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Mechanistic studies of the pyrolysis of 1-pyrazolines Wigfield, Yuk-Yung 1969

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MECHANISTIC STUDIES OF THE PYROLYSIS OF 1-PYRAZOLINES BY YUK-YUNG WIGFIELD B.Sc. Hong Kong B a p t i s t C o l l e g e , 1962. M.A. St. Franc i s Xavier U n i v e r s i t y , 1964. A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY i n the Department o f Chemistry We accept t h i s t h e s i s as conforming to the r e q u i r e d standard THE UNIVERSITY OF BRITISH COLUMBIA May, 1969 In p r e s e n t i n g t h i s t h e s i s i n p a r t i a l f u l f i l m e n t o f t h e r e q u i r e m e n t s f o r an a d v a n c e d d e g r e e a t t h e U n i v e r s i t y o f B r i t i s h C o l u m b i a , I a g r e e t h a t t h e L i b r a r y s h a l l make i t f r e e l y a v a i l a b l e f o r r e f e r e n c e a n d S t u d y . I f u r t h e r a g r e e t h a t p e r m i s s i o n f o r e x t e n s i v e c o p y i n g o f t h i s t h e s i s f o r s c h o l a r l y p u r p o s e s may be g r a n t e d b y t h e Head o f my D e p a r t m e n t o r b y h i s r e p r e s e n t a t i v e s . I t i s u n d e r s t o o d t h a t c o p y i n g o r p u b l i c a t i o n o f t h i s t h e s . i s f o r f i n a n c i a l g a i n s h a l l n o t be a l l o w e d w i t h o u t my w r i t t e n p e r m i s s i o n . D e p a r t m e n t o f Chemistry The U n i v e r s i t y o f B r i t i s h C o l u m b i a V a n c o u v e r 8, C a n a d a Date 25th A p r i l , 1969. To Don A b s t r a c t The geometric stereoisomers of 3-carbomethoxy-3-methyl-4-bromo-l-p y r a z o l i n e have been prepared. Both compounds have been found to be h i g h l y unstable and are transformed r e a d i l y i n t o the hydrobromide s a l t o f 3-methyl-4-carbomethoxypyrazole. This transformation r e q u i r e s p r e f e r e n t i a l m i g r a t i o n of a carbomethoxy group over a methyl group. A stepwise mechanism i s proposed f o r t h i s rearranagement. P y r o l y s i s of 3-carbomethoxy-3-cyano-4-methyl-4-aryl-l-pyrazoline, (Z)-and (E)- gives predominantly the o l e f i n expected f o r concerted m i g r a t i o n w i t h e l i m i n a t i o n o f n i t r o g e n . The t r a n s i t i o n s t a t e i s described by a s t r u c t u r e i n which there i s no bond breaking of C(5)-N bond. This mechanism i s supported by ( i ) the l a c k of a C(5) secondary a-deuterium k i n e t i c isotope e f f e c t , ( i i ) the negative value of the entropy of a c t i v a t i o n , and ( i i i ) the migratory a p t i t u d e s between various s u b s t i t u t e d a r y l groups. The p o s s i b i l i t y of a s h o r t - l i v e d intermediate i s not completely r u l e d out. However, the lack of a l a r g e e f f e c t o f solvent p o l a r i t y on the r a t e of r e a c t i o n and the s t e r e o s p e c i f i c i t y of the r e a c t i o n suggest the intermediate of the p y r a z o l i n e p y r o l y s i s cannot be a z w i t t e r i o n w i t h j f r e e r o t a t i o n about the C(3)-C(4) bond. - i v -TABLE OF CONTENTS Page TITLE PAGE ... . i ABSTRACT . . i i i TABLE OF CONTENTS i v LIST OF TABLES v i LIST OF FIGURES v i i i ACKNOWLEDGEMENTS X INTRODUCTION 1 Mechanism of P y r a z o l i n e P r e p a r a t i o n 1 Mechanism o f P y r a z o l i n e P y r o l y s i s 5 (I) I o n i c Mechanism , - 6 ( I I ) D i r a d i c a l Mechanism 14 ( I I I ) Concerted Mechanism 20 (IV) TT-Cyclopropane Intermediate 24 OBJECT OF THE PRESENT WORK .' 3 2 RESULTS AND DISCUSSION .. 34 S e c t i o n I. M i g r a t i o n o f a Carbomethoxy Group i n a Bromo-p y r a z o l i n e to Pyrazole Conversion 34 (I) S t r u c t u r e Proof of the Rearranged Product 37 ( i ) The S p e c t r a l Evidence 3 7 ( i i ) By Conversion i n t o the Free Pyrazole 38 ( i i i ) By Conversion i n t o the Carboethoxy D e r i v a t i v e . 3 9 ( I I ) M e c h a n i s t i c Studies of 1,2-Carbomethoxy M i g r a t i o n . . . 4 0 ( I I I ) Thermal Decomposition o f 3-carbomethoxy-4-bromo-3 , 5 , 5 - t r i m e t h y l - l - p y r a z o l i n e , (E)- 4 7 - V -Page S e c t i o n I I . Mech a n i s t i c Studies o f the P y r o l y s i s o f 1-P y r a z o l i n e s , 48 (I) The Synthesis of 1-Pyrazolines 49 ( i ) P y r a z o l i n e s w i t h one s u b s t i t u e n t at C(4) 49 ( i i ) P y r a z o l i n e s w i t h two s u b s t i t u e n t s at the C(4) p o s i t i o n s 53 ( I I ) P y r a z o l i n e P y r o l y s i s . Product I d e n t i f i c a t i o n and Q u a n t i t a t i v e A n a l y s i s 62 ( I I I ) K i n e t i c Studies 89 (IV) M e c h a n i s t i c C o n s i d e r a t i o n ; 100 ( i ) E f f e c t o f Deuterium S u b s t i t u t i o n at C(5) 100 ( i i ) Solvent E f f e c t s and A c t i v a t i o n Parameters o f _ P y r o l y s i s 104 ( i i i ) M i g r atory Aptitudes 109 SUMMARY OF MECHANISTIC CONCLUSIONS 114 EXPERIMENTAL H 6 General ...... 116 S e c t i o n I 117 Se c t i o n I I 124 BIBLIOGRAPHY 149 - v i -LIST OF TABLES Table Page I Chemical s h i f t s of methyl a-cyano-B,B-disubstituted a c r y l a t e i n 6 u n i t s 5 2 I I Synthesis of 3-carbomethoxy-3-cyano-4-methyl - 4-aryl-l-p y r a z o l i n e s 5 4 I I I Chemical s h i f t s o f 3-carbomethoxy-3-cyano - 4-aryl - 4-methyl-l-p y r a z o l i n e s i n 6 u n i t s 5 5 IV Chemical s h i f t s of u n d e r l i n e d groups ( i n 5 u n i t s ) used f o r percentage a n a l y s i s of 1-pyrazoline p y r o l y s i s 7 1 V Decomposition o f 3-carbomethoxy-3-cyano-4-methyl-4-p_-n i t r o p h e n y l - 1 - p y r a z o l i n e , (E)- 7 4 VI Decomposition of 3-carbomethoxy-3-cyano-4-methyl -4-phenyl-1-p y r a z o l i n e , (E)- 7 5 VII Decomposition o f 3-carbomethoxy-3-cyano-4-methyl-4-p_-methoxyphenyl-l-pyrazoline, (E)- 7 6 V I I I Decomposition o f 3-carbomethoxy-3-cyano-4-methyl - 4-aryl-l-p y r a z o l i n e s , (Z)- 7 7 IX Decomposition of 3-carboethoxy-3-cyano-4-methyl - 4-aryl-l-p y r a z o l i n e s • 8 1 X The summary of r a t e constants and the a c t i v a t i o n parameters i n the p y r o l y s i s of 1-pyrazolines ^ 0 XI C a l c u l a t e d h a l f - l i v e s f o r 3-carbomethoxy-3-cyano - 4 ,4-dimethyl-1-pyrazoline and 3-carbomethoxy-3-cyano-4,4-cyclopentane-l-p y r a z o l i n e 1 0 4 - V l l -Table Page XII Rate constants of p y r o l y s i s o f 3-carbomethoxy-3-methyl-l-p y r a z o l i n e and 3-cyano-3-methyl-l-pyrazoline 106 X I I I R e l a t i v e migrations between a r y l s and methyl i n 3-carbo-methoxy-3-cyano-4-aryl-4-methyl-l-pyrazolihes (EJ- 114 XIV The n.m.r. sp e c t r a o f 3-carbomethoxy-3-methyl-4-bromo-l-p y r a z o l i n e s (Z)- and (E)- 121 - v i i i -LIST OF FIGURES Figure Page I Mechanism o f 1-pyrazoline formation 2 II I o n i c mechanism o f p y r o l y s i s o f 1-pyrazolines . 6 I I I I o n i c mechanism f o r the p y r o l y s i s o f c i s - and trans-3,4-dimethyl-3-carbomethoxy-l-pyrazolines 8 IV Products from the p y r o l y s i s o f 3-m e t h y l - 3 - a c e t y l - l -p y r a z o l i n e H V Products from the p y r o l y s i s o f c i s - and trans-3,5-dimethy1-3 - a c e t y l - l - p y r a z o l i n e s 12 VI R a d i c a l mechanism f o r p y r o l y s i s of 3 , 5 - d i a r y l - l -p y r a z o l i n e s 20 VII Decomposition of c i s - and trans-3-methyl-4-ethyl-3-carbo-methoxy-1-pyrazolines 21 V I I I Concerted mechanism f o r 1-pyrazoline p y r o l y s i s 21 IX K i n e t i c s t u d i e s of the p y r o l y s i s o f 4-m e t h y l - l - p y r a z o l i n e and i t s C(4)-deuterated analog . 25 X P y r o l y s i s of c i s - and trans-4-deuterio-3-methyl-1-pyrazoline. 26 XI The e l e c t r o n i c s t r u c t u r e o f trimethylene 29 XII Stepwise mechanism o f 1,2-carbomethoxy m i g r a t i o n 42 X I I I Concerted mechanism o f 1,2-carbomethoxy m i g r a t i o n 42 XIV N.m.r. spectrum o f 3-carbomethoxy-3-cyano-4-methyl-4-p-methoxyphenyl-1-pyrazoline, (E)- / 57 XV N.m.r. spectrum o f 3-carbomethoxy-3-cyano-4-methyl-4-p-n i t r o p h e n y l - l - p y r a z o l i n e , (Z)- 58 - i x -Figure Page XVI Thermal decomposition of 3-carbomethoxy-4-phenyl-2-pyrazole.. 63 XVII Thermal decomposition of 3-carbomethoxy-3-methyl-4-phenyl-1-pyrazoline, (E) - 64 XVIII Thermal decomposition o f 3-carbomethoxy-3-cyano-4-methyl-4-a r y l - 1 - p y r a z o l i n e s , (E)- 66 XIX Thermal decomposition of 3-carbomethoxy-3-cyano-4-methyl-4-a r y l - 1 - p y r a z o l i n e s , (Z)- 71 XX N.m.r. spectrum o f decomposition products of 3-carbomethoxy-3-cyano-4-methyl-4-phenyl-l-pyrazoline, (E)- 73 XXI The Arrhenius p l o t s f o r 3-carbomethoxy-3-cyano-4-methyl-4-a r y l - l - p y r a z o l i n e s , (E) - . ^2 XXII " The f i r s t order r a t e p l o t s f o r p y r o l y s i s o f 3-carbomethoxy-3-cyano-4-methyl-4-p_-nitrophenyl-l-pyrazolines, (E)- and (ZJ- 93 XXIII The f i r s t order r a t e p l o t s f o r p y r o l y s i s o f 3-carbomethoxy-3-cyano-4-methyl-4-p_-methoxyphenyl-l-pyrazoline, (EJ- (119) i n nitrobenzene and t e t r a l i n 94 XXIV The f i r s t order r a t e p l o t s f o r p y r o l y s i s o f p y r a z o l i n e 119 i n t e t r a l i n and i n d e c a l i n 95 XXV The f i r s t order r a t e p l o t f o r p y r o l y s i s of p y r a z o l i n e 119 i n f ormamide 96 XXVI The f i r s t order r a t e p l o t s f o r p y r o l y s i s of 3-carbomethoxy-. 3-cyano-4-methyl-4-phenyl-l-pyrazoline, (E)- and the corresponding 5,5-dideuterated compound i n nitrobenzene 97 XXVII K i n e t i c apparatus 1 4 4 ACKNOWLEDGEMENTS The author i s h i g h l y indebted to Dr. D.E. McGreer f o r h i s h e l p f u l d i s c u s s i o n s and i n v a l u a b l e guidance throughout t h i s research p r o j e c t . G r a t e f u l acknowledgement i s a l s o made to the N a t i o n a l Research Co u n c i l of Canada f o r the award of a s c h o l a r s h i p , 1968-1969. INTRODUCTION The a d d i t i o n of diazoalkanes to a,g-unsaturated n i t r i l e s or carbonyl compounds to form 1-pyrazolines (1-5) and the p y r o l y s i s of these 1-pyrazolines to form the corresponding cyclopropanes and o l e f i n i c d e r i v a t i v e s (6-8) have been known f o r many years. Both the a d d i t i o n and p y r o l y s i s mechanisms have r ^N "N 2 N -> cyclopropanes + o l e f i n s R = H, a l k y l Y = C0 2R, COR, CN been the subje c t of extensive d i s c u s s i o n , and i n p a r t i c u l a r , the mechanism f o r the p y r o l y s i s of 1-pyrazolines i s s t i l l not f i n a l l y s e t t l e d . I t i s the purpose o f t h i s t h e s i s to examine t h i s r e a c t i o n i n some d e t a i l i n the hope that a b e t t e r understanding of the mechanism may be achieved. Mechanism of P y r a z o l i n e P r e p a r a t i o n The mechanism of the a d d i t i o n o f a diazoalkane to an a,3-unsaturated carbonyl compound has been e s t a b l i s h e d r e c e n t l y by Huisgen and coworkers (9-11) to be a concerted m u l t i p l e - c e n t e r a d d i t i o n , s i m i l a r to the 1,3 d i p o l a r a d d i t i o n r e a c t i o n , r a t h e r than thestepwise i o n i c mechanism (12,13) p r e v i o u s l y - 2 -proposed. These routes to p y r a z o l i n e s are shown i n Figure I . R = H, a l k y l , a r y l Y = COOCH3, C0CH 3, CN, N0 2 Evidence favouring the concerted pathway i s provided by: (a) r e t e n t i o n of stereochemistry of c i s and trans o l e f i n s i n the p y r a z o l i n e products; (b) r a t e constant independent o f solvent d i e l e c t r i c constant; (c) l a r g e r a t e dependence on s t e r i c f a c t o r s and (d) large.negative entropies o f a c t i v a t i o n (9,10,14). A c c o r d i n g l y , the l e s s i o n i c and more s t e r i c a l l y r e s t r i c t e d p o l y c e n t r e a d d i t i o n mechanism i s favoured. On the other hand, Overberger and coworkers (15) prepared a mixture of c i s - and t r a n s - 5 , 5 - b i s - ( p - a n i s y l ) - 1 - p y r a z o l i n e s by r e a c t i o n o f p-methoxy styrene w i t h p-methoxyphenyldiazomethane. The formation o f c i s isomer was r a t i o n a l i z e d by a stepwise mechanism f o r the a d d i t i o n . However, the con-ce r t e d mechanism would a l s o give a mixture o f c i s and trans isomers. I t has been shown (7,12) that the carbon a to the n i t r o g e n i n the . - 3 -diazoalkane adds to the double bond at the carbon 8 to the carbonyl group i n the o l e f i n . However, Parham and coworkers (16) had shown by t r a c e r s t u d i e s t h a t d i s u b s t i t u t e d diazomethane adds to n i t r o o l e f i n of the type RCH=CHNC"2 to give p y r a z o l i n e s i n which the d i a z o n i t r o g e n atom became attached to the B-carbon of n i t r o o l e f i n . The c i s a d d i t i o n of diazomethane w i t h the formation of a s i n g l e p y r a z o l i n e product was shown f o r the a d d i t i o n to methyl t i g l a t e ( l a ) and methyl angelate (lb) to give c i s - and trans-3,4-dimethyl-3-carbomethoxy-l-pyrazolines (2a and 2b) (17) r e s p e c t i v e l y . CH_ CH_ H COOCH + C H 2 N 2 .CH, COOCH, l a 2a H CH, CH, y 3 COOCH3+ C H 2 N 2 H CH. CH, COOCH, l b 2b This f e a t u r e of the p y r a z o l i n e synthesis provides a means of o b t a i n i n g isomeric p y r a z o l i n e s d i f f e r i n g only i n t h e i r diastereomeric r e l a t i o n s h i p a t the C("3) and C(4) p o s i t i o n s l i k e 2a. and 2b. Several other isomeric p y r a z o l i n e s have been prepared as mixtures and t h e i r s e paration i n t o p a i r s of geometric isomers has been achieved i n various ways, f o r example, c i s -and trans-3,5-dimethyl-3-carbomethoxy-1-pyrazolines (3a and 3b) by d i s t i l -l a t i o n (18), c i s - and trans_-3,5-dimethyl-l-pyrazolines (4a and 4b) by 4 -vapour-phase chromatography (19), and c i s - and t r a n s - 3 , 5 - b i s - ( p - a n i s y l ) - 1 -p y r a z o l i n e (5a and 5b) by c r y s t a l l i z a t i o n (15). CH, I rnr CH 3 V COOCH, 3a CH, r*icooGH_ M 3 3b rCH; CH 3 N 4a CH, CH£* 4b p-CH 3OC 6H 4 C 6H 4OCH 3- £ 5a C 6H 4OCH 3-£ p-CH-OCJi, N — 3 6 4 5b I f the 3 - p o s i t i o n o f the 3 - s u b s t i t u t e d p y r a z o l i n e i s s u b s t i t u t e d by hydrogen, t a u t o m e r i z a t i o n between N=N and N-C(3) can occur due to the i n f l u -ence o f the s u b s t i t u e n t . G e n e r a l l y , t h i s occurs when the 3-substituent i s s t r o n g l y e l e c t r o n withdrawing. For example, the a d d i t i o n of diazomethane to methyl a c r y l a t e gives 3-carbomethoxy-2-pyrazoIine (6) (3) , which i s more s t a b l e , due to the conjugation, than the 3-carbomethoxy-l-pyrazoline ( 7). The occurrence o f 7 as a d i s t i n c t intermediate has been shown (20) by the i s o l a t i o n o f 7. - 5 -CH2=CHCOOCH3 + CH 2N 2 COOCH, •H N X COOCH, H S u b s t i t u t i o n o f the 3-hydrogens by other groups lead to 1-pyrazolines which can be tautomerized to 5-pyrazolines by treatment with a c i d , base or heat. For example, heating of 3-cyanopyrazoline 8_ i n d i f f e r e n t s o l v e n t s gave the corresponding 5-pyrazolines together with decomposition products (21). ••1—(••• COOC2H5 R » - ' COOC 2H 5 CN •. Mechanism o f P y r a z o l i n e P y r o l y s i s The thermal decomposition of 1-pyrazolines has been reported to y i e l d product mixtures c o n t a i n i n g cyclopropanes and o l e f i n s (7,12,22-28) i n some in s t a n c e s , w h ile i n ot h e r s , mixtures a l s o contained the corresponding 2-p y r a z o l i n e s (29) or no o l e f i n s (3,30) at a l l . Several decomposition mechanisms have been proposed and are summarized and discussed i n d i v i d u a l l y below. -- 6 -(I) I o n i c Mechanism The i o n i c mechanism of p y r o l y s i s of 1-pyrazolines i n v o l v e s two p o s s i b l e i n t e r m e d i a t e s , the n i t r o g e n - f r e e z w i t t e r i o n (11) or the diazonium i o n intermediate (15) depending on the degree of bond breaking of C(5)-N(l) i n the t r a n s i t i o n s t a t e . The mechanism i s shown i n Figure I I . H R' J ^ COOR (a) N 10 H R \ 4 - / R 5 . H 2C + 11 H, 12^ R ^ r o l R ? f t hydride s h i f t R CH 3 COOR 13 R C H 2=C-Q^H . R COOR 14 H R R V C — Y COOR QH 2 + 15 •* 12 14 Figure I I - I o n i c mechanism of p y r o l y s i s of 1-pyrazolines. - 7 -Step a i n Figure I I i n v o l v e s a complete l o s s o f n i t r o g e n to g i v e the z w i t t e r i o n 11, which presumably could be s t a b i l i z e d by d e r e a l i z a t i o n of the p o s i t i v e and negative charge by s u b s t i t u e n t s on C(3) and C(5). Ring c l o s u r e i n intermediate 1_1_ gives cyclopropane (12) and a hydride s h i f t gives the a, 3-unsaturated e s t e r (13). Formation of the 8,y-unsaturated o l e f i n (14) i s p o s s i b l e by a C(4)-C(3) proton s h i f t . I f the carbon-nitrogen bonds i n p y r a z o l i n e 10_ do not break simultaneously, a diazonium i o n intermediate (15) could be formed as i n step b. Loss o f n i t r o g e n from species 1_5 w i t h con-c e r t e d r i n g c l o s u r e w i l l give cyclopropane (12) , whereas l o s s of n i t r o g e n w i t h hydride migrations gives o l e f i n 1_3 and w i t h proton m i g r a t i o n gives o l e f i n 14. The e a r l y i n v e s t i g a t i o n of the i o n i c mechanism of p y r o l y s i s of 1-pyrazo-l i n e s (13,31) were based on r a t h e r l i m i t e d i n f o r m a t i o n obtained from the product d i s t r i b u t i o n s . Recently Van Auken and Rinehart (17) i n v e s t i g a t e d the stereochemistry of the thermal and p h o t o l y t i c decomposition o f two isomeric p y r a z o l i n e s . The p y r o l y s i s of trans-3,4-dimethyl-3-carbomethoxy-1-pyrazoline (2b) gave methyl 2,3-dimethyl-3-butenoate (16), trans-1,2-dimethyl-l-carbomethoxycyclopropane (17b), cis-1,2-dimethyl-l-carbomethoxy-cyclopropane (17a) and methyl 2,3-dimethyl-2-butenoate (18) i n the r a t i o 0.15:1.22:1.00:1.16. P y r o l y s i s of the corresponding c i s p y r a z o l i n e 2a gave the same compounds i n the r a t i o 0.24:0.70:1.00:3.73. The p y r o l y s i s . of these p y r a z o l i n e s proceeded w i t h only a s l i g h t degree o f s t e r e o s e l e c t i v i t y : 1.22:1.00 i n favour o f the trans cyclopropane 17b from the trans p y r a z o l i n e 2b and 1.00:0.70 i n favour of the c i s cyclopropane 17a from the c i s p y r a z o l i n e 2a. The r e s u l t s were explained by an e l a b o r a t i o n o f the i o n i c mechanism discussed above. The proposed mechanism i s shown i n Figure I I I . - 8 -H COOCH, CH. CH, 2a - methyls c i s o r 2b = methyls trans H N ^ C H 3 ' < COOCH, C H 3 N 2 19 - N , H CH. > — < COOCH, CH, CH, 20 I. H COOCH, CH, CH, 21 C H 3 CH_ I / 3 H 2C=C — CH^ 16 COOCH, H CH . C H 3 3 C 0 0 C H 3 17b H.. . COOCH, CH / X 3 C H 3 17a C H 3/ ^COOCH3 18 Figure I I I - I o n i c mechanism f o r the p y r o l y s i s of c i s and trans 3,4-dimethyl-3-carbomethoxy-1-pyrazolines. In order to e x p l a i n the f a c t that the isomeric cyclopropanes are formed i n almost equal amounts, r o t a t i o n about the C(3)-C(4) bond was p o s t u l a t e d to take p l a c e i n e i t h e r intermediate 1_9 or 20_ before c y c l i z a t i o n to c y c l o -propane. I t was expected that the z w i t t e r i o n 20_ and i t s s i n g l e t d i r a d i c a l resonance form 21 should c y c l i z e immediately, that i s , before r o t a t i o n could occur. The small s t e r e o s e l e c t i v i t y observed was explained by the suggestion - 9 -t h a t step c, l o s s of n i t r o g e n i n going from 1_9 to 20, i s s l i g h t l y f a s t e r than r o t a t i o n i n 1_9_. Some b a r r i e r to r o t a t i o n i s provided i n t h a t i t i n v o l v e s consecutive e c l i p s e d i n t e r a c t i o n o f methyl-carbomethoxy and methylene diazonium-methyl. The energy b a r r i e r f o r r o t a t i o n i n 1_9_ was t h e r e f o r e estimated to be g r e a t e r than the energy of a c t i v a t i o n f o r step c. However, there are two observations which disfavour "this proposed i n t e r -mediate 19_: ( i ) the r a t i o s o f cyclopropane to o l e f i n f o r the p y r o l y s i s o f the two p y r a z o l i n e s are d i f f e r e n t , the r a t i o was 1.70:3.97 f o r the c i s p y r a z o l i n e 2a and 3.22:1.31 f o r the trans p y r a z o l i n e 2b. This s i g n i f i c a n t d i f f e r e n c e i n product d i s t r i b u t i o n cannot be explained by an intermediate such as 19, which would be, the same intermediate f o r both p y r a z o l i n e s . ( i i ) i f the l i f e t i m e of intermediate 1_9 was s u f f i c i e n t l y long to permit r o t a t i o n s , then one would expect r e v e r s a l of step a, which would give some " p y r a z o l i n e w i t h i n v e r s i o n of geometry at C(3). However, i t was shown t h a t p a r t i a l p y r o l y s i s o f c i s - 3 , 4 - d i m e t h y l - 3-carbomethoxy-l-pyrazoline (2a) gave no rearrangement i n the recovered p y r a z o l i n e sample (17).-McGreer and coworkers (18,32,33) have done a c o n s i d e r a b l e amount-.-of^ work concerning the p o s s i b i l i t y o f an i o n i c intermediate i n the thermal- . -decomposition of 1-pyrazolines. I f the intermediate i s , as was suggested by Van Auken and Rinehart (17), a ring-opened diazonium i o n , there should*-be development of p o s i t i v e charge at C(5) of the p y r a z o l i n e i n the t r a n s l a -t i o n s t a t e . A t y p i c a l carbonium i o n rearrangement such as m i g r a t i o n o f a n . _ a l k y l group from C(4) to C(5) would i n d i c a t e such a charge development on C(5). Wagner-Meerwein rearrangements and r e l a t e d r e a c t i o n s c l e a r l y demonstrate that a l k y l groups can r e a d i l y migrate to a p o s i t i v e c enter. However, the m i g r a t i o n of a l k y l groups to a r a d i c a l center or. an anion.center_ - 10 -are p r e d i c t e d to be much l e s s favourable (34). A c c o r d i n g l y , a s e r i e s of 4,4-dialkyl-3-cyano-3-carbomethoxy-l-pyrazolines (22) were prepared and pyr o l y z e d under v a r i o u s c o n d i t i o n s (32). A l k y l m i g r a t i o n from C(4) to C(5) to give a,8-unsaturated es t e r s (24) were indeed observed. Another supporting COOCH. CN 'N' 22 < COOCH. CN N 2 23 COOCH, < N :N 24 f a c t o r f o r the intermediate 23_ i s the k i n e t i c s t u d i e s o f the decomposition of two 4,4-dialkyl-3-cyano-3-carbomethoxy-l-pyrazolines. The r a t e s o f decomposition increase w i t h i n c r e a s i n g solvent p o l a r i t y . Such a r a t e increase would be expected i f the t r a n s i t i o n s t a t e f o r the p y r o l y s i s i s more p o l a r than the s t a r t i n g m a t e r i a l . On the other hand, s t r u c t u r e 23, through r o t a t i o n around the s i n g l e bond, would be a n t i c i p a t e d to give a n e a r l y 50:50 mixture of the o l e f i n s from the mig r a t i o n of e i t h e r group at C(4). But the product d i s t r i b u t i o n o f p y r o l y s i s of 4,4-dimethyl-3-cyano-3-carbomethoxy-l-pyrazoline (25) shown as f o l l o w s , does not give the expected r a t i o , e s p e c i a l l y i n t e t r a c h l o r o e t h y l e n e which y i e l d e d an 8:1 mixture of two p o s s i b l e o l e f i n s . These product a n a l y s i s r e s u l t s could be explained by assuming that the methyl group migrates concerted w i t h n i t r o g e n l o s s . C O O C H , C N N 2 5 C O O C H . C O O C H , - / N :N neat benzene t e t r a c h l o r o e t h y l e n e 3 9 % 3 8 5 7 3 9 % 2 8 5 2 2 % 3 4 3 8 The i o n i c mechanism i s a l s o supported by the p y r o l y s i s of three 3 - a c e t y l -1 - p y r a z o l i n e s ( 3 3 ) . I f the intermediate has a s t r u c t u r e such as 23^ there should a l s o be a b u i l d up i n the molecule of negative charge at C ( 3 ) , which i s presumably d e l o c a l i z e d i n t o the electron-withdrawing groups attached to C ( 3 ) . The products obtained by p y r o l y s i s of these p y r a z o l i n e s are shown i n Figure IV and V r e s p e c t i v e l y . 2 6 Figure IV - Products from the p y r o l y s i s of 3 - m e t h y l - 3 - a c e t y l - l - p y r a z o l i n e . - 12 -27 Figure V - Products from the p y r o l y s i s of c i s - and trans-3,5-dimethyl-3--a c e t y l - l - p y r a z o l i n e s . -I The formation o f dihydrofuran d e r i v a t i v e s 26_ and 27_ from the p y r o l y s i s o f 3 - m e t h y l - 3 - a c e t y l - l - p y r a z o l i n e (28), c i s - and t r a n s - 3 , 5 - d i m e t h y l - 3 - a c e t y l - l -p y r a z o l i n e (29a and 29b) can be explained i f an i o n i c intermediate 3_0 i s formed w i t h negative charge b u i l t up on C(3) of the p y r a z o l i n e systems. As t h i s negative charge i s d e l o c a l i z e d onto the carbonyl oxygen, the oxygen w i l l be able to p a r t i c i p a t e in a r i n g c l o s u r e r e a c t i o n to give dihydrofuran d e r i v a t i v e s . However, i n the p y r o l y s i s of c i s - and trans-3,5-dimethyl-3-a c e t y l - 1 - p y r a z o l i n e (29a and 29b) under various c o n d i t i o n s , the c i s . isomer 29a y i e l d s the dihydrofuran product while the trans isomer 29b y i e l d s l i t t l e or none of t h i s product. For such to be the case, the - 13 -R R products \ + 0 30 intermediate 3_0 cannot have f r e e r o t a t i o n around the C(3)-C(4) bond s i n c e f r e e r o t a t i o n around t h i s bond should allow both isomers 29a and 29b to y i e l d the same amount of dihydrofuran product. R e s t r i c t i o n of t h i s r o t a t i o n implies that there i s some bonding ( e i t h e r i o n i c or p a r t i a l l y covalent) between C(3) and N i n the t r a n s i t i o n s t a t e . With r o t a t i o n r e s t r i c t e d around the C(3)-C(4) bond, the r e a c t i o n of 30_ w i l l s t i l l be i n f l u e n c e d by s t e r i c f a c t o r s present i n the o r i g i n a l p y r a z o l i n e . Thus, p y r a z o l i n e 29a w i t h the methyl s u b s t i t u e n t s c i s to each other would t w i s t i n such a way that the carbonyl group would be forced under the r i n g towards C(5) and i n a p o s i t i o n favourable f o r r i n g c l o s u r e to.oxygen. On the other hand, the trans isomer 29b would t w i s t to f o r c e the carbonyl away from C(5). I t appears, t h e r e f o r e , that the conformation of the s t a r t i n g 1-pyrazoline, as w e l l as solvent and r e l e c t r o n i c effects., are important f a c t o r s i n the thermal decomposition r e a c t i o n . A s i m i l a r type of r e a c t i o n was r e c e n t l y observed by Crawford and Cameron (35) i n the p y r o l y s i s of 3 - v i n y l - l - p y r a z o l i n e (31) and 3-isopropenyl-3-methyl-1-pyrazoline (33) as shown below: - 14 -33 34 97% 3% In the conformers 3_2 and 34, the methylene carbons are i n a favourable p o s i t i o n f o r c l o s u r e to C(5) to form cyclopentenes. ( I I ) D i r a d i c a l Mechanism The d i r a d i c a l intermediate of p y r o l y s i s of 1-pyrazolines was suggested . by Cohen and coworkers (36) and Overberger and coworkers (15,37,38) r e s p e c t i v e l y . Cohen proposed the r a d i c a l mechanism on the b a s i s of the k i n e t i c s t u d i e s of p y r o l y s i s o f 2,3-d i a z a b i c y c l o [2.2.1] 2-heptene (35) i n the gas phase (36). Decomposition of compound 35_ i n gas phase gave f i r s t order k i n e t i c s w i t h an a c t i v a t i o n energy, E = 37.3 kcal/mole, and an entropy of a c t i v a t i o n , a + AS = 8.7 e.u. At 250°, the r a t e constant f o r the decomposition of c i s azo - 15 -C m 35 36 37 b i c y c l i c compound 35_ i s about 430 times l a r g e r than that f o r the trans a c y c l i c analog, azo-bis-2-propane. The increase i n r a t e i s due l a r g e l y to the energy of a c t i v a t i o n being more favourable by 3.6 kcal/mole f o r c i s azo compound 55, which i s caused by the r e l i e f o f s t r a i n i n the b i c y c l i c s t r u c t u r e . The high entropy of a c t i v a t i o n , 12-15 e.u. f o r the decomposition of a l i p h a t i c azo compounds i n d i c a t e s a simultaneous rupture of two bonds (39,40) and i n c i p i e n t formation of a n i t r o g e n molecule and two r a d i c a l s i n the t r a n s i t i o n s t a t e . In the decomposition of the r i g i d b i c y c l i c azo compound 35, w h i l e two C-N bonds might w e l l be breaking simultaneously, only two fragments are being formed and the b i r a d i c a l 36_ q u i c k l y leads t o the observed product bicyclo[2.1.0]pentane (37). Therefore the entropy of a c t i v a t i o n o f +8.7 e.u., which i s lower than when three fragments are formed, i s high enough to be c o n s i s t e n t w i t h the simultaneous rupture of two C-N bonds to form the b i r a d i c a l , and the r e a c t i o n i s not of the molecular or four center type i n which the new C-C bond was formed simultaneously