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Mechanistic studies of the decomposition of 1-pyrazolines Szilagyi, Sandor 1974

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MECHANISTIC STUDIES OF THE DECOMPOSITION OF l-PYRAZOLINES by SANDOR SZILAGYI M.Sc, Brock U n i v e r s i t y , 1969 A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY i n the Department of CHEMISTRY We accept t h i s t h e s i s as conforming to the req u i r e d standard THE UNIVERSITY OF BRITISH COLUMBIA FEBRUARY, 1974 In p r e s e n t i n g t h i s t h e s i s in p a r t i a l f u l f i l m e n t o f the r equ i r emen t s f o r an advanced degree at 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 , I ag ree that the L i b r a r y s h a l l make i t f r e e l y a v a i l a b l e f o r r e f e r e n c e and s tudy . I f u r t h e r agree 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 purposes may be g r a n t e d by the Head o f my Department or by h i s r e p r e s e n t a t i v e s . It i s u n d e r s t o o d that 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 not be a l l owed w i thout my w r i t t e n p e r m i s s i o n . Department The U n i v e r s i t y o f B r i t i s h Co lumbia Vancouver 8, Canada ABSTRACT A s e r i e s of p y r a z o l i n e s having a carbomethoxy group on C-3 and a bridge (number of the carbon atoms = 3, 4, 5) connecting C-3 and C-4 was synthesized and s t u d i e d . l-Carbomethoxy-2,3-diazabicyclo (3.3.0)oct-2-ene-5d^ was a l s o prepared and the o v e r a l l deuterium k i n e t i c isotope e f f e c t determined. The c a l c u l a t i o n s concerning the s p e c i f i c deuterium k i n e t i c isotope e f f e c t s f o r the d i f f e r e n t processes involved i n the thermolysis led to values s i m i l a r to those obtained from other experiments w i t h the exception of t h a t f o r cyclopropane formation which was found to have a " i n v e r s e " isotope e f f e c t 3-tert-Butyl-3-carbomethoxy-1-pyrazoline was synthesized and i t s thermal and photo decomposition s t u d i e d . The e f f e c t o f the s i z e o f the e s t e r group on product d i s t r i b u t i o n was a l s o examined by undertaking a product study on 3-methyl-3-carbethoxy-1-pyrazoline and 3-methyl-3-carbo-tert-butoxy-1-pyrazoline. c i s - and trans-3-Methyl-3-carbomethoxy-l-pyrazoline-4d^ and t r a n s -3-methyl-carbethoxy-l-pyrazoline-4d^ were prepared. K i n e t i c s t u d i e s were done on the trans isomers and the s p e c i f i c deuterium k i n e t i c isotope effects were c a l c u l a t e d from the measured o v e r a l l k i n e t i c isotope e f f e c t s . The n.m.r. s t u d i e s of 1-methyl-l-carbomethoxy-cyclopropane-2d^ obtained by both the thermal and s e n s i t i z e d photo-decomposition o f c i s - and trans-3-methyl-3-carbomethoxy-l-pyrazoline-4dj revealed that each of the samples i s o l a t e d ( c o l l e c t e d from the gas chromatograph) from the four decomposition products contained equal amounts of c i s - and trans-1-methyl-1-carbomethoxycyclopropane-2- d^. E s p e c i a l l y these r e s u l t s , but a l s o the thermal and photo-decomposition of c i s - and trans-3-methyl-4-tert-butyl-3-carbomethoxy-l-p y r a z o l i n e s , suggested that the cyclopropane formation occurred v i a a d i r a d i c a l intermediate i n which the f r e e r o t a t i o n about the carbon-carbon bond would be reduced or prevented by b u l k y s u b s t i t u e n t s . The formation of deuterated 3 , y - o l e f i n i c e s t e r s and e t h y l and methyl angelate-4d^ as w e l l as e t h y l and methyl t i g l a t e - 3 d ^ from the t r a n s -isomers corroborated McGreer's suggestion f o r s t e r e o s p e c i f i c o l e f i n formation. K i n e t i c and product s t u d i e s done on a s e r i e s o f c i s - and t r a n s -3- methyl-4-alkyl-3-carbomethoxy-l-pyrazolines ( a l k y l = i s o p r o p y l , i s o b u t y l and t e r t - b u t y l ) provided a d d i t i o n a l proof f o r s t e r e o s p e c i f i c o l e f i n formation and a l s o s u b s t a n t i a t e d the idea of r e s t r i c t e d or - iv -prevented r o t a t i o n about the carbon-carbon bond i n the 1,3-diradical intermediate. Since both c i s - and trans - 3-methyl - 4-tert-butyl - 3-carbomethoxy-l-p y r a z o l i n e s gave only cyclopropane product upon thermolyses i n c o n t r a s t to most p y r a z o l i n e s i t became p o s s i b l e to undertake a d i r e c t measure-ment of the secondary g deuterium k i n e t i c isotope e f f e c t f o r cyclopropan formation. - V -TABLE OF CONTENTS . Page TITLE PAGE i ABSTRACT i i TABLE OF CONTENTS v LIST OF TABLES x i i i ACKNOWLEDGEMENTS x i v INTRODUCTION PREPARATION OF PYRAZOLINES 1 MECHANISM OF PYRAZOLINE DECOMPOSITION 1 I. Ionic mechanism 2 I I . D i r a d i c a l mechanism 12 I I I . Concerted mechanism 33 (a) Retro D i e l s - A l d e r r e a c t i o n s 34 (b) Concerted o l e f i n formation 35 (c) Cyclopropane r i n g a s s i s t e d decompositions 37 OBJECTIVE OF PRESENT RESEARCH DISCUSSION 43 I. Some of the general features of thermal decomposition of 1-pyrazolines which served as a b a s i s f o r research plans. 46 I I . 3 - A l k y l p y r a z o l i n e s 47 - v i -l l i . K i n e t i c and product s t u d i e s o f 1-carbomethoxy-2,3-diazabicyclo(3.3.0)oct-2-ene and i t s analogue-5d^ 52 IV. Stereochemical f a c t o r s a f f e c t i n g o l e f i n formation 57' (a) The e f f e c t o f the s i z e of the e s t e r group on o l e f i n formation, 3-methyl-3-carbalkoxy-l-p y r a z o l i n e s 57 (b) The e f f e c t o f the s i z e of the a l k y l group at C-4 on o l e f i n formation 60 (c) Deuterium k i n e t i c isotope e f f e c t of o l e f i n formation, k i n e t i c and product s t u d i e s on 3-methyl-3-carbalkoxy-l-pyrazolines-4d 1 63 (d) B , Y - 0 l e f i n formation 66 V. Mechanistic c o n s i d e r a t i o n o f cyclopropane formation 68 VI. P h o t o l y s i s o f p y r a z o l i n e s 73 SUMMARY 75 EXPERIMENTAL 79 I. General statements 79 I I . P reparation o f 3-methyl-3-cyano-l-pyrazoline 80 I I I . P reparation o f 3-tert-butyl-3-carbomethoxy-1-p y r a z o l i n e 80 (a) Preparation of methyl 2-tert-butylpropen-2-oate 80 1. 3,3-Dimethyl-2-oxobutanoic a c i d 81 2. Methyl 3,3-dimethyl-2-oxobutanoate 81 3. Methyl 2,3,3-trimethyl-2-hydroxybutanoate 81 4. Methyl 2-tert-butylpropen-2-oate i 82 (b) Preparation of 3-tert-butyl-3-carbomethoxy-l-p y r a z o l i n e 83 IV. Product s t u d i e s of 3-tert-butyl-3-carbomethoxy-1-p y r a z o l i n e and the synthesis of methyl ( Z ) - 2 - t e r t -butylbuten-2roate 84 - v i i -(a) Thermal decomposition o f 3 - t e r t - b u t y l - 3 -carbomethoxy-l-pyrazoline 84 (b) D i r e c t p h o t o l y s i s of 3-tert-butyl-3-carbomethoxy-1-pyrazoline 87 (c) S e n s i t i z e d p h o t o l y s i s o f 3 - t e r t - b u t y l - 3 -carbomethoxy-l-pyrazoline 87 V. Preparation o f l-carbomethoxy-2,3-diazabicyclo(3.3.0)oct-2-ene and i t s analogue-5d^ 88 (a) Preparation of l-carbomethoxy-2,3-diazabicyclo (3.3.0)oct-2-ene 88 1. 1-Cyclopentenecarboxylic a c i d 89 2. 1-Carbomethoxycyclopentene 90 3. l-Carbomethoxy-2,3-diazabicyclo(3.3.0)oct-2-ene 90 (b) Preparation of l-carbomethoxy-2,3-diazabicyclo (3.3.0)oct-2-ene-5d 1 91 1. 1-Cyclopentenecarboxylic acid-2d^ 91 2. l-Carbomethoxycyclopentene-2d^ 91 3. l-Carbomethoxy-2,3-diazabicyclo(3.3.0)oct-2-ene-5d 1 92 VI. Product s t u d i e s of l-carbomethoxy-2,3-diazabicyclo (3.3.0)oct-2-ene a n d , i t s analogue-5d^ 92 (a) Thermal decomposition of l-carbomethoxy-2,3-diazabicyclo(3.3.0)oct-2-ene and i t s analogue-5d^ 92 (b) Photolyses of l-carbomethoxy-2,3-diazabicyclo(3.3.0)oct-2-ene and i t s analogue-5d 1 94 V I I . Preparation of l-carbomethoxy-2,3-diazabicyclo(4.3.0)non-2-ene and l-carbomethoxy-2,3-diazabicyclo(5.3.0)dec-2-ene 95 V I I I . Product s t u d i e s of l-carbomethoxy-2,3-diazabicyclo(4.3.0)non-2-ene 98 IX. Product studies of l-carbomethoxy-2,3-diazabicyclo(5.3.0)dec-2-ene 99 X. 3-Methyl-3-carbo-tert-"butoxy-l-pyrazolone. 100 Preparation of c i s - and trans-3-methyl-4-alky1-3-carbomethoxy p y r a z o l i n e s (a) General procedure f o r the p r e p a r a t i o n of B-hydroxy e s t e r s 1. Methyl 2,4-dimethyl-3-hydroxypentanoate 2. Methyl 2,5-dimethyl-3-hydroxyhexanoate 3. Methyl 2,4,4-dimethyl-3-hydroxypentanoate (b) General procedure f o r the p r e p a r a t i o n of o l e f i n e s t e r s 1. Methyl (E)- and (Z)-2,4-dimethylpenten-2-oate 2. Methyl (E)- and (Z)-2,5-dimethylhexen-2-oate 3. Methyl (E)- and (Z)-2,4,4-trimethylpenten-2-oate (c) P y r a z o l i n e s 1. cis-3-Methyl-4-isopropyl-5-carbomethoxy-1-pyrazoline 2. trans-3-Methyl-4-isopropyl-3-carbomethoxy-1-pyrazoline 3. cis-3-Methyl-4-isobutyl-3-carbomethoxy-1-pyrazoline 4. trans-3-Methyl-4-isobutyl-3-carbomethoxy-1-pyrazoline 5. cis-3-Methyl-4-tert-butyl-3-carbomethoxy-1 p y r a z o l i n e 6. trans-3-Methyl-4-tert-butyl-3-carbomethoxy 1-pyrazoline Preparation of c i s - and t r a n s - 3 - m e t h y l - 4 - t e r t - b u t y l -3-carbomethoxy-1-pyrazoline-4d^ (a) Preparation of methyl 2,4,4-trimethyl-3-ketopentanoate (b) Preparation of methyl 2,4,4-trimethyl-3-hydroxypentanoate-3d 1 - i x -(c) Preparation of methyl (E)- and (Z)-2,4,4-trimethylpenten-2-oate-3d 111 (d) Preparation of c i s - and trans-3-methyl-3-carbomethoxy-l-pyrazoline-4d 1 112 1. cj 1s-3-Methyl-4-tert-butyl-3-carbomethoxy l - p y r a z o l i n e - 4 d ^ 112 XIII. XIV. XV. XVI. XVII. XVIII. XIV. 2. trans-3-Methyl-4-tert-butyl-3-carbomethoxy-l - p y r a z o l i n e - 4 d j 112 Preparation of trans-3-methyl-3-carbethoxy-l-p y r a z o l i n e - 4 d ^ 113 Product s t u d i e s of trans-3-methyl-3-carbethoxy-l-p y r a z o l i n e - 4 d j 113 (a) Thermal decomposition of trans-3-methy1-3-c a r b e t h o x y - l - p y r a z o l i n e - 4 d ^ 113 (b) D i r e c t p h o t o l y s i s of trans-3-methy1-3-ca r b e t h o x y - l - p y r a z o l i n e - 4 d ^ 115 Preparation of 3-methyl-3-carbethoxy-l-pyrazoline 116 Preparation of trans-3-methyl-3-carbomethoxy-l - p y r a z o l i n e - 4 d ^ 117 Product studies of trans-3-methyl-3-carbomethoxy-l - p y r a z o l i n e - 4 d ^ 118 (a) Thermal decomposition 118 (b) D i r e c t p h o t o l y s i s of trans-3-methyl-3-carbomethoxy-1-pyrazoline-4d^ 119 (c) S e n s i t i z e d p h o t o l y s i s of trans-3-methyl-3-carbomethoxy-l-pyrazoline-4d^ 120 Preparation of cis3-methyl-3-carbomethoxy-l-p y r a z o l i n e - 4 d ^ 120 Product s t u d i e s of cis-3-methy1-3-carbomethoxy-1-pyrazoline 122 (a) Thermal decomposition 122 (b) S e n s i t i z e d p h o t o l y s i s 122 - X -XX. Product s t u d i e s of c i s - and trans-3-methyl-4-alky1-3-carbomethoxy-l-pyrazolines 122 1. Thermal decompositions 122 (a) cis-3-Methyl-4-isopropyl-3-carbomethoxy-1-pyrazoline 125 (b) trans-3-Methyl-4-isopropyl-3-carbomethoxy-l-pyrazoline 126 (c) cis-3-Methyl-4-risobutyl-3-carbomethoxy-1-pyrazoline 126 (d) trans-3-Methyl-4-isobutyl-3-carbomethoxy-1-pyrazoline 127 (e) cis-3-Methyl-4-tert-butyl-3-carbomethoxy-1-pyrazoline 128 (f) trans-3-Methyl-4-tert-butyl-3-carbomethoxy-1-pyrazoline 128 2. P h o t o l y t i c decompositions 128 KINETIC MEASUREMENTS 129 General procedure f o r k i n e t i c runs 129 I. Rate constants, a c t i v a t i o n parameters and o v e r a l l deuterium k i n e t i c isotope e f f e c t of 3-methyl-3-carbomethoxy-l-pyrazoline and trans-3-methyl-3-carbomethoxy-l-pyrazoline-4dj 134 (a) Rate constants 134 (b) O v e r a l l deuterium k i n e t i c isotope e f f e c t s 134 (c) Corrected o v e r a l l deuterium k i n e t i c isotope e f f e c t s 135 (d) S p e c i f i c deuterium k i n e t i c isotope e f f e c t s 135 1. Deuterium k i n e t i c isotope e f f e c t s f o r 3 , y - o l e f i n .formation 135 2. Deuterium k i n e t i c isotope e f f e c t f o r cyclopropane formation 135 - x i -3. Deuterium k i n e t i c isotope e f f e c t f o r methyl angelate formation 136 4. Deuterium k i n e t i c isotope e f f e c t f o r methyl t i g l a t e formation 136 I I . Rate constants, a c t i v a t i o n parameters and o v e r a l l deuterium k i n e t i c isotope e f f e c t of 3-methyl-3-c a r b e t h o x y - l - p y r a z o l i n e and trans-3-methyl-3-c a r b e t h o x y - l - p y r a z o l i n e - 4 d j 137 (a) Rate constants 137 (b) O v e r a l l deuterium k i n e t i c isotope e f f e c t s 137 (c) Corrected o v e r a l l deuterium k i n e t i c isotope e f f e c t s 138 (d) S p e c i f i c deuterium k i n e t i c isotope e f f e c t s 139 1. Deuterium k i n e t i c isotope e f f e c t f o r g , Y - o l e f i n formation 139 2. Deuterium k i n e t i c isotope e f f e c t f o r cyclopropane formation 139 3. Deuterium k i n e t i c isotope e f f e c t f o r e t h y l angelate formation 140 4. Deuterium k i n e t i c isotope e f f e c t f o r e t h y l t i g l a t e formation 140 I I I . Rate constants and a c t i v a t i o n parameters of c i s -and trans-3-methyl-4-alkyl-3-carbomethoxy-l-pyrazolines 141 IV. Rate constants, a c t i v a t i o n parameters and deuterium k i n e t i c i s otope e f f e c t of c i s - 3 - m e t h y l - 4 - t e r t - b u t y l -3-carbomethoxy-l-pyrazoline and i t s analogue-4d^ 141 V. Rate constants, a c t i v a t i o n parameters and deuterium k i n e t i c isotope e f f e c t o f t r a n s - 3 - m e t h y l - 4 - t e r t - b u t y l -3-carbomethoxy-l-pyrazoline and i t s analogue-4d^ 142 VI. Rate constants, a c t i v a t i o n parameters and o v e r a l l dueterium k i n e t i c isotope e f f e c t of 1-carbomethoxy-2,3-diazabicyclo(3.3.0)oct-2-ene and i t s analogue-5d^ 143 (a) O v e r a l l deuterium k i n e t i c isotope e f f e c t s 144 1. Deuterium k i n e t i c isotope e f f e c t f o r 3 , y - o l e f i n formation 144 - x i i -2. Deuterium k i n e t i c i s otope e f f e c t f o r cyclopropane formation 145 3. Deuterium k i n e t i c i s otope e f f e c t f o r a , 3 - o l e f i n formation 145 V I I . Rate constant and a c t i v a t i o n parameters of l-carbomethoxy-2,3-diazabicyclo(4.3.0)non-2-ene 145 REFERENCES 146 APPENDIX - ERRORS 150 1 - x i i i -LIST OF TABLES Table VI IX Page I Decomposition products of exo-5,6-dideutero-2,3-diazabicyclo(2.2.l)hept-2-ene 13 II Decomposition product of exo- and endo-5-methoxy-2,3-diazabicyclo(2.2.l)hept-2-ene 17 I I I The a c t i v a t i o n parameters and r e l a t i v e r a t e s o f a s e r i e s of t r i c y c l i c azo compounds ^9 IV The a c t i v a t i o n parameters and r e l a t i v e r a t e s of a s e r i e s o f c y c l i c azo compounds having c y c l o p r o p y l i n group^exo and endo p o s i t i o n 41 \! The y i e l d s of o l e f i n i c and cyclopropane products of a s e r i e s o f 3-methyl-3-carbalkoxy-l-pyrazolines upon thermolysis 57 The product d i s t r i b u t i o n of c i s - and trans_-3-methyl-4-alkyl-3-carbomethoxy-l-pyrazolines upon thermolysis 60 VI I The coupling constants and decomposition products of a s e r i e s of b i c y c l o p y r a z o l i n e s 78 V I I I Decomposition products of 5-methyl-3-carbo-tert- butoxy-1 - p y r a z o l i n e 101 Photoproducts of trans-5-methyl-3-carbethoxy-l-p y r a z o l i n e - 4 d 1 115 - x i v -ACKNOWLEDGEMENTS I would l i k e to thank Professor D. E. McGreer f o r h i s h e l p , p a r t i c u l a r l y i n the i n t e r p r e t a t i o n of n.m.r. sp e c t r a throughout t h i s research p r o j e c t . I am indebted to Professor J . B. Farmer f o r h i s v a l u a b l e advice on temperature c o n t r o l systems, Professor L. D. Hayward f o r h i s h e l p f u l d i s c u s s i o n s concerning stereochemistry, and Pro f e s s o r R. E. Pincock f o r h i s comments on t h i s t h e s i s . I wish to thank Miss P. Watson, Mr. W. Lee and Dr. E. Koster f o r the n.m.r. spectra and Mr. P. Borda f o r the microanalyses. I a l s o wish to thank Mr. J . Molnar and e s p e c i a l l y Mr. S. Rak f o r t h e i r help i n designing the glass equipment. F i n a l l y I would l i k e to acknowledge the f i n a n c i a l support of the Nat i o n a l Research Council of Canada and the U n i v e r s i t y of B r i t i s h Columbia. - I -INTRODUCTION PREPARATION OF PYRAZOLINES The a d d i t i o n o f diazoalkanes to a c t i v a t e d carbon-carbon double* bonds to give p y r a z o l i n e s has been known f o r q u i t e some time (1,2,3) but the mechanistic d e t a i l s of the r e a c t i o n s were revealed i n 1958 by Huisgen and co-workers (4,5). They c l a s s i f i e d them as 1,3-c y c l o a d d i t i o n s , however, s t u d i e s i n d i c a t e d that these r e a c t i o n s proceeded v i a i s o p o l a r t r a n s i t i o n s t a t e s . The 1,3-dipolar f o r m u l a t i o n of t h i s r e a c t i o n i s convenient f o r p r e d i c t i n g r e s u l t s (6). The f a c t that these r e a c t i o n s are one step m u l t i c e n t e r and s t e r e o s p e c i f i c , permits us t o synthesize 1-pyrazolines o f known stereochemistry. U s u a l l y the a-carbon o f the diazoalkane binds to the carbon ft t o the a c t i v a t i n g group, although Parham and h i s co-workers (7) have found that c e r t a i n n i t r o o l e f i n s reacted w i t h diazoalkanes to give both o r d i n a r y and "reverse" a d d i t i o n products. MECHANISM OF PYRAZOLINE DECOMPOSITION The pioneering work of von Auwers and Konig (3) on p y r a z o l i n e decomposition was focused e x c l u s i v e l y on the i s o l a t i o n and i d e n t i f i -*N0TE: The a d d i t i o n of diazoalkanes to o l e f i n s c o n t a i n i n g no a c t i v a -t i n g groups can be e f f e c t e d by.the use of pressure (8,9,10,11). - 2 -c a t i o n of the components i n the product mixtures. They concluded that the cyclopropane d e r i v a t i v e s were formed w i t h f u l l r e t e n t i o n of the stereochemistry of the parent p y r a z o l i n e s , but no attempt was made to e x p l a i n the r e s u l t s . The general s t e r e o s p e c i f i c i t y was assumed to be v a l i d f o r q u i t e some time due to inadequate separation and a n a l y t i c a l tech-niques. In 1962, Jones and T ai (12,13) found that i t was not stereo-s p e c i f i c , although some degree of s t e r e o s e l e c t i v i t y was shown. Th e i r f i n d i n g s were s u b s t a n t i a t e d by van Auken and Rinehart (14) and McGreer, et a l . (15,16,17). I. I o n i c mechanism: One of the f i r s t suggestions concerning the mechanism of 1-pyrazoline decomposition was an i o n i c pathway (14,18,19) i n which the intermediate, depending upon the degree of bond breaking, could be e i t h e r a n i t r o g e n free z w i t t e r i o n or a diazonium ion. - 3 -However, the f o l l o w i n g f a c t s d i s f a v o r t h i s mechanism: a) the r e l a t i v e i n s e n s i t i v i t y o f decomposition rapes to solvent p o l a r i t y . b) product d i s t r i b u t i o n s do not change s i g n i f i c a n t l y i n going from apolar s o l v e n t s to p o l a r ones as one might expect on the grounds that p o l a r solvents by s t a b i l i z i n g the z w i t t e r i o n s would allow greater e q u i l i b r a t i o n of the i o n i c intermediate and would r e s u l t i n decreased s t e r e o s e l e c t i v i t y . c) l a c k of t y p i c a l carbonium i o n rearrangement products which r e a d i l y occur i n other systems having carbonium i o n intermediates. d) H s h i f t s are r a r e . - 4 -To counteract the d e f i c i e n c y of a clean-cut i o n i c mechanism, van Auken and Rinehart (14) suggested that the n i t r o g e n f r e e z w i t t e r i o n was a resonance form of a s i n g l e t d i r a d i c a l , and could undergo c y c l i z a t i o n . C H C H : H 7 2 C H 3 { C 0 0 C H 3 C H 2 C H , C H , H 8 \ C O O C H , An i o n i c mechanism was proposed by McGreer et_ al_. (20,21) f o r the thermal decomposition of 4,4'-dialkyl-3-cyano-3-carbo-methoxy-l-p y r a z o l i n e s 9_ as w e l l as f o r the dihydrofuran formation observed i n the decomposition 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 15_ and 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 s . In the former system due to the two s t r o n g l y e l e c t r o n withdrawing groups i n C-3 one might expect that the bond breaking of C-3 to n i t r o g e n i s w e l l advanced over the bond breaking of C-5 to n i t r o g e n g i v i n g the intermediate a p o l a r character. The r a t e s t u d i e s i n s o l v e n t s w i t h d i f f e r e n t p o l a r i t i e s p r i n c i p a l l y support the idea of the i o n i c intermediate but the v a r i a t i o n i n the r a t e with the solvent p o l a r i t y does not c o r r e l a t e w i t h other p o l a r reactions - 5 -i n s i m i l a r media. The formation of o l e f i n i c products can be explained by the concerted migration o f the a l k y l groups w i t h n i t r o g e n e x t r u s i o n . The thermal decomposition 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 (21) provided a r a t h e r complex product mixture: 18 19 20 The 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 s (21) gave s i m i l a r products wit h the f o l l o w i n g two exceptions: 1) the cyclopropane product c o n s i s t s of a mixture of c i s - and trans-1,2-dimethyl-1-acetyl-cyclopropanes. 