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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 . S c , 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 t h e Department o f CHEMISTRY  We a c c e p t t h i s t h e s i s as c o n f o r m i n g t o t h e required standard  THE UNIVERSITY OF BRITISH COLUMBIA FEBRUARY, 1974  In  presenting  this  an a d v a n c e d  degree  the  shall  I  Library  further  for  scholarly  by h i s of  agree  this  thesis  in p a r t i a l  fulfilment  of  at  University  of  Columbia,  the  make  it  available  for  that permission for extensive  p u r p o s e s may  representatives. thesis  freely  British  for  be g r a n t e d  It  financial  is  gain  Department Columbia  shall  requirements  reference copying of  I  agree  and this  not  copying or  be a l l o w e d  for  that  study. thesis  t h e Head o f my D e p a r t m e n t  understood that  written permission.  The U n i v e r s i t y o f B r i t i s h V a n c o u v e r 8, C a n a d a  by  the  or  publication  without  my  ABSTRACT  A s e r i e s o f p y r a z o l i n e s h a v i n g a carbomethoxy group on C-3 a b r i d g e (number o f t h e carbon atoms = 3, 4, 5) c o n n e c t i n g C-3 C-4  was  s y n t h e s i z e d and s t u d i e d .  (3.3.0)oct-2-ene-5d^  was  s p e c i f i c deuterium  deuterium  The c a l c u l a t i o n s c o n c e r n i n g  k i n e t i c i s o t o p e e f f e c t s f o r the d i f f e r e n t  i n v o l v e d i n the t h e r m o l y s i s l e d t o v a l u e s s i m i l a r t o t h o s e from o t h e r experiments f o r m a t i o n which was  the  processes  obtained  w i t h the exception of t h a t f o r cyclopropane  found t o have a " i n v e r s e " i s o t o p e e f f e c t  3-tert-Butyl-3-carbomethoxy-1-pyrazoline thermal and photo d e c o m p o s i t i o n  was  s y n t h e s i z e d and i t s  studied.  The e f f e c t o f the s i z e o f the e s t e r group on p r o d u c t was  and  l-Carbomethoxy-2,3-diazabicyclo  a l s o p r e p a r e d and t h e o v e r a l l  k i n e t i c i s o t o p e e f f e c t determined.  and  distribution  a l s o examined by u n d e r t a k i n g a p r o d u c t s t u d y on 3-methyl-3-  c a r b e t h o x y - 1 - p y r a z o l i n e and  3-methyl-3-carbo-tert-butoxy-1-pyrazoline.  c i s - and t r a n s - 3 - M e t h y l - 3 - c a r b o m e t h o x y - l - p y r a z o l i n e - 4 d ^ 3 - m e t h y l - c a r b e t h o x y - l - p y r a z o l i n e - 4 d ^ were p r e p a r e d .  Kinetic studies  were done on t h e t r a n s isomers and the s p e c i f i c d e u t e r i u m i s o t o p e e f f e c t s were c a l c u l a t e d from t h e measured o v e r a l l isotope effects. cyclopropane-2d^  and t r a n s -  kinetic kinetic  The n.m.r. s t u d i e s o f 1-methyl-l-carbomethoxyo b t a i n e d by b o t h t h e t h e r m a l and s e n s i t i z e d  d e c o m p o s i t i o n o f c i s - and  photo-  trans-3-methyl-3-carbomethoxy-l-pyrazoline-  4dj r e v e a l e d t h a t each o f t h e samples i s o l a t e d ( c o l l e c t e d from the gas chromatograph) from t h e f o u r d e c o m p o s i t i o n equal amounts o f c i s - and 2- d^.  products  trans-1-methyl-1-carbomethoxycyclopropane-  E s p e c i a l l y t h e s e r e s u l t s , but a l s o the t h e r m a l and  decomposition  o f c i s - and  p y r a z o l i n e s , suggested  contained  photo-  trans-3-methyl-4-tert-butyl-3-carbomethoxy-l-  that the cyclopropane  formation occurred v i a  a d i r a d i c a l i n t e r m e d i a t e i n w h i c h t h e f r e e r o t a t i o n about t h e carbon bond would be reduced  carbon-  o r p r e v e n t e d by b u l k y s u b s t i t u e n t s .  The f o r m a t i o n o f d e u t e r a t e d 3 , y - o l e f i n i c e s t e r s and e t h y l and a n g e l a t e - 4 d ^ as w e l l as e t h y l and methyl  methyl  t i g l a t e - 3 d ^ from the t r a n s -  isomers c o r r o b o r a t e d McGreer's s u g g e s t i o n 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 p r o d u c t 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- m e t h y l - 4 - a l k y l - 3 - c a r b o m e t h o x y - l - p y r a z o l i n e s  (alkyl = isopropyl,  i s o b u t y l and t e r t - b u t y l ) p r o v i d e d a d d i t i o n a l p r o o f f o r s t e r e o s p e c i f i c o l e f i n f o r m a t i o n and a l s o s u b s t a n t i a t e d t h e i d e a o f 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 - d i r a d i c a l intermediate. S i n c e 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 o n l y c y c l o p r o p a n e p r o d u c t upon t h e r m o l y s e s 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 t o u n d e r t a k e a d i r e c t measurement o f t h e secondary formation.  g deuterium k i n e t i c i s o t o p e e f f e c t f o r cyclopropan  - V  -  TABLE OF CONTENTS . Page  TITLE PAGE  i  ABSTRACT  i i  TABLE OF CONTENTS  v  LIST OF TABLES  xiii  ACKNOWLEDGEMENTS  xiv  INTRODUCTION PREPARATION OF PYRAZOLINES  1  MECHANISM OF PYRAZOLINE DECOMPOSITION  1  I.  I o n i c mechanism  2  II.  D i r a d i c a l mechanism  12  III.  C o n c e r t e d 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 I.  II.  43  Some o f t h e g e n e r a l f e a t u r e s o f t h e r m a l d e c o m p o s i t i o n o f 1 - p y r a z o l i n e s which served as a b a s i s f o r r e s e a r c h plans.  46  3-Alkylpyrazolines  47  - v i -  lli.  IV.  K i n e t i c and p r o d u c t s t u d i e s o f 1-carbomethoxy-2,3d i a z a b i c y c l o ( 3 . 3 . 0 ) o c t - 2 - e n e and i t s analogue-5d^  52  Stereochemical factors a f f e c t i n g o l e f i n formation  57'  (a)  (b) (c)  The e f f e c t o f t h e s i z e o f t h e e s t e r group on o l e f i n formation, 3-methyl-3-carbalkoxy-lpyrazolines  57  The e f f e c t o f t h e s i z e o f t h e a l k y l group a t C-4 on o l e f i n f o r m a t i o n  60  Deuterium k i n e t i c i s o t o p e e f f e c t o f o l e f i n f o r m a t i o n , k i n e t i c and p r o d u c t s t u d i e s on 3-methyl-3-carbalkoxy-l-pyrazolines-4d  63  B,Y- l fi  66  1  (d) V. VI.  0  e  n  formation  Mechanistic c o n s i d e r a t i o n o f cyclopropane  formation  68  Photolysis of pyrazolines  73  SUMMARY  75  EXPERIMENTAL  79  I. II. III.  G e n e r a l statements  79  Preparation o f 3-methyl-3-cyano-l-pyrazoline  80  Preparation of  3-tert-butyl-3-carbomethoxy-1-  pyrazoline (a)  (b) IV.  80  P r e p a r a t i o n o f methyl  2-tert-butylpropen-2-oate  80  1.  3,3-Dimethyl-2-oxobutanoic  acid  2.  M e t h y l 3,3-dimethyl-2-oxobutanoate  81  3.  Methyl 2,3,3-trimethyl-2-hydroxybutanoate  81  4. Methyl 2-tert-butylpropen-2-oate Preparation of 3-tert-butyl-3-carbomethoxy-lpyrazoline  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 and t h e s y n t h e s i s o f methyl ( Z ) - 2 - t e r t butylbuten-2roate  81  i  82 83  84  - vii -  (a)  (b) (c) V.  Thermal d e c o m p o s i t i o n o f 3 - t e r t - b u t y l - 3 carbomethoxy-l-pyrazoline  84  Direct photolysis of 1-pyrazoline  87  3-tert-butyl-3-carbomethoxy-  Sensitized photolysis of 3-tert-butyl-3carbomethoxy-l-pyrazoline  87  Preparation o f l-carbomethoxy-2,3-diazabicyclo(3.3.0)oct2-ene and i t s analogue-5d^ 88 (a)  (b)  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)oct2-ene  90  Preparation of l-carbomethoxy-2,3-diazabicyclo (3.3.0)oct-2-ene-5d  91  1.  1-Cyclopentenecarboxylic acid-2d^  91  2.  l-Carbomethoxycyclopentene-2d^  91  3.  l-Carbomethoxy-2,3-diazabicyclo(3.3.0)oct2-ene-5d  92  1  1  VI.  Product s t u d i e s o f l - c a r b o m e t h o x y - 2 , 3 - d i a z a b i c y c l o (3.3.0)oct-2-ene a n d , i t s analogue-5d^ (a) (b)  VII.  VIII. IX. X.  92  Thermal d e c o m p o s i t i o n o f l-carbomethoxy-2,3d i a z a b i c y c l o ( 3 . 3 . 0 ) o c t - 2 - e n e and i t s analogue-5d^ P h o t o l y s e s o f l-carbomethoxy-2,3d i a z a b i c y c l o ( 3 . 3 . 0 ) o c t - 2 - e n e and i t s a n a l o g u e - 5 d  92  1  94  Preparation o f l-carbomethoxy-2,3-diazabicyclo(4.3.0)non2-ene and l - c a r b o m e t h o x y - 2 , 3 - d i a z a b i c y c l o ( 5 . 3 . 0 ) d e c 2-ene 95 Product s t u d i e s o f l-carbomethoxy-2,3diazabicyclo(4.3.0)non-2-ene  98  Product s t u d i e s o f l-carbomethoxy-2,3diazabicyclo(5.3.0)dec-2-ene  99  3-Methyl-3-carbo-tert-"butoxy-l-pyrazolone.  100  P r e p a r a t i o n o f c i s - and t r a n s - 3 - m e t h y l - 4 - a l k y 1 - 3 carbomethoxy p y r a z o l i n e s (a)  (b)  (c)  G e n e r a l p r o c e d u r e f o r the p r e p a r a t i o n o f B-hydroxy e s t e r s 1.  Methyl  2,4-dimethyl-3-hydroxypentanoate  2.  M e t h y l 2,5-dimethyl-3-hydroxyhexanoate  3.  M e t h y l 2,4,4-dimethyl-3-hydroxypentanoate  General procedure f o r the p r e p a r a t i o n of o l e f i n esters 1.  M e t h y l ( E ) - and 2-oate  (Z)-2,4-dimethylpenten-  2.  M e t h y l ( E ) - and 2-oate  (Z)-2,5-dimethylhexen-  3.  Methyl ( E ) - and ( Z ) - 2 , 4 , 4 - t r i m e t h y l p e n t e n 2-oate  Pyrazolines 1.  cis-3-Methyl-4-isopropyl-5-carbomethoxy1-pyrazoline  2.  trans-3-Methyl-4-isopropyl-3-carbomethoxy1-pyrazoline  3.  cis-3-Methyl-4-isobutyl-3-carbomethoxy1-pyrazoline  4.  trans-3-Methyl-4-isobutyl-3-carbomethoxy1-pyrazoline  5.  cis-3-Methyl-4-tert-butyl-3-carbomethoxy-1 pyrazoline  6.  trans-3-Methyl-4-tert-butyl-3-carbomethoxy 1-pyrazoline  P r e p a r a t i o n o f 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)  P r e p a r a t i o n o f methyl 2 , 4 , 4 - t r i m e t h y l - 3 ketopentanoate  (b)  P r e p a r a t i o n o f methyl 2 , 4 , 4 - t r i m e t h y l - 3 hydroxypentanoate-3d 1  - ix -  (c)  (d)  P r e p a r a t i o n o f methyl ( E ) - and trimethylpenten-2-oate-3d  (Z)-2,4,4-  P r e p a r a t i o n o f c i s - and t r a n s - 3 - m e t h y l - 3 carbomethoxy-l-pyrazoline-4d 1  1.  2.  XIII. XIV.  XVII.  XIV.  112  trans-3-Methyl-4-tert-butyl-3-carbomethoxyl-pyrazoline-4dj  112  1  Product s t u d i e s o f t r a n s - 3 - m e t h y l - 3 - c a r b e t h o x y - l pyrazoline-4dj  113  Thermal d e c o m p o s i t i o n o f trans-3-methy1-3carbethoxy-l-pyrazoline-4d^  113  D i r e c t p h o t o l y s i s o f trans-3-methy1-3carbethoxy-l-pyrazoline-4d^  115  Preparation of 3-methyl-3-carbethoxy-l-pyrazoline  116  Preparation of trans-3-methyl-3-carbomethoxyl-pyrazoline-4d^  117  Product s t u d i e s o f l-pyrazoline-4d^  118  trans-3-methyl-3-carbomethoxy-  (a)  Thermal d e c o m p o s i t i o n  118  (b)  D i r e c t p h o t o l y s i s of trans-3-methyl-3carbomethoxy-1-pyrazoline-4d^  119  S e n s i t i z e d p h o t o l y s i s of trans-3-methyl-3carbomethoxy-l-pyrazoline-4d^  120  (c)  XVIII.  cj s-3-Methyl-4-tert-butyl-3-carbomethoxy l-pyrazoline-4d^  113  (b)  XVI.  112  Preparation of trans-3-methyl-3-carbethoxy-lpyrazoline-4d^  (a)  XV.  111  Preparation of pyrazoline-4d^  cis3-methyl-3-carbomethoxy-l120  Product s t u d i e s o f cis-3-methy1-3-carbomethoxy1-pyrazoline  122  (a)  Thermal d e c o m p o s i t i o n  122  (b)  Sensitized photolysis  122  -  XX.  X  -  Product s t u d i e s o f c i s - and t r a n s - 3 - m e t h y l - 4 - a l k y 1 3-carbomethoxy-l-pyrazolines  122  1.  122  Thermal d e c o m p o s i t i o n s (a) (b)  cis-3-Methyl-4-isopropyl-3-carbomethoxy1-pyrazoline trans-3-Methyl-4-isopropyl-3carbomethoxy-l-pyrazoline  126  cis-3-Methyl-4-risobutyl-3-carbomethoxy1-pyrazoline  126  (d)  trans-3-Methyl-4-isobutyl-3-carbomethoxy1-pyrazoline  127  (e)  cis-3-Methyl-4-tert-butyl-3-carbomethoxy1-pyrazoline  128  trans-3-Methyl-4-tert-butyl-3-carbomethoxy1-pyrazoline  128  (c)  (f) 2.  Photolytic  decompositions  KINETIC MEASUREMENTS G e n e r a l procedure I.  125  128 129  f o r k i n e t i c runs  129  Rate c o n s t a n t s , 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 i s o t o p e e f f e c t o f 3-methyl-3c a r b o m e t h o x y - l - p y r a z o l i n e and t r a n s - 3 - m e t h y l - 3 carbomethoxy-l-pyrazoline-4dj  134  (a)  Rate c o n s t a n t s  134  (b)  O v e r a l l deuterium k i n e t i c i s o t o p e 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 i s o t o p e effects  135  S p e c i f i c deuterium k i n e t i c i s o t o p e e f f e c t s  135  (d)  1.  2.  Deuterium k i n e t i c i s o t o p e e f f e c t s f o r 3 , y - o l e f i n .formation  135  Deuterium k i n e t i c i s o t o p e e f f e c t f o r cyclopropane formation  135  - xi -  3.  4.  II.  Rate c o n s t a n t s  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 effects  138  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  3.  4.  VI.  136  (a)  2.  V.  Deuterium k i n e t i c i s o t o p e e f f e c t f o r methyl t i g l a t e f o r m a t i o n  137  1.  IV.  136  Rate c o n s t a n t s , a c t i v a t i o n parameters and o v e r a l l d e u t e r i u m k i n e t i c i s o t o p e e f f e c t o f 3-methyl-3c a r b e t h o x y - l - p y r a z o l i n e and t r a n s - 3 - m e t h y l - 3 carbethoxy-l-pyrazoline-4dj  (d)  III.  Deuterium k i n e t i c i s o t o p e e f f e c t f o r methyl angelate formation  Deuterium k i n e t i c i s o t o p e e f f e c t f o r g,Y-olefin formation  139  Deuterium k i n e t i c i s o t o p e e f f e c t f o r cyclopropane formation  139  Deuterium k i n e t i c i s o t o p e e f f e c t f o r ethyl angelate formation  140  Deuterium k i n e t i c i s o t o p e e f f e c t f o r ethyl t i g l a t e formation  140  Rate c o n s t a n t s and a c t i v a t i o n parameters o f c i s and t r a n s - 3 - m e t h y l - 4 - a l k y l - 3 - c a r b o m e t h o x y - l - p y r a z o l i n e s  141  Rate c o n s t a n t s , a c t i v a t i o n parameters and d e u t e r i u m k i n e t i c isotope effect of cis-3-methyl-4-tert-butyl3 - c a r b o m e t h o x y - l - p y r a z o l i n e and i t s analogue-4d^  141  Rate c o n s t a n t s , a c t i v a t i o n parameters and d e u t e r i u m k i n e t i c isotope effect of trans-3-methyl-4-tert-butyl3 - c a r b o m e t h o x y - l - p y r a z o l i n e and i t s analogue-4d^  142  Rate c o n s t a n t s , a c t i v a t i o n parameters and o v e r a l l d u e t e r i u m k i n e t i c i s o t o p e e f f e c t o f 1-carbomethoxy2 , 3 - d i a z a b i c y c l o ( 3 . 3 . 0 ) o c t - 2 - e n e and i t s analogue-5d^  143  (a)  144  O v e r a l l 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 i s o t o p e e f f e c t f o r 3,y-olefin formation  144  - xii -  2.  3.  VII.  Deuterium k i n e t i c i s o t o p e e f f e c t f o r cyclopropane formation  145  Deuterium k i n e t i c i s o t o p e e f f e c t f o r a,3-olefin formation  145  Rate c o n s t a n t and a c t i v a t i o n parameters o f l-carbomethoxy-2,3-diazabicyclo(4.3.0)non-2-ene  145  REFERENCES  146  APPENDIX - ERRORS  150  1  - xiii -  LIST OF TABLES  Table  I  Page Decomposition  products o f exo-5,6-dideutero-  2,3-diazabicyclo(2.2.l)hept-2-ene II  Decomposition p r o d u c t o f exo- and endo-5-methoxy2,3-diazabicyclo(2.2.l)hept-2-ene  III  The a c t i v a t i o n parameters  The a c t i v a t i o n parameters  17  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 t r i c y c l i c azo compounds IV  13  ^9  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 h a v i n g c y c l o p r o p y l in group^exo and endo p o s i t i o n \!  