w i t h the rupture of the two C-N bonds. A s i m i l a r thermal decomposition of the b i c y c l i c system was observed by Roth and M a r t i n (41), and by A l l r e d and Smith (42). Gas phase p y r o l y s i s of-exo-5,6-dideuterio-2,3-diazabicyclo[2.2.1]2-heptene (38) gave a 1:3 mixture o f c i s - and trans-2,3-dideuterio-bicyclo[2.1.0]pentanes (41). - 16 -38 c i s trans 25% 75% The predominant i n v e r s i o n of stereochemistry i n the product was a t t r i b u t e d to concerted e l i m i n a t i o n of n i t r o g e n w i t h accompanying back-side p - o r b i t a l overlap i n the t r a n s i t i o n s t a t e . Another e x p l a n a t i o n f o r t h i s net i n v e r s i o n of stereochemistry i n the products was given by A l l r e d and Smith during the thermolysis of exo- and endo-5-methoxy-2,5-diazabicyclo [2.2.1] 2-heptane (39a and 39b) (42). The i n v e r s i o n was p o s t u l a t e d to r e s u l t from the formation of the s t r u c t u r a l l y i n v e r t e d pyramidal d i r a d i c a l as a consequence of r e c o i l from the energy r e l e a s e d by C-N bond breaking. Ring c l o s u r e before complete e q u i l i b r a t i o n accounts f o r the excess product of i n v e r t e d s t r u c t u r e . - 17 -- 18 -Overberger and coworkers s t u d i e d the thermal and photochemical decomposition and the k i n e t i c s o f a s e r i e s o f 3 , 5 - d i a r y l s u b s t i t u t e d - 1 -p y r a z o l i n e s (15,37,38). The p y r o l y s i s of t r a n s - 3 , 5 - d i p h e n y l - l - p y r a z o l i n e (40) and t r a n s - 3 , 5 - b i s - ( p - c h l o r o p h e n y l ) - 1 - p y r a z o l i n e (41) was reported to give only the corresponding t r a n s - 1 , 2 - d i a r y l c y c l o p r o p a n e s . The p h o t o l y t i c decomposition o f trans p y r a z o l i n e £1 gave only the trans-1,2-diphenyl cyclopropane (42b) and e l e c t r o n s p i n resonance s t u d i e s of t h i s decomposition i n d i c a t e d the presence o f f r e e r a d i c a l s i n t h e i r s i n g l e t s t a t e . These r e s u l t s suggested a f r e e r a d i c a l mechanism f o r the thermal decomposition o f 3,5-d i a r y l - l - p y r a z o l i n e s . The s t e r e o s p e c i f i c decomposition of trans p y r a z o l i n e s 40 and 41_ was r a t i o n a l i z e d as a r e s u l t of f a s t c o upling o f the intermediate b i r a d i c a l s s i n c e no evidence o f t r i p l e t s t a t e r a d i c a l s was found. However, a reexamination (38) of the thermal and p h o t o l y t i c decomposition o f t r a n s -3,5-diphenyl-1-pyrazoline (40) showed that the r e a c t i o n s were not completely s t e r e o s p e c i f i c ; the products c o n s i s t e d of trans-1,2-diphenylcyclopropane (42b) and cis-1,2-diphenylcyclopropane (42a) shown as f o l l o w s : Ph Ph Ph Ph Ph 1N Ph'' 40 42b 42a p h o t o l y t i c 88% 12% thermal 89% 11% The thermal and p h o t o l y t i c decompodition of c i s - and t r a n s - 3 , 5 - b i s - ( p - a n i s y l ) • 1-pyrazolines (5a and 5b) were a l s o i n v e s t i g a t e d . The product compositions are shown as f o l l o w s : - 19 -pCH3OC6H-4 H ^ N N C 6H 4OCH 3-p Ar Ar Ar Ar c i s (5a) trans (5b) C I S thermal 43.0 p h o t o l y t i c 57.2 thermal 6.7 p h o t o l y t i c 0.7 trans 57.0 42.8 93.3 99.3% The n o n - s t e r e o s p e c i f i c product formation from the decomposition o f 3,5-d i a r y l - l - p y r a z o l i n e s i n d i c a t e s that there i s some degree of bond r o t a t i o n i n the b i r a d i c a l intermediate before c o u p l i n g . The formation of r e l a t i v e l y l a r g e amounts of trans-cyclopropane from c i s p y r a z o l i n e 5_a i n d i c a t e s there i s c o n s i d e r a b l e r o t a t i o n around the C-C bond i n the b i r a d i c a l . Overberger, t h e r e f o r e , proposed a f r e e - r a d i c a l pathway f o r p y r a z o l i n e decomposition shown i n Figure VI. A k i n e t i c study on the 3 , 5 - d i a r y l - l - p y r a z o l j . n e s showed t h a t c i s -p y r a z o l i n e decomposed f a s t e r than the t r a n s - p y r a z o l i n e w i t h a concomitantly s m a l l e r a c t i v a t i o n energy (15). This was explained as the r e s u l t o f grea t e r s t r a i n o f the C-N bond and the increased s t e r i c hindrance o f the two a r y l s u b s t i t u e n t s i n c i s p y r a z o l i n e 5a. The b i r a d i c a l from the c i s 1-pyrazoline would have s u f f i c i e n t energy to have f r e e r o t a t i o n around the C-C bond before coupling due to the decreased s t a b i l i t y o f the r i n g and the f a c t that cis-cyclopropane i s the l e s s s t a b l e isomer." - 2 0 -H Figure VI - R a d i c a l mechanism f o r p y r o l y s i s of 3 , 5 - d i a r y l - l - p y r a z o l i n e s . ( I l l ) Concerted Mechanism McGreer and coworkers (43) i n v e s t i g a t e d the products from the thermal decomposition of c i s - and trans-3-methyl-4-ethyl-3-carbomethoxy-1-pyrazolones (43a and 43b) . The composition i s shown i n Figure V I I . The major cyclo-. propanes 44a and 44b obtained had the stereochemistry opposite to the p y r a z o l i n e s 43a and 43b from which they were formed r e s p e c t i v e l y , and the o l e f i n s 45a and 45b were formed by a s t e r e o s p e c i f i c process. The p o l a r i t y of solvent had l i t t l e e f f e c t on the r a t e . These r e s u l t s suggested a concerted hydrogen m i g r a t i o n w i t h l o s s of n i t r o g e n i n the o l e f i n - f o r m i n g step as i l l u s t r a t e d by the intermediates 46a and 46b as shown i n Figure V I I I . S i m i l a r l y , m i g r a t i o n of the same hydrogen to C(3) would give the 8,y-unsaturated system with trans geometry. - 21 -CH_CH 3 ^ H C H 3 COOCH, N COOCH3 + a l k y l ^ ^COOCH methyl H • y 3 H | ~"3 COOCH, CH, c i s (43a) trans (43b) c i s trans trans c i s (44a) (44b) (45b) (45a) 31 9 0 56 4% 11 72 13 0 4% Figure VII - Decomposition o f c i s - and trans-3-methy1-4-ethyl-3-carbomethoxy-1-pyrazolines. H CH, 46b Figure V I I I - Concerted mechanism f o r 1-pyrazoline p y r o l y s i s - 22 -The geometry of the pyrazolones, as i n f e r r e d from n.m.r. spectroscopy (18,19) appears to be s i m i l a r to that of cyclopentene and has the f o l d e d arrangement 47, w i t h an angle between the two planes of approximately 155°. From the n.m.r. s p e c t r a of 43a and 43b, the p r e f e r r e d conformations of the CH_ COOCH, 3 3 47 48a 48b p y r a z o l i n e s were shown to have the C(4) hydrogen i n the pseudo-axial p o s i t i o n and the C(4) e t h y l group i n the pseudo-equatorial p o s i t i o n (48a and 48b). One might, t h e r e f o r e , expect the l o s s of n i t r o g e n t o occur more e a s i l y from the si d e c i s to hydrogen on C(4), s i n c e that i s the p r e f e r -ed conformation of 43a and 43b. I t was suggested (44) th a t the advantage gained by concerted m i g r a t i o n of hydrogen i s s u f f i c i e n t to overcome the adverse s t e r i c f a c t o r present i n t r a n s i t i o n s t a t e s 46a and 46b. The formation o f cyclopropane occurs through a s l i g h t l y d i f f e r e n t t r a n s i t i o n s t a t e (probably l e s s p o l a r ) s i n c e the cyclopropane to o l e f i n r a t i o decreases w i t h i n c r e a s i n g s olvent p o l a r i t y . A concerted process i s favoured s i n c e the energy of the t r a n s i t i o n s t a t e f o r t h i s would d i f f e r only s l i g h t l y from t h a t f o r the o l e f i n - f o r m i n g r e a c t i o n . Two p o s s i b i l i t i e s f o r n i t r o g e n e l i m i n a t i o n are considered ( i ) l o s s o f n i t r o g e n by s t r e t c h i n g v i b r a t i o n i n the plane of C(3), C(4) and C(5) w i t h formation of two p - o r b i t a l s at C(3) and C(5) towards each other l e a d i n g to product w i t h r e t e n t i o n c o n f i g u r a t i o n ( i i ) l o s s o f n i t r o g e n by s t r e t c h i n g v i b r a t i o n p e r p e n d i c u l a r to - 23 -the plane of C(3), C(4) and C(5) w i t h formation of two p - o r b i t a l s at C(3) and C(5) roughly p a r a l l e l to each other. The s t e r i c i n t e r f e r e n c e between C(3) and C(5) s u b s t i t u e n t s would r e s u l t i n i n v e r s i o n at one of these cen t e r s . The concerted mechanism f o r the o l e f i n - f o r m i n g r e a c t i o n was f u r t h e r supported by the k i n e t i c s t u d i e s o f 3-carbomethoxy-3-methyl-l-pyrazoline (49) (45). There was l i t t l e or no e f f e c t i n the r a t e of p y r o l y s i s of 49 on changing the sol v e n t p o l a r i t y . This suggests that there i s l i t t l e or no development of charge i n the t r a n s i t i o n s t a t e f o r the p y r o l y s i s of 49_. Al s o s u b s t i t u t i o n of two deuterium atoms at the C(5) p o s i t i o n s of 49_ and 3-cyano-3-methyl-l-pyrazoline (51) showed a r a t e constant o f p y r o l y s i s i n n-bu t y l p h t h a l a t e of 22% l e s s than that o f the corresponding hydrogen s u b s t i t u t e d p y r a z o l i n e s . / COOCH, H„ 49 COOCH, 50 CN H 2 N 51 4* CN Do^N 4 * 52 V kD = kC49)/k(50) = 1.22 k H / k D = k ( 5 1 ) A ( 5 2 ) =1.23 i n i i - b u t y l p h t h a l a t e i n n - b u t y l p h t h a l a t e - 24 -The above secondary a-deuterium isotope e f f e c t s correspond to a t r a n s i t i o n s t a t e where C(5)-N bond i s breaking. Furthermore, s u b s t i t u t i o n o f two deuterium atoms at the C(4) p o s i t i o n (53) of p y r a z o l i n e 4_9 showed a r a t e constant o f p y r o l y s i s i n n-butyl p h t h a l a t e of 36% slower than that of p y r a z o l i n e 49. A f t e r c o r r e c t i o n f o r the composition of o l e f i n formed from p y r o l y s i s o f both 49_ and 53, the r a t e constant of 53_ became 94% slower than t h a t o f 49. r-coocH, 2 f r - c o o c h 3 49 53 - • . For p y r a z o l i n e p y r o l y s i s : k^/k^ = k(49)/k(53) = 1.36 For o l e f i n - f o r m i n g r e a c t i o n : ^ A g ' = 1-94 This deuterium e f f e c t , ^ A g = 1.94, on the o l e f i n forming r e a c t i o n which i s l a r g e l y primary, t h e r e f o r e , supports the e a r l i e r suggestions of a concerted hydrogen m i g r a t i o n w i t h l o s s of n i t r o g e n i n the o l e f i n - f o r m i n g step. (IV) Tr-Cyclopropane Intermediate K i n e t i c s t u d i e s i n v e s t i g a t e d by Crawford and Mishra (46), f o r the p y r o l y s i s o f 4-methyl-l-pyrazoline (54) and i t s C(4) deuterated p y r a z o l i n e , (55) gave cyclopropane and o l e f i n product i n n e a r l y 50:50 r a t i o . The o v e r a l l k i n e t i c deuterium isotope e f f e c t was 1.07 while the e f f e c t of deuterium on the product forming step i n d i c a t e d a k i n e t i c isotope e f f e c t f o r step I I I of 1.80 (see Figure I X ) . - 25 -CH 3 \ (D)H' 1 54 = H at C(4) 55 = D at C(4) H(D) intermediate I I CH(D) I I I CH(D) CH. H(D) -» CH_-C-CH_(D) CH. Figure IX - K i n e t i c s t u d i e s of p y r o l y s i s of 4-methyl-l-pyrazoline and i t s C(4)-deuterated analog. This suggested to Crawford (46) th a t the hydrogen m i g r a t i o n takes place a f t e r the r a t e determining t r a n s i t i o n s t a t e s and he suggested an intermediate common to both cyclopropane and o l e f i n formation, and makes the concerted hydrogen m i g r a t i o n improbable i n these p y r a z o l i n e systems. The s t r u c t u r e of t h i s intermediate has been suggested to be a planar symmetric molecule w i t h a iT-bond between two of the carbons i n the c y c l o -propane r i n g , c a l l e d " i r-cyclopropane" (56) shown below. N • N -> product 56 - 26 -Further evidence to support the s t r u c t u r e of t h i s intermediate was found i n the p y r o l y s i s of 3-methyl-l-pyrazoline (47). The proposed i n t e r -mediate (57) produced from thermolysis of 3-methyl-l-pyrazoline has a plane o f symmetry through the four carbons. To t e s t t h i s symmetry, c i s - and H 57 t r a n s - 4 - d e u t e r i o - 3 - m e t h y l - l - p y r a z o l i n e s (58a and 58b), both capable of producing the intermediate 59_ were prepared f o r p y r o l y s i s . I f intermediate 58a 58b D Figure X - P y r o l y s i s of c i s - and trans-4-deuterio-3-methyl-T-pyrazolines. - 27 -59 has a s u f f i c i e n t l i f e t i m e to become completely f r e e o f n i t r o g e n , the product r a t i o s should be independent o f the i n i t i a l stereochemistry. However, i f i t i s a concerted hydrogen m i g r a t i o n mechanism as suggested by McGreer, i l l u s t r a t e d by s t r u c t u r e 60,then the product r a t i o of cyclopropane and o l e f i n from p y r a z o l i n e s 58a and 58b should be d i f f e r e n t ; more of 60a would be formed from c i s p y r a z o l i n e 58a than from trans p y r a z o l i n e 58b. The experimental r e s u l t s found are e n t i r e l y c o n s i s t e n t w i t h the intermediate 59_ and do not a l l o w f o r the p o s s i b i l i t y o f a concerted m i g r a t i o n o f only that hydrogen t r a n s o i d to the departing n i t r o g e n as i n intermediate 60. D D 60 60a Crawford and Mishra (48) a l s o suggested that there i s some form o f i n t e r a c t i o n between the two t e r m i n a l methylenes i n t h e i r proposed i n t e r -2 mediate. The p r o x i m i t y o f the two sp carbons could indeed allow some pir-pTr bonding to form species 61, a " I T -cyclopropane". T h e i r c a l c u l a t i o n s 61 i n d i c a t e d that i n t e r a c t i o n o f the p - o r b i t a l s does not al l o w the " d i r a d i c a l " to be a p a i r o f f r e e l y r o t a t i n g r a d i c a l s and suggested a bonding energy o f - 28 -8-12 kcal/mole. This species would appear to be a s a t i s f a c t o r y intermediate which then has an a c t i v a t i o n energy f o r conversion to cyclopropane and o l e f i n . Hoffman (49,50) has made a d e t a i l e d t h e o r e t i c a l study of trimethylene. Extended Huckel c a l c u l a t i o n s on t h i s species gave the energy r e l a t i v e to cyclopropane as a f u n c t i o n of C-C-C angle and r o t a t i o n of the t e r m i n a l methylene groups. Two minima were observed on the ground s t a t e c o n f i g u r a -t i o n p o t e n t i a l s u r f a c e , corresponding r e s p e c t i v e l y to an opened cyclopropane (62) and to the trimethylene intermediate (65) where the t e r m i n a l methylenes are coplanar w i t h the three-carbon chain. A c o n s i d e r a t i o n of the e l e c t r o n i c s t r u c t u r e o f the ground s t a t e trimethylene can help to r a t i o n a l i z e the s t e r e o s p e c i f i c i t y observed i n the cyclopropane formation from some 1-p y r a z o l i n e s : - 29 -The molecular o r b i t a l s formed from the combination of the t e r m i n a l 2p o r b i t a l s are shown, 64_ and 65_ corresponding to the "ir_-cyclopropane" and " I T .cyclopropane" i n t e r m e d i a t e , r e s p e c t i v e l y , as proposed by Crawford and Mishra (48). Hofmann found t h a t at l a r g e C-C-C angle, the mixing o f the 64 d5 symmetric (S) antisymmetric"(A) c e n t r a l methylene group, d e s t a b i l i z i n g the S l e v e l , dominate (see Figure X I ) , w h i l e at small angle the d i r e c t 1 , 3 - i n t e r a c t i o n s t a b i l i z i n g the S l e v e l wins out. The tri m e t h y l e n e intermediate l i e s i n the former r e g i o n Figure XI - The e l e c t r o n i c s t r u c t u r e of trimethylene and i t i s apparent t h a t a species w i t h two e l e c t r o n s i n A l e v e l (see Figure XI) should c l o s e to give a cyclopropane i n a conrotatory manner. This - 30 -c o n r o t a t i o n d i s r o t a t i o n conrotatory c l o s i n g i s needed to r a t i o n a l i z e the observed preference f o r i n v e r s i o n of stereochemistry i n the p y r a z o l i n e to cyclopropane p y r o l y s i s s t u d i e d by Crawford and by McGreer. The energy d i f f e r e n c e between the S and A l e v e l s i s small enough to a l l o w an e q u i l i b r i u m p o p u l a t i o n of the S l e v e l which would c l o s e to give a cyclopropane i n a d i s r o t a t o r y manner. This can e x p l a i n the cyclopropane products w i t h r e t a i n e d geometry. However, the r e s u l t s of Overberger et_.al_. (15,37,38) cannot be explained by the above theory. In two cases the major cyclopropane products have the same stereochemistry as that of the s t a r t i n g p y r a z o l i n e s . A l s o , t h i s "iT-cyclopropane" intermediate cannot be used to e x p l a i n the r e s u l t s obtained by McGreer and Wu (43) (see Figure V I I ) . The p r e f e r r e d conformation of c i s - and trans-3-methyl-4-ethyl-5-carbomethoxy-1-pyrazoline (43a and 43b) was such that the e t h y l group w i l l be i n a pseudo e q u a t o r i a l p o s i t i o n (48a and 48b). Loss of n i t r o g e n from 48a and 48b on the s i d e c i s to hydrogen at C(4) would give the two "iT-cyclopropane" intermediates 66a and 66b r e s p e c t i v e l y . However, m i g r a t i o n of hydrogen from these intermediates would lead to o l e f i n s w i t h d i f f e r e n t stereochemistry from t h a t which was found experimentally. I f the formation of the "ir-cyclopropane" i n t e r mediates proceeded through t r a n s i t i o n s t a t e s s i m i l a r to intermediates 46a - 31 -66a 66b and 46b (which a c t u a l l y a r i s e from conformational i n v e r s i o n of 48a and 48b), then the intermediates formed would be 67b and 67a r e s p e c t i v e l y . 67b 67a M i g r a t i o n of H from intermediates 67b and 67a would lead to o l e f i n s w i t h the c o r r e c t stereochemistry. However, r o t a t i o n as i n d i c a t e d by the arrows i n 67b and 67a (conrotation) give the major cyclopropane product, c o n r o t a t i o n i n opposite d i r e c t i o n gives the minor cyclopropane products. Thus by a p p l y i n g t h i s mechanism to e x p l a i n McGreer's r e s u l t s (43) two i n c o n s i s t e n t features emerge: ( i ) l o s s of n i t r o g e n from the s i d e c i s to the e t h y l group i s s t e r i c a l l y unfavourable, e s p e c i a l l y without the "pushing" a s s i s t a n c e of concerted hydrogen m i g r a t i o n ; ( i i ) the question of why one mode of c o n r o t a t i o n i s favoured over the other i s not e a s i l y answered. - 32 -Object of the Present Work From the i n t r o d u c t i o n , i t can be seen that there are s e v e r a l p o s s i b l e mechanisms of p y r o l y s i s of 1-pyrazolines proposed by d i f f e r e n t groups of workers. No one mechanism could be used to e x p l a i n the decomposition of every 1-pyrazoline w i t h d i f f e r e n t s u b s t i t u e n t s and stereochemistry. Among a l l the decompositions of 1-pyrazolines known, only i n f i v e (25,68-71) (32) d i d a l k y l m i g r a t i o n from C(4) to C(5) occur g i v i n g a,3-unsaturated e s t e r s . These r e s u l t s were explained as carbonium i o n rearrangements w i t h an i o n i c intermediate (see I n t r o d u c t i o n ) . These f i v e 1-pyrazolines are s u b s t i t u t e d by a l k y l groups at both p o s i t i o n s of C(4), t h e r e f o r e , i f any o l e f i n s are obtained, a l k y l migrations have to take p l a c e . Furthermore i n 1-pyrazoline R = R- = CH_ R = R . = C 2H. R = C H 3 , R r = C 2 H 5 R + R. = (CH-) 4 , R + R x = ( C H 2 ) 5 22 the s u b s t i t u e n t s R and R^ are the same, except i n 69_ where R = CH_ and R^ = C 2H_, even then the e l e c t r o n e g a t i v i t y of these two groups are very s i m i l a r . Product a n a l y s i s o f p y r o l y s i s o f these p y r a z o l i n e s would not e x p l a i n whether the o l e f i n s obtained are due to the m i g r a t i o n of one a l k y l group or both a l k y l groups s u b s t i t u t e d at the C(4) p o s i t i o n . I f the o l e f i n s formed are due to the m i g r a t i o n of only one a l k y l group at the C(4) p o s i t i o n , then the preference o f . m i g r a t i o n of one a l k y l group over the other due to e i t h e r e l e c t r o n i c or s t e r i c e f f e c t could a l s o not be evaluated s i n c e the two a l k y l groups are i n d i s t i n g u i s h a b l e . I t was t h e r e f o r e , - 33 -considered d e s i r a b l e to i n v e s t i g a t e the migratory apt i t u d e s of some d i s t i n c t -i v e l y d i f f e r e n t groups at the C(4) p o s i t i o n s of d i f f e r e n t s u b s t i t u t e d 1-pyrazolines i n order to a i d e v a l u a t i o n of the s t r u c t u r e of the i n t e r -mediate. A survey of the l i t e r a t u r e showed that f o r a l l the decompositions of d i f f e r e n t 1 - p y r a z o l i n e s , i f one of the p o s i t i o n s at C(4) i s s u b s t i t u t e d by hydrogen, then the o l e f i n s obtained are always those r e s u l t i n g from m i g r a t i o n of t h i s hydrogen e i t h e r to C(3) or 0 ( 5 ) . I t was a l s o of i n t e r e s t to determine whether any group migrated p r e f e r e n t i a l l y t o hydrogen. RESULTS AND DISCUSSION S e c t i o n 1 M i g r a t i o n of a Carbomethoxy Group i n a Bromopyrazoline t o P y r a z o l i n e Conversion ( 5 1 ) . In order to e v a l u l a t e the migratory a p t i t u d e s of bromine and hydrogen i n the o l e f i n - f o r m i n g r e a c t i o n o f p y r a z o l i n e p y r o l y s i s , the p y r o l y s i s o f 3-carbomethoxy-3-methyl-4-bromo-1-pyrazoline, (E)- (72a) was considered. Compound 72a was prepared by r e a c t i o n of diazomethane w i t h methyl B-bromo-a-methacrylate, (E)- (75a) i n ether s o l u t i o n . ' Evaporation o f t h i s ether s o l u t i o n gave an o i l y m a t e r i a l 72a, which rearranged immediately at room temperature to a c r y s t a l l i n e s o l i d , l a t e r i d e n t i f i e d as hydrobromide s a l t . of 3-methyl-4-carbomethoxypyrazole (74). P y r a z o l i n e 72a was very unstable as a neat l i q u i d , i n chloroform and acetone, comparatively s t a b l e i n t e t r a c h l o r o e t h y l e n e ( f o r l e s s than 1/2 h r ) , and more s t a b l e i n ether s o l u t i o n ( f o r more than Br . CH_ CH.OOC CH - 35 -three hrs ). I t was a l s o very unstable i n a c i d s o l u t i o n . In the p r e p a r a t i o n of t h i s p y r a z o l i n e , i t was necessary to wash a l l the glassware w i t h 10% aqueous sodium hydroxide before r i n s i n g w i t h d i s t i l l e d water. P y r a z o l i n e 72a could not be i s o l a t e d pure; however, c o n c l u s i v e evidence f o r i t s s t r u c t u r e could be found i n the nuclear magnetic resonance (n.m.r.) s p e c t r a i n t e t r a c h l o r o e t h y l e n e and deuteriochloroform s o l u t i o n s . I t i s w e l l known th a t the p y r a z o l i n e s formed from r e a c t i o n of o l e f i n s and diazomethane r e t a i n the stereochemistry of the s t a r t i n g o l e f i n (9-11) . Therefore the expected s t r u c t u r e of p y r a z o l i n e formed from the r e a c t i o n of o l e f i n 73a and diazomethane would be 3-carbomethoxy-3-methyl-4-bromo-l-pyrazoline, (E)- (72a). However f o r the purposes of d i s c u s s i o n of the subsequent rearrangement,it was e s s e n t i a l to r i g o r o u s l y exclude the p o s s i b i l i t y o f formation of 3-bromo-4-carbomethoxy-4-methyl-l-pyrazoline, (E)- (75). For Br CH, CH_ Br .4 3 - 3 H V _ 3 / COOCH, CH300C'*' n * " * H 72a 75 s t r u c t u r e 72a, there should be coupling between protons at the C(4) and C(5) p o s i t i o n s i n the n.m.r. spectrum which should then show an A2B p a t t e r n con-s i s t i n g of a doublet r e p r e s e n t i n g the two protons at the C(5) p o s i t i o n and a t r i p l e t r e p r e s e n t i n g the proton at the C(4) p o s i t i o n . For s t r u c t u r e 75, there should be no coupling between the protons at C(3) and C(5) and the n.m.r. spectrum should show two s i n g l e t s each r e p r e s e n t i n g the protons at C(3) and C(5). Since the p y r a z o l i n e formed from o l e f i n 73a and diazomethane i s very u n s t a b l e , the ether s o l u t i o n c o n t a i n i n g t h i s p y r a z o l i n e was r o t a r y evaporated at 0°. S h o r t l y before a l l the ether had been removed, CDC1- c o n t a i n i n g 1% of tetramethyl s i l a n e was added and the n.m.r. spectrum taken immediately. This p y r a z o l i n e was s u f f i c i e n t l y s t a b l e i n CDC1_ f o r a n.m.r. spectrum t o be taken, but not stable enough to allow t h i s spectrum to be i n t e g r a t e d . Attempts to i n t e g r a t e t h i s spectrum were unsuccessful and the spectrum i n t e g r a t e d ~ : for the rearranged product 74_ i n s t e a d . The n.m.r. spectrum showed peaks at 6 5.0 (doublet, J = 4.7 Hz, ^ - 0 ( 5 ) ) , 4.58 ( t r i p l e t , J = 4.7 Hz., H-C(4)), 3.73 ( s i n g l e t , -C00CH-) and 1.98 p.p.m. ( s i n g l e t , CH3-C(3)). An attempt to decouple the peaks at 6 5.0 and 4.58 p.p.m.on a Var i a n A-100 model instrument was unsuccessful because the peaks were too c l o s e together. However, at 100 M Hz, the doublet and t r i p l e t at 6 5.0 and 4.58 p.p.m. r e s p e c t i v e l y s t i l l showed a coupling constant o f 4.7 Hz i n d i c a t i n g that they were i n f a c t a true doublet and t r i p l e t , not peaks caused by any si d e bands or i m p u r i t i e s . This presence of an A-B p a t t e r n i n the n.m.r. spectrum t h e r e f o r e confirmed that the s t r u c t u r e of the p y r a z o l i n e was 72a r a t h e r than 75. The d e s c r i p t o r s (EJ- and (Z)- are proposed f o r use i n p y r a z o l i n e s to s p e c i f y the stereochemistry o f the s u b s t i t u e n t s . This i s a method used by Blackwood et_.al_. (52) with some m o d i f i c a t i o n . The reference plane used i n i i. . the p y r a z o l i n e i s the C(3)-C(4)-C(5) plane. That c o n f i g u r a t i o n i n which the s u b s t i t u e n t o f the highest p r i o r i t y (53) on one carbon i s on the same s i d e of the reference plane as another s u b s t i t u e n t of highest p r i o r i t y o f the adjacent carbon i s represented by the d e s c r i p t o r Z_ (zusammen) . That con- . f i g u r a t i o n i n which these groups are on '[ opposite sides i s assigned the d e s c r i p t o r E_ (entgegen) . Two examples are shown below. These d e s c r i p t o r s E_ - 37 -CH 3 C00CH 3 © (Z) J and Z are u s e f u l when each of the two adjacent carbons i n one s t r u c t u r e i s s u b s t i t u t e d by more than one f u n c t i o n a l group. In these cases the usual c i s and trans nomenclature can lead to some confusion. (I) S t r u c t u r a l Proof o f the Rearranged Product 7£ ( i ) The S p e c t r a l Evidence: The p y r a z o l i n e 72a on standing at room temperature i n neat s o l u t i o n was converted i n t o a c r y s t a l l i n e s o l i d , l a t e r , i d e n t i f i e d as the hydrobromide s a l t of l-H-3-methyl-4-carbomethoxypyrazole (74). Compound 74 was very s o l u b l e i n water and alcoho] but s p a r i n g l y s o l u b l e i n chloroform, acetone and c t e t r a c h l o r i d e . In aqueous s o l u t i o n i t showed an a c i d t e s t to litmus paper and formed a white p r e c i p i t a t e on a d d i t i o n of s i l v e r n i t r a t e i n d i c a t i n g the presence o f bromide i o n . A flame t e s t of 7_4 on a copper wire a l s o i n d i c a t e d the presence o f bromine. This s o l i d showed n.m.r. peaks at 6 2.32 ( s i n g l e t , 3H, methyl), 3.70 ( s i n g l e t , 3H, -C00CH3) and 7.90 p.p.m. ( s i n g l e t , 1H, v i n y l proton ) and i t s i n f r a r e d ( i . r . ) spectrum showed abso r p t i o n at 3-4.5 u (broad), i n d i c a t i n g the presence of an ammonium s a l t and 5.82 u (strong) i n d i c a t i n g the presence of a conjugated e s t e r group. These s p e c t r a suggested the s t r u c t u r e of the rearranged product could be e i t h e r the hydrobromide s a l t of l-H-3-methyl-4-carbomethoxypyrazole (74) or the hydrobromide s a l t of l-H-3-- 3 8 -carbomethoxy-4-methylpyrazole ( 7 6 ) CH-OOC 3 > CH. + N " H.Br" 7 4 CH, COOCH, N H.Br" 7 6 ( i i ) By Conversion i n t o the Free Pyrazole The 3 , 4 - d i s u b s t i t u t e d p y r a z o l e (77) was obtained by d i s s o l v i n g the hydrobromide s a l t 74, the rearranged product of p y r a z o l i n e 72a, i n water, b a s i f y i n g the aqueous s o l u t i o n w i t h sodium bicarbonate and e x t r a c t i n g the pyraz o l e w i t h chloroform. The mi c r o a n a l y s i s of t h i s p y r a z o l e 77 confirmed-i t s s t r u c t u r a l formula to be C,H oN o0 . Compound 77 was very s o l u b l e i n methanol, chloroform, acetone and water. In ueuteriochloroform, i t showed n.m.r. peaks at <5 2.54 ( s i n g l e t , 3H, methyl), 2.83 ( s i n g l e t , 3H, -COOCH.), and 7.95 p.p.m. ( s i n