2) the trans compound gave p r a c t i c a l l y no dihydrofuran d e r i v a t i v e . According to McGreer et_ a l . , an i o n i c pathway could be r e s p o n s i b l e f o r the dihydrofuran formation i n which the intermediate (22) has a negative charge d e l o c a l i z e d i n t o the carbonyl oxygen and i f i t i s i n a favorable p o s i t i o n , i t w i l l be able to p a r t i c i p a t e i n the r i n g c l o s u r e ; 21 22 23 - 7 -because the 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 gave no dihydro-furan, the intermediate i n th a t case could not undergo f r e e r o t a t i o n around the C-3 - C-4 bond to take up a fav o r a b l e conformation f o r r i n g c l o s u r e . McGreer et_ a l . (21) assumed 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 t r o g e n . The intermediate (22) 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, was s t i l l 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 and by solvent p o l a r i t y as w e l l . The s t u d i e s o f 3-cyano-3-carbethoxy-1-pyrazoline systems (22) showed th a t the formation o f the o l e f i n i c products occurred v i a a s t e r e o s e l e c t i v e process. To e x p l a i n t h i s s t e r e o s e l e c t i v i t y Hamelin and C a r r i e assumed th a t there was 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 24, 26 and 28, 30 or t h e i r Newman p r o j e c t i o n s 25, 27 and 29, 31. Upon decomposition the f i r s t two conformers give r i s e t o 32_ and 3_3 while the two l a t t e r t o 34_ and 35_ by methyl and a r y l m i g r a t i o n besides cyclopropane d e r i v a t i v e s . They suggested two mechanistic pathways f o r the o l e f i n formation, a concerted one i n which migration and the n i t r o g e n l o s s occur simultaneously and a stepwise path g i v i n g r i s e to an intermediate i n which the rearrange-ment i s f a s t e r than the r o t a t i o n around the C-3 - C-4 bond. The intermediates f o r the l a t t e r pathway were suggested to be i o n i c s p ecies, 36_ and 37 from conformers 2_8_ and 30_ r e s p e c t i v e l y . The existence of an e q u i l i b r i u m between 36 and 37 was excluded on the - 8 -grounds that such an e q u i l i b r i u m would have allowed r o t a t i o n around the C-3 - C-4 bond le a d i n g t o the intermediate 38_ which i n turn would have given r i s e to (Z)-32. This compound was not found i n the decom-p o s i t i o n product mixture of 24_ and 26. Since both the concerted and the i o n i c mechanisms could adequately e x p l a i n the formation of o l e f i n i c product, the authors f e l t t h a t k i n e t i c s t udies would have to be done to see whether the bond breakage of C-3 and C-4 carbons to nitrogens take place s u c c e s s i v e l y or simultaneously. The product s t u d i e s a l s o i n d i c a t e d that the a r y l groups had a b e t t e r migratory a p t i t u d e than the methyl. A r C N N 28 // N C O O C 2 H 5 H 5 C 2 00C C H . N // N 30 A r C H , C N A r C O O C 2 H 5 29 C H 3 H c C o O O C I C N N = N 31 H _ C o 0 0 C A r o 2 r - C H 2 N ® 'CN -8 38 A r C 0 0 C o H c H H 5 C 2 C N (£)-12_ A r - C H p C O O C J - L • c 2 5 C H 3 C N 34 Ar COOCLH. H H 5 C 2 C N 35 C N - S A r C H 3 ^ " C H 2 N 2 + C O O C H , 36 "25 A r H 5 C 2 O O C C N - S C H 3 — C H 2 N 2 + 37 - 10 -The k i n e t i c s t u d i e s done on a s e r i e s of 3-cyano-3-carbomethoxy p y r a z o l i n e s s u b s t i t u t e d at C-4 with a methyl and a r y l groups (phenyl, p-methoxyphenyl or p-nitrophenyl) and on t h e i r analogues dideuterated the at C-5 (22) provided the value of/secondary a - k i n e t i c isotope e f f e c t ; kH r — = 1.01 ± 0.07; This suggested t h a t very l i t t l e bond breaking of the C-5 to n i t r o g e n occurred i n the t r a n s i t i o n s t a t e . The proposed t r a n s i -t i o n s t a t e 39 was p o l a r w i t h increased c o n s t r a i n t s i n the degrees of freedom compared to the s t a r t i n g m a t e r i a l . This was supported by the negative values of entropy of a c t i v a t i o n , -3.19, -5.65 and -9.58 e.u. f o r the d i f f e r e n t p y r a z o l i n e s . A r\ > N 39 The product d i s t r i b u t i o n i n d i c a t e d that the stereochemistry of the p y r a z o l i n e plays an important r o l e i n determining the stereochemistry of the products and there was no r o t a t i o n t a k i n g place around the C-3 -C-4 bond i n the t r a n s i t i o n s t a t e . An i n t e r e s t i n g i o n i c pathway was proposed by Huisgen and Eberhard (24) f o r the decomposition of c i s - and trans-3-methyl-5,5-diphenyl-l-p y r a z o l i n e - 3 , 4 - d i c a r b o x y l a t e 40_, 41_ i n DMF or DMSO i n the presence o f a strong base (NaH i n DMF and dimsylsodium i n DMSO) at room temperature. - 11 -When the two p y r a z o l i n e s were t r e a t e d w i t h the above mentioned bases i n DMF or DMSO n i t r o g e n e l i m i n a t i o n took place and the s o l u t i o n became red, l a s t i n g f o r days under proper care. H K ^ C O O C H 3 C H ^ O O C U M P h 2 f > < X C 0 0 C H 3 P h J > < < C O O C H 3 N = N C H 3 1 N = = I C H 3 C O O C H 3 N = N * C O O C H 3 P h — ^ C ^ — C H 3 Ph C O O C H 3 4 3 . Ph C O O C H 3 45 4 2 The existence o f the l - p y r a z o l i n e - 4 - y l anion 42 as an intermediate was proved by e s t a b l i s h i n g a c i s - trans e q u i l i b r i u m i n NaOMe, MeOH s o l u t i o n without l o s s of N 2 < By using deuterated s o l v e n t s , the expected - 12 -d e u t e r a t i o n of the anion was found to be made f a s t e r than i t s c y c l o -r e v e r s i o n . 12 The anion 42_ e l i m i n a t e s n i t r o g e n 10 times f a s t e r than does the n e u t r a l p y r a z o l i n e , and the products are o l e f i n i c e s t e r s 45_ i n greater than 97% y i e l d . The n e u t r a l p y r a z o l i n e s gave mainly cyclopropanes of mixed stereochemistry. K i n e t i c s t u d i e s i n d i c a t e d that the 1,3-cycloreversion to a l l y l anion and ^ has an a c t i v a t i o n energy more than 12 k c a l mol ' lower than that of the p y r a z o l i n e to cyclopropane process. I I . D i r a d i c a l mechanism: Since a c y c l i c azo compounds decompose v i a f r e e r a d i c a l i n t e rmediates, i t seemed reasonable to assume the same mechanism f o r c y c l i c azo com-pounds. Cohen and co-workers (25,26) were the f i r s t to i n v e s t i g a t e the k i n e t i c s of the decomposition of 2,3-diazabicyclo(2.2.1.)hept-2-ene 46^  and 2 , 5 - d i a z o b i c y c l o ( 2 .2. 2 . )oct-2-ene 48^  i n the gas phase and compare the obtained data w i t h those of a c y c l i c azo compounds. - 13 -They have suggested a d i r a d i c a l pathway with the simultaneous breakage of the two C-N bonds f o r the thermal decomposition of 46 and 48. 46 decomposed about 400 times f a s t e r than 48_ and has lower a c t i v a t i o n energy and entropy of a c t i v a t i o n which was presumable due to the more h i g h l y s t r a i n e d s t r u c t u r e of 46. Roth and M a r t i n (27) have used exo-5,6-dideutero-2,3-diazobicyclo(2.2.l)hept-2-ene 50_ to study the stereochemistry o f the decomposition. D VA D 5L 52 The r a t i o o f the c i s - and trans-2,3-dideuteriobicyclo(2.1.0)pentanes v a r i e d widely with the mode of decompositions and with the p h y s i c a l s t a t e of the sample. T A B L E I Decomp. prod, of exo-5,6-dideutero-2,3-diazabicyclo(2.2.l)hept-2-ene. Products Mode of decomp. p h y s i c a l s t a t e o f 51 52 the sample A gas phase 25% 75% hv " " low pressure 50% 50% 11 " " high pressure 40% 60% 11 benzene 40% 60% s o l i d 66% 33% - 14 -According to t h e i r e x p l a n a t i o n , the predominant i n v e r s i o n was due to the concerted e l i m i n a t i o n of n i t r o g e n with accompanying back-side p - o r b i t a l overlap. 50 The low s t e r e o s e l e c t i v i t y (75%) i n d i c a t e s that the overlap i n the t r a n s i t i o n s t a t e i s incomplete. T h e i r theory seemed to be supported by the product d i s t r i b u t i o n i n the gas phase p y r o l y s i s of endo-5-methyl-2,3-diazabicyclo(2.2.1) hept-2-e'ne which showed somewhat lower stereo-s e l e c t i v i t y (60%) due to the s t e r i c hindrance by the methyl group i n the t r a n s i t i o n s t a t e . - 15 -To e x p l a i n the r e t e n t i o n found i n the decomposition products with respect to the parent azo compound, the f o l l o w i n g t r a n s i t i o n s t a t e can be envisaged (28). Later Roth and M a r t i n (29) proposed a two step mechanism f o r the decom-p o s i t i o n of 5_0_ i n v o l v i n g a t r a n s i t o r y n i t r o g e n c o n t a i n i n g d i r a d i c a l . The i n v e r s i o n was a t t r i b u t e d to the development of a 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 leading to bicyclopentane- and n i t r o g e n . According to them, the energy requirement f o r i n v e r s i o n was s u p p l i e d by the r e c o i l energy re l e a s e d by the C-N bond breakage. N = N » 58c - 16 -While maintaining the concept of a d i r a d i c a l pathway f o r the decom-p o s i t i o n o f b i c y c l o p y r a z o l i n e s a d i f f e r e n t approach was used by A l l r e d and Smith (28) to e x p l a i n the stereochemical course of the r e a c t i o n . They have s t u d i e d the thermal and photodecomposition o f the exo and endo epimers of 5-methoxy-2,3-diazabicyclo(2.2.l)hept-2-ene 59_, 60_. The d i f f e r e n t modes of decompositions have r e s u l t e d i n a widely d i f f e r -i n g r a t i o o f 61_ and 62^ shown i n Table I I . The thermal e q u i l i b r a t i o n study showed that 62 i s the more s t a b l e isomer. - 17 -TABLE II Decomp. prod, of exo- and endo-5-methoxy-2,3-diazabicyclo(2.2.l)hept-2-ene Products Comp. Mode o f decomp. p h y s i c a l s t a t e o f sample 62_ 61_ 5 9 l i A * K 63% 37% 60 } s e a l e d t u b e 93.6% 6.4* 59 1 h pentane s o l u t i o n 42% 58% 60 v p i p e r y l e n e added 84% 16% 59 i , 9 7 % •$% 60 } h v c r y s t a l l i n e ^ ^ 59 .benzophenone . , 78% 22% 60 Sensitized, phot. cyclohexane y g % n % The r e s u l t s were r a t i o n a l i z e d i n terms of an e q u i l i b r a t i n g , epimeric p a i r of pyramidal 1,3 - d i r a d i c a l s . They have a l s o proposed that the i n v e r s i o n i s a consequence of r e c o i l energy r e l e a s e d by C-N bond break-i n g . *Note 1. The excess product of i n v e r t e d s t r u c t u r e i n d i c a t e s t h a t r i n g c l o s u r e occurs before the two epimeric d i r a d i c a l s can f u l l y e q u i l i -b r ate. Benzophenone s e n s i t i z e d p h o t o l y s i s produced the same product mixture from both isomers. The most p l a u s i b l e e x p l a nation of these r e s u l t s i s t h a t the pyramidal d i r a d i c a l can i n t e r c o n v e r t at l e a s t s e v e r a l times before s p i n i n v e r s i o n occurs. The f i r s t d i r e c t observation of f r e e r a d i c a l species by e.s.r. spectroscopy was achieved by Overberger et a l . (31,32,33) i n the photo-Note #1. The r e c o i l mechanism has been questioned on t h e o r e t i c a l ground by C o l l i n s , George and T r i n d l e (30). - 18 -decomposition of 3 , 5 - d i a r y l - l - p y r a z o l i n e s (the thermal processes f a i l e d t o show any s i g n o f f r e e r a d i c a l s ) . L a t e r r e p o r t s on the d e t e c t i o n o f fr e e r a d i c a l s by e.s.r. w i l l be discussed on pages 28 and 32. Crawford and co-workers (34) have accumulated considerable evidence f o r a d i r a d i c a l pathway i n v o l v i n g a 1 , 3 - d i r a d i c a l or 0,0-trimethylene l i k e intermediate i n the thermal decomposition o f p y r a z o l i n e s . The k i n e t i c s t u d i e s on a s e r i e s of methyl s u b s t i t u t e d p y r a z o l i n e s showed a stepwise decrease i n a c t i v a t i o n energies upon methyl s u b s t i t u t i o n on the C-3 and C-5 p o s i t i o n s . This general decrease was i n t e r p r e t e d i n the suggestion that both carbon n i t r o g e n bonds are broken i n the t r a n s i t i o n s t a t e . However, the obtained one k c a l mol ' decrease f o r each methyl group i s comparable t o some conformational f a c t o r s encountered i n c y c l i c compounds, thus the increase i n r a t e could a r i s e from an increase i n ground s t a t e energies. In order to remove any conformational c o m p l i c a t i o n s , deuterated p y r a z o l i n e s were used and the obtained r e s u l t s confirmed the previous assumption that both carbon-nitrogen bonds are breaking i n the r a t e determining step (35). K i n e t i c s t u d i e s done on 3 - v i n y l - l - p y r a z o l i n e and 3 - v i n y l - l - p y r a z o l i n e - 5 , 5 ^ 2 a l s o supported the idea of simultaneous breakage o f both carbon-nitrogen bonds i n the t r a n s i t i o n s t a t e (36). The f a c t that c i s - and t r a n s - 3,5-dimethyl-l-pyrazolines 63 and 65 are not i n t e r c o n v e r t e d during t h e i r decomposition removes the p o s s i b i l i t y of an i n t e r c o n v e r s i o n through a n i t r o g e n c o n t a i n i n g i n t e r -mediate 64_ but i t does not r u l e out the p o s s i b l e existence of an azo - 19 -d i r a d i c a l favored by s e v e r a l researchers (10,29,41). 6 6 C H 3 K i n e t i c and product s t u d i e s done on 4- m e t h y l - l - p y r a z o l i n e and i t s 4-d^ isomer (34) l e d to the c o n c l u s i o n that the cyclopropanes came from a common n i t r o g e n f r e e intermediate s i n c e the product a n a l y s i s showed a s u b s t a n t i a l decrease i n o l e f i n formation i n going from the nondeuterated p y r a z o l i n e to the deuterated one while the k o v e r a l l k i n e t i c i s otope e f f e c t was found to be _H = 1.07. kD - 20 -67 52 .3% 4 7 . 7 % 67 deuteroted 66 .0% 34 .7% I f we assume that _J1 = 1.0 f o r cyclopropane formation, the o l e f i n ]. kD formation w i l l have ^ = 1.80. I t can be seen from the o v e r a l l k i n e t i c i sotope e f f e c t t h a t i n the r a t e determining step, a n i t r o g e n f r e e intermediate forms (nitrogen f r e e because s t u d i e s have been s u b s t a n t i a t i n g the simultaneous breakage of both C-N bonds) which undergoes a competitive r i n g c l o s u r e and hydrogen s h i f t e x h i b i t i n g d i f f e r e n t k i n e t i c i s o t o p e e f f e c t s f o r each. The geometry of the t r a n s i t i o n s t a t e was d e r i v e d from k i n e t i c s t u d i e s done on methyl s u b s t i t u t e d p y r a z o l i n e s . The i n t r o d u c t i o n o f one methyl group at C-4 has very l i t t l e e f f e c t , whereas two methyl groups cause a great deal of decrease i n the r e l a t i v e r a t e . - 21 -CH3 H^ C^ ^^ ^ r ^ i r S N = N N = N N = N £3 67 68 relative rate 1.0 0.97 0.0079 S i m i l a r l y to eye1opentane ? the pyrazolones have an envelope l i k e geometry with an angle about 155° between the two planes. This angle presumably decreases as the carbon-nitrogen bonds lengthen. In the case of the monomethyl p y r a z o l i n e , the n i t r o g e n departs t r a n s t o the methyl causing only very s l i g h t s t e r i c compression. But i n the 4,4-dimethylpyrazoline one methyl i s c i s t t o the departing n i t r o g e n and a large s t e r i c compression r e s u l t s i n s u b s t a n t i a l r a t e decrease. The geometry of 70 i s a n a t u r a l consequence of the azo l i n k contrac-o o t i o n from 1.25 A to 1.09 A as the formation of the TT bond i n n i t r o g e n - 22 -progresses. A l t e r n a t i v e l y , the slow r a t e would a l s o be expected i f an increase i n C-3 - C-4 - C-5 bond angle were to occur, thus decreasing the CH^-C-CH^ angle and r e s u l t i n g i n s t e r i c compression i n the t r a n s i -t i o n s t a t e . The planar geometry f o r the t e r m i n a l methylenes i n the intermediate i s supported by the o l e f i n i c products of c i s - and trans-dimethyl-1-p y r a z o l i n e . The m i g r a t i o n of a hydrogen from C-4 i n 73_ to e i t h e r C-3 or C-5 gives only trans-2-pentene 74 while the m i g r a t i o n of a C-4 n i t r o g e n i n 76 r e s u l t s i n trans-2-pentene 74_ and cis-2-pentene 77 and 75 gave - 23 -al s o cyclopropane products w i t h predominant i n v e r s i o n of stereochemistry of the parent p y r a z o l i n e s . The intermediate can be looked upon as a 2 1,3 d i r a d i c a l having pn - pn bonding between the neighboring sp carbons. According to spectroscopic n o t a t i o n , i t would be a irg-cyclopropane. C a l c u l a t i o n s i n d i c a t e d that the 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 allow the " d i r a d i c a l " to behave as two independent r a d i c a l s and a l s o suggested 8-12 Kcal mol * bonding energy. H H -rrq cyclopropane 78 H H 77- u cyclopropane 79 Hoffmann(37,38) c a l c u l a t e d the energy o f trimethylene r e l a t i v e to cyclopropane as a f u n c t i o n of the C-C-C angle and r o t a t i o n of the terminal 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 surface corresponding to an opened cyclopropane 80_ and to the trimethylene intermediate 81_ where the term i n a l methylenes are coplanar w i t h three carbons. - 24 -Hoffmann a l s o found t h a t t h e m i x i n g o f t h e o r b i t a l s o f t h e c e n t r a l methylene group d e s t a b i l i z e s t h e S l e v e l a t l a r g e a n g l e s and s t a b i l i z e s t h e A l e v e l a t s m a l l a n g l e s . S A —H-83 I t i s apparent t h a t 8_3 s h o u l d c l o s e t o c y c l o p r o p a n e i n a c o n r o t a t o r y manner r e s u l t i n g i n i n v e r s i o n a t one c e n t e r compared t o t h e o r i g i n a l - 25 -pyrazoline i f the trimethylene i s properly substituted. 82_ would close i n a d i s r o t a t o r y manner leading to retention. Calculations showed that species 82_ and 83 are not greatly d i f f e r e n t i n energy and there may be an equilibrium between them which could explain why the cyclopropane formation i s s t e r e o s e l e c t i v e only. Crawford and Erickson (39) have investigated whether the intermediate produced upon thermolysis of 85_ has a plane of symmetry through the four carbons. §4 85 86 If t h i s assumption i s v a l i d , the c i s - and trans- 4-deutero-3-methyl-1-pyrazoline upon thermolysis should give the same intermediates and eventually the same product composition. The experimental r e s u l t s were in excellent agreement with the p r e d i c t i o n s . The trimethylene intermediate suggested for pyrazoline thermolysis bears formal s i m i l a r i t i e s to an adduct obtained by addition of a s i n g l e t methylene to an o l e f i n . To see whether the trimethylene intermediate i s involved i n the s i n g l e t addition process, a study was undertaken by - 2 6 -C r a w f o r d a n d A l i ( 4 0 ) . The compounds c h o s e n were c i s - and t r a n s -3 , 4 - d i m e t h y l - l - p y r a z o l i n e and t h e i r C - 5 , 5 -d^ i s o m e r s w h i c h w o u l d p r o v i d e upon t h e r m o l y s i s i n t e r m e d i a t e s h a v i n g t h e same s p i n s t a t e a n d s t o i c h i o m e t r y as t h e a d d u c t s o f s i n g l e t m e t h y l e n e t o c i s - and t r a n s -b u t e n e s . The k i n e t i c i s o t o p e e f f e c t i n d i c a t e d t h a t t h e p r i m a r y c a r b o n t o n i t r o g e n bond was a l s o b r e a k i n g i n t h e r a t e d e t e r m i n i n g s t e p . The p r o d u c t d i s t r i b u t i o n l e d t o t h e c o n c l u s i o n t h a t t h e t h e r m o l y s i s i s n o t s t e r e o s p e c i f i c and t h e t r i m e t h y l e n e i n t e r m e d i a t e s a r e n o t on t h e r e a c t i o n c o o r d i n a t e i n t h e a d d i t i o n o f a s i n g l e t m e t h y l e n e t o c i s - a n d t r a n s -b u t e n e . The t h e r m o l y s i s o f (3R: 5R) - ( + ) - t r a n s _ - 3 , 5 - d i m e t h y l p y r a z o l i n e 87_ done b y C r a w f o r d and M i s h r a (41) p r o d u c e d c i s - and t r a n s - d i m e t h y l c y c l o -p r o p a n e s 8 9 , 90 and some o l e f i n i c p r o d u c t . - 27 -Only 23% of the trans-cyclopropane 90 showed optical activity, S : S configuration indicating double inversion. If the intermediate 88 were a symmetrical species, as i t had been suggested, i t would give only a racemic mixture of trans-cyclopropane. There are two alternative mechanisms which could account for the double inversion . a) one which has been proposed by Roth and Martin (29) involving a nitrogen containing diradical intermediate. 90 b) the other based on a pyramidal diradical intermediate idea put forward by Allred and Smith (28). Quantum mechanical calculations predicted that the ground state of the trimethylenemethane should be a t r i p l e t diradical. By assuming that - 28 -the 4-methylene-l-pyrazoline decomposes v i a a d i r a d i c a l pathway i t seemed the most convenient source t o generate t h i s s p e c ies. Indeed Dowd (42) showed by e.s.r. t h a t 4-methylene-l-pyrazoline 9_3 upon p h o t o l y s i s at low temperature i n hexaflourobenzene s o l u t i o n or i n s o l i d m a t r i x , produced the d e s i r e d t r i p l e t d i r a d i c a l 94_ which had been p r e d i c t e d by t h e o r e t i c a l c a l c u l a t i o n . 