41  The y i e l d s o f o l e f i n i c and c y c l o p r o p a n e p r o d u c t s of a series of 3-methyl-3-carbalkoxy-l-pyrazolines upon t h e r m o l y s i s  VI  The p r o d u c t d i s t r i b u t i o n o f c i s - and trans_-3-methyl4 - a l k y l - 3 - c a r b o m e t h o x y - l - p y r a z o l i n e s upon t h e r m o l y s i s  VII  Decomposition  78  p r o d u c t s o f 5 - m e t h y l - 3 - c a r b o - t e r t - butoxy-  1-pyrazoline IX  60  The c o u p l i n g c o n s t a n t s and d e c o m p o s i t i o n p r o d u c t s 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  VIII  57  101  Photoproducts o f t r a n s - 5 - m e t h y l - 3 - c a r b e t h o x y - l pyrazoline-4d  1  115  - xiv -  ACKNOWLEDGEMENTS  I would l i k e t o thank P r o f e s s o r 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 t h e i n t e r p r e t a t i o n o f n.m.r. s p e c t r a throughout t h i s research project. I am i n d e b t e d t o P r o f e s s o r 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, P r o f e s s o r L. D. Hayward f o r h i s h e l p f u l discussions concerning  s t e r e o c h e m i s t r y , and P r o f e s s o r R. E. P i n c o c k  f o r h i s comments on t h i s t h e s i s . I w i s h t o thank M i s s P. Watson, Mr. W. Lee and Dr. E. K o s t e r f o r the n.m.r. s p e c t r a and Mr. P. Borda f o r t h e m i c r o a n a l y s e s . I a l s o wish t o 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 h e l p i n d e s i g n i n g t h e g l a s s equipment. F i n a l l y I would l i k e t o acknowledge t h e f i n a n c i a l support  o f the  N a t i o n a l Research C o u n c i l o f Canada and t h e U n i v e r s i t y o f B r i t i s h Columbia.  -I-  INTRODUCTION  PREPARATION OF PYRAZOLINES The a d d i t i o n o f d i a z o a l k a n e s  t o a c t i v a t e d carbon-carbon d o u b l e *  bonds t o g i v e p y r a z o l i n e s has been known f o r q u i t e some t i m e (1,2,3) but t h e m e c h a n i s t i c  d e t a i l s o f t h e r e a c t i o n s were r e v e a l e d 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 t h a t 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 . of t h i s r e a c t i o n i s convenient  The 1 , 3 - d i p o l a r  formulation  f o r predicting results (6).  The f a c t t h a t t h e s e r e a c t i o n s a r e one s t e p 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 , p e r m i t s us t o s y n t h e s i z e stereochemistry.  1 - p y r a z o l i n e s o f known  U s u a l l y t h e a-carbon o f t h e d i a z o a l k a n e b i n d s t o  t h e carbon ft t o t h e a c t i v a t i n g group, a l t h o u g h Parham and h i s c o workers (7) have found t h a t c e r t a i n n i t r o o l e f i n s r e a c t e d w i t h diazoalkanes  t o g i v e b o t h o r d i n a r y and " r e v e r s e " a d d i t i o n p r o d u c t s .  MECHANISM OF PYRAZOLINE DECOMPOSITION  The p i o n e e r i n g work o f von Auwers and Konig decomposition  *N0TE:  (3) on p y r a z o l i n e  was f o c u s e d e x c l u s i v e l y on t h e i s o l a t i o n and i d e n t i f i -  The a d d i t i o n o f d i a z o a l k a n e s  t o 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 o f p r e s s u r e  (8,9,10,11).  - 2 -  c a t i o n o f t h e components i n t h e p r o d u c t  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 o f t h e  stereochemistry  o f t h e p a r e n t p y r a z o l i n e s , b u t no attempt was made t o  explain the r e s u l t s .  The g e n e r a l s t e r e o s p e c i f i c i t y was assumed t o be  v a l i d f o r q u i t e some time due t o i n a d e q u a t e s e p a r a t i o n and a n a l y t i c a l niques.  In  tech-  1962, Jones and T a i (12,13) found t h a t i t was not s t e r e o -  s p e c i f i c , although  some degree o f s t e r e o s e l e c t i v i t y was shown.  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 R i n e h a r t  Their  (14) and McGreer,  et a l . (15,16,17).  I.  I o n i c mechanism: One o f t h e f i r s t s u g g e s t i o n s  decomposition  concerning  t h e mechanism o f 1 - p y r a z o l i n e  was an i o n i c pathway (14,18,19) i n which t h e i n t e r m e d i a t e ,  depending upon t h e degree o f bond b r e a k i n g , c o u l d 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 t o s o l v e n t  polarity. b)  p r o d u c t d i s t r i b u t i o n s do n o t change s i g n i f i c a n t l y i n g o i n g  a p o l a r s o l v e n t s t o p o l a r ones as one might expect on the  from  grounds t h a t  p o l a r s o l v e n t s 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 a l l o w g r e a t e r equilibration  o f the i o n i c i n t e r m e d i a t e  and would r e s u l t i n d e c r e a s e d  stereoselectivity. c)  l a c k o f t y p i c a l carbonium i o n rearrangement p r o d u c t s  which  r e a d i l y occur i n o t h e r systems h a v i n g carbonium i o n i n t e r m e d i a t e s . d)  H  s h i f t s are r a r e .  - 4 -  To c o u n t e r a c t and R i n e h a r t  the d e f i c i e n c y o f a c l e a n - c u t  i o n i c mechanism, van Auken  (14) suggested t h a t the n i t r o g e n f r e e z w i t t e r i o n was  resonance form o f a s i n g l e t d i r a d i c a l , and  CH  2  {  CH: H  C H  c o u l d undergo c y c l i z a t i o n .  C H 3  CH,  \ H  C O O C H ,  3  7  An  2  CH,  C00CH  a  8  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-lp y r a z o l i n e s 9_ as w e l l as f o r the d i h y d r o f u r a n decomposition of 3-methyl-3-acetyl-l-pyrazoline 3,5-dimethyl-3-acetyl-l-pyrazolines. two  breaking The  o f C-5  o f C-3  15_ and  o b s e r v e d i n the c i s - and  In the former system due  s t r o n g l y e l e c t r o n w i t h d r a w i n g groups i n C-3  the bond b r e a k i n g  formation  one  transto  the  might expect t h a t  t o n i t r o g e n i s w e l l advanced o v e r the bond  t o n i t r o g e n g i v i n g the i n t e r m e d i a t e  a polar  rate studies i n solvents with d i f f e r e n t p o l a r i t i e s  character. principally  support the i d e a o f the i o n i c i n t e r m e d i a t e but the v a r i a t i o n i n the  rate  w i t h the s o l v e n t p o l a r i t y does not c o r r e l a t e w i t h o t h e r p o l a r r e a c t i o n s  - 5 -  in similar  media.  The f o r m a t i o n o f o l e f i n i c p r o d u c t s  can be e x p l a i n e d  by the c o n c e r t e d m i g r a t i o n o f t h e 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 d e c o m p o s i t i o n  of 3-methyl-3-acetyl-l-pyrazoline  p r o v i d e d a r a t h e r complex product  mixture:  (21)  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 p r o d u c t s w i t h t h e f o l l o w i n g two e x c e p t i o n s : 1)  t h e c y c l o p r o p a n e p r o d u c t c o n s i s t s o f a m i x t u r e o f c i s - and  trans-1,2-dimethyl-1-acetyl-cyclopropanes. 2)  t h e t r a n s compound gave p r a c t i c a l l y no d i h y d r o f u r a n d e r i v a t i v e .  A c c o r d i n g t o McGreer et_ a l . , an i o n i c pathway c o u l d be r e s p o n s i b l e f o r t h e d i h y d r o f u r a n f o r m a t i o n i n which t h e i n t e r m e d i a t e  (22) has a  n e g a t i v e charge d e l o c a l i z e d i n t o t h e c a r b o n y l oxygen and i f i t i s i n a f a v o r a b l e p o s i t i o n , i t w i l l be a b l e t o p a r t i c i p a t e i n t h e r i n g c l o s u r e ;  21  22  23  -  7  -  because t h e 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 d i h y d r o furan, the intermediate  i n t h a t case c o u l d n o t undergo f r e e r o t a t i o n  around t h e C-3 - C-4 bond t o t a k e up a f a v o r a b l e c o n f o r m a t i o n closure.  for ring  McGreer et_ a l . (21) assumed some b o n d i n g ( e i t h e r i o n i c o r  p a r t i a l l y c o v a l e n t ) between C-3 and n i t r o g e n .  The i n t e r m e d i a t e (22)  w i t h r o t a t i o n r e s t r i c t e d around t h e C-3 - C-4 bond, was s t i l l by s t e r i c f a c t o r s p r e s e n t  influenced  i n t h e o r i g i n a l p y r a z o l i n e and by s o l v e n t  p o l a r i t y as w e l l . The  s t u d i e s o f 3 - c y a n o - 3 - c a r b e t h o x y - 1 - p y r a z o l i n e systems (22)  showed t h a t t h e f o r m a t i o n o f t h e o l e f i n i c p r o d u c t s o c c u r r e d 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 t h a t t h e r e was a c o n f o r m a t i o n a l  equilibrium f o r  each p y r a z o l i n e 24, 26 and 28, 30 o r t h e i r Newman p r o j e c t i o n s 25, 27 and 29, 31.  Upon d e c o m p o s i t i o n t h e f i r s t two conformers g i v e  r i s e t o 32_ and 3_3 w h i l e t h e two l a t t e r t o 34_ and 35_ by methyl and a r y l migration besides two m e c h a n i s t i c  cyclopropane d e r i v a t i v e s .  They suggested  pathways f o r t h e o l e f i n f o r m a t i o n , a c o n c e r t e d  one  i n which m i g r a t i o n and t h e n i t r o g e n l o s s o c c u r s i m u l t a n e o u s l y and a stepwise  p a t h g i v i n g r i s e t o an i n t e r m e d i a t e  i n which t h e r e a r r a n g e -  ment i s f a s t e r than t h e r o t a t i o n around t h e C-3 - C-4 bond. intermediates  The  f o r t h e l a t t e r pathway were suggested t o be i o n i c  s p e c i e s , 36_ and 37 from conformers 2_8_ and 30_ r e s p e c t i v e l y . e x i s t e n c e o f an e q u i l i b r i u m between 36 and 37 was excluded  The on t h e  - 8 -  grounds t h a t such an e q u i l i b r i u m would have a l l o w e d r o t a t i o n around the C-3 - C-4 bond l e a d i n g t o t h e i n t e r m e d i a t e 38_ which i n t u r n would have g i v e n r i s e t o (Z)-32.  T h i s compound was n o t found i n t h e decom-  p o s i t i o n p r o d u c t m i x t u r e o f 24_ and 26. S i n c e b o t h t h e c o n c e r t e d and t h e i o n i c mechanisms c o u l d  adequately  e x p l a i n the formation o f 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 u d i e s would have t o be done t o see whether t h e bond breakage o f C-3 and C-4 carbons t o n i t r o g e n s t a k e p l a c e s u c c e s s i v e l y o r s i m u l t a n e o u s l y . The product  s t u d i e s a l s o i n d i c a t e d t h a t t h e a r y l groups had a  b e t t e r m i g r a t o r y a p t i t u d e than the m e t h y l .  C N Ar  H  C  5  00C  2  N // N  28  C O O C  2  H  N // N  CH.  30 Ar  5  C H  CH, C N  HcCoOOC  3  C N  I  Ar C O O C  2  H  N = N  5  29 H_C 00C  31  A r  o 2 o  C00C H  Ar  r - C H 'CN  2  -8  5  CN  2  Ar  COOCJ-L  •  C  c  (£)-12_  38  A r - C H p c  H  N ® H  o  2 5  COOCLH.  H C H  C N  3  H  34  5  C  C N  2  35 C N -  S A  r  Ar  H C H  3  ^  "CH N + 2  2  5  C  2  O O C C H  CN 3  —  C O O C H ,  36  "25  37  - S  CH N + 2  2  - 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 o f 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 a t C-4 p-methoxyphenyl a t C-5 k  or  w i t h a methyl  and a r y l groups ( p h e n y l ,  p - n i t r o p h e n y l ) and on t h e i r analogues d i d e u t e r a t e d the  (22) p r o v i d e d the v a l u e o f / s e c o n d a r y  a - k i n e t i c isotope e f f e c t ;  H  r — = 1.01 ± 0.07; C-5  This  suggested  t h a t v e r y l i t t l e bond b r e a k i n g o f t h e  t o n i t r o g e n o c c u r r e d i n the t r a n s i t i o n s t a t e .  t i o n s t a t e 39 was  The proposed t r a n s i -  p o l a r w i t h i n c r e a s e d c o n s t r a i n t s i n the  degrees o f freedom compared t o the s t a r t i n g m a t e r i a l .  T h i s was  by the n e g a t i v e v a l u e s o f e n t r o p y o f a c t i v a t i o n , -3.19, -5.65 -9.58  e.u.  supported and  f o r the d i f f e r e n t p y r a z o l i n e s .  Ar  \  >  N  39 The p r o d u c t d i s t r i b u t i o n i n d i c a t e d t h a t the s t e r e o c h e m i s t r y o f t h e p y r a z o l i n e p l a y s an i m p o r t a n t r o l e i n d e t e r m i n i n g the s t e r e o c h e m i s t r y o f t h e p r o d u c t s and t h e r e was no r o t a t i o n t a k i n g p l a c e around t h e C-3 C-4  bond i n the t r a n s i t i o n  state.  An i n t e r e s t i n g i o n i c pathway was (24) f o r t h e d e c o m p o s i t i o n  proposed by Huisgen and  i n DMF  Eberhard  o f c i s - and t r a n s - 3 - m e t h y l - 5 , 5 - d i p h e n y l - 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 a s t r o n g base (NaH  -  and d i m s y l s o d i u m  o r DMSO i n t h e presence i n DMSO) a t room  of  temperature.  - 11 -  When t h e two p y r a z o l i n e s i n DMF o r DMSO n i t r o g e n  were t r e a t e d w i t h t h e above mentioned bases  e l i m i n a t i o n took p l a c e and t h e s o l u t i o n became  r e d , l a s t i n g f o r days under p r o p e r  H K ^ C O O C H  Ph  2 f  N  > <  =  care.  C H ^ O O C U  3  XC00CH3 N  C  H  M  P h J > <  3  1  N = =  I  <  C O O C H  C  H  3  3  COOCH3  N  =  N  *  4 2  COOCH3  Ph—^ ^— 3 C  Ph  C H  COOCH3 4 3 .  COOCH3  Ph  45  The  existence  o f t h e l - p y r a z o l i n e - 4 - y l a n i o n 42 as an i n t e r m e d i a t e  was proved by e s t a b l i s h i n g a c i s - t r a n s e q u i l i b r i u m i n NaOMe, MeOH s o l u t i o n without loss o f N  2 <  By u s i n g d e u t e r a t e d s o l v e n t s , t h e expected  - 12 -  d e u t e r a t i o n o f t h e a n i o n was found t o be made f a s t e r than i t s c y c l o reversion. 12 The a n i o n 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 t h a n does t h e  n e u t r a l p y r a z o l i n e , and t h e p r o d u c t s a r e o l e f i n i c e s t e r s 45_ i n g r e a t e r 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 m a i n l y c y c l o p r o p a n e s o f  mixed s t e r e o c h e m i s t r y . K i n e t i c studies i n d i c a t e d that the 1,3-cycloreversion to a l l y l a n i o n and ^  has an a c t i v a t i o n energy more than 12 k c a l mol ' lower  than t h a t o f t h e p y r a z o l i n e t o c y c l o p r o p a n e p r o c e s s . II.  D i r a d i c a l mechanism: S i n c e 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 r m e d i a t e s ,  i t seemed r e a s o n a b l e t o assume t h e same mechanism f o r c y c l i c azo compounds.  Cohen and co-workers (25,26) were t h e 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 o f the decomposition o f 2 , 3 - d i a z a b i c y c l o ( 2 . 2 . 1 . ) h e p t - 2 - e n e 46^ and 2 , 5 - d i a z o b i c y c l o ( 2 .2. 2 . ) o c t - 2 - e n e  48^ i n t h e gas  phase and  compare t h e o b t a i n e d d a t a w i t h those o f a c y c l i c azo compounds.  - 13 -  They have suggested a d i r a d i c a l pathway w i t h t h e s i m u l t a n e o u s  breakage  o f t h e two C-N bonds f o r t h e t h e r m a l d e c o m p o s i t i o n o f 46 and 48.  46  decomposed about 400 t i m e s f a s t e r t h a n 48_ and has lower a c t i v a t i o n and e n t r o p y o f a c t i v a t i o n which was presumable  energy  due t o t h e more h i g h l y  s t r a i n e d s t r u c t u r e o f 46. Roth and M a r t i n (27) have used diazobicyclo(2.2.l)hept-2-ene  exo-5,6-dideutero-2,3-  50_ t o s t u d y t h e s t e r e o c h e m i s t r y o f t h e  decomposition.  D  VA 5L  D  52  The r a t i o o f t h e c i s - and t r a n s - 2 , 3 - d i d e u t e r i o b i c y c l o ( 2 . 1 . 0 ) p e n t a n e s v a r i e d w i d e l y w i t h t h e mode o f d e c o m p o s i t i o n s and w i t h t h e p h y s i c a l s t a t e o f t h e sample. TABLE  I  Decomp. p r o d , o f e x o - 5 , 6 - d i d e u t e r o - 2 , 3 - d i a z a b i c y c l o ( 2 . 