g l e t , 1H, v i n y l p r oton). I t a l s o showed i . r . a bsorption at 2.85 u (medium) i n d i c a t i n g the presence of a secondary amine group and 5.90 v (strong) i n d i c a t i n g the presence of an a,g-unsaturated e s t e r . However, the m e l t i n g p o i n t o f pyra z o l e 77 (93-94° ) suggests i t s s t r u c t u r e to be l-H-3-methyl-4-carbomethoxypyrazole s i n c e the melti n g p o i n t o f the other isomer, l-H-3-carbomethoxy-4-methylpyrazole (78) i s 171-171.5°, (54). CH.OOC o > CH, CH. COOCH, •H H 7 7 7 8 - 39 -In order to confirm the s t r u c t u r e of the i s o l a t e d p yrazole 77_ to be l-H-3-methyl-4-carbomethoxypyrazole, s a l t 76_ was prepared v i a o x i d a t i o n of 3-carbomethoxy-4-methyl-2-pyrazoline with bromine i n chloroform at 15° (55). This s a l t was d i f f e r e n t from the rearranged product 74_ i n i t s i n s o l u b i l i t y i n c o l d water and a l c o h o l . The p y r a z o l e 78_ was i s o l a t e d by d i s s o l v i n g s a l t 76 i n b o i l i n g water and then b a s i f y i n g the aqueous s o l u t i o n w i t h sodium bicarbonate. Pyrazole 78, m.p. 171-171.5° , p r e c i p i t a t e d on c o o l i n g . The p y r a z o l e 77, obtained from the rearranged product 74, d i f f e r e d from , p y r a z o l e 7_8 i n three aspects. F i r s t l y t h e i r m e l t i n g p o i n t s were d i f f e r e n t . Secondly, compound 7_8 was i n s o l u b l e i n c o l d water, chloroform or acetone whereas compound 77_ was very s o l u b l e i n these s o l v e n t s . T h i r d l y , i n dimethyl s u l f o x i d e - d ^ , they showed d i f f e r e n t n.m.r. peaks. Compound 78_ showed n.m.r. peaks at 6 2.24 ( s i n g l e t , 3H, methyl group), 3.81 ( s i n g l e t , 3H, -COOCHj) and 7.61 p.p.m. ( s i n g l e t , 1H, v i n y l p r o t o n ) , whereas the other p y r a z o l e showed n.m.r. peaks ( i n DMS0-d6) at 6 2.40 ( s i n g l e t , 3H, methyl group), 3.73 ( s i n g l e t , 3H, -C00CH3) and 7.95 ( s i n g l e t , 1H, v i n y l p r o t o n ) . This evidence thus confirmed t h a t the p y r a z o l e obtained from rearranged product 7_4 has s t r u c t u r e 77. ( i i i ) By Conversion i n t o the Carboethoxy D e r i v a t i v e To f u r t h e r confirm the s t r u c t u r e of the rearranged p y r a z o l e 7_7 to be l-H-3-methyl-4-carbomethoxypyrazole, i t was converted i n t o the correspond-i n g carboethoxy d e r i v a t i v e 79_ by h y d r o l y s i s i n t o the corresponding a c i d w i t h base and then r e - e s t e r i f i c a t i o n using absolute ethanol and hydrogen c h l o r i d e gas. The n.m.r. spectrum 6 1.34 ( t r i p l e t , J = 7.0 Hz, 3H, -CH2CH_3), 4.33 ( q u a r t e t , J = 7.0 Hz, 2H, -CH_2CH3) , 2.56 ( s i n g l e t , 3H, methyl at C(3)) and 7.99 p.p.m. ( s i n g l e t , H, v i n y l proton at C(5)) confirmed the r e s u l t i n g - 40 -compound to be the corresponding carboethoxy d e r i v a t i v e . The melti n g p o i n t of t h i s carboethoxy d e r i v a t i v e 79_ (m.p. 46-48° .') was i d e n t i c a l w i t h t h a t o f 3-methyl-4-carboethoxypyrazole recorded i n the l i t e r a t u r e (56) (m.p. 46° ). CH.OOC f HOOC. OH H r CH C H 00C 3 C 2H 50H > HC1 gas CH, H r 7 7 7 9 ( I I ) M e c h a n i s t i c Studies of 1,2-Carbomethoxy M i g r a t i o n From the above r e s u l t s , i t i s c l e a r that the r e a c t i o n o f methyl 3-bromo-a-methacrylate ; (E)- w i t h diazomethane gives 3-carbomethoxy-3-methyl-4-bromo-1-pyrazole (E)-, which then q u i c k l y undergoes e l i m i n a t i o n o f HBr and rearrange-ment i n t o the hydrobromide s a l t o f 3-methyl-4-carbomethoxypyrazole. Simple e l i m i n a t i o n of s u b s t i t u e n t s i n p y r a z o l i n e s can be found i n the l i t e r a t u r e (57). Parham and coworkers (58) have presented evidence to i n d i c a t e that these r e a c t i o n s are both a c i d and base c a t a l y z e d . They suggest 1he decomposition.of 3-n i t r o p y r a z o l i n e s 80_ by a l k a l i probably take p l a c e by the removal of a proton from C(4) f o l l o w e d by a s h i f t of the C(4) e l e c t r o n s i n t o the r i n g and the simultaneous e l i m i n a t i o n o f the n i t r o group as an anion (E2-mechanism). The HO R R ' m N 80 rx NO, R ^ R 1 ^ NH N' N0 2 + H 20 - 41 -hydrogen atom at C(4) i s attached t o a carbon-carbon-nitrogen system s i m i l a r to t h a t found i n a - p i c o l i n e and the increased a c i d i t y observed i n such a system i s u s u a l l y explained by resonance s t a b i l i z a t i o n o f the r e s u l t i n g i o n . (-C-C=N <—» C=C-N-). The decomposition of 3 - n i t r o p y r a z o l i n e 80_ by treatment w i t h strong mineral a c i d s was suggested (58) to take p l a c e by an a c i d - c a t a l y z e d i o n i z a t i o n o f the n i t r o group f a c i l i t a t e d by the c o o r d i n a t i o n w i t h a proton w i t h subse-quent or simultaneous e x p u l s i o n of a proton at C(4). H R R NO NH 2 + H + N R NO, R - » UNO, 80 In the present s t u d i e s of p y r a z o l i n e 72a, a r o m a t i z a t i o n r e s u l t e d from the e l i m i n a t i o n of hydrogen bromide, and 1,2-migration of the carbomethoxy group occurred i n preference to the e l i m i n a t i o n of n i t r o g e n and formation of cyclopropane and o l e f i n products. Two p o s s i b l e mechanisms can be proposed f o r a m i g r a t i o n of t h i s type, the stepwise and the concerted mechanism. The stepwise mechanism i n v o l v e s a p r i o r l o s s of hydrogen bromide c a t a l y z e d e i t h e r by base to remove the proton at C(5), or by a c i d to remove the bromine at C(4), to form a double bond between C_ and C^, f o l l o w e d by attack of t h i s double bond at the carbonyl center at C(3) to form the intermediate 81. Bond rearrangements of 81 would lead to product 74 as shown i n Figure X I I . - 42 -CHLOOC CH H 2Br Figure XII - Stepwise mechanism of 1,2-carbomethoxy m i g r a t i o n . The concerted mechanism i n v o l v e s l o s s of bromide i o n with simultaneous' 1,2-migration o f the carbomethoxy group, as shown i n Figure X I I I . A s i m i l a r 74 Figure X I I I - Concerted mechanism of 1,2-carbomethoxy m i g r a t i o n - 43 -concerted mechanism was a l s o proposed by Parham (16) i n the s t u d i e s o f 4 - n i t r o p y r a z o l i n e 8_2 to give p y r a z o l e 83_ by a c i d i c c a t a l y s t . R' and R = a r y l groups 83 The p r e f e r e n t i a l m i g r a t i o n o f a carbomethoxy group over a methyl during a c i d c a t a l y z e d a r o m a t i z a t i o n i s not without precedent. A number of dienones s u b s t i t u t e d on the 4 - p o s i t i o n by an a l k y l group and a c a r b o a l k o x y l group undergo s i m i l a r a c i d c a t a l y z e d (59) and photochemical r e a c t i o n s (60). Kropp (60) observed the 1,2-carboethoxy m i g r a t i o n during the photochemical r e a c t i o n o f the c y c l o p r o p y l analog (84) o f 3-keto,-9-carbomethoxy-A'1" hexahydronapthalene and proposed a stepwise mechanism as shown below. - 44 -Jorgenson and C l a r k (61) on the other hand, observed the 1,2-carboethoxy m i g r a t i o n i n the thermal r e a c t i o n o f the bicyclic[2.1.0]pentane (g5) a n ( j proposed a stepwise mechanism as shown: 85 - 45 -I t can be seen then i n l i t e r a t u r e that there are examples of both concerted and stepwise mechanisms. In order to ob t a i n evidence regarding the mechanism of rearrangement, the e f f e c t of change of stereochemistry at C(3) of pyra-z o l i n e 72a was considered. Since 1,2-migrations of the concerted mechanism are known to be favoured i n f i v e and s i x membered r i n g s when the mig r a t i n g and l e a v i n g groups are trans t o each other, the e f f e c t of r e v e r s i n g stereo-chemistry at C(3) of p y r a z o l i n e 72a would be expected, i f the concerted mechanism were i n o p e r a t i o n , to have a marked e f f e c t on the rearrangement path, l e a d i n g to methyl m i g r a t i o n r a t h e r than carbomethoxy m i g r a t i o n . I f , however, the stepwise mechanism represented the c o r r e c t pathway, i t would be a n t i c i p a t e d t h a t carbomethoxy m i g r a t i o n would be favoured r e g a r d l e s s of the stereochemistry at C(3), owing to the u t i l i z a t i o n of the e l e c t r o n i c s t r u c t u r e of the e s t e r group i n the formation o f the intermediate 8JL A c c o r d i n g l y , 3-carbomethoxy-3-methyl-4-bromo-l-pyrazoline, (Z)- (72b) was prepared from the r e a c t i o n o f methyl 3-bromo-a-methacrylate, (Z> (73b) w i t h H CH, \ / 3 CH.OOC CH_ H CH. C H J , > ' 3 N : rS 3 3 2*2 % * Br Br COOCH e t h e r 3 H 2Br" 73b 72b 74 diazomethane. The s t r u c t u r e o f p y r a z o l i n e 72b was confirmed by the n.m.r. ( i n t e t r a c h l o r o e t h y l e n e ) spectrum which showed peaks at 6 1.52 ( s i n g l e t , 3H, methyl group), 3.85 ( s i n g l e t , 3H, -COOCH3), 4.20 ( t r i p l e t , J = 5.4 Hz., 1H, proton at C ( 4 ) ) , and 5.04 p.p.m. (doublet, J = 5.4 Hz., 2H, protons at C( 5 ) ) . These n.m.r. peaks were d i f f e r e n t i n p o s i t i o n to those obtained - 46 -from p y r a z o l i n e 72a i n the same solvent (see Experimental S e c t i o n 1, Table XIV). Further measurement of the p h y s i c a l p r o p e r t i e s o f p y r a z o l i n e 72b were not p o s s i b l e owing to the i n s t a b i l i t y o f t h i s compound. The p y r a z o l i n e 72b decomposed i n a s i m i l a r way as p y r a z o l i n e 72a t o the hydrobromide s a l t 74, m.p. 175-177.5° , i d e n t i c a l i n a l l respects w i t h that obtained by the rearrangement o f p y r a z o l i n e 72a. Furthermore, the pyra-z o l e d e r i v e d from t h i s s a l t was i d e n t i c a l w i t h 3-methyl-4-carbomethoxypyra-~ zol e i n both mel t i n g p o i n t and s p e c t r a l data. Since both C(3) epimers rearranged w i t h carbomethoxy m i g r a t i o n , the stepwise mechanism which i n v o l v e s the p r i o r l o s s o f hydrogen bromide f o l l o w e d by m i g r a t i o n of carbomethoxy group i s favoured over the concerted mechanism. In t h i s case, a c i d c a t a l y s i s i s presumably r e q u i r e d to a c t i v a t e one molecule (by formation o f i t s s a l t ) towards e l i m i n a t i o n by another molecule o f p y r a z o l i n e . Further evidence f o r the stepwise rearrangement mechanism i s th a t the dehydrobromination r e a c t i o n alone can be observed i n other bromopyrazolines to give s u b s t i t u t e d pyrazoles (62,63). An example (62) of t h i s i s the base c a t a l y z e d r e a c t i o n of 3-bromo-3,5,5-trimethyl-l-pyrazoline (86) which on treatment w i t h a l k o x i d e reacted to give 5-H-3,5,5-trimethylpyrazole (87) and 3-methylene-5,5-dimethylpyrazoline (88) as shown below:. Br CH 3 RO" N CH_ r . i i ^ 2 CH- C H 3 C H 3 86 8_7 88 Treatment o f 87 w i t h a c i d gives methyl m i g r a t i o n to form 3,4,5-trimethylpyrazole. - 4 7 -( I I I ) Thermal Decomposition 3-carbomethoxy-4-bromo-3,5,5-trimethyl-l-p y r a z o l i n e , (E)-Since a r o m a t i z a t i o n of p y r a z o l i n e s 72a and 72b occurred i n preference to the e l i m i n a t i o n of n i t r o g e n w i t h formation o f cyclopropane and o l e f i n products, the o r i g i n a l i n t e r e s t of studying the r e l a t i v e migratory a p t i t u d e o f bromine and hydrogen was f o i l e d . In order to prevent pyrazole formation, the p r e p a r a t i o n of 3-carbomethoxy-3,5,5-trimethyl-4-bromo-l-pyrazoline, (E) (89) was considered. With s u b s t i t u t i o n of two methyl groups at both of the C(5) p o s i t i o n s , dehydrobromination followed by rearrangement of a s u b s t i t u e n t i n p y r a z o l i n e 89_to give a s u b s t i t u t e d p y r a z o l e could not take p l a c e . . Compound 89_ was prepared from r e a c t i o n of methyl 8-bromo-a-methacrylate, (E)- (73a) and dimethyldiazomethane. S t r u c t u r e 89_ was confirmed by s p e c t r a l data: n.m.r. (CC1 4), 6 4.26 ( s i n g l e t , 1H, proton at C ( 4 ) ) , 3.78 ( s i n g l e t , 3H, methyl e s t e r ) , 1.59, 1.49 and 1.41 p.p.m. ( a l l s i n g l e t s , 3H each, one methyl at C(3) and two at C ( 5 ) ) , i . r . A l i c*' : f i l m 5.72 'u (strong) i n d i c a t i n g unconjugated e s t e r groups. M i c r o a n a l y s i s of t h i s p y r a z o l i n e 89_ a l s o give the c o r r e c t molecular formula CgH^Br^C^. . Heating 89 i n neat s o l u t i o n at 130° showed e v o l u t i o n of hydrogen bromide which turned litmus paper r e d , the s o l u t i o n turned black and n i t r o g e n bubbled out over a 7 hr p e r i o d . The r e s u l t i n g products i s o l a t e d from vapour phase chromatography were: a,y,y-trimethylangelicalactone(90) :_; and a-methylene-y,Y-dimethylbutyric lactone (91) i n r a t i o o f 79:21 r e s p e c t i v e l y . Br Br (CH 3) 2CN \ _ / _ i 3 o o r f = = X " J " 2 y=<^ » I *'C00CH3 > + I H C00CH 3 / ^ N ^ N 7 \ Q ^ 0 7 ^ 0 - ^ 0 • 73a 89 90_ 91 + HBr +. N„ - 48 -The s t r u c t u r e o f lactone 9_0 was e s t a b l i s h e d by s p e c t r a l data: the n.m.r. spectrum (CDCT-) showed peaks at 6 1.45 ( s i n g l e t , 6H, two methyl groups at the y - p o s i t i o n ) , 1.87 (doublet, J = 1.4 Hz, 3H, methyl at a - p o s i t i o n ) , and CHC1 7.05 p.p.m. (quarte t , J .=' 1.4 Hz, 1H, v i n y l proton at 6); i . r . X 3 5.72 u (strong) r e p r e s e n t i n g a conjugated lactone carbonyl and 5.84 u(medium) r e p r e s e n t i n g C=C. M i c r o a n a l y s i s o f lactone 90 was c o n s i s t e n t w i t h the molecular formula C_H^-0_. The s t r u c t u r e o f lactone 91_ was e s t a b l i s h e d by s p e c t r a l data only due t o low y i e l d . N.m.r. spectrum (CDC1-) o f 9_1 showed peaks at 6 1.40 ( s i n g l e t , 6H, two methyl groups at the y - p o s i t i o n ) , 2.72 ( t r i p l e t , J = 3.0 Hz, 2H, two protons at the g - p o s i t i o n ) , 5.57 and 6.18 p.p.m. (both t r i p l e t s , J = 3.0 Hz, 2H, two methylene p r o t o n s ) ; i . r . spectrum showed CHC1 absorptions at ^ m a x 3 5.70 u(strong) i n d i c a t i n g the presence o f a 5-membered r i n g lactone carbonyl and 5.99 u (medium), i n d i c a t i n g the presence o f C=C. , '. Again i n the thermal decomposition o f p y r a z o l i n e 89,loss o f hydrogen bromide took p l a c e f o l l o w e d by rearrangement o f f u n c t i o n a l groups i n preference to the formation of the cyclopropane and o l e f i n products;. ;^ Se c t i o n I I Mecha n i s t i c Studies of the P y r o l y s i s o f 1-Pyrazolines The r e s u l t s d escribed i n S e c t i o n I , although e x c i t i n g and unexpected, had so f a r not achieved the i n i t i a l purpose o f determining r e l a t i v e migratory a p t i t u d e s o f v a r i o u s groups as a means o f e l u c i d a t i n g r e a c t i o n mechanism and the nature o f intermediates. To f u r t h e r pursue t h i s o b j e c t i v e more experiments were planned t o evaluate the migratory a p t i t u d e s o f such f u n c t i o n a l i t i e s as methoxy, hydrogen, methyl and various s u b s t i t u t e d a r y l groups. This i n f o r m a t i o n was supplemented by isotope e f f e c t s t u d i e s , determination o f a c t i v a t i o n parameters, solvent e f f e c t s and stereochemical , - 49 -e f f e c t s w i t h the view of shedding f u r t h e r l i g h t on the mechanism of p y r a z o l i n e p y r o l y s i s . (I) The Synthesis of 1-Pyrazolines ( i ) P y r a z o l i n e s w i t h one s u b s t i t u e n t at C (4) In order to study the migratory aptitudes of methoxy and hydrogen groups i n the o l e f i n - f o r m i n g r e a c t i o n of p y r a z o l i n e p y r o l y s i s , the s y n t h e s i s of 3-carbomethoxy-3-methyl-4-methoxy-l-pyrazoline, (E)- (92). a compound w i t h both methoxy and hydrogen at C(4),was considered. I t was expected t h a t a methoxy group w i t h two lone p a i r s of e l e c t r o n s on oxygen would migrate t o a p o s i t i v e or r a d i c a l center b e t t e r than hydrogen. In order to prepare t h i s compound, methyl B-methoxy-a-methacrylate, (E)- (93) was t r e a t e d w i t h diazomethane under a v a r i e t y o f c o n d i t i o n s , i n c l u d i n g the use of BF_ as a c a t a l y s t . However, the two reagents failed to give the d e s i r e d p y r a z o l i n e , probably due to the double bond i n the s t a r t i n g o l e f i n , w i t h i t s e l e c t r o n donating methoxy group, being too e l e c t r o n r i c h to r e a c t w i t h the 1,3-dipole, diazomethane. To study the migratory a p t i t u d e s of phenyl (p-methoxyphenyl or p - n i t r o -phenyl) and hydrogen, 3-carbomethoxy-3-cyano-4-phenyl-l-pyrazoline, .(E)-(94) and the corresponding p-methoxyphenyl (95) and p - n i t r o p h e n y l - 1 -p y r a z o l i n e (96) were considered. Attempts to prepare these p y r a z o l i n e s 94-96 from the r e a c t i o n of methyl a-cyanocinnamate (97a) or the correspond-i n g p-methoxyphenyl (98) or p - n i t r o p h e n y l o l e f i n s (99a) w i t h diazomethane gave an intermediate which decomposed immediately at 0° to give a q u a n t i t a -t i v e y i e l d o f methyl a-cyano-B-methylcinnamate, (E)- (100a) or the corresponding p-methoxyphenyl (101) or p - n i t r o p h e n y l o l e f i n s (102a). P y r a z o l i n e s 94 and 9_5 were l i q u i d and were too unstable to i s o l a t e under any c o n d i t i o n s . - 50 -H' X = H CH 30 NO, 'COOCH .CN CH 2N 2 97a 98 99a 94 95 96 101 102a .CN CH 3 COOCH3 100a However, ( E ) - p - n i t r o p h e n y l p y r a z o l i n e , 96^  was a white c r y s t a l l i n e s o l i d which decomposed immediately a f t e r i s o l a t i o n i n t o o l e f i n 102a. The intermediates 94-96 were expected to be p y r a z o l i n e s r a t h e r than an i o n i c intermediate on the b a s i s t h a t ( E ) - p - n i t r o p h e n y l p y r a z o l i n e , 96 i s o l a t e d gave m.p. ca, 45° and n i t r o g e n gas could be seen bubbling out during m e l t i n g . A l s o many r e l a -t i v e l y s t a b l e p y r a z o l i n e s with s u b s t i t u e n t s s i m i l a r to those on 105 and 104 haye been prepared by a d d i t i o n of diazomethane to o l e f i n s such as 105 and 106. Sx H X = H COOEt COOEt 105 X = N0 2 106 CH 2N 2 j j / COOEt f \ COOEt 103 104 - 51 -The p r e p a r a t i o n of methyl a-cyano-B-methyl-p-substituted cinnamate, (E)- (100a, 101 and 102a) by r e a c t i o n of diazomethane w i t h the correspond-i n g methyl cx-cyano-p-substituted cinnamate (97a, 98 and 99a) proved to be a u s e f u l s t e r e o s p e c i f i c s y n t h e t i c approach to o l e f i n s . Cope's method of s y n t h e s i z i n g these o l e f i n s by condensation of acetophenone (or the correspond-i n g p-methoxy or p - n i t r o acetophenone) with methyl cyanoacetate gave a lower y i e l d w i t h non-separable (Z)- and (E)- isomers i n t h e i r e q u i l i b r i u m composi-t i o n (65). However, usi n g the method of reacting diazomethane w i t h o l e f i n s 97a,98 and 99a, the corresponding ( E ) - o l e f i n s 100a, 101 and 102a were obtained pure i n q u a n t i t a t i v e y i e l d . S i m i l a r r e a c t i o n s were a l s o observed by Hamelin, Vandeven and C a r r i e (66,73). Reaction of-the e t h y l a-cyano-p-substituted cinnamates, (E)- (107-111) w i t h diazomethane y i e l d e d q u a n t i t a t i v e l y the corresponding e t h y l a-cyano-g-meth y l - p - s u b s t i t u t e d cinnamates,(E)- (112-116). CI 108 113 N0 2 109 114 C H3 no 115 CH 30 111 H 6 In attempts to prepare methyl a-cyanocinnamate, (Z)- (97b) and methyl a-cyano-p-nitrocinnamate (99b), the corresponding (E)-isomers 97a and 99a o r e s p e c t i v e l y were i r r a d i a t e d at 2537 A i n ether s o l u t i o n . P u r i f i c a t i o n of. - 52.-the geometrical isomers obtained a f t e r i r r a d i a t i o n by e i t h e r d i s t i l l a t i o n (for the phenyl d e r i v a t i v e ) or r e c y r s t a l l i z a t i o n ( f o r the p_-nitrophenyl d e r i v a t i v e ) r e s u l t e d only i n formation of ( E ) - o l e f i n s 97a and 99a. An attempt t o prepare the (Z)-isomer of p y r a z o l i n e 9_4_ from a mixture o f o l e f i n s 97a and 97b and diazomethane gave only p y r a z o l i n e 94_ and i t s p y r o l y s i s product 100a. Examination o f the r e a c t i o n mixture a f t e r p a r t i a l r e a c t i o n showed that a l l of the o l e f i n 97b o r i g i n a l l y present had disappeared and had presumably been converted to the more s t a b l e isomer 97a. The s t r u c t u r e of the (E)-phenyl o l e f i n , 100a and the (E)-p-nitrophenyl o l e f i n 102a were confirmed by t h e i r n.m.r. sp e c t r a being i d e n t i c a l w i t h those recorded i n the l i t e r a t u r e (67). The structure of.the (E)-p-methoxyphenyl o l e f i n 101 was established.by the chemical s h i f t of the. methyl e s t e r and B-methyl groups being s i m i l a r to those of o l e f i n s 100a and 102a but d i s t i n c t l y d i f f e r e n t from those o f the (Z)-isomers 100b and 102b as shown i n Table I. Table I Chemical s h i f t s of methyl ct-cyano-B,B-disubstituted a c r y l a t e s i n 5 u n i t s R. CN R 2 ^ N COOCH-Chemical s h i f t o f Compound ^ R 2 R l R 2 C 0 ° C-3 C-3° R e f * 100a C 6 H 5 C H 3 7 .41 2 .65 3. .84 (66) 100b CH. C 6 H 5 6 .9-7.4( a ) 2 .50 3. .61 t h i s work 101 £-CH 30C 6H 4 U D C H 3 6 .98;7.52( b ) .24;7.34 ( C ) 2 .70 3.90 § 3.92 " 102a £ - N 02 C6 H4 C H 3 8 2 .73 3. .91 (66) 102b C H 3 p-N0 2C 6H 4 8 .27;7.33(-d-) 2 .57 3, .68 t h i s work ^ m u l t i p l e t , doublet, J = 8.8 Hz, ^ doublet; J = 8.8 Hz, ^ doublet, J = 8.5 Hz, - 53 -Both o l e f i n s 100b and 102b have been reported i n the l i t e r a t u r e (67), but never i s o l a t e d pure. In t h i s work,(Z)-phenyl o l e f i n 100b was prepared by i r r a d i a t i o n of the corresponding (E)-isomer 100a i n ether s o l u t i o n ; on con c e n t r a t i o n o f the r e a c t i o n mixture, the (Z)-isomer 100b c r y s t a l l i z e d out p r e f e r e n t i a l l y and was i s o l a t e d by s u c t i o n f i l t r a t i o n . (Z)-p-Nitrophehyl o l e f i n 102b was prepared by heat i n g the corresponding (E)-isomer 102a at 150° f o r 2 hrs to give a 1:1 mixture of the (Z)- and (E)-isomers. Compound 102b was i s o l a t e d from t h i s mixture by s l u r r y i n g the mixture w i t h a large, excess o f ether which p r e f e r e n t i a l l y d i s s o l v e d o l e f i n 102a. Since the cyano-1-pyrazolines 94-96 were not s u f f i c i e n t l y s t a b l e to be i s o l a t e d , the r e l a t i v e l y more s t a b l e 3-carbomethoxy-3-methyl-4-phenyl-l-p y r a z o l i n e (117) was prepared from the r e a c t i o n of a-methylcinnamic a c i d , (E)- w i t h two equivalents o f diazomethane. The s t r u c t u r e o f p y r a z o l i n e 117 C^Hg ^ 3 C 6 H 5 v . C H 3 CH„N„ X = / 2 2 , H-- ' / \ o O H 2 m 0 l e S COOCH, N 3 117 was e s t a b l i s h e d by i t s n.m.r. spectrum which showed a t r i p l e t at 6 3.64 and a doublet at 6 4.88 p.p.m. (coupling constant = 10 Hz). This AB 2 p a t t e r n r e p r e s e n t i n g protons at C(4) and C(5), s i m i l a r to that o f bromopyrazolines 72a and 72b (See Results and D i s c u s s i o n , S e c t i o n I ) , confirmed the s t r u c t u r e of p y r a z o l i n e 117. ( i i ) P y r a z o l i n e s w i t h two s u b s t i t u e n t s at the C(4) p o s i t i o n s The r e a c t i o n o f methyl a-methylcinnamate, (E)- w i t h diazomethane required. - 54 -over a week to form the (E)-3-methylpyrazoline 117, probably due to s t e r i c hindrance of the s t a r t i n g o l e f i n . This s i t u a t i o n would be expected t o be even worse f o r methyl a,g-dimethylcinnamate, (E)- so compounds i n t h i s s e r i e s were not pursued. A c c o r d i n g l y , methyl a-cyano-3-methyl-p-substituted cinnamates were considered f o r r e a c t i o n w i t h diazomethane to give the corresponding p y r a z o l i n e s w i t h r e t a i n e d stereochemistry. These r e a c t i o n s were deemed h i g h l y s a t i s f a c t o r y on the f o l l o w i n g bases:-( i ) the r e a c t i o n times were very short (2-4 hrs ) , probably due to the o l e f i n i c double bonds being more p o l a r ; ( i i ) the p y r a z o l i n e s obtained were c r y s t a l l i n e i n many cases and could be p u r i f i e d very e a s i l y by r e c r y s t a l l i z a -t i o n ; ( i i i ) the p y r a z o l i n e s were very s t a b l e i n c r y s t a l l i n e form and no p r e c a u t i o n was needed i n s t o r i n g them except to keep them at 0° ; ( i v ) the c r y s t a l l i n e s o l i d could be weighed very a c c u r a t e l y , and t h i s was of consider-able advantage i n e s t i m a t i n g end p o i n t s i n the k i n e t i c s t u d i e s . The new p y r a z o l i n e s obtained are l i s t e d i n Table I I . . ' Table I I Synthesis of 3-carbomethoxy-3-cyano-4-methyl-4-aryl-l-pyrazolines. R 2 | • COOCH R 3 7 k N ^ N  R 3 S t a r t i n g o l e f i n s P y r a z o l i n e s R l R2 ' R 3 100a 118a C 6 H 5 C H 3 H 101 119 p-CK 30C 6H 4 CH 3 H 102a 120a p-NC 2C 6H 4 CH3__ ' H 100b 118b CH 3 C 6 H 5 , H [ 102b 120b CH 3 p-N0 2C 6H 4 H 100a 121 C 6 H 5 CH 3 D - 5 5 . -P y r a z o l i n e s 118a, 119a, 120a and 120b were white c r y s t a l l i n e s o l i d s , r e l a t i v e l y s t a b l e at room temperature. T h e i r s t r u c t u r e s were e s t a b l i s h e d by t h e i r n.m.r. s p e c t r a (see Table I I I ) and m i c r o a n a l y t i c a l data. The s t r u c t u r e o f the l i q u i d p y r a z o l i n e 118b,which r e a d i l y decomposed at room temperature, was v e r i f i e d by i t s n.m.r. spectrum only (see Table I I I ) . Table I I I Chemical s h i f t s o f 3-carbomethoxy-3-cyano-4-aryl-4-methyl-l-p y r a z o l i n e s i n 6 u n i t s . P y r a z o l i n e s Ar CH_ at C(4) Chemical s h i f t s o f MeO C00CH_ H- at C(5) 118a 119 120a 118b 120b 121 7.32 (a) 6.87, 7.12 (9.0 Hz) (b) 7.37, 8.20 (9.0 Hz) 7.0-7.45 ( a ) 7.42, 8.22 (8.5 Hz) 7.32 ( a ) 1.47 1.48 1.54 1.44 1.50 1.47 3.80 3.94 3.95 4.05 3.35 3.52 3.94 .78, 5.30 (18.0 Hz) (b) ,75, (17 5.30 .7 Hz) (b) .94, 5.35 (16.4 Hz) 5.20 5.2f> (b) (a) (b) m u l t i p l e t doublet w i t h coupling constant i n brackets I t i s i n t e r e s t i n g to note that the two protons at C(5) are apparently not equivalent i n the c o n f i g u r a t i o n where the a r y l and e s t e r groups are trans to each other, whereas these protons do appear to be equivalent i n the p y r a z o l i n e s i n which the a r y l and e s t e r groups are i n the c i s c o n f i g u r a t i o n ; i n the former case, the two protons showed an AB s p l i t t i n g p a t t e r n w h i l e i n the l a t t e r case they appeared as a s i n g l e peak. This d i f f e r e n c e i s presumably caused by the f a c t t h a t the r i n g s are not planar and thus the - 56 -s h i e l d i n g and d e s h i e l d i n g by the -N=N- group and the other s u b s t i t u e n t s i s dependent on the conformational p o s i t i o n o f the two protons at C(5). One example o f t h i s d i f f e r e n c e i s shown by the n.m.r. s p e c t r a i n Figure XIV and Figure XV. The s t r u c t u r e o f the 5, 5 - d i d e u t e r i o p y r a z o l i n e 121 was e s t a b l i s h e d by i t s s i m i l a r n.m.r. spectrum to that of the corresponding non-deuterated p y r a z o l i n e 118a with the exception of the absence o f the peaks at 6 4.78 and 5.30 p.p.m. The extent of d e u t e r a t i o n (80%) was estimated by n.m.r. i n t e g r a t i o n at 6 4.78 and 5.30 p.p.m. re p r e s e n t i n g the hydrogen atoms at C(5) r e l a t i v e to peaks at <5 1.47 or 3.94 p.p.m. re p r e s e n t i n g the t o t a l p y r a z o l i n e c o n c e n t r a t i o n . This value was confirmed by the r e l a t i v e abund-ance o f mass s p e c t r a l peaks at m/e = 215, corresponding to non-deuterated p y r a z o l i n e l e s s the weight o f n i t r o g e n ; 216, corresponding to mono-deuterated p y r a z o l i n e l e s s the weight of n i t r o g e n , and 217, corresponding to di d e u t e r -ated p y r a z o l i n e w i t h l o s s o f n i t r o g e n which were i n the r a t i o 15:10:75. In the p r e p a r a t i o n o f a l l p y r a z o l i n e s using the r e a c t i o n o f diazomethane and a c t i v a t e d o l e f i n , the p y r a z o l i n e s obtained were a l l s i n g l e isomers formed s t e r e o s p e c i f i c a l l y w i t h r e t e n t i o n o f stereochemistry from the s t a r t -i n g o l e f i n s . However, i n the syn t h e s i s o f the (E ) - p - n i t r o p h e n y l p y r a z o l i n e 120a from o l e f i n 102a and diazomethane, 30% of the t o t a l product was found to be the corresponding 5-pyrazoline (122) and 17% to be the (Z)-p-n i t r o p h e n y l p y r a z o l i n e 120b. One a t t r a c t i v e r a t i o n a l e f o r the production o f t h i s l a t t e r compound i n v o l v e d a stepwise a d d i t i o n o f diazomethane to the (E)-p-nitrophenyl o l e f i n 102a to give intermediate 123a fol l o w e d by bond r o t a t i o n and then r i n g c l o s u r e . I t i s , however, g e n e r a l l y considered that a d d i t i o n of diazomethane to o l e f i n s i n v o l v e s a c i s concerted mechanism (9-11), 2.0 _> 4.0 5.'0 PPM(T) 6.0 7J3 ty> ' 9.0 lb \f •'• • • • • • i • • • • • • • - • i • • • • • • • i i • '• • • • • • • i • .' • • I • • • • i • • • • I • • • • i • • • • I • • • • i • • • • I Figure XIV - N.m.r. spectrum of 3-carbomethoxy-3-cyano-4-methyl-4-p-methoxyphenyl-l-)•:;:' pyrazoline, (E)- (119) in CDC1_. Figure XV - N.m.r.v spectrum of 3-carbomethoxy-3-cyano-4-methyl-4-p-nitrophenyl-l-p y r a z o l i n e , (Z)- (120b) i n CDC1 3. , - 59 -p-N0 2C 6H CN CH 3 C00CH 3 102a Ar C H 2 N 2 CH_.