93 94a The e.s.r. spectrum a l s o i n d i c a t e d that the d i r a d i c a l had a t h r e e f o l d (or higher) a x i s of symmetry. K i n e t i c s t u d i e s done by Crawford and Cameron (43) showed that both Ea = 32.6 Kcal mol * and AS^ = 1.1 e.u. were lower f o r 93 than f o r -1 + 1-pyrazoline 7_3 (Eq = 42.2 Kcal mol , AS 1 11.2 e.v.) These are con-s i s t e n t w i t h the expectation that a t r i p l e t has a lower p r o b a b i l i t y of formation. To check that a symmetrical intermediate 94b was indeed i n v o l v e d , 4-methylene-l-pyrazoline-3,3-d^ had been prepared and decomposed. - 29 -Such a species would be expected to give methylene-cyclopropanes i n the f o l l o w i n g r a t i o expected found The explanation f o r t h i s n o n s t a t i s t i c a l d i s t r i b u t i o n i s that by a v i r t u e ofysecondary isotope e f f e c t i n the product determining step the dideutero methylenegroup i s slower to r o t a t e i n t o the r i n g conformation than are the diprotiomethylene groups. - 30 -H-H \ c / H I I H D 97 The isotope e f f e c t was found t o be _M. = 1.37. k D By preparing and p y r o l y s i n g the 4-methylene-l-pyrazoline-3,3,6,6-d 98 and using the value of/'isotope e f f e c t , they were able to p r e d i c t the product r a t i o s calculated 7 3 . 2 % 26.2% observed 7 3 . 8 % 26 .2% I t i s known that the simple trimethylene methane 94a undergoes a f a s t r i n g c l o s u r e before i t could add t o o l e f i n i c acceptors. Berson et a l . - 31 -(44,45,46) hoped to suppress the r i n g c l o s u r e by i n c o r p o r a t i n g the trimethylene methane i n t o a r i n g system 101 which would give a h i g h l y s t r a i n e d hydrocarbon 103 on r i n g c l o s u r e . 102 CH. X " ' 103 Indeed, the intermediate, 2 - i s o p r o p y l i d e n e c y c l o p e n t a n e - l , 3 - d i y l 102 underwent c y c l o a d d i t i o n with o l e f i n s . One of the most i n t e r e s t -i n g r e a c t i o n s of 101 i s the " a z o - t r a n s f e r " r e a c t i o n . 104 105 The r e s u l t i n g cycloadduct 104 can be converted by a h y d r o l y s i s -d e c a r b o x y l a t i o n - o x i d a t i o n sequence to a fused azo-compound 105 isomeric with 101. The stereochemistry of the intermediate 102 was revealed when the dideuterated isomer of 101 was decomposed th e r m a l l y i n the presence of dimethyl maleate. - 3 2 -50% C00CH 3 D COOCH3 50% 108 That shows t h a t i n the intermediate 107 the r i n g and proximal s i d e -chain carbons are coplanar, or become coplanar before being trapped. Perhaps one of the most impressive proofs f o r the intermediacy of 1 , 3 - d i r a d i c a l species i n the photodecomposition o f p y r a z o l i n e s was presented by Kaplan et a l . (47,48). They not only i d e n t i f i e d the ground s t a t e t r i p l e t d i r a d i c a l obtained by the i r r a d i a t i o n of 3H-indazol d e r i v a t i v e s but could t r a p them with butadiene. - 33 -The assumption that the adduct formed v i a a two step a d d i t i o n maintain-in g the s p i n conservation was a l s o s u b s t a n t i a t e d by e.s.r. s t u d i e s . I I I . Concerted mechanism. Up to date there have been only a few reports c l a i m i n g concerted pathways f o r decomposition of c y c l i c azo compounds. Those which have been published can be c l a s s i f i e d i n t o the f o l l o w i n g three groups: a) r e t r o D i e l s - A l d e r r e a c t i o n s b) concerted o l e f i n formation c) cyclopropane r i n g a s s i s t e d decompositions. - 34 -(a) Retro D i e l s - A l d e r r e a c t i o n s . The unusual f e a t u r e of t h i s r e a c t i o n i s that no n i t r o g e n e x t r u s i o n takes p l a c e c o n t r a r y t o the m a j o r i t y of azo compound fragmentation. Hinshaw and A l l r e d (49) have observed t h i s k i n d of decomposition when they thermolyzed the r a t h e r complex t r i c y c l i c azo compound 114. 10 mol 0.25 mol 0.5mol 0.25mol 0.75 They suggested that 117 was formed by a r e t r o D i e l s - A l d e r r e a c t i o n . H 114 118 117 Retro D i e l s - A l d e r r e a c t i o n was found to be (50) the only pathway f o r the thermal decomposition two geometrical isomeric azo system at the bridgehead 119. I J20 119. J21 Ph - 35 -(b) Concerted o l e f i n formation: Using n.m.r. data McGreer et a l . (51) determined the p r e f e r r e d conformations of c i s - and trans_-3,5-dimethyl-3-carbomethoxy-l-pyrazolines which upon thermolysis gave o l e f i n i c and cyclopropane products. The stereochemistry of the o l e f i n i c e s t e r s w i t h respect to the p r e f e r r e d conformation of the parent p y r a z o l i n e s showed that the o l e f i n i c products were formed i n a s t e r e o s p e c i f i c manner. They assumed that one of the C-4 hydrogens which was trans to the nitrogens would concertedly migrate i n the t r a n s i t i o n s t a t e with the n i t r o g e n e x t r u s i o n t o C-5 a,3-unsaturated e s t e r and to C-3 to give 3 , Y - o l e f i n i c e s t e r s with trans geometry. They als o suggested that the r a t i o of the a, 3- and 3,y-esters would be the measure of the m i g r a t i o n a l . p t i t u d e of the hydrogen as a hydride or a proton. 7 H COOCH3 CH, H N 123fl COOCH 3 H CH: C H 3 — C H 2 COOCH3 124. 122 H:. 123b. COOCH3 COOCH, CH, COOCH N H - 1 // -N C H 3  126 CH, COOCH3 125_ COOCH3 £ k > Z—N H COOCH, X 127 b C H 3 CHj — CH2 CH3 128 - 36 -McGreer and Wu (52) have proposed a similar transition state for the stereospecific olefin formation in the thermal decompositions of the geometrically isomeric c i s - and trans_-3-methy 1-4-ethyl-3-carbomethoxy-1-pyrazoline. According to the preferred conformations, the C-4 hydrogen is in the pseudo axial and the C-4 ethyl group in the pseudo equatorial position. C O O C H ^ C H 3 - C H 2 W _ N 129 130 C O O C H : But in the reaction, some conformational change w i l l take place, 130 changes to 1_32_ and 129 to 131. C H 2 — C H 3 J5L / i v / C h 3 C H 3 - C H 2 C H 3 m C O O C H 3 C H 3 C O O C H 3 C H 2 - C H 3 132 A C O O C H 3 C H j - C H - C O O C H 3 J 3 5 H,M^f — >=< C H 3 C H 3 C H 3 C H 3 — C H 2 — C - C H ^ 0 C H 2 C 0 0 C H 3 133 - 37 -The advantage gained by the concerted migration of the hydrogen must be sufficient to overcome the steric compression in the transition state. The cyclopropanes were formed with predominant retention with respect to the parent pyrazoline. (c) Cyclopropane ring assisted decompositions: Exceptionally high rate and stereospecificity have been observed in the thermal decomposition of cyclic azo compounds having fused cyclopropane rings. The studies have also indicated that the orienta-tion of the cyclopropane ring i s c r i t i c a l in determining the reaction pathway. Berson and Olin (53) have reported that the cyclopropane ring had a complete control over the stereochemical course of the decomposi-tion of the following azo compounds; 136 J37 138 139 - 38 -The high degree of stereospecificity and rate would suggest that the reaction should be a concerted orbital symmetry allowed retro Diels-Alder reaction i f the photochemical decomposition did not give exactly the same products. The authors f e l t that in these cases factors other than orbital symmetry had complete control over the reaction. They introduced the concept of extrasymmetric factor as a general term for influences other than orbital symmetries which play a decisive role in determining the course of the reactions. Allred et_ a l . (54) have also found a 10*^ times rate enhancement in the thermal decomposition of 140 in comparison to 2,3-diazanorbornene. 140 141 The authors attributed the rate enhancement to the intervention of an orbital-symmetry allowed process. The transition state is most likely the following: 142 a N 142 b N=N - 39 -They argue that i f the r e a c t i o n s were d i r a d i c a l at l e a s t some 2 4 t r a n s - t r i c y c l o (3.1.0.0. ' ) hexane 144 would form which i s s t a b l e under the r e a c t i o n c o n d i t i o n . Tanida e_t al_. (55) found l a t e r 144 i n the p h o t o l y t i c product mixture of 140. The works o f A l l r e d , Johnson (56) and Trost et_ al_. (57,58) e t c . , provide evidence f o r the importance of the geometrical f a c t o r s i n v o l v e d i n the c y c l o p r o p y l p a r t i c i p a t i o n . They have prepared a s e r i e s o f t r i c y c l i c compounds i n which the bridgeheads and the c y c l o p r o p y l groups were connected w i t h carbon bridges d i f f e r i n g i n lengths. 143 144 TABLE I I I The a c t i v a t i o n parameters and r e l a t i v e r a t e s of a s e r i e s of t r i c y c l i c azo compounds. - 4 0 -- 41 -Data i n d i c a t e that 147 decomposes t o a d i r a d i c a l intermediate w h i l e , 1 4 9> 1 5 1 f o l l o w a concerted, o r b i t a l symmetry allowed pathway. be explained by the o r i e n t a t i o n o f the c y c l o p r o p y l r i n g s . In 140, 145. 149, 151 the c y c l o p r o p y l o r b i t a l s are more fa v o r a b l y o r i e n t e d i n the t r a n s i t i o n s t a t e s f o r overlap as the C -N bonds break. A l l r e d and Voohees (59) have compared the i n f l u e n c e o f the c y c l o -propyl group being i n exo- and endo- p o s i t i o n s on the thermal r e a c t i v i t y of the azo compounds. The considerable d i f f e r e n c e i n r e a c t i v i t y among the compounds can TABLE IV The a c t i v a t i o n parameters and r e l a t i v e r a t e s o f a s e r i e s o f c y c l i c azo compounds having c y c l o p r o p y l groups exo> and endo p o s i t i o n s . COMPOUND E Q KcQl/mol AsVu re I. rate 44.6 10.5 1.0 N 48 - 42 -A l l a v a i l a b l e c r i t e r i a c l e a r l y i n d i c a t e that 155 decomposes by a d i r a d i c a l pathway without p a r t i c i p a t i o n of the cyclopropane r i n g . - * 3 -OBJECTIVE OF PRESENT RESEARCH The mechanistic details of thermo- and photodecompositions of cyclic azo compounds are s t i l l under intensive investigation. The survey of results and explanations indicates that the decomposition may involve single or mutliple pathways depending upon the substituent pattern and the mode of decomposition. A considerable amount of work has been done in these laboratories under the direction of Dr. D. E. McGreer on pyrazoline systems having an electron withdrawing group (acetyl, carbomethoxy, cyano) on C-3. As a continuation of the earlier research the studies were conducted mainly on 3-methyl-3-carbomethoxy-l-pyrazolines bearing different alkyl groups, deuterium or both on C-4. Snyder's observation (60) that the replacement of the C-3 methyl group for an ethyl in the 3-methyl-3-carbomethoxy-l-pyrazoline decreased the rate of decomposition initiated the preparation and study of 3-tert-butyl-3-carbomethoxy-1-pyrazoline which showed exceptional thermal st a b i l i t y . Crawford (9) and Bergman (10) reported that the incorporation of the pyrazoline ring in a bicyclic structure increased the amount - 44 -of o l e f i n i c products upon th e r m o l y s i s r e l a t i v e to the simple system. In the hope that a s i m i l a r system which i n a d d i t i o n has a carbomethoxy group next t o the N=N double bond would behave s i m i l a r l y 1-carbomethoxy-2,3-diazabicyclo(3.3.0)oct-2-ene was prepared. Indeed the p y r o l y s i s o f t h i s compound provided as much as 80% o l e f i n i c product. I t a l s o appeared worthwhile t o s y n t h e s i z e l-carbomethoxy-2,3-diazabicyclo(3.3.0) oct-2-ene-5dj and the next two members of the s e r i e s . Since McGreer and Masters have undertaken a thorough study of l-methyl-l-carbomethoxy-l-pyrazoline-4d2, i t seemed t o be c h a l l e n g i n g to prepare s t e r e o s p e c i f i c a l l y monodeuterated p y r a z o l i n e s to o b t a i n the s p e c i f i c deuterium k i n e t i c i s otope e f f e c t s f o r the d i f f e r e n t processes i n v o l v e d i n p y r a z o l i n e decomposition. Snyder (60) has a l s o observed that the 3-methyl-3-carbobutoxy-l-p y r a z p l i n e e x h i b i t e d a lower r a t e of decomposition than the correspond-i n g methyl e s t e r . Since he has not done any product study i t seemed i n t e r e s t i n g to see the changes i n product d i s t r i b u t i o n too. The s t u d i e s o f Van Auken et_ al_. (14) on the decomposition of c i s - and trans-3,4-dimethyl-3-carbomethoxy-1-pyrazo1ines and McGreer et a l . (52) on c i s - and trans-3-methy1-4-ethyl-3-carbomethoxy-l-p y r a z o l i n e s have shown a c e r t a i n p a t t e r n : s t e r e o s p e c i f i c o l e f i n formation and an i n crease i n the amount o f cyclopropane products with the i n c r e a s i n g s i z e of the C-4 a l k y l s u b s t i t u e n t s . In order to o b t a i n some more informa t i o n about the p a t t e r n the f o l l o w i n g a l k y l s u b s t i t u e n t s were placed i n both c i s and t r a n s p o s i t i o n a t C-4: i s o p r o p y l , i s o b u t y l and t e r t - b u t y l . I t was a l s o a n t i c i p a t e d that one of these p y r a z o l i n e s would give only cyclopropane product - 45 -which could lead to a clean-cut measurement of the deuterium kinetic isotope effect concerning the cyclopropane formation. DISCUSSION I. Some of the general features o f thermal decomposition o f  1-pyrazolines which served as a b a s i s f o r research plans Snyder's work (60) has shown that the r a t e o f decomposition o f 1-pyrazolines was increased by such s u b s t i t u e n t s as carbomethoxy, a c e t y l , cyano and methyl groups at p o s i t i o n 3 and 5, but the s u b s t i t u -t i o n o f a methyl group at C-4 caused a r a t e decrease. S i m i l a r but more d e t a i l e d r e s u l t s are presented i n Master's t h e s i s (61). He made a comparison o f r e l a t i v e r a t e s o f the s u b s t i t u t e d p y r a z o l i n e s at 109.4°C i n n-butyl phthalate solvent and found that the e l e c t r o n withdrawing a b i l i t y o f the s u b s t i t u e n t s at C-3 had a large e f f e c t on the r a t e o f p y r o l y s i s . The r a t e increases i n going from the 3-carbomethoxy to the 3-acetyl and to the 3-cyano p y r a z o l i n e s roughly c o r r e l a t e d with the i n c r e a s i n g e l e c t r o n withdrawing power o f the above mentioned groups. In the case o f the 3-acetyl and 3-cyano-l-pyrazolines, not only the r a t e o f decomposition i s changed but new products appear; dihydro-furans and HCN. The reexamination o f the product s t u d i e s done on 3-methyl-3-cyano-l-pyrazoline lead to s l i g h t l y d i f f e r e n t r e s u l t s than - 47 -those obtained by I. Masters (61). The gas chromatographic a n a l y s i s i n s t e a d o f s i x peaks gave only four. The f i r s t peak was most l i k e l y HCN ( c h a r a c t e r i s t i c almond odor and p o s i t i v e benzidine blue t e s t ) . The other three a n g e l o n i t r i l e , 1-methyl-l-cyano-cyclopropane and t i g l o n i t r i l e , i d e n t i c a l to those found by I. Masters. The samples a l s o contained a small amount o f s o l i d m a t e r i a l . Up to date there has not been a thorough study concerning the mechanistic d e t a i l s o f HCN formation. There i s an eight to t e n f o l d r a t e increase and a small AH decrease upon s u b s t i t u t i o n o f a methyl group at the f i v e p o s i t i o n , while the stereochemistry of the methyl group changes the r a t e of decomposition very l i t t l e but a l t e r s the product d i s t r i b u t i o n consider-ably. The s u b s t i t u t i o n of a second methyl group at C-5 causes a decrease i n the r a t e of fragmentation. I I . 3 - A l k y l p y r a z o l i n e s 3-tert-Butyl-3-carbomethoxy-1-pyrazoline: Snyder (60) found that the s u b s t i t u t i o n o f an e t h y l group f o r the methyl at C-3 reduced the r a t e of n i t r o g e n e v o l u t i o n . Although no explanation was given by the author, i t was most l i k e l y due t o the f a c t that the e t h y l group i s b u l k i e r than the methyl. U n f o r t u n a t e l y product s t u d i e s have not been done t o see the e f f e c t on the product d i s t r i b u t i o n . - 48 -This compound had to be heated up to 160° to e f f e c t decomposition at a reasonable r a t e . This leads to the c o n c l u s i o n that 156 i s one o f the most s t a b l e p y r a z o l i n e s having an a l k y l and carbomethoxy groups at C-5. N C 0 0 C H 3 —1 = fert-butyl 156 This compound turned out to be one of the most s t a b l e 1-pyrazolines t o the present having a carbomethoxy and an a l k y l s u b s t i t u e n t at C-3. * To decompose i t at a reasonable r a t e i t should be heated up to 160°C. I t s n.m.r. spectrum i n d i c a t e s t h a t the hydrogen of the two methylenes e x h i b i t an almost f i r s t o r d er ABMN s p i n system. I t was p o s s i b l e t o c a l c u l a t e the best values f o r the s i x c o u p l i n g constants and chemical s h i f t s u s i n g a computer program. H = 5.497 x A H D = 5.839 T o JAB = : -17. 416 Hz JAM = 3. 876 Hz JAN = 9. 807 Hz JBM = 9; 336 Hz JBN = 7. 950 Hz JMN = : -13. 176 Hz 8.130 T H = 8.446 T N K i n e t i c s t u d i e s c o u l d not be done on i t u s i n g our apparatus because o f the r e l a t i v e l y h i g h temperature t o o b t a i n a c o n v e n i e n t l y measurable r a t e . - 49 -On the b a s i s o f the n.m.r. s p e c t r a o f 3,3-dimethyl- and 3-methyl-3-carbomethoxy-1-pyrazolines, (51 ) i n which the two C-4 and C-5 hydrogens form an ABO^ s p i n system i m p l i c a t i n g the equivalence o f the C-4 hydrogens which i s the consequence o f the f a c t t h a t both conforma-t i o n s are e q u a l l y populated at room temperature, one can conclude that the p y r a z o l i n e 156 i s locked i n one conformation by the l a r g e t e r t b u t y l group. To determine the p r e f e r r e d conformation of 156 one should most reasonably p l a c e the t e r t b u t y l group i n the pseudo e q u a t o r i a l p o s i t i o n ( i f the t e r t b u t y l group were pseudo a x i a l the non-bonding i n t e r a c t i o n s between the pseudo a x i a l hydrogen i n C-5 and the t e r t b u t y l group would be c o n s i d e r a b l e ) . H Q COOCH 3 The i n s p e c t i o n of n.m.r. s p e c t r a of other p y r a z o l i n e s shows that the s i g n a l of the methyl i n a pseudo a x i a l carbomethoxy group appears around 6.38x and that i n a pseudo e q u a t o r i a l around 6.15T due to the s h i e l d i n g and d e s h i e l d i n g e f f e c t o f the N=N double bond r e s p e c t i v e l y . r 50 -The peak, due to the carbomethoxy group i n the n.m.r. spectrum of 156, i s at 6.35T s u b s t a n t i a t i n g the former assumption. Perhaps i t i s worth while to mention t h a t the carbomethoxy group of 164 cannot be i n any other p o s i t i o n but i n pseudo a x i a l and appears at 6.37T c l o s e t o the value of 156. The stereochemistry of the o l e f i n i c product obtained from thermolysis a l s o supports t h i s assumption i n accordance with McGreer's o l e f i n formation scheme. C H 3 COOCH 3 158 35 .4% + cycloprop. products 159 6 4 . 