2 . l ) h e p t - 2 - e n e . Mode o f decomp. A hv 11 11  physical state of the sample gas phase " " low p r e s s u r e " " high pressure benzene solid  Products 51 52 25% 50% 40% 40% 66%  75% 50% 60% 60% 33%  - 14 -  A c c o r d i n g t o 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 t o the c o n c e r t e d p-orbital  e l i m i n a t i o n o f n i t r o g e n w i t h accompanying  due  back-side  overlap.  50  The  low s t e r e o s e l e c t i v i t y ( 7 5 % )  t r a n s i t i o n s t a t e i s incomplete. by the product  i n d i c a t e s t h a t the o v e r l a p i n the  T h e i r t h e o r y seemed t o be  supported  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 o f endo-5-methyl-  2 , 3 - d i a z a b i c y c l o ( 2 . 2 . 1 ) hept-2-e'ne s e l e c t i v i t y (60%) due the t r a n s i t i o n s t a t e .  which showed somewhat lower  t o the s t e r i c h i n d r a n c e  stereo-  by the methyl group i n  - 15 -  To e x p l a i n t h e r e t e n t i o n found i n t h e d e c o m p o s i t i o n p r o d u c t s w i t h r e s p e c t t o t h e p a r e n t azo compound, t h e 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 e n v i s a g e d (28).  L a t e r Roth and M a r t i n  (29) proposed a two s t e p mechanism f o r t h e decom-  p o s i t i o n o f 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 t o t h e development o f a b a c k - s i d e 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 bicyclopentaneAccording  and n i t r o g e n .  t o them, t h e energy r e q u i r e m e n t 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 r e l e a s e d by t h e C-N bond breakage.  N=N»  58c  - 16 -  While m a i n t a i n i n g t h e concept o f a d i r a d i c a l pathway f o r t h e decomp 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) t o e x p l a i n t h e s t e r e o c h e m i c a l c o u r s e o f t h e r e a c t i o n . They have s t u d i e d t h e t h e r m a l and p h o t o d e c o m p o s i t i o n o f t h e exo and endo epimers o f 5 - m e t h o x y - 2 , 3 - d i a z a b i c y c l o ( 2 . 2 . l ) h e p t - 2 - e n e 59_, 60_. The d i f f e r e n t modes o f d e c o m p o s i t i o n s have r e s u l t e d i n a w i d e l y d i f f e r i n g r a t i o o f 61_ and 62^ shown i n T a b l e I I .  The t h e r m a l e q u i l i b r a t i o n s t u d y showed t h a t 62 i s t h e more s t a b l e isomer.  - 17 -  TABLE I I Decomp. p r o d , o f exo- and endo-5-methoxy2,3-diazabicyclo(2.2.l)hept-2-ene Comp.  Mode o f decomp. l  5 9  60  i  }  59 60  s  1  h  59  i }  59 60  Products 61_  e  a  l  e  d  *  A t  u  b  K e  63% 93.6%  37% 6.4*  42% 84%  58% 16%  pentane s o l u t i o n p i p e r y l e n e added  v  60  62_  p h y s i c a l s t a t e o f sample  97%  ,  crystalline  h v  .benzophenone S e n s i t i z e d , phot.  •$%  ^  . , cyclohexane  ^ 78%  22%  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 o f an e q u i l i b r a t i n g , e p i m e r i c p a i r o f p y r a m i d a l 1,3 - d i r a d i c a l s .  They have a l s o proposed  i n v e r s i o n i s a consequence o f r e c o i l energy r e l e a s e d by C-N ing.  *Note 1.  t h a t the bond break-  The excess p r o d u c t o f 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 o c c u r s b e f o r e t h e two e p i m e r i c d i r a d i c a l s can f u l l y brate.  Benzophenone s e n s i t i z e d p h o t o l y s i s produced  m i x t u r e from b o t h i s o m e r s .  equili-  the same p r o d u c t  The most p l a u s i b l e e x p l a n a t i o n o f t h e s e  r e s u l t s i s t h a t t h e p y r a m i d a l d i r a d i c a l can i n t e r c o n v e r t a t l e a s t s e v e r a l times b e f o r e s p i n i n v e r s i o n o c c u r s . The f i r s t d i r e c t o b s e r v a t i o n o f f r e e r a d i c a l s p e c i e s by e . s . r . s p e c t r o s c o p y was  Note #1.  a c h i e v e d by Overberger  e t a l . (31,32,33) i n the  The r e c o i l mechanism has been q u e s t i o n e d 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 ( 3 0 ) .  photo-  - 18 -  decomposition o f 3 , 5 - d i a r y l - l - p y r a z o l i n e s (the thermal processes t o show any s i g n o f f r e e r a d i c a l s ) .  failed  L a t e r r e p o r t s on t h e d e t e c t i o n o f  f r e e r a d i c a l s by e . s . r . w i l l be d i s c u s s e d on pages 28 and 32. Crawford and co-workers (34) have accumulated c o n s i d e r a b l e 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 o r l i k e intermediate  i n t h e thermal  evidence  0,0-trimethylene  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 o f 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 d e c r e a s e i n a c t i v a t i o n e n e r g i e s upon methyl s u b s t i t u t i o n on t h e C-3 and C-5 p o s i t i o n s . i n the suggestion transition state.  T h i s g e n e r a l d e c r e a s e was i n t e r p r e t e d  t h a t b o t h carbon n i t r o g e n bonds a r e b r o k e n i n t h e However, t h e o b t a i n e d one k c a l mol ' d e c r e a s e f o r  each methyl group i s comparable t o some c o n f o r m a t i o n a l  f a c t o r s encountered  i n c y c l i c compounds, t h u s t h e i n c r e a s e i n r a t e c o u l d a r i s e from an i n c r e a s e i n ground s t a t e e n e r g i e s . complications, deuterated confirmed breaking  the previous  In o r d e r t o remove any  conformational  p y r a z o l i n e s were used and t h e o b t a i n e d r e s u l t s  assumption t h a t b o t h c a r b o n - n i t r o g e n  i n the rate determining  step  bonds a r e  ( 3 5 ) . 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 s u p p o r t e d the i d e a o f s i m u l t a n e o u s breakage o f b o t h c a r b o n - n i t r o g e n  bonds i n t h e  t r a n s i t i o n s t a t e (36). The f a c t t h a t c i s - and t r a n s - 3 , 5 - d i m e t h y l - l - p y r a z o l i n e s  63 and  65 a r e n o t i n t e r c o n v e r t e d d u r i n g t h e i r d e c o m p o s i t i o n removes t h e p o s s i b i l i t y o f an i n t e r c o n v e r s i o n t h r o u g h a n i t r o g e n c o n t a i n i n g  inter-  mediate 64_ b u t i t does n o t r u l e out t h e p o s s i b l e e x i s t e n c e o f an azo  - 19 -  d i r a d i c a l f a v o r e d by s e v e r a l r e s e a r c h e r s  (10,29,41).  66  K i n e t i c and p r o d u c t  C  H  3  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  i t s 4-d^ isomer (34) 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  and  cyclopropanes  came from a common n i t r o g e n f r e e i n t e r m e d i a t e s i n c e t h e p r o d u c t a n a l y s i s showed a s u b s t a n t i a l d e c r e a s e i n o l e f i n f o r m a t i o n i n g o i n g from t h e n o n d e u t e r a t e d p y r a z o l i n e t o t h e d e u t e r a t e d overall  kinetic  one w h i l e t h e  k i s o t o p e e f f e c t was found t o be _H = 1.07. D k  - 20 -  67 67  deuteroted  I f we assume t h a t _J1 = 1.0 ]. D f o r m a t i o n w i l l have ^ = 1.80.  52.3%  47.7%  66.0%  34.7%  f o r cyclopropane formation,  the o l e f i n  k  I t can be seen from the o v e r a l l k i n e t i c i s o t o p e e f f e c t t h a t i n the r a t e d e t e r m i n i n g  step, a nitrogen free 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 t h e s i m u l t a n e o u s breakage o f b o t h C-N bonds) which undergoes  a competitive  ring closure  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  o f t h e t r a n s i t i o n s t a t e was d e r i v e d  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 . one methyl group a t C-4 has v e r y  from k i n e t i c  The i n t r o d u c t i o n o f  l i t t l e e f f e c t , whereas two m e t h y l  groups cause a g r e a t d e a l o f d e c r e a s e i n t h e r e l a t i v e r a t e .  - 21 -  CH  r^i  N= £3  N  H^C^^^^  3  rS  N= N 67  relative rate 1.0  N = N 68  0.97  S i m i l a r l y t o eye1opentane  ?  0.0079  t h e p y r a z o l o n e s have an envelope  like  geometry w i t h an angle about 155° between t h e two p l a n e s .  T h i s angle presumably d e c r e a s e s lengthen.  as t h e c a r b o n - n i t r o g e n bonds  In t h e case o f the monomethyl p y r a z o l i n e , t h e n i t r o g e n  d e p a r t s t r a n s t o t h e methyl c a u s i n g o n l y v e r y s l i g h t s t e r i c But i n t h e 4 , 4 - d i m e t h y l p y r a z o l i n e  one methyl  n i t r o g e n and a l a r g e s t e r i c compression  compression.  i s cis t o the departing t  results i nsubstantial rate  decrease. The geometry o f 70 i s a n a t u r a l consequence o f the azo l i n k c o n t r a c o  o  t i o n from 1.25 A t o 1.09 A as  t h e f o r m a t i o n o f 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 s l o w r a t e would a l s o be expected i f an  i n c r e a s e i n C-3  - C-4  - C-5 bond a n g l e were t o o c c u r , thus d e c r e a s i n g  t h e CH^-C-CH^ a n g l e 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 tion state. The p l a n a r geometry f o r t h e t e r m i n a l methylenes  i n the i n t e r m e d i a t e  i s s u p p o r t e d by t h e o l e f i n i c p r o d u c t s o f c i s - and t r a n s - d i m e t h y l - 1 pyrazoline.  The m i g r a t i o n o f a hydrogen  from C-4  i n 73_ t o e i t h e r C-3  or  C-5  g i v e s o n l y t r a n s - 2 - p e n t e n e 74 w h i l e the m i g r a t i o n o f a C-4 n i t r o g e n i n 76 r e s u l t s i n t r a n s - 2 - p e n t e n e 74_ and c i s - 2 - p e n t e n e 77 and 75 gave  - 23 -  a l s o cyclopropane  p r o d u c t s w i t h predominant i n v e r s i o n o f s t e r e o c h e m i s t r y  of the parent p y r a z o l i n e s .  The i n t e r m e d i a t e can be l o o k e d upon as a 2  1,3 d i r a d i c a l h a v i n g carbons.  pn  - pn bonding between t h e n e i g h b o r i n g sp  A c c o r d i n g t o s p e c t r o s c o p i c n o t a t i o n , i t would be a i r g -  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 n o t a l l o w t h e " d i r a d i c a l " t o behave as two independent r a d i c a l s and a l s o suggested  H  8-12 K c a l mol * bonding energy.  H  H  -rrq cyclopropane  H  77- u cyclopropane  78  79  Hoffmann(37,38) c a l c u l a t e d t h e energy o f t r i m e t h y l e n e r e l a t i v e to cyclopropane  as a f u n c t i o n o f t h e C-C-C angle and r o t a t i o n o f t h e  t e r m i n a l methylene groups.  Two minima were observed  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 cyclopropane  on t h e ground t o an opened  80_ and t o 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 81_ where t h e  t e r m i n a l methylenes a r e c o p l a n a r w i t h t h r e e  carbons.  - 24 -  Hoffmann methylene the  A  also  found  that  the mixing  group d e s t a b i l i z e s t h e  level  at small  o f the o r b i t a l s of the central  S level  at large  angles  and  stabilizes  angles.  S  A —H83  It  i s apparent  that  8_3  should  manner r e s u l t i n g i n i n v e r s i o n  close  a t one  to cyclopropane  center  in a  compared t o t h e  conrotatory original  - 25 -  p y r a z o l i n e i f the t r i m e t h y l e n e i s p r o p e r l y s u b s t i t u t e d .  82_ would c l o s e  i n a d i s r o t a t o r y manner l e a d i n g t o r e t e n t i o n . C a l c u l a t i o n s showed t h a t s p e c i e s 82_ and i n energy and why  t h e r e may  the cyclopropane  83 a r e not g r e a t l y d i f f e r e n t  be an e q u i l i b r i u m between them which c o u l d e x p l a i n  formation  i s s t e r e o s e l e c t i v e only.  Crawford and E r i c k s o n (39) have i n v e s t i g a t e d whether the i n t e r m e d i a t e produced upon t h e r m o l y s i s o f 85_ has through the f o u r  a p l a n e o f symmetry  carbons.  §4  85  86  I f t h i s assumption i s v a l i d , the c i s - and  t r a n s - 4-deutero-3-methyl-  1 - p y r a z o l i n e upon t h e r m o l y s i s s h o u l d g i v e the same i n t e r m e d i a t e s e v e n t u a l l y the same product  composition.  The  experimental  and  r e s u l t s were  i n e x c e l l e n t agreement w i t h the p r e d i c t i o n s . The bears  trimethylene intermediate  formal  suggested  f o r pyrazoline thermolysis  s i m i l a r i t i e s to an adduct o b t a i n e d by a d d i t i o n o f a s i n g l e t  methylene t o an o l e f i n .  To see whether the t r i m e t h y l e n e  i s i n v o l v e d i n the s i n g l e t a d d i t i o n p r o c e s s , a study was  intermediate undertaken  by  - 26 -  Crawford and A l i (40).  The compounds c h o s e n w e r e c i 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 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 s t o i c h i o m e t r y as t h e butenes.  -d^  effect  having the  coordinate  i n the  and  and  trans-  the primary carbon  rate determining step.  product d i s t r i b u t i o n l e d t o the conclusion that and t h e  would  same s p i n s t a t e  indicated that  t o n i t r o g e n b o n d was a l s o b r e a k i n g i n t h e  trans-  isomers which  adducts of s i n g l e t methylene to c i s -  The k i n e t i c i s o t o p e  stereospecific  and  The  the thermolysis i s  trimethylene intermediates  a r e n o t on t h e  a d d i t i o n o f a s i n g l e t methylene to c i s -  and  not  reaction  trans-  butene. The t h e r m o l y s i s o f  ( 3 R : 5R) - ( + ) - t r a n s _ - 3 , 5 - d i m e t h y l  done b y C r a w f o r d a n d M i s h r a propanes  89,  (41)  produced c i s -  90 a n d some o l e f i n i c p r o d u c t .  p y r a z o l i n e 87_  and t r a n s - d i m e t h y l c y c l o -  - 27 -  Only 23% of the trans-cyclopropane 90 showed o p t i c a l a c t i v i t y , S : S configuration i n d i c a t i n g double inversion. 88 were a symmetrical  I f the intermediate  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 f o r the double inversion . a)  one which has been proposed by Roth and Martin (29) involving  a nitrogen containing d i r a d i c a l intermediate.  90 b)  the other based on a pyramidal d i r a d i c a l intermediate idea put  forward by A l l r e d and Smith (28).  Quantum mechanical  calculations predicted that the ground state of  the trimethylenemethane should be a t r i p l e t d i r a d i c a l .  By assuming that  - 28 -  the 4 - m e t h y l e n e - l - p y r a z o l i n e  decomposes v i a a d i r a d i c a l pathway i t seemed  t h e most c o n v e n i e n t s o u r c e t o g e n e r a t e t h i s s p e c i e s . showed by e . s . r . t h a t 4 - m e t h y l e n e - l - p y r a z o l i n e  Indeed Dowd (42)  9_3 upon p h o t o l y s i s a t low  temperature i n h e x a f l o u r o b e n z e n e s o l u t i o n o r i n s o l i d m a t r i x ,  produced  t h e d e s i r e d t r i p l e t d i r a d i c a l 94_ w h i c h had been p r e d i c t e d b y t h e o r e t i c a l calculation.  93  94a  The e . s . r . spectrum a l s o i n d i c a t e d t h a t t h e d i r a d i c a l had a t h r e e f o l d (or h i g h e r ) a x i s o f symmetry. K i n e t i c s t u d i e s done by C r a w f o r d and Cameron (43) showed t h a t b o t h Ea = 32.6 K c a l 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 K c a l mol  s i s t e n t with the expectation of  + , AS  1  11.2 e.v.)  