^ > 6 CN "•COOCH. r i n g c l o s u r e — —» 120a N 2 123a bond r o t a t i o n COOCH ' CN r i n g c l o s u r e — - > 120b and t h e r e f o r e i t was considered necessary to i n v e s t i g a t e more thoroughly the above evidence f o r a stepwise a d d i t i o n . When excess of o l e f i n 102a was allowed to re a c t w i t h diazomethane, the products showed 59% of the ( E ) - o l e f i n 102a, 25% of the corresponding (ZJ-o l e f i n 102b, 10% of the (E ) - p y r a z o l i n e 120a and 6% of the (Z) - p y r a z o l i n e 120b. Thus, the formation of p y r a z o l i n e 120b might be due to the isome r i z a -t i o n o f the ( E ) - o l e f i n 102a, c a t a l y z e d by the base present i n the system, to form the ( Z ) - o l e f i n 102b which then reacted w i t h diazomethane i n concerted f a s h i o n to give the ( Z ) - p y r a z o l i n e 120b. This c i s - t r a n s i s o m e r i z a t i o n o f o l e f i n s i n the presence of a n i o n i c reagents or r a d i c a l s as w e l l as - 6 0 -photochemical i s o m e r i z a t i o n have been thoroughly i n v e s t i g a t e d (68). Diazo-methane i n ether prepared from N-nitroso-N-methylurea and 50% of sodium hydroxide was d i s t i l l e d and the d i s t i l l a t e together with ether was d r i e d over an a c i d i c d r y i n g reagent (calcium c h l o r i d e ) to complete removal o f any tr a c e o f NaOH present. Reaction w i t h excess of o l e f i n 102a s t i l l gave 53% • of the ( E ) - o l e f i n 102a, 8% of the ( Z ) - o l e f i n 102b, 28% of the (E ) - p y r a z o l i n e 120a and 11% o f the ( Z ) - p y r a z o l i n e 120b. The percentage o f each product was analyzed by the i n t e g r a l i n the n.m.r. spectrum of the f o l l o w i n g chemical s h i f t p o s i t i o n s , i n 6 u n i t s : Ar \ CH 3 62.73 C N C00CH_3 63.91 ™ 3 \ _ / C N Ar " C00CH-62.57 63.68 p.p.m. 102a 102b Ar C N 120a COOCH, N —3 64.05 CH 3> Ar*' Ar = P-N0 2C 6H 4 C N 120b C00CH. 63.52 p.p.nr. The ( Z ) - / ( E ) - o l e f i n r a t i o and ( Z ) - / ( E ) - p y r a z o l i n e r a t i o were both lower than i n the case when the diazomethane used was not d i s t i l l e d but the con-t i n u e d presence o f the ( Z ) - o l e f i n s 102b and the ( Z ) - p y r a z o l i n e 120b i n d i c a t e d that they were not s o l e l y derived from the i s o m e r i z a t i o n of the - 61 -( E ) - o l e f i n 102a c a t a l y z e d by NaOH. However, compound 102a when mixed w i t h p y r a z o l i n e s 120a or 120b r e s p e c t i v e l y i n ether s o l u t i o n i n the absence of diazomethane was found to isomerize i n t o i t s geometrical isomer 102b (12%). The formation of the ( Z ) - p y r a z o l i n e 120b t h e r e f o r e could be r a t i o n -a l i z e d by the i s o m e r i z a t i o n of the ( E ) - o l e f i n 102a, c a t a l y z e d by the (E)-p y r a z o l i n e 120a formed, to the ( Z ) - o l e f i n 102b. I t i s i n t e r e s t i n g on the other hand t h a t r e a c t i o n of the pure ( Z ) - o l e f i n 102b w i t h diazomethane gave only the ( Z ) - p y r a z o l i n e 120b. I f the a d d i t i o n of diazomethane to the (Z)-o l e f i n 102b was a stepwise i o n i c mechanism, intermediate 123b should be formed. Bond r o t a t i o n of intermediate 123b would give intermediate 123a r i n g c l o s u r e o f which should y i e l d the ( E ) - p y r a z o l i n e 120a as w e l l as the (Z)-isomer 120b. The absence of the ( E ) - p y r a z o l i n e 120a i n t h i s case suggests t h a t the mechanism of the a d d i t i o n r e a c t i o n of diazomethane cannot be a stepwise one. S i m i l a r l y , o l e f i n 102b could a l s o be isomerized by the ( Z ) - p y r a z o l i n e 120b to the ( E ) - o l e f i n 102a which would then r e a c t w i t h diazomethane to give the ( E ) - p y r a z o l i n e 120a. This was not observed. The r a t e of r e a c t i o n of the ( Z ) - o l e f i n o f t h i s type w i t h diazomethane was found to be twice as f a s t as the corresponding (E)-isomer. This was determined by f o l l o w i n g the r e a c t i o n of a 1:1 mixture of (E)- and (Z)-phenyl o l e f i n 100a _. _ i and 100b w i t h diazomethane to give (E)- and (Z)-phenylpyrazoline 118a and 118b and determining the r a t e o f r e a c t i o n by f o l l o w i n g the i n t e g r a l of the f o l l o w i n g chemical s h i f t p o s i t i o n s . - 62 COOCH_ 63.84 p.p.m. 62.50' CH, CN C^Hr ' \ COOCH, 6 b —o 63.61 p.p.m. 100a 100b C 6 H . CH_ CN "f^coc C00CH_ N i ^ 63.94 p.p.m. 118a CH, C 6 H 5 CN I 'rnr COOCH, "^ N ' 63.35 p.p.m. 118b The absence o f the ( E ) - p - n i t r o p h e n y l p y r a z o l i n e 120a from the r e a c t i o n o f diazomethane w i t h the (Z) - p - n i t r o p h e n y l o l e f i n J02b can t h e r e f o r e be r a t i o n -a l i z e d as a r e s u l t o f the r a t e of t h i s r e a c t i o n being f a s t e r than the r a t e of c i s - t r a n s i s o m e r i z a t i o n of o l e f i n 102b c a t a l y z e d by the (Z ) - p y r a z o l i n e 120b formed. The formation o f the 5-pyrazoline 122 can be r a t i o n a l i z e d as a r e s u l t of a 1,3 proton s h i f t i n p y r a z o l i n e 120a (21) . . p-N0 2C 6H 4 CH CN COOCH, H 120a p-N0 2C 6H 4 -> CH. CN COOCH, 122 (I I ) P y r a z o l i n e P y r o l y s i s . Product I d e n t i f i c a t i o n and Q u a n t i t a t i v e A n a l y s i s 3-Carbomethoxy-4-phenyl-2-pyrazoline (124) (provided by Dr. D.E. McGreer) was p y r o l y z e d i n neat s o l u t i o n at 190° to give methyl B-methylcinnamate, (E)-(125a) (90.7%) and methyl 3-phenyl-3-buten 0ate (126) (9.3%) as shown i n Figure XVI. These products were i s o l a t e d by vapour phase chromatography, (v.p.c.) and the percentages found by the i n t e g r a t i o n of the area underneath each peak on the v.p.c. chart recorder. - 63 -C\HP COOCH-CH. COOCH, H C,'HC _ / 3 \ / 6 5 N / N C 6 H 5 / X H " H / X C H 2 C 0 0 C H 3 H 124 125a 126 hv CH_ H 3 N = / + 125a C , H C / X COOCH-D O O 125b Figure XVI - Thermal decomposition of 3-carbomethoxy-4-phenyl-2-pyrazoline. The s t r u c t u r e of the a,3-unsaturated e s t e r 125a was established by the mel t i n g p o i n t of t h i s compound being the same as that reported i n the l i t e r -ature (69). The stereochemistry of the ( E ) - o l e f i n 125a was based on the n.m.r. spectrum of t h i s compound and that of the (Z)-isomer (125b) obtained from i r r a d i a t i o n o f o l e f i n 125a. For a,B-unsaturated e s t e r s , groups c i s to the e s t e r groups show a greater down-field chemical s h i f t than those trans to the e s t e r group (67). The assignment o f the stereochemistry to compound 125a was t h e r e f o r e based on the f a c t that i n the n.m.r. s p e c t r a , the B-methyl o f compound 125a gave a peak at 6 2.52 p.p.m. whereas that of o l e f i n 125b occurred at 6 2.08 p.p.m. v The s t r u c t u r e of the B,y-unsaturated e s t e r 126 was e s t a b l i s h e d by the n.m.r. spectrum alone. The presence o f two s i n g l e t peaks at 6 5.45 and 5.16 p.p.m. i n d i c a t i n g the two v i n y l protons at the C(4) p o s i t i o n s , and a - 6 4 -s i n g l e peak at 6 3.40 p.p.m. i n d i c a t i n g the two methylene protons at the C(2) p o s i t i o n s , confirmed the s t r u c t u r e . 3-Carbomethoxy-3-methyl-4-phenyl-l-pyrazoline, (E)- (117) was pyr o l y z e d i n neat s o l u t i o n at 160° to give methyl 2-methyl-3-phenyl-3-buteneoate (127) ( 8 % ) , methyl a,B-dimethylcinnamate, (E)- (128) (62.4%) and l-carbomethoxy-l-methyl-2-phenylcyclopropane, (E)- (129a) (29.6%) as shown i n Figure XVII. The products were i s o l a t e d by v.p.c. and percentages found -by the i n t e g r a t i o n o f the area underneath each peak on v.p.c. chart recorder. ^ V — / " 3 H , C 6 H 5 C 6 H 5 V / C H 3 C 6 V > C H 3 I 'COOCH > /=K^ / ^ X \ / -.COOCH, N , T CHCH, I 3 COOCH, H CHCH, CH, COOCH, N I  3 3 3 117 127 128 129a Figure XVII - Thermal decomposition of 3-carbomethoxy-3-methyl-4-phenyl-l-p y r a z o l i n e , (E)-The s t r u c t u r e o f the g,y-unsaturated e s t e r 127 and a, 6-unsaturated e s t e r 128 were established by t h e i r n.m.r. s p e c t r a being i d e n t i c a l to those report e d i n the l i t e r a t u r e (70). Consistent m i c r o a n a l y t i c a l data o f o l e f i n 128 were a l s o obtained. The s t r u c t u r e o f cyclopropane 129a was e s t a b l i s h e d by the m i c r o a n a l y s i s and the n.m.r. spectrum o f t h i s compound. The presence of three quartets i n the n.m.r. spectrum (CCl^) at 6 2.80 ( J = 6.75 and 9.0 Hz), 1.65 ( J =4.25 and 9.0 Hz) and 1.08 p.p.m. (J = 4.25 and 6.75 Hz) i n d i c a t e d compound 129a to be a cyclopropane (71). The stereochemistry of cyclopropane 129a was e s t a b l i s h e d by comparison of the n.m.r. spectrum o f t h i s compound with that of i t s isomer 129b, i s o l a t e d from the r e a c t i o n o f methyl methacrylate and phenyldiazomethane (72): 6 1.45 ( s i n g l e t , methyl at C ( l ) ) , 1.10 (quarte t , J = 4.5 and 8.5 Hz, 1H), 1.87 (quarte t , J = 4.5 and. 6.5 Hz, 1H), 2.17 (qu a r t e t , J = 6.5 and 8.5 Hz, 1H), 3.21 ( s i n g l e t , methyl - 65 -ester) and 7.12 p.p.m. ( s i n g l e t , a r y l p r o t o n s ) . The higher f i e l d . r e s o n a n c e of the methyl group (6 0.95 p.p.m.) and lower f i e l d resonance of the e s t e r group (6 3.68 p.p.m.) i n the n.m.r. spectrum of cyclopropane 129a suggested the stereochemistry of t h i s compound. Decomposition of 3-carbomethoxy-3-cyano-4-methyl-4-p-nitrophenyl-l-p y r a z o l i n e , (E)- (120a) was c a r r i e d out i n benzene, nitrobenzene and t e t r a l i n r e s p e c t i v e l y at 70° and i n formamide at 30°. S i x or seven products 130a, 130b, 131a,131b, 132a, 132b and/or 133 (where Ar = J D - N O - C ^ T ) were obtained depending on the s o l v e n t s used. The percentages of these products i n d i f f e r e n t solvents, are shown i n Table V. The (E)-p-nitrophenyl o l e f i n 130a was p u r i f i e d by p r e p a r a t i v e l a y e r chromatography on s i l i c a , developed w i t h ether and carbon t e t r a c h l o r i d e (1:2) (R^ = 0.39). M i c r o a n a l y s i s of t h i s compound gave r e s u l t s c o n s i s t e n t w i t h the molecular formula of C 1 3H--N-0 4. The (Z)-isomer 130b was obtained together w i t h o l e f i n 130a ((Z)-:(E)-isomer r a t i o = 52:49) when the chromato-.. graphy was performed on alumina i n s t e a d of s i l i c a . The s t r u c t u r e o f both isomers 130a and 130b were e s t a b l i s h e d by the presence of a t r i p l e t and a quartet i n the n.m.r. s p e c t r a of these compounds: f o r the (E)-isomer 130a, 6 1.10 ( t r i p l e t , J = 7.5 Hz, -CH-CH.), 2.91 p.p.m. (qu a r t e t , J = 7.5 Hz, -CH-CH.), f o r the (Z)-isomer 130b: 6 1.06 ( t r i p l e t , J = 7.5 Hz, -CH-CH.) and 3.16 p.p.m. (q u a r t e t , J = 7.5 Hz, -CH-CH.). Nuclear magnetic resonance was a l s o used f o r assignment o f stereochemistry of these two o l e f i n s . The assignments are based on the f a c t that the chemical s h i f t f o r the B-methyl groups occurs at higher f i e l d when trans to the carboalkoxy group whereas the reverse i s t r u e f o r the y - m e t h y l group (67). Since i n o l e f i n 130a, the e t h y l group showed n.m.r. peaks i n which 3-CH-- i s ' i n lower f i e l d than that of o l e f i n 130b whereas y-CH- i s i n higher f i e l d than t h a t o f o l e f i n 130b, - 66 -Ar CN 4 CH - £ „««™, A r C N C 0H C CN A r v >CN I •% COOCH, A v V _ / A 2 5 \ _ / • . V — / „ ^ C„H r COOCH, ' Ar ' N COOCH, CH ' V 'COOCH, 120a Ar = p - N O ^ ^ 130a 130b 131a 118a Ar = C,HC 134a 134b 135a o o ~ 119 Ar = p-CH 30C 6H 4 137a 137b 138a CH 3 CN \ > ArCH_ CN CH_ CN-Ar V COOCH C H 3 N COOCH ArCH / ^ COOCH Ar = 2-N0 2C 6H 4 131b 132a 132b Ar = C,HC 135b 136a 136b o o Ar = p-CH,0C,H. 138b — 3 6 4 139a 139b Ar CN COOCH, CH ^ / N N ^ Ar = p-N0 2C 6H 4 133 Figure XVIII - Thermal decomposition of 3-carbomethoxy-3-cyano-4-methyl-4-a r y l - l - p y r a z o l i n e , (E)-- 67 -the e t h y l group was assigned the c i s c o n f i g u r a t i o n w i t h respect to the e s t e r group f o r o l e f i n 130a and the trans c o n f i g u r a t i o n i n o l e f i n 130b. The (E)-cyclopropane 131a was i s o l a t e d from the s i l i c a p r e p a r a t i v e p l a t e developed w i t h ether and c a r b o n t e t r a c h l o r i d e (1:2) (R^ = 0.29), and the corresponding (Z)-isomer 131b by s u c t i o n f i l t r a t i o n o f pyr o l y z e d pro-ducts from (Z) -£-nitrophenylpyrazoline 120b. The m i c r o a n a l y s i s of these cyclopropanes gave the molecular formula C^-H- 2^2®4' ^ e s t r u c t u r e °f these cyclopropanes were e s t a b l i s h e d by the r e l a t i v e l y high f i e l d s i n g l e t s at 6 1.62 and 1.81 p.p.m. due to the methyl groups i n the n.m.r. s p e c t r a o f c y c l o -propanes 131a and 131b r e s p e c t i v e l y . The s t e r e o c h e m i s t r i e s were assigned on the basis of the thermal rearrangements of these compounds. At high temperatures (ca. 200° ), the cyclopropane w i t h the methyl group c i s to the carbo-methoxy group w i l l undergo s t r u c t u r a l rearrangement i n t o methyl 2-cyano-4-aryl-4-pentenoate (_40_) whereas that w i t h the methyl group trans to the carbomethoxy group w i l l not (32). When (E)- and (Z)-cyclopropanes 131a and 131b were heated r e s p e c t i v e l y at 175° f o r 2 hrs , the (E)-isomer 131a rearranged i n t o 3,y-unsaturated e s t e r 140 whereas the corresponding (Z) isomer 131b d i d not. Therefore cyclopropane 131a has the c o n f i g u r a t i o n i n when methyl i s c i s to the carbomethoxy group. The s t r u c t u r e of o l e f i n 140 H,C) C — 0CH_ H H 2 \ _ Q / 3 A \ / C 0 0 C H A r / V ' * C N " > / N / C H 7 131a 140 3 Ar = p-NO-C^H - 6 8 -was confirmed by the n.m.r. peaks at 6 5.47 amd 5.59 ( s i n g l e t , two v i n y l p r o t o n s ) , 3.56 (quarte t , J = 5.8 and 9.0 Hz, 1H at C ( l ) ) , 3.21 (q u a r t e t , J = 1.0 and 5.8 Hz, 1H at C(2)) and 3.12 p.p.m. (qu a r t e t , J = 1.0 and 3.0 Hz, 1H at C(2)) and i . r . a b sorption at 5.74 u (strong) i n d i c a t i n g the presence of an unconjugated e s t e r group. N e i t h e r o f the p_-nitrobenzyl o l e f i n s 132a and 132b could be i s o l a t e d pure due to the very high b o i l i n g p o i n t s o f these compounds. However, the s t r u c t u r e s of these compounds were confirmed by the presence o f four s i n g l e t peaks i n the n.m.r. spectrum o f t h i s mixture at 6 2.35 and 2.26 p.p.m. repre-s e n t i n g the methyl group of p_-nitrobenzyl o l e f i n s 132a and 132b r e s p e c t i v e l y , and at <5 4.07 and 4.36 p.p.m. re p r e s e n t i n g the two methylene protons adjacent t o a C=C group i n compound 132a and 132b r e s p e c t i v e l y . The f a c t that the methyl group o f o l e f i n 132a e x h i b i t s a lower chemical s h i f t than t h a t o f o l e f i n 132b and v i c e versa f o r the methyl protons i n d i c a t e s compound 132a t o be the (E)-isomer and o l e f i n 132b to be the (Z)-isomer. p_-Nitrophenyl-5-pyrazoline 133 was i s o l a t e d by s l u r r y i n g the s o l i d obtained from the p y r o l y s i s of the (E)-p_-nitrophenyl-l-pyrazoline 120a i n t e t r a c h l o r o e t h y l e n e w i t h ether. The m i c r o a n a l y s i s showed the molecular formula of t h i s compound to be C-j^H^N^O,^. The s t r u c t u r e was e s t a b l i s h e d by the presence of n.m.r. peaks at 6 6.51 (broad) i n d i c a t i n g the presence of N-H and 6.81 p.p.m. ( s i n g l e t ) r e p r e s e n t i n g the v i n y l proton at the C(5) p o s i t i o n . The disappearance of the peak at 6 6.51 p.p.m. when was allowed to exchange w i t h 5-pyrazoline 133 i n deuteriochloroform s o l u t i o n v e r i f i e d the presence of the N-H group. 3-Carbomethoxy-3-cyano-4-methyl-4-phenyl-l-pyrazoline, (E)- (118a) was decomposed i n benzene and nitrobenzene at 70° , i n t e t r a l i n at 60° and i n neat s o l u t i o n at room temperature. S i x products: the (E)- and (Z)-- 69 -phenyl o l e f i n s 134a and 134b, the (E)- and (ZJ-benzyl o l e f i n s 136a and 136b, and the (E)- and (Z_)-cyclopropanes 135a and 135b were obtained i n a l l cases. The percentages o f these products i n d i f f e r e n t s o l v e n t s are shown i n Table VI. The (E)- and (Z)-phenyl o l e f i n s 134a and 134b were i s o l a t e d together and isomerized i n t o a 1:1 mixture by v.p.c. The s t r u c t u r e s and stereo-c h e m i s t r i e s o f these o l e f i n s were proved by the i d e n t i t y of t h e i r n.m.r. s p e c t r a w i t h those reported i n the l i t e r a t u r e (57). The (E)- and (ZJ-benzyl o l e f i n s 136a and 136b were a l s o i s o l a t e d a f t e r i s o m e r i z a t i o n i n t o a 1:1 mixture by v.p.c. The s t r u c t u r a l and stereochemical nature of these o l e f i n s was determined by n.m.r. i n a s i m i l a r way as f o r the correspond-i n g p_-nitrobenzyl o l e f i n s 132a and 132b. Furthermore, o l e f i n 136b was obtained i n over 90% y i e l d from p y r o l y s i s o f the (Z)-phenyl p y r a z o l i n e 120b i n benzene and could be f u r t h e r p u r i f i e d by d i s t i l l a t i o n . M icro-a n a l y t i c a l data o f t h i s d i s t i l l a t e was c o n s i s t e n t w i t h a molecular formula of C^-Hj-NO-. An attempt to i s o l a t e the (E)-cyclopropane 135a by v.p.c. r e s u l t e d i n i t s rearrangement i n t o methyl 2-cyano-4-phenyl-4-pentenoate. The percentage o f the (Z)-cyclopropane 135b obtained from p y r o l y s i s o f e i t h e r the (E)-phenylpyrazoline 118a or the (Z)-isomer 118b was too low to permit i s o l a t i o n . The presence of these two cyclopropanes i n the p y r o l y s i s products was shown by the presence of some n.m.r. peaks i n s i m i l a r chemical s h i f t p o s i t i o n s to those of the p-nitrophenylcyclopropanes 131a and 131b. 3-Carbomethoxy-3-cyano-4-methyl-4-p-methoxyphenyl-1-pyrazoline, (E)-(119) was p y r o l y z e d r e s p e c t i v e l y i n benzene, nitrobenzene, t e t r a l i n and d e c a l i n at 70° , i n neat l i q u i d at room temperature and i n formamide at 30° . Fi v e or s i x products o f the (E)- and/or (Z)-p-methoxyphenyl o l e f i n s - 70 -137a and 137b, the (E)- and (Z)-cyclopropanes 138a and 138b, the (E)- and (Z)-p-methoxybenzyl o l e f i n s 139a and 139b were obtained depending on the so l v e n t s used. The percentages o f these compounds from d i f f e r e n t s o l v e n t s are shown i n Table V I I . Attempts to i s o l a t e these products by l a y e r chromato-graphy or vapour phase chromatography were u n s u c c e s s f u l . However, the presence o f these and only these products was e s t a b l i s h e d by t h e i r n.m.r. peaks being i n extremely s i m i l a r p o s i t i o n s to the corresponding groups i n the r e l a t e d compounds obtained from p y r o l y s i s o f the (E)-phenylpyrazoline 118a and ( E ) - p - n i t r o p h e n y l p y r a z o l i n e 120a. 3-Carbomethoxy-3-cyano-4-methyl-4-phenyl-l-pyrazoline, (Z)- (118b) was decomposed i n benzene, nitrobenzene and i n neat l i q u i d r e s p e c t i v e l y at 70°, . and a l s o i n neat s o l u t i o n at room temperature. Three products, 1-carbomethoxy-1-cyano-2-methyl-2-phenylcyclopropane, (Z)- (135b), methyl a-cyano-6-benzyl-cr o t o n a t e , (E)- (136a) and the corresponding ( Z ) - o l e f i n 136b were obtained i n a l l cases. 3-Carbomethoxy-3-cyano-4-methyl-4-p-nitrophenyl-l-pyrazoline, (Z)- (120b) was decomposed i n bezene and nitrobenzene r e s p e c t i v e l y at 70°[.. Three products, l-carbomethoxy-l-cyano-2-methyl-2-p-nitrophenylcyclopropane, (Z)- (131b), methyl a-cyano-8-p-nitrobenzylcrotonate, (E)- and ( Z ) - , 132a and 132b were obtained i n both cases. These products were already i d e n t i f i e d as mentioned above. The percentages o f these products are shown i n Table V I I I . , The percentages o f each compound from the pyrolys e s o f the phenylpyra-z o l i n e s 118a and 118b, p-methoxyphenylpyrazoline 119 and p - n i t r o p h e n y l p y r a z o l i n e s 120a and 120b were determined by n.m.r. (CDC1-) i n t e g r a t i o n of the un d e r l i n e d groups o f each compound shown i n Table IV. - 71 -CH CN Ar* N' COOCH,' 'N 3 C H 3 \ / C N ArCH 2 CN CH 3 CN -* Ar -r\f''- COOCH* ) = < + CH 3 C00CH 3 ArCH 2 C00CH 3 118b Ar = C H r o b 135b 120b Ar = p-NO C f iH 4 131b 136a 132a 136b 132b Figure XIX - Thermal decomposition of 3-carbomethoxy-3-cyano-4-methyl-4-aryl-1-pyrazoline, (Z)-Table IV, Chemical s h i f t s of unde r l i n e d groups ( i n 6 u n i t s ) used f o r percentage a n a l y s i s o f 1-pyrazoline p y r o l y s i s Ar ' • CN 130a  134a 137a Ar CN \ _ / . CH 3CH 2 COOCH 1.05 0.97 1.00 CH3CH CN / — \ Ar COOCH -3 130b  134b 137b 3.65 3.48 3.57 131a  135a 138a COOCH, 1.62 1.50 1.50 131b  135b 138b CH, Ar . 3.53 3.33 3.42 C00CH 3 ArCH 2 CN \ / CH_3' COOCH3 132a 2.30 2.18 139a 2.20 136a CN A r C H ^ N C 0 0 C H 3  132b 2.20 4.28 136b 2.07 4.11 139b 2.10 4.03 Ar V CH, H N ^NH CN COOCH, 133 v i n y l H 6.81; NH 6.51 p.p.m. - 72 -These u n d e r l i n e d groups showed chemical s h i f t s that were w e l l separated from other groups and thus provided an accurate means of a n a l y z i n g the percentage o f each compound by the n.m.r. i n t e g r a l o f these groups. A t y p i c a l example of these s p e c t r a i s shown i n Figure XX. The i n t e g r a l o f the methyl groups i n the ( E ) - a r y l o l e f i n s 130a, 134a, and 137a gives the percentages of both the (Z)- and (E)-isomers of the corresponding o l e f i n s . However the i n t e g r a l s o f methyl e s t e r i n the ( Z ) - a r y l o l e f i n s 130b, 134b, and 137b give the percentages of only these compounds. Thus, the d i f f e r e n c e o f these two values w i l l g i v e the percentages o f the '(E)-isomers 130a,134a and 137a r e s p e c t i v e l y . When benzene was used as the p y r o l y s i s s o l v e n t , the chemical s h i f t s o f some of the u n d e r l i n e d groups were very c l o s e to those o f other groups. ~ A c c o r d i n g l y , the s o l v e n t was evaporated and deute r i o c h l o r o f o r m was used as n.m.r. so l v e n t i n s t e a d . In nitrobenzene, the u n d e r l i n e d groups showed chemical s h i f t p o s i t i o n s s l i g h t l y d i f f e r e n t from those of the corresponding groups shown i n Table IV, but s u f f i c i e n t l y w e l l separated from other groups to give accurate percentages. The solvent peaks of t e t r a l i n d i d not overlap w i t h the peaks of the u n d e r l i n e d groups except those of the p_-nitrophenyl-5-p y r a z o l i n e 133. In t h i s case and i n the case where d e c a l i n was used as the p y r o l y s i s s o l v e n t , the s o l v e n t s were d i s t i l l e d by bulb to bulb d i s t i l l a t i o n i n vacuo at room temperature and CDCT, was used as the n.m.r. s o l v e n t . When formamide was used as the p y r o l y s i s s o l v e n t , most of the products were i n -s o l u b l e i n t h i s s o l v e n t and were d i s s o l v e d i n an equal volume of d e u t e r i o -chloroform. The two s o l u t i o n s were i n t e g r a t e d under i d e n t i c a l c o n d i t i o n s to give the percentage y i e l d o f each compound. A summary of p y r o l y s i s o f each p y r a z o l i n e and percentage o f each product i s shown i n Table V, V I , VII and V I I I 2.0 3.0 4.0 slo .pm^T\ . 6 ; ° . . 7 ; ° . 8 ; ° . 9 ; ° . ft Figure^ XX - N.m.r. spectrum of p y r o l y s i s products from 3-earbomethoxy-3-cyano-4-methyl-4-p h e n y l - l - p y r a z o l i n e , ( E)- (118a) i n CDC1_. T A B L E V Decomposition o f Q J ••' I CO, 0 2CH 3 , Ar = p-N0 2C 6H 4-of Products Solvent Temp. Time A r ^ y CN Et Et .CN-X CH C0 2CH 3 A r C0 2CH 3 Ar 3 CN CH CN " % — / ArCH_ .CN CH CN ''CO CH A r y V''CO-CH_ , 3 X 1 2 3 CH CO CH 3 ArCH CO CH c A ( a ) D D 70° 2 hrs. 52.8 6.0 17.0 4.0 12.4 7.8 it I I 53.0 6.0 17.0 3.7 .13.0 7.3 C6 H5 N°2 ii it 37.2 12.6 8.0 8.6 15.4 18.3 T e t r a l i n ^ I I 36.4 12.2 7.5 8.7 16.3 18.7 I I I I 25.4 27.1 20.3 6.78 10.3 10.3 f c") Formamide 30° 10 min 48.6 8.7 3.9 21.5 8.4 7.9 (a) (b) (c) 11.5% o f t o t a l products was found t o be the corresponding 5-pyrazoline. 23.4% o f t o t a l products was found to be the corresponding 5-pyrazoline. 9.1% o f t o t a l products was found to be the corresponding 5 - p y r a z o l i n e . TABLE VI Decomposition of , Ar = C,H_ o b % o f products Solvents Temp. Time A: Et / CN CO.CH3 Et XCN Ar Ar CH C0 2CH 3 CN CH__ i V CO.CH- Ar V 2 3 CN ArCH, CN CH, CN CO-CH, / — \ • — v 2 3 CH CO CH ArCH 2 CO CH (A) C 6H 5 70° tt 2 hrs tt 52.0 53.4 1.0 1.7 12.9 11.2 3.4 3.4 26.5 25.2 4.1 5.3 A 140° 2 hrs 31.8 20.0 13 3 17.1 15.0 A + p y r i -„ dine r . t . tt 29 hrs equilb r i u m 50 32.4 3 19.6 13 13 3 3 18 18 13' 13 C 6H 5N0 2 70° (a) 51.2 3.6 4.2 9.6 19.3 12.1 it tt '(b) 51.0 3.9 4.4 9.0 20.2 11.6 tt it (c) 50.7 3.9 3.8 9.6 20.3 12.7 T e t r a l i n 60° 8 hrs 29.6 20.4 8.7 8.7 19.6 13.1 Neat r . t . 2 months 50.4 2.8 4.9 9.8 19.6 12.6 C 6H 5N0 2 70° 2hrs (d) 47.75 3.9 2.0 9.9 20.4 15.8 (a) (b) (c) (d) 0.1 gm heated at 5 h r s . 0.5 gm heated at 5 h r s . over 5 h r s . p e r i o d 0.1 gm added at ho u r l y i n t e r v a l p r o v i d i n g a t o t a l o f 0.5 gm sample, decomposition .of the corresponding 5 , 5 - d i d e u t e r i o p y r a z o l i n e 121. p-MeOC,H,, - 6 4 CN TABLE VII Decomposition o f CH, > C 0 2 C H 3 Ar = p-MeOC,H. i - 6 4 % of Products Solvent Temp. Time Ar CN Et CN A r v _ C N C H 3 v _» C N ArCti. ,CN CH, CN E t / _ X C 0 2 C H _ A/. XC0 2CH_ C H3* V " C 0 2 C H 3 A t ^ C ° 2 C H 3 CH^ X C 0 2 _ H _ 'Arclk-'cO-OT-C 6 H 6 70° 2 hrs ; 46.7 0 8.3 3.6 37.8 3.5 it I I 47.3 0 7.6 3.0 38.6 3.5 C 6H 5N0 2 it I I 51.7 0 2.0 7.8 27.3 11.2 I I I I 52.1 0 2.0 7.8 27.3 10.7 T e t r a l i n 60° 8 hrs 38.9 11.1 0 5.6 27.8 16.7 Neat r . t . 2 months 50.0 3.6 2.7 1.8 32.8 9.1 D e c a l i n 70° 5 hrs 43.8 o 14.95 3.1 27.8 10.3 Formamide 30° 10 min 40.9 7.3 5.6 11.5 18.9 15.0 • , -CH_ . CN 3 V • TABLE V I I I Decomposition o f A \ \ A r k J C ° 2 C H 3 N % o f Products Ar Solvent Temp. Time C H 3 V / C N Ar' V C0 2CH 3 ArCH„ CN 2 \ _ / CH 3/ ^C0 2CH 3 CH_ CN 3 \ _ / ArCH^ x C 0 2 C H 3 ' C 6 H 5 C 6 H 6 70° 2 hrs 3.6 5.2 91.1 it C 6H 5N0 2 it I I 0 35.5 64.5 I I Neat r . t . 24 hrs 3.1 0 96.6 I I I I 70° 5 min 8.0 12.2 79.8 P - N 0 2 C 6 H 4 C 6 H 6 70° 4 hrs 15.5 6.9 77.6 I I C6 H5 N°2 ti 20 min " 8.2 8.2 83.5 - 78 -An important f e a t u r e can be observed from these t a b l e s ; the major o l e f i n s obtained from p y r a z o l i n e p y r o l y s i s r e t a i n the same stereochemistry as the s t a r t i n g p y r a z o l i n e s . However, small amounts of the o l e f i n products w i t h i n v e r s i o n o f stereochemistry as the s t a r t i n g p y r a z o l i n e s were a l s o obtained, f o r example the ( Z ) - a r y l o l e f i n s 130b, 134b and 137b and the ( Z ) - p - n i t r o b e n z y l , benzyl and p-methoxybenzyl o l e f i n s 132b, 136b and 139b from the (E)-p-n i t r o p h e n y l p y r a z o l i n e 120a, the (E)-phenylpyrazoline 118a and the (E)-p-methoxyphenylpyrazoline 119 r e s p e c t i v e l y . These products were, at f i r s t , r a t i o n a l i z e d as the r e s u l t o f an i o n i c intermediate 123a formed during the p y r o l y s i s . Bond r o t a t i o n of intermediate 123a fol l o w e d by l o s s o f n i t r o g e n w i t h simultaneous m i g r a t i o n o f a l k y l or a r y l groups from C(4) to C(5) would lead to o l e f i n s w i t h i n v e r t e d stereochemistry. Furthermore, the (Z)-phenyl * o l e f i n s w i t h r e t e n t i o n of stereochemistry bond r o t a t i o n o l e f i n s w i t h i n v e r s i o n of stereochemistry Ar 3 W N CN "tOOCH, Ar ± - > C H -CN COOCH. 