5 % The d i r e c t p h o t o l y s i s i n isopentane at 3100 A gave the f o l l o w i n g products: H C O O C H 3 160 160 i s most l i k e l y formed v i a a 1 , 2 - d i r a d i c a l i n t e r m e d i a t e * and not by a reverse 1,3-cyclo a d d i t i o n . The mechanism of the formation of the 1 , 2 - d i r a d i c a l and the other photoproducts 158, 159 i s not c l e a r yet. The benzophenone s e n s i t i z e d p h o t o l y s i s at 3500 A gave only cyclopropane product. A more d e t a i l e d d i s c u s s i o n w i l l be given l a t e r . - 52 -I I I . K i n e t i c and product s t u d i e s o f l-carbomethoxy-2,3-diazabicyclo  (3.3.0)-oct-2-ene and i t s analogue-5d]. In order to gain some more informa t i o n about the i n f l u e n c e o f stereochemistry o f the parent p y r a z o l i n e over the product d i s t r i b u t i o n upon thermolysis a p y r a z o l i n e system was inc o r p o r a t e d i n t o a r i g i d s t r u c t u r e by connecting C-3 and C-4 with a s h o r t , three-membered bri d g e t o exclude p o s s i b l e conformational i n t e r c o n v e r s i o n . Compounds having s h o r t e r one (62) or two-membered bridges (63) seem to undergo a m e c h a n i s t i c a l l y complex fragmentation. The other i n t e r e s t i n g f e a t u r e o f the 2,3-diazabicyclo(3.3.0)-oct-2-ene and i t s d e r i v a t i v e s that the suggested trimethylene i n t e r -mediate cannot e a s i l y achieve the 0.0 geometry as i n the case o f simple p y r a z o l i n e s due to the s t r a i n caused by the r e l a t i v e l y short * chain. Schneider and Crawford (9) reported the f o l l o w i n g product d i s t r i b u t i o n o f 160 upon thermolysis at 200°C, 67.7% 18.8% 13.5% AHJ = 38.5 Kcal/mol A St = 6.67 e.u. * A l i and Crawford (40) pointed out that the intermediacy o f 0.0 trimethylene alone could not account f o r the double i n v e r s i o n observed i n the cyclopropane product. ** C a l c u l a t i o n based on Schneider and Crawford r e s u l t s . - 53 H A N ° = f N C O O C H 3 N 164 C O O C H 3 K C00CH 3 K C O O C H 3 17 + 165 166 CH: K COOCH. C H , at 130-131 °C 19.6% at 240-260°C 31.6% (in injection port) A S * =-2.62e.u. 70.0% 56.7% AH= 28.3 Kcal. 10.2% 10.8% 168 H 3 C C H 3 H 3 C C O O C H 3 C H 3 C H 3 C O O C H 3 CH^ 169 170 30% CH=C—CH C O O C H 3 C H 3 COOCH3 CH^CHg 171 3 172 3 3 6 6 % 4 % A H * = 33£ A S * = 7.9 ,CH, N CHji in gas phase w 174 79% A H * = 39.0 Kcal Van Auken et d . (14) 176 177 2 1 % AS* = 6.3 e.u. Crawford et g i (40) - 54 -I t i s i n t e r e s t i n g to note that 168 gave l e s s o l e f i n i c products than 164 i n s p i t e o f the form and s t r u c t u r a l s i m i l a r i t y (n.m.r. data, namely coupling constants do not conform). This d i f f e r e n c e can be best a t t r i b -uted to the d i f f e r e n c e i n f l e x i b i l i t y between the two p y r a z o l i n e s . The thermolysis of 1-carbomethoxy-2,3-diazabicyclo(3.3.0)-oct-3-ene-5-d 1 gave r i s e to a product mixture shown below: 3 C O O C H 3 D CH2D CH 2 180 181 182 183 at 130-131 °C at 240-26Q° (injection port) 34.3 42.7 58.1 47.7 7.5 9.3 - 55 -The comparison of product d i s t r i b u t i o n s of 160 and 164 shows that the e l e c t r o n withdrawing carbomethoxy group not only decreases the temperature r e q u i r e d to b r i n g about decomposition but a l s o d r a s t i c a l l y a l t e r s the o l e f i n cyclopropane r a t i o . S i m i l a r behavior can a l s o be found among monocyclic p y r a z o l i n e s , 84, 184 and 185. The formation of o l e f i n i c products 166 and 167 most l i k e l y f o l l o w s concerted pathways s i m i l a r to those proposed by McGreer (51,52) v i a t r a n s i t i o n s t a t e s 178 and .179 r e s p e c t i v e l y . The large amount of o l e f i n i c compound i n the product mixture seems to i n d i c a t e that the C-5 hydrogen may be i n a favorable p o s i t i o n f o r mi g r a t i o n . Since Bergman et_ al_. (10) have suggested a near planar p y r a z o l i n e r i n g s t r u c t u r e f o r both exo- and endo-2-methyl-5,4-diazabicyclo[3.5.0]oct-3-enes on the b a s i s of coupling constants (J = 3.0 Hz f o r the exo r b v trans and J c ^ s = 7.0 Hz f o r the endo compounds) i t i s worthwhile to compare the coupling constants of 164 (J = 8.5 Hz and J . =3.3 Hz) with those r trans c i s obtained by Bergman*. The coupling constants d i f f e r c o n s i d e r a b l y unless we assume that the pseudoaxial hydrogen H^ ( c i s to Hx) appears at a lower f i e l d than the pseudoequatorial hydrogen, H^ because of the d e s h i e l d i n g e f f e c t o f the carbomethoxy group. However n.m.r. data o f c i s - and t r a n s -3,5-dimethyl-3-carbomethoxy-l-pyrazolines (51) do not seem to s u b s t a n t i a t e t h i s assumption since the chemical s h i f t values of the pseudoaxial hydrogens were found to be almost i d e n t i c a l i n both isomers. Consequently Bergman's stereochemical argument i s not a p p l i c a b l e to 164. Unfortunately there are no data a v a i l a b l e on the chemical s h i f t values of C-2 protons. - 56 -kH The relatively large T — =1.24 overall deuterium kinetic isotope effect for kD and the change in product distribution corroborate McGreer's idea of con-certed olefin formation. If the olefinic and cyclopropane products came from a common intermediate and no significant changes regarding the bonding situation of deuterium were taking place in the transition state of the rate determining step as in the case of 4-methyl-l-pyrazoline-4d^ (34) the overall kinetic isotope effectswould be quite small while changes in the product ratios would only be significant. The kinetic isotope effect for the individual reaction which were obtained from the overall deuterium kinetic isotope effect and the product distributions are as follows. kH T— for 3,y-olefin formation = 1.68 kD kH r — for a,B-olefin formation = 1.49 kD kH T— for cyclopropane formation = 0.71 KD The "inverse" value for cyclopropane formation is contrary to other findings in the monocyclic pyrazolines but i t cannot be attributed to experimental errors. The substitution of deuterium at C-5 caused a con-siderable increase in the activation parameters (AH* = 32.4 kcal mol 1, AS^ = 7.17 e.u.) relative to those (AH* 28.3 kcal mol - 1, AS* -2.62 e.u.) for 164. The change in product distribution upon the different mode of fragmen-tation (flask and injection port) may be attributed to the effect of phase changes. However, the low vapor pressure of the pyrazoline at the temperature of the injection port must also be considered. - 57 -The d i r e c t p h o t o l y s i s of 164 and 180 (3100 A) gave only c y c l o -propane products i n greater than 98% y i e l d . Because of the easy access to s t a r t i n g m a t e r i a l s and diazomethane and the high y i e l d , i t seems to be an i d e a l p r e p a r a t i v e route to b i c y c l o (3.1.0)hexane d e r i v a t i v e s . IV. Stereochemical f a c t o r s a f f e c t i n g o l e f i n formation (a) The e f f e c t of the s i z e of the e s t e r group on o l e f i n formation, 3-methyl-3-carbalkoxy-1-pyrazolines. Inspection of Table V shows that the i n t r o d u c t i o n of a second methyl group at C-3 of 3-methyl-1-pyrazoline r e s u l t s i n a s l i g h t i n c r e a s e i n the y i e l d of cyclopropane d e r i v a t i v e upon thermolysis while the i n t r o -duction of a carbomethoxy group brings about a s u b s t a n t i a l change i n product d i s t r i b u t i o n . The replacement of the methyl group of the carbo-methoxy by e t h y l and t e r t - b u t y l groups causes a small decrease i n the y i e l d of the o l e f i n i c products. TABLE V The y i e l d s of o l e f i n i c and cyclopropane products of a s e r i e s of 3-methyl-3-carbalkoxy-l-pyrazplines upon thermolysis - 58 -COMPOUND OLEFINIC PROD, CYCLOPROPANE PROD. C H 3 6 . 7 % 9 3 . 3 % N N in gas phase Crawford, M ishra (34) 84 C H 3 CH N N 3 — I I— Crawford, Mishra (34) 1 8 4 3.3 % 96.7 % in gas phase 15 % 85 % pure 3 3 . 2 % (16) 6 6 . 8 % r ^ N s s | < C C H 3 informamide 5 5 . 5 % 4 4 . 5 % N = N COOCH 3 McGreer, Masters (61) 1 8 5 C H 3 P u r* I | \ 2 9 - 6 % 7 0 , 4 % I I C O O C H ? — C H 3 N N 2 5 in this work 186 ^ N / C H 3 C H 3 pure I T ^ C O O C - C H , N = N I 0 2 5 . 9 % 7 4 . 1 % 187 C H 3 in this work - 59 -The n.m.r. s p e c t r a of 184, 185 and 186 showed that the C-4 hydrogens are equivalent leading to the co n c l u s i o n that both conformations are e q u a l l y populated. This i s not the case w i t h 187 and probably the conformation i n which the carboxy t e r t - b u t y l group i s i n the pseudo-e q u a t o r i a l p o s i t i o n i s s l i g h t l y favored over the other. A c l o s e i n s p e c t i o n o f Table V r e v e a l s t h a t the s u b s t i t u t i o n of a carbomethoxy f o r a methyl group b r i n g s about s i g n i f i c a n t changes i n product d i s t r i b u t i o n . Simple stereochemical arguments cannot account f o r t h i s change s i n c e the methyl group i s not much l a r g e r i n s i z e than the carbomethoxy group. The assumption that the o l e f i n s are a l s o formed v i a a 1 , 3 - d i r a d i c a l intermediate s i m i l a r to that proposed by Crawford (34) i s untenable because i t cannot e x p l a i n the s t e r e o s p e c i f i c o l e f i n formation observed by McGreer et al_ (51,52), besides i f we accept Ruchard's (64) c l a i m t h a t the methyl and the carbomethoxy groups have about the same s t a b i l i z i n g e f f e c t s on simple r a d i c a l centres (both decrease spi n d e n s i t y ) we should expect s i m i l a r product d i s t r i b u t i o n s from both 184 and 185 which i s not the case. A v i a b l e explanation which can account f o r the s t e r e o s p e c i f i c o l e f i n formation was put forward by McGreer e£ al_. (51). They proposed a concerted path and pointed out the stereochemical requirements f o r o l e f i n formation. Product studies done i n solve n t s w i t h d i f f e r i n g p o l a r i t y (61) showed that those which had higher p o l a r i t y favored the o l e f i n - 60 -formation. This i s a c l e a r i n d i c a t i o n that the t r a n s i t i o n s t a t e f o r o l e f i n formation i s more p o l a r than that f o r cyclopropane formation. The other i n t e r e s t i n g feature of the thermal decomposition i s the change i n product d i s t r i b u t i o n brought about by the s i z e of the a l k y l group i n the e s t e r p a r t . I t i s d i f f i c u l t to give a c l e a r e xplanation of i t but i t seems that i t i s due to stereochemical changes i n the t r a n s i t i o n s t a t e . (b) The e f f e c t o f the s i z e o f the a l k y l group i n C-4 on o l e f i n  formation, cis_- and trans-3-methyl-4-alkyl-3-carbomethoxy-l- p y r a z o l i n e s . The works of van Auken et^ al_. (14) and McGreer et_ al_. (52) i n d i c a t e d that the s i z e and the p o s i t i o n of the a l k y l group i n C-4 a l s o a f f e c t the product d i s t r i b u t i o n . TABLE VI The product d i s t r i b u t i o n of c i s - and trans-3-methyl-4-alkyl-3-carbomethoxy-1-pyrazolines upon t h e r m o l y s i s . - 61 -COMPOUND COOCH, N 1 6 8 CYCLO PRO PANES OLEFIN a,$ OLEFIN & r cis trans Z E 17.6% 12.32% 65 .75% 4 . 0 % van Auken etal.|4 c N' 188 :N COOCH 3 28 .3% 34.57% 3 2 . 8 4 % 4.25% van Auken et al. 14 COOCH: N' 129 31 .0% 9.% 0 5 6 % 4 . 0 % McGreer et al.52 —''"I^  . / " C O O C H : N 130 189 1 1 . 0 % 7 2 % 1 3 % 0 4 , 0 % 4 3 . 0 % 3 .6% 0 48.9 % 4.2 % in this work COOCH: N' 1 9 0 0 91 .7% 8.3 % 0 0 in this work - 62 -COMPOUND CYCLOPROPANES OLEFIN. a.B OLEFlN./3.y cis trgns Z E C 0 0 C H 3 N 191 4 2 . 7 % 0 0 4 4 . 0 % 13.0% in this work y~~ l c o ° c H 3 i0j°o/o 79- i% iq°o/o ° c N in this work 192 M - COOChU 1 0 0 % 0 0 0 0 N in this work 193 ' " Y ^ " C 0 0 C H 3 0 100% 0 0 0 N ^ in this work 194 " c i s means that the a l k y l and the methyl groups are c i s to each other. The f o l l o w i n g general remarks can be based on the r e s u l t s shown i n Table IV: - Trans- p y r a z o l i n e s tend to give more cyclopropane products than the c i s - ones. - The b u l k i e r the a l k y l group at C-4, the more cyclopropane w i l l form. The extreme case i s the t e r t - b u t y l group when no o l e f i n formation has been observed. - 63 -- The s t e r e o s e l e c t i v i t y o f cyclopropane formation i s higher i n the case of t r a n s - p y r a z o l i n e s . - The o l e f i n formation i s s t e r e o s p e c i f i c , c o r r o b o r a t i n g McGreer et^ al_. f i n d i n g s . (c) Deuterium k i n e t i c isotope e f f e c t of o l e f i n formation, k i n e t i c  and product s t u d i e s on 3-methyl-3-carbalkoxy-l-pyrazolines-4d^ The c a t a l y t i c r e d u c t i o n of sodium (E)-g-bromomethacrylate with D2 i n D2O and the subsequent work-up provided an a c i d mixture c o n t a i n i n g 89% (E)-, 9% (Z)-methacrylic a c i d - 3 d 1 and 2% m e t h a c r y l i c a c i d . This mixture was converted to the corresponding p y r a z o l i n e s and used up f o r product s t u d i e s . Further experiments i n d i c a t e d that i t was p o s s i b l e to o b t a i n (E)-methacrylic acid-3d^ f r e e of the (Z)-isomer by changing r e a c t i o n c o n d i t i o n s . U n f o r t u n a t e l y the process became so slow and cumbersome that the a v a i l a b l e equipment seemed inadequate f o r prepara-t i o n of the r e q u i r e d 3-4g o f p y r a z o l i n e f o r k i n e t i c s t u d i e s . Most of the mono-deuterated m e t h a c r y l i c a c i d used i n t h i s study was the z-isomer and was made by the method of Towells (68). This isomer when reacted w i t h diazomethane gives trans-3-methyl-3-c a r b a l k o x y - l - p y r a z o l i n e s - 4 d 1 (217). Perhaps the best proof of the s t e r e o s p e c i f i c o l e f i n formation was obtained from the product d i s t r i b u t i o n s o f trans-5-methyl-3-carbomethoxy-l - p y r a z o l i n e - 4 d j 199 and trans-3-methyl-3-carbethoxy-l-pyrazoline-4d^ 210. < / C 0 0 C H 3 " 9 O O C H 3 A C O O C H 3 C H 3 C O O C H 3 CH, C H , - K C H j - A ^ C H - ^ H + A | + ^ + ^ 3 C H 3 C H 3 H C H 3 H COOCH 3 J95 J96 J97 4 . 5 % 64.4 14.3% H D i > f C 0 0 C H 3 A COOCH 3 ) f c O O C H 3 I XN C H 3 ^ C H = C D — C H + ^ - f C H 3 C H 3 200 202 C H 2 = C H — CD 1 9 8 1 6 . 4 % D H COOCH 3 ^ C O O C H 3 H ^ C H 3 CH , C H 3 C H 3 C H 3 CHD COOCH 3 D COOCH-201_ 203 . ^ 0 4 205 3 5 % 69.3% 9.7% 1 7 . 7 % COOEt COOB r^. - A - *>- C H p — C H — CH NT C H 3  186 2 0 6 4 , 2 % iCOOEt COOEt A I C H , - C H 2 = C D — C H N 210 211 C H 3 COOEt I C H , = C H — CD C H 3 212 3 . 6 % A COOEt C H 3 207 7 0 . 4 CH, COOEt M H C H 3 2 0 8 1 2 . 6 % C H , C H 3 H COOEt 209 1 3 . 0 % D H COOEt F CH: 213_ H D COOCH: 7 C H , 214 H CH, CH ZD COOEt 215 C H 3 C H 3 D COOEt 216 7 4 . 0 % 8 . 9 % 1 3 . 2 % - 66 -The s u b s t a n t i a l decrease i n the amount o f deuterated angelates can be best explained by the scheme o f concerted o l e f i n formation COOR H CH, H CH 2D COOR 218 COOR H X C H 3 X D COOR 219 The formation of angelates are retarded by the " r e l a t i v e l y s m a l l " kH primary deuterium isotope e f f e c t ^— = 1.74 f o r the methyl e s t e r and D k - 1.6 f o r the e t h y l e s t e r , while the formation o f t i g l a t e s i s D k H subjected to a secondary a - k i n e t i c isotope e f f e c t , T — = 1.1 f o r both D e s t e r s . (d) B , y - o l e f i n formation. The thermolysis o f trans-3-methyl-3-carbomethoxy-l-pyrazoline-4d^ provided 6 , y - o l e f i n i c product i n 3.5% y i e l d . The i n t e g r a t i o n o f the n.m.r. spectrum o f the i s o l a t e d compound showed that i t c o n s i s t e d of two components 200, 201. Their formation can be envisaged as f o l l o w s - 67 -D /CCX)CH3 C H 2 = C — CH 200 \ CH, H C00CH. I / CH?—C — CD \ 201 C 0 0 C H 3 The n.m.r. spectrum a l s o i n d i c a t e d that 200 was present i n l a r g e r amounts as a n t i c i p a t e d i f i t s formation was slowed by a secondary deuterium isotope e f f e c t (the n.m.r. spectrum was not good enough to measure the i n d i v i d u a l components q u a n t i t a t i v e l y ) . The o v e r a l l kH k i n e t i c isotope e f f e c t f o r both was found to be r — = 1.4. S i m i l a r kD r e s u l t s were obtained from the trans-3-methyl-3-carbethoxy-l- p y r a z o l i n e -kH 4d ; 7— = 1.3. The f a c t that 3 , Y - o l e f i n i c e s t e r s do not appear i n 1 K D the decomposition product mixtures o f a l l p y r a z o l i n e s , although t h e i r s t r u c t u r e e l e c t r o n i c a l l y i s very s i m i l a r , may i n d i c a t e that the only governing f a c t o r i n t h e i r formation i s the stereochemistry, i . e . , the geometrical p o s i t i o n o f the C-4 hydrogen i n the t r a n s i t i o n s t a t e . - 68 -V. Mechanistic c o n s i d e r a t i o n o f cyclopropane formation. Product s t u d i e s showed that 193 and 194 gave only cyclopropanes on thermolysis w i t h f u l l r e t e n t i o n o f the stereochemistry o f the parent p y r a z o l i n e s . The d i r e c t and s e n s i t i z e d photolyses o f both p y r a z o l i n e s gave r i s e to the same cyclopropane products as d i d the thermolyses. r\4 C H 3 A or \/ COOCH: N hi/ or Ph 2CO + hz/ COOCH 3 194 221 These r e s u l t s excluded the p o s s i b i l i t y of a symmetry c o n t r o l l e d concerted r e a c t i o n on the grounds t h a t d i r e c t p h o t o l y s i s should have given products w i t h opposite stereochemistry w i t h respect to th a t obtained by t h e r m o l y s i s . S i m i l a r r e s u l t s have been reported by Berson and O l i n - 69 -(53) and Schmit (65) although Inagaki and Fukui (66) could e x p l a i n these f i n d i n g s by using the o r b i t a l i n t e r a c t i o n theory. The two remaining mechanistic p o s s i b i l i t i e s are the e n e r g e t i c a l l y concerted symmetry d i s a l l o w e d and d i r a d i c a l pathways. The thermal decomposition of c i s - and trans-3-methy1-carbomethoxy-1-pyrazoline-d^ provided the same mixture; 1:1 of c i s - and t r a n s - 1 -methyl-l-carbomethoxy-cyclopropane-2-d 1. The benzophenone s e n s i t i z e d p h o t o l y s i s gave i d e n t i c a l r e s u l t s with those of thermolysis concerning the r a t i o o f the two isomers i n the deutero cyclopropane products, while the d i r e c t p h o t o l y s i s e x h i b i t e d a s l i g h t ^5% r e t e n t i o n . This means that the d i r a d i c a l i n ground s i n g l e t s t a t e i s not considerably d i f f e r e n t from the e x c i t e d s i n g l e t s t a t e concerning the r i n g c l o s u r e . In f a c t , there are two processes competing with each other, r o t a t i o n and r i n g c l o s u r e . I t seems that the bond r o t a t i o n i s f a s t e r . In the case of s e n s i t i z e d p h o t o l y s i s the t r i p l e t d i r a d i c a l i s produced. I t s r i n g c l o s u r e i s - 70 -delayed by the r e l a t i v e l y slow process o f s p i n i n v e r s i o n . The energy p r o f i l e o f the r e a c t i o n i s possibly., the f o l l o w i n g : c pyrazoline cyclopropane Reaction coordinat The f a c t that the s t e r e o s e l e c t i v i t y o f the cyclopropane formation increases with the bul k i n e s s of the C-4 s u b s t i t u e n t s , p a r t i c u l a r l y i n the case o f t r a n s - p y r a z o l i n e s , i s an i n d i c a t i o n that there i s a competition between r i n g c l o s u r e and r o t a t i o n . The bulky s u b s t i t u e n t s hinder or r u l e out r o t a t i o n e n t i r e l y even i f the thermodynamically - 71 -less f a vorable cyclopropane isomer formation has t o take p l a c e . I t i s claimed by s e v e r a l authors (23,34,36) that simultaneous rupture of the two C-N bonds occurs during the decomposition of 1-pyrazolines. However, the inferences about the nature o f the bond cleavage, whether i t i s concerted or stepwise (10.29), have been made from i n d i r e c t evidence, mainly from deuterium k i n e t i c isotope e f f e c t s and product s t u d i e s done mostly on more or l e s s symmetrically sub-s t i t u t e d p y r a z o l i n e s . Conceivably i t i s p o s s i b l e that a l t e r i n g the s t r u c t u r e o f the reactant such that the rupture o f the C-N bonds are no longer equivalent i n the t r a n s i t i o n s t a t e , i . e . , one of the two C-N bonds i s being broken to a l a r g e r degree than the other. Unfortu-n a t e l y , our r e s u l t s , which w i l l be disc u s s e d , do not allow one to draw any d e f i n i t e c o n c l u s i o n about the bond breakage. The f a c t t h a t 193 and 194 gave only cyclopropanes upon decomposition made i t p o s s i b l e to determine k i n e t i c isotope e f f e c t s f o r cyclopropane formation c l e a r l y . The ra t e measurements on c i s -and trans-3-methyl-4- /-butyl-3-carbomethoxy-l-pyrazoline-4-d 1 provided k ' k 1 r — = 1.093 ± 0.0078 and . J i = 1.069 ± 0.024 r e s p e c t i v e l y . S i m i l a r r e s u l t s were obtained from the k i n e t i c s t u d i e s done on trans-3-methyl-3-KH carbomethoxy-l-pyrazoline-4-d 1, — = 1.06 and trans-3-methyl-3-are i n l i n e with those obtained by McGreer and Masters r^- = 1.20 f o r kD two deuterions although a b i t lower than Crawford's 13%. - t e r t -- 72 -The f l u c t u a t i o n s i n the values of t t - f o r cyclopropane formation KD can be a t t r i b u t e d t o the e r r o r made i n the k i n e t i c measurements as w e l l as i n the gas chromatographic a n a l y s i s of the i n d i v i d u a l com-ponents o f the product mixture. The reverse k i n e t i c isotope e f f e c t c a l c u l a t e d f o r cyclopropane kH formation (V— =0.71) i n the thermal decomposition o f 1-carbomethoxy-D 2,3-diazabicyclo(3.3.0)oct-2-ene and i t s analogous-5d^ means that the r e a c t i o n i s not slowed down but a c c e l e r a t e d by deuterium contrary t o other r e s u l t s . An acceptable e x p l a n a t i o n o f t h i s i r r e g u l a r i t y i s d i f f i c u l t to give at t h i s time unless we assume that the formation o f the bicyclo(3.1.0)hexane d e r i v a t i v e 165 i s favored on account of the s m a l l e r s t e r i c requirement f o r deuterium. (Since hydrogen and deuterium have very s i m i l a r s i z e s , but the lower zero p o i n t energy o f C-D i m p l i e s a sm a l l e r amplitude f o r the v i b r a t i o n l e a d i n g to a sm a l l e r s t e r i c requirement.) Although i t i s d i f f i c u l t to s i n g l e out one of the s e v e r a l , r a t h e r c o n t r o v e r s i a l explanations concerning the o r i g i n o f the secondary 8 - k i n e t i c isotope e f f e c t and use i t as a base to e l u c i d a t e the measured e f f e c t s , the most of t e n encountered argument a p p l i e s the concept of hyperconjugation. Hoffman (37,38) has shown th a t the hyperconjugation plays an important r o l e i n the s t a b i l i z a t i o n o f s i n g l e t trimethylene species. Because o f hyperconjugation, the d i f f e r e n c e i n v i b r a t i o n a l energy between the C-H bond and the C-D bond i n the t r a n s i t i o n s t a t e i s l e s s than i t i s i n the ground s t a t e so the r e a c t i o n i s slowed by s u b s t i t u t i o n of deuterium f o r hydrogen. - 73 -S i m i l a r l y , Crawford and Mishra a t t r i b u t e d the observed k i n e t i c i s otope e f f e c t t o hyperconjugation. The slower