3.4.1, p 83), the e u t e c t i c form can e x i s t f o r indeterminable lengths of time at t h i s temperature i n contact w i t h s o l v e n t . 181 SOLVENT Figure 32. Schematic r e p r e s e n t a t i o n of the two p o s s i b l e ternary 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 at -78°. (a) R- and S-enantiomers form a e u t e c t i c mixture. (b) R- and S-enantiomers form a racemate. Although (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 periods of time at -78°. 182 Although the original samples in both of the above recrystallization sequences were the eutectic form (having been produced at 150°), the firs 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 first 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 will be found closer to the 1,1'-binaphthyl edge of the diagram, and y will be in the (single phase) solution region. At -78°, y will be in the (three- phase) R + S + solution region, so that precipitation can occur. If equilibrium in this eutectic ternary system is attained, then the solution w i l l have composition b (racemic). The solid, however, will have a higher activity x' than i t originally had (x). When x' is filtered from the solution and redissolved in acetone, the allover composition will now be y f (which, in this example, is in the two-phase R + solution region) at -78°. On attainment of equilibrium, the solid will be fully resolved R and the solution composition will 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° is particularly slow, a solid material having a rotation greater than x 1 may separate, leaving a meta- 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 are separated, net r e s o l u t i o n has been performed. Such n o n e q u i l i b r i u m methods of r e s o l u t i o n , u s u a l l y accomplished be seeding racemic s o l u t i o n s , have been t r i e d w i t h a number of p a i r s of enantio- 85 mers. In our 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 process i s probably operating to some extent, 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 not give m a t e r i a l w i t h the same r o t a t i o n . The l i m i t of r e s o l u t i o n which we have determined (+238°, -245°) should perhaps be r e f e r r e d to as a "phase l i m i t " of r e s o l u t i o n , s i n c e the t e r m i n a l s o l i d s o l u t i o n s ^ 0 ' e x i s t i n g at the edges of the bin a r y R- and S- l , 1 ' - b i n a p h t h y l phase diagram (Fi g u r e 14 ( a ) , p 80) may have a composition range of a few percent. The R and S c r y s t a l s obtained may thus be s l i g h t l y o p t i c a l l y impure. In t h i s t h e s i s , the value [a] = ±245° i s however taken as the 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, "percent 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 f i g u r e . 184 APPENDIX B T )H CALCULATION OF AG AS A FUNCTION OF TEMPERATURE In S e c t i o n 3.3.2.3 (p 73), the statement was made that the enantio - t r o p i c o r d e r i n g of racemic 1,1'-binaphthyl m o d i f i c a t i o n s ( F i g u r e 11 ( b ) , p 67) could be proven by c a l c u l a t i n g the f r e e energy d i f f e r e n c e between the racemate (low-melting) form and the racemic e u t e c t i c (high-melting) L->H form, AG , as a f u n c t i o n of temperature. However, a c a l c u l a t i o n of t h i s d i f f e r e n c e at 150°C (423°K) usi n g m e l t i n g e n t h a l p i e s and ent r o p i e s of the two m o d i f i c a t i o n s gave a numerical r e s u l t , 212 + 490 c a l mole \ which was very imprecise when the l i m i t s of 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 temperature L->H T r e s u l t i n g from an expression of AG as a f u n c t i o n of temperature would a l s o be imprecise. However i f our o r i g i n a l g oal of determining 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 obtained L~*H from the c a l c u l a t i o n of the temperature dependence of AG , i f only to see i f i t increases or decreases w i t h temperature. R e f e r r i n g again to Figure 11, the monotropic system possesses an imaginary s o l i d - s o l i d t r a n s i t i o n point i n the region where the melt 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, the t r a n s i t i o n p o i n t i s at lower temperatures. Therefore, some d i s t i n c t i o n between the two can be made by n o t i n g whether or not the f r e e energy surfaces f o r racemate or e u t e c t i c converge or diverge i n going to lower temperatures from 150°C. 185 The f r e e energy d i f f e r e n c e at any temperature can be c a l c u l a t e d i f the enthalpy and entropy d i f f e r e n c e s are known as a f u n c t i o n of temperature. These, i n t u r n , can be c a l c u l a t e d from the 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 of temperature, as f o l l o w s . Enthalpy and entropy are f u n c t i o n s of s t a t e . Therefore, the enthalpy change i n going from the racemate to the racemic e u t e c t i c ( i . e . , L->H) at any temperature T i s equal to the enthalpy change i n t a k i n g the racemate from T to 150°C (423°K), plus the change on going to the e u t e c t i c form at 150°C (which i s known), plus the change on b r i n g i n g the e u t e c t i c back to T. That i s : AH L->H 423 C L dT + A H ™ + p 423 C H dT 423 P L H where C and C are heat c a p a c i t i e s at constant pressure of the low-P P (racemate) and high-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 . This expression s i m p l i f i e s t o : [25] AH L->H 423 (C L - CH) dT P P + AH L->H 423 Entropy can be t r e a t e d i n a s i m i l a r f a s h i o n : [26] AS L->H 423 (C L - c H) 4? P P T + AS L->H 423 The f r e e energy d i f f e r e n c e at temperature T i s t h e r e f o r e : 