123a COOCH, 123b - 79 -o l e f i n 134b and the (Z)-benzyl o l e f i n 136b were obtained i n lower y i e l d from the (E)-phenylpyrazoline 118a when benzene was used as a p y r o l y s i s solvent than when nitrobenzene was used in a s i m i l a r p y r o l y s i s . S i m i l a r y i e l d s were observed f o r s i m i l a r pyrolyses o f the (E)-p-methoxyphenylpyrazoline 119 and the ( E ) - p - n i t r o p h e n y l p y r a z o l i n e 120a. This was c o n s i s t e n t w i t h the supposition that nitrobenzene, being a more p o l a r solvent than benzene, could s t a b i l i z e the i o n i c intermediate 123a b e t t e r , and thus the degree o f bond r o t a t i o n t o -intermediate 123b would be higher . • On the other hand, p a r t i a l decomposition o f the (E)-phenylpyrazoline 118a and the (E)-p-methoxyphenylpyrazoline 119 i n neat l i q u i d " at room temperature d i d not lead to recovery o f any p y r a z o l i n e s w i t h i n v e r t e d stereo-chemistry. Furthermore, s i m i l a r p y r o l y s i s o f the (Z)-phenylpyrazoline 118b and the ( Z ) - p - n i t r o p h e n y l p y r a z o l i n e 120b r e s p e c t i v e l y d i d not give the same r a t i o o f geometrical i s o m e r i c o l e f i n s . T h i s should not be the case i f the p y r o l y s i s proceeds v i a the i o n i c i n termediate. When a mixture o f the (E)-phenyl o l e f i n 134a (with 2% of the. (Z)-isomer 134b) and the (E)-benzyl o l e f i n 136a (with 20% of the (Z)-isomer 136b) were allowed to isomerize i n deuteriochloroform c a t a l y z e d by a t r a c e of p y r i d i n e , the r a t e o f i s o m e r i z a t i o n f o r the (E)-phenyl o l e f i n 134a t o the (Z)-isomer 134b was found t o be f a s t e r than t h a t f o r the (E)-benzyl olefin,© 136a to i t s (Z)-isomer 136b; Since the ( Z ) - / ( E ) - r a t i o s f o r benzyl o l e f i n , " p-methoxybenzyl o l e f i n and p - n i t r o b e n z y l o l e f i n were l a r g e r than those of phenyl o l e f p-methoxyphenyl o l e f i n s and p- n i t r o p h e n y l o l e f i n i n p y r o l y s i s of the (E)-ph e n y l p y r a z o l i n e 118a, the (E)-p-methoxyphenylpyrazoline 119 and the (E)-p - n i t r o p h e n y l p y r a z o l i n e 120a, i t i s considered that the (Z)-isomer o f benzyl (or j>-substituted benzyl) o l e f i n 136b (or 139b, 132b) and phenyl (or p-s u b s t i t u t e d phenyl) o l e f i n 134b (or 137b, 130b) were formed from the base - 80 -i s o m e r i z a t i o n s o f the corresponding ( E ) - o l e f i n s . This r a t i o n a l i z a t i o n was f u r t h e r confirmed by the i s o m e r i z a t i o n of (Z)-benzyl o l e f i n 136b (with 5% of the (E)-isomer 136a) i n benzene s o l u t i o n i n t o a mixture of (Z)- and (E)-isomers (53.9:46.1) c a t a l y z e d by decomposing 3-carbomethoxy-3-cyano-4-ethyl-4-phenyl-1-pyrazoline (141) at 70°. P y r a z o l i n e 141 was chosen because the decomposition products d i d not possess any n.m.r. peaks that would overlap w i t h those of methyl groups i n benzyl o l e f i n s 136a and 136b. This r e s u l t suggests that o l e f i n products w i t h i n v e r t e d stereochemistry as the s t a r t i n g p y r a z o l i n e may a r i s e from c i s - t r a n s i s o m e r i z a t i o n of o l e f i n s (formed w i t h r e t e n t i o n of stereochemistry) c a t a l y z e d by the decomposing p y r a z o l i n e s . That the i s o m e r i z a t i o n was greater i n nitrobenzene than i n benzene was probably due to the s o l u b i l i t i e s of decomposing p y r a z o l i n e s being g r e a t e r i n nitrobenzene. This i s f u r t h e r supported by the f a c t t h a t the c i s - t r a n s i s o m e r i z a t i o n of o l e f i n s r e s u l t i n g from both methyl or a r y L migrations were gre a t e r i n t e t r a l i n , a l e s s p o l a r s o l v e n t but having higher p y r a z o l i n e s o l u b i l i t y than nitrobenzene. Hamelin and C a r r i e (21,72,74) s t u d i e d the decomposition of 3-carboethoxy-3-cyano-4-methyl-4-aryl-l-pyrazolines (142 and 143) i n b o i l i n g toluene. The products of these decompositions were e t h y l a-cyano-8-p-substituted benzylcrotonate (144), e t h y l a-cyano-B-ethyl-p-substituted cinnamate (145) and l-carbomethoxy-l-cyano-2-methyl-2-p-substituted phenylcyclopropane (146) (74). The percentages o f d i f f e r e n t p y r o l y s i s products are shown i n Table IX. The percentages of the products l i s t e d i n Table IX were analyzed by vapour phase chromatography or polarography. In b o i l i n g toluene geometric isomers o f both crotonates 144 and cinnamates 145 were obtained, f o r example, - 81 -p-XC 6H 4 CH. 142 CN COOC 2H 5 CH. p-XC 6H 4-CN 143 COOC2H5 (p-XC 6H 4CH 2)(CH 3)C=C(CN)COOC 2H 5  144 (p-XC 6H 4)(C 2H 5)C=C(CN)COOC 2H 5 145 (p-XC 6H 4) (CH 3)C — C ( C N ) (COOC2H 5) C H„ 146 Table IX Decomposition o f 3-carboethoxy-3-cyano-4-methyl-4-aryl-l-pyrazolines. CH 30 CI H CH 3 X 142 143 142 143 142 143 142 143 % of 144 48 78 36 88 29 35 74 % of 145 18 5 42 2 41 35 6 % o f 146 18 4 25 7 0 19 7 when X = H, the (E)-and -isomer r a t i o of cinnamate 144 was 30:70 and that o f crotonate 145 was 50 :50 (72) The present work shows that these o l e f i n s isomerize thermally as w e l l as c a t a l y t i c a l l y , f o r example, methyl. B-methyl-a-cyanocinnamate, (E)- isomerized at 140° with *-\/2 ~ 123 min. - 82 -Al s o i s o l a t i o n by vapour phase chromatography o f the p y r o l y s i s products from 3-carbomethoxy-3-cyano-4-methyl-4-phenyl-l-pyrazoline, (E)- (118a)gave a 1:1 (E)- and (Z)- mixture o f 8-ethylcinnamates (134a and 134b) and 3-benzylcrotonates (136a and 136b). But a n a l y s i s of the crude products by n.m.r. integration showed a d i f f e r e n t r a t i o (see Table V I ) . Thus, the (Z)-and (E)- r a t i o of o l e f i n s obtained from v.p.c. may not be the primary product r a t i o s . Hamelin and C a r r i e (21), on the other hand, s t u d i e d the decomposi-t i o n o f p y r a z o l i n e s at room temperature and found that the formation of the two e s t e r n i t r i l e s 144 and 145 were s t e r e o s e l e c t i v e and the geometric isomers o f o l e f i n s depended mainly on the geometry of s t a r t i n g p y r a z o l i n e . The formation of o l e f i n s from p y r a z o l i n e p y r o l y s i s was thus concluded by C a r r i e to be s t e r e o s e l e c t i v e and a mechanism f o r t h i s p y r o l y s i s was p o s t u l a t e d on t h i s b a s i s . The r a d i c a l mechanism was demonstrated t o be improbable from the f a c t t h a t l i t t l e v a r i a t i o n of r e l a t i v e p r o p o r t i o n s of products obtained was observed i n thermal decomposition i n the presence o f e i t h e r an i n h i b i t o r of r a d i c a l r e a c t i o n s , p - t - b u t y l c a t e c h o l , or an i n i t i a t o r o f r a d i c a l r e a c t i o n s , benzoylperoxide. Two p o s s i b l e mechanisms were suggested on the b a s i s o f s t e r e o s e l e c t i v e formation o f o l e f i n s : ( i ) m i g r a t i o n of groups concerted w i t h l o s s of n i t r o g e n ; and ( i i ) the formation o f an i o n i c intermediate w i t h the r a t e o f rearrangement i n t o o l e f i n s being much f a s t e r than r o t a t i o n around the C(3)-C(4) bond. These mechanisms were c o n s i s t e n t w i t h the experimental r e s u l t s . The existence of a conformational e q u i l i b r i u m f o r each p y r a z o l i n e allows e x p l a n a t i o n of why the p y r o l y s i s of two geometric isomeric p y r a z o l i n e s give d i f f e r e n t product r a t i o s (21). For p y r a z o l i n e s w i t h the aromatic groups trans to e s t e r , the conformers 147a and 148a, represented by Newman p r o j e c t i o n 149a and 150a, are i n - 83 -e q u i l i b r i u m . The formation of o l e f i n s 145 and 144 r e s u l t from the m i g r a t i o n of groups i n conformer 149 and 150 r e s p e c t i v e l y . COOC-H-147a _ H 2C 00 148a C0 2C 2H 5 149a Ar H 5 S ° 2 C - ^ j ^ C N N" 150a *N A r ^ j CN C 2 H 5 " C O O C 2 H 5 ArCH 2 y CN CH, C00C2H_ 145 (E)- 144 ( E ) -- 84 -The e q u a t o r i a l bond at C(4) i s p a r a l l e l to C(3)-N(2j and C(5)-N(l) bonds. Thus the group i n e q u a t o r i a l p o s i t i o n at C(4) i s i n a fav o r a b l e p o s i t i o n f o r i t s t r ans e l i m i n a t i o n from C(4) and migrates t o C(5) w i t h l o s s of n i t r o g e n which i s trans t o the mi g r a t i n g group. This formation of o l e f i n s f o l l o w s a mechanism-similar to the E 2 e l i m i n a t i o n mechanism. This hypothesis allows -formation o f s t e r e o s p e c i f i c ( E ) - o l e f i n s 145 and 144 when the p y r a z o l i n e s were decomposed at room temperature, i . e . , when the i s o m e r i z a t i o n s of o l e f i n s were not observed. When aromatic groups are trans to e s t e r , conformer 149a f a v o r i n g m i g r a t i o n o f methyl i s a more s t a b l e conformer. However o l e f i n 144 obtained from migrations of the a r y l groups i n conformer 150a were formed i n many cases i n higher percentages than o l e f i n s 145 r e s u l t i n g from m i g r a t i o n o f methyl i n conformer 149a. This was explained as a r e s u l t o f the migratory a p t i t u d e of the a r y l groups being higher than t h a t of the methyl group. For p y r a z o l i n e s w i t h the aromatic groups c i s to e s t e r , the conformers 147b and 148b, represented by Newman p r o j e c t i o n s 149b and 150b, are i n e q u i l i b r i u m . The d i f f e r e n c e o f s t a b i l i t y between conformers 149b and 150b. i s very much l e s s than t h a t between 149a and 150a. Predominant formation o f the ( Z ) - o l e f i n 145 i s t h e r e f o r e normal s i n c e the a r y l groups migrate i n preference to methyl. This hypothesis was f u r t h e r supported by the decomposition o f 3-carboethoxy-3-cyano-4,4-diphenyl-1-pyrazoline which gave e t h y l a-cyano-B-benzylcinnamate (153) w i t h ( E ) - / ( Z ) - = 95/5. The predominant formation o f ( E ) -o l e f i n suggests that the conformer 151 i s much more s t a b l e than 152. - 85 -CH„ Ar N / ^ H 5C.0 2C N COOC2H-147b 148b CH. NC Ar \\ C0 2C 2H 5 149b CH, H 5C 20 2C CN N 150b A r C H 2 \ _ / C°2 C2 H5 / ^ CH. CN Ar CO.C-H-\__/ 2 2 5 C 2H 5 / ^ CN 145 (Z)- 144 (Z)-- 86 -C0 2C 2H 5 C 6 H 5 H.C 20 2C C 6 H 5 CN 152 C,H_V CN 6 5 \ _ _ / / \ C 6H.CH 2 C0 2C 2H 5 C 6 H 5 C H 2 \ / CN C 6 H 5 / X c 0 2 C 2 H 5 153 (E)- 154 (Z)-The f o l l o w i n g c o n s i d e r a t i o n s were made by Hamelin and C a r r i e i n co n s i d e r i n g the i o n i c mechanism. I f the i o n i c mechanism was the fav o r a b l e one, the conformer 147a (where a r y l i s trans to ester) would lead to the 2 intermediate 155 where the el e c t r o n s at C(3) were SP h y b r i d i z e d and d e l o c a l i z e d i n t o the s u b s t i t u e n t s ( n i t r i l e and es t e r ) at C(3). E l i m i n a t i o n of methyl p e r p e n d i c u l a r to the plane o f C(3) would give the (E)-cinnamate 145 which i s c o n s i s t e n t w i t h the experimental r e s u l t . S i m i l a r l y , conformer 148a would lea d to intermediate 156 and then the (Z)-crotonate 144. - 87 -Ar C 0 2 C 2 H 5 147a H 5C 2 0 2C CH 3 N 148a 6r a 2 C 2 H 5 155 H 5C 2 0 2C 156 CH 2N 2 Ar C N C 2 H / X C O 2 C 2 H 5 145 (E)-ArCH, CN \ / c n / > O 2 C 2 H 5 144 (E)-The existence of conformational e q u i l i b r i u m o f intermediates 155 and 156 was excluded because such an e q u i l i b r i u m allows r o t a t i o n around the C ( 3 ) - C ( 4 ) bond. Under t h i s c o n d i t i o n there would be no reason to exclude intermediate 157 which would lead to the (Z)-isomer of o l e f i n 145. However.the formation - 88 -6" Ar H 5 C 2 ° 2 C L / M \ C H J ; C 2 H 5 C N 3 \ 2 2. CN 6-157 145 (Z)-of the (Z)-isomer was not observed and thus i n the hypothesis of an open int e r m e d i a t e , the rearrangement must be s u f f i c i e n t l y r a p i d to exclude the p o s s i b i l i t y of r o t a t i o n around C(3)-C(4) bond. Thus the conformation of the p y r a z o l i n e remains the determining f a c t o r whether the p y r o l y s i s r e a c t i o n proceeds v i a a concerted mechanism or an open intermediate. In the present s t u d i e s , the decomposition of 3-carbomethoxy-3-cyano-4-methyl-4-phenyl-l-pyrazoline, (E) (118a) and the corresponding p-methoxy-ph e n y l p y r a z o l i n e (119) at room temperature gave a mixture of the (E)- and (Z)-isomers of a r y l o l e f i n s (134a and 134b; 137a and 137b) and the (EJ-and (Z)-isomers of benzyl and p-methoxybenzyl o l e f i n s (136a and 136b; 139a and 139b). These r e s u l t s are not c o n s i s t e n t w i t h those obtained by Hamelin and C a r r i e (21) In order t o evaluate the two p o s s i b l e mechanisms suggested by C a r r i e (21), k i n e t i c s t u d i e s of the p y r o l y s i s of 1-pyrazolines are necessary. This w i l l p rovide f u r t h e r i n f o r m a t i o n about the p o l a r i t y o f the intermediate and the degree of bond breaking of the C(3)-N and C(5)-N bonds i n the t r a n s i t i o n s t a t e . - 89 -( I I I ) K i n e t i c Studies Previous work by Snyder (75) has shown t h a t the decomposition of 1-p y r a z o l i n e s f o l l o w s f i r s t order k i n e t i c s . The r a t e expression f o r a f i r s t order decomposition r e a c t i o n i s the f o l l o w i n g , 2.305 , a o . k = — - — log 1 t 6 a -x — o where k = f i r s t order r a t e constant: a = i n i t i a l c o n c e n t r a t i o n o f the ' o re a c t a n t and x = amount of reac t a n t which has decomposed i n time i n t e r v a l t , l e a v i n g a_-x unreacted. One mole of 1-pyrazoline gives one mole of n i t r o g e n gas upon complete decomposition, hence the co n c e n t r a t i o n changes w i t h time are most conveniently f o l l o w e d by measuring the r a t e of formation o f n i t r o g e n . Expression 1_ now becomes . 2.303 . V°P _ k = - r - l o g v ^ v 1 where V°° = the volume of n i t r o g e n , at standard temperature and pressure, equivalent to the i n i t i a l c o n c e n t r a t i o n of the p y r a z o l i n e and V = the volume of n i t r o g e n , at S.T.P., equivalent to the amount of p y r a z o l i n e decomposed i n time i n t e r v a l t , l e a v i n g V ° ° - V s t i l l unreacted. A g r a p h i c a l p l o t o f the q u a n t i t y l o g V ^ / C V ^ - V ) versus t w i l l r e s u l t i n a s t r a i g h t l i n e . The slope o f the l i n e m u l t i p l i e d by 2.303 w i l l be equal to the r a t e constant, k. A l e a s t squares method of f i t t i n g the s t r a i g h t l i n e s was considered to be o f no r e a l advantage over those obtained by a g r a p h i c a l p l o t (45). Therefore, a l l r a t e constants were obtained from the best s t r a i g h t l i n e s drawn through the g r a p h i c a l p l o t s . The r e s u l t s o f the k i n e t i c s t u d i e s are summaried i n Table X , and the f i r s t order p l o t s are shown i n Figure X X I I - X X V I . TABLE X The Summary of the Rate Constants and the A c t i v a t i o n Parameters i n the P y r o l y s i s o f 1-Pyrazolines Compound Solvent No. of runs Temp. ° C Average k x 10 4 ( s e c - 1 ) A H + kcal/mole t A S e.u. Nitrobenzene 2 44.85 2.06 C-H_ 6 5 \ S CN 3 49.82 3.73 22.2 -5.67 C H r- C0 2CH 3 3 2 54.85 64.90 6.41 17.91 118a T e t r a l i n 2 54.84 2.046 C 6 H 5 \ CH. • .CN J . CO. N ^ » C ° 2 C H 3 Nitrobenzene 49.82 3.71 (a) 121 -MeOC,H 6 «i CH'*' 119 CN •C0 2CH 3 Nitrobenzene 2 2 6 2 Ca l c . C a l c . 44.85 49.82 54.84 64.90 34.95 75.23 2.52 4.26 7.3610.10 19.19 0.86 49.82 (b) 20.8 -9.58 Table X (continued) Compound Solvent No. o f runs Temp. °C Average k x 10 4 sec"-* AH + kcal/mole AS1" e .u. -MeOC.H 6 T e t r a l i n C a l c . 34. 95 0 024 j 2 54. 84 2 78 2 75. 23 27 56 D e c a l i n 2 75. 23 15 05 Formamide 2 34. 95 88 47 Nitrobenzene 2 44. 85 2 06 2 49. 82 3 77 2 54. 84 6 57 2 64. 90 18 .89 T e t r a l i n 2 54. 84 1 56 Nitrobenzene 2 54. 84 9 28 -N0 2C 6H. CN _. M CC- CH_ -_.N 2 3 23.0 -3.19 CH. -N02C6H4'-CN I * CO, ^ N N ^ 120b 0 2CH 3 (a) 0>) Value of k c o r r e c t e d to account f o r incomplete d e u t e r a t i o n (80.)• E r r o r l i m i t s are expressed as the average d e v i a t i o n from the mean. - 92 -Figure XXI - Arrhenius p l o t s f o r 3-carbomethoxy-3-cyano-4-methyl-4-a r y l - l - p y r a z o l i n e s , (E)-i - 93 -Figure XXII - F i r s t order r a t e p l o t s f o r p y r o l y s i s o f 3-carbomethoxy-3-cyano-4-methyl-4-p-nitrophenyl-l-pyrazolines, (EJ- and (ZJ-- 94 -Figure XXIII - F i r s t order r a t e p l o t s f o r p y r o l y s i s o f 3-carbomethoxy-3-cyano-4-methyl-4-p-methoxyphenyl-1-pyrazoline, (E)-(119) i n nitrobenzene and t e t r a l i n - 95 -Figure XXIV - F i r s t order r a t e p l o t s f o r p y r o l y s i s of p y r a z o l i n e 119 i n t e t r a l i n and d e c a l i n - 96 -Figure XXV - F i r s t order r a t e p l o t f o r p y r o l y s i s of p y r a z o l i n e 119 i n formamide - 97 -Figure XXVI - F i r s t order r a t e p l o t f o r p y r o l y s i s of 3-carbomethoxy-3-cyano-4-methyl-4-phenyl-l-pyrazoline, (E)~ and the corresponding 5,5-dideuterated compound i n nitrobenzene r - 98 -The a c t i v a t i o n parameters were obtained from the E y r i n g equation, 3_. k _ V -AH+/RT AS +/R 3 h e e — t t where k D = Boltzmann's constant, h = Planck's constant, and AH and AS are D the enthalpy and entropy of a c t i v a t i o n r e s p e c t i v e l y . The logarithm form of equation 3 i s : k i n T i n 1 r _ A H \ AS + . l o g T = 10.319 - 7 ( 4 ^ 7 4 ) + 4 7 5 7 4 4 _ A p l o t of l o g (k/T) vs. 1/T gave a s t r a i g h t l i n e where slope m u l t i p l i e d by "t" *t* *f* 4.574 gave AH . S u b s t i t u t i n g t h i s AH back i n t o equation 4_ gave AS . The p l o t s o f l o g (k/T) vs. 1/T are shown i n Figure XXI. The values of AH + and AS^ are given i n Table IX. There are s e v e r a l f a c t o r s which w i l l a f f e c t the accuracy of the r a t e constants and a c t i v a t i o n parameters obtained. The e r r o r s of measurement of time and of the i n i t i a l amount of p y r a z o l i n e (V 0 0) are very small (< 1%). Several groups of workers have shown (76,77) that thorough a g i t a t i o n of the r e a c t i o n s o l u t i o n i s necessary when vo l u m e t r i c measurement of an evolved gas i s to be made. The r a t e o f a g i t a t i o n o f the s o l u t i o n should be s u f f i c i e n t l y h i g h so that the r a t e of escape of n i t r o g e n from the s o l u t i o n i s not r a t e determining. The magnetic s t i r r i n g employed i n t h i s work gave thorough and r e p r o d u c i b l e a g i t a t i o n of the r e a c t i o n s o l u t i o n as demon-s t r a t e d by the good r e p r o d u c i b i l i t y of the k i n e t i c r e s u l t s . The temperature of the o i l bath was kept to w i t h i n - 0.05°. However, the accuracy of the temperature readings i s decreased when stem c o r r e c t i o n s are necessary. The temperatures are considered accurate to ± 0.1° or b e t t e r . From equation 4, t h i s temperature v a r i a t i o n corresponds to an e r r o r of about 1-2% i n . - 99 -the r a t e constant. With the other f a c t o r i n c l u d e d the average e r r o r i n the r a t e constant w i l l be c l o s e t o i 3%. The maximum e r r o r i n the values f o r A H ^ i s estimated to be about t 5%. A s m a l l v a r i a t i o n i n the value f o r A H ^ r e s u l t s i n a r e l a t i v e l y l a rge v a r i a -t t t i o n i n the value f o r A S . Hence the e r r o r i n the values f o r A S given i n Table X can be as great as ±2-4 e.u. The f o l l o w i n g checks were made to show th a t a l a r g e change i n the c o n c e n t r a t i o n of the p y r a z o l i n e d i d not a f f e c t the r a t e o f decomposition: ( i ) The r a t e of pyrolysis of 3-carbomethoxy-3-cyano-4-methyl-4-p-methoxy-p h e n y l - l - p y r a z o l i n e , (E)- (119) was determined i n nitrobenzene at 54.84° by the u s u a l procedure (V ca. 40 ml). However, a known amount of p y r a z o l i n e 119 was added t o nitrobenzene so t h a t ( c a l c . ) became 53.68 ml, i . e . , the c o n c e n t r a t i o n o f p y r a z o l i n e was increased approximately 40%. The r a t e - 4 - 1 constant obtained was 7.71 x 10 sec , reasonably comparable to the average -4 -1 value of 7.36 x 10 sec obtained when the usual c o n c e n t r a t i o n was employed. ( i i ) Another known amount of the (E)-p-methoxyphenylpyrazoline 119 was used i n nitrobenzene at 54.84° so t h a t V ( c a l c . ) equaled to 18.79 ml., i . e . , the c o n c e n t r a t i o n of p y r a z o l i n e was decreased over 50%. The r a t e - 4 - 1 ' -4 constant obtained, 7.64 x 10 sec , was i n good agreement w i t h 7.36 x 10 sec obtained from runs made at normal c o n c e n t r a t i o n . ^ I t was observed i n some cases that the p l o t s of l o g V /(V^-V^) vs* time f a i l e d to show a l i n e a r r e l a t i o n s h i p during the f i r s t 10% of the r e a c t i o n time as expected for a f i r s t order k i n e t i c s p l o t . This was probably due to the a d d i t i o n of s o l i d p y r a z o l i n e i n t o solvent which took a c e r t a i n time t o d i s s o l v e and e q u i l i b r a t e w i t h the s o l v e n t . - 100 -(IV) Mechanistic Considerations A survey o f the l i t e r a t u r e i n d i c a t e s t h a t there are four major mechanisms f o r p y r a z o l i n e p y r o l y s i s proposed by d i f f e r e n t groups of workers ( f o r d e t a i l see I n t r o d u c t i o n ) : ( i ) concerted, ( i i ) i r-cyclopropene intermediate ( i i i ) d i r a d i c a l ( i v ) i o n i c . . The present d i s c u s s i o n i s to propose one of these mechanisms f o r the p y r o l y s i s o f 1-pyrazolines studded i n t h i s work. -In order to i n v e s t i g a t e the mechanism one must consider the t r a n s i t i o n s t a t e of the r e a c t i o n . -( i ) E f f e c t of Deuterium S u b s t i t u t i o n at C(5) The d e s c r i p t i o n of the t r a n s i t i o n s t a t e f o r the p y r a z o l i n e p y r o l y s i s must begin w i t h d i s c u s s i o n on the degree of bond breaking of the carbon-n i t r o g e n bonds. In p a r t i c u l a r , does one carbon-nitrogen bond break before the other to give a n i t r o g e n c o n t a i n i n g i n t e r m e d i a t e , f o r example 123a, and 123b, or i s there simultaneous rupture of both carbon-nitrogen bonds as found by Crawford and coworkers? The study o f isotope e f f e c t s on r e a c t i o n r a t e s has developed i n t o a v a l u a b l e mechanistic t o o l (77). S e l t z e r has e x t e n s i v e l y s t u d i e d the p y r o l y s i s of a c y c l i c azo compounds. K i n e t i c s t u d i e s on the p y r o l y s i s of azobis-a-phenylethane (158) (79), a-phenylethylazo-2-propane (159) (80), a-phenyl-ethylazomethane (160) (81) and a-deuterium d e r i v a t i v e s o f these compounds have shown th a t f o r 158 both carbon-nitrogen bonds are breaking e q u a l l y i n the t r a n s i t i o n s t a t e , f o r 159 both carbon-nitrogen bonds are breaking simultaneously but to a d i f f e r e n t degree and f o r 160 only the a-phenylethyl carbon-nitrogen bond i s breaking i n the t r a n s i t i o n s t a t e . These r e s u l t s have been r e c e n t l y c o r r e l a t e d with a primary n i t r o g e n isotope e f f e c t (82). S e l t z e r reported t h a t the secondary a-deuterium isotope e f f e c t i n the - 101 -r a d i c a l decomposition of azobis-a-phenylethane-a,a-d2 i s k^Ap = 1-27 (73). The secondary a-deuterium e f f e c t has been found to r e s u l t i n k^A^ - 1.15 per deuterium atom f o r a considerable number of " l i m i t i n g " s o l v o l y t i c r e a c t i o n s (83,84). Since the e f f e c t found by S e l t z e r i s approximately twice as l a r g e as those encountered i n r e a c t i o n s l e a d i n g to the breaking of one bond, i t was taken as evidence f o r both C-N bonds breaking simultaneously i n the t r a n s i t i o n s t a t e o f the r a t e - c o n t r o l l i n g step. H,C CH, H,C CH, 3, I 3 3 | I 3 1 slow 1 1 <f> — C — N — N C <i> > <j> — C N=N C — $ I I I I H(D) H(D) H(D) H(D) I t was suggested (18) t h a t c y c l i c azo compounds such as p y r a z o l i n e s might behave i n a s i m i l a r manner. Crawford found s i m i l a r secondary k i n e t i c i s o tope e f f e c t s f o r a number of a - d e u t e r a t e d - l - p y r a z o l i n e s (35,85), f o r example, k H A D = 1.55 ( c o r r e c t e d to 1 05°) f o r the_>pyrolysis of 1-pyrazoline-3,3,5,5-d^ (86). This l a r g e e f f e c t i s expected i f both carbon-nitrogen bonds are undergoing simultaneous cleavage i n the t r a n s i t i o n s t a t e . Recently, the secondary k i n e t i c isotope e f f e c t o f some unsymmetric 1-p y r a z o l i n e s , 3-methyl-3-carbomethoxy-l-pyrazoline (49), 3-methyl-3-cyano-l-p y r a z o l i n e (51) and t h e i r C-5 dideuterated compounds have been s t u d i e d (45). In n - b u t y l ph t h a i ate k^Ap of both p y r a z o l i n e s 49 and 51_ gave a value of 1.22 which corresponds t o a t r a n s i t i o n s t a t e where the C(5)-N bond i s breaking. The r a t e constants f o r 3-carbom?thoxy-3-cyano-4-methyl-4-phenyl-l-p y r a z o l i n e , (E)- (118a) and the corresponding 5,5-dideuterated p y r a z o l i n e (121) are given i n Table X. - 102 -V CN CN N 118a 121 In nitrobenzene at 49.82 k /k = k (118a)/k(121) = 3.73/3.71 = 1.03 i 0.01 The above secondary a-deuterium isotope e f f e c t corresponds to a t r a n s i t i o n s t a t e where the C(5)-N bond i s not breaking. The e f f e c t o f a-deuterium s u b s t i t u t i o n on the product d i s t r i b u t i o n i s s m a l l . Table VI shows t h a t the p y r o l y s i s o f 5,5-dideuterated p y r a z o l i n e 121 gives a s m a l l e r amount of cyclopropane than f o r the p y r o l y s i s of the parent compound 118a. I f the C(5) deuterium s u b s t i t u t i o n e f f e c t s the C(4) to C(5) m i g r a t i o n a change i n the amount of a,B-unsaturated e s t e r would be expected. A s l i g h t i n c r e a s e i n phenyl m i g r a t i o n was observed i n s t e a d . These f a c t o r s suggest t h a t the e f f e c t of deuterium s u b s t i t u t i o n at C(5) i s to s l i g h t l y decrease the r a t e of cyclopropane formation which i s l e s s than 15% of t o t a l r e a c t i o n product. The a-deuterium k i n e t i c i s o t o p e e f f e c t found i n t h i s work c l e a r l y suggests that a n i t r o g e n f r e e intermediates such as 161, 162 or 163 i s not formed. I t t h e r e f o r e r u l e s out the "tT-cyclopropane" intermediate 163 suggested by Crawford (48). Since the C(5)-N bond i s not breaking i n the t r a n s i t i o n s t a t e , the concerted mechanism (18,44), which i n v o l v e s bond cleavages of both C(5)-N(l) and C(3)-N(2) bonds i n the t r a n s i t i o n s t a t e w i t h - 103 -Ar > CN Ar ' CN J \ J CH„. „Ar CH3* j 'COOCHj CHj 161 162 'C00CH3 H C00CH 3 simultaneous trans m i g r a t i o n of a group from C(4) to C(5) t o gi v e the o l e f i n products, i s a l s o not a p p l i c a b l e i n the present work. The intermediate o f p y r o l y s i s o f 3-carbomethoxy-3-cyano-4-methyl-4-aryl-l-pyrazoline 118a, must be a n i t r o g e n c o n t a i n i n g intermediate such as 123a, 164 or 165. Since the p y r o l y s i s of p y r a z o l i n e s 119, 120a, 118b and 120b proceed w i t h h i g h l y s i m i l a r product d i s t r i b u t i o n , r a t e constants i n d i f f e r e n t s o l v e n t s and a c t i v a t i o n parameters to those of phe n y l p y r a z o l i n e 118a, i t would appear h i g h l y probable t h a t intermediate o f the type 123a, 164 or 165 are a l s o i n v o l v e d i n the p y r o l y s i s o f these p y r a z o l i n e s . Ar CN Ar ^  > CN Ar ^  . CN <J*> COOCH. 