r a t e of decomposition of 4-deuterated monocyclic p y r a z o l i n e s i s experimental f a c t - i t does not matter f o r most purposes how t h i s can be p a r t i t i o n e d among the various p o s s i b l e causes ( i n d u c t i v e , s t e r i c , hyperconjugative e f f e c t s , bond str e n g t h changes with h y b r i d i z a t i o n ) . VI. P h o t o l y s i s of p y r a z o l i n e s . , The c y c l o a d d i t i o n r e a c t i o n i n v o l v i n g thermal a d d i t i o n o f d i a z o -methane to a carbon-carbon double bond shows a l l the stereochemical p r o p e r t i e s o f a concerted symmetry allowed process and theory supports t h i s view. There are a few examples of thermally induced r e v e r s a l or c y c l o r e v e r s i o n of t h i s r e a c t i o n . A much more frequent observation i s a photochemical c y c l o r e v e r s i o n . Such a process would not be expected to be symmetry allowed, however a l l stereochemical i n f o r m a t i o n i n the l i t e r a t u r e shows i t to be s t e r e o s p e c i f i c as expected f o r a concerted r e a c t i o n . Such s t e r e o s p e c i f i c i t y was not found i n the photodecomposition of trans-3-methyl-3-carbethoxy-1-pyrazoline-4d . The d i r e c t p h o t o l y s i s of trans-3-methyl-3-carbethoxy-1-pyrazoline-4 d j , 210 provided e t h y l methacrylate-3d^ i n 14.2% y i e l d . The n.m.r. spectrum of the i s o l a t e d compound showed 75% r e t e n t i o n with respect to the - 74 -s t a r t i n g m a t e r i a l . In order t o see whether any c i s - t r a n s i s o m e r i z a t i o n was t a k i n g place during i r r a d i a t i o n a sample c o n t a i n i n g *methyl c i s -methacrylate-3-dj was photolysed f o r 8 hours (same time as f o r the py r a z o l i n e ) and i t s n.m.r. spectrum recorded. Another sample c o n t a i n -i n g deuterated methyl methacrylate and cis-3-methy1-4-tert-butyl-3-carbomethoxy p y r a z o l i n e was i r r a d i a t e d f o r 8 hours. The n.m.r. s p e c t r a of both compounds showed p r a c t i c a l l y no changes. These experiments suggest t h a t the carbon-carbon bond cleavage occurs by a mechanism other than 1,3-dipolar c y c l o r e v e r s i o n . Although there i s no informa t i o n a v a i l a b l e to date on the mechanistic d e t a i l s of carbon-carbon bond cleavage i t most l i k e l y takes place by a non-concerted way. Results can be best explained by the intermediacy of a 1 , 2 - d i r a d i c a l 223 which can undergo r o t a t i o n and double bond formation. D \ / C 0 0 C H 2 - C H , H \ ^COOCH - C H , ^ C — C f 3 „ > — C ^ 2 3 H ' ^ C H , D * ^ C H , 223 3 225 3 t / C O O C H 2 - C H 3 C — c . H C H , 74% 224 XOOCH--CH, ^ C = C ^ 2 3 LT C H , 26% 226 * The e t h y l e s t e r was not a v a i l a b l e . -16-SUMMARY Many authors have pointed out (21,22,23) that the stereochemical factors present in the pyrazoline play an important role in determining both the product distribution and product stereochemistry. In order to evaluate the stereochemical effects brought about by different substituents the pyrazoline ring i t s e l f should be scrutinized. It has been known for quite some time that the structure of the pyrazoline ring, like that of cyclopentene, resembles a folded envelope (52). H v 73a T 73 b The n.m.r. studies indicated that the pyrazoline structure is quite mobile; i t undergoes rapid conformational interconversion at room temperature. However, McGreer et_ al_. (52) postulated that certain substituted pyrazolines may have a preference for one conformation. They have also calculated angle ex's for monocyclic pyrazolines using J . and J coupling constants and the Karplus equation. On the C I S "CTcHlS - 7 6 -basis of these stereochemical facts about pyrazolines and the stereo-chemistry of olefinic products they put forward a suggestion concerning the mechanism of olefin formation. According to the mechanism proposed the olefin formation often takes place from the less stable conformation. Consequentl i t seemed evident that i f conformational interconversion was a pre-requisite for olefin formation the introduction of a suitably bulky substituent which could prevent that would rule out the olefin forming reaction. Inspection of Table V I reveals that the tert-butyl group placed on C-4 not only eliminated the olefin forming pathway but gave rise to only one cyclopropane product. On the other hand the incorpora-tion of the pyrazoline ring in a bicyclic system led to 164, 2 2 7 , 2 2 8 which produced large amounts of olefinic products upon thermolysis, Table V I I . Considering these results one can come to the conclusion that in these bicyclic systems the atoms, especially the C-5 hydrogens, are held in such a geometrical arrangement which fa c i l i t a t e s olefin formation. The findings presented in Table V and Table V I in accord with the deuterium kinetic isotope effects for olefin formation corroborate McGreer's proposal that the olefin forming process involved in the thermal decomposition of 3-carbomethoxy-1-pyrazolines is a concerted reaction. Another interesting feature of the olefin forming reaction is that the position of the carbomethoxy group may also affect the olefin-cyclopropane ratio. Table V I indicates that the cis-pyrazolines tend - 77 -to g i v e a higher percentage of o l e f i n i c products than the corresponding trans ones. Considering the t r a n s i t i o n s t a t e f o r t h i s step f o r c i s -p y r a z o l i n e s the carbomethoxy group i s under the p y r a z o l i n e r i n g . I t i s conceivable that the e s t e r group i n t h i s p o s i t i o n might f a c i l i t a t e o l e f i n formation more than i n the e q u a t o r i a l p o s i t i o n . The product s t u d i e s of c i s - and t r a n s - 3 - m e t h y l - 4 - t e r t - b u t y l - 3 -carbomethoxy-l-pyrazolines and c i s - and trans-3-methyl-3-carbomethoxy-l - p y r a z o l i n e s - 4 d ^ provided an unambiguous evidence f o r the i n t e r -mediacy of a d i r a d i c a l i n the cyclopropane forming r e a c t i o n s . The intermediate i s assumed t o be a 1 , 3 - d i r a d i c a l which can undergo r o t a t i o n around C - l and C-2 bond before r i n g c l o s u r e occurs i n the absence of s t e r i c hindrance caused by s u b s t i t u e n t s . TABLE VII The coupling constants and decomposition products of a s e r i e s of b i c y c l o p y r a z o l i n e s - 78 -COMPOUND COUPLING CONSTANT DECOMPOSITION PRODUCTS (at 1 3 1 ° ) O(trans) J(cis) olefin/3,7 cycloprop. olefin a, (3 H (trans) _ N // •N H COOCH 3 (cis) 164 8.5 Hz 3.3Hz 1 0 . 2 % 19.6% 7 0 . 0 % D N // COOCH 3 180 7 . 5 % 3 4 . 3 % 58.1% . N 4 COOCH, 6.3Hz 7.5Hz 4 . 5 % 15 .3% 80 .2% 2 2 7 N i f COOCH: 8.5Hz 4.5 Hz 4 . 2 % 18.6% 7 7 . 2 % 2 2 8 - 7 ? -EXPERIMENTAL I. General statements B o i l i n g p o i n t s are uncorrected. They were determined by M e t t l e r FP1 m e l t i n g and b o i l i n g p o i n t apparatus. A l l i n f r a r e d s p e c t r a were measured on l i q u i d f i l m s between sodium c h l o r i d e p l a t e s w i t h a Perkin-Elmer Model 457 G r a t i n g I n f r a r e d Spectrophotometer. A l l u l t r a v i o l e t s p e c t r a were recorded on a Perkin-Elmer Model 202 Spectrophotometer. 60 MHz n u c l e a r magnetic resonance s p e c t r a were recorded on a Varian A s s o c i a t e s Model A-60 Spectrometer by Miss P. Watson. 100 MHz nuclear magnetic resonance s p e c t r a were recorded on a Varian Associates Model XL-100 Spectrometer by Dr. E. Koster. The analyses were done on an Aerograph Model A-90-P and an Aerograph Model A-90-P3. The elemental microanalyses were performed by Mr. P. Borda of t h i s Department. - 80 -I I . P reparation o f 3-methyl-3-cyano-l-pyrazoline M e t h a c r y l o n i t r i t e and diazomethane i n ether s o l u t i o n was allowed to stand i n a c o l d room f o r s e v e r a l hours. A f t e r evaporating the ether, the p y r a z o l i n e was d i s t i l l e d i n vacuum i n a modified b u l b - t o -bulb d i s t i l l a t i o n apparatus. Bath temp.: 50-55° (0.03 - 0.05 mm). The product was a c l e a r l i q u i d and i t s s p e c t r a l p r o p e r t i e s were i d e n t i c a l to those reported by Masters [61]. Anal. Calcd. f o r C H N : C, 55.04; H, 6.42, Found: C, 55.13; H, 6.57. I t was decomposted by hea t i n g at 120°C f o r three hours. I I I . P r e p a r a t i o n o f 3-tert-butyl-3-carbomethoxy-1-pyrazoline (a) P r e p a r a t i o n o f methyl 2-tert-butylpropen-2-oate. The f o l l o w i n g equations i l l u s t r a t e the s y n t h e t i c scheme; 229 H C — C H : II 0 230 • K M n Q . — H C—COOH 4 II 0 C H 3 231 H C — COOCH 3 — MeMgl-*- - 4 — C—C00CH3 0 OH t C-160 CH2=C—COOCH3 232 C H 2 N 2 orMeOH rnCH 2 Cl 2 SO CI-- 81 -1. 3,3-Dimethyl-2-oxobutanoic a c i d 230_ (70). A 120 g of KMn04 and 40 g of NaOH were d i s s o l v e d i n 3 l i t r e of water and 40 g of pinacolone was added dropwise over a p e r i o d of 2 hours. The o x i d a t i o n was s l i g h t l y exothermic and r e q u i r e d some c o o l i n g . A f t e r 12 hours o f s t i r r i n g at room temperature, the p r e c i p i t a t e d MnG^ was f i l t e r e d o f f , the aqueous s o l u t i o n a c i d i f i e d with 260 ml cc HC1, and the a c i d e x t r a c t e d w i t h three 200 ml p o r t i o n s of ether. The e t h e r a l e x t r a c t was d r i e d (MgSO^), concentrated g i v i n g 46 g (88.5%) which was used without f u r t h e r p u r i f i c a t i o n ; n.m.r. (CC1 4) T 1.63 (s, 1, COOH), T 8.76 ( s , 9, (CH3)3C). 2. Methyl 3,3-dimethyl-2-oxobutanoate 231 The e s t e r i f i c a t i o n of the a c i d i n i t i a l l y was accomplished w i t h CH^N^ i n ether s o l u t i o n . A f t e r d r y i n g over MgSO^, the ether was evaporated and the product d i s t i l l e d : b.p.: 83-85° (52 mm), 160.1° (755 mm); n D 1.4082; i r 1710 cm (est e r and ketone C=0); n.m.r. (CC1 4) x 6.18 (s , 3, C00CH_3); 8.77 (s , 9, (CH ) 3 C ) . Anal. Calcd. f o r C H^Cy C, 58.30; H, 8.33. Found: C, 58.38; H, 8.55. 3. Methyl 2,3,3-trimethyl-2-hydroxybutanoate 232 Methyl magnesium i o d i d e made from 2.6 g of Mg turn i n g s and 14.5 g of CH 3~I i n 80 ml of ether was added slo w l y to 14.4 g of 231 i n 50 ml dry ether which was cooled i n a dryice-acetone - 82 -ACETONE bath. The exothermic r e a c t i o n y i e l d e d an orange s l u s h which was added to 50 ml i c e - c o l d 10% HC1. The organic phase was separated, washed w i t h ^ 0 and 5% NaHCO^, d r i e d over MgSO^, concentrated and d i s t i l l e d g i v i n g 12.5 g (80%) c o l o u r l e s s l i q u i d ; b.p.: 75-77° (20 mm); n 2 ° D 1.4295; i r 3550 cm"1 (OH), 1735 cm"1 (CO e s t e r ) ; n.m.r. (CC1 4) T 6.22 (*>, 3, C00CH 3), 8.71 (s , 3, CH_3), 9.04 (s, 9, ( C H 3 ) 3 C ) ; the presence o f OH was v e r i f i e d by adding D2O to the sample. Anal. Calcd. f o r C_H-,0_: C, 59.95; H, 10.06. Found: C, 59.72; H, 10.26. 4. Methyl 2-tert-butylpropen-2-oate. 160 To a s t i r r e d s o l u t i o n o f 11.6 g of 232 , 12 g o f p y r i d i n e and 30 ml of toluene, 10 g of t h i o n y l c h l o r i d e was added over a p e r i o d of 1 hour. A f t e r the a d d i t i o n o f t h i o n y l c h l o r i d e the mixture was r e f l u x e d and s t i r r e d f o r 5 hours. The h e a t i n g was discontinued and when the temperature i n the f l a s k dropped to 50-52°, 100 ml of petroleum ether was added slo w l y . The dark mixture was allowed to cool to room temperature. The s o l i d i f i e d byproduct was f i l t e r e d o f f and washed with 50 ml of petroleum ether. The f i l t r a t e washed with 50 ml of water, 50 ml of 5% NaHC0 3 s o l u t i o n and 50 ml of water. A f t e r d r y i n g (MgS0 4) the petroleum ether was removed by f l a s h evaporation and the remain-i n g dark l i q u i d was d i s t i l l e d through a 2 inch Vigreux column. - 83 -(During this d i s t i l l a t i o n extremely bad smelling gases evolved.) The fraction coming between 143-150° was collected and r e d i s t i l l e d , 2 0 giving 4.2 g (40.5 %) of 160 ; b.p.: 146.8°; n D 1.4273; i r 1725 cm"1 (C=0 ester), 1620 cm"1 (C=C); n.m.r. (CC14) x 4.10 (s, 1, H cis to the ester group), 4.50 (s, 1, H), 6.30 (s, 3, C00CH_3), 8.82 ( s , 9, (CHj) 3C). Anal. Calcd. for CgH^O^ C, 67.56; H, 9.93. Found: C, 67.66; H, 10.28. (b) Preparation of 3-tert-buty1-3-carbomethoxy-1-pyrazoline. This pyrazoline was prepared by addition of diazomethane to methyl 3,3-dimethyl-2-methylene butanoate in ether solution. After 48 hours of standing at room temperature, the ether was flash evaporated and the crude pyrazoline purified by vacuum d i s t i l l a t i o n using a modified bulb-to-bulb d i s t i l l a t i o n apparatus: bath temp. 65-70°, 0.05 mm; 20 -1 n D 1.4673; uv max (95% C^OH) 328 my; i r 1730 cm (ester C=0), 1560, 1568 cm"1 (N=N); n.m.r. (CC14) T 5.00 - 6.00 (m, 2, C-5), 6.35 ( s , 3, C00CH_3), 8.14 - 8.60 (m, 2, C-4), 9.96 ( s , 9, (CH^C), (more information on n.m.r. spectrum of 156 can be found on page 48. Anal. Calcd. for C„HL„No0,,: C, 58.65; H, 8.76. Found: C, 58.50; H, 8.45. - 84 -IV. Product s t u d i e s o f 3 - t e r t - b u t y l - 3 - c a r b o m e t h o x y - 1 - p y r a z o l i n e the s y n t h e s i s o f methyl ( Z ) - 2 - t e r t - b u t y l b u t e n - Z - o a t e . (a) Thermal d e c o m p o s i t i o n o f 3-tert-buty1-3-carbomethoxy-1-p y r a z o l i n e . In a 5 ml round bottom f l a s k e quipped w i t h a condenser, 1 g o f p y r a z o l i n e was h e a t e d at 160° f o r 4 h o u r s . The p r o d u c t , a y e l l o w i s h l i q u i d was a n a l y s e d on a 6' by 1/4" diameter copper column packed with 20% P o l y m-phenyl e t h e r ( 5 - r i n g ) on chromosorb P; f l o w r a t e 80 ml He/min, column temp. 135°. Two components were s e p a r a t e d and c o l l e c t e d o f f the gas chromatograph. On th e b a s i s o f t h e i r n.m.r. s p e c t r a the f o l l o w i n g s t r u c t u r e s were a s s i g n e d t o them. HN / c=c / \ CH 3 C00CH 3 158 Methyl ( Z ) - 2 - t e r t - b u t y l b u t e n - 2 - o a t e (158), b .p.:164.7° (754 mm); n 2 0 D 1.4331; i r 1730 cm" 1 ( e s t e r C=0), 1635 cm" 1 (C=C); n.m.r. (CC1 4) t 4.30 - 4.68 (q, 1, J=6.4 Hz, o l e f i n i c ) , 6.36 ( s , 3, C00CH 3), 8.41 (d, 3, J=7.0 Hz, CH_3) , 8.93 ( s , 9, ( C H ^ C ) . - 85 -Anal. Calcd. f o r C 9 H 1 6 ° 2 : C, 69.19; H, 10.32. Found: C, 69.20; H, 10.22. The geometric assignment was based on previous observation made by Fraser (71), McGreer (17,52), and i n t h i s work, t h a t the o l e f i n i c proton s i g n a l s of JZ o l e f i n i c e s t e r s of general formula: l^-CH^CR^COOCH^ appear between T 3-4 which i s somewhat lower than those of the E isomers at T 4-5 due t o the d e s h i e l d i n g e f f e c t of the e s t e r c a r b o n y l . This i s supported by the f a c t , as i t was pointed out i n the D i s c u s s i o n , t h a t the bulky t e r t - b u t y l group does not allow conformational i n t e r -conversion and the o l e f i n i s thus being formed s t e r e o s p e c i f i c a l l y so that only the Z isomer can form. Several attempts were made to o b t a i n 158 by a way other than from p y r a z o l i n e . I t seemed reasonable to f o l l o w a s y n t h e t i c sequence s i m i l a r to the p r e p a r a t i o n of 160, but i n s t e a d of a d d i t i o n , r e d u c t i o n took place when ethylmagnesium was bromide used. H —I C-COOCH, E t M g B r > , —j C-C00CH, + CH =CH-I || 6 I | 3 2 2 0 231_ OH 233 I t i s known that a l k y l l i t h i u m compounds do not have the r e d u c t i v e p r o p e r t i e s of Grignard reagents but they add l e s s s e l e c t i v e l y to ^ C - C O O C H , II 3 0 231 carbonyl groups. L i E t , H 2 0 , H C l - C O O C H 3 O H 234 - 86 -Into a 250 ml three necked round bottom f l a s k equipped w i t h a mechanical s t i r r e r , a rubber septum, a vent with a C a C ^ dr y i n g tube and a gas i n l e t tube, 3.6 g of methyl 3,3-dimethyl-2-oxybutanoate and 40 ml of ether ( d i s t i l l e d from CaH 2) were placed. The f l a s k was cooled i n a DRY ICE - propanol bath and purged w i t h dry oxygen-free n i t r o g e n f o r 10 minutes. To t h i s s o l u t i o n 45 ml (about 10% excess] 22% o f e t h y l l i t h i u m s o l u t i o n was added by a s y r i n g e . The mixture was allowed to come to room temperature w h i l e the s t i r r i n g was con-t i n u e d , and poured i n t o 130 ml of i c e - c o l d 10% HC1. The organic l a y e r was separated, washed w i t h 30 ml 5% NaHCO., s o l u t i o n and 50 ml water. A f t e r d r y i n g over MgSO^, the ether and benzene were removed by f l a s h evaporation and the r e s u l t i n g y e l l o w i s h l i q u i d d i s t i l l e d i n vacuum. The f r a c t i o n coming over between 55-75°, 1.5 mm, was c o l l e c t e d . I t contained 234 with some other i m p u r i t i e s , y i e l d 18 g ^  41%; n.m.r. (CC1 4) T 6.14 (s , 3, C00CH 3), 6.90 ( s , 1, OH), 8.0 - 8.5 (m, 2, -CH_2) , 8.96 ( s , 9 (CH 3)„C). Unstable at room temperature. The same dehydration procedure as was used to prepare 160, was used to obta i n 1_58 i n s i m i l a r 40% y i e l d . The n.m.r. spectrum was i d e n t i c a l with those obtained from 1_56 upon t h e r m o l y s i s . The gas chromatographic a n a l y s i s of the crude product i n d i c a t e d the absence o f the E isomer. E q u i l i b r i u m of Z_ o l e f i n a l s o f a i l e d to produce the E_ isomer. The other product 159 i s 1-tert-buty1-1-carbomethoxy cyclopropane, 20 -1 b.p. : 154.6°; n D 1.4379; i r 3100 and 3040 cm (cyclopropane hydrogens), - 87 -1750 cm (est e r C=0); n.m.r. (CC1 4) T 6.48 (s, 3, C00CH_3), 9.02 ( s , 9+2, (CH 3) 3C + CH-CH ( c i s to the carbomethoxy), 9.21 (m, 2, CH-CH ( t r a n s ) ) . Anal. Calcd. f o r C 9 H 1 6 0 2 : C> 69.19; H, 10.33. Found: C, 69.55; H, 10.49. (b) D i r e c t p h o t o l y s i s o f 3-tert-butyl-3-carbomethoxy-1-pyrazoline. A 0.5 g sample o f p y r a z o l i n e was d i s s o l v e d i n 50 ml.isopentane and photolysed i n a Rayonet Photochemical Reactor using 3100 A lamps u n t i l the sample showed no t y p i c a l N=N bond absorption i n the uv. The solvent was evaporated and the product mixture was analyzed by gas chromatography. (The same column and co n d i t i o n s were used as f o r the a n a l y s i s o f thermal decomposition products.) 160 CH 2 = C COOCH3 6.1 % ret time : 7.2 min 158 5,2% 10.4 CH 3 C O O C H 3 159 C O O C H 3 88.6% 14.4 (c) S e n s i t i z e d p h o t o l y s i s of 3-tert-butyl-3-carbomethoxy-l-p y r a z o l i n e . Five grams o f benzophenone and 0.5 g of p y r a z o l i n e were d i s s o l v e d i n 50 ml of isopentane (saturated s o l u t i o n of benzophenone). The - 88 -s o l u t i o n was i r r a d i a t e d i n a Rayonet Photochemical Reactor f o r 24 hours using 3500 A lamps. A f t e r s e v e r a l r e p e t i t i o n s of the evaporation, c o o l i n g and f i l t r a t i o n c y c l e a p r a c t i c a l l y benzophenone f r e e product had been obtained which was found to be only the cyclopropane product 159.; V. Preparation o f 1-carbomethoxy-2,3-diazabicyclo(3.3.0)oct-2-ene and i t s analogue-5d^. (a) Preparation of l-carbomethoxy-2,3-diazabicyclo(3.3.0)oct-2-ene. N=N 3 2 The f o l l o w i n g s y n t h e t i c sequence was chosen f o r the p r e p a r a t i o n of 238. - 89 -1. 1-Cyclopentenecarboxylic a c i d . One gram o f NaBH^ was d i s s o l v e d i n 40 ml of methanol c o n t a i n i n g 1 ml of NaOH s o l u t i o n at -2°C. To t h i s t u r b i d s o l u t i o n 15.5 g of 2-carboethoxycyclopentanone; was added while the temperature was kept at 0°C. The mixture was s t i r r e d overnight at room temperature and then 200 ml o f water was added and the r e s u l t i n g s o l u t i o n was a c i d i f i e d with 10% HC1 to pH^3. The product was e x t r a c t e d w i t h chloroform, washed with 10% Na2C0 3 and water, and d r i e d over MgSO^. Evaporation o f c h l o r o -form y i e l d e d 16.0 g of crude product which was dehydrated w i t h 30 g of triphenylphosphine i n a s o l u t i o n of 150 ml dry CCl^. (See page 104.) - 90 -The crude product was p u r i f i e d by vacuum d i s t i l l a t i o n . Y i e l d was: 10.5 g (70.5%), b.p.: 92-93° (25 mm); i r 1715 cm"1 ( e s t e r C=0) 1622 cm"1 (C=C). The e s t e r was added t o a s o l u t i o n c o n t a i n i n g 3.2g NaOH i n 10 ml of H 20 and 20 ml of methanol and kept at 70°C f o r 24 hours. Then i t was d i l u t e d with 100 ml of H^O and a c i d i f i e d with 40 ml of 10% HC1. The free a c i d was e x t r a c t e d twice with 50 ml of ether. The ether e x t r a c t s were combined and d r i e d over MgSCy A f t e r evaporation o f the ether, the s o l i d m a t e r i a l was c r y s t a l l i z e d from hot petroleum ether (30-60°). Y i e l d : 78%, 6.2 g of white c r y s t a l s , m.p. 123°. The a c i d was e s t e r i f i e d with diazomethane a f t e r a p o r t i o n had been taken f o r a n a l y t i c a l purposes. 2. 1-Carbomethoxycyclopentene. i r 1720 cm"1 ( e s t e r C=0), 1630 cm"1 (C=C); n.m.r. (CC1 4) T 3.34 ( s , 1, o l e f i n i c H), 6.34 (1, 3, C00CH_3), 7.48 (m, 4, C-3 and C-5 H's), 7.97 (m, 2, C-4 H's). Anal. Calcd. f o r C^H^Oy C, 66.64; H, 7.99. Found: C, 66.76; H, 8.06. 3. 