186 [27] A G £ * = AH™ - T A s f L~*H We are i n t e r e s t e d i n f i n d i n g whether A G T i n c r e a s e s or decreases w i t h temperature from 150°C t o , say, room temperature. As a f i r s t (and r a t h e r crude) approximation, we can assume that the enthalpy and entropy L^H L-*H d i f f e r e n c e s AH^ and AS^ are independent of temperature i n the range of i n t e r e s t . Thus, AH^ = AH^^-j a n u AS^, = AS423 > a n ° l t ; c a n ° e s e e n from Equations 25 and 26 that t h i s approximation amounts to assuming that the heat c a p a c i t i e s of both m o d i f i c a t i o n s are i d e n t i c a l i n t h i s temperature L H range, i . e . , C = C . The approximation g r e a t l y s i m p l i f i e s Equation 27, Lr*"H and s u b s t i t u t i o n of our enthalpy and entropy values at 150 C gives AG ,̂ as a f u n c t i o n of temperature: r 9 8 1 A _L+H _ .„Lr>H Lr>H [28] A G T = A H 4 2 3 - T A S ^ = (1620 - 4.33T) c a l m o l e - 1 L-*H The equation becomes that of a s t r a i g h t l i n e , having a negative AG^ value at 150°C, a zero value at 102°C, and becoming more p o s i t i v e at Lr̂ H lower temperatures (Figure 33). Taking the u n c e r t a i n t i e s i n A H 4 2 3 a n ^ Lr*"H A S 4 2 3 i n d i v i d u a l l y (dotted l i n e s , Figure 33), the u n c e r t a i n t y i n x i s 102° i 52°C. This approximation t h e r e f o r e i n d i c a t e s that the system i s e n a n t i o t r o p i c w i t h the racemate s t a b l e below about 102°C. However, we have observed 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 103). Taking these two observations together, we should more c o r r e c t l y con- clude that the e u t e c t i c i s s t a b l e at l e a s t from 150°C to 76°C, w i t h the racemate becoming s t a b l e at lower temperatures. 187 Figure 33. Relation of the free energy d i f f e r e n c e between racemate and racemic e u t e c t i c form of 1,1 1-binaphthyl to temperature. F i r s t approxi- L H mation, assuming C - C = 0 (see t e x t ) . Dotted l i n e s are uncertainties P P i n AG T caused by errors i n AH^^ and AS^^, taken i n d i v i d u a l l y . 188 L H As a second approximation, the q u a n t i t y C - C can be assumed P P constant from room temperature to 150°C. Equations 25 and 26 can be i n t e g r a t e d to g i v e : [29] A H ™ = ( C L - C H) (423 - T) + 1620 c a l mole 1 T p p [30] A S ™ = 2.303 ( C L - C H) l o g (~) + 4.33 c a l deg "'mole 1 T p p T The q u a n t i t y (C^ - C^) was determined on the d.s.c. The procedure 4^ i n v o l v e d using a sapphire standard ( f o r which i s known a c c u r a t e l y as a f u n c t i o n of temperature) and measuring f o r both the racemate and the e u t e c t i c ([a] = -8°, i . e . , almost racemic) form. The r e s u l t s are L H l i s t e d i n Table XVII. Although the C - C values at each temperature P P 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 l a r g e i n d i v i d u a l u n c e r t a i n t i e s are reduced by a f a c t o r of /To by t a k i n g the mean of ten v a l u e s . The d i f f e r e n c e - C H Is t h e r e f o r e -13 ± 4 c a l P P A - 1 1 " I deg 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 (Equation 27) i s p l o t t e d against temperature, the s o l i d l i n e i n Figure 34 r e s u l t s . The e r r o r i n L~*H L-*-H L-*-H AG m introduced 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,„„, AS, 0 0, and T 423 423 L H L H C - C i s a l s o shown (dotted 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 those i n AH^^ a n d A^423' As i n the f i r s t approximation, the most probable value of the f r e e energy d i f f e r e n c e becomes l e s s negative as the temperature i s lowered from 150°C, becoming zero at about 86°C. This most probable t r a n s i t i o n temper- ature T i s c l o s e to the lowest observed 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. Second approxi- L H mation, assuming C - C = constant (see text). Dotted lines are un- P P certainties in AG 1 _ > H caused by errors in AH 1^, AS 1 ^ and C L - C , taken T 423 423 p p individually. 190 Table XVII Heat Capacities at Constant Pressure for Low-Melting (Racemate) and High Melting (Eutectic) Forms of l , l ' - B i n a p h t h y l Temperature < v . c H - c L, P P , -1 , • -1 -1 , -1 -1 -1 C K c a l deg mole c a l deg mole c a l deg mole 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 Mean: 13.07 approximation therefore also implies that the racemic 1,1'-binaphthyl system i s enantiotropic, with 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 approximation involves the determination of C - C as a P P function of temperature. The i n d i v i d u a l heat capacity differences i n L H Table XVII were f i t t e d to a polynomial of the type C - C = -2 a + bT + cT to obtain: 191 c = • 180.5 + 58.6 + 0.3511 i 0.1066 + 8.528 x 10 + 6 + 2.589 x 1 0 + 6 This polynomial"'' 0 8' 3 was s u b s t i t u t e d i n Equations 25 and 26, and the three Equations 25, 26 and 27 were solved simultaneously f o r AH , AS and x. x x The t r a n s i t i o n temperature x was 84°C, not much d i f f e r e n t from the value E~*"H L"*"H obtained from the second approximation. AH and AS were 772 c a l x x mole 1 and 2.16 c a l deg "'"mole \ r e s p e c t i v e l y . These thermodynamic c a l c u l a t i o n s , performed w i t h the measurements made w i t h the d i f f e r e n t i a l scanning c a l o r i m e t e r , y i e l d an imprecise value of x but support an e n a n t i o t r o p i c o r d e r i n g of racemic 1,1'-binaphthyl m o d i f i c a t i o n s . A more exact value of the t r a n s i t i o n temperature could 59b be obtained w i t h the very p r e c i s e methods of a d i a b a t i c c a l o r i m e t r y .

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