3 > ' COOCH, 3 " 123a 164 165 Ion p a i r intermediate 123a represents one where the C(3)-N bond i s broken h e t e r o l y t i c a l l y . Intermediates r e s u l t i n g from the homolytic cleavage of C(3)-N bond i s represented by the d i r a d i c a l intermediate 164. Free r o t a t i o n around the C(3)-C(4) bond i n the i o n p a i r intermediate 123a and d i r a d i c a l intermediate 164 i s p o s s i b l e . Intermediate 165 represents a h e t e r o l y t i c cleavage o f C(3)-N bond with r e s t r i c t i o n o f r o t a t i o n around C(3)-C(4) bond due t o e i t h e r the e l e c t r o s t a t i c f o r c e between C(3) and N i n the t r a n s i t i o n s t a t e or the l i f e time o f intermediate 123a being too short to a l l o w any r o t a t i o n around C(3)-C(4). - 104 -( i i ) Solvent E f f e c t s and A c t i v a t i o n Parameters of P y r o l y s i s Solvent e f f e c t s on decomposition r a t e s should y i e l d i n f o r m a t i o n on the p o l a r i t y o f the t r a n s i t i o n s t a t e , and h o p e f u l l y would allow one to s e l e c t the best r e p r e s e n t a t i o n of the intermediate of p y r o l y s i s from among the three p o s s i b l e n i t r o g e n - c o n t a i n i n g intermediates 123a, 164 and 165. A p r e l i m i n a r y study (32) of so l v e n t e f f e c t s on the p y r o l y s i s o f 3-carbomethoxy-3-cyano-4,4-dim e t h y l - 1 - p y r a z o l i n e (25) and 3-carbomethoxy-3-cyano-4,4-cyclopentane-l-p y r a z o l i n e (70) showed that the p o l a r i t y of the so l v e n t has a marked e f f e c t on the r a t e o f decomposition. The h a l f - l i f e f o r the thermal decomposition o f p y r a z o l i n e s 2_5 and 70_ was found t o i n c r e a s e w i t h an i n c r e a s e i n solvent p o l a r i t y . This i s shown i n Table XI. A l a r g e r solvent dependence f o r 3-carbomethoxy-3-cyano-4-methyl-4-aryl-l-pyrazolines 118a, 119 and 120a has been observed i n the Table XI C a l c u l a t e d h a l f - l i v e s f o r p y r o l y s i s o f 3-carbomethoxy-3-cyano-4,4-d i a l k y l - l - p y r a z o l i n e s (25 and 70). Solvents x\/2 a t 5 3 ° f o r — t l / 2 a t 2 0 ° f o r — 23 98 16 — — 65 13 19 -i 0.5 k i n e t i c s t u d i e s reported here. The r a t e of p y r o l y s i s of the (E)-p-methoxy-ph e n y l p y r a z o l i n e 119 increases upon going from d e c a l i n to formamide (Table X).. The r e l a t i v e r a t e constant o f t h i s p y r a z o l i n e 119 i n d e c a l i n , t e t r a l i n and nitrobenzene at 75.23° are 1:1.83:3.30 and t h a t i n t e t r a l i n , nitrobenzene 3 and formamide at 34.95° are 1:35.8:3.68 x 10 . The corresponding (E)-B u t y l ether T e t r a l i n Benzene Nitrobenzene Formamide - 105 -p h e n y l p y r a z o l i n e 118a and ( E ) - p - n i t r o p h e n y l p y r a z o l i n e 120a showed a s i m i l a r order of r e l a t i v e r a t e constants i n d i f f e r e n t s o l v e n t s as that of p y r a z o l i n e 119. For example, i n t e t r a l i n and nitrobenzene at 54.84°, the r e l a t i v e r a t e constant f o r (E)-p-methoxyphenylpyrazolene 119 was 1:2.65, whereas that f o r (E)-phenylpyrazoline 118a was 1:3.2 and that f o r ( E ) - p - n i t r o p h e n y l p y r a z o l i n e 120a was 1:4.2. -The formation of a z w i t t e r i o n should be f a c i l i t a t e d much more by an increase of solvent p o l a r i t y . The r a t e of c y c l o a d d i t i o n of tetracyanoethylene w i t h 4-methoxystyrene shows a solvent dependence of n e a r l y 10^, the quaterniz-a t i o n o f t r i p r o p y l a m i n e w i t h methyl i o d i d e a l s o has a spread o f 10^, and 3 the a d d i t i o n of p i p e r i d i n e t o methyl p r o p i o l a t e one of 10 over the solvent range cyclohexane t o a c e t o n i t r i l e ( 8 7 ) . The r e l a t i v e r a t e constants o f (E)-p-methoxyphenylpyrazoline 119 i n d e c a l i n , t e t r a l i n and nitrobenzene increase moderately. However, comparison of r a t e constants in.these 3 s o l v e n t s w i t h that i n formamide at 34.95° gives a spread of over 10 . Furthermore, the r e s u l t r e p o r t e d here i s d e f i n i t e l y d i f f e r e n t from the s o l v e n t effect on the decomposition r a t e of 3-carbomethoxy-3-methyl-l-pyrazoline (49) and 3-cyano-3-methyl-1-pyrazoline (51) where the r a t e of p y r o l y s i s were found to decrease w i t h i n c r e a s i n g solvent p o l a r i t y (45) as shown i n Table X I I . These r e s u l t s thus suggest that there i s some charge develop-ment i n the t r a n s i t i o n s t a t e of p y r o l y s i s of 3-carbomethoxy-3-cyano-4-methyl-4 - a r y l p y r a z o l i n e s 118a, 119, 120a, 118b and 120b. Since the secondary k i n e t i c i sotope e f f e c t i n d i c a t e s t h a t the C(5)-N bond i s not breaking i n the t r a n s i t i o n s t a t e , the p o l a r i t y of the intermediate would then a r i s e only from the h e t e r o l y t i c cleavage of the C(3)-N bond. The d i r a d i c a l intermediate 164 i s not considered t o be a h e l p f u l r e p r e s e n t a t i o n of the intermediate i n - 106 -Table XII Rate constants of p y r o l y s i s of 3-carbomethoxy-3-methyl-l-pyrazoline -1 4 (49) and 3-cyano-3-methyl-l-pyrazoline (51) , sec x 10 Solvents 49 at 127° 51_ at 109.4° T e t r a l i n 7.31 7.68 n-Buty l p h t h a l a t e 5.63 7.34 Nitrobenzene 3.81 4.03 Formamide 2.54 the present s t u d i e s of p y r o l y s i s . This intermediate would a r i s e as a r e s u l t o f homolytic cleavage. The c o n c l u s i o n t h a t the d i r a d i c a l intermediate i s not a good r e p r e s e n t a t i o n of the intermediate i s f u r t h e r supported by the a c t i v a t i o n parameters of the p y r o l y s i s o f 1-pyrazolines. The a c t i v a t i o n energy of the p y r o l y s i s r e a c t i o n both i n the vapour phase (36,88) and i n s o l u t i o n (45) has been e x t e n s i v e l y s t u d i e d . In vapour phase (88), Ea, the a c t i v a t i o n energy, of d i f f e r e n t p y r a z o l i n e p y r o l y s e s was found to be 36-42 kcal/mole whereas AS^, the entropy of a c t i v a t i o n , was 4-11 e.u. depending on the number of methyls t s u b s t i t u t e d i n the molecules. In s o l u t i o n (45), AH , the enthalpy of t a c t i v a t i o n , was found to be 27-37 kcal/mole and AS , entropy of a c t i v a t i o n , 0.6-16 e.u. depending on the s u b s t i t u e n t s on the molecules and the s o l v e n t s used. Both Cohen and Crawford (36,88) suggest the r a d i c a l intermediate on the b a s i s o f the h i g h value of the entropy of a c t i v a t i o n obtained being c o n s i s t e n t w i t h the simultaneous rupture of two C-N bonds to form a b i r a d i c a l . A concerted mechanism f o r the o l e f i n - f o r m i n g r e a c t i o n from p y r a z o l i n e p y r o l y s i s i n s o l u t i o n was suggested (45) on the b a s i s o f a secondary deuterium k i n e t i c i s otope e f f e c t at C(5) and a primary k i n e t i c i s otope e f f e c t at the C(4) p o s i t i o n . - 107 -The present i n v e s t i g a t i o n of a c t i v a t i o n parameters f o r p y r o l y s i s o f p y r a z o l i n e s 118a, 119 and 120a shows values d e f i n i t e l y d i f f e r e n t from those c i t e d above. The enthalpy o f a c t i v a t i o n , AH^, f o r these p y r a z o l i n e s i s f 22.2, 20.8 and 23.0 kcal/mole and entropy of a c t i v a t i o n , AS , i s -5.7, -9.6, and -3.2 e.u. r e s p e c t i v e l y . The low enthalpy o f a c t i v a t i o n observed here i n comparison w i t h the r e s u l t o f Crawford (88) and Masters (45) suggested a d i f f e r e n t low energy r e a c t i o n pathway f o r the present s t u d i e s o f p y r o l y s i s . The low energy o f a c t i v a t i o n i s probably due to.the s t a b i l i z a t i o n o f the anion formed at C(3) i n the intermediate by the e l e c t r o n withdrawing s u b s t i t u e n t s at C(3). This suggestion i s considered to be j u s t i f i e d s i n c e Crawford (88) suggested the b i r a d i c a l intermediate on the b a s i s of the decrease i n a c t i v a t i o n energy due to s t r a i n r e l i e f i n 2,3-diazobicyclo[2.2,l]hept-2-ene (35) (E = 36.9 kcal/mole) i n comparison w i t h c i s 3, 5 - d i m e t h y l - l - p y r a z o l i n e 166 (E = 40.3 k c a l ) . The enthalpy o f a c t i v a t i o n f o r the present work i s ca. 13-20 kcal/mole lower than that observed by Crawford and 4-15 kcal/mole lower than that observed by Masters. These d i f f e r e n c e s i n enthalpy o f t a c t i v a t i o n are much grea t e r than the AAH of pyrazolines 35_ and 166 a t t r i b u t e d to s t r a i n r e l i e f . 35 166 - 108 -The entropy o f a c t i v a t i o n , AS^, found i n the present work i s small and negative whereas that o f the other p y r a z o l i n e s i s c o n s i s t e n t l y small and p o s i t i v e . A unimolecular d i s s o c i a t i o n r e a c t i o n where the t r a n s i t i o n s t a t e must be a much loo s e r c o l l e c t i o n o f atoms because o f the extensive bond breaking that occurs (and thus allows more t r a n s l a t i o n a l and v i b r a t i o n a l degrees o f freedom than i s p e r m i s s i b l e i n the o r i g i n a l molecule) i s l i k e l y to have a p o s i t i v e entropy o f a c t i v a t i o n l i k e those shown by Crawford and Masters. Negative entropy of a c t i v a t i o n i m p l i e s that ( i ) the r e s t r i c t i o n on motion i n the t r a n s i t i o n s t a t e i s grea t e r than that i n the i n i t i a l s t a t e or ( i i ) there i s formation of charge i n the t r a n s i t i o n s t a t e which " f r e e z e s " out the solvent molecules (89). The o r i e n t a t i o n o f solvent molecules around an i o n g r e a t l y r e s t r i c t s i t s freedom o f motion and r e s u l t s i n negative entropy of a c t i v a t i o n . Since the present r e a c t i o n i s a unimolecular r e a c t i o n , the f i r s t f a c t o r cannot be the c o n t r i b u t i n g f a c t o r f o r negative entropy o f a c t i v a t i o n . The negative value thus suggests an i o n i c c h a r a c t e r i n the t r a n s i t i o n s t a t e as i l l u s t r a t e d i n intermediates 123a or 165. _________ ( Since an i o n p a i r intermediate i s considered to be the h e l p f u l represent-a t i o n f o r the present s t u d i e s , two explanations are provided f o r the stereo-s p e c i f i c i t y of the o l e f i n products formed: ( i ) the intermediate can not have f r e e r o t a t i o n around the C(3)-C(4) bond. R e s t r i c t i o n of t h i s r o t a t i o n i m p l i e s t h a t there i s some bonding ( e i t h e r i o n i c or p a r t i a l l y covalent) between C(3) and N i n the t r a n s i t i o n s t a t e . With r o t a t i o n r e s t r i c t e d around the C(3)-C(4) bond, the r e a c t i o n o f an intermediate w i l l s t i l l be i n f l u e n c e d by s t e r i c f a c t o r s present i n the o r i g i n a l p y r a z o l i n e , ( i i ) i f there i s r o t a t i o n around the C(3)-C(4) bond then the r a t e of formation of o l e f i n product form t h i s intermediate i s much f a s t e r than the r a t e of bond r o t a t i o n . - 109 The moderate solvent e f f e c t on r a t e of p y r o l y s i s i n d e c a l i n , t e t r a l i n and nitrobenzene favours the f i r s t e x p l a n ation. In formamide the r a t e i s 3 10 times f a s t e r ; , t h i s may be the r e s u l t o f C(3)-N bond being more p o l a r i n formamide than i n the f i r s t three s o l v e n t s . Thus, the r e s u l t s of the s t e r e o s p e c i f i c i t y of the o l e f i n products formed i n d i c a t e that intermediate 165 i s the best r e p r e s e n t a t i o n of the intermediate formed from p y r o l y s i s o f 3-carbomethoxy-3-cyano-4-methyl-4-a r y l - l - p y r a z o l i n e s . ( i i i ) M i g r a t o r y Aptitudes In order to understand the mechanism of p y r o l y s i s , the migratory ap t i t u d e s o f d i f f e r e n t groups, hydrogen, methyl, phenyl, p-methoxyphenyl and p - n i t r o p h e n y l , from C(4) to C(5) of 1-pyrazolines were s t u d i e d i n the present work. A vast amount of work has been done i n the f i e l d o f 1,2-s h i f t s , such as p i n a c o l rearrangements, i n which carbonium ions are i n v o l v e d . In general, a r y l groups c o n t a i n i n g e l e c t r o n donating s u b s t i t u e n t s i n the p a r a - p o s i t i o n i n v a r i a b l y migrate i n preference to phenyl i n carbonium ions. In p a r t i c u l a r , p-methoxyphenyl, without exception, migrates i n preference t o phenyl (90-92). A r y l groups c o n t a i n i n g p a r a - e l e c t r o n withdrawing groups (e.g., NO-, CN, CI etc.) are i n v a r i a b l y poorer m i g r a t i n g groups than phenyl i n 1,2-aryl migrations to e l e c t r o n d e f i c i e n t centers (93,94). The gross d i s t i n c t i o n s among a r y l groups, a l k y l groups and hydrogen atoms i n the m a j o r i t y of rearrangements, once the carbonium ions are formed,are that hydrogen atoms migrate i n preference to a r y l groups and a r y l groups i n t u r n migrate i n preference to a l k y l groups (95,96).' R e l a t i v e l y few s t u d i e s have been c a r r i e d out on the migratory aptitudes of d i f f e r e n t a r y l groups i n r a d i c a l rearrangements. B a r t l e t t and Cotman - 1 1 0 -(93) found that the thermal decomposition o f n i t r o - s u b s t i t u t e d peroxide (167) i n benzene y i e l d approximately four times as much p-nitrophenol as phenol, i n c o n t r a s t to the a c i d c a t a l y z e d decomposition of 167 i n which no benzo-phenone was observed. <J> p-nitrophenol (32%) 1 A ' (j>-C-C-0-H — - — • phenol (8-10%) p-NC^-C^-H^ £-nitrobenzophenone (14%) p - n i t r o t r i p h e n y l c a r b i n o l (23%) 167 biphenyl (trace) This r e s u l t showed t h a t p - n i t r o p h e n y l had a grea t e r migratory a p t i t u d e (ca. 8 to 1) than phenyl. C u r t i n and K a r i e r (97) found t h a t treatment o f 3,3 -diphenyl-3-p-nitrophenylpropionaldehyde(168) w i t h t e r t i a r y - b u t y l peroxide at 140° gave predominantly 2-p-nitrophenyl-l,1-diphenylethylene (169) as. the rearranged product. The migratory a p t i t u d e of p- n i t r o p h e n y l was estimated to be at l e a s t 8 times that of phenyl. <j> <J> H • t BuO • ' <f>-C-CH2-CH0 1 4 Q O » 4>-C-CH2 * cf>2C=C-C6H4N02-p p-N0 2C 6H 4 P " N 0 2 C 6 H 4 168 169 The e f f e c t o f the p-methoxy group on a r y l 1,2 r a d i c a l m i g r a t i o n are l e s s c l e a r cut. However, s t u d i e s on the d i s s o c i a t i o n o f hexaarylethanes have shown that s u b s t i t u e n t s which should be capable o f s t a b i l i z i n g the r e s u l t i n g t r i a r y l m e t h y l r a d i c a l s (e.g., p-CH^, p-NC>2, p-OCH^, etc.) do indeed enhance the degree of d i s s o c i a t i o n (98-102). Results showed t h a t p-methoxyphenyl enhances the d i s s o c i a t i o n constant of hexaarylethane by a - I l l -f a c t o r o f 4 r e l a t i v e to phenyl. F i n a l l y , the preference of p-methoxyphenyl over phenyl i n 1,2-migration t o a r a d i c a l center was r e c e n t l y shown i n the p h o t o l y s i s of 4-phenyl-4-p-methoxyphenylcyclohex-2-ene-l-one (103). The 1,2-aryl migratory aptitudes to a r a d i c a l center are p - n i t r o p h e n y l migrates i n preference to p-methoxyphenyl which migrates i n preference to phenyl. In the present s t u d i e s o f p y r a z o l i n e p y r o l y s i s , hydrogen i n v a r i a b l y migrates i n preference to any a r y l groups. This i s shown i n the decomposition of 3-carbomethoxy-3-cyano-4-aryl-l-pyrazoline intermediates 9£ to 96, 3-carbomethoxy-4-phenyl-2-pyrazoline (124) and 3-carbomethoxy-3-methyl-4-p h e n y l - l - p y r a z o l i n e (117) where hydrogen and p - s u b s t i t u t e d a r y l s are the s u b s t i t u e n t s at the C(4) p o s i t i o n s o f the 1-pyrazoline. L i t e r a t u r e r e s u l t s (25,26) a l s o show that when hydrogen i s one of the s u b s t i t u e n t s at C(4), the.... o l e f i n s formed from p y r o l y s i s c o n s i s t e n t l y are the r e s u l t o f hydrogen m i g r a t i o n to e i t h e r the C(5) or C(3) p o s i t i o n s . The migratory a p t i t u d e s between a r y l and methyl groups are l e s s s t r a i g h t f o r w a r d For 3-carbomethoxy-3-cyano-4-methyl-4-aryl-l-pyrazolines, (E)- (118a, 119 and 120a) where methyl and a r y l s are the s u b s t i t u e n t s at the C(4) p o s i t i o n and where a r y l groups are trans, to the carbomethoxy groups, . methyl migrates to the C(5) p o s i t i o n to y i e l d o l e f i n i c products to a l a r g e r extent than a r y l groups i n a s i m i l a r m i g r a t i o n . On the other hand, f o r the corresponding (Z_)-aryl p y r a z o l i n e s 118b and 120b where methyl and a r y l s are the s u b s t i t u e n t s at the C(4) p o s i t i o n but where a r y l groups are c i s t o carbomethoxy groups, m i g r a t i o n o f methyl to the C(5) p o s i t i o n to y i e l d o l e f i n i c products was not observed i n e i t h e r case. Two f a c t o r s are thus considered to be important f o r p y r o l y s i s of 1-pyrazolines: ( i ) the stereochemistry of s u b s t i t u e n t s at C(4) r e l a t i v e to s u b s t i t u e n t s at C(3) - 112 -( i i ) the migratory aptitudes between the two s u b s t i t u e n t s at the C(4) p o s i t i o n . The stereochemistry of a r y l groups r e l a t i v e to the s u b s t i t u e n t s " at the C(3) p o s i t i o n i n the ( Z ) - p y r a z o l i n e s 118b and 120b i s the same as t h a t of methyl r e l a t i v e to the s u b s t i t u e n t s at C(3) i n the ( E ) - p y r a z o l i n e s 118a, 119 and 120a. The lack of methyl m i g r a t i o n i n the ( Z ) - p y r a z o l i n e 118b and 120b thus i n d i c a t e s t h a t , other f a c t o r s being equal, a r y l groups migrate from C(4) to C(5) to give o l e f i n i c products i n preference to the methyl. The major methyl m i g r a t i o n observed i n the ( E ) - p y r a z o l i n e s suggests th a t the stereochemistry of s u b s t i t u e n t s p l a y a more important p a r t than the migratory a p t i t u d e s of these two s u b s t i t u e n t s . I t has been suggested by McGreer (32) that groups c i s to carbomethoxy groups appear to be i n a b e t t e r p o s i t i o n f o r m i g r a t i o n . The f a c t that the r a t e constant of p y r o l y s i s of the ( Z ) - p - n i t r o p h e n y l p y r a z o l i n e 120b where a r y l i s c i s to the carbomethoxy group i s 1.4 times f a s t e r than that of the corresponding (E)-isomer 120a where a r y l i s trans t o the carbomethoxy group suggests the stereochemistry of p y r a z o l i n e 120b being a p r e f e r a b l e one f o r m i g r a t i o n . The hydrogen at C(4), on the other hand, migrates p r e f e r e n t i a l l y whether c i s or trans to the e s t e r group (44). Thus the migratory aptitudes of s u b s t i t u e n t s at the C(4) p o s i t i o n to C(5) of 1-pyrazolines t o y i e l d o l e f i n i c products are:hydrogen migrates i n preference to a r y l groups which migrate i n preference to a l k y l groups. This i s the same order as observed f o r m i g r a t i o n t o a carbonium i o n center.. The migratory a p t i t u d e s between d i f f e r e n t a l k y l groups can be observed i n p y r o l y s i s of 4-alkyl-4-methyl-3,3-dicyano-l-pyrazolines 170 (104) where the stereochemistry o f the two d i f f e r e n t a l k y l groups r e l a t i v e to the cyano groups at C(3) i s the same. The more h i g h l y s u b s t i t u t e d a l k y l groups - 113 -are i n v a r i a b l y the mi g r a t i n g groups. = 1, 2 or 3 170 The migratory aptitudes o f d i f f e r e n t a r y l groups can be derived from the percentage o f d i f f e r e n t p y r o l y s i s products o f the ( E ) - a r y l p y r a z o l i n e 118a, 119 and 120a l i s t e d i n Tables V, VI and V I I . I t has been suggested by McGreer (18) th a t the mechanism o f the formation o f cyclopropane d e r i v a -t i v e from 1-pyrazolines i s d i f f e r e n t from t h a t o f o l e f i n i c d e r i v a t i v e s . Since the percentages o f cyclopropanes formed are mostly l e s s than 15%, the migratory aptitudes of p-methoxyphenyl, phenyl and p- n i t r o p h e n y l can be c a l c u l a t e d r e l a t i v e to the percentages o f m i g r a t i o n o f methyl groups i n the same p y r a z o l i n e s . Table X I I I shows that the m i g r a t i o n of a r y l versus methyl i s such t h a t p-methoxyphenyl > phenyl > p- n i t r o p h e n y l i n benzene and t e t r a l i n as p y r o l y s i s solvents. This i s the same order as that expected f o r 1,2-aryl migrations to carbonium i o n center. The migratory order o f these a r y l groups thus f u r t h e r i n d i c a t e s t h a t the i o n i c intermediate 165 i s the best r e p r e s e n t a t i o n s i n c e the order o f 1,2-aryl migrations to r a d i c a l centers i s p - n i t r o p h e n y l > p-methoxyphenyl > phenyl. The f a c t t h a t the r a t e constant for the ( E ) - a r y l p y r a z o l i n e s 118a, 119 and 1 2 0 a . e s p e c i a l l y the (E)-phenylpyrazoline 118a and the (E)-p-n'itrophenyl-p y r a z o l i n e s 120a.are r e l a t i v e l y the same i n the same s o l v e n t , yet the product d i s t r i b u t i o n s are d i f f e r e n t f o r these p y r a z o l i n e s suggests the e l e c t r o n i c - 114 -Table X I I I R e l a t i v e m i g r a t i o n between a r y l s and methyls i n 3-carbomethoxy-3-cyano-4-methyl-4-aryl-l-pyrazolines, (E)-Solvent Ar % o f CH^ m i g r a t i o n % of Ar m i g r a t i o n M i g r a t i o n o f Ar/CH^ C 6 H 6 p-MeOC.H. — 6 4 47.0 41.2 0.78 C 6 H 5 53.6 30.6 - 0.57 n P - N 0 2 C 6 H 4 58.9 20.3 0.35 C6 H5 N°2 p-MeOC-H. — 6 4 51.9 38.3 0.74 I I C 6 H 5 54.8 32.1 0.575 I I p-N0 2C 6H 4 49.2 34.3 0.695 T e t r a l i n p-MeOC6H4 50.0 44.5 0.89 I I C 6 H 5 50.0 32.4 0.65 it p-N0 2C 6H 4 54.5 20.6 0.38 e f f e c t o f the a r y l groups pla y s an important r o l e only i n the product forma-t i o n step but not i n the rate-determining formation of the intermediate. This c o n s t i t u t e s f u r t h e r evidence against a la r g e development o f p o s i t i v e charge on C(5) i n the t r a n s i t i o n s t a t e . Summary of Mechanistic Conclusions Seven independent types of evidence having some bearing on the mechanism i n v o l v e d i n the p y r o l y s i s o f 3-carbomethoxy-3-cyano-4-aryl-4-methyl-l-p y r a z o l i n e s have been obtained. These are: ( i ) determination o f the C(5) deuterium k i n e t i c i s otope e f f e c t , ( i i ) the e f f e c t o f solvent p o l a r i t y on the r a t e o f r e a c t i o n , ( i i i ) determination of enthalpy of a c t i v a t i o n , (iv)._ determination o f the entropy o f a c t i v a t i o n ; (v) i n v e s t i g a t i o n of migratory ) aptitu d e s of a v a r i e t y of groups; ( v i ) determination of the e f f e c t of stereo-chemistry o f the p y r a z o l i n e on that of the product, and ( v i i ) i n v e s t i g a t i o n o f the e f f e c t o f C(4) s u b s t i t u t i o n on the r a t e of r e a c t i o n . - 115 -The l a c k o f any k i n e t i c i s o t o p e e f f e c t has been u t i l i z e d to r u l e out f u r t h e r c o n s i d e r a t i o n o f a concerted mechanism or the mechanism i n v o l v i n g a TT-cyclopropane intermediate s i n c e the C(5)-N bond has c l e a r l y not been broken i n the r a t e - c o n t r o l l i n g step. The l a c k o f any appreciable r a t e depend-ence on the nature of the C(4) s u b s t i t u e n t and the marked r a t e dependence on solvent p o l a r i t y are a l s o i n c o n s i s t e n t w i t h these two mechanisms. The two remaining mechanisms are those i n which the C(3)-N bond i s broken i n the rate-determining step, e i t h e r by homolytic cleavage to give a d i r a d i c a l i ntermediate or by h e t e r o l y t i c cleavage to g i v e an i o n p a i r . The l a t t e r mechanism i s favoured on the b a s i s o f the marked r a t e dependence on s o l v e n t , the values f o r both a c t i v a t i o n parameters ( i n p a r t i c u l a r , the negative entropy o f a c t i v a t i o n ) and the order o f the migratory a p t i t u d e s found.. Sinc e , however, the r e a c t i o n i s s t e r e o s p e c i f i c , i t i s c l e a r that a f r e e i o n i n which stereochemistry at C(3) r e l a t i v e to C(4) can be l o s t , i s not i n v o l v e d . A c c o r d i n g l y an intermediate i s favoured i n which some i o n i c i n t e r a c t i o n between N and C(3) i s s t i l l remaining. EXPERIMENTAL General B o i l i n g p o i n t s were determined by micro i n v e r t e d c a p i l l a r y method (105) and m e l t i n g p o i n t s were recorded on a Fisher-Johns b l o c k . Both b o i l i n g p o i n t s and m e l t i n g p o i n t s are uncorrected. I n f r a r e d ( i . r . ) s p e c t r a were obtained on a Perkin-Elmer model 237-B spectrophotometer i n F i s h e r spectro grade chloroform s o l u t i o n . Nuclear magnetic resonance (n.m r.) s p e c t r a were performed i n deuteriochloroform s o l u t i o n , unless otherwise i n d i c a t e d , w i t h t e t r a m e t h y l s i l a n e as i n t e r n a l standard, on a V a r i a n A-60, HA-100 or J e l c o C-60 instrument. U l t r a v i o l e t (u.v.) s p e c t r a were measured on a Cary 14 spectrophotometer i n methanol s o l u t i o n . Thin l a y e r and p r e p a r a t i v e l a y e r chromatography were performed on s i l i c a g e l G to which 3% of General E l e c t r o n i c phosphor No. 118-2-7 had been added to f a c i l i t a t e the d e t e c t i o n o f u l t r a v i o l e t absorbing compounds. Vapour phase chromograms (v.p.c.) were obtained on an Aerograph Model A-90-P w i t h thermal c o n d u c t i v i t y d e t e c t o r . Chromatograms were recorded on a Honeywell Model E l e c t r o n i k 15 graphic recorder and were converted t o d i g i t a l data by peak area. - 117 -Se c t i o n I Methyl (±) a,g-dibromoisobutyrate This compound was prepared by the procedure of Ford and Waters (106). A s o l u t i o n o f Br. (12.0 ml, 0.225 mole) i n c a r b o n t e t r a c h l o r i d e (12.5 ml, d r i e d over MgSO^) was added to methyl methacrylate (Aldrich Chemical Co. Inc., 22.5 gm., 0.225 mole) cooled i n a f r e e z i n g mixture, at such a r a t e t h a t the temperature d i d not exceed 20°C. The r e a c t i o n mixture was l e f t overnight at room temperature. The solvent was r o t a r y evaporated and then d i s t i l l e d under vacuo, w i t h methyl (±)-a,g-dibromoisobutyrate passing over at 102-104°/9-10 mm. (48.1 gm, 77%). This compound was washed twice w i t h 10% aqueous sodium bicarbonate s o l u t i o n and then w i t h water, d r i e d over calcium c h l o r i d e and r e f r a c t i o n a t e d y i e l d i n g 35.0 gm of methyl (_)-a,g-dibromo-?n 17 i s o b u t y r a t e , b.p. 93-95°/8-9 mm.; n^ 1.508 ( l i t n j 1.5092); n.m.r. (CC1 4), 6 4.23 (doublet, J = 10 Hz, 1H, g-proton), 3.73 (doublet, J = 10 Hz, 3H, g-CH_), 3.83 ( s i n g l e t , 3H, -COOCH.) and 6 2.01 p.p.m. ( s i n g l e t , 3H, a-CH_). Methyl g-bromo-a-methylacrylate, (E)- (73_a) This compound was prepared by the procedure o f Bieber (107). To 55 gm (0.21 mole) o f methyl (i)-a, g-dibromoisobutyrate was added dropwise 4.9 gm (0.21 mole) o f sodium i n 56.5 gm of d r i e d methanol, c o n t a i n i n g t r a c e o f p h e n o l p h t h a l e i n , u n t i l one drop r e q u i r e d 10 minutes f o r complete d e c o l o r i z a -t i o n . Sodium bromide was removed by f i l t r a t i o n and washed with methanol. The washings and f i l t r a t e were combined and r o t a r y evaporated t o ca h a l f volume and NaBr was again removed. Most of the solvent was removed, the semi-gelatinous residue was t r e a t e d w i t h water (30 ml ) and the p r e c i p i t a t e d " - 118 -o i l e x t r a c t e d w i t h carbon t e t r a c h l o r i d e . The d r i e d s o l u t i o n was evaporated and then d i s t i l l e d under vacuo y i e l d i n g 20 gm (0.11 mole) of methyl, g-bromo-a-methacrylate-(E) (64-67°/15 mm.), b.p. 162-163°, n.m.r. (CC1 4) 6 2.0 (doublet, J = 1.5 Hz, 3H, ct-methyl), 3.75 ( s i n g l e t , 3H, -C00CH-) and 7.47 . p.p.m. (qu a r t e t , J = 1.5 Hz, 1H, C=C-H). DL-erythro-2,3-dibromo-2-methylsuccinic a c i d This compound was prepared by the procedure of Rappe and Anderson (108). 94.2 gm (0.72 mole) o f mesaconic a c i d (Eastman Organic Chem., Rochester, N.Y.) was d i s s o l v e d i n 108 gm of water, heated t o b o i l i n g and 127 gm (41 ml 0.88 mole) of bromine was added over one hour. The water was then removed on a hot water bath under reduced pressure. The residue was allowed to c o o l and kept at room temperature f o r 16 h r s . The c r y s t a l l i n e s o l i d was s l u r r i e d w i t h benzene (2 x 80 ml ) and washed with nitromethane (20 ml.). R e c r y s t a l l i z a t i o n from hot nitromethane y i e l d e d 132.4 gm (0.46 mole, 63%) of DL-erythro-2,3-dibromb-2-methylsuccinic a c i d , m.p. 194-195° ( l i t . m.p. 196-197°), n.m.r. (D-0) 6 5.20 ( s i n g l e t , 1H, -C-CH) and 2.19 p.p.m. ( s i n g l e t , 3H, CH_-C(2)). g-bromo-a-methacrylic a c i d , (Z) This compound was prepared by the procedure of Rappe and Anderson (108). 