1-Carbomethoxy-2,3-diazabicyclo(3.3.0)oct-2-ene. F i v e grams o f 1-carbomethoxy-cyclopentene was allowed to stand w i t h an excess of diazomethane i n ether s o l u t i o n at room temperature f o r a week. The ether was f l a s h evaporated and the r e s u l t i n g compound was p u r i f i e d by vacuum d i s t i l l a t i o n u s i n g a bulb-to-bulb d i s t i l l a t i o n apparatus, bath temperature 50° (0.005 mm). Y i e l d , - 91 -6.1 g (90%); i r 1732 cm"1 (ester C=0), 1552 cm"1 (N=N); n.m.r. (CCl^) x 5.47 (dd, 1, pseudoequatorial hydrogen on C-4, J^g = 18.7, «!,.,.,,__ =8.3 Hz), 5.61 (dd, 1, pseudoaxial hydrogen on C-4, 373.115 J , R = 18.7 Hz, J . = 3.3 Hz), 7.73 (dd, 1, C-5H, J = 8.5 Hz, 6.29 (s, 3, COOCH3), 7.41 (m, 2, C-8 H's), 8.58 (m, 4, C-6 and C-7 H's). Anal. Calcd. for C-H^O-N.: C, 57.12; H, 7.19. Found: C, o LZ Z Z 56.68; H, 7.10. (b) Preparation of l-carbomethoxy-2,3-diazabicyclo(3.3.0) 2-ene-5dj. Basically the same synthetic sequence was followed as 164 but tead of NaBH^, NaBD^ (98% isotopic purity) was used. 1. 1-Cyclopentenecarboxylic acid-2d^. White crystals from petroleum ether, m.p.: 119°; n.m.r. (CDCl^) x 7.42 (m, 4 C-3 and C-5 H's), 8.00 (m, 2, C-4 H's), -1.89 (s, 1, COOH). Anal. Calcd. for C^HJDO. C, 63.70; H, 7.24. Found: o / z C, 63.79; H, 7.27 2. 1-Carbomethoxycyclopentene-2d^. The esterification of the deuterated acid with diazomethane gave a liquid i r 1720 cm"1 (ester C=0), 1630 cm"1 (C=C); n.m.r. (CC14) x 6.32 (s, 3, C00CH_3), 7.50 (m, 4, C-3 and C-5 H's), 8.02 (m, 2, C-4 H's), peak at 2.97due to the olefinic proton being absent. - 92 -3. 1-Carbomethoxy-2,3-diazabicyclo(3.3.0)oct-2-ene-5d1. The methyl ester was allowed to stand with an excess of diazomethane in ether solution for a week at room temperature. The work up was identical to that described earlier in the case of non deuterated compound. i r 1732 cm"1 (ester C=0), 1552 cm"1 (N=N); n.m.r. (CC14) T 5.0 (d, 1, pseudoequatorial hydrogen on C-4), 5.0 (d, 1, pseudoaxial hydrogen on C-4), 6.29 (s, 3, COOCHp, 7.41 (m, 2, C-8 H's), 8.58 (m, 4, C-6 and C-7 H's). Anal. Calcd. for C-H^DO,,N •. C, 56.80; H, 7.25. Found: o i l i. 2. C, 56.36; H, 7.11. VI. Product studies of l-carbomethoxy-2,3-diazabicyclo(3.3.0)oct-2-ene and i t s analogue-5dj. (a) Thermal decomposition of l-carbomethoxy-2,3-diazabicyclo(3.3.0) oct-2-ene and i t s analogue-5d]L. The thermal decomposition of the pyrazolines in a small round bottom flask equipped with a condenser at 131° provided a yellowish liquid consisting of three components. The products were separated by a 15' long V diameter copper column packed with 20% Apiazon J on Chrom P, at 160-165°C, 100 ml He/min. The compounds were collected off the gas chromatograph and their i r and n.m.r. spectra were recorded. - 93 -The following structure was assigned to the compound having 7.1 min retention time. (D)183 J2 lJ(D) CH 2 C O O C H 3 i r 3060 cm"1 (=CH2), 1735 cm"1 (ester C=0) , 1650 cm - 1 (C=C); n.m.r. (CC14) T 5.00 (m, 2, =CH2), 6.33 (s, 3, C00CH3), 6.80 (m, 1, C-l H), 7.72 (m, 4, C-3 and C-5 H's), 8.10 (m, 2, C-4 H's). The n.m.r. spectrum of the deuterated compound lacked the signal at T 6.80. The next peak, ret. time 10 min was due to 1-carbomethoxy-bicyclo(3.1.0)hexane 165 (D) 181 C O O C H 3 i r 3010 cm A (cyclopropane H's), 1730 cm 1 (ester C=0); n.m.r. (CCl^) x 6.40 (s, 3, C0OCH_3), 8.29 (m, 6, C-2, C-3 and C-4 H's), 8.71 and 9.29 (m, 3, cycloprop H's). The n.m.r. spectrum of the deuterated showed essentially identical spectrum with the exception of peaks appearing at T 8.71 and 9.29 due to the presence of deuterium. - 94 -The last peak, ret. time 11.1 min was due to 2-methyl-l-carbomethoxy-cyclopent-l-ene. C-3 H's). The n.m.r. spectrum of the 2-(methyl-d^)-1-carbomethoxy cyclopent-l-ene showed an identical spectrum with the exception of the smaller, broader peak at T 7.94 due to -CH^ D. (b) Photolyses of l-carbomethoxy-2,3-diazabicyclo(3.3.0)oct-2-In a Rayonet Photochemical reactor samples of 0.5 g pyrazolines in 30 ml of ether were irradiated for 12 hours using 3100 A lamps. The etheral solution was concentrated and analysed in the same manner described above. In both cases only cyclopropane products were isolated. 3 i r 1725 cm (ester C=0), 1660 cm" (C=C); n.m.r. ( C C l ^ T 6.36 (s, 3, C00CH3), 7.52 (m, 4, C-4 and C-5 H's), 7.94 (s, 3, CH 3), 8.20 (m, 2, ene and i t s analogue-5d,. - 95 -VII. Preparation o f l-carbomethoxy-2,3-diazabicyclo(4.3.0)non-2-ene  and l-carbomethoxy-2,3-diazabicyclo(5.3.0)dec-2-ene. The f o l l o w i n g s y n t h e t i c sequence was used to prepare the two compounds (72): (CH 2) n 0 + NaCN NaHSCh 239 240 (CH 2) n HCi H 20 242 In a three-necked round-bottom f l a s k equipped with mechanical s t i r r e r and a dropping f u n n e l , 2.6 g NaCN was d i s s o l v e d i n 20 ml o f water. A f t e r c o o l i n g the s o l u t i o n to -50° i n a c o o l i n g bath, 5 g ketone ( c y c l o -hexanone, cycloheptanone f r e s h l y d i s t i l l e d ) was added. To t h i s - 96 -mixture a solution of 12 g NaHSO^ dissolved in 25 ml of water was added slowly, then the reaction mixture was allowed to come to room temperature while the st i r r i n g was continued for 2 hours. The product was extracted with three 50 ml portions of ether, the ether flash evaporated and the residue refluxed with 30 ml of 36% HC1 for 4 hours. The pinkish liquid was diluted with 100 ml of water and extracted with three 50 ml portions of ether. The organic phases were combined and dried (MgSO^). The esterification with CH^^ and the following flash evaporation of the ether provided a brownish liquid 5.3 g, which was used without purifica-tion. Into a 100 ml three-necked round-bottom flask equipped with a mechanical st i r r e r , a condenser topped with a drying tube and a dropping funnel the crude ^ 5.3 g oxy-ester, 6.0 g pyridine and 40 ml of toluene were placed. To this mixture 6.0 g of SOC^ was added over a period of 2 hours and then the mixture was refluxed for 5 hours. The dark reaction mixture was cooled to room temperature which brought about some solidification in the mixture. Thirty m i l l i l i t e r s of petroleum ether (30-60) was added and then the solid material was fi l t e r e d off and washed with 30 ml of petroleum ether. The combined f i l t r a t e s were washed with 50 ml of water, 50 ml of 5% HC1, 50 ml of water, 50 ml of 5% NaHCO^ solution and 50 ml of water in this order. After drying (MgSO^) the petroleum ether was flash evaporated. The remaining dark solution was fraction d i s t i l l e d . (During the d i s t i l l a t i o n extremely bad smelling gases were formed.) - 97 -The fraction collected between 190-200° contained the 1-carbomethoxy-cyclohex-l-ene, which was purified by an additional d i s t i l l a t i o n , 2.2 g (31%) b.p.: 194.1°; i r 1725 cm - 1 (ester C=0), 1660 cm"1 (C=C); n.m.r. (CC14) x 3.08 (m, 1, o l e f i n i c ) , 6.37 (s, 3, C00CH_3), 7.84 (m, 4, C-3 and C-6 H's), 8.41 (m, 4, C-4 and C-5 H's). In the case of 1-carbomethoxy-cyclohept-l-ene the fraction which came over between 210-220 was r e d i s t i l l e d to obtain the ester, 2.4 g (30%) b.p.: 216.7°; i r n.m.r. (CC14) T 2.86 (tr. 1, ol e f i n i c ) , 6.37 (s, 3, COOCH,,), 7.64 (m, 4, C-3 and C-7 H's), 8.38 (m, 6, C-4, C-5 and C-6 H's). The esters were allowed to stand with an excess of diazomethane in ether solution for a week. After the flash evaporation of ether the residues were d i s t i l l e d using a bulb-to-bulb d i s t i l l a t i o n apparatus. 1-Carbomethoxy-2,3-diazabicyclo(4.3.0)non-2-ene; bath temp: 52° (0.002 mm); i r 1740 cm - 1 (ester C=0), 1545 cm"1 (N=N); n.m.r. (CC14) T 5.51 (dd, 1, pseudoaxial H on C-4, = 7.5 Hz, = 16.5 Hz), 5.84 (dd, 1, pseudoequatorial H on C-4, J D V = 6.4 Hz), 6.27 (s, 3, C00CH_), — D A O 7.65 (m, 1, C-5 H), 8.50 (m, 8, C-6, C-7, C-8 and C-9 H's). Anal. Calcd. for CnH,^N^O^: C, 59.34; H, 7.75 Found: C, 59.07: 9 14 2 2 H, 7.86. 1-Carbomethoxy-2,3-diazabicyclo(5.3.0)dec-2-ene; bath temp: 57° (0.003 mm); i r 1740 cm"1 (ester C=0), 1545 cm - 1 (N=N); n.m.r. (CC14) T 5.53 (dd, 1, pseudoequatorial H on C-4 = 8.5 Hz, J _ = 18.0 Hz), -98 -5.73 (dd, 1, pseudoaxial H on C-4, J D V = 4.5 Hz, J . D = 18.0 Hz), 6.28 — D A — A D (s 3, C00CH3), 7.40 (m, 1, C-5 H), 8.52 ( m 10, C-6, C-7, C-8, C-9 and C-10 H's). Anal. Calcd. for C,nH,.NJ).: C, 61.19; H, 8.21. Found: C, 60.82; ID lb 2. Z H, 8.32. VIII. Product studies of l-carbomethoxy-2,3-diazabicyclo(4.3.0)non- 2-ene. In a 5 ml round bottom flask equipped with a condenser 0.5 g pyrazoline was placed and heated at 131° for 6 hours. The preliminary test on a t . l . c . plate showed that the product mixture consisted of three components. The gas chromatographic analysis using a 15' long V diameter copper column packed with 20% Apiezon J on Chrom. P.; column temp. 180-185; flow rate 120 ml He/min showed only two peaks indicating that two of the components were not separated. Samples were collected off the gas chromatograph and their i r and n.m.r. spectra were recorded. The f i r s t peak, ret. time 28 min was due to 249 - 99 -i r 3100 cm"1 (exocyclic =CH2), 1730 cm"1 (ester C=0), 1655 cm"1 (C=C); n.m.r. (CC14) T 5.39 (d, 2, =CH2), 6.39 (s, 3, COOCHj), 6.94 (m, 1, C-l H), 8.01 (m, 4, C-3 and C-6 H's), 8.52 (m, 4, C-4 and C-5 H's). The other peak, ret. time 41 min was due to the following two compounds: The ratio of the two were estimated from the integrations of the carbo-methoxy peaks in the n.m.r. spectrum. IX• Product studies of l-carbomethoxy-2,3-diazabicyclo(5.5.0)dec-2-ene. The pyrazoline was decomposed in a similar fashion to that of at 145°. The t . l . c . test indicated the presence of three components. The gas chromatographic analysis using 15' copper column packed with 20% Apiezon J on Chrom. P., column temp 190-195; flow rate 120 ml He/min, showed two peaks. Samples were collected off the gas chromatograph and their n.m.r. spectra recorded. The f i r s t peak, ret. time 28 min, was due to the following olefin: - 100 -n.m.r. (CC14) T 5.14 (s, 2, =CH2), 6.37 ( s, 3., COOCH3), 6.94 (m, 1, C-l H), 8.10 (m, 10, C-3, C-4, C-5, C-6, C-7 H's). The other peak, ret. time 34 min, was due to the following two compounds: C 0 0 C H 3 The ratio of the two were estimated from the integration of the carbo-methoxy peaks .in the n.m.r. spectrum. X. 3-Methyl-3-carbo-tert-butyl-l-pyrazoline. The pyrazoline was made from commercial tert-butyl methacrylate and diazomethane. The crude product was purified by vacuum d i s t i l l a -tion using a bulb-to-bulb d i s t i l l a t i o n apparatus; bath temp.: 65-70° (0.03 mm). Its properties were identical to those reported by Snyder (60). n.m.r. (CC14) T 5.42 (m, 2, C-5 H's), 7.89 (m, 1, C-4 H), 8.56 (s, 12, (CH 3) 3C + CH_3 on C-3). Two grams of sample were decomposed at 127° and the obtained product mixture was analysed on a 20' copper column packed with 20% di-iso-decylphthalate on Chrom W column temp.: 155°, flow rate 120 ml He/min. The average deviations were calculated from three gas chromatographic analyses of the same sample. - 101 -3,Y-olefin = 4.50 ± 0.32% ret. time 8.6 min cyclopropane = 74.13 ± 0.77% 10.5 " angelate = 11.45 ± 0.31% 12.0 " tiglate = 9.94 ± 0.22% 15.0 11 XI. Preparation of ci s - and trans-3-methyl-4-alkyl-3-carbomethoxy pyrazolines, cis trans CH 3 R COOCH3 CH 3 H H £cOOCH3 H ^1 h R = iso-propyl 189 190 = iso-butyl 191 192 = tert-butyl 1_93 194 The preparation of pyrazolines followed the usual procedure in which the a,3-olefinic esters were treated with diazomethane in ether solution at room temperature. It is worth noting that the size of the alkyl group has a profound effect on the rate of cycloaddition. When R = iso-propyl, i t requires 2 treatments in two weeks, when R = tert-butyl i t takes 4-5 treatments in 5 months to achieve 85-90% conversion of the Zolefins. The E isomers are somewhat more reactive. It was anticipated from the beginning that a few stereospecifically deuterated pyrazolines would also be required to study kinetic isotope effects. Consequently such synthetic sequences were chosen which could provide starting materials for both deuterated and undeuterated - 102 -a,B-olefinic esters. The dehydration of 8-hydroxy esters, which could be obtained in good yield by the Reformatsky reaction, were favored over other poss i b i l i t i e s for the preparation of olefinic esters because their oxydation to 6-keto esters and reduction with NaBD^  followed by dehydration could give the required B-deutero olefinic esters. (a) General procedure for the preparation of B-hydroxy esters. Into a three necked flask equipped with a mechanical st i r r e r , reflux condenser topped with a CaC^ drying tube and a pressure equi-librating- dropping funnel, 50 ml of dry ether, 22.5 g (0.3 m) Zn metal (Mesh 30) and a few crystals of iodine were placed. The mixture was refluxed and stirred for 30 min to activate the Zn. The heating was discontinued and a mixture of 0.3 m methyl a-bromopropionate and 0.32 m of aldehyde (both freshly d i s t i l l e d ) was added dropwise. The colour change of the mixture indicated the start of the reaction. The rest of the mixture and 450 ml of dry ether were added to the reaction mixture over a period of 2 hours. After the addition the mixture was refluxed for 4 hours then cooled and 300 ml of water added to i t . The voluminous white precipitate was dissolved by addition of the necessary amount of 20% l^SO^. The organic phase was separated and the water phase was extracted with three 100 ml portions of ether. The combined ether solution was washed with 100 ml of 1% H^ SO^ , 200 ml of water, 200 ml of 5% NaHCO^. After drying (MgSO^), the ether was flash-- 103 -evaporated. The residue was d i s t i l l e d i n vacuum. The f r a c t i o n s c o n t a i n i n g the B-hydroxy e s t e r s came over between 100-135° (25-30 mm). 1. Methyl 2,4-dimethyl-3-hydroxypentanoate from isobutyraldehyde and methyl a-bromopropionate CH_—CH—CH—CH—COOCH. I l l 3 CH 3 OH CH 3 25_5 Y i e l d : 78.8%; n 2°D 1.4349; i r 3520 cm - 1 (OH), 1735 cm"1 (ester C=0); n.m.r. (CC1 4) -x 6.36 (s , 3, C00CH_3), 6.18 (m, 1, C-3 H), 7.52 (m, 2, C-2 on, d OH), 8.33 (m, 1, C-4 H), 9.01 (m, 9, CH 3 H's on C-2 and C-3, C-4 H's). Anal. Calcd. f o r CoH,^0,: C, 59.97; H, 10.06. Found: o l b o C, 59.67; H, 10.31. 2. Methyl 2,5-dimethyl-3-hydroxyhexanoate from isovaleraldehyde and methyl a-bromopropionate CH,—CH—CH„—CH—CH—COOCH 3 I 2 I I CH 3 OH CH 3 256^ Y i e l d : 67.1%; n_2°D 1.4351; i r 3500 cm"1 (OH), 1760 cm"1 (ester C=0); n.m.r. (CC1 4) x 6.36 (s, 3, C00CH 3), 7.65 (m, 1, C-3 H), 8.70 (m, 2, C-2 H and OH), 8.90 (d, 3, CH 3 on C-2), 9.12 (dd, 6, CHI on C-5). Anal. Calcd. f o r C 9 H l g 0 3 : C, 62.04, H, 10.41. Found: C, 61.94; H, 10.46. 3. Methyl 2,4,4-trimethyl-3-hydroxypentanoate from pivaldehyde and methyl a-bromopropionate CH_ I 3 CH 7—C CH—CH—COOCH, 257 CH, OH CH, - 104 -Y i e l d : 70.0%; n 2°D 1.4380; i r 355 cm"1 (OH), 1725 cm"1 (ester C=0); n.m.r. (CC1 4) T 6.32 (s, 3, C00CH 3), 6.40 (m, 1, C-3 H), 7.40 (m, 2, C-2 H and OH), 8.73 (d, 3, CH_3 on C-2), 9.02 (s, 9, CH 3 ) 3 C ) . Anal. Calcd. f o r CgH^O.^ C, 62.04; H, 10.41. Found: C, 61.81; H, 10.45. (b) General procedure f o r the p r e p a r a t i o n of o l e f i n i c e s t e r s . The dehydration of the 3-hydroxy e s t e r s was e f f e c t e d by tr i p h e n y -phosphine and carbon t e t r a c h l o r i d e which served as reagent and s o l v e n t . Into a 1 l i t e r round bottom f l a s k equipped w i t h a condenser topped with a d r y i n g tube, 0.2 m of 3-hydroxy e s t e r , 0.22 m t r i p h e n y l phosphine and 400 ml of dry carbon t e t r a c h l o r i d e were placed. The s o l u t i o n was r e f l u x e d f o r 24 hours. The excess C C l ^ and the formed CHC1 3 were evaporated on a r o t a r y evaporator. The semi s o l i d mass was worked up with 200 ml of petroleum ether (30-60). A f t e r keeping at 0° f o r a few hours, the s o l i d m a t e r i a l was f i l t e r e d o f f and the cake washed with 50-70 ml of i c e c o l d petroleum ether. The evaporation of petroleum ether provided a y e l l o w i s h o i l s t i l l c o n t a i n i n g some s o l i d m a t e r i a l . The p u r i f i c a t i o n of the crude o l e f i n s was achieved by vacuum d i s t i l -l a t i o n . The o l e f i n i c products came over between 80-120° at 25-30 mm. The E and Z isomers as w e l l as the 3 , y - o l e f i n i c byproducts were separated and c o l l e c t e d by gas chromatography using a 25' long 3/4" diameter copper column packed with 20% carbowax 4000 monostearate. The i n d i v i d u a l o l e f i n s are,as f o l l o w s : - 105 -1. Methyl (E)- and (Z)-2,4-dimethylpenten-2-oate from 255. Y i e l d : 65.0% CH CH,—CH—CH=C COOCH, J j S CH (E) - 258_ (Z) - 259 (E)-isomer; b.p.: 163.3°; n D 1.4395; i r 1730 cm (e s t e r C=0), 1650 cm"1 (C=C); n.m.r. (CC1 4) x 3.56 (d, 1, o l e f i n i c , J : 4.4 Hz), 6.34 (s, 3, C00CH_3), 7.50 (m, 1, C-4 H) , 8.22 (d, 3, CH_3 on C-2) , 8.98 (d, 6, ( C H ^ - ) . Anal. Calcd. f o r CgH^O^ C, 67.60; H, 9.86. Found: C, 67.78; H, 9.69. (Z)-isomer; b.p.: 150.1°, n D 1.4345; i r 1740 cm (est e r (C=0), 1650 cm - 1 (C=C, very s m a l l ) ; n.m.r. (CC1 4) x 4.29 (d, 1, o l e f i n i c J = 3.8 Hz), 6.33 (s, 3, C00CH 3), 6.75 (m, 1, C-4 Hz), 8.17 (s, 3, CH 3 on C-2), 8.97 (d, 6, C H ^ C ) . Anal. Calcd. f o r CgH^O^ C, 67.60; H, 9.86. Found: C, 67.87; H, 9.89. 2. Methyl (E)- and (Z)-2,5-dimethylhexen-2-oate from 256. CH_—CH—CH_ —CH=C COOCH, 3 | 2 3 C H 3 (E) - 260_ (Z) - 261 - 106 -(E)-isomer; b.p.: 189.1°; i r 1725 cm"1 (ester C=0), 1655 cm" (C=C); n.m.r. (CC14) x 3.36 (t, 1, ol e f i n i c ) , 6.33 fs, 3, C00CH3), 8.00 (m, 2, C-4 H's), 8.13 ( s, 3, CH3 on C-2), 8.49 (m, 1, C-5 HO, 9.05 (d, 6, (CH 3) 2). Anal. Calcd. for CgH^Oy C, 69.23; H, 10.25. Found: C, 68.96; H, 10.36. (Z)-isomer; b.p.: 175.4°; i r 1725 cm"1 (ester C=0), 1650 cm - 1 (C=C); n.m.r. (CC14) x 4.11 (t, 1, ol e f i n i c ) , 6.31 (s, 3, C00CH3), 6.76 (m, 2, C-4 H's), 8.15( s, 3, CH_3 on C-2), 8.36 (m, 1, C-5 H), 9.10 (d, 6, (CH 3) 2). Anal. Calcd. for CgH^Cy C, 69.23; H, 10.25. Found: C, 69.01; H, 10.10. 3. Methyl (E)- and (Z)-2,4,4-trimethylpenten-2-oate from 257. CH —C CH=C COOCH (E) - 262_ CH3 (Z) - 263 Yield: 80.0% (E)-isomer; b.p.: 180.6?; n 2 0D 1.4458; i r 1720 cm"1 (ester (C=0), 1645 cm"1 (C=C); n.m.r. (CC14) x 3.37 (m, 1, ol e f i n i c ) , 6.37 (s, 3, C00CH3), 8.10 (s, 3, CH_3 on C-2), 8.80 (s, 9, (CH_3)3C). Anal. Calcd. for C-H^O • C, 69.23; H, 10.25. Found: C, 69.33; H, 10.06. - 107 -(Z)-isomer; b.p.: 162.3°; n/uD 1.4322, i r 1740 era"1 (ester C=0), 1660 cm"1 (C=C); n.m.r. (CC14) T 4.60 (m, 1. ol e f i n i c ) , 6.33 (s, 3, C00CH3), 8.19 (d, 3, CHj on C-2 J = 1.6 Hz), 8.91 (s, 9, (CH 3) 3C). Anal. Calcd. for CgH^Oy C, 69.23; H, 10.24. Found: C, 69.55; H, 9.98. (c) Pyrazolines. 1. cis-3-Methyl-4-isopropyl-3-carbomethoxy-1-pyrazoline. A liquid which so l i d i f i e s on long standing at low temperature (-5°); i r 1762 cm"1 (ester C=0), 1550 cm"1 (N=N); n.m.r. (CC14) T 5.23 (dd, 1, pseudoequatorial C-5 H, J T R A N S = 8.4 Hz, = 17.0 Hz, 6.20 (dd, 1. pseudoaxial C-5 H, J . = 9.6 Hz, J = 17.0 Hz, r —cis ' -gem 6.23 (s, 3, COOCH_3), 8.20 (m, 2, C-4 H and CH-(CH 3) 2), 8.81 (s, 3, CH3 on C-3), 9.13 (d, 6, (CH_3)2-CH). Anal. Calcd. for c 9 ^ 1 ( ^ 2 0 2 : C, 58.67; H, 8.75. Found: C, 58.32; H, 8.60. 2. trans-3-Methy1-4-isopropyl-5-carbomethoxy-1-pyrazoline. Liquid; i r 1740 cm 1 (ester C=0), 1557 cm 1 (N=N); n.m.r. (CC1.) r 5.70 (dd, 1. pseudoequatorial C-5 H, J = 8.2 Hz, J = 17.2 1 4' ' —trans -gem 601 (dd, 1, pseudoaxial C-5 H, J . = 9.8 Hz, J = 17.2 Hz, r —cis ' -gem 6.30 (s, 3, C00CH3), 8.66(m, 2, C-4 H and CH-(CH ) ) , 9.05 (d, 6, (CH ) -CH), 8.30 (s, 3, CHj on C-3). Anal. Calcd. for C_H.,No0o: C, 58.67; H, 8.75. Found: y io / i C, 58.78; H, 8.90. - 108 -3. cis-3-Me thy1-4-i sobuty1-3-carbomethoxy-1-pyraz o1 ine. Liquid; i r 1760 cm"1 (ester C=o), 1550 cm"1 (N=N); n.m.r. (CC14) T 5.12 (dd, 1, pseudoequatorial C-5 H, J _ T R A N S = 8 - 8 H Z > J = 17.6 Hz), 6.17 (dd, 1, pseudoaxial C-5 H, J . = 9.8 Hz, —gem — c i s = 17.6 Hz), 6.21 ( s , 3, C00CH_3) , 7.72 (m, 1, C-4 H), 8.79 (s, 3, CH3 on C-3), 9.14 (m, 9, (Cii^-CJi-CH^-) . Anal. Calcd. for CinHloN.0_: C, 60.51; H, 9.14. Found: 1U l o 2 2. C, 60.60; H, 9.28. 4. trans-3-Methyl-4-isobutyl-3-carbomethoxy-l-pyrazoline. Liquid; i r 1740 cm"1 (ester C=0), 1555 cm"1 (N=N); n.m.r. (CC14) T 5.19 (dd, 1, pseudoequatorial C-5 H, £ t r a n s = 8.4 Hz, J = 16.4 Hz), 6.10 (dd, 1, pseudoaxial C-5 H, J . = 9.8 Hz, — gem — c i s J ^ e m = 16.4 Hz), 6.33 ( s, .3, C00CH_3), 8.16 (m, 1, C-4 H), 8.40 (s, 3, CH_3 on C-3), 9.12 (m, 9, (CH_3)2~CH-CH2). Anal. Calcd. for C i nH 1 oN o0 • C, 60.51; H, 9.14. Found: 1U l o 2 2 C, 60.8; H, 9.20. 