These a r e con-  t h a t a t r i p l e t has a lower p r o b a b i l i t y  formation. To check t h a t a s y m m e t r i c a l i n t e r m e d i a t e  94b was i n d e e d i n v o l v e d ,  4 - m e t h y l e n e - l - p y r a z o l i n e - 3 , 3 - d ^ had been p r e p a r e d and decomposed.  - 29 -  Such a s p e c i e s would be expected t o g i v e methylene-cyclopropanes  in  the f o l l o w i n g r a t i o  expected found  The e x p l a n a t i o n 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 t h a t by a v i r t u e ofysecondary  isotope e f f e c t i n the product determining  the d i d e u t e r o methylenegroup conformation  step  i s slower t o r o t a t e i n t o the r i n g  than a r e t h e d i p r o t i o m e t h y l e n e  groups.  - 30 -  H \  c  / H  H-  I  I  H  D  97  The i s o t o p e e f f e c t was found t o be _M. = 1.37. k  By p r e p a r i n g and p y r o l y s i n g t h e  D  4-methylene-l-pyrazoline-3,3,6,6-d  98 and u s i n g t h e v a l u e of/'isotope e f f e c t , they were a b l e t o p r e d i c t the p r o d u c t  ratios  calculated  73.2%  26.2%  observed  73.8%  26.2%  I t i s known t h a t t h e s i m p l e t r i m e t h y l e n e methane 94a undergoes a f a s t r i n g c l o s u r e b e f o r e i t c o u l d add t o o l e f i n i c a c c e p t o r s .  Berson e t a l .  - 31 -  (44,45,46) hoped t o 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 t r i m e t h y l e n e methane i n t o a r i n g system 101 which would g i v e a h i g h l y s t r a i n e d h y d r o c a r b o n 103 on r i n g c l o s u r e .  CH.  X"' 102  Indeed, t h e i n t e r m e d i a t e , 102 underwent  103  2-isopropylidenecyclopentane-l,3-diyl  cycloaddition with o l e f i n s .  One o f t h e most i n t e r e s t -  i n g r e a c t i o n s o f 101 i s t h e " 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 c y c l o a d d u c t 104 can be c o n v e r t e d 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 t o a f u s e d azo-compound 105  isomeric  w i t h 101. The s t e r e o c h e m i s t r y dideuterated  o f the i n t e r m e d i a t e  102 was r e v e a l e d when t h e  isomer o f 101 was decomposed t h e r m a l l y i n t h e presence o f  d i m e t h y l maleate.  - 32 -  50%  C00CH  D  3  COOCH3  50%  108  That shows t h a t i n t h e i n t e r m e d i a t e 107 t h e r i n g and p r o x i m a l c h a i n carbons  a r e c o p l a n a r , o r become c o p l a n a r b e f o r e b e i n g  side-  trapped.  Perhaps one o f t h e most i m p r e s s i v e p r o o f s f o r t h e i n t e r m e d i a c y o f 1 , 3 - d i r a d i c a l species i n the photodecomposition p r e s e n t e d by Kaplan e t a l . (47,48). state t r i p l e t diradical  o f p y r a z o l i n e s was  They n o t o n l y i d e n t i f i e d t h e ground  o b t a i n e d by t h e i r r a d i a t i o n o f 3 H - i n d a z o l  d e r i v a t i v e s b u t c o u l d t r a p them w i t h  butadiene.  - 33 -  The assumption t h a t t h e adduct formed v i a a two s t e p a d d i t i o n m a i n t a i n i n g t h e s p i n c o n s e r v a t i o n 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 .  III.  Concerted  mechanism.  Up t o date t h e r e have been o n l y a few r e p o r t s c l a i m i n g c o n c e r t e d pathways f o r d e c o m p o s i t i o n  o f c y c l i c azo compounds.  Those which have  been p u b l i s h e d can be c l a s s i f i e d i n t o t h e f o l l o w i n g t h r e e groups: a)  retro Diels-Alder reactions  b)  concerted o l e f i n  c)  cyclopropane  formation  ring assisted  decompositions.  -  (a)  34 -  Retro D i e l s - A l d e r r e a c t i o n s . The u n u s u a l f e a t u r e o f t h i s r e a c t i o n i s t h a t no n i t r o g e n  t a k e s p l a c e c o n t r a r y t o t h e m a j o r i t y o f azo compound Hinshaw and A l l r e d  extrusion  fragmentation.  (49) have o b s e r v e d t h i s k i n d o f d e c o m p o s i t i o n when  they t h e r m o l y z e d t h e 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 s u g g e s t e d t h a t 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  R e t r o D i e l s - A l d e r r e a c t i o n was found t o be (50) t h e o n l y pathway f o r the t h e r m a l  d e c o m p o s i t i o n two g e o m e t r i c a l  i s o m e r i c azo system a t t h e  b r i d g e h e a d 119.  I  Ph  J20  119.  J21  - 35 -  (b)  Concerted o l e f i n  formation:  U s i n g n.m.r. d a t a McGreer e t a l . (51) d e t e r m i n e d the p r e f e r r e d c o n f o r m a t i o n s o f c i s - and  trans_-3,5-dimethyl-3-carbomethoxy-l-pyrazolines  which upon t h e r m o l y s i s gave o l e f i n i c and c y c l o p r o p a n e p r o d u c t s . The stereochemistry  o f the o l e f i n i c e s t e r s w i t h r e s p e c t t o the p r e f e r r e d  c o n f o r m a t i o n o f the p a r e n t p y r a z o l i n e s showed t h a t the o l e f i n i c p r o d u c t s were formed i n a s t e r e o s p e c i f i c manner. hydrogens which was the t r a n s i t i o n  t r a n s t o the n i t r o g e n s would c o n c e r t e d l y m i g r a t e i n  s t a t e w i t h t h e n i t r o g e n e x t r u s i o n t o C-5  e s t e r and t o C-3  a,3-unsaturated  t o g i v e 3 , Y - o l e f i n i c e s t e r s w i t h t r a n s geometry.  a l s o suggested t h a t the r a t i o o f the a, 3measure o f the m i g r a t i o n a l a  They assumed t h a t one o f the C-4  and 3 , y - e s t e r s would be  . p t i t u d e o f the hydrogen as a h y d r i d e CH,  proton.  123fl  COOCH  H  H  N 3  CH —CH 3  COOCH3 122  the or  CH: COOCH3  124.  7  H  2  They  H:.  123b.  COOCH3  CH,  CH,  COOCH,  125_  COOCH3  COOCH N  //  H-1  -N CH  COOCH3 £k>Z—N  3  126  127 b  CH  H  COOCH,  X  CHj — CH2  CH3  3  128  - 36 -  McGreer and Wu (52) have proposed a s i m i l a r t r a n s i t i o n state f o r the stereospecific o l e f i n formation i n the thermal decompositions of the geometrically isomeric c i s - and trans_-3-methy 1-4-ethyl-3carbomethoxy-1-pyrazoline. According to the preferred conformations, the C-4 hydrogen i s in the pseudo axial and the C-4 ethyl group i n the pseudo equatorial position.  COOCH^ C H 3 - C H 2  W _  N  129  COOCH:  130  But i n the reaction, some conformational change w i l l take place, 130  changes to 1_32_ and 129 t o 131. CH — CH 2  J5L  / i v  /  C  h  3  CH -CH  3  3  COOCH CH -CH 2  132  A  C  CH  3  H  3  COOCH  3  m  3  3  —  COOCH3  H,M^f CH  2  >=<  CHj-CH-  C H  3  C H  COOCH3  3  — C H  2  — C - C H ^ CH 133  2  0  C  0  0  C  H  3  3  C H  3  J35  - 37 -  The advantage gained by the concerted migration of the hydrogen must be s u f f i c i e n t to overcome the s t e r i c compression i n the t r a n s i t i o n state.  The cyclopropanes were formed with predominant retention with  respect to the parent pyrazoline.  (c)  Cyclopropane ring assisted  decompositions:  Exceptionally high rate and s t e r e o s p e c i f i c i t y have been observed in the thermal decomposition of c y c l i c azo compounds having fused cyclopropane rings.  The studies have also indicated that the orienta-  t i o n of the cyclopropane ring i s c r i t i c a l i n determining the reaction pathway. Berson and O l i n (53) have reported that the cyclopropane ring had a complete control over the stereochemical course of the decomposition of the following azo compounds;  136  J37  138  139  - 38 -  The high degree of s t e r e o s p e c i f i c i t y and rate would suggest that the reaction should be a concerted o r b i t a l symmetry allowed retro D i e l s Alder reaction i f the photochemical decomposition did not give exactly the same products.  The authors f e l t that i n these cases factors other  than o r b i t a l symmetry had  complete control over the reaction.  They  introduced the concept of extrasymmetric factor as a general term f o r influences other than o r b i t a l symmetries which play a decisive role i n determining the course of the reactions. A l l r e d et_ a l . (54) have also found a 10*^ times rate enhancement in the thermal decomposition of 140 i n comparison to  140  2,3-diazanorbornene.  141  The authors attributed the rate enhancement to the intervention of an orbital-symmetry allowed process.  The t r a n s i t i o n state i s most  l i k e l y the following:  142 a  142 b  N  N=N  - 39 -  They argue t h a t i f t h e r e a c t i o n s were d i r a d i c a l a t 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 t h e r e a c t i o n c o n d i t i o n .  143  144  T a n i d a e_t al_. (55) found l a t e r 144 i n t h e p h o t o l y t i c p r o d u c t m i x t u r e o f 140. The works o f A l l r e d , Johnson  (56) and T r o s t et_ al_. (57,58) e t c . ,  p r o v i d e e v i d e n c e f o r t h e importance o f t h e g e o m e t r i c a l  factors involved  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 p r e p a r e d a s e r i e s o f t r i c y c l i c compounds i n which t h e b r i d g e h e a d s and the c y c l o p r o p y l groups were connected w i t h carbon b r i d g e s  d i f f e r i n g i n lengths.  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 o f a s e r i e s o f t r i c y c l i c azo compounds.  -  40  -  - 41 -  Data i n d i c a t e t h a t 147 decomposes t o a d i r a d i c a l i n t e r m e d i a t e ,  1 4 9  >  1 5 1  f o l l o w a concerted,  The c o n s i d e r a b l e  o r b i t a l symmetry a l l o w e d pathway.  d i f f e r e n c e i n r e a c t i v i t y among t h e compounds can  be e x p l a i n e d by t h e o r i e n t a t i o n o f t h e c y c l o p r o p y l r i n g s . 149,  while  I n 140, 145.  151 t h e c y c l o p r o p y l o r b i t a l s a r e more f a v o r a b l y o r i e n t e d i n t h e  t r a n s i t i o n s t a t e s f o r o v e r l a p as t h e C - N bonds break. A l l r e d and Voohees (59) have compared t h e i n f l u e n c e o f the c y c l o p r o p y l group b e i n g  i n exo- and endo- p o s i t i o n s on t h e t h e r m a l r e a c t i v i t y  o f the azo compounds.  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 h a v i n g 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  N  48  EQ  KcQl/mol  44.6  AsVu  10.5  re I. rate  1.0  - 42 -  A l l available  c r i t e r i a clearly indicate  a d i r a d i c a l pathway w i t h o u t p a r t i c i p a t i o n  t h a t 155 decomposes by  o f the cyclopropane  ring.  -*3-  OBJECTIVE OF PRESENT RESEARCH  The mechanistic d e t a i l s of thermo- and photodecompositions of c y c l i c azo compounds are s t i l l under intensive investigation.  The  survey of r e s u l t s 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 i n these laboratories under the d i r e c t i o n of Dr. D. E. McGreer on pyrazoline systems having an electron withdrawing group (acetyl, carbomethoxy, cyano) on C-3. As a continuation of the e a r l i e r research the studies were conducted mainly on 3-methyl-3-carbomethoxy-l-pyrazolines bearing d i f f e r e n t a l k y l groups, deuterium or both on C-4. Snyder's observation (60) that the replacement of the C-3 methyl group for an ethyl i n the 3-methyl-3-carbomethoxy-l-pyrazoline decreased the rate of decomposition i n i t i a t e d the preparation and study of 3-tert-butyl-3-carbomethoxy-1-pyrazoline which showed exceptional thermal s t a b i l i t y . Crawford (9) and Bergman (10) reported that the incorporation of the pyrazoline ring i n a b i c y c l i c structure increased the amount  - 44 -  o f o l e f i n i c p r o d u c t s upon t h e r m o l y s i s r e l a t i v e t o the s i m p l e system. In t h e hope t h a t a s i m i l a r system which i n a d d i t i o n has a carbomethoxy group n e x t t o t h e N=N  double bond would behave s i m i l a r l y  2,3-diazabicyclo(3.3.0)oct-2-ene  was  prepared.  1-carbomethoxy-  Indeed t h e p y r o l y s i s  o f t h i s compound p r o v i d e d as much as 80% o l e f i n i c p r o d u c t .  I t also  appeared w o r t h w h i l e t o s y n t h e s i z e l - c a r b o m e t h o x y - 2 , 3 - d i a z a b i c y c l o ( 3 . 3 . 0 ) o c t - 2 - e n e - 5 d j and the n e x t two members o f t h e s e r i e s . S i n c e McGreer and M a s t e r s have undertaken a thorough s t u d y o f l - m e t h y l - l - c a r b o m e t h o x y - l - p y r a z o l i n e - 4 d 2 , i t seemed t o be c h a l l e n g i n g t o p r e p a r e 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 t o 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 o t o p e e f f e c t s f o r the d i f f e r e n t processes involved i n p y r a z o l i n e decomposition. Snyder (60) has a l s o observed t h a t the 3 - m e t h y l - 3 - c a r b o b u t o x y - 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 o f d e c o m p o s i t i o n t h a n the c o r r e s p o n d i n g methyl e s t e r .  S i n c e he has not done any p r o d u c t s t u d y i t seemed  i n t e r e s t i n g t o see t h e changes i n p r o d u c t d i s t r i b u t i o n t o o . The s t u d i e s o f Van Auken et_ al_. (14) on the d e c o m p o s i t i o n o f c i s - and t r a n s - 3 , 4 - d i m e t h y l - 3 - c a r b o m e t h o x y - 1 - p y r a z o 1 i n e s et a l . (52) on c i s - and  and McGreer  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 :  stereospecific  olefin  f o r m a t i o n and an i n c r e a s e i n t h e amount o f c y c l o p r o p a n e p r o d u c t s w i t h the i n c r e a s i n g s i z e o f the C-4  alkyl substituents.  In order  t o o b t a i n some more i n f o r m a t i o n about t h e p a t t e r n t h e 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 p l a c e d i n b o t h 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  also anticipated  t h a t one o f t h e s e p y r a z o l i n e s would g i v e o n l y c y c l o p r o p a n e p r o d u c t  - 45 -  which could lead to a clean-cut measurement of the deuterium k i n e t i c isotope effect concerning  the cyclopropane  formation.  DISCUSSION  I.  Some o f t h e g e n e r a l 1-pyrazolines  features o f thermal decomposition o f  which s e r v e d  as a b a s i s f o r r e s e a r c h  plans  Snyder's work (60) has shown t h a t t h e r a t e o f d e c o m p o s i t i o n o f 1-pyrazolines  was i n c r e a s e d 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 a t p o s i t i o n 3 and 5, b u t t h e s u b s t i t u t i o n o f a methyl group a t C-4 caused a r a t e d e c r e a s e . S i m i l a r b u t more d e t a i l e d r e s u l t s a r e p r e s e n t e d i n M a s t e r ' 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 t h e s u b s t i t u t e d  p y r a z o l i n e s a t 109.4°C i n n - b u t y l p h t h a l a t e  s o l v e n t and found t h a t t h e  e l e c t r o n w i t h d r a w i n g a b i l i t y o f t h e s u b s t i t u e n t s a t C-3 had a l a r g e e f f e c t on t h e r a t e o f p y r o l y s i s .  The r a t e i n c r e a s e s i n g o i n g from  the 3-carbomethoxy t o t h e 3 - a c e t y l and t o t h e 3-cyano p y r a z o l i n e s roughly  c o r r e l a t e d w i t h t h e i n c r e a s i n g e l e c t r o n w i t h d r a w i n g power o f  the above mentioned groups. In t h e case o f t h e 3 - a c e t y l and 3 - c y a n o - l - p y r a z o l i n e s ,  not only  the r a t e o f d e c o m p o s i t i o n i s changed b u t new p r o d u c t s appear; f u r a n s and HCN.  dihydro-  The r e e x a m i n a t i o n o f t h e p r o d u c t s t u d i e s done on  3-methyl-3-cyano-l-pyrazoline lead t o 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 o b t a i n e d by I . Masters  -  (61).  