50 gm (0.172 mole) of DL-erythro-2,3-dibromo-2-methyl s u c c i n i c a c i d was s l u r r i e d w i t h 50 ml of water. Bromothymol blue was added arid the s o l u t i o n t i t r a t e d w i t h aqueous Na_,C0_ (20% by weight) t i l l the blue colour of the i n d i c a t o r p e r s i s t e d (pH 6-7). The f l a s k was immersed i n t o b o i l i n g water and was r a p i d l y t i t r a t e d w i t h Na.CO- s o l u t i o n from a dropping funnel t o maintain the blue colour o f the i n d i c a t o r . Low b o i l i n g product was d i s t i l l e d - 119 -o f f during the r e a c t i o n . A f t e r 30 min , the f l a s k was cooled by immersion i n t o an ice-water bath. The s o l u t i o n was washed w i t h ether to remove, most o f the i n d i c a t o r and b a s i c i m p u r i t i e s . A f t e r a c i d i f y i n g w i t h cone. HC1, the s o l u t o n was e x t r a c t e d w i t h petroleum ether (b.p. 30-60°) (4 x 50 ml ) which removed the (E)- a c i d (1.5 gm ) and most o f the r e s i d u a l i n d i c a t o r , the aqueous s o l u t i o n was then e x t r a c t e d w i t h ether (6 x 50 ml ). The e t h e r e a l e x t r a c t was washed with water, d r i e d over Na2S0^ and r o t a r y evaporated to give 2.8 gm o f brown l i q u i d , c o n t a i n i n g (E)- and (Z)-isomers o f g-bromo-a-m e t h a c r y l i c a c i d i n a 20:80% r a t i o r e s p e c t i v e l y , as estimated by the v i n y l proton s i g n a l r a t i o of the n.m.r. spectrum; n.m.r. o f the (Z)-isomer (CCl^) 6 2.07 (doublet, J - 1.5 Hz, 3H, CH_3 at a ) , 6.75 p.p.m. (qu a r t e t , J = 1.5 Hz, 1H, proton at g) . Methyl g-bromo-a-methacrylate, (Z)- (73b) To 2.8 gm of (Z)- and (E)- mixture o f g-bromo-a-methacrylic a c i d (4:1) was added excess diazomethane i n ether at room temp. Immediate r o t a r y evaporation o f ether gave the corresponding methyl e s t e r s . The brown e s t e r s o l u t i o n was d i s t i l l e d i n a bulb to bulb d i s t i l l a t i o n apparatus at room temperature w i t h an acetone and dry i c e c o l d t r a p . 1.9 gm of colour-l e s s (Z)- and (E)- mixture o f methyl g-bromo-a-methacrylate (73b and 73a) (72:28, measured by n.m.r.) was obtained from the cold t r a p . N.m.r. (neat, e x t e r n a l TMS) of (Z)-isomer 5.6.52 (q u a r t e t , J = 1.5 Hz, 1H, -(CH 3)C=CH-), • 3.65 ( s i n g l e t , 3H, -C00CH_3) and 1.87 p.p.m. (doublet, J = 1.5 Hz, 3H, -(CH 3)C=CH-). N-nitroso-N-methyl urea This compound was prepared according to the procedure o f F. Arndt - 120 -(109). 300 gm of urea was d i s s o l v e d i n a s o l u t i o n o f 101 gm. (1.5 moles) of methyl amine h y d r o c h l o r i d e , 300 ml of water and a few drops of cone. HC1. The mixture was b o i l e d g e n t l y under r e f l u x f o r 3 hrs and v i g o r o u s l y f o r 1/4 hr. A f t e r c o o l i n g to room temperature, 110 gm (1.5 moles) o f 98% sodium n i t r a t e was d i s s o l v e d i n i t . The r e a c t i o n mixture was then c h i l l e d w i t h i c e and added t o an i c e - c o l d s o l u t i o n o f 102 gm H 2 S ° 4 C 5 8 m l > 3 o N ) i n 660 gm of i c e with s t i r r i n g at such a r a t e t h a t the temperature remained below 5°. The N-nitroso-N-methyl urea, (117 gm , 1.29 moles, 86%) which rose to the surface as white c r y s t a l s was c o l l e c t e d by s u c t i o n f i l t r a t i o n , . washed with i c e c o l d water and d r i e d by s u c t i o n t o constant weight. Diazomethane (109) , , ' \ . • . In a 500 ml c o n i c a l f l a s k were placed 60 ml of 50% aqueous KOH s o l u t i o n and 200 ml of anhydrous ether. The mixture was cooled to 5° and 20.6 gm. (0.20 mole) of N-nitroso-N-methyl urea was added with s t i r r i n g at such a r a t e that the temperature remained below 5°. the orange coloured diazomethane-ether s o l u t i o n (60% y i e l d ) was decanted from the aqueous l a y e r , washed w i t h 100 ml of i c e c o l d water and d r i e d over anhydrous KOH p e l l e t s f o r 2 h r s . 3-Carbomethoxy-3-methyl-4-bromo-l-pyrazoline, (Z)- (72a) A l l glassware used f o r p r e p a r a t i o n o f t h i s compound were r i n s e d once w i t h 10% aqueous NaOH s o l u t i o n and then three times with d i s t i l l e d water. . To 5.0 gm (0.028 mole) of methyl 8-bromo-a-methacrylate, (E)- i n ether (25 ml ) was added excess of diazomethane-ether s o l u t i o n dropwise w i t h s t i r r i n g at room temperature. The r e s u l t i n g r e a c t i o n mixture was y e l l o w but became c o l o u r l e s s on standing overnight. Rotary evaporation of ether s o l u t i o n at 0° gave an o i l y product o f 3-carbomethoxy-3-methyl-4-bromo-l-pyrazoline, - 121 -(E ) - ; n.m.r.: 6 5.0 (doublet, J = 4.7 Hz, 2H, H_ 2C(5)), 4.58 ( t r i p l e t , J = 4.7 Hz, 1H, HC(4)), 3.73 ( s i n g l e t , 3H, - C O O C H p and 1.98 p.p.m. ( s i n g l e t , 3H, CH_ 3-C(3)). No other p h y s i c a l data were obtained owing to the i n s t a b i l i t y o f t h i s compound. 3-Carbomethoxy-3-methyl-4-bromo-l-pyrazoline, (Z)- (72b) This compound was prepared by the above procedure from 1.9 gm o f methyl g-bromo-a-methacrylate, (ZJ- (co n t a i n i n g 28% of (E)-isomer) to give an o i l y p y r a z o l i n e mixture. The n.m.r. spectrum given i n Table XIV, i n d i c a t e s the presence o f 55% of ( Z ) - p y r a z o l i n e , 20% of ( E ) - p y r a z o l i n e and 25% o f unreacted ( Z ) - o l e f i n . Table XIV The n.m.r. s p e c t r a of 3-carbomethoxy-3-methyl-4-bromo-l-pyrazoline (Z)- and (E)- i n C^Cl^ ^ n & u n i t s w i t h e x t e r n a l tetramethyl s i l a n e r eference C(5)(doublet) C ( 4 ) ( t r i p l e t ) CH^-ester CH 7 at C(3) 72a: (E) 5.12 ( J = 4.7 Hz) 4.72 ( J =4.7 Hz) 3.79 1.91 72b: (Z) 5.04 ( J = 5.4 Hz) 4.20 ( J = 5.4 Hz) 3.85 1.52 3-Carbomethoxy-3,5,5-trimethyl-4-bromo-l-pyrazoline, (E)- (89) A mixture of 11.60 gm (0.050 mole) of s i l v e r oxide and 60.0 ml of anhydrous ether was cooled to -60°. To t h i s were added simultaneously s . 3.6 gm (0.050 mole) o f acetone hydrazone (prepared by I.M. Masters (45)) and 5.3 gm (0.30 mole) o f methyl g-bromo-a-methacrylate, (E)- (73a) w i t h s t i r r i n g over a p e r i o d of two mins (2-diazopropane prepared i n s i t u (110)). The r e s u l t i n g mixture was allowed to warm up to -25° and s t i r r e d at that - 122 -temperature f o r 3 hrs , before f i n a l warming t o room temperature. The black p r e c i p i t a t e was f i l t e r e d , the f i l t r a t e evaporated and twice f r a c t i o n a l l y d i s t i l l e d under vacuo to give 2.0 gm (8 mmoles) of 3-carbomethoxy-3,5,5-t r i m e t h y l - 4 - b r o m o - l - p y r a z o l i n e , (E)- (89), b.p. 80°/0.25mm., n.m.r. (CC1 4) 6 4.26 ( s i n g l e t , 1H, H-C(4)), 3.78 ( s i n g l e t , 3H, -COOCH.), 1.59, 1.49 and 1.41 p.p.m. ( s i n g l e t s , 9H, CH. at C. and C.), i . r . A ^ ' f l l m 5.72 y (stron g , e s t e r c a r b o n y l ) . Anal, c a l c d . f o r C0H_.BrN.O.: C, 38.58; H, 5.28. Found: o 13 2. 2. C, 38.30; H, 5.11. P y r a z o l i n e Decomposition 3-Carbomethoxy-3-methyl-4-bromo-l-pyrazoline, (E)- (72a) was warmed to room temperature f o r 5 min. A vigorous r e a c t i o n took place w i t h e v o l u t i o n of hydrogen bromide - to give q u a n t i t a t i v e y i e l d of the hydrobromide s a l t o f 3-methyl-4- carbomethoxypyrazole (74), m.p. 175-177.5° (white needles, e t h a n o l ) , n.m.r. (D.O) 6 2.32 ( s i n g l e t , 3H, CH_-C(4)), 3.70 ( s i n g l e t , 3H, -COOCH.) and 7.96 p.p.m. ( s i n g l e t , 1H, H-C(5)). I . r . A 3-4.5 y (broad, ammonium HI—IX s a l t ) and 5.82 y (stron g , conjugate e s t e r ) . The s a l t was d i s s o l v e d i n water (10 ml) t r e a t e d w i t h d i l u t e sodium bicarbonate u n t i l the s o l u t i o n became b a s i c , and the solution e x t r a c t e d w i t h chloroform (3 x 20 ml.). Evaporation o f the chloroform gave the corresponding p y r a z o l e 77_ (80%) , m.p.. 93-94° (white needles, methanol), i . r . A 2.85 (-NH) 5.90 y (strong, conjugate e s t e r ) , n.m.r. 6 2.54 ( s i n g l e t , 3H, CH_-C(3)), 3.83 ( s i n g l e t , 3H, -COOCH.) and 7.95 p.p.m. ( s i n g l e t , 1H, H-C(5)). U.v. A 270 (e 8.722 x 1 0 4 ) , 220 my (e 1.058 x 1 0 5 ) . A n a l . Calcd. f o r C,HQN.O-: C, 51.42; H, 5.75; N, 20.00. Found: C, 51.49; H, 5.85; N, 19.89. In a s i m i l a r way, 3-carbomethoxy-3-methyl-4-bromo-l-pyrazoline, (Z)- f (72b) (mixed w i t h 28% of the (E)-isomer) decomposed to the same hydrobromide 74, m.p. 175-177.5°. Treatment o f t h i s s a l t w i t h d i l u t e sodium bicarbonate - 123 -y i e l d e d the corresponding py r a z o l e 77 (76%), m.p. 93-94°, n.m.r. 6 2.55 ( s i n g l e t , 3H, CH 3-C(3)), 3.85 ( s i n g l e t , 3H, -COOCH_3) , 8.00 p.p.m. ( s i n g l e t , 1H, H-C(5)). P y r o l y s i s of 3-carbomethoxy-3,5,5-trimethyl-4-bromo-l-pyrazoline (89) at 130° f o r 7 hrs y i e l d e d hydrogen bromide gas and n i t r o g e n . The b l a c k . s o l u t i o n was d i s t i l l e d i n vacuo and the mixture separated by vapour phase chromatography (DEGS, 185°, 50 p . s . i . ) to give a , y , Y - t r i m e t h y l A ' - a n g e l i c a -lactone (90) r e t e n t i o n time = 21 min , (79%), m.p. 56-58° (white n e e d l e s ) , n.m.r. 6 1.45 ( s i n g l e t , 6H, ( C H _ 3 ) 2 - C ( Y ) ) , 1.87 (doublet, J = 1.4 Hz, 3H, CH -C(a)) and 7.05 p.p.m. (qu a r t e t , J = 1.4 Hz, 1H, H - C ( B ) ) . I . r . X 5.72 (str o n g , C=0), and 5.84 y (medium, C=C) . Anal. Calcd. f o r C ^ ^ C y C, 66.70; H, 7.99. Found: C, 66.79; and H, 7.95%. The other product was a - m e t h y l e n e - Y , Y - d i m e t h y l b u t y r i c lactone (91), r e t e n t i o n time = 24.4 min, (21%)", i . r . X 5.70 (str o n g , C=0) and 5.99 u (medium, C=C), n.m.r. 6 1 . 4 0 n i c i x ( s i n g l e t , 6H, ( C H 3 ) 2 - C ( y ) ) , 2.72 ( t r i p l e t , J = 3.0 Hz, 2H, H 2 C ( 3 ) ) , 5.57 and 6.18 p.p.m. (both t r i p l e t , J = 3.0 Hz, 2H, C=CH_2) . 3-Carbomethoxy-4-methylpyrazole (78) This compound was prepared by the procedure of Parham and Hasek (55). To a s o l u t i o n o f 5.7 gm (0.04 mole) of 3-carbomethoxy-4-methyl-2-pyrazoline (prepared from the r e a c t i o n o f methyl crotonate and diazomethane (25)) i n 20 ml of chloroform was added dropwise a s o l u t i o n o f 3 ml of bromine i n 5 ml of chloroform at such a r a t e that the temperature d i d not exceed 15°. A f t e r b o i l i n g f o r 5 min the p r e c i p i t a t e o f the py r a z o l e hydrobromide (7.2 gm , 0.03 mole) was f i l t e r e d . A s o l u t i o n of 1.2 gm (5.4 mmoles) of t h i s s a l t i n b o i l i n g water was t r e a t e d w i t h sodium bicarbonate. On c o o l i n g , a white p r e c i p i t a t e was c o l l e c t e d and r e c r y s t a l l i z e d from water to give 0.7 gm (5 mmoles, 92.5%) of 3-carbomethoxy-4-methylpyrazole (78), m.p. 1 7 1 - . - 124 -171.5° ( l i t . m.p. 172° (5 4 ) ) , n.m.r. (dimethyl sul£oxide-d6), 6 2.24 ( s i n g l e t , 3H, CH_-C(4)), 3.81 ( s i n g l e t , 3H, -COOCH.) and 7.61 p.p.m. ( s i n g l e t , 1H, H-C(5)), i . r . x N u ^ 0 1 314 (medium, -NH) and 5.92 my (str o n g , conjugated c a r b o n y l ) . 3-Methyl-4-carboethoxypyrazole (79) A s o l u t i o n o f 0.5 gm (3.5 mmoles) of 3-methyl-4-carbomethoxypyrazole i n 10 ml o f 10% sodium hydroxide was heated under r e f l u x f o r 3 h r s . A f t e r c o o l i n g and n e u t r a l i z a t i o n w i t h concentrated h y d r o c h l o r i c a c i d , 0.3 gm (2.4 mmoles, 68%) of the f r e e base was c o l l e c t e d . A s o l u t i o n of the a c i d i n 20 ml o f absolute ethanol satura t e d w i t h dry hydrogen c h l o r i d e at 0° was r e f l u x e d f o r 3 h r s . A f t e r c o o l i n g , the s o l u t i o n was made b a s i c w i t h sodium bicarbonate and the product was taken up i n t o chloroform (3 x 20 m l ) . Evaporation of the solvent gave 0.37 gm (2.4 mmoles, .100%) of an o i l y m a t e r i a l , 3-methyl-4-carboethoxypyrazole (79), which c r y s t a l l i z e d on stan d i n g , m.p. 46-48° ( l i t . m.p. 46° (56)), n.m.r. 6 1.34 ( t r i p l e t , J = 7 Hz, 3H, -CH.CH.), 4.33 (quar t e t , J = 7 Hz, 2H, -C00-CH--), 2.56 ( s i n g l e t , 3H, CH_-C(3)) and 7.99 p.p.m. ( s i n g l e t , 1H, H-C(5)). S e c t i o n I I Methyl B-methoxy-ct-methacrylate, (E)- (93) This compound was prepared according to the procedure of Shaw and Warrener (111). 93.6 gm (0.337 mole) of methyl (_)-a,g-dibromoisobutyrate ( f o r p r e p a r a t i o n o f t h i s compound, see Experimental, S e c t i o n I) i n 100 ml. o f methanol was added to a hot s o l u t i o n of 16.6 gm (2.72 mole) of sodium i n 200 ml o f methanol at such a r a t e s u f f i c i e n t t o keep the mixture b o i l i n g - 125 -Next morning the p r e c i p i t a t e d sodium bromide was f i l t e r e d and washed w i t h methanol. The washings and f i l t r a t e were combined and evaporated t o ca h a l f volume and sodium bromide was again removed. Most of the solvent was removed, the semi-gelatinous residue was t r e a t e d w i t h water (60 ml ) and . the p r e c i p i t a t e d o i l e x t r a c t e d i n t o ether. The d r i e d s o l u t i o n was evaporated and the r e s i d u e heated with f r e s h l y fused sodium b i s u l p h a t e (0.3 gm ) at 170° under a small fractionating column u n t i l e v o l u t i o n o f methanol was complete. The r e s i d u e f r a c t i o n a t e d i n vacuo y i e l d e d methyl 3-methoxy-ct-methacrylate, (E)- (93) passing over at 75-78°/15 mm. (31.7 gm , 0.244 mole, 12%), b.p. 167.5-168.5°; n^ 1.4365 ( l i t n* 1.455); n.m.r. (CC1 4): <5 7.21 ( q u a r t e t , J = 1.5 Hz, 1H, -HC=C(CH_)-), 3.82 and 3.65 (both s i n g l e t , 3H. each, -C00CH_), and 1.67 p.p.m. (doublet, J = 1.5 Hz, 3H, -HC-C(CH_)-).' Attempted p r e p a r a t i o n o f 3-carbomethoxy-3-methyl-4-methoxy-l-pyrazoline  (92) (a) by r e a c t i o n of methyl 8-methoxy-a-methacrylate, (E)- (93) and diazomethane. Excess of diazomethane ( f o r p r e p a r a t i o n , see Experimental S e c t i o n I) i n ether was added to a s o l u t i o n of methyl 3-methoxy-a-methacrylate, (E)-(93) i n ether. Evaporation of the r e a c t i o n mixture a f t e r a week at room temperature l e d to recovery of s t a r t i n g m a t e r i a l . (N.m.r. spectrum was i d e n t i c a l to the s t a r t i n g o l e f i n . ) (b) by r e a c t i o n o f methyl 3-methoxy-a-methacrylate, (E)- (93) diazomethane and boron t r i f l u o r i d e Excess diazomethane i n anhydrous ether was added to 5.0 gm (38.5 mmoles) of the o l e f i n 93 and 5.1 gm (38.5 mmoles) of boron t r i f l u o r i d e etherate ( d i s t i l l e d t w i c e ) . A f t e r 24 hrs at room temperature, the r e a c t i o n mixture ; - - 126 -was e x t r a c t e d w i t h 5% aqueous bicarbonate s o l u t i o n (30 ml ) and then water, (30 ml ). Evaporation of the d r i e d ether s o l u t i o n gave a res i d u e w i t h an i d e n t i c a l n.m.r. spectrum to the s t a r t i n g o l e f i n 93. Methyl a-cyanocinnamate, (E)- (97a) (113) To 5 gm (0.05 mole) o f methyl cyanoacetate was added a s o l u t i o n o f 0.3 gm (6.5 mmoles) o f sodium i n 20 ml of methanol. 5.0 gm (0.047 moles) of benzaldehyde was added to t h i s a l k a l i n e r e a c t i o n mixture. A f t e r 24 hrs at room temperature, the s o l i d was f i l t e r e d , washed twice w i t h water and d r i e d to give methyl a-cyanocinnamate, (E)- (97a), 66% y i e l d ; m.p. 90-91° ( l i t . m.p. 89°) (113), (white needles, methanol), n.m.r. 5 3.92 ( s i n g l e t , 3H, -C00CH_3), 8.21 ( s i n g l e t , 1H, C=C-H) and 7.83-8.10 p.p.m. ( m u l t i p l e t , 5H, C 6 » 5 - ) • Methyl a-cyano-p-methoxycinnamate, (E)- (98) Condensation of 3.0 gm (0.03 mole) of methyl cyanoacetate and 3.8 gm (0.028 mole) o f p-methoxybenzaldehyde c a t a l y z e d by 0.18 gm (8.8 mmoles) o f sodium i n the same manner described above gave the t i t l e compound 98_ i n 77% y i e l d ; m.p. 96-96.5 ( l i t . m.p. 94-96 (67) (white needles, methanol); n.m.r. 6 3.98 ( s i n g l e t , 3H, C-0-CH_3), 3.95 ( s i n g l e t , 3H, -C00CH_3), 8.21 ( s i n g l e t , 1H, -C=CH), 8.04 and 8.21 p.p.m. (both doublet, J = 8.7 Hz, 4H, - C ^ - ) . Methyl a-cyano-p-nitrocinnamate, (E)- (99a) This compound was prepared by condensation of 5.0 gm (0.05 moles) o f methyl a-cyanoacetate w i t h 7.1 gm (0.047 mole) of p-nitrobenzaldehyde c a t a l y z e d by 0.3 gm (6.5 mmoles) o f sodium i n the same manner as described above but at 0° f o r 2 h r s . The s o l i d obtained was washed w i t h methanol and - 127 -twice r e c r y s t a l l i z e d from methanol to give pure product 99a, 43% y i e l d ; m.p. 177-178° (white n e e d l e s ) ; n.m.r. 6 4.02 ( s i n g l e t , 3H, -C00CH_), 8.34 ( s i n g l e t , 1H, -C=CH), 8.15 and 8.41 p.p.m. (both doublet, J = 8.8 Hz, 4H, 4 -C\H,-); u.v. A 302 mu (e 2.177 x 10 ); i . r . A 5.76 u (stron g , -C=0), 6—4 max v -" • • max v • ' • 4.51 (medium, -C=N). Since the me l t i n g p o i n t of compound 99a was not the same as recorded i n the l i t e r a t u r e (67), the m i c r o a n a l y s i s was necessary. Anal. Calcd. f o r ^ H-N-O^ C, 56.89; H, 3.47; N, 12.07. Found: C, 56.91; H, 3.62; N, 12.08. Methyl a-cyano-8-methylcinnamate, (E)- (100a) To methyl a-cyanocinnamate, (E)- (97a) i n benzene was added excess o f diazomethane i n ether ( f o r p r e p a r a t i o n o f diazomethane, see Experimental, S e c t i o n I ) . Evaporation of the s o l u t i o n at0° immediately a f t e r a d d i t i o n gave an o i l y s o l u t i o n which decomposed very r e a d i l y i n neat s o l u t i o n or i n a v a r i e t y o f so l v e n t s i n t o methyl a-cyano-B-methylcinnamate, (E)- (100a) (100%), b.p. 122°/0.2 mm., m.p. 43-44° (white needles, ether a t -60°);. n.m.r. (CC1 4), 6 2.65 ( s i n g l e t , 3H, CH_ at 8), 3.84 ( s i n g l e t , 3H, -C00CH_); and 7.45 p.p.m. ( s i n g l e t , 5H, C^H_-). This n.m.r. spectrum was i d e n t i c a l w i t h that recorded i n the l i t e r a t u r e (67). -Methyl a-cyano-B-methyl-p-methoxycinnamate, ( E ) - (101) Reaction of methyl a-cyano-p-methoxycinnamate, (E)- (98) w i t h d i a z o — methane i n the same manner as described above gave compound 101, 100% y i e l d ; m.p. 90.5-92° ( l i t . m.p. 73-74°) (112). (White needles, methanol and water); n.m.r. 6 2.70 ( s i n g l e t , 3H, CH_ at 8), 3.90 and 3.92 (both s i n g l e t , 3H each,, -C00CH_ and C-0-CH-), 6.98 and 7.52 p.p.m. (both doublet, J = 8.8 Hz, 4H, -CM.-); i . r . A 4.51 (medium, C=N) and 5.80 u (s t r o n g , conjugated e s t e r ) ; 128 u.v. X 320 (e 1.231 x 10 4) and 240 my (e 4.375 x 10 3) . Anal. Calcd. f o r max v J p «. ; C 1 3H 1 3N0 3: C, 67.50; H, 5.67; N, 6.06. Found: C , 67.79; H, 5.81; N , 5.98. Methyl a-cyano-B-methyl-p-nitrocinnamate, (E) - (102a) A d d i t i o n of diazomethane, i n ether to methyl a-cyano-£-nitro-cinnamate, (E)- (99a) i n benzene at room temperature f o r 1 hr gave white needles c y r s t a l s , m.p. ca_ 45° (decomp.). Attempt to i s o l a t e t h i s intermediat was unsuccessful owing to i t s ready decomposition i n t o compound 102a (100%), m.p. 119-121° (white needles, methanol), i . r . ^ m a x 4.50 y (medium, C H N ) and 5.80 y (stro n g , conjugated e s t e r ) ; n.m.r. 6 2.75 ( s i n g l e t , 3H, CH_3-G-B), 3.93 ( s i n g l e t , 3H, -C00CH_3), 7.63 and 8.83 p.p.m. (both doublet, J = 8.8 Hz, 4H, -C.H,-), u.v. X 281.(e 1.448 x 10 4) and 240 my (e 8.112 x 1 0 3 ) . 6-4 J max J . Since the m.p. was not the same as recorded i n the l i t e r a t u r e (67), the m i c r o a n a l y s i s of t h i s compound was necessary. Anal. Calcd. f o r C^H^I^O^: C, 58.55; H, 4.09; N, 11.39. Found: C, 58.62; H, 4.29; N, 11.49. Methyl a-cyano-8-methylcinnamate, (Z)- (100b) A s o l u t i o n of 8.0 gm of d i s t i l l e d methyl a-cyano-B-methylcinnamate, (E) o (100a) i n 75 ml. ether was i r r a d i a t e d i n a s i l i c a tube at 75 W, 250 V, 2537 A f o r 2 days. Evaporation of ether and f i l t r a t i o n of the r e s u l t i n g s o l u t i o n gave c r y s t a l l i n e methyl a-cyano-B-methylcinnamate, (Z)- (100b) (3.0 gm.) m.p. 75-76° (white needles, ether at -60°), i . r . X 452 (medium, C=N) and r J max . J 5.80 y (stro n g , conjugated e s t e r c a r b o n y l ) ; n.m.r. (CCl^) : 6 2.50 ( s i n g l e t , 3H, CH -C(B)), 3.60 ( s i n g l e t , 3H, - C O O C F y and 6.95-7.40 p.p.m. ( m u l t i p l e t , 5H, -C,H_-); u.v. X _ 276 (e 1.021 x 10 4) and 225 my fe 6.858 x 1 0 3 ) . 6—5 max Anal. Calcd. f o r C 1 2 H n N 0 2 : C, 71.64; H, 5.51; N, 6.96. Found: C, 71.78; H, 5.57; N, 7.08. - 129 -Methyl g-methyl-a-cyano-p-nitrocinnamate, (Z)- (102b) 2.0 gm of methyl g-methyl-ct-cyano-p-nitrocinnamate, (E)- (102a) was heated at 150° f o r 2 hrs cooled and s l u r r i e d w i t h ether (3 x 70 ml ). The remaining s o l i d (0.4 gm ) was r e c r y s t a l l i z e d three times from methanol to give pure (Z_)-isomer 102b (0.5 gm ) , (pale y e l l o w f l a k e s ) , m.p. 158-159° i . r . X 4-51 u (medium, C=N ) and 5.76 u ( s t r o n g , c a r b o n y l ) ; n.m.r. nicLx 6 2.57 ( s i n g l e t , 3H, CH--C(g)), 3.70 ( s i n g l e t , 3H, -C00CH-), 7.33 and 8.27 p.p.m. (both doublet, J = 8.5 Hz, 4H, - C ^ - ) ; u.v. ^ m a x 280 my (e 1.369 x 1 0 4 ) . Anal. Calcd. f o r c12tiio^2°4: C' 58-55' H> 4*09' N» n-39-Found: C, 58.57; H, 4.17; N, 11.53. Methyl ot-cyano-g-ethylcinnamate This compound was prepared by the procedure of Cope (65). Methyl cyanoacetate (0.125 mole, 12.38 gm ) , propiophenone (0.175 mole, 21.4 gm ) and the c a t a l y s t p i p e r i d i n e (0.005 mole, 0.43 gm ) were placed i n a 100 ml: modified C l a i s e n f l a s k w i t h 30 ml of 99.8% a c e t i c a c i d , and the mixture d i s t i l l e d s l o w l y f o r 4 h r s . The heating being r e g u l a t e d so that the temperature of the vapour remained between 105 and 115°. The volume of the d i s t i l l a t e (wet a c e t i c a c i d p l u s a small amount of ketone) was 30 ml. The r e s i d u e was then cooled, washed w i t h water (2 x 25 ml ) and d i s t i l l e d i n vacuo, the product, methyl a-cyano-g-ethylcinnamate (E)- and (Z)- (1:1) (2.8 gm ) p a s s i n g over at 124-126°/0.2 mm., w i t h 90% recovery of s t a r t i n g m a t e r i a l s . N.m.r. spectrum of the products, <5 1.03 ( t r i p l e t , J = 7.5 Hz, 6H, CH_-C(g)), 2.87 and 3.IT (both q u a r t e t , J = 7.5 Hz, 2H each, CH--C(g)) of (Z)- and (IE)-isomer r e s p e c t i v e l y ) , 3.60 and 3.73 (both s i n g l e t , 3H each, -COOCH. of the (Z)- and (E)-isomer r e s p e c t i v e l y ) , 7.0-7.5 p.p.m. ( m u l t i p l e t 10H, C^H.-), was i d e n t i c a l w i t h t h a t recorded i n l i t e r a t u r e (67). - 130 3-Carbomethoxy-3-methyl-4-phenyl-l-pyrazoline, (E)- (117) To a s o l u t i o n of a-methylcinnamic a c i d ( A l d r i c h Chem. Co.) i n ether was added at l e a s t a t h r e e - f o l d excess of diazomethane i n ether. A f t e r a week at room temperature, the r e a c t i o n mixture was r o t a r y evaporated t o give an o i l y l i q u i d , d i s t i l l a t i o n i n vacuo gave the pure p y r a z o l i n e 117, b.p. 126°/0.2 mm. N.m.r. <5 1.17 ( s i n g l e t , 3H, CH_3 at C ( 3 ) ) , 3.80 ( s i n g l e t , 3H, -C00CH 3), 3.64 ( t r i p l e t , J = 10 Hz, 1H, H at C ( 4 ) ) , 4.88 (doublet, J = 10 Hz, 2H, H_2-C(5)) and 7.10 p.p.m. ( m u l t i p l e t , 5H, C ^ - ) . 3-Carbomethoxy-3-cyano-4-methyl-4-phenyl-l-pyrazoline, (E)- (118a) . Reaction o f methyl a-cyano-B-methylcinnamate, (E)- (100a) w i t h one mole of diazomethane or r e a c t i o n o f methyl a-cyanocinnamate, (E)- (97a) w i t h two moles of "diazomethane i n ether at room temperature f o r 4 hrs then at -4° overnight gave white c r y s t a l s . These c r y s t a l s were f i l t e r e d and washed with c o l d ether (to remove the decomposition p r o d u c t ) , to give pure pyra-z o l i n e 118a, m.p. 93-94° (decomposed) (white needles, e t h e r ) , n.m.r. 6 1.47 ( s i n g l e t , 3H, CH_ 3-C(4)), 3.94 ( s i n g l e t , 3H, - C O O C H p , 4.78 and 5.30 (both doublet, J g e m = 18 Hz, 2H, H_2-C(5)) and 7.32 p.p.m. ( m u l t i p l e t , 5H, CgHg-); i . r . X f f l a x 5.70 (s t r o n g , C=0) and 4.52 y (medium, -C=N) .. A nal. Calcd. f o r C^H^N,^: C, 64.16; H, 5.39; N, 17.27. Found: C, 63.95; H, 5.51; N, 17.16. 3-Carbomethoxy-3-cyano-4-methyl-4-p-methoxyphenyl-l-pyrazoline, (E)- (119) This product 119 was obtained by r e a c t i o n o f methyl a-cyano-B-methyl-p-methoxycinnamate, (E)- (101) or methyl a-cyano-p-methoxycinnamate (98) with diazomethane f o l l o w e d by p u r i f i c a t i o n i n the same manner as described above (except r e a c t i o n time at room temperature r e q u i r e d 24 hrs ) , 100% y i e l d , m.p. 82-83° (decomp.) (white needles, e t h e r ) , i . r . X 5.75 (s t r o n g , C=0), and - 131 -4.51 V (weak, C=N); n.m.r. « 1.48 ( s i n g l e t , 3H, CH-- C( 4))> 3.95 ( s i n g l e t , 3H, -COOCH ) , 3.80 ( s i n g l e t , 3H, -CO-CH ) , 4.75 and 5.30 (both doublets, J = 17.7 Hz, H 2 - C ( 5 ) ) , 6.87 and 7.12 p.p.m. (both doublets, J = 9.0 Hz, 4H, -C,H.-). Anal. Calcd. f o r C. .H.-N.0,: C, 61.53; H, 5.53; N, 15.37. Found: 6--4 • 14 IS 3 3 ' ' • ' ' ' C, 61.41; H, 5.71; N, 15.21. 3-Carbomethoxy-3-cyano-4-methyl-4-p-nitrophenyl-l-pyrazoline, (E)- (120a) Reaction o f methyl a-cyano-8-methyl-p-nitrocinnamate, (E)- (102a) with one mole o f diazomethane i n ether at room temp, f o r 2 hrs gave white c r y s t a l s . The c r y s t a l s were f i l t e r e d and washed w i t h ether to give p y r a z o l i n e 120a 50% y i e l d ; m.p. 101-102° (decomp.) (white powder, e t h e r ) ; i . r . X 5.74 y (st r o n g , -C=0), n.m.r. 5 1.54 ( s i n g l e t , 3H, CH_-C(4)), 4.05 ( s i n g l e t , 3H, -C00CH_), 4.94 and 5.35 (both doublet, J g e _ •= 16.4 Hz, 2H, H_ 2-C(5)), 7.37 and 8.20 p.p.m. (both doublet, J = 9.0 Hz, 4H, - C ^ - ) . Anal. Calcd. f o r C 1 3 H 1 2 N 4 0 4 : C, 54.15; H, 4.20; N, 19.43. Found: C, 54.20; H, 4.30; N, 19.20. Evaporation of the f i l t r a t e gave a mixture of ( E ) - p y r a z o l i n e (120b) ( 2 % ) , 3-carbomethoxy-3-cyano-4-methyl-4-p-nitrophenyl-l-pyrazoline-(_Z) (17.2%), n.m.r. 61.50 ( s i n g l e t , 3H, CH_-C(4)), 3.52 ( s i n g l e t , 3H, -C00CH_), 5.26 ( s i n g l e t , 2H, H 2 - C ( 5 ) ) , 7.42 and 8.22 p.p.m. (both doublet, J = 8.5 Hz, 4H, -C^H^-) and 3-carbomethoxy-3-cyano-4-methyl-4-p-nitrophenyl-5-pyrazoline, (E)- (133) (30%), n.m.r. 6 1.67 ( s i n g l e t , 3H, CH_-C(4)), 4.00 ( s i n g l e t , 3H, -C00CH_), 6.51 (broad, 1H, N-H), 6.81 ( s i n g l e t , 1H, H-C(5)), 7.60. and 8.27 p.p.m. (both doublet, J = 8.8 Hz, 4H, -CM_^-) . The product r a t i o was measured by the i n t e g r a t i o n o f the n.m.r. spectrum.. - 132 -3-Carbomethoxy-3-cyano-4-methyl-4-phenylpyrazoline, (Z)- (118b) This l i q u i d p y r a z o l i n e 118b was obtaned i n q u a n t i t a t i v e y i e l d from r e a c t i o n o f methyl a-cyano-B-methylcinnamate, (Z)- (100b) w i t h one mole o f diazomethane i n ether f o r 2 hrs at room temperature f o l l o w e d by evaporation of s o l v e n t at 0° ; n.m.r. 6 1.44 ( s i n g l e t , 3H, CH_ 3-C(4)), 3.35 ( s i n g l e t , 3H, -C00CH_3), 5.20 ( s i n g l e t , 2H, F£2-C(5)) and 7.0-7.45 p.p.m. ( m u l t i p l e t , 5H, C^H^-). No f u r t h e r p h y s i c a l constants could be obtained owing to i t s ready decomposition. 3-Carbomethoxy-3-cyano-4-methyl-4-p-nitrophenyl-l-pyrazoline, (Z)- (120b) Reaction of methyl a-cyano-B-methyl-p-nitrocinnamate (Z)- (102b) i n benzene with one mole o f diazomethane i n ether at room temperature f o r 2 hrs fol l o w e d by evaporation o f so l v e n t at 0° gave ye l l o w s o l i d which was washed and then r e c r y s t a l l i z e d from c o l d ether gave pure p y r a z o l i n e 120b i n 100% y i e l d , m.p. 90-91° (decomp.) (white powder); i . r . X 5.75 p (stron g , • m a x -C=0); n.m.r. 6 1.50 ( s i n g l e t , 3H, CH - C ( 4 ) ) , 3.52 ( s i n g l e t , 3H, -COOCH_3), 5.26 ( s i n g l e t , 2H, H 2 - C ( 5 ) ) , 7.42 and 8.22 p.p.m. (both doublets, J = 8.5 Hz, 4H, - C ^ - ) . Anal. Calcd. f o r C 1 3 H 1 2 N 4 ° 4 : c> 54.14; H, 4.20; H, 19.43. Found: C, 54.08; H, 4.20; N, 19.41. 3-Carbomethoxy-3-cyano-4-ethyl-4-phenyl-l-pyrazoline, (ZJ- and (E)- ^ (1:1) (141) These l i q u i d p y r a z o l i n e s 141 were obtained i n q u a n t i t a t i v e y i e l d from r e a c t i o n o f methyl a-cyano-B-ethylcinnamate, (Z)- and (E)- (1:1) with diazomethane i n ether, n.m.r. 6 1.16 ( t r i p l e t , J = 7.0 Hz, 6H, -CH2-CH_3) of both isomers), 3.45 (qu a r t e t , J = 7.0 Hz, 4H, CH3-CH_2-C(4) o f both isomers), 3.30 ( s i n g l e t , 3H, -COOCH- o f the (Z)-isomer), 3.90 ( s i n g l e t , 3H, -COOCH o f - 133 -the (IE)-isomer), 4.80 and 5.31 (both doublet, J = 17.5 Hz, 2H, H -C(5) of the (E)-isomer), 5.20 ( s i n g l e t , 2H, H -C(5) o f the (Z)-isomer) and 6.90-7.50 p.p.m. ( m u l t i p l e t , 10H, C^H-- of both isomers). No f u r t h e r p h y s i c a l constants could be obtained due to i t s ready decomposition. Diazomethane-d-Dideuteriodiazomethane was prepared by modification o f a procedure given by Crawford (35). To an e t h e r e a l s o l u t i o n o f diazomethane (prepared from 30 gm of N-nitroso-N-methylurea) was added a s o l u t i o n of 2 gm of K-CO- i n 40 ml of 99.8% DO (Merck Sharp and Dohme). The mixture was s t i r r e d f o r 12 hrs at 0° . The aqueous l a y e r was removed and the e t h e r e a l s o l u t i o n d r i e d over K-CO- followed by a d d i t i o n of a f r e s h s o l u t i o n o f 2 gm. of K--CO i n 40 ml of 99.8% D-0. The mixture was s t i r r e d f o r another 12 hrs at 0° ; the aqueous l a y e r was removed and the yellow e t h e r e a l s o l u t i o n d r i e d over sodium s u l f a t e f o r s e v e r a l h r s . The s o l u t i o n was f i l t e r e d and used immediately. The y i e l d s were g e n e r a l l y low because much diazomethane was l o s t during the exchange. When sh o r t e r exchange time was allowed, or when exchange was c a r r i e d out without s t i r r i n g , the amount o f deuterium s u b s i t u t i o n dropped.