5. cis-3-Methyl-4-tert-butyl-3-carbomethoxy-l-pyrazoline. Liquid; i r 1760cm"1 (ester C=0), 1550 cm - 1 (N=N),; n.m.r. (CC14) T 5.29 (dd, 1, pseudo equatorial C-5 H, J T R A N S = 8.3 Hz, J = 17.0 Hz), 6.05 (dd, 1, pseudoaxial C-5 H, J . = 11.6 Hz, -gem ' r - c i s ' ^gem = 1 7 ' ° H Z^> 6 - 2 2 (s> '3> C00CH3), 8.76 (s, 3, CH_3) , 9.12 (s, 9, (CH^C; Anal. Calcd. for CinH.oN.0o: C, 60.51; H, 9.14. Found: 1U l o 2 2 C, 60.52; H, 9.00. - 109 -6. trans-3-Methyl-4-tert-butyl-3-carbomethoxy-l-pyrazoline. Liquid; i r 1740 cm"1 (ester C=0), 1550 cm - 1 (N=N); n.m.r. (CC1 ) 5.28 (dd, 1, pseudoequatorial C-5 H, J = 8.7 Hz, J = 17.0 Hz), 5.98 (dd, 1, pseudoaxial C-5 H, J . = 11.8 Hz, —gem * * > —cis J = 17.0 Hz), 6.40 (s, 3, COOCH ), 8.29 (s, 3, CH_ on C-3), §6111 O j 9.09 ( s, 9, (CH 3) 3C). Anal. Calcd. for C i nH l oN o0 o: C, 60.51; H, 9.14. Found: C, 60.56; H, 9.06. XII. Preparation of c i s - and trans-3-methyl-4-tert-butyl-3-carbomethy-l-pyrazoline-4d-| . (a) Preparation of methyl 2,4,4-trimethyl-3-ketopentanoate. The Reformatski reaction provided methyl 2,4,4-trimethyl-3-hydroxypentanoate which was oxidized to the corresponding B-keto ester by means of RiX^/NalO^: CH_ CH_ CH_ CH_ I I Ru02 | | CH_—C CH--CH--COOCH, „ T ^ * CH --C---C---CH--C00CH, 3 j j r 3 NalO^ | || 257 C H 3 ° H C H 3 ° 264 Into a 1 l i t e r three-necked round-bottom flask equipped with a mechanical stir r e r (preferably with a large sti r r i n g blade), a condenser and a dropping funnel, 100 ml of water, 17.4 g (0.1 m) B-hydroxy ester dissolved in 200 ml of carbon tetrachloride and 200 mg RuO^  were placed. The solution of 27 g of sodium metaperiodate in 400 ml of water was added over a period of 4 hours to the stirred - 110 -reaction mixture. To control the pH of the mixture during the reaction 80 ml of 10% NaHCO^ solution was also added in small portions. After the addition of sodium metaperiodate the mixture was stirred for 2 hours, 100 mg of RuC^ was added and warmed to 70° for 2 hours. The organic phase showed a blackish-yellow colour indicating the presence of RuO^, the end of reaction. After cooling i t to room temperature, the excess oxidizing agent was destroyed by addition of isopropanol. The separated organic phase was dried (MgS04) and d i s t i l l e d giving 12.8 g (82%) b.p.: 115-119° (0.5 mm). The quality of the product was checked by gas chromatography using a 12' long stainless steel column packed with 20% Zonyl C-7 on Chrom. W; column temp 170°; flow rate 60 ml He/min. The crude product contained 1-2% of starting material. After the vacuum d i s t i l l a t i o n the gas chromatogram showed less than 0.5% starting material; n.m.r. (CC14) T 6.17 (q, 1, C-2 H), 6.37 ( s, 3, C00CH3), 8.83 (s, 9, (CH 3) 3C), 8.93 (d, 3, CH_3 on C-2). Anal. Calcd. for CgH^Cy C, 62.71; H, 9.36. Found: C, 62.40; H, 9.33. (b) Preparation of methyl 2,4,4-trimethyl-3-hydroxypentanoate-In a 100 ml round bottom flask 30 ml of CHj-OD (98% isoltopic purity), 0.1 ml of 30% NaOD in D^ O were placed. This mixture was cooled to -10° and 0.55 g of NaBD4 (isotopic purity 98%). (The NaBD4 was only partially dissolved.) To this mixture 8.3 g methy 2,4,4-trimethyl-3-ketppentanoate was added slowly and stirred (magnetic) - I l l -overnight. The reaction product was taken up in 150 ml of water, the pH adjusted to ^  3 with 10% HC1 and extracted with three 50 ml portions of ether. The combined etheral extract was washed with 20 ml of 5% NaHCOj solution, dried (MgSO^) and concentrated. The vacuum d i s t i l -lation (140-150° at 10-15 mm) provided 7.2 g (85%) product; n.m.r. (CC14) T6.32(S, 3, C00CH3), 7.40 (m, : 2, C-2 H and OH), 8.73 (d, 3, CH3 on C-2), 9.02 (s, 9, (CH 3) 3C), peak at T 6.40 was absent. Anal. Calcd. for CgH^DOy C, 61.71; H, 10.40. Found: C, 61.82; H, 10.57. (c) Preparation of methyl (E)- and (Z)-2,4,4-trimethylpenten-2-oate-3di. The same procedure was used as for the non deuterated compounds. The olefinic mixture (5.0 g) contained 52% E and 47% Z isomers. Their separation was achieved by preparative gas chromatography, obtaining I. 8 g E and 1.4 g Z isomers. 1. (E)-isomer; i r 1720 cm - 1 (ester C=0), 1645 cm"1 (C=C); n.m.r. (CC14) T 6.37 (s, 3, C00CH3), 8.10 (s, 3, CH_3 on C-2), 8.80 (s, 9, (CH^j^D), the peak at 3.37 due to the olefinic proton was absent. Anal. Calcd. for C gH 1 5D0 2: C, 68.79; H, 10.67. Found: C, 68.99; H, 10.15. - 112 -2. (Z)-isomer; i t contained 1-2% (E)-isomer; i r 1740 cm 1 (ester (C=0), 1660 cm"1 (C=C); n.m.r. (CC14) T 6.33 (s, 3, C00CH_3), 8.19 (s, 3, CH3 on C-2), 8.91 (s, 9, (CR^C), the peak at T 4.60 due to the ole f i n i c proton was absent. Anal. Calcd. for CgH^DO^ C, 68.79; H, 10.67. Found: C, 69.08; H, 10.84. (d) Preparation of c i s - and trans-3-methyl-4-tert-butyl-3-carbomethoxy-l-pyrazoline-4d^. 1. cis-3-Methyl-4-tert-butyl-3-carbomethoxy-l-pyrazoline-4d-| . The treatment of 1.6 g (E)-olefin with diazomethane in ether provided 1.82 g crude pyrazoline which was purified by vacuum d i s t i l l a t i o n (see the procedure for the undeuterated compound). n.m.r. (CC14) x 5.28 (d, 1, pseudoequatorial C-5 H), 6.08 (d, 1, pseudoaxial C-5 H), 6.10 ( s, 3, C00CH_3), 8.69 (s, 3, CH3 on C-2), 9.00 (s, 9, (CH 3) 3C). Anal. Calcd. for C 1 QH DN^: c, 60.26; H, 9.61. Found: C, 60.32; H, 9.63. 2. trans-3-Methyl-4-tert-butyl-3-carbomethoxy-l-pyrazoline-4d-^. The treatment of 1.3 g olefin with diazomethane in ether solution gave 1.25 g crude product which was purified by the same way as the undeuterated: n.m.r. (CC14) x 5.35 (d, 1, pseudoequatorial C-5 H), 6.01 (d, 1, pseudoaxial C-5 H), 6.40 (s, 3, COOCH,), - 113 -8.29 (s, 3, CH3 on C-3), 9.09 (s, 9, (CH^C). Anal. Calcd. for c 1 0 H i 7 D N 2 ° 2 : C ' 6 0- 2 6> H> 9 - 6 1 - Found: C, 60.50; H. 944. XIII. Preparation of trans-3-methyl-3-carbethoxy-l-pyrazoline-4d^. The precursor, ethyl (2)-methacrylate-3-dj was prepared by the method of Fowells et^ al_. (68 ) using Merck Sharp et Dohm reagents (98% isotopic purity). Its n.m.r. spectrum was identical with those reported by Fowells et a l . , indicating the presence of 10% undeuterated compound. The crude ester was treated with diazomethane and purified by vacuum d i s t i l l a t i o n using a bulb-to-bulb d i s t i l l a t i o n apparatus, bath temp.: 55° (0.05 - 0.1 mm); n.m.r. (CC14) x 5.48 (d, 2, C-5 H's), 5.82 (q, 2, ester -CH2), 8.08 (m, 1, C-4 H), 8.48 (s, 3, CH3 on C-2), 8.77 (t, 3, ester CH 3). XIV. Product studies of trans-3-methyl-3-carbethoxy-l-pyrazoline-4dj. (a) Thermal decomposition of trans-3-methyl-5-carbethoxy-l-pyrazoline-4dj. The products of the thermolysis of trans-3-methyl-3-carbethoxy-l-pyrazoline-4d^ at 127° were analysed on a 20' long, V diameter copper column packed with 20% diisodecyl phthalate on Chrom. W., column temp 135°, flow rate 80 ml He/min. The structural assignments were based on the n.m.r. spectra. - 114 -The following compounds were identified: 1. Ethyl 2-methylbuten-2-oate-d1, 3,y-olefinic ester, ret. time: 12.4 min. The quite complex n.m.r. spectrum indicates the presence of the following three compounds: CH I CH2=CH—CD—COOCH2—CH3 212_ CH I CH2=CD—CH—COOCH2—CH3 211_ CH, CH2=CH—CH—COOCH2—CH3 265_ n.m.r. (CC14) T 4.96 (m, 2, CH_2=), 5.95 (q, 2 ester CH_2), 7.00 (m, C-3 H), 8.75 (m, ester CH3, CH_3 on C 2 and C-2 H) . 2. l-Methyl-l-carbethoxycyclopropane-2dj, ret. time: 16.6 min. n.m.r. (CC14) T 6.03 (q, 2, ester CH 2), 8.80 fs, 3, CH_3), 8.81 (tr. ester CH_3 overlapping with the cyclopropane hydrogens), 9.48 (cyclopropane H), The ethyl ester was converted to hydrazide whose n.m.r. spectrum indicated the presence of the following two isomers: D CONH-NH-H CH, 50% H C0NH— NH, D CH: 267 - 115 -3. E t h y l angelate-4d^, r e t . time: 18.6 min. n.m.r. (CCl^) x 4.00 (1, o l e f i n i c ) , 5.89 (q, 2, e s t e r CH_2), 8.19 (.S.l, CH_3 and CJH^D), 8.77 ( t , 3, e s t e r CH^). (Due to sep a r a t i o n d i f f i c u l t i e s only a small amount of compound could be c o l l e c t e d , consequently the i n t e g r a t i o n was hampered by a large n o i s e to s i g n a l r a t i o . However, the shape and the i n t e g r a t i o n o f the methyl s i g n a l s c l e a r l y showed that the deuterium was incorporated on the methyl group attached to the g-carbon. 4. E t h y l t i g l a t e - S d j , r e t . time: 25.5 min, n.m.r. (CC1 4) x 3.39 (broad, 0.10 - 0.2 due to the undeuterated e t h y l t i g l a t e , the i n t e g r a t i o n was hampered by the la r g e noise t o s i g n a l r a t i o ) , 5.85 (q, 2, e s t e r CH_2), 8.23 (s, 6, CH 3's), 8.73 ( t , 3, e s t e r CH 3). (b) D i r e c t p h o t o l y s i s of trans-3-methyl-3-carbethoxy-l-pyrazoline-Three grams of p y r a z o l i n e was d i s s o l v e d i n 50 ml of isopentane and i r r a d i a t e d f o r 15 hours i n a Rayonet Photochemical r e a c t o r u s i n g 3100 A lamps. The c a r e f u l evaporation o f the isopentane y i e l d e d a product mixture c o n t a i n i n g the f o l l o w i n g components: E t h y l methacrylate-Sd! 14.2% r e t . time 10.5 min. g,Y-o l e f i n - d j 5.7% 12.4 min. Cyclopropane prod-dj^ 71.0% 16.6 min. E t h y l angelate-dj 4.4% 18.6 min. E t h y l t i g l a t e - d j 4.7% 25.2 min. TABLE IX Photoproducts of trans-3-methy1-3-carbethoxy-l - p y r a z o l i n e - 4 d ^ - 116 -The analysis was performed under the same condition described earlier for the analysis of the product mixture obtained from thermolysis. Only the ethyl methacrylate-Sdj and the 1-methyl-l-carbethoxycyclopropane-2d^ were collected off the gas chromatograph, the latter was trans-formed into i t s hydrazid and the n.m.r. spectra of both were recorded. The n.m.r. spectrum of the isolated ethyl methacrylate-Sd^ showed a considerable change 0.26; 0.74 in the relative areas of the two peaks at T 3.96 and 4.54 with respect to the starting material in which the areas had been 0.1; 0.9. (A detailed description of the n.m.r. spectrum of the ethyl (Z-)methacrylate-3d1 is given by Fowells et_ al_. (68). l-Methyl-l-hydrazidocyclopropane-2d 1 (CC14) x 6.20 (broad, 3, NH-NH_2), 8.70 (s, 3, CH_3), 8.25 (m, 1.35 cycloprop), 9.43 (m, 1.65, cycloprop). The relative areas indicated that the following two isomers were present. D C O - N H — N H 2 H C 0 - N H - N H 2 H C H 3 D C H 3 2 6 6 2 6 J ~55% -45% XV. Preparation of 3-methyl-3-carbethoxy-l-pyrazoline. Commercial ethyl methacrylate was treated with diazomethane in 20 ether. The workup was similar to other pyrazolines. n D 1.4492; n.m.r. (CC14) x 5.50 (t, 2, C-5 H's), 5.81 (q, 2, ester CH_2), 8.02 (m, 1, C-4 H), 8.50 (s, 3, CH_3 on C-3), 8.76 (t, 3, ester CH 3). Anal. Calcd. for C?H12N Oy C, 53.82; H, 7.68. Found: C, 53.64; H, 7.66. - 117 -The products of thermal decomposition were analysed on the same column, on the same day, under the same conditions as described earlier for i t s analogous-4d^. The separated components with the exception of ethyl angelate also served as components for making up authentic mixtures. XVI. Preparation of trans-3-methyl-3-carbomethoxy-l-pyrazoline-4di. The precursor methyl (Z)-methacrylate-3d^ was prepared from the corresponding ethyl ester because of the low (5%) yield reported by Fowells ejt al_. (68) by the direct preparation. Sixteen grams of crude ethyl ester was saponified with 100 ml of M sodium hydroxyde solution at room temperature. ,The solution was fil t e r e d and the f i l t r a t e extracted with 50 ml of ether to remove byproducts. The clear solution was cooled to -2° and acidified with 65 ml of 2 m HC1. The acid was extracted with three 50 ml portions of ether, dried (MgSO^) and esterified with diazomethane. Its n.m.r. spectrum was identical with that reported by Fowells e_t al_. (68 ). They claimed on the basis of the expanded peak at T 3.96 with relative area 0.1 that i t was due to the undeuterated isomer not to the (E)-isomer. In order to obtain more further proof on the presence of methyl methacrylate the methyl group was decoupled by irradiation which resulted in a coalesce of the six peaks (doublet of a quartet) into a doublet with J u „ = 1.8 Hz. Identical coupling constant was obtained from the H1 H2 experiment done with simple methyl methacrylate. - 118 -The crude ester was treated with diazomethane in ether and purified by vacuum d i s t i l l a t i o n ; n.m.r. (CCip x 5.43 (d, 1, C-5 H), 5.55 (d, 1, C-5), 6.32 (s, 3, COOCH_3), 8.55 (s, 3, CH 3), 8.61 (m, 1, C-4 H). XVII. Product studies of trans-3-methyl-3-carbomethoxy-l-pyrazoline-4dV. . (a) Thermal decomposition. Two grams of pyrazoline was decomposed thermally (at 127°) and the products were analysed on a 30' long V diameter copper column packed with 15% diisodecylphthalate on Chrom. W; column temp.: 110°; flowrate 80 ml He/min. The individual components were collected off the gas chromatograph and their n.m.r. spectra were recorded. 1. B,Y-01efinic ester; ret. time: 8.2 min; n.m.r. (CCl^) x 4.88 (broad, 2, =CH2), 5.06 (m ^  0.2, =CH), 6.35 (s, 3, C00CH_3), 6.74 (m, ^  0.7 - .8, C-2 H), 8.75 (s, 3, CH_3). The integration of the peaks indicated that the sample consisted of two compounds D CH, . H CH_ I I I I 3 CH 2=C—CH—C00CH 3, CH 2=C—CD—C00CH 3 200 201 major component. (The accuracy of the integration was reduced by the large signal to noise ratio.) 2. l-Methyl-l-carbomethoxycyclopropane-2d^; ret. time: 11.4 min; n.m.r. (CC14) x 6.41 (s, 3, C00CH_3), 8.74 (s, 3, CH_3), 8.92 (s, 1.5, cyclopropane H's cis to carbomethoxy), 9.47 (s, 1.5, cyclopropane H's). The integration of the peaks at x 8.92 - 119 -and 9.47 indicated that the sample was a 1:1 mixture of the two isomers. COOCH: H COOCH: H C H 3 202 - 5 0 % D C H 3  203 -50% 3. Methyl angelate-4d 1; ret. time: 12.5 min; n.m.r. (CC14) x 4.00 (broad, 1, ol e f i n i c ) , 6.30 (s, 3, C00CH_3), 8.16 (s + shoulder, ^ 5, CH,, C^D). The n.m.r. spectrum clearly indicated that the deuterium was on C-4 whose hydrogens appeared at some-what lower fields due to the deshielding effect of the carbo-methoxy group. 4. Methyl tiglate-3d^; ret. time: 17.3 min; n.m.r. (CCl^) T 3.33 (broad, very small, due to the undeuterated isomer), 6.31 ( s , 3, C00CH3), 8.20 ( s , 6, the two CH_3). (b) Direct photolysis of trans-3-methy1-3-carbomethoxy-1-pyrazoline-4di. The photolysis was carried out in a Rayonet Photochemical reactor in isopentane solution using 3100 X lamps. The workup was similar to that described earlier for the ethyl ester. No quantitative analysis was done on the product mixture and only the cyclopropane product was - 120 -collected. The n.m.r. spectrum indicated a 45:55 mixture of 202 and 203. (c) Sensitized photolysis of trans-3-methyl-3-carbomethoxy-l-pyrazoline-4di. Three grams of benzophenone and 0.3 g pyrazoline was dissolved in 30 ml isopentane and photolyzed using 3500 A lamps. The workup followed a repetition of an evaporation-cooling-filtration cycle t i l l about 0.5 - 0.6 ml yellowish liquid was obtained s t i l l containing some benzophenone. The decomposition products were d i s t i l l e d off the benzophenone in a bulb-to-bulb apparatus (bath temp.: 140-150°) and separated by gas chromatography. Only the cyclopropane derivative was collected and i t s n.m.r. spectrum recorded, showing that the sample consisted of 50:50 mixture of 202 and 203. XVIII. Preparation of cis_-3-methyl-3-carbomethoxy-l-pyrazoline-4d|. The preliminary experiments showed that the bromine in B-bromo methacrylic acid could be replaced by hydrogen using copper-activated Zn-dust in refluxing methanol. The application of deuterated reagents gave a mixture containing 80 - 89% (E) and (Z)-methacrylic acid-3dj. Procedure: into a three-necked round bottom flask equipped with a mechanical stir r e r and a condenser 10 g of dry sodium (Z)-B-bromomethacrylate, 30 ml of CH3-0D, 4 ml of D20 and 5 ml of 38% DC1 in D„0 were added and stirred for 10 minutes. Ten grams of predried - 121 -Zn dust and 0.05 g C ^ C ^ were added at once. The slurry was refluxed and stirred for 24 hours. The mixture was cooled to room temperature and 100 ml 10% HC1 added to i t . The freed acid was extracted with two 30 ml portions of ether, dried (MgSO^) and esterified with diazomethane. Yield: 3.1 g (62%) estimated by gas chromatography. Catalytic reduction of sodium (E)-3-bromomethacrylate in 0^0 in the presence of equivalent amounts of NaOD or Et^N also gave (E)- and (Z)-methacrylic acid -3d^. The ratio of the E and Z isomers present in the product mixture was dependent on the activity and the amount of catalyst used. By applying only a small amount (0.5 - 1.0% of the sodium salt) of catalyst, 5% Pd or Pt on charcoal product mixtures were obtained containing 95 - 98% E isomer. The methods drawback is the relatively long reaction time of 2-3 days. During the reaction some polymerization has also taken place. The workup was similar to that described for the Zn reduction. Yields varied between 25 - 40%; n.m.r. (CCl^) x 3.98 (q, 1, olefinic H cis to the carbomethoxy), 4.54 (broad, small, olefinic H trans to the carbomethoxy), 6.32 (s, 3, COOCH,,), 8.12 (d, 3, CH_3). The origin of the small peak at x 4.54 was attributed to the Z isomer on the basis of n.m.r. studies. The methyl group was decoupled by irradiation with the result that the six peaks (doublet of a quartet) at x 4.54 collapsed into a singlet. The ester was treated with diazomethane in ether. The evaporation of ether resulted in a yellowish liquid, the crude pyrazoline which was d i s t i l l e d in vacuum; n.m.r. (CCl d) x 5.30 ( s , 1, C-5 H), 5.41 ( s , - 122 -1, C-5 H), 6.19 ( s, 3, COOQy, 7.49 ( t t , 1, C-4 H), 8.41 ( s , 3, CH_3). XIX. Product s t u d i e s o f cis-3-methyl-3-carbomethoxy-l-pyrazoline. (a) Thermal decomposition. I t was done i n the same way des c r i b e d e a r l i e r f o r the trans-isomer. Q u a n t i t a t i v e product a n a l y s i s has not been done and the cyclopropane product was c o l l e c t e d only. I t s n.m.r. spectrum i n d i c a t e d that the sample c o n s i s t e d of the two isomers (b) S e n s i t i z e d p h o t o l y s i s . I t was done i n the same way as described f o r the trans-isomer. The r e s u l t s were a l s o i d e n t i c a l . XX. Product studies o f c i s - and trans-3-methyl-4-alkyl-3-carbomethoxy-1-pyrazolines. 1. Thermal decomposition. General procedure. In a 5 ml round bottom f l a s k equipped w i t h a condenser 1.0 - 1.5 g p y r a z o l i n e was placed and heated i n an o i l bath at an appropriate temperature f o r a p e r i o d ten h a l f l i f e time. The r e s u l t i n g product mixture was analysed by gas chromatography. The s t r u c t u r e assignment of the i n d i v i d u a l components were based on t h e i r n.m.r. and i . r . s p e c t r a . In some cases there was not enough sample a v a i l a b l e f o r i s o l a t i o n : d u e to the low y i e l d s and r e t e n t i o n - 123 -times were used for identification. The thermal decomposition of c i s - and trans-3-methyI-4-alkyl-3-carbomethoxy-1-pyrazolines produced a mixture consisting of c i s - and trans-cyclopropane derivatives of (E) and (Z) olefinic esters (a,3) and 3,y-olefinic esters. R CH: COOCH: CIS 268 COOCH: CH: trans 269 R C H 3 R COOCH 3 H X C H 3 C O O C H 3 C H 3 C H 3 E Z 270 C H 3 271 R — C — C H — C O O C H , II 3 C H 2 272_ In order to determine the stereochemistry of the l-methyl-2-alkyl-l-carbomethoxy cyclopropanes i t was necessary to find out whether the two alkyl groups, i.e. R and methyl, were cis or trans to each other. The assignment was based on the comparison between the f i r s t - 124 -and the last member of a series and the assumption that i f they showed similar patterns in n.m.r. spectroscopy, rate of saponification and gas chromatographic retention times they should have similar stereo-chemistry. The n.m.r. spectra of the cis isomers showed a proton signal around T 9.6 due to the cyclopropane hydrogen while the trans isomer exhibits no signal in this region. The rate of saponification of the cis isomers are higher than for the trans ones due to stereo-chemical grounds (14). The trans isomers tend to have a shorter gas chromatographic retention time on most columns packed with polar or semipolar stationary phases on Chrom. P or W. Probably the best proof would be to synthesize the cyclopropane products by way of stereospecific methylene addition to the olefinic ester. One unsuccessful attempt has been made to add methyl generated by the method of Simons-Smith to both; methyl(E)- and (Z)-2,4,4-trimethylpentene-2-oate. The amount of B,y-olefinic esters in the product mixtures are quite small, in most cases n.m.r. spectroscopy was used to identify them. The stereochemical assignment for the a,B-olefinic esters was based on n.m.r. spectroscopy and retention times. When the methyl group is cis to the carbomethoxy i t s signal tends to appear at lower f i e l d because of the deshielding effect of the carbomethoxy group. On most columns packed with polar or semipolar stationary phases the Z isomers have shorter retention times. - 125 -(a) cis-3-Methyl-4-isopropyl-5-carbomethoxy-1-pyrazoline. The analysis was carried out on a 20' long copper column packed with 20% diisodeylphthalate on Chrom. P.; column temp.: 165°; flow-rate 120 ml He/min. 1. The f i r s t peak, ret. time: 8.1 min was due to methyl .2— methyl-3-isopropylbuten-3"-oate; n.m.r. (CC14) T 4.57 (broad, 2, =CH2), 6.37 ( s , 3, C00CH_3) , 7.00 (q, 1, C-2 H), 8.64 (d, 3, CH_3 on C-2), 9.24 (m, 7, CH(CH ) 2 ) . 2. trans-1-Methyl-2-isopropyl-1-carbomethoxycyc1opropane; ret. time: 1.2 min; n.m.r. (CC14) T 6.39 (s, 3, C00CH3), 8.74 ( s , 3, CH3 on e y e ) , 8.97 (m, 10, CH(CH_3)2 and cyclopropyl H's). 3. cis-1-Methyl-2-isopropyl-1-carbomethoxycyclopropane; ret. time: 15.0 min; n.m.r. (CC14) T 6.40 (s, 3, C00CH_3), 8.73 (s, 3, CH3 on cyclpr.), 9.00 (overlapping, 9, CH(CH 3) 2 and cyclo-propyl H's), 9.66 (s, 1, cycloprop. H). 4. Methyl (E)-2,3,4-trimethylpenten-2-oate; ret. time: 19.4 min; n.m.r. (CC14) T 6.40 (s, 3, COOCj^), 9.19 (m, 1, C-4 H), 8.22 (s, 6, CH3's on C-2 and C-3), 9.09 (d, 6, )CH_3)2 C) . - 126 -(b) trans-3-Methyl-4-isopropyl-3-carbomethoxy-l-pyrazoline. It was decomposed at 150°. The resulting product mixture was analysed on the same column under the same conditions as that of c i s -isomer. 