The gas chromatographic  i n s t e a d o f s i x peaks gave o n l y f o u r . HCN  The  f i r s t peak was  most  ( 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 b e n z i d i n e b l u e  The o t h e r t h r e e a n g e l o n i t r i l e , 1 - m e t h y l - l - c y a n o - c y c l o p r o p a n e t i g l o n i t r i l e , i d e n t i c a l t o t h o s e found by I . M a s t e r s . a l s o c o n t a i n e d a s m a l l amount o f s o l i d m a t e r i a l . has not been a thorough HCN  analysis  The  likely  test). and samples  Up t o date t h e r e  s t u d y c o n c e r n i n g the m e c h a n i s t i c d e t a i l s o f  formation. There i s an e i g h t t o t e n f o l d r a t e i n c r e a s e and a s m a l l  AH  decrease upon s u b s t i t u t i o n o f a methyl  group at t h e f i v e p o s i t i o n ,  w h i l e t h e s t e r e o c h e m i s t r y o f the methyl  group changes t h e r a t e o f  decomposition ably.  The  decrease  II.  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 c o n s i d e r -  s u b s t i t u t i o n o f a second methyl  group a t C-5  causes a  i n the r a t e of fragmentation.  3-Alkylpyrazolines 3-tert-Butyl-3-carbomethoxy-1-pyrazoline: Snyder (60) found t h a t t h e s u b s t i t u t i o n o f an e t h y l group f o r t h e  methyl  at C-3  reduced t h e r a t e o f n i t r o g e n e v o l u t i o n .  e x p l a n a t i o n was  Although  g i v e n by t h e a u t h o r , i t was most l i k e l y due t o t h e  f a c t t h a t t h e e t h y l group i s b u l k i e r than t h e m e t h y l .  Unfortunately  p r o d u c t s t u d i e s have not been done t o see the e f f e c t on t h e distribution.  no  product  - 48 -  T h i s compound had t o be h e a t e d at a reasonable  rate.  up t o 160° t o e f f e c t  decomposition  T h i s l e a d s t o t h e c o n c l u s i o n t h a t 156 i s one o f  t h e most s t a b l e p y r a z o l i n e s h a v i n g an a l k y l and  carbomethoxy groups a t  C-5.  C 0 0 C H  = ert-butyl  —1  3  f  N 156  T h i s compound t u r n e d o u t t o be one o f t h e most s t a b l e 1 - p y r a z o l i n e s t o t h e p r e s e n t h a v i n g a carbomethoxy and an a l k y l s u b s t i t u e n t a t C-3.  * To decompose i t a t a r e a s o n a b l e  r a t e i t s h o u l d be h e a t e d up t o 160°C.  I t s n.m.r. s p e c t r u m i n d i c a t e s t h a t t h e hydrogen o f t h e two m e t h y l e n e s e x h i b i t an a l m o s t f i r s t o r d e r 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 t h e b e s t v a l u e s f o r t h e s i x c o u p l i n g c o n s t a n t s and c h e m i c a l s h i f t s u s i n g a computer program. : -17. 416 Hz AB J  =  J  AM  =  3. 876 Hz  J  AN  =  9. 807 Hz  J  BM  =  9; 336 Hz  J  BN  =  7. 950 Hz  J  MN  =  : -13. 176 Hz  H  A  H  D  o  = 5.497 x = 5.839 T 8.130 T  H  N  = 8.446 T  K i n e t i c s t u d i e s c o u l d n o t be done on i t u s i n g o u r a p p a r a t u s because of the r e l a t i v e l y high temperature t o o b t a i n a conveniently measurable r a t e .  - 49 -  On t h e b a s i s o f the n.m.r. s p e c t r a o f 3 , 3 - d i m e t h y l - and 3-methyl3 - c a r b o m e t h o x y - 1 - p y r a z o l i n e s , (51 ) i n which t h e two C-4 and hydrogens form an ABO^  C-5  s p i n system i m p l i c a t i n g t h e e q u i v a l e n c e o f t h e  C-4 hydrogens w h i c h i s t h e consequence o f t h e f a c t t h a t b o t h conformat i o n s are e q u a l l y p o p u l a t e d at room t e m p e r a t u r e , one can c o n c l u d e t h a t the p y r a z o l i n e 156 i s l o c k e d i n one c o n f o r m a t i o n by t h e l a r g e t e r t b u t y l group.  To d e t e r m i n e t h e p r e f e r r e d c o n f o r m a t i o n o f 156 one s h o u l d  most r e a s o n a b l y p l a c e t h e t e r t b u t y l group i n t h e pseudo e q u a t o r i a l position  ( i f the t e r t b u t y l group were pseudo a x i a l t h e non-bonding  i n t e r a c t i o n s between t h e pseudo a x i a l hydrogen i n C-5 and t h e t e r t b u t y l group would be  considerable).  H  Q  COOCH  3  The i n s p e c t i o n o f n.m.r. s p e c t r a o f o t h e r p y r a z o l i n e s shows t h a t the s i g n a l o f t h e methyl i n a pseudo a x i a l carbomethoxy group appears around 6.38x and t h a t i n a pseudo e q u a t o r i a l around 6.15T due t o t h e 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 t h e N=N  double bond r e s p e c t i v e l y .  50 -  r  The peak, due t o t h e carbomethoxy  group i n t h e n.m.r. spectrum o f 156,  i s a t 6.35T s u b s t a n t i a t i n g t h e former assumption. w h i l e t o mention t h a t t h e carbomethoxy o t h e r p o s i t i o n but i n pseudo the  axial  Perhaps i t i s w o r t h  group o f 164 cannot be i n any and appears at 6.37T c l o s e t o  v a l u e o f 156. The s t e r e o c h e m i s t r y o f t h e o l e f i n i c p r o d u c t o b t a i n e d from t h e r m o l y s i s  a l s o s u p p o r t s t h i s assumption i n accordance w i t h McGreer's  olefin  f o r m a t i o n scheme.  CH  3  158  COOCH 35.4%  + cycloprop. products 159  64.5%  The d i r e c t p h o t o l y s i s i n i s o p e n t a n e at 3100 A gave t h e f o l l o w i n g products:  3  H  COOCH  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 a reverse 1,3-cyclo a d d i t i o n . 1,2-diradical  The mechanism o f the f o r m a t i o n o f t h e  and t h e o t h e r p h o t o p r o d u c t s  158, 159 i s not c l e a r y e t .  The benzophenone s e n s i t i z e d p h o t o l y s i s cyclopropane  i n t e r m e d i a t e * and n o t by  a t 3500 A gave o n l y  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 g i v e n  later.  - 52 -  I I I . K i n e t i c and p r o d u c t  studies o f  l-carbomethoxy-2,3-diazabicyclo  (3.3.0)-oct-2-ene and i t s a n a l o g u e - 5 d ] . In o r d e r t o g a i n some more i n f o r m a t i o n about t h e 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 t h e product  distribution  upon t h e r m o l y s i s a p y r a z o l i n e system was i n c 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 c o n n e c t i n g C-3 and C-4 w i t h a s h o r t , three-membered bridge t o exclude p o s s i b l e conformational  interconversion.  h a v i n g s h o r t e r one (62) o r two-membered b r i d g e s a m e c h a n i s t i c a l l y complex  Compounds  (63) seem t o undergo  fragmentation.  The o t h e r i n t e r e s t i n g f e a t u r e o f t h e 2 , 3 - d i a z a b i c y c l o ( 3 . 3 . 0 ) oct-2-ene and i t s d e r i v a t i v e s t h a t t h e suggested t r i m e t h y l e n e mediate cannot e a s i l y a c h i e v e  t h e 0.0 geometry as i n t h e case o f  s i m p l e p y r a z o l i n e s due t o t h e s t r a i n caused by t h e r e l a t i v e l y * chain. Schneider  inter-  short  and Crawford (9) r e p o r t e d t h e f o l l o w i n g p r o d u c t  d i s t r i b u t i o n o f 160 upon t h e r m o l y s i s a t 200°C,  67.7%  *  AHJ  = 38.5 K c a l / m o l  A St  = 6.67 e.u.  18.8%  13.5%  A l i and Crawford (40) p o i n t e d out t h a t t h e i n t e r m e d i a c y o f 0.0 t r i m e t h y l e n e a l o n e c o u l d n o t account f o r t h e double i n v e r s i o n observed i n t h e c y c l o p r o p a n e product. ** C a l c u l a t i o n based on S c h n e i d e r and Crawford r e s u l t s .  - 53  H  A  N  ° = f  COOCH3  N  C00CH  K  N 164  K  3  17 +  165  COOCH3  166  at 130-131 ° C 19.6% at 240-260°C 31.6% (in injection port) AS*  AH=  CH  3  H C  3  CH, 10.2% 10.8%  28.3 Kcal.  C O O C H 3  3  COOCH.  CH:  70.0% 56.7%  =-2.62e.u.  H C  K  C O O C H 3  C  H  CH  3  C O O C H 3  3  CH=C—CH 169  168  C O O C H 3  170  CH^  30% AH*  = 33£  AS*  CH  3  171  COOCH3 3  172  66%  CH^CHg 3  4%  = 7.9 Van Auken et d . (14)  ,CH,  N CHji  w  174  176  79%  in gas phase  AH*  = 39.0 Kcal  177 21%  A S * = 6.3 e.u. Crawford et g i (40)  3  - 54 -  I t i s i n t e r e s t i n g t o n o t e t h a t 168 gave l e s s o l e f i n i c p r o d u c t s than 164 i n s p i t e o f t h e form and s t r u c t u r a l s i m i l a r i t y c o u p l i n g c o n s t a n t s do n o t conform).  (n.m.r. d a t a , namely  T h i s d i f f e r e n c e can be b e s t a t t r i b -  u t e d t o t h e d i f f e r e n c e i n f l e x i b i l i t y between t h e two p y r a z o l i n e s . The t h e r m o l y s i s o f 1 - c a r b o m e t h o x y - 2 , 3 - d i a z a b i c y c l o ( 3 . 3 . 0 ) - o c t - 3 ene-5-d  1  gave r i s e t o a p r o d u c t m i x t u r e shown below:  3  D  COOCH3  180 at 130-131 °C at 2 4 0 - 2 6 Q ° (injection port)  181 34.3 42.7  CH D  CH  2  182 58.1 47.7  183 7.5 9.3  2  - 55 -  The comparison  o f p r o d u c t d i s t r i b u t i o n s o f 160 and 164 shows  t h a t t h e e l e c t r o n w i t h d r a w i n g carbomethoxy group n o t o n l y d e c r e a s e s t h e temperature r e q u i r e d t o b r i n g about d e c o m p o s i t i o n b u t 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 m o n o c y c l i c p y r a z o l i n e s , 84, 184 and 185. The f o r m a t i o n o f o l e f i n i c p r o d u c t s 166 and 167 most l i k e l y  follows  c o n c e r t e d pathways s i m i l a r t o 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 l a r g e amount o f o l e f i n i c  compound i n t h e p r o d u c t m i x t u r e seems t o i n d i c a t e t h a t t h e C-5 hydrogen may be i n a f a v o r a b l e p o s i t i o n f o r m i g r a t i o n . S i n c e Bergman et_ al_. (10) have suggested a near p l a n a r 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 b o t h exo- and e n d o - 2 - m e t h y l - 5 , 4 - d i a z a b i c y c l o [ 3 . 5 . 0 ] o c t 3-enes on t h e b a s i s o f c o u p l i n g c o n s t a n t s ( J = 3.0 Hz f o r t h e exo trans and J ^ 7.0 Hz f o r t h e endo compounds) i t i s w o r t h w h i l e t o compare t h e r  b  v  =  c  s  c o u p l i n g c o n s t a n t s o f 164 ( J = 8.5 Hz and J . = 3 . 3 Hz) w i t h those trans cis r  o b t a i n e d by Bergman*.  The c o u p l i n g c o n s t a n t s d i f f e r c o n s i d e r a b l y u n l e s s  we assume t h a t t h e p s e u d o a x i a l hydrogen H^ ( c i s t o Hx) appears a t a lower f i e l d than t h e p s e u d o e q u a t o r i a l hydrogen, e f f e c t o f t h e carbomethoxy group.  However n.m.r. d a t a o f c i s - and t r a n s -  3,5-dimethyl-3-carbomethoxy-l-pyrazolines t h i s assumption  H^ because o f t h e d e s h i e l d i n g  (51) do n o t seem t o s u b s t a n t i a t e  s i n c e the chemical s h i f t values o f the pseudoaxial  hydrogens were found t o be almost i d e n t i c a l i n b o t h isomers.  Consequently  Bergman's s t e r e o c h e m i c a l argument i s n o t a p p l i c a b l e t o 164.  U n f o r t u n a t e l y t h e r e a r e no d a t a a v a i l a b l e on t h e c h e m i c a l s h i f t v a l u e s o f C-2 p r o t o n s .  - 56 -  k  H  The r e l a t i v e l y large T — =1.24 o v e r a l l deuterium k i n e t i c isotope effect for D k  and the change i n product d i s t r i b u t i o n corroborate McGreer's idea of concerted o l e f i n formation.  I f the o l e f i n i c and cyclopropane products came  from a common intermediate and no s i g n i f i c a n t changes regarding the bonding s i t u a t i o n of deuterium were taking place i n the t r a n s i t i o n state of the rate determining step as i n the case of 4-methyl-l-pyrazoline-4d^ (34) the overall k i n e t i c isotope effectswould be quite small while changes i n the product r a t i o s would only be s i g n i f i c a n t . The kinetic isotope effect f o r the individual reaction which were obtained from the o v e r a l l deuterium k i n e t i c isotope effect and the product distributions are as follows. H T— D  f o r 3,y-olefin formation  = 1.68  H r— D  f o r a,B-olefin formation  = 1.49  H T— D  for cyclopropane formation  = 0.71  k  k  k  k  k  K  The "inverse" value for cyclopropane  formation i s contrary to other  findings i n the monocyclic pyrazolines but i t cannot be attributed to experimental errors.  The substitution of deuterium at C-5 caused a con-  siderable increase i n the activation parameters (AH* = 32.4 kcal mol , 1  AS^ = 7.17 e.u.) r e l a t i v e to those (AH* 28.3 kcal m o l , AS* -2.62 e.u.) -1  for 164. The change i n product d i s t r i b u t i o n upon the d i f f e r e n t mode of fragmentation (flask and i n j e c t i o n 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 o f 164 and propane p r o d u c t s  180  (3100 A) gave o n l y c y c l o -  i n g r e a t e r than 98% y i e l d .  Because o f the easy  access  t o s t a r t i n g m a t e r i a l s and diazomethane and the h i g h y i e l d , i t seems t o be an i d e a l p r e p a r a t i v e r o u t e t o b i c y c l o (3.1.0)hexane d e r i v a t i v e s .  IV.  Stereochemical (a)  The  factors affecting olefin  formation  e f f e c t o f the s i z e o f the e s t e r group on o l e f i n  formation,  3-methyl-3-carbalkoxy-1-pyrazolines. I n s p e c t i o n o f Table V shows t h a t the i n t r o d u c t i o n o f a second methyl group a t C-3  of 3-methyl-1-pyrazoline  the y i e l d o f c y c l o p r o p a n e  results i n a s l i g h t increase i n  d e r i v a t i v e upon t h e r m o l y s i s w h i l e the  intro-  d u c t i o n o f a carbomethoxy group b r i n g s 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 o f the methyl group o f the  carbo-  methoxy by e t h y l and t e r t - b u t y l groups causes a s m a l l d e c r e a s e 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 o f o l e f i n i c and c y c l o p r o p a n e of 3-methyl-3-carbalkoxy-l-pyrazplines  products  of a s e r i e s  upon t h e r m o l y s i s  - 58 -  COMPOUND  C H  N  OLEFINIC PROD,  3  6.7%  N  84  in gas phase  CH N  N  1 8 4  r^  N s s  CH  |<C  N = N 1 8 5  I  3  in gas phase  15 %  pure  33.2%  informamide  55.5%  I  N = N 187  2  3  66.8% 44.5%  (61)  ur  N 186 N  / C H  (16)  P *  3  ?  N  96.7 %  85 %  McGreer, Masters  3  |\ I COOCH —CH  I  ^  3.3 % Crawford, Mishra (34)  — II—  COOCH  93.3%  Crawford, M ishra (34)  3  C H 3  CH  CYCLOPROPANE PROD.  C H  9  -  6  %  70,4%  3  5  in this work  pure  3  T^COOC-CH, I CH  2  0 3  25.9% in this work  74.1%  - 59 -  The n.m.r. s p e c t r a o f 184, 185 and 186 showed t h a t t h e C-4 hydrogens  are e q u i v a l e n t leading t o the c o n c l u s i o n that both conformations  are equally populated.  T h i s i s n o t t h e case w i t h 187 and p r o b a b l y t h e  c o n f o r m a t i o n i n which t h e carboxy t e r t - b u t y l group i s i n t h e pseudoe 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 o t h e r . 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 o f 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 s t e r e o c h e m i c a l arguments cannot  account  f o r t h i s change s i n c e t h e m e t h y l group i s n o t much l a r g e r i n s i z e t h a n t h e carbomethoxy  group.  