--3-Carbomethoxy-3-cyano-4-methyl-4-pheny1-5,5-dideuterio-1-pyrazoline, (E)- (121) This compound 121 was prepared i n the same manner as that of the co r r e s -ponding non-deuterated p y r a z o l i n e 118a, except that dideuteriodiazomethane was used. The n.m.r. spectrum i n d i c a t e d that deuterium s u b s t i t u t i o n on C_ was at l e a s t 80%. The percentage was obtained from the i n t e g r a t i o n o f C_ doublets at 4.78 and 5.30 p.p.m., and a l s o from the mass sp e c t r a at m/e = 125 (representing non-deuterated p y r a z o l i n e w i t h l o s s of n i t r o g e n ) , 126 - 134 -(representing mono-deuteriopyrazoline with l o s s of N^) and 127 (representing the d i d e u t e r i o p y r a z o l i n e w i t h l o s s o f N 2 ) • P y r a z o l i n e Decomposition 3-Carbomethoxy-3-methyl-4-phenyl-l^pyrazoline, (E)- (117) was pyr o l y z e d i n neat s o l u t i o n at 160° f o r 2 h r s . The products were i s o l a t e d by vapour phase chromatography (DC-550, 200°, 50 p . s . i . ) i n t o three pure components: methyl 2-methyl-3-phenylbut-3-enoate (127) ( 8 % ) ; r e t e n t i o n time = 17.6 min. n.m.r. (CC1 4) 6 7.23 ( m u l t i p l e t , 5H, C ^ - ) , 5.37 and 5.22 ( s i n g l e t , 2H, H_2-C=C), 3.60 ( s i n g l e t , 3H, -C00CH_3) and 1.40 p.p.m. (doublet, J = 6.0 Hz, 3H, -CH-CH^), (This n.m.r. spectrum was i d e n t i c a l w i t h that recorded i n l i t e r a t u r e (70), methyl a,B-dimethylcinnamate, (E)- (128) (62.4%); r e t e n t i o n time = 20.2 min ; n.m.r. (CC1 4) 6 7.22 ( m u l t i p l e t , 5H, C ^ - ) , 3.78 ( s i n g l e t , 3H, -C00CH3) 2,30 (qu a r t e t , J = 1.5 Hz, 3H, CH_ 3-C(B)), and 1.76 p.p.m. (qu a r t e t , J = 1.5 Hz, 3H, CH_ 3-C(a)), (This spectrum was i d e n t i c a l w i t h that recorded i n the l i t e r a t u r e (70)). (Anal. Calcd. f o r C 1 2 H 1 4 ° 2 : ' C» 7 5 - 7 7 J H, 7.42. . Found: C, 75.62; H, 7.62) and 1-carbomethoxy-1-methyl-2-phenyl-cyclopropane, (E)- (129a) (29.6%); r e t e n t i o n time = 22.3 min ; n.m.r. (CC1 4) 6 7.22 ( m u l t i p l e t , 5H, C ^ - ) , 3.68 ( s i n g l e t , 3H, -C00CH_3), 2.80 (quarte t , =6.75 and J . = 9.0 Hz, 1H), 1.65 (qu a r t e t , J =4.25 and J . = trans c i s . • ' • . , . g e m c i s 9.0 Hz, 1H), 1.08 (qu a r t e t , J = 4.25 and J = 6.75 Hz, 1H) and 0.95 . • n gem trans p.p.m. ( s i n g l e t , 3H, CH -C-1); i . r . X 5.78y (s t r o n g , -C=0). Ana l . Calcd. f o r C 1 2 H 1 4 0 2 : C, 75.77; H, 7.42. Found: C, 75.70; H, 7.40. 3-Carbomethoxy-4-phenyl-2-pyrazoline (124) (provided by Dr. D.E. McGreer) was p y r o l y z e d i n neat s o l u t i o n at 190° f o r 4 h r s . The products were i s o l a t e d by vapour phase chromatography (20% DC-550 on 60/80 Chrom W., 215°, 50 i p . s . i . ) i n t o 2 pure compounds: methyl B-methylcinnamate, (E)- (125a) (90.7%); - 135 -r e t e n t i o n time = 17.2 min ; m.p. 30-31° ( l i t . m.p. 29-30° (69)); n.m.r. 6 7.30 ( m u l t i p l e t , 5H, C ^ . - ) , 6.05 (quarte t , J = 1.2 Hz, 1H, -C(CH_)=CH), 3.63 ( s i n g l e t , 3H, -COOCH.) and 2.52 p.p.m. (doublet, J = 1.2 Hz, 3H, -CH=C(CH_)-), and methyl 3-phenylbut-3-enoate (126) (9.3%); r e t e n t i o n time = 12.8 min ; n.m.r. (CC1 4) 6 7.25 ( m u l t i p l e t , 5H, CgH.-), 5.45 and 5.16 (both s i n g l e t s , 2H, H.-C=C-), 3.55 ( s i n g l e t , 3H, -COOCH.) and 3.40 p.p.m. ( s i n g l e t , 2H, -C-CH--C). The stereochemistry o f methyl B-methylcinnamate, (E)-(125a) was confirmed by i r r a d i a t i o n of the p y r o l y s i s products i n a s i l i c a o tube at 2537 A , 75 W, 250 V f o r 48 h r s . The corresponding (Z)-isomer 125b (46.8%), n.m.r. 6 2.08 (doublet, J = 1.5 Hz, 3H, CH.-C(B)), 3.48 ( s i n g l e t , 3H, -COOCH.), 5.89 (qu a r t e t , J = 1.5 Hz, -CH=C(CH_)-) and 7.0-7.50 p.p.m. ( m u l t i p l e t , 5H, -C^H.) was observed together w i t h the (E)-isomer 125a (22.7%) and methyl 3-phenyl-3-butenoate (30.5%). 3-Carbomethoxy-3-cyano-4-methyl-4-p-methoxyphenyl-l-pyrazoline-(E) (119) was decomposed r e s p e c t i v e l y i n benzene and nitrobenzene at 70° f o r 2 hrs i n d e c a l i n at 70° f o r 5 hrs , t e t r a l i n at 60° f o r 8 hrs , formamide at 30° f o r 10 min and i n neat s o l u t i o n at room temperature f o r two months. When benzene and d e c a l i n were used as decomposition s o l v e n t s , the solve n t s were evaporated under reduced pressure and product compositions were analyzed by n.m.r. s p e c t r a i n CDC1-. When nitrobenzene and t e t r a l i n were used as decomp-o s i t i o n s o l v e n t s , the product compositions were measured d i r e c t l y by n.m.r. s p e c t r a i n the same s o l v e n t s . When formamide was used, the products i n s o l u b l i n t h i s s o l v e n t were d i s s o l v e d i n equal volume o f deuteriochloroform and the product compositions were measured by the n.m.r. s p e c t r a i n both s o l v e n t s measured under i d e n t i c a l c o n d i t i o n s . The product compositions o f these v a r i o u s decompositions are l i s t e d i n Results and D i s c u s s i o n , Table V I I . - 136 -3-Carbomethoxy-3-cyano-4-methyl-4-phenyl-l-pyrazoline-(E) (118a) was decomposed r e s p e c t i v e l y i n benzene and nitrobenzene at 70° f o r 2 h r s , , i n t e t r a l i n at 60° . f o r 8 hrs and i n neat at room temperature f o r 2 months. The product compositions of these decompositions, measured by the same methods as des c r i b e d f o r the corresponding p-methoxypyrazoline, are l i s t e d i n R e s u lts and D i s c u s s i o n , Table VI. 3-Carbomethoxy-3-cyano-4-methyl-4-p-nitrophenyl-l-pyrazoline-(E) (120a) was decomposed r e s p e c t i v e l y i n benzene, nitrobenzene and t e t r a l i n at 70° f o r 2 hrs and i n formamide at 30° f o r 10 min. The product compositions o f these decompositions, measured i n the same manner as described f o r the correspond-in g p-methoxypyrazoline, are l i s t e d i n Results and D i s c u s s i o n , Table V. 3-Carbomethoxy-3-cyano-4-methyl-4-phenyl-l-pyrazoline (Z)- (118b) was decomposed r e s p e c t i v e l y i n benzene and nitrobenzene at 70° f o r 2 hrs , i n a neat s o l u t i o n at room temperature f o r 24 hrs and at 70° at 5 min. The product compositions, measured by n.m.r. s p e c t r a , are l i s t e d i n Results and D i s c u s s i o n , Table V I I I . 3-Carbomethoxy-3-cyano-4-methyl-4-p-nitrophenyl-1-pyrazoline, (Z)-(120b) was decomposed r e s p e c t i v e l y i n benzene at 70° f o r 4 hrs and i n nitrobenzene at 70° f o r 20 min. The product compositions, measured by n.m.r. s p e c t r a , are l i s t e d i n Results and D i s c u s s i o n , Table V I I I . 3-Carbomethoxy-3-cyano-4-methyl-4-p-nitrophenyl-5-pyrazoline (133) This compound p r e c i p i t a t e d from p y r o l y s i s o f the corresponding 1-p y r a z o l i n e 120a i n t e t r a c h l o r o e t h y l e n e together w i t h some methyl a-cyano-3-eth y l - p - n i t r o c i n n a m a t e , (_)- (130a). Tne s o l i d was c o l l e c t e d and s l u r r i e d w i t h ether. F i l t r a t i o n y i e l d e d the pure 5 - p y r a z o l i n e , m.p. 171-172.5° (white needles, chloroform), n.m.r. 6 1.67 ( s i n g l e t , 3H, CH_-C(4)), 4.00 137 -( s i n g l e t , 3H, -COOCH_3), 6.51 (broad, 1H, -NH) , 6.81 ( s i n g l e t , 1H, H-C(5)j, 7.60 and 8.27 p.p.m. (both doublet, J = 8.8 Hz, 4H, -C.H.-); i . r . x n U ^ D l  r r 6—4 max 4 5.75 y (s t r o n g , -C=0), mass spectrum, m/e = 288, u.v. X 267 (e 1.860 x 10 ) my. Anal. Calcd. f o r C ^ H ^ N ^ : C, 54.14; H, 4.20; N, 19.43. Found: C, 54.17; H, 4.35; N, 19.29. The s t r u c t u r e o f t h i s p y r a z o l i n e was confirmed by D^ O exchange i n the n.m.r. spectrum: on a d d i t i o n o f D^ O i n CDCl^ s o l u t i o n , the peak at 6 6.48 p.p.m. disappeared. Methyl a-cyano-B-ethyl-p-nitrocinnamate, (E)- (130a) The decomposition products from 3-carbomethoxy-3-cyano-4-methyl-4-p-n i t r o p h e n y l - 1 - p y r a z o l i n e , (E)- (120a) i n benzene were separated by prepara-t i v e l a y e r chromatography w i t h C C l ^ and ether (2:1 r a t i o ) as s o l v e n t . . E x t r a c t i o n o f s i l i c a w i t h chloroform and evaporation of the solvent y i e l d e d the d e s i r e d o l e f i n 130a, R f = 0.39, m.p. 100-101° (white needles,. methanol), i . r . X 4.52 (medium, C E N ) and 5.77 y (st r o n g , -C=0), n.m.r. nicLX 6 1.05 ( t r i p l e t , J = 7.5 Hz, 3H, -CH 2-CH 3), 3.15 (qu a r t e t , J = 7.5 Hz, 2H, CH3-CH_2-C=C-), 3.91 ( s i n g l e t , 3H, -C00CH_3), 7.54 and 8.32 p.p.m. (both doublet, J = 8.5 Hz, 4H, - C ^ - ) ; u.v. X 275 (e 1.898 x 10 4) and 245 my ' 6-4 J ' max v • (e 1.133 x 1 0 4 ) . Anal. Calcd. f o r C ^ H ^ N ^ : C, 59.98; H, 4.65; N, 10.76. Found: C, 59.78; H, 4.63; N, 10.88. Methyl a-cyano-B-ethyl-p_-nitrocinnamate (Z)- (130b) 3-carb6methoxy-3-cyano-4-methyl-4-p-nitrophenyl-l-pyrazoline (2.0 gm ) was decomposed i n t e t r a c h l o r o e t h y l e n e (5.0 ml ) at 70° f o r 1 hr The s o l u t i o n was cooled to room temperature; the s o l i d was c o l l e c t e d by s u c t i o n f i l t r a t i o n and p u r i f i e d by alumina l a y e r chromatography e l u t e d by c h l o r o -form. E x t r a c t i o n of alumina at = 0.8 w i t h hot chloroform and evaporation - 138 -of t h i s s olvent y i e l d e d the t i t l e d compound 130b (52.3%), n.m.r. 6 1.10 ( t r i p l e t , J = 7.5 Hz, 3H, -CH2CH_3) , 2.91 (q u a r t e t , J = 7.5 Hz, 2H, -CH_2CH3), 3.68 ( s i n g l e t , 3H, -C00CH 3), 7.32 and 8.27 p.p.m. (both doublet, J = 9.0 Hz, 4H, -C^H^). The corresponding (E)-isomer 130a (48.7%) was a l s o obtained together w i t h the t i t l e d compound. l-Carbomethoxy-l-cyaho-2-'p-nitrophenyl-2-methylcyclopropane, (E) - (131a) ' In s i m i l a r manner as described f o r i s o l a t i o n o f the (E)-cinnamate 130a, e x t r a c t i o n of s i l i c a at = 0.29 with hot chloroform and evaporation of s o l v e n t y i e l d e d the d e s i r e d cyclopropane, (50%) together w i t h methyl ocyano-3-p-nitrobenzylcrotonate,(Z_)- and (E)-isomers (1:1). R e c r y s t a l l i z a t i o n of t h i s mixture four times from methanol gave the a n a l y t i c a l l y pure c y c l o -propane 131a, m.p. 142-143° (white needles), i . r . X m a x 4.52 (medium, -CEN) and 5.80 y (stro n g , -C=0); n.m.r. <5 1.62 ( s i n g l e t , 3H, CH 3-C(2)), 2.18 ( s i n g l e t , 2H, H_ 2C(3)), 3.90 ( s i n g l e t , 3H, -C00CH 3), 7.52 and 8.25 p.p.m. (doublet, J = 8.8 Hz, 4H, - C ^ - ) . Anal. Calcd. f o r C 1 3 H 1 2 N 2 ° 4 : C> 5 9- 9 8> H, 4.65; N, 10.76. Found: C, 59.78; H, 4.63; N, 10.88. The stereochemistry o f cyclopropane 131a was e s t a b l i s h e d by heating the crude sample at 175° f o r 3 h r s . Rearrangement took place to give methyl 2-cyano-4-p-nitrophenylpent-4-enoate (140), p u r i f i e d by p r e p a r a t i v e l a y e r chromatography using HCC1 as s o l v e n t , R,. = 0.43, i . r . X 4.50 (medium, -C=N) and 5.74 y (stro n g , -C=0); n.m.r. 6 3.12 (quartet, J = 1.0 Hz, gem J = 9.0 Hz, 1H, H-CH-CH), 3.21 (quart e t , J g g m = 1.0 Hz, J = 5.8 Hz, 1H, H-CH-CH-), 3.56 (q u a r t e t , J = 5.8 and 9.0 Hz, 1H, H 2C-CH-), 3.73 ( s i n g l e t , 3H, -C00CH 3), 5.47 and 5.59 (both s i n g l e t s , 2H, H_2C=C-), 7.55 and 8.21 p.p.m. (both doublets, J = 8.5 Hz, 4H, -CM,-); u.v. X 277.5 (e 1.766 x 10 4) . ' . 6-4 J ' max J and 217.5 (e 9.114 x 10 3) my.. -.139 -Methyl:a-cyano-8-p-nitrobenzylcrotonate, (Z)- and (E)- (132b and 132a) In s i m i l a r manner as described f o r i s o l a t i o n of the (E)-cinnamate 130a e x t r a c t i o n of s i l i c a at = 0.20 w i t h hot chloroform and evaporation of the solvent y i e l d e d a (Z)- and (E)- mixture of the d e s i r e d o l e f i n as a yel l o w o i l y l i q u i d ; n.m.r. spectrum o f the (Z)-isomer 132b: 6 2.26 ( s i n g l e t , 3H, CH_C=C-), 3.92 ( s i n g l e t , 3H, -C00CH_), 4.36 ( s i n g l e t , 2H, ArCH.-C-), 7.48 and 8.24 p.p.m. (both doublets, J = 8.5 Hz, 4H, -C^H^-). (E)-isomer 132a: 6 2.35 ( s i n g l e t , 3H, CH_C=C-), 3.90 ( s i n g l e t , 3H, -C00CH-), 4.07 ( s i n g l e t , 2H, ArCH.-C-), 7.51 and 8.26 p.p.m. (both d o u b l e t s , J = 8.5 Hz, 4H, - C ^ - ) . An attempt t o p u r i f y t h i s mixture by d i s t i l l a t i o n under vacuo was unsuccess-f u l due to the high b o i l i n g p o i n t o f these o l e f i n s . l-Carbomethoxy-l-cyano-2-methyl-2-p-nitrophenylcyclbpropane, (Z)- (131b) This cyclopropane was i s o l a t e d from p y r o l y s i s o f 3-carbomethoxy-3-cyano-4-methyl-4-p-nitrophenyl-l-pyrazoline, (Z)- (120b) i n neat s o l u t i o n . S u c t i o n f i l t r a t i o n gave the d e s i r e d cyclopropane (10%), m.p. 167.5-168.5° (white needles, methanol); i . r . X 4.50 p (medium, -C=N) and 5.75 u (strong; n._L_c -C=0), n.m.r. 6 1.81 ( s i n g l e t , 3H, CH.-C(2)), 1.88 and 2.48 (both doublets, Jgem = 5 , 8 H z ' 2 H ' M. 2 C( 3))> 3 * 5 9 ( s i n g l e t , 3H, -C00CH_), 7.46 and 8.22 p.p.m. (both doublets, J = 8.8 Hz, 4H, - C ^ - ) . A n a l . Calcd. f o r C 1 3 H 1 2 N 2 0 4 : C ' 59.98; H, 4.65; N, 10.76. Found: C, 59.78; H, 4.47; N, 10.67i The stereochemistry of cyclopropane 131b was confirmed by heating the sample at 170° f o r 2 h r s . during which no rearrangement i n t o methyl-2-cyano-4-p-nitrophenylpent-4-enoate was observed. Methyl a-cyano-6-benzyl-crotonate, (Z)- (136b) This compound was obtained from the decomposition of 3-carbomethbxy-3-cyano-4-methyl-4- :phenylpyrazoline, (Z)- i n benzene s o l u t i o n . D i s t i l l a t i o n I - 140 -of the decomposition products y i e l d e d the d e s i r e d o l e f i n (over 90%), i . r . Xmax* f l l m 4 - 5 2 A n - m - r - 6 2 - 1 0 ( s i n g l e t , 3H, CH_3C=C-) , 3.75 ( s i n g l e t , 3H, -C00CH 3), 4.11 ( s i n g l e t , 2H, C ^ C H ^ - ) , and 7,0-7.5 ( m u l t i p l e t , 5H, C ^ - ) ; i . r . X L I Q ' f l l m 4.52 y(medium, - C E N ) , and 5.78 y (str o n g , -C=0), u.v. X max J max 231 (6 1.478 x 10 4)my. Anal. Calcd. f o r C ^ H ^ N C y C, 72.54; H, 6.09; N, 6.50. Found: C, 72.74; H, 6.29; N, 6.30." I s o l a t i o n of Decomposition Products by v.p.c. The products obtained from decomposition of 3-carbomethoxy-3-cyano-4-methyl-4-phenylpyrazoline, (E) - (118a) showed only one spot from t h i n l a y e r chromatography performed on either alumina or s i l i c a w i t h petroleum ether (30-60°), benzene, chloroform, ether or various combinations of two of these s o l v e n t s . One spot was a l s o obtained from the corresponding p-methoxyphenylpyrazoline. However, the products from the former p y r a z o l i n e 118a were separated by v.p.c. (DC-550, 220°, 50 p . s . i . ) i n t o four components: (1) r e t e n t i o n time = 27.9 min , (2) r e t e n t i o n time = 30.6 min (3) 32.8 min and (4) 39.0 min. The samples under the f i r s t three peaks were c o l l e c t e d together and i t s n.m.r. (CCl^) spectrum showed a mixture of three compounds: (1) methyl a-cyano-3-ethylcinnamate, (E)- (134a) (36.5%), n.m.r. 6 1.03 ' ( t r i p l e t , - J = 5.4 Hz, 3H, -CH 2CH 3), 3.08 (quartet, J = 5.4 Hz, 2H, -C=C(CH_2CH3)-), 3.84 ( s i n g l e t , 3H, -COOCHj) and 7.0-7.5 p.p.m. ( m u l t i p l e t , 5H, C ^ - ) ; (2) methyl a-cyano-B-ethylcinnamate, (Z)- (134b) (39.5%); n.m.r.6 1.06 ( t r i p l e t , J = 5.5 Hz, 3H, -CH 2CH 3), 2.84 (quar t e t , J = 5.5 Hz, 2H, C=C-CH2-CH3), 3.60 . ( s i n g l e t , 3H, -C00CH_3) and 7.0-7.50 p.p.m. ( m u l t i p l e t , 5H, C ^ - ) ; and (3) methyl 2-cyano-4-phenyl-4-pentenoate (24%); 6 3.69 ( s i n g l e t , 3H, -C00CH_3), 5.30 and 5.44 (both s i n g l e t , 1H each, H_2C=C-) and 7.0-7.5 ( m u l t i p l e t , 5H, -C A l ) . The two hydrogen peaks at C(3) of the l a t t e r compound were hidden - 141 -under the two quartets o f the f i r s t two compounds. The r a t i o s o f these three compounds were obtained from the i n t e g r a t i o n of the methyl e s t e r peak of each sample. The l a s t peak from the v.p.c. was c o l l e c t e d s e p a r a t e l y t o give a mixture o f methyl a-cyano-B-benzylcrotonate, (E)- (136a) (59%), n.m.r. (CC1 4) : 6 2.35 ( s i n g l e t , 3H, CH_3C=C-), 3.92 ( s i n g l e t , 2H, C gH CH_2C=C--), 3.89 ( s i n g l e t , 3H, -COOCH3) and 7.15-7.5 p.p.m. ( m u l t i p l e t , 5H, C ^ - ) and methyl a-cyano-g-benzylcrotonate, (Z)- (136b) (41%), n.m.r. 6 2.24 ( s i n g l e t , 3H, CH 3C=C-), 4.26 ( s i n g l e t , 2H, C ^ C H ^ C ) , 3.92 ( s i n g l e t , 3H, -COOCHj) and 7.15-7.5 p.p.m. ( m u l t i p l e t , 5H, C^Hg-). The r a t i o o f these two compounds were obtained from the i n t e g r a t i o n of the methyl or carbomethoxy groups. I s o m e r i z a t i o n of Methyl a-cyano-B-benzylcrotonate, (E)- and Methyl a~ cyano-g-ethylcinnamate, (E)- by p y r i d i n e 0.2 gm of 3-carbomethoxy-3-cyano-4-methyl-4-phenyl-l-pyrazoline, (EJ-(118a) was pyr o l y z e d i n benzene at 70° f o r 2 hrs and the s o l u t i o n r o t a r y evaporated to give methyl a-cyano-B-benzylcrotonate, (EJ- (136a) (26.5%) and methyl a«cyano-B-ethylcinnamate, (E)- (134a) (53%) as the major products ( f o r composition of other products see Table V I ) . A t r a c e of p y r i d i n e i n deuteri o c h l o r o f o r m was added to t h i s mixture and the n.m.r. spectrum was taken p e r i o d i c a l l y . ~ These n.m.r. s p e c t r a showed that methyl a-cyano-g-benzylcrotonate reached i t s i s omeric e q u i l i b r i u m ( ( E ) - : (Z)-:58:42) w i t h i n one day whereas methyl . a-cyano-B-ethylcinnamate ((E)-:(Z)-:64:36) r e q u i r e d s i x days (four days, at room temperature and two days at 50°). Further heating o f the mixture at 50° d i d not change the composition o f these isomers. - 142 -Iso m e r i z a t i o n of methyl ct-cyano - g-benzylcrotonate, (Z)- (136b) by 1-p y r a z o l i n e • 0.61 gm (2.37 mmoles) of 3-carbomethoxy-3-cyano-4-ethyl-4-phenyl-l-p y r a z o l i n e , (Z)- and (E)- (1:1) (141) was allowed to mix with 0.0961 g (0.46 mmoles) of methyl ct-cyano - g-benzylcrotonate, (Z)- (136b) (together with 5.2% of i t s (E)-isomer) i n benzene at 70° f o r 4 h r s . The n.m.r. of the r e s u l t i n g mixture showed that the o l e f i n was isomerized by the decomposing p y r a z o l i n e i n t o i t s isomeric mixture (Z)-:(E)-=54:46. The r a t i o were measured by the i n t e g r a t i o n o f methyl peaks at 6 2.11 and 2.25 p.p.m. of (Z)- and (E)-isomers r e s p e c t i v e l y . Thermal i s o m e r i z a t i o n of methyl ct-cyano -g-methylcinnamate, (E)- (100a) Methyl a-cyano -g-methylcinnamate, (E)- (100a) i n s i x separate sealed tubes was heated i n an o i l bath at 140°. One tube was taken out every 10 mins and the c i s - t r a n s i s o m e r i z a t i o n r e a c t i o n was quenched by p u t t i n g t h i s tube i n i c e s a l t mixture. The composition o f (Z)- and (E)-isomer i n each tube was measured by the i n t e g r a l o f the chemical s h i f t p o s i t i o n s at 6 2.65 and 3.84 p.p.m. repr e s e n t i n g the percentage of the (E)-isomer and 6 2.50 and 3.60 p.p.m. re p r e s e n t i n g the percentage of the (Z)-isomer. A f i r s t order, k i n e t i c p l o t was obtained w i t h t - ^ _ = 122.8 min f o r t h i s r e a c t i o n . The r e a c t i o n reached an e q u i l i b r i u m mixture a f t e r h a l f an hour with (E)-:(Z)-= 66.5:33.5. K i n e t i c Measurements  Solvents The s o l v e n t s used f o r k i n e t i c s were p u r i f i e d as f o l l o w s : T e t r a l i n (reagent grade, F i s h e r Chem. Co.) was d r i e d over calcium c h l o r i d e f o r 24 hrs and d i s t i l l e d twice under reduced pressure, b.p. 77° - 143 -(20 mm.), n 2 5 1.5389 ( l i t . n 2 5 1.53919) (114). Nitrobenzene (reagent grade, B r i t i s h Drug House) was washed w i t h d i l u t e H-SO^, NaHC0_ s o l u t i o n and f i n a l l y w i t h water. A f t e r d r y i n g over calcium c h l o r i d e , the nitrobenzene was d i s t i l l e d twice under reduced pressure; b.p. 87° (20 mm.), n^ 1.5521 ( l i t . n^ 1.5529) (115). Formamide (Eastman White Label) was d i s t i l l e d twice under reduced pressure b.p. 104° (15 mm.), n 2 3 1.4454 ( l i t . n 2 2 , 7 1.44530) (115). D e c a l i n (reagent grade, F i s h e r Chem. Co.) was d r i e d over calcium c h l o r i d e f o r 24 hrs and d i s t i l l e d twice under reduced pressure, b.p. 72° 18 IS (15 mm.), n j 1.4755 ( l i t . n j 1.46994) (115). Solutes The f o l l o w i n g a n a l y t i c a l l y pure p y r a z o l i n e s were used f o r the k i n e t i c measurement. (For p r e p a r a t i o n of these p y r a z o l i n e s see Experimental S e c t i o n I I , p. 130). 3-Carbomethoxy-3-cyano-4-methyl-4-phenyl-l-pyrazoline, (E)-(118a); 3-carbomethoxy-3-cyano-4-methyl-4-p-methoxyphenyl-l-pyrazoline, (E)-(119); 3-carbomethoxy-3-cyano-4-methyl-4-p-nitrophenyl-l-pyrazoline, (E)-(120a); 3-carbomethoxy-3-cyano-4-methyl-4-p-nitrophenyl-l-pyrazoline, (ZJ-(120b); and 3-carbomethoxy-3-cyano-4-methyl-4-phenyl-5,5-dideuterio-l-p y r a z o l i n e , (E)- (121). K i n e t i c Apparatus The r a t e s o f decomposition of the 1-pyrazolines were determined by v o l u m e t r i c measurement of the r a t e o f formation of n i t r o g e n . The apparatus used f o r the k i n e t i c determinations i s shown i n Figure XXVII. The design i s s i m i l a r to that o f Peterson e_t.al_. (116) w i t h m o d i f i c a t i o n s made where r e q u i r e d . The heating bath E c o n s i s t e d of a 4 l i t r e s t a i n l e s s s t e e l beaker set i n s i d e a l a r g e s olvent can and w e l l i n s u l a t e d w i t h glass wool. The heat - 144 -A. Reaction Vessel H. Water Jacket B. Nitrogen I n l e t I. Buret, 50 ml C. Sample I n l e t , B19 J o i n t J . Constant Temperature Water Pump D. Magnetic S t i r r e r K. Three-way Stopcock E. O i l Bath L. Three-way Stopcock F. Condenser M. U-tube Manometer G. C a p i l l a r y Tubing N. Bubbler Figure XXVII - K i n e t i c Apparatus - 145 -exchange medium was Dow Corning S i l i c o n e f l u i d (DC-550). A la r g e f l e x i b l e c o i l e d h eating u n i t provided a constant heat input and a smaller heating u n i t was c o n t r o l l e d by a thermoregulator and r e l a y c i r c u i t . The temperature c o n t r o l was t o w i t h i n 1 0.05°. The contents o f the r e a c t i o n f l a s k A were s t i r r e d by an a i r - d r i v e n magnetic s t i r r e r D (Bromwell). The f i l t e r e d a i r supply was re g u l a t e d by means of screw clamp to provide a constant s t i r r i n g speed. The connections between the condenser F and the measuring buret (50 ml ) I c o n s i s t e d of c a p i l l a r y tubing to reduce.errors due to f l u c t u a t i n g room temperature. A constant temperature water pump J was employed to s t a b i l i z e the temperature i n water j a c k e t s o f the measuring buret and the condenser. The evolved n i t r o g e n was measured over mercury. A U-tube manometer M f i l l e d w i t h n -butyl p h t h a l a t e was attached to the buret to ensure that the pressure i n s i d e the apparatus was equal to the atmospheric pressure when a reading was taken. Time was recorded by an e l e c t r i c , chronometer (lab-Chron). The thermometer used ranging from 0-100° was c a l i b r a t e d against a N.B.S. c a l i b r a t i o n thermometer. A glass spoon was used f o r i n t r o d u c i n g the sample i n t o the r e a c t i o n f l a s k . K i n e t i c Measurements The general procedure f o r a run was as f o l l o w s . ' The temperature of the o i l bath E was set at the r e q u i r e d temperature, the r e a c t i o n f l a s k A, w i t h 50 ml of s o l v e n t , was immersed and s t i r r i n g was commenced. The stopcocks K and L were set so that the expanding a i r and n i t r o g e n could escape through the bubbler N. A steady stream of n i t r o g e n ( p u r i f i e d by 50% aqueous NaOH s o l u t i o n c o n t a i n i n g 15 gm of p y r o g a l l i c a c i d and then CaC^ and NaOH) was passed through stopcock B i n t o the system f o r 30 min. Stopcock B was - 146 -then clo s e d and the system allowed to e q u i l i b r a t e f o r 30 min. At the end of t h i s p e r i o d the mercury l e v e l was set to zero and L was closed from N. Stopcock C was opened, c r y s t a l l i n e p y r a z o l i n e was introduced i n t o the s o l u t i o n by the gl a s s spoon and C cl o s e d again c o n c u r r e n t l y w i t h the chronometer being s t a r t e d . The gl a s s spoon and the sample was weighed before the a d d i t i o n on an a n a l y t i c a l balance. Re-weighing the empty spoon gave the amount of p y r a z o l i n e t r a n s f e r r e d to the f l a s k . From the amount o f p y r a z o l i n e added the volume of n i t r o g e n evolved at t°° could be c a l c u l a t e d by the f o l l o w i n g formula: V°° = W t * °f s a m P j - e x 22414 at standard temperature and pressure molecular wt. r r the readings were taken as f o l l o w s : the mercury i n the buret was lowered to such a l e v e l t h a t the i n s i d e pressure o f the system was about 2-3 cm l e s s than the atmospheric pressure. When the p r e s s u r e of both i n s i d e and out o f the system approached e q u a l i t y the volume o f n i t r o g e n evolved and the time were recorded. In t h i s way readings could be taken i n l e s s than h a l f a minute. The frequency of the volume reading depended on the h a l f l i f e o f the decompositions; u s u a l l y about 30-40 readings were taken f o r each run. The c l o s e readings were necessary i n order to determine the p o i n t o f e q u i l i b r a t i o n between solvent and s o l u t e . The atmospheric pressure was recorded p e r i o d i c a l l y during a run. Reactions were g e n e r a l l y followed to 80% completion, . " When formamide was used as s o l v e n t , the r a t e o f n i t r o g e n e v o l u t i o n was so f a s t t h a t i t r e q u i r e d one person to c o n t r o l the pressure of the system and read out the volume o f n i t r o g e n w h i l e another person recorded t h i s volume" - 147 -and the time when the volume was read. In t h i s way, volume readings could be recorded every 20 seconds. A f t e r each run, the volume readings were c o r r e c t e d t o standard tempera-tur e and pressure t o give V (or c a l c u l a t e d from the amount of p y r a z o l i n e used was converted to the volume of n i t r o g e n at that temperature and pressure when the volume readings V were taken), and the r a t e constants (see Results and D i s c u s s i o n , Table X ) . Most of the k i n e t i c runs gave good s t r a i g h t l i n e p l o t s to 80% completion. When s l i g h t d e v i a t i o n from l i n e a r i t y occur, they were a t t r i b u t e d to solvent vapour e f f e c t s . K i n e t i c Conditions (a) f o r e l e c t r o n i c e f f e c t o f a r y l groups i n 1-pyrazolines The r a t e s o f decomposition o f the (E)-phenylpyrazoline 118a,(E)-p-methoxyphenylpyrazoline 119 and ( E ) - p - n i t r o p h e n y l p y r a z o l i n e 120a were measured i n nitrobenzene at 44.85°, 49.82°, 54.84° and 64.90° r e s p e c t i v e l y . At l e a s t two runs were done f o r each decomposition i n order to e s t a b l i s h the r e p r o d u c i b i l i t y o f these k i n e t i c measurements. The r a t e constant of each decomposition and the a c t i v a t i o n parameters c a l c u l a t e d from the Arrhenions Equations are summarized i n Results and D i s c u s s i o n , Table X . The Arrhenions p l o t s o f each p y r a z o l i n e are shown i n Figure X X I . (b) f o r the stereochemical e f f e c t o f a r y l groups i n 1-pyrazolines The r a t e s o f decomposition o f p - n i t r o p h e n y l p y r a z o l i n e s 120a and 120b were measured i n nitrobenzene at 54.84° . Two runs were performed f o r each decomposition. The r a t e constants o f these decompositions are l i s t e d i n Table X and the f i r s t order r a t e p l o t s are shown i n Figure X X I I . (c) f o r solvent e f f e c t o f 1-pyrazclines The r a t e o f decomposition o f the ( E ) - a r y l p y r a z o l i n e s 118a, 119 and 120a were measured i n t e t r a l i n at 54.84° and a l s o the (E)-p-methoxyphenylpyrazoline - 148 -119 i n t e t r a l i n and d e c a l i n r e s p e c t i v e l y at 75.28° , and formamide at 34.95° At l e a s t two runs were performed f o r each decomposition. 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