1. trans-l-Methyl-2-isopropyl-l-carbomethoxycyclopropane; ret. time: 11.2 min; i t s n.m.r. spectrum was described earlier. 2. cis-1-Methyl-2-isopropyl-l-carbomethoxycyclopropane; ret. time: 15.0 min; it s n.m.r. spectrum was described earlier. 3. Methyl (Z)-2,3,4-trimethylpenten-2-oate; ret. time: 16.5 min; n.m.r. (CC14) x 6.32 (s, 3, COOCi^), 6.70 (m, 1, C-4 H), 8.19 (s, 3, CH3 on C-2), 8.37 (s, 3, CH5 on C-3), 9.00 (d, 6, (CH3)2CH). (c) cis-3-Methyl-4-isobutyl-3-carbomethoxy-1-pyrazoline. It was decomposed at 150° and the analysis was carried out on a 20' long copper column packed with 20% diisodecylphthalate on Chrom. P; column temp.: 165°; flowrate 130 ml He/min. The following compounds were identified: 1. Methyl 2,5-dimethyl-3-methylenehexen-3-oate; ret. time: 13.8 min; n.m.r. (CC14) x 5.15 (d, 2, CH_2=), 6.38 (s, 3, C00CH_3), 8.10 (m, 1, C-2 H), 8.78 (s, 3, CH_3 on C-2), 9.10 (m, 9, ( C H ^ -CH-CH2). - 127 -2. cis-1-Methy1-2-i sobuty1-1-carbomethoxy eye1opropane; ret. time: 18.6 min; n.m.r. (CC14) T 6.39 (s, 3, C00CH3), 8.73 (m, 2, CH_2-CH), 8.78 (s, 3, CH3 on cycloprop.), 9.08 (d, 6, (CH_3)2D, J_ = 6.0 Hz), 9.68 (d (unresolved), 1, cyclopropane H). 3. Methyl E-2,3,5-trimethylhexen-3-oate; ret. time: 21.0 min; n.m.r. (CC14) T 6.33 (s, 3, C00CH_3), 8.07 (m, 5, CH_3 on C-2 and C-4 H's), 8.17 (s, 3, CH3 on C-3), 9.08 (d, 7, (CHg) CH, J = 8.0 Hz). (d) trans-3-Methyl-4-isobutyl-3-carbomethoxy-l-pyrazoline. It was decomposed and the resulting product mixture analysed in the same way as for the product mixture of the cis isomer. 1. The f i r s t peak, ret. time: 14.0 min, was due to trans-1-methyl-2-isobutyl-l-carbomethoxycyclopropane; n.m.r. (CC14) T 6.21 ( s , 3, C00CH3), 8.60 ( s , 3, CH_3 on cyclopr.), 9.00 (m, 12 (CH3)2CH-CH2- and cyclopropane H's). 2. Methly (Z)-2,3,5-trimethylhexen-3-oate; ret. time: 17.8 min; n.m.r. (CC14), (due to poor separation the sample also contained cis -1-methyl - 2- isobutyl-1 -carbomethoxy cyclopropane); T 6.37 ( s , 3, C00CH3), 8.24 (complex, 6, CH_3*s on C-2 and C-3), 9.05 (complex, 9, (CH_3)2-CH-CH2~). - 128 -3. cis_-l-Methyl-2-isobutyl-l-carbomethoxy cyclopropane. It was described earlier. (e) cis-3-Methyl-4-tert-butyl-3-carbomethoxy-1-pyrazoline. It was decomposed at 155° giving only one product, l-methyl-2-tert-butyl-l-carbomethoxycyclopropane; b.p. 190.3°; n.m.r. (CCl^) T 6.38 (s, 3, C00CH_3), 8.76 (s, 3, CH_3 on cyclopr.), 8.95 (s, 11, (CH 3) 3C and cyclopropr. H's), 9.40 (d, 1, cyclopropyl H). Anal. Calcd for C i r iH 1 o0 • C, 70.48; H, 10.65. Found: C, 70.77; H, 10.33. (f) trans-3-Methyl-4-tert-butyl-3-carbomethoxy-l-pyrazoline. It gave only cyclopropane product trans-1-methyl-2-tert-butyl-1-carbomethoxycyclopropane; b.p. 173.7°; n.m.r. (CCl^) T 6.40 (s, 3, C00CH_3), 8.75 (s, 3, CH_3 on cyclopr.), 9.08 (s, 11, (CH 3) 3C and cycloprop. H). Anal. Calcd for C,„H l o0 •. C, 70.48; H, 10.65. Found: C, 70.22; IU l o 1. H, 10.67. 2. Photodecompositions The direct and benzophenone sensitized photolyses of c i s - and trans-3-methy1-4-tert-butyl-1-carbomethoxy-1-pyrazolines gave only cis- and trans-l-methyl-2-tert-butyl-l-carbomethoxycyclopropanes respectively. The procedures for photolyses and work-up have been described earlier. KINETIC MEASUREMENTS The r a t e s of decomposition of p y r a z o l i n e s were determined by vol u m e t r i c measurements o f the evolved n i t r o g e n u s i n g a s l i g h t l y modified apparatus described by Peterson and coworkers (69). The r e a c t i o n f l a s k was immersed i n a constant temperature bath made by the Haake Company. The thermostat could maintain the d e s i r e d temperature w i t h i n ±0.02 - 0.05°C under 155° as claimed by the manufacturer but above that the range became ±0.1°C. The s o l v e n t d i - ( n - b u t y l ) - p h t h a l a t e reagent grade was d i s t i l l e d twice at reduced pressure. For k i n e t i c runs standard s o l u t i o n of p y r a z o l i n e s were prepared so that about 1 ml o f p y r a z o l i n e s o l u t i o n would y i e l d around 30 ml of n i t r o g e n . General Procedure f o r K i n e t i c Runs Forty-n i n e ml of d i - ( n - b u t y l ) - p h t h a l a t e was preheated at the appro-p r i a t e temperature, s t i r r e d and purged w i t h n i t r o g e n f o r 30 minutes, then when the n i t r o g e n b u b b l i n g stopped i t was s t i r r e d f o r an a d d i t i o n a l 30 minutes to al l o w e q u i l i b r a t i o n . The s o l u t i o n o f the p y r a z o l i n e was i n j e c t e d by a sy r i n g e through a rubber septum. A l l runs were fo l l o w e d - 130 -up to 80% completion and then kept for 10 half lives in the bath to obtain the final volume. The experimental and the calculated f i n a l volumes were within ± 2%. The barometric pressure changes were also monitored during the kinetic runs. The kinetic runs with deuterated compounds were done immediately after the corresponding nondeuterated pyrazolines. The rate constants were calculated on Hewett-Packard's desk calculator using the method of least squares. Since the deuteration of the trans-3-methy1-3-carbomethoxy-1-pyrazoline-4d^ and the trans-3-methyl-3-carbethoxy-l-pyrazoline-4d^ was only 90% correction had to be made in the rate of decomposition. The corrections were based on the assumption that the decompositions of the pyrazolines and their analogous -4d^ are concurrent reactions, then the rate constants for the mixtures can be expressed as follows: The measured over-all deuterium kinetic isotope effect is given by eqn. (2). D meas = 0.1 k„ + 0.9 k, D CD (2) k, D meas D - 131 -If we assume that the individual processes involved in pyrazoline decompositions are parallel reactions we can calculate the specific deuterium kinetic isotope effects for each separate pathway from the over-all kinetic isotope effect and the product distributions. The rate constant for the thermolysis of a pyrazoline can be expressed as follows: kH = k l H + k2H + •••• + knH ( 3 ) Similarly, the rate constant for the thermal decomposition of a deuterated pyrazoline can be given as kD = k l D + k2D + •••• + knD ( 4 ) where k 1 u, k„ u, k „ are the rate constants for the individual IH 2H nH reactions involved in the decomposition of a pyrazoline and K1D' k2D' knD a r e t n e r a t e c o n s t a n , t s concerning the deuterated compound. According to the rate law the formation of the individual reaction products can be expressed as dC 1 H " d t - = klH CH ' ( 5 ) - 132 -d CnH ~dt~ = knH CH ' ( 6 ) d C l D -ar - = k l D CD > ' w dC n D ~dt~ = knD CD ( 8 ) where C 1 L J, C „ are the concentration of products and C,~, C are the IH nH c ID nD concentration of the deuterated products. Dividing eqn. (5) by eqn. (6), and eqn. (7) by eqn. (8) we obtain, dcm knH ( ' nD knD The integration of eqn. (9) and eqn. (10), assuming that C 1 U, C-„, i n Zn , C and C i n, C_n, C _ = 0 at t = 0, yields the results, nH nH ^ • ^ C12J nD KnD - 133 -It follows that, C1H : C2H : > , : CnH K1H : K2H :' ' : knH ^ C l D : C 2 D : " " " : C n D = klD : k2D : ,---" : knD ( 1 4 ) The division of eqn. (3) by k 1 u and eqn. (4) by k i r i yields, In ID IH IH IH = 1 • ^ • .... * ^ = B (16) klD K1D K1D Dividing eqn. (15) by eqn. (16) we get, kH k l H A kD B k l D The rearrangement and substitution of D for _H give, *D~ k l H _ BD k l D A (17) (18) The values of A and B are obtained from product studies and D from kinetic measurements. - 134 -I. Rate constants, a c t i v a t i o n parameters and o v e r a l l deuterium k i n e t i c isotope e f f e c t of 3-methyl-3-carbomethoxy-l-pyrazoline and t r a n s -3-methy1-3-carbomethoxy-1-pyrazoline-4d (a) Rate constants. Name of compound t' 3 kx] L0- 4 3-methyl-3-carbomethoxy- 122, .85 3, .43 AH = 33, .45 k c a l 1-pyrazoline 122, .85 3. ,25 AS = 9, .52 e.u. 124, .85 4. ,31 124. ,85 4. ,54 127. .27 5. .37 127, .26 5. .36 90% trans-3-methvl-3- 122. ,85 2. .91 AH = 33. ,60 k c a l carbomethoxy-1-pyrazoline- 124. ,85 3. ,87 AS = 9, .61 e.u. 4 d l s + 10% undeuterated 127. ,32 4. .65 isomer (b) O v e r a l l deuterium k i n e t i c isotope e f f e c t s . , 3.43 + 3.25 i n-4 Ji = 2 X 1 0 = 1.15 kD 2.91 x IO" 4 , 4.31 + 4.54 i n-4 k„ = x 10 n _ Z kD 3.87 x 10" 4 , 5.37 + 5.36 1 A-4 - 2 X 1 0 k -4 H 4.65 x 10 1.14 1.16 - 135 -(c) Corrected o v e r a l l deuterium k i n e t i c isotope e f f e c t s , 1. kH ~ = 1.18 kD 2. kH 1.16 ^ 1.17 RD = 3. kH k 1 - 1 8 (d) S p e c i f i c deuterium k i n e t i c isotope e f f e c t s . 1. Deuterium k i n e t i c isotope e f f e c t f o r 3 , y - o l e f i n formation: = i + M i l + M l + 1 6 d i = 2 2 . 1 4 kg,Y H 4.5 4.5 4.5 -V = ! + «L1 + 9 ^ + 17,7 = 2 ? - 6 2 k 3 , Y D 3.5 3.5 3.5 kH V Y H 22.14 kH 1.17 , - - 1.46 k r k D 27.62 'D 0.80 k6' YD 2. Deuterium k i n e t i c isotope e f f e c t f o r cyclopropane formation: kH 4.5 . 14.3 16.5 , r r = + 1 + + = 1 . 5 5 kcyc I t 64.4 64.4 64.4 H kD 3.5 . 9.7 17.7 1 = + 1 + + = 1.46 k c y c D 69.3 69.3 69.3 - 136 -k c y c H 1.55 1.46 kcyc 1.17 1.06 = 1.10 Dueterium k i n e t i c isotope e f f e c t f o r methyl angelate formation: kH 4.5 64.4 . 16.5 = + + 1 + = 6.95 kang„ 14.3 14.3 14.3 n = hi + * L 1 + : + 17V7 = 1 0 _ 3 2 kang 9.7 9.7 9.7 kH k a n g H = 6.95 = 1.17 = ? 4 k D 10.32 k 0.673 kang D Deuterium k i n e t i c isotope e f f e c t f o r methyl t i g l a t e formation kH 4.5 64.4 14.3 , , = + + + 1 = 6.04 k t i g H 16.5 16.5 16.5 kD 3.5 69.3 9.7 . _ ^ = + + + 1 = 5.66 k t i g D 17.7 17.7 17.7 - 137 -k t i g . 6.04 5.66 k t i g r k, _H 1.17 1.07 1.09 I I . Rate constants, a c t i v a t i o n parameters and o v e r a l l deuterium k i n e t i c isotope e f f e c t of 3-methyl 3-carbethoxy-l-pyrazoline and t r a n s - 3 -methyl-3-carbethoxy-l-pyrazoline-4d (a) Rate constants. Name of compound t° kxlO 3-methyl-3-carbethoxy- 117, .89 1 .74 AH = 33. .20 k c a l 1-pyrazoline 117, .89 1 .83 AS = 8, .67 e. u. 119, .81 2 .11 119, .81 2. .21 122, ,95 3 .14 127, .01 4 .71 126, ,95 4, .63 trans-3-methy1-3- 117. ,89 1. .65 AH : = 32, ,37 k c a l carbethoxy-1-pyrazoline- 117. ,89 1, .67 AS : = 6. 14 e .u. 4 " d l 119. ,81 1, .98 122. 95 2, .82 126. 95 4. .18 127. 01 4, .30 (b) O v e r a l l deuterium k i n e t i c isotope e f f e c t . 1. (1-74 + 1-83) x 10" 4 = 1 > 0 ? (1.65 + 1.67) x 10" 4 - 138 -(2.11 + 2.21) 2 = 1.09 1.98 3.14 x 10" 4 2.82 x 10" 4 4.63 x 10" 4 4.18 x 10" 4 4.71 x 10 4 4.30 x 10" 4 1.11 1.11 1.09 Corrected overall deuterium kinetic isotope effects, 1.78 = 1.070 0.178 + 0.9 K Q kH — = 1.08 k D ^ - i . i : kH 1 ^ — = 1. l.> k D — = 1.13' a, 1.12 k D - 139 -5. k — = 1.10 (d) S p e c i f i c deuterium k i n e t i c isotope e f f e c t s . 1. Deuterium k i n e t i c isotope e f f e c t f o r 8 , Y - o l e f i n formation: = 1 + + 12,6 + 12L0 = 2 3 8 6 k g,Y H 4.2 4.2 4.2 = ! + 1^1 + 8 ^ + Ihl = 27.81 k g J Y D 3.6 3.6 3.6 kH kg' TH 23.86 kH 1.12 1.30 k D 27.81 k Q 0.858 V Y D 2. Deuterium k i n e t i c isotope e f f e c t f o r cyclopropane formation: k H 4.2 12.6 13.0 . = + 1 + + = 1.424 k c y c H 70.4 70.4 70.4 k D = 3.6 + + 8.9 + 13.2 = 1.345 k c y c Q 74.4 74.4 74.4 - 140 -k C y C H 1.424 kH 1.12 - — - = 1.06 k D 1.345 k D 1.058 kc y c D Deuterium k i n e t i c isotope e f f e c t f o r e t h y l angelate formation _ Y = ±1 + Z ^ l + 1 + 13^0 = y _ 9 5 kang H 12.6 12.6 12.6 kD _ 3.6 + 7JL4 + 1 + 1^2 = n > 2 4 7 kang D 8.9 8.9 8.9 kH k a n g H _ 7.95 kH 1.12 — — — — 1 .bo k D 11.247 k D 0.707 ' k a n g D • Deuterium k i n e t i c isotope e f f e c t f o r e t h y l t i g l a t e formation: kH 4.2 70.4 12.6 . , n n A = + + + 1 = 7.704 k t i g u 13.0 13.0 13.0 n kH 3.6 74.4 8.9 = + + + 1 = 7.583 k t i g D 13.2 13.2 13.2 kH k t l g H = 7,704 = U 2 _ = 1 1 Q k D 7.583 ! k D 1.015 k t i g D - 141 -Rate constants and a c t i v a t i o n parameters o f c i s - and tr a n s - 3 -methyl-4-akyl-3-carbomethoxy-1-pyrazolines. Name of compound t° cis-3 - m e t h y l - 4 - i s o - 141.0 propyl-3-carbomethoxy-1- 147.0 py r a z o l i n e 151.0 151.3 trans-3-methyl-4-iso- 156.5 propyl-3-carbomethoxy-l- 160.5 py r a z o l i n e 164.5 169.6 cis-3 - m e t h y l - 4 - i s o - 144.5 butyl-3-carbomethoxy- 147.0 1-pyrazoline 154.5 kxlO sec 1.61 AH =36.60 k c a l mol 2.74 AS = 11.75 e.u. 4.40 4.79 1.59 AH =34.50 k c a l mol 2.71 AS = 3.91 e.u. 4.41 5.77 2.14 AH =35.30 k c a l mol 2.80 AS = 8.55 e.u. 5.85 trans-3-methy1-4-iso-butyl-3-carbomethoxy-1-pyrazoline 144.5 147.1 150.0 152.5 0.78 0.94 1.36 1.68 AH = 35.00 k c a l mol AS = 5.76 e.u. Rate constants, a c t i v a t i o n parameters and deuterium k i n e t i c isotope e f f e c t of cis-3-methy1-4-tert-butyl-3-carbomethoxy-1-p y r a z o l i n e and i t s analogue-4d Name of compound t' 3 -4 kxlO s e i cis-3-methy1-4-tert- 141, .00 2.02 buty1-3-carbomethoxy- 147, .00 3.73 1-pyrazoline 151, .00 5.17 151, .39 5.39 151. .49 5.51 154, .20 6.97 154, .50 7.57 f 1 AH = 35.67 k c a l m o l - 1 AS = 9.90 - 142 --4 -1 Name of compound t° kxlO sec ci s - 3 - m e t h y l - 4 - t e r t - 151.39 4.49 AH =36.36 k c a l mol' butyl-3-carbomethoxy- 151.49 5.01 AS = 11.32 e.u. l- p y r a z o l i n e - 4 - d 154.20 6.44 154.50 6.89 (a) Deuterium k i n e t i c isotope e f f e c t s . kH = 5.39 x 10" 4 k 4.94 x 10" 4 D 2. S\ = 5.51 x 10 4 k D 5.01 x 10" 4 k -4 _H = 6.97 x 10 k Q 6.44 x 10" 4 k -4 _H = 7.57 x 10 k 6.89 x 10" 4 D 1.091 1.099 1.082 1.098 = 1.093 ± 0.008 Rate constants, a c t i v a t i o n parameters and deuterium k i n e t i c isotope e f f e c t of trans-3-methyl-4-tert-butyl-3-carbomethoxy-1-pyrazoline and i t s analogue-4d Name of compound t° kxlO sec 1.28 AH =36.20 k c a l mol 1.31 AS = 8.80 e.u. 1.59 1.97 2.30 trans-3-methy1-4- 148.70 t e r t - b u t y l - 3 - c a r b o - 148.84 methoxy-l-pyrazoline 150.96 153.30 154.00 - 143 -Name of compound t° k x l 0 ~ 4 s e c ' trans-3-methyl-4- 148.84 1.20 AH = 36.67 k c a l mol' t e r t - b u t y l - 3 - c a r b o - 150.96 1.48 AS = 9.74 e.u. methoxy-l-pyrazoline- 153.30 1.89 4 d r (a) Dueterium k i n e t i c isotope e f f e c t s . 1. kH 1.31 x 10" k D 1.20 x 10" 4 kH 1.59 x 10" 4 D = 1.091 kn. 1.48 x 10" 4 1.074 * 1.069 ± 0.024 = 1.97 x 10" 4 k n 1.89 x 10" 4 1.042 D Rate constants, a c t i v a t i o n parameters and o v e r a l l deuterium k i n e t i c isotope e f f e c t o f l-carbomethoxy-2,3-diazabicyclo(3.3.0) oct-2-ene and i t s analogue-5d^. Name of compound t° kxlO 4 1-carbomethoxy-•2,3- 127. .75 7, .82 AH = 28. 30 k c a l mol d i a z a b i c y c l o ( 3 . 3.0) 128. .74 8. .45 AS = -2 .62 e.u. oct-2-ene 129. .74 9. ,40 131. .74 11. ,22 132. .74 12. ,01 1-carbomethoxy-•2,3- 127. ,75 6. ,20 AH = 32. 40 k c a l mol d i a z a b i c y c l o ( 3 . 3.0)- 128. ,74 6. ,64 AS = 7 .17 e.u. oct-2-ene-5d^ 129. ,74 7. ,53 131. ,74 9. ,27 132. ,74 10. ,06 - 144 -(a) O v e r a l l deuterium k i n e t i c isotope e f f e c t . k H 7.82 x 10 4 k D 6.20 x 10"4 — - 8 - 4 5 x 10"4 k D 6.64 x 10"4 3. 9.40 x 10"4 k D 7.53 x 10"4 •k _ 4. _ H 1.122 x 10 k D 9.27 x 10"4 = 1.26 1.27 = 1.25 ^ 1.24 1.21 5- — - 1-201 x 10"3 = k Q 1.006 x 10"3 (b) S p e c i f i c deuterium k i n e t i c i s otope e f f e c t s . 1. Deuterium k i n e t i c isotope e f f e c t f o r B,y o l e f i n formation: _ A . = l + I L i + = 9.78 k g , Y H 10.2 10.2 1 + 34,3 + S*A __ 1 3 _ 3 2 3 k 3 , Y D 7.5 7.5 k H V Y H „ = _^78_ = 0 > ? 3 4 ^ = 1 > 6 8 kD 13.323 k Q V YD - 145 -2. Deuterium k i n e t i c isotope e f f e c t f o r cyclopropane formation: kH _ 10.2 ^ . 7.0 + 1 + T 7 T ~ T " = 5.09 kc7c~ 19.6 19.6 H kD = 7.5 58.1 = 2.91 kcTc^ " 34.3 34.3 kcy°u 5 09 k u — $ = = 1.745 _» = 0.71 kD 2.91 k [ ) _ kcycD 3. Deuterium k i n e t i c isotope e f f e c t f o r a , B - o l e f i n formation: k H 1 0 - 2 • 1 9 " 6 + 1 = 1.4257 kD _ 7.5 + 344 + 1 ^ ka,eD 58.1 58.1 kH - ^ 2 5 7 . = 0.83 ^ = 1.49 kR 1.72 — - FD k ,en a D V I I . Rate constants and a c t i v a t i o n parameters of 1-carbomethoxy- 2,5-diazabicyclo(4.3.0)non-2-ene. Name of compound t° kxlO 4 l-carbomethoxy-2,3- 128.74 8.21 AH = 29.5 k c a l mol" 1 d i a z a b i c y c l o ( 3 . 3 . 0 ) - 131.74 10.81 AS =0.13 e.u. non-2-ene 132.74 11.81 -IH -REFERENCES 1. E. 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M i s h r a and R.J. Crawford, Can. J . Chem., 46, 3305 (1968). 68. W. F o w e l l s , C. Schuerch, F.A. Bovey and F.P. Hood, J . Am. Chem. Soc. , 89_, 1396 (1967) . 69. P.E. P e t e r s o n and J . E . Duddey, J . Am. Chem. S o c , 88_, 4990 (1966). 70. H. Glucksmann, Mon. t u e r Chem., 10, 771 (1889). 71. R.R. F r a s e r , Can. J . Chem., 38, 549 (1960). 72. B e i l s t e i n , Handbuch der O r g a n i s c h e n Chemie., H., V o l . IX, 22, 44. - 150 -APPENDIX This appendix i s aimed at c o r r e c t i n g a d e f i c i e n c y i n the t h e s i s i n the omission o f e r r o r l i m i t s f o r much of the data. Many s t u d i e s have been reported i n t h i s t h e s i s and that of Masters (61) on the r a t e o f decomposition o f 3-methyl-3-carbomethoxy-l-pyrazoline. The average e r r o r i s as high as 5% but i n s p i t e of changing operators and equipment the values reported at 127° were the same w i t h i n the e r r o r l i m i t s . I t i s f e l t that the major source of e r r o r i s i n our i n a b i l i t y to reproduce and maintain the temperature at a given value. The varia n c e i n data can be reduced to 1% by doing a s e r i e s of consecutive runs without a l t e r i n g the temperature c o n t r o l s on the constant tempera-t u r e bath. For t h i s reason runs f o r determining the k i n e t i c i s otope e f f e c t were done one a f t e r the other and a l t e r n a t i n g p r o t i o and d e u t e r i o samples. A f u r t h e r source o f e r r o r s comes from combining r a t e data and product composition data as was necessary to i s o l a t e the deuterium isotope e f f e c t s f o r i n d i v i d u a l r e a c t i o n s . I t should be noted that the iso t o p e e f f e c t f o r cyclopropane formation from the 4 - t e r t - b u t y l d e r i v a -t i v e s i s not subject to these q u a l i f i c a t i o n s as i n these cases the only product was a cyclopropane product. To i l l u s t r a t e the effect, o f e r r o r s i n the product mixture a n a l y s i s on the de r i v e d isotope e f f e c t s we w i l l consider one set of data which - 151 -leads to the apparently anomalous i n v e r s e isotope e f f e c t f o r the c y c l o -propane formation from l-carbomethoxy-2,3-diaza-bicyclo(3.3.0)oct-2-ene (164) (see p. 143). The data given on page 53 are d e r i v e d from the f o l l o w i n g r e s u l t s of vapor chromatographic analyses at 160° (see p. 92). Percent product d i s t r i b u t i o n from p y r o l y s i s o f 164 with average d e v i a t i o n s cyclopropane 165 a , 3 - o l e f i n 166 B , y - o l e f i n 167 21.0 68.0 10.7 20.5 69.0 10.7 20.5 69.0 10.3 19.0 70.2 10.6 19. 2 70.8 10.0 18.7 73.0 8.3 18.6 70.5 11.0 19.6 ± 0.9 70.1 ± 1.5 10.2 ± 0.9 - 152 -Percent product d i s t r i b u t i o n from p y r o l y s i s of 164-5d,. cyclopropane 181 ct,B-olefin 182 8,Y-olefin 167 34.7 58.0 • • 7.2 34.7 57.5 7.7 33.8 59.2 7.0 34.6 58.4 7.0 34.2 57.3 8.4 34.2 57.3 8.4 34.4 59.6 7.1 34.4 ± 0.3 58.2 ± 0.7 7.5 ± 0.5 C l e a r l y the largest r e l a t i v e error i s i n the minor component. T h e s e data were used to c a l c u l a t e the deuterium isotope e f f e c t f o r t h e cyclopropane d e r i v a t i v e on p. 143 and y i e l d e d a value for k^/ kjj o f 0.71. I f we make use of probable errors (0.845 x average deviation) carry the errors through the c a l c u l a t i o n s *theprobable e r r o r i n the s p e c i f i c deuterium isotope e f f e c t can be c a l c u l a t e d . kH _ 10.2 ± 0.8 70.1 ± 1.3 k c y c H 19:6 ± 0.8 + 19.6 ± 0.8" 1. F. Daniels, Mathematical Preparation f o r Physical Chemistry, McGraw H i l l , 1956, p. 224. - 155 -= .52 ± 0.05 + 1 + 3.57 ± 0.16 = 5.09 ± 0.16 kD 7.5 ± 0.4 . 58.2 ±0.7 + 1 + k c y c D 34.4 ± 0.3 34.4 ± 0.3 0.22 ± 0.1 + 1 + 1.09 ± 0.03 = 2.91 ± 0.03 k H / . k c / C D 5.09 ± 0.16 .__ . _ ./ / k n X kc7c7 = 2.91 ± 0.03 = 1 7 5 +~ °-° 6 u H ^ = t nnl = °' 7 1 ± 0 ' 0 3 or ±4% k c y c D 1.75 ± 0.06 A survey of the data suggest t h a t i n general the probable e r r o r i s w i t h i n 5% except i n the cases of c a l c u l a t i o n s on minor components. For example, the B , y - o l e f i n 167 gives a s p e c i f i c k^Ap of 1.68 ± 0.10 or 6%. F i n a l l y the values of AH* and AS* which are d e r i v e d from r a t e data at v a r i o u s temperatures w i l l a l s o show a p p r e c i a b l e e r r o r s . I f we assume 5% accuracy i n the r a t e constants and a temperature i n t e r v a l of 10°C, the maximum e r r o r i n AH* can be estimated by the equation 2 given by Wiberg •p i Y 1 6 = 2R T , _ T a 2. K.B. Wiberg, " P h y s i c a l Organic Chemistry", McGraw-Hill, 1940, p. 378. - 154 -a i s the f r a c t i o n a l e r r o r i n the r a t e constant 6 i s the maximum e r r o r i n AH*. By usi n g temperatures of 130 and 140°C we f i n d 6 = 3.3 kcal/mole or ±10% For the maximum e r r o r i n AS* the f o l l o w i n g equation can be used T + 2T'T 6 = 8.3 e.u. C l e a r l y the values o f AH^ and AS* measured from a 10° i n t e r v a l have too l a r g e a probable e r r o r to be used i n any d e f i n i t i v e way. 

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