The assumption t h a t t h e o l e f i n s  are also  formed v i a a 1 , 3 - d i r a d i c a l i n t e r m e d i a t e s i m i l a r t o t h a t proposed by Crawford (34) i s u n t e n a b l e because i t cannot e x p l a i n t h e s t e r e o s p e c i f i c o l e f i n f o r m a t i o n observed by McGreer e t a l _ (51,52), b e s i d e s i f we accept Ruchard's  (64) c l a i m t h a t t h e m e t h y l and t h e carbomethoxy  groups have about t h e same s t a b i l i z i n g e f f e c t s on s i m p l e r a d i c a l centres  (both d e c r e a s e s p i n d e n s i t y ) we s h o u l d expect s i m i l a r p r o d u c t  d i s t r i b u t i o n s from b o t h 184 and 185 which i s n o t t h e case.  A viable  e x p l a n a t i o n which can account f o r t h e s t e r e o s p e c i f i c o l e f i n f o r m a t i o n was put f o r w a r d by McGreer e£ al_. (51).  They proposed a c o n c e r t e d  path and p o i n t e d out t h e s t e r e o c h e m i c a l r e q u i r e m e n t s f o r o l e f i n formation.  Product s t u d i e s done i n s o l v e n t s w i t h d i f f e r i n g  polarity  (61) showed t h a t t h o s e which had h i g h e r p o l a r i t y f a v o r e d t h e o l e f i n  - 60 -  formation.  T h i s i s a c l e a r i n d i c a t i o n t h a t 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 The  i s more p o l a r t h a n t h a t f o r c y c l o p r o p a n e  o t h e r i n t e r e s t i n g f e a t u r e o f the t h e r m a l  formation.  decomposition i s  the change i n p r o d u c t d i s t r i b u t i o n brought about by the s i z e o f the a l k y l group i n the e s t e r p a r t .  It i s d i f f i c u l t to give a  e x p l a n a t i o n o f i t but i t seems t h a t i t i s due i n the t r a n s i t i o n (b)  The  clear  to stereochemical  changes  state.  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  f o r m a t i o n , cis_- and  on o l e f i n  trans-3-methyl-4-alkyl-3-carbomethoxy-l-  pyrazolines. The works o f van Auken et^ al_. (14) and McGreer et_ al_. (52) indicated  t h a t the s i z e and the p o s i t i o n  o f the a l k y l group i n C-4  a f f e c t the p r o d u c t d i s t r i b u t i o n .  TABLE VI The  p r o d u c t d i s t r i b u t i o n o f c i s - and  trans-3-methyl-4-alkyl-3-  c a r b o m e t h o x y - 1 - p y r a z o l i n e s upon t h e r m o l y s i s .  also  - 61 COMPOUND  CYCLO PRO PANES  COOCH,  cis  trans  17.6%  12.32%  N  OLEFIN a,$ Z  OLEFIN & r  E 65.75%  4.0%  van Auken etal.|4  1 6 8  c N' :N  COOCH  28.3%  34.57%  van Auken et al. 14  COOCH: N'  31.0%  9.%  129  N  4.25%  3  188  —''"I^  32.84%  0  56%  4.0%  McGreer et al.52  ./"COOCH:  11.0%  72%  13% 0  4,0%  0  4.2 %  130  43.0%  3.6%  in this work  189  COOCH: N' 1 9 0  48.9 %  0  91.7%  8.3 %  0 in this work  0  - 62 -  COMPOUND  CYCLOPROPANES cis  C00CH  OLEFIN. a.B OLEFlN./3.y  trgns  Z  0  0  42.7%  E 44.0%  3  13.0%  in this work  N  191  y~~ l  co  N  °  cH3  °  i0j o/o  79  -  i%  °  iq o/o  °  c  in this work  192  M  - COOChU  100%  0  0  N 193  '"Y  0  in this work  ^"C00CH  3  0  ^ 194  100%  0  0  0  in this work  N  "  0  c i s means t h a t t h e a l k y l and t h e methyl groups a r e c i s t o each o t h e r . The f o l l o w i n g g e n e r a l remarks c a n be  based on t h e r e s u l t s shown  i n T a b l e IV: - Trans- p y r a z o l i n e s tend t o g i v e more c y c l o p r o p a n e p r o d u c t s than t h e c i s - ones. - The b u l k i e r t h e a l k y l group a t C-4, t h e more c y c l o p r o p a n e w i l l form.  The extreme case i s t h e t e r t - b u t y l group when no o l e f i n  f o r m a t i o n has been observed.  - 63 -  - The  s t e r e o s e l e c t i v i t y of cyclopropane  formation i s higher i n  the case o f t r a n s - p y r a z o l i n e s . - The  o l e f i n f o r m a t i o n 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_.  (c)  findings.  Deuterium k i n e t i c i s o t o p e e f f e c t o f o l e f i n f o r m a t i o n , and p r o d u c t  The i n D2O 89%  s t u d i e s on  kinetic  3-methyl-3-carbalkoxy-l-pyrazolines-4d^  c a t a l y t i c r e d u c t i o n o f sodium (E)-g-bromomethacrylate w i t h  D2  and t h e subsequent work-up p r o v i d e d an a c i d m i x t u r e c o n t a i n i n g  ( E ) - , 9%  (Z)-methacrylic acid-3d  1  and  2% m e t h a c r y l i c a c i d .  m i x t u r e was  converted  t o the c o r r e s p o n d i n g  f o r product  studies.  F u r t h e r e x p e r i m e n t s i n d i c a t e d t h a t i t was  This  p y r a z o l i n e s and used  up possible  t o o b t a i n ( E ) - m e t h a c r y l i c a c i d - 3 d ^ f r e e o f the ( Z ) - i s o m e r by c h a n g i n g reaction conditions.  U n f o r t u n a t e l y the p r o c e s s became so slow  cumbersome t h a t the a v a i l a b l e equipment seemed i n a d e q u a t e t i o n o f the r e q u i r e d 3-4g  f o r prepara-  ofpyrazoline for kinetic studies.  Most o f the mono-deuterated m e t h a c r y l i c a c i d u s e d i n t h i s was  and  t h e z-isomer and was made by t h e method o f T o w e l l s  i s o m e r when r e a c t e d w i t h diazomethane g i v e s carbalkoxy-l-pyrazolines-4d  1  (68).  study This  trans-3-methyl-3-  (217).  Perhaps the b e s t p r o o f o f the s t e r e o s p e c i f i c o l e f i n f o r m a t i o n  was  o b t a i n e d from the p r o d u c t d i s t r i b u t i o n s o f t r a n s - 5 - m e t h y l - 3 - c a r b o m e t h o x y l - p y r a z o l i n e - 4 d j 199 and 210.  trans-3-methyl-3-carbethoxy-l-pyrazoline-4d^  <  - K  /  C  C  0  H  0  C  H  " 9  3  O  O  C  H  3  - A ^ C H - ^ H  j  +  C  H  CH  A C O O C H 3  A  |  3  +  CH  3  ^ CH  J95  J96  J97  4.5%  64.4  14.3%  CH,  ^  +  H  3  CH,  COOCH3  3  H  3  COOCH 1 9 8 1 6 . 4 %  H D  i  > I  X  N  f  C  0  CH  0  3  C  H  3  COOCH  A  ^CH=CD—CH C H  )fcOOCH  3  +  ^ - f  3  CH  200  3  202 D  COOCH  3  3  H  ^COOCH  3  H ^ C H  CH,  3  CH  3  C H = C H — CD 2  3 201_  203.  35%  69.3%  C  H  C H  3  CHD COOCH ^04 9.7%  3  D  205  COOCH-  1 7 . 7 %  3  COOEt  r ^ .-  COOB  A COOEt  - A *>- C H p — C H — CH  NT  CH  186  CH  3  206 4,2%  3  CH,  COOEt  CH,  CH  H  CH  H  COOEt  M  3  208  207 70.4  3  209 13.0%  12.6%  D H iCOOEt CH,  A  COOEt  COOEt I -CH =CD—CH  F  2  N  CH  210  211  CH:  3  213_  H D COOEt I  COOCH:  7  C H , = C H — CD CH  H  CH,  CH  COOEt  D  CH D Z  3  CH,  212  214  3.6%  74.0%  3  CH  3  COOEt  215  216  8.9%  13.2%  - 66 -  The s u b s t a n t i a l decrease  i n t h e amount o f d e u t e r a t e d a n g e l a t e s can be  b e s t e x p l a i n e d by t h e scheme o f c o n c e r t e d o l e f i n  formation  H  H  COOR  CH D 2  CH,  COOR  218  COOR  HX  CH  X  D  3  COOR  219  The f o r m a t i o n o f a n g e l a t e s a r e r e t a r d e d by t h e " r e l a t i v e l y s m a l l " H i s o t o p e e f f e c t ^— = 1.74 f o r t h e methyl e s t e r and D - 1.6 f o r t h e e t h y l e s t e r , w h i l e t h e f o r m a t i o n o f t i g l a t e s i s D k H s u b j e c t e d t o a secondary a - k i n e t i c i s o t o p e e f f e c t , T — = 1.1 f o r both D esters. k  p r i m a r y deuterium k  (d)  B , y - o l e f i n formation.  The t h e r m o l y s i s o f  trans-3-methyl-3-carbomethoxy-l-pyrazoline-  4d^ p r o v i d e d 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 t h e i s o l a t e d compound showed t h a t i t c o n s i s t e d o f two components 200, 201. T h e i r f o r m a t i o n can be e n v i s a g e d as f o l l o w s  - 67 -  D  /  CCX)CH  C H = C — CH \  3  2  200  CH,  H C00CH. I / CH?—C — CD \ C00CH 201  The n.m.r. spectrum a l s o i n d i c a t e d t h a t amounts as a n t i c i p a t e d deuterium isotope  i f  3  200 was p r e s e n t i n l a r g e r  i t s f o r m a t i o n was slowed by a secondary  e f f e c t (the n.m.r. spectrum was n o t good enough  t o measure t h e 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  H e f f e c t f o r b o t h was found t o be r — = 1.4. D k  k i n e t i c isotope  Similar  k  r e s u l t s were o b t a i n e d from t h e t r a n s - 3 - m e t h y l - 3 - c a r b e t h o x y - l - p y r a z o l i n e H ; 7— = 1.3. k  4d  1  K  The f a c t t h a t  3 , Y - o l e f i n i c e s t e r s do n o t appear i n  D  the d e c o m p o s i t i o n p r o d u c t m i x t u r e s o f a l l p y r a z o l i n e s , a l t h o u g h t h e i r structure  e l e c t r o n i c a l l y i s v e r y s i m i l a r , may i n d i c a t e t h a t t h e o n l y  governing f a c t o r i n t h e i r formation i s the stereochemistry, i . e . , the g e o m e t r i c a l p o s i t i o n o f t h e C-4 hydrogen i n t h e 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 t h a t 193 and 194 gave o n l y  cyclopropanes  on t h e r m o l y s i s w i t h f u l l r e t e n t i o n o f t h e s t e r e o c h e m i s t r y o f t h e 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 p h o t o l y s e s o f b o t h  p y r a z o l i n e s gave r i s e t o t h e same c y c l o p r o p a n e  p r o d u c t s as d i d t h e  thermolyses.  r\4 C  H  3  COOCH 194  A or hi/ or  N  \/  COOCH:  P h C O + hz/ 2  3  221  These r e s u l t s e x c l u d e d t h e p o s s i b i l i t y o f a symmetry c o n t r o l l e d c o n c e r t e d r e a c t i o n on t h e grounds t h a t d i r e c t p h o t o l y s i s s h o u l d have g i v e n products w i t h opposite stereochemistry w i t h respect t o t h 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 r e p o r t e d by Berson and O l i n  - 69 -  (53) and Schmit (65) a l t h o u g h I n a g a k i and F u k u i  (66) c o u l d e x p l a i n  these f i n d i n g s by u s i n g t h e o r b i t a l i n t e r a c t i o n t h e o r y . The two r e m a i n i n g m e c h a n i s t i c p o s s i b i l i t i e s a r e t h e e n e r g e t i c a l l y c o n c e r t e d symmetry d i s a l l o w e d and d i r a d i c a l pathways. The thermal d e c o m p o s i t i o n  o f c i s - and trans-3-methy1-carbomethoxy-  1 - p y r a z o l i n e - d ^ p r o v i d e d t h e same m i x t u r e ; 1:1 o f 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  results  w i t h t h o s e o f t h e r m o l y s i s c o n c e r n i n g t h e r a t i o o f t h e two isomers i n the deutero c y c l o p r o p a n e p r o d u c t s , w h i l e t h e d i r e c t p h o t o l y s i s exhibited a s l i g h t ^5% r e t e n t i o n .  T h i s means t h a t t h e 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 n o t c o n s i d e r a b l y d i f f e r e n t from t h e 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 . processes  In f a c t , t h e r e a r e two  competing w i t h each o t h e r , r o t a t i o n and r i n g c l o s u r e . I t  seems t h a t t h e bond r o t a t i o n i s f a s t e r .  In t h e case o f s e n s i t i z e d  p h o t o l y s i s t h e t r i p l e t d i r a d i c a l i s produced.  Its ring closure i s  - 70 -  d e l a y e d by t h e r e l a t i v e l y slow p r o c e s s 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 t h e r e a c t i o n i s possibly.,  the following:  c  pyrazoline cyclopropane  Reaction coordinat The increases  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 with the bulkiness  formation  o f t h e 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 t h a t t h e r e 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 b u l k y  substituents  h i n d e r o r r u l e out r o t a t i o n e n t i r e l y even i f t h e t h e r m o d y n a m i c a l l y  - 71 -  l e s s f a v o r a b l e c y c l o p r o p a n e isomer f o r m a t i o n has t o t a k e p l a c e . I t i s c l a i m e d by s e v e r a l a u t h o r s  (23,34,36) t h a t s i m u l t a n e o u s  r u p t u r e o f t h e two C-N bonds o c c u r s d u r i n g t h e d e c o m p o s i t i o n o f 1-pyrazolines.  However, t h e i n f e r e n c e s about t h e n a t u r e o f t h e bond  cleavage, whether i t i s c o n c e r t e d o r s t e p w i s e  (10.29), have been made  from i n d i r e c t e v i d e n c e , m a i n l y from d e u t e r i u m k i n e t i c i s o t o p e e f f e c t s and p r o d u c t s t u d i e s done m o s t l y on more o r l e s s s y m m e t r i c a l l y subs 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 t h e r e a c t a n t such t h a t t h e r u p t u r e o f t h e C-N bonds a r e no l o n g e r e q u i v a l e n t i n t h e t r a n s i t i o n s t a t e , i . e . , one o f t h e two C-N bonds i s b e i n g broken t o a l a r g e r degree t h a n t h e o t h e r .  Unfortu-  n a t e l y , our r e s u l t s , which w i l l be d i s c u s s e d , do n o t a l l o w one t o draw any d e f i n i t e c o n c l u s i o n about t h e bond  breakage.  The f a c t t h a t 193 and 194 gave o n l y c y c l o p r o p a n e s  upon  d e c o m p o s i t i o n made i t p o s s i b l e t o determine k i n e t i c i s o t o p e e f f e c t s f o r cyclopropane  f o r m a t i o n c l e a r l y . The r a t e measurements on c i s -tertand t r a n s - 3 - m e t h y l - 4 - / - b u t y l - 3 - c a r b o m e t h o x y - l - p y r a z o l i n e - 4 - d p r o v i d e d k ' k r — = 1.093 ± 0.0078 and . J i = 1.069 ± 0.024 r e s p e c t i v e l y . Similar results 1  1  were o b t a i n e d from the k i n e t i c s t u d i e s done on t r a n s - 3 - m e t h y l - 3 H c a r b o m e t h o x y - l - p y r a z o l i n e - 4 - d , — = 1.06 and t r a n s - 3 - m e t h y l - 3 K  1  are i n l i n e w i t h those o b t a i n e d by McGreer and M a s t e r s r^- = 1.20 f o r D two d e u t e r i o n s a l t h o u g h a b i t lower than Crawford's 13%. k  - 72 -  The  f l u c t u a t i o n s i n the values o f t t - f o r cyclopropane D  formation  K  can be a t t r i b u t e d t o t h e e r r o r made i n t h e k i n e t i c measurements as w e l l as i n t h e gas chromatographic ponents o f t h e p r o d u c t  a n a l y s i s o f t h e i n d i v i d u a l com-  mixture.  The r e v e r s e k i n e t i c i s o t o p e e f f e c t c a l c u l a t e d f o r c y c l o p r o p a n e H f o r m a t i o n (V— = 0 . 7 1 ) i n t h e t h e r m a l d e c o m p o s i t i o n D k  2,3-diazabicyclo(3.3.0)oct-2-ene  o f 1-carbomethoxy-  and i t s analogous-5d^ means t h a t t h e  r e a c t i o n i s n o t slowed down b u t a c c e l e r a t e d by d e u t e r i u m other r e s u l t s .  contrary t o  An a c c e p t a b l e 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 t o g i v e a t t h i s t i m e u n l e s s we assume t h a t t h e f o r m a t i o n o f the bicyclo(3.1.0)hexane  d e r i v a t i v e 165 i s f a v o r e d on account o f  the s m a l l e r s t e r i c requirement  f o r deuterium.  ( S i n c e hydrogen and  deuterium have v e r y s i m i l a r s i z e s , b u t t h e lower zero p o i n t energy o f C-D i m p l i e s a s m a l l e r a m p l i t u d e f o r t h e v i b r a t i o n l e a d i n g t o a s m a l l e r s t e r i c requirement.)  A l t h o u g h i t i s d i f f i c u l t t o s i n g l e out one o f t h e  s e v e r a l , rather c o n t r o v e r s i a l explanations concerning the o r i g i n o f t h e secondary  8 - k i n e t i c i s o t o p e e f f e c t and use i t as a base t o e l u c i d a t e  t h e measured e f f e c t s , t h e most o f t e n encountered concept  of  hyperconjugation.  argument a p p l i e s t h e  Hoffman (37,38) has shown t h a t t h e  h y p e r c o n j u g a t i o n p l a y s an i m p o r t a n t r o l e i n t h e s t a b i l i z a t i o n o f singlet trimethylene species.  Because o f h y p e r c o n j u g a t i o n , t h e  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 t h e C-H bond and t h e C-D bond i n t h e 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 t h e ground s t a t e so t h e r e a c t i o n i s slowed by s u b s t i t u t i o n o f d e u t e r i u m  f o r hydrogen.  - 73 -  S i m i l a r l y , Crawford and M i s h r a a t t r i b u t e d the observed k i n e t i c i s o t o p e effect to hyperconjugation.  The  slower r a t e of decomposition  of  4 - d e u t e r a t e d m o n o c y c l i c p y r a z o l i n e s i s e x p e r i m e n t a l f a c t - i t does n o t m a t t e r 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  v a r i o u s p o s s i b l e causes ( i n d u c t i v e , s t e r i c , h y p e r c o n j u g a t i v e e f f e c t s , bond s t r e n g t h changes w i t h h y b r i d i z a t i o n ) .  VI.  Photolysis of pyrazolines., 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 t h e r m a l a d d i t i o n o f d i a z o -  methane t o a carbon-carbon  double bond shows a l l the s t e r e o c h e m i c a l  p r o p e r t i e s o f a c o n c e r t e d symmetry a l l o w e d p r o c e s s and t h e o r y s u p p o r t s t h i s view.  There are a few examples o f t h e r m a l l y induced  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 . i s a photochemical  reversal  A much more f r e q u e n t o b s e r v a t i o n  c y c l o r e v e r s i o n . Such a p r o c e s s would not  be  expected t o be symmetry a l l o w e d , however a l l s t e r e o c h e m i c a l 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 t o 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 . photodecomposition  Such s t e r e o s p e c i f i c i t y was not found i n the 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 o f t r a n s - 3 - m e t h y l - 3 - c a r b e t h o x y - 1 - p y r a z o l i n e 4 d j , 210 p r o v i d e d e t h y l m e t h a c r y l a t e - 3 d ^  i n 14.2% y i e l d .  The n.m.r.  spectrum o f the i s o l a t e d compound showed 75% r e t e n t i o n w i t h r e s p e c t t o t h e  - 74 -  starting material.  In o r d e r 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 p l a c e d u r i n g 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 m e t h a c r y l a t e - 3 - d j was p h o t o l y s e d f o r 8 hours p y r a z o l i n e ) and i t s n.m.r. spectrum  recorded.  (same time as f o r t h e Another sample c o n t a i n -  i n g d e u t e r a t e d methyl m e t h a c r y l a t e and c i s - 3 - m e t h y 1 - 4 - t e r t - b u t y l - 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 h o u r s . o f both compounds showed p r a c t i c a l l y no changes. suggest t h a t t h e carbon-carbon  The n.m.r. s p e c t r a  These  experiments  bond c l e a v a g e o c c u r s by a mechanism other  than 1 , 3 - d i p o l a r c y c l o r e v e r s i o n .  A l t h o u g h t h e r e i s no i n f o r m a t i o n  a v a i l a b l e t o date on t h e m e c h a n i s t i c d e t a i l s o f carbon-carbon c l e a v a g e i t most l i k e l y t a k e s p l a c e by a n o n - c o n c e r t e d  bond  way.  R e s u l t s can be b e s t e x p l a i n e d by t h e i n t e r m e d i a c y o f 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 f o r m a t i o n .  D\ /C00CH -CH, ^C—Cf H '^CH, 223 3 2  3  „  t H  C—c.  /COOCH -CH 2  3  CH,  H\ ^COOCH - C H , >—C^ 2 3 D *^CH, 225 3  XOOCH--CH, ^C=C^ LT CH, 2  74%  26%  224  226  * The e t h y l e s t e r was n o t a v a i l a b l e .  3  -16-  SUMMARY  Many authors have pointed out (21,22,23) that the stereochemical factors present i n the pyrazoline play an important r o l e i n determining both the product d i s t r i b u t i o n and product stereochemistry. to evaluate the stereochemical  In order  e f f e c t s brought about by d i f f e r e n t  substituents the pyrazoline r i n g i t s e l f should be s c r u t i n i z e d . It has been known for quite some time that the structure o f the pyrazoline ring, l i k e that o f cyclopentene, resembles a folded envelope (52). H  v  73a  T  73 b  The n.m.r. studies indicated that the pyrazoline structure i s quite mobile; i t undergoes rapid conformational temperature.  interconversion at room  However, McGreer et_ al_. (52) postulated that c e r t a i n  substituted pyrazolines may have a preference  for one conformation.  They have also calculated angle ex's for monocyclic pyrazolines using J . and J CIS  "CTcHlS  coupling constants  and the Karplus equation.  On the  -  76  -  basis of these stereochemical facts about pyrazolines and the stereochemistry of o l e f i n i c products they put forward a suggestion concerning the mechanism of o l e f i n formation. According to the mechanism proposed the o l e f i n formation often takes place from the less stable conformation.  Consequentl  i t seemed evident that i f conformational interconversion was a prerequisite f o r o l e f i n formation the introduction of a suitably bulky substituent which could prevent that would rule out the o l e f i n forming reaction.  Inspection of Table V I  reveals that the t e r t - b u t y l group  placed on C-4 not only eliminated the o l e f i n forming pathway but gave r i s e to only one cyclopropane product.  On the other hand the incorpora-  t i o n of the pyrazoline ring i n a b i c y c l i c system led to 164, 2 2 7 , 2 2 8 which produced large amounts of o l e f i n i c products upon thermolysis, Table V I I .  Considering these r e s u l t s one can come to the conclusion  that i n these b i c y c l i c systems the atoms, e s p e c i a l l y the C-5  hydrogens,  are held i n such a geometrical arrangement which f a c i l i t a t e s o l e f i n formation. The findings presented i n Table V  and Table V I  i n accord with  the deuterium k i n e t i c isotope effects for o l e f i n formation corroborate McGreer's proposal that the o l e f i n forming process involved i n the thermal decomposition of 3-carbomethoxy-1-pyrazolines  i s a concerted  reaction. Another interesting feature of the o l e f i n forming reaction i s that the position of the carbomethoxy group may also affect the o l e f i n cyclopropane r a t i o .  Table  V I indicates that the cis-pyrazolines tend  - 77 -  t o g i v e a h i g h e r p e r c e n t a g e o f o l e f i n i c p r o d u c t s t h a n the t r a n s ones.  Considering  corresponding  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 t h e carbomethoxy group i s under the p y r a z o l i n e r i n g . i s conceivable  t h a t t h e e s t e r group i n t h i s p o s i t i o n might  It  facilitate  o l e f i n f o r m a t i o n more than i n the e q u a t o r i a l p o s i t i o n . The  p r o d u c t s t u d i e s o f c i s - and  carbomethoxy-l-pyrazolines  trans-3-methyl-4-tert-butyl-3-  and c i s - and  trans-3-methyl-3-carbomethoxy-  l - p y r a z o l i n e s - 4 d ^ p r o v i d e d an unambiguous e v i d e n c e f o r the mediacy o f a d i r a d i c a l i n t h e c y c l o p r o p a n e forming intermediate  reactions.  The  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 b e f o r e r i n g c l o s u r e o c c u r s  i n the absence o f  s t e r i c h i n d r a n c e caused by s u b s t i t u e n t s .  TABLE V I I  The  inter-  coupling constants  and d e c o m p o s i t i o n p r o d u c t s  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  O(trans) J(cis)  _N  H  8.5 Hz  //  •N  (trans)  H  COOCH  3.3Hz  DECOMPOSITION PRODUCTS (at 131°)  olefin/3,7 cycloprop. olefin a, (3  10.2%  19.6%  70.0%  7.5%  34.3%  58.1%  3  (cis) 164  D //  N  COOCH  3  180  . N  4  6.3Hz  7.5Hz  4.5%  15.3%  80.2%  8.5Hz  4.5 Hz  4.2%  18.6%  77.2%  COOCH, 227  N if COOCH: 228  -7?-  EXPERIMENTAL  I.  General  statements  B o i l i n g p o i n t s are u n c o r r e c t e d .  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 a p p a r a t u s . 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 P e r k i n - E l m e r 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 r e c o r d e d on a P e r k i n - E l m e r Model 202  Spectrophotometer. 60 MHz  n u c l e a r magnetic  V a r i a n A s s o c i a t e s Model A-60 n u c l e a r magnetic  resonance  s p e c t r a were r e c o r d e d on a  Spectrometer by M i s s P. Watson.  100  MHz  resonance s p e c t r a were r e c o r d e d on a V a r i a n A s s o c i a t e s  Model XL-100 Spectrometer by Dr. E. K o s t e r . The a n a l y s e s were done on an Aerograph Model A-90-P and  an  Aerograph Model A-90-P3. The e l e m e n t a l m i c r o a n a l y s e s were performed by Mr. P. o f t h i s Department.  Borda  - 80 -  II.  Preparation of  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 e t h e r s o l u t i o n was a l l o w e d t o s t a n d i n a c o l d room f o r s e v e r a l h o u r s .  A f t e r evaporating the  e t h e r , t h e 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 m o d i f i e d b u l b - t o bulb d i s t i l l a t i o n apparatus.  Bath temp.:  The p r o d u c t was a c l e a r l i q u i d  50-55° (0.03 - 0.05 mm).  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 t o t h o s e r e p o r t e d by M a s t e r s [ 6 1 ] . Anal. Calcd. f o r C H N : Found:  C, 55.04; H, 6.42,  C, 55.13; H, 6.57.  I t was decomposted by h e a t i n g a t 120°C f o r t h r e e  III. Preparation of  3-tert-butyl-3-carbomethoxy-1-pyrazoline  (a) P r e p a r a t i o n o f m e t h y l  2-tert-butylpropen-2-oate.  The f o l l o w i n g e q u a t i o n s i l l u s t r a t e  t h e s y n t h e t i c scheme;  230  •KMnQ.—H  C—CH:  229 H  II  4  0  C — COOCH  231 H  3  t  CCH=C—COOCH3 160  —  MeMgl-*- - 4 —  CH N 2  C—COOH  0  2  3  C—C00CH 3  OH  232  2  orMeOH r n C H C l  II  CH  0  2  hours.  SO CI-  2  - 81 -  1.  3,3-Dimethyl-2-oxobutanoic A 120 g o f KMn0  4  a c i d 230_ ( 7 0 ) .  and 40 g o f NaOH were d i s s o l v e d i n 3 l i t r e  o f water and 40 g o f p i n a c o l o n e was added dropwise o v e r 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 e x o t h e r m i c 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 a t room t e m p e r a t u r e ,  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 , t h e aqueous s o l u t i o n a c i d i f i e d w i t h 260 ml c c HC1, and t h e a c i d e x t r a c t e d w i t h t h r e e 200 ml p o r t i o n s o f e t h e r .  The e t h e r a l e x t r a c t was d r i e d  (MgSO^),  c o n c e n t r a t e d g i v i n g 46 g (88.5%) which was used w i t h o u t f u r t h e r p u r i f i c a t i o n ; n.m.r. (CC1 ) T 1.63 ( s , 1, COOH), T 8.76 ( s , 9, 4  (CH ) C). 3  2.  3  M e t h y l 3,3-dimethyl-2-oxobutanoate  231  The e s t e r i f i c a t i o n o f t h e a c i d i n i t i a l l y was a c c o m p l i s h e d w i t h CH^N^ i n e t h e r s o l u t i o n .  A f t e r d r y i n g o v e r MgSO^, t h e  e t h e r was e v a p o r a t e d and t h e p r o d u c t d i s t i l l e d : 160.1° (755 mm); n  D 1.4082; i r 1710 cm  b.p.:  83-85° (52 mm),  ( e s t e r and ketone C=0);  n.m.r. (CC1 ) x 6.18 (s , 3, C00CH_ ); 8.77 (s , 9, (CH ) C ) . 4  3  Anal. Calcd. f o r C H^Cy  3  C, 58.30; H, 8.33.  Found:  C, 58.38; H, 8.55.  3.  Methyl 2,3,3-trimethyl-2-hydroxybutanoate  232  M e t h y l magnesium i o d i d e made from 2.6 g o f Mg t u r n i n g s and 14.5 g o f CH ~I i n 80 ml o f e t h e r was added s l o w l y t o 14.4 g 3  of  231 i n 50 ml d r y e t h e r which was c o o l e d i n a d r y i c e - a c e t o n e  - 82 -  ACETONE b a t h .  The e x o t h e r m i c 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 t o 50 ml i c e - c o l d 10% HC1.  The o r g a n i c phase  was s e p a r a t e d , washed w i t h ^ 0 and 5% NaHCO^, d r i e d o v e r MgSO^, c o n c e n t r a t e d 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 b.p.: 75-77° (20 mm);  n °D  1.4295; i r 3550 cm"  2  1  liquid;  (OH), 1735 cm"  1  (CO e s t e r ) ; n.m.r. (CC1 ) T 6.22 (*>, 3, C00CH ), 8.71 ( s , 3, 4  3  CH_ ), 9.04 ( s , 9, ( C H ) C ) ; t h e presence o f OH was v e r i f i e d by 3  3  3  a d d i n g D 2 O t o t h e sample. A n a l . C a l c d . 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. To a s t i r r e d s o l u t i o n o f 11.6 g o f  160 232 , 12 g o f p y r i d i n e  and 30 ml o f t o l u e n e , 10 g o f t h i o n y l c h l o r i d e was added o v e r a p e r i o d o f 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  m i x t u r e was r e f l u x e d and s t i r r e d f o r 5 h o u r s .  The h e a t i n g was  d i s c o n t i n u e d and when t h e temperature i n t h e f l a s k dropped t o 50-52°, 100 ml o f p e t r o l e u m e t h e r was added s l o w l y . m i x t u r e was a l l o w e d t o c o o l t o room temperature.  The dark  The s o l i d i f i e d  b y p r o d u c t was f i l t e r e d o f f and washed w i t h 50 ml o f p e t r o l e u m ether. NaHC0  3  The f i l t r a t e washed w i t h 50 ml o f w a t e r , 50 ml o f 5% s o l u t i o n and 50 ml o f water.  A f t e r d r y i n g (MgS0 ) t h e 4  p e t r o l e u m e t h e r was removed by f l a s h e v a p o r a t i o n and t h e remaini n g dark l i q u i d was d i s t i l l e d t h r o u g h a 2 i n c h V i g r e u x column.  - 83 -  (During this d i s t i l l a t i o n extremely bad smelling gases evolved.) The f r a c t i o n coming between 143-150° was c o l l e c t e d and r e d i s t i l l e d , 20  giving 4.2 g (40.5 %) o f 160 1725 cm"  ; b.p.: 146.8°; n  (C=0 ester), 1620 cm"  1  1  D 1.4273; i r  (C=C); n.m.r. (CC1 ) x 4.10 4  (s, 1, H c i s to the ester group), 4.50 (s, 1, H), 6.30 (s, 3, C00CH_ ), 8.82 ( s , 9, (CHj) C ) . 3  3  Anal. Calcd. f o r 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 3,3-dimethyl-2-methylene  butanoate i n ether solution.  to methyl  After 48 hours  of standing at room temperature, the ether was flash evaporated and the  crude pyrazoline p u r i f i e d 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: n  20  -1 D 1.4673; uv max (95% C ^ O H ) 328 my; i r 1730 cm (ester C=0),  1560, 1568 cm"  1  (s,  bath temp. 65-70°, 0.05 mm;  (N=N); n.m.r. (CC1 ) T 5.00 - 6.00 (m, 2, C-5), 6.35 4  3, C00CH_ ), 8.14 - 8.60 (m, 2, C-4), 9.96 ( s , 3  9, ( C H ^ C ) ,  (more  information on n.m.r. spectrum of 156 can be found on page 48. Anal. Calcd. for C„HL„N 0,,: o  H, 8.45.  C, 58.65; H, 8.76.  Found:  C, 58.50;  - 84  IV.  Product the  studies of  3-tert-butyl-3-carbomethoxy-1-pyrazoline  s y n t h e s i s o f methyl  (a)  Thermal  -  (Z)-2-tert-butylbuten-Z-oate.  decomposition  of  3-tert-buty1-3-carbomethoxy-1-  pyrazoline. In  a 5 ml  round  pyrazoline  was  liquid  analysed  was  P o l y m-phenyl c o l u m n temp. the  gas  heated  N  c=c / \  CH  3  158  t  2 0  D  8.41  160°  equipped  with  f o r 4 hours.  The  6' by 1/4"  a  ( 5 - r i n g ) on Two  ( d , 3,  product,  chromosorb  P;  f l o w r a t e 80  components were s e p a r a t e d On  1 g  of  a yellowish  and  ml  He/min,  collected  t h e b a s i s o f t h e i r n.m.r. s p e c t r a to  off  the  them.  /  C00CH  i r 1730  - 4.68  a condenser,  d i a m e t e r copper column packed w i t h  3  ( Z ) - 2 - t e r t - b u t y l b u t e n - 2 - o a t e (158),  1.4331;  4.30  flask  s t r u c t u r e s were a s s i g n e d  H  n  on  ether 135°.  at  chromatograph.  following  Methyl  bottom  ( q , 1,  J=7.0 Hz,  cm"  (ester  1  J=6.4 Hz, CH_ ) , 8.93 3  C=0),  1635  olefinic), ( s , 9,  b.p.:164.7° cm" 6.36  (754  mm);  (C=C); n.m.r.  1  ( s , 3,  (CH^C).  C00CH ), 3  (CC1 ) 4  20%  - 85 -  Anal. Calcd. f o r C H,  °  H 9  1 6  : 2  C, 69.19; H,  10.32.  Found:  C,  69.20;  10.22. The  g e o m e t r i c assignment was  by F r a s e r proton  ( 7 1 ) , McGreer (17,52),  based on p r e v i o u s o b s e r v a t i o n made and  i n t h i s work, t h a t the o l e f i n i c  s i g n a l s o f JZ o l e f i n i c e s t e r s o f g e n e r a l f o r m u l a :  appear between T 3-4  which i s somewhat lower t h a n those  isomers at T 4-5  t o the d e s h i e l d i n g e f f e c t  T h i s i s supported  due  by the f a c t , as i t was  t h a t the b u l k y t e r t - b u t y l conversion  l^-CH^CR^COOCH^ o f the E  o f the e s t e r c a r b o n y l .  p o i n t e d out i n the D i s c u s s i o n ,  group does not a l l o w c o n f o r m a t i o n a l  inter-  and the o l e f i n i s t h u s b e i n g formed s t e r e o s p e c i f i c a l l y  t h a t o n l y the Z isomer can  form.  S e v e r a l a t t e m p t s were made t o o b t a i n 158 by a way from p y r a z o l i n e .  so  I t seemed r e a s o n a b l e  other  than  t o f o l l o w a s y n t h e t i c sequence  s i m i l a r t o the p r e p a r a t i o n o f 160, but i n s t e a d o f a d d i t i o n , r e d u c t i o n took p l a c e when ethylmagnesium was  bromide used. H  —I I  C-COOCH, || 6  E  0  231_  t  M  g  B  r  >, —j I  C-C00CH, + | 3  CH  OH  233  =CH2  2  I t i s known t h a t a l k y l l i t h i u m compounds do not have the p r o p e r t i e s o f G r i g n a r d r e a g e n t s but they add c a r b o n y l groups. L i E t , H ^  C - C O O C H ,  I  0  231  3  2  less s e l e c t i v e l y  reductive to  0 ,  HCl -COOCH3 OH  234  - 86 -  I n t o a 250 ml t h r e e necked round bottom f l a s k equipped w i t h a m e c h a n i c a l s t i r r e r , a r u b b e r septum, a vent w i t h a C a C ^ d r y i n g tube and a gas i n l e t t u b e , 3.6 g o f m e t h y l  3,3-dimethyl-2-oxybutanoate  and 40 ml o f e t h e r ( d i s t i l l e d from CaH ) were p l a c e d . 2  The f l a s k was  c o o l e d i n a DRY ICE - p r o p a n o l b a t h and purged w i t h d r y o x y g e n - f r e e n i t r o g e n f o r 10 m i n u t e s .  To t h i s s o l u t i o n 45 ml (about 10% e x c e s s ]  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 m i x t u r e  was a l l o w e d t o come t o room t e m p e r a t u r e w h i l e t h e s t i r r i n g was cont i n u e d , and poured i n t o 130 ml o f i c e - c o l d 10% HC1.  The o r g a n i c l a y e r  was s e p a r a t e d , washed w i t h 30 ml 5% NaHCO., s o l u t i o n and 50 ml w a t e r . A f t e r d r y i n g o v e r MgSO^, t h e e t h e r and benzene were removed by f l a s h e v a p o r a t i o n and t h e 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 o v e r between 55-75°, 1.5 mm, was c o l l e c t e d . contained  It  234 w i t h some o t h e r i m p u r i t i e s , y i e l d 18 g ^ 41%; n.m.r.  (CC1 ) T 6.14 ( s , 3, C 0 0 C H ) , 6.90 ( s , 1, OH), 8.0 - 8.5 (m, 2, -CH_ ) , 4  3  8.96 ( s , 9 (CH )„C). 3  2  U n s t a b l e a t room t e m p e r a t u r e .  The same d e h y d r a t i o n p r o c e d u r e as was used t o p r e p a r e 160, was used t o o b t a 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 w i t h t h o s e o b t a i n e d from 1_56 upon t h e r m o l y s i s . The gas c h r o m a t o g r a p h i c a n a l y s i s o f t h e c r u d e p r o d u c t i n d i c a t e d t h e absence o f t h e E i s o m e r .  E q u i l i b r i u m o f Z_ o l e f i n a l s o f a i l e d t o  produce t h e E_ isomer. The o t h e r p r o d u c t  159 i s 1 - t e r t - b u t y 1 - 1 - c a r b o m e t h o x y  20 -1 b.p. : 154.6°; n D 1.4379; i r 3100 and 3040 cm  cyclopropane,  (cyclopropane hydrogens),  - 87 -  1750 cm  ( e s t e r C=0); n.m.r. (CC1 ) T 6.48 ( s , 3, C00CH_ ), 9.02 ( s , 4  3  9+2, ( C H ) C + CH-CH ( c i s t o the carbomethoxy), 3  3  Anal. Calcd. f o r  C  H 9  0 1  6  : 2  C  9.21 (m, 2, CH-CH  > 69.19; H, 10.33.  Found:  (trans)).  C, 69.55;  H, 10.49.  (b)  Direct photolysis 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 m l . i s o p e n t a n e and p h o t o l y s e d i n a Rayonet P h o t o c h e m i c a l R e a c t o r u s i n g 3100 A lamps u n t i l t h e sample showed no t y p i c a l N=N bond a b s o r p t i o n i n t h e uv. The s o l v e n t was e v a p o r a t e d and t h e p r o d u c t m i x t u r e was a n a l y z e d by gas chromatography.  (The same column and c o 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  160 C H  2  =C  COOCH  3  158 CH  159  (c)  3  products.)  6.1 % ret time : 7.2 min 5,2%  COOCH3  COOCH3  88.6%  10.4  14.4  Sensitized photolysis o f 3-tert-butyl-3-carbomethoxy-lpyrazoline.  F i v e grams o f benzophenone and 0.5 g o f p y r a z o l i n e were d i s s o l v e d i n 50 ml o f i s o p e n t a n e ( s a t u r a t e d s o l u t i o n o f 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 P h o t o c h e m i c a l R e a c t o r f o r 24 hours  u s i n g 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 o f t h e e v a p o r a t i o n , 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 p r o d u c t had been o b t a i n e d which was  found t o be o n l y the c y c l o p r o p a n e p r o d u c t  159.;  V.  Preparation of  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)oct2-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 of  238.  chosen f o r t h e p r e p a r a t i o n  - 89 -  1.  1-Cyclopentenecarboxylic acid. One gram o f NaBH^ was d i s s o l v e d i n 40 ml o f methanol  c o n t a i n i n g 1 ml o f NaOH s o l u t i o n a t -2°C. To t h i s  turbid  s o l u t i o n 15.5 g o f 2 - c a r b o e t h o x y c y c l o p e n t a n o n e ; was added w h i l e t h e temperature was kept a t 0°C.  The m i x t u r e was s t i r r e d  o v e r n i g h t a t room temperature and t h e n 200 ml o f w a t e r was added and t h e 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 w i t h 10% HC1 t o pH^3. The p r o d u c t was e x t r a c t e d w i t h c h l o r o f o r m , washed w i t h 10% Na2C0  3  and w a t e r , and d r i e d o v e r MgSO^.  Evaporation o f chloro-  form y i e l d e d 16.0 g o f crude p r o d u c t which was d e h y d r a t e d w i t h 30 g o f t r i p h e n y l p h o s p h i n e i n a s o l u t i o n o f 150 ml d r y C C l ^ . (See page 104.)  - 90 -  The crude p r o d u c t was p u r i f i e d by vacuum d i s t i l l a t i o n . was:  10.5 g ( 7 0 . 5 % ) , b.p.:  1622 cm"  92-93° (25 mm); i r 1715 cm"  Yield ( e s t e r C=0)  1  (C=C).  1  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 o f H 0 and 20 ml o f methanol and k e p t a t 70°C f o r 24 h o u r s .  Then  2  i t was d i l u t e d w i t h 100 ml o f H^O and a c i d i f i e d w i t h 40 ml o f 10% HC1.  The f r e e  a c i d was e x t r a c t e d t w i c e w i t h 50 ml o f e t h e r .  The e t h e r e x t r a c t s were combined  and d r i e d o v e r MgSCy  After  e v a p o r a t i o n o f t h e e t h e r , t h e 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 h o t p e t r o l e u m e t h e r (30-60°).  Yield:  78%, 6.2 g o f w h i t e  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 w i t h diazomethane  after a portion  had been t a k e n f o r a n a l y t i c a l p u r p o s e s .  2.  1-Carbomethoxycyclopentene. ir  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_ ), 7.48 (m, 4, C-3 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  w i t h an e x c e s s o f diazomethane for  a week.  i n e t h e r s o l u t i o n a t room t e m p e r a t u r e  The e t h e r was f l a s h e v a p o r a t e d and t h e r e s u l t i n g  compound was p u r i f i e d b y vacuum d i s t i l l a t i o n distillation  was a l l o w e d t o s t a n d  using a bulb-to-bulb  a p p a r a t u s , b a t h t e m p e r a t u r e 50° (0.005 mm).  Yield,  - 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, COOCH ), 7.41 (m, 2, C-8 H's), 8.58 (m, 3  4, C-6 and C-7 H's). Anal. Calcd. for C-H^O-N.: o  C, 57.12; H, 7.19.  Found:  C,  LZ Z Z  56.68; H, 7.10.  (b)  Preparation of  l-carbomethoxy-2,3-diazabicyclo(3.3.0)  2-ene-5dj.  B a s i c a l l y 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. o / z  C, 63.70; H, 7.24.  Found:  C, 63.79; H, 7.27 2.  1-Carbomethoxycyclopentene-2d^. The e s t e r i f i c a t i o n o f the deuterated acid with diazomethane  gave a l i q u i d  i r 1720 cm"  1  (ester C=0), 1630 cm"  1  (C=C);  n.m.r. (CC1 ) x 6.32 (s, 3, C00CH_ ), 7.50 (m, 4, C-3 and C-5 H's), 4  3  8.02 (m, 2, C-4 H's), peak at 2.97due to the o l e f i n i c proton being  absent.  - 92 -  3.  1-Carbomethoxy-2,3-diazabicyclo(3.3.0)oct-2-ene-5d . 1  The methyl ester was allowed to stand with an excess o f diazomethane i n ether solution for a week at room temperature. The work up was i d e n t i c a l to that described e a r l i e r i n the case of non deuterated compound.  i r 1732 cm"  1  (ester C=0),  1552 cm"  (N=N); n.m.r. (CC1 ) T 5.0  1  4  (d, 1, pseudoequatorial hydrogen on C-4), 5.0 hydrogen on C-4), 6.29  (s, 3, COOCHp, 7.41  (d, 1, pseudoaxial  (m, 2, C-8 H's),  8.58  (m, 4, C-6 and C-7 H's). Anal. Calcd. f o r C-H^DO,,N •. C, 56.80; H, 7.25. oil i. 2. C, 56.36; H,  VI.  Found:  7.11.  Product studies of l-carbomethoxy-2,3-diazabicyclo(3.3.0)oct-2ene 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 i n a small round bottom f l a s k equipped with a condenser at 131° provided a yellowish l i q u i d consisting of three components. long V  The products were separated by a 15'  diameter copper column packed with 20% Apiazon J on Chrom P,  at 160-165°C, 100 ml He/min.  The compounds were collected o f f the  gas chromatograph and t h e i r i r and n.m.r. spectra were recorded.  - 93 -  The following structure was assigned to the compound having 7.1  min  retention time.  CH  i r 3060 cm"  1  (CC1 ) T 5.00 4  7.72  (=CH ), 1735 cm"  1  2  COOCH3  2  (ester C=0) , 1650 cm  (m, 2, =CH ), 6.33 2  lJ(D)  J2  (D)183  -1  (s, 3, C00CH ), 6.80  (m, 4, C-3 and C-5 H's), 8.10  3  (m, 2, C-4 H's).  of the deuterated compound lacked the signal at T  (C=C); n.m.r. (m, 1, C-l H), The n.m.r. spectrum  6.80.  The next peak, r e t . time 10 min was due to 1-carbomethoxybicyclo(3.1.0)hexane COOCH3 165 (D) 181  i r 3010 cm x 6.40  A  (cyclopropane H's), 1730 cm  (s, 3, C0OCH_ ), 8.29 3  (m, 3, cycloprop H's).  1  (ester C=0); n.m.r. (CCl^)  (m, 6, C-2, C-3 and C-4 H's), 8.71 and  The n.m.r. spectrum of the deuterated showed  e s s e n t i a l l y i d e n t i c a l spectrum with the exception of at T 8.71  9.29  and 9.29 due to the presence of deuterium.  peaks appearing  - 94 -  The last peak, r e t . time 11.1 min was due to  2-methyl-l-carbomethoxy-  cyclopent-l-ene.  3  i r 1725 cm  (ester C=0), 1660 cm"  (C=C); n.m.r. ( C C l ^ T 6.36 (s, 3,  C00CH ), 7.52 (m, 4, C-4 and C-5 H's), 7.94 (s, 3, CH ), 8.20 (m, 2, 3  C-3 H's).  3  The n.m.r. spectrum of the 2-(methyl-d^)-1-carbomethoxy  cyclopent-l-ene showed an i d e n t i c a l spectrum with the exception o f the smaller, broader peak at T 7.94 due to -CH^D.  (b)  Photolyses of l-carbomethoxy-2,3-diazabicyclo(3.3.0)oct-2ene and i t s analogue-5d,.  In a Rayonet Photochemical reactor samples o f 0.5 g pyrazolines i n 30 ml of ether were i r r a d i a t e d f o r 12 hours using 3100 A lamps.  The  etheral solution was concentrated and analysed i n the same manner described above. isolated.  In both cases only cyclopropane products were  - 95 -  VII. P r e p a r a t i o n o f l - c a r b o m e t h o x y - 2 , 3 - d i a z a b i c y c l o ( 4 . 3 . 0 ) n o n - 2 - e n e 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 t o p r e p a r e t h e two compounds (72):  (CH ) 2  n  239 240  0 +  NaCN NaHSCh  (CH ) 2  HCi H0  n  2  242  In a t h r e e - n e c k e d round-bottom f l a s k equipped w i t h m e c h a n i c a l and a d r o p p i n g 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. c o o l i n g t h e s o l u t i o n t o -50° i n a c o o l i n g b a t h , 5 g ketone hexanone, c y c l o h e p t a n o n e f r e s h l y d i s t i l l e d ) was added.  (cyclo-  To t h i s  stirrer After  - 96 -  mixture a solution o f 12 g NaHSO^ dissolved i n 25 ml of water was added slowly, then the reaction mixture was allowed to come to room temperature while the s t i r r i n g was continued f o r 2 hours.  The product was extracted  with three 50 ml portions of ether, the ether f l a s h evaporated and the residue refluxed with 30 ml of 36%  HC1 f o r 4 hours.  The pinkish l i q u i d  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  e s t e r i f i c a t i o n with CH^^ and the following f l a s h evaporation of the ether provided a brownish l i q u i d 5.3 g, which was used without p u r i f i c a tion. Into a 100 ml three-necked round-bottom  flask equipped with a  mechanical s t 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 t h i s mixture 6.0 g of SOC^ was added over a period  of 2 hours and then the mixture was refluxed f o r 5 hours.  The dark  reaction mixture was cooled to room temperature which brought about some s o l i d i f i c a t i o n i n the mixture.  T h i r t y m i l l i l i t e r s of petroleum  ether (30-60) was added and then the s o l i d material was f i l t e r e d o f f 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 i n t h i s order. (MgSO^) the petroleum ether was f l a s h evaporated. dark solution was f r a c t i o n d i s t i l l e d . bad smelling gases were formed.)  A f t e r drying  The remaining  (During the d i s t i l l a t i o n extremely  - 97 -  The f r a c t i o n collected between 190-200° contained the 1-carbomethoxycyclohex-l-ene, which was p u r i f i e d 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.  (CC1 ) x 3.08 (m, 1, o l e f i n i c ) , 6.37 (s, 3, C00CH_ ), 7.84 (m, 4, C-3 4  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 f r a c t i o n 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. (CC1 ) T 2.86 ( t r . 1, o l e f i n i c ) , 6.37 (s, 3, COOCH,,), 7.64 (m, 4, 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 i n 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: (0.002 mm); i r 1740 cm  -1  (ester C=0), 1545 cm"  1  T 5.51 (dd, 1, pseudoaxial H on C-4, (dd, 1, pseudoequatorial H on C-4, J  (N=N); n.m.r. (CC1 ) 4  = 7.5 Hz, D  V  52°  = 16.5 Hz), 5.84  = 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. f o r C H,^N^O^: 9 14 2 2 n  C, 59.34; H, 7.75  Found:  C, 59.07:  H, 7.86. 1-Carbomethoxy-2,3-diazabicyclo(5.3.0)dec-2-ene; (0.003 mm); i r 1740 cm"  1  (ester C=0), 1545 cm  T 5.53 (dd, 1, pseudoequatorial H on C-4  -1  bath temp:  57°  (N=N); n.m.r. (CC1 ) 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 .  (s  3, C00CH ), 7.40 3  C-10  (m, 1, C-5 H), 8.52  = 18.0 Hz),  6.28  (  m  10, C-6, C-7, C-8, C-9 and  H's). Anal. Calcd. f o r C, H,.NJ).: ID lb 2. Z n  H,  D  — A D  — D A  C, 61.19; H, 8.21.  Found:  C, 60.82;  8.32.  VIII.  Product studies of l-carbomethoxy-2,3-diazabicyclo(4.3.0)non2-ene. In a 5 ml round bottom flask equipped with a condenser 0.5 g  pyrazoline was placed and heated at 131° f o r 6 hours.  The preliminary  test on a t . l . c . plate showed that the product mixture consisted of three components. V  The gas chromatographic analysis using a 15' long  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 o f f the gas chromatograph and t h e i r i r and n.m.r. spectra were recorded. The f i r s t peak, r e t . time 28 min was due to  249  - 99 -  i r 3100 cm"  (exocyclic =CH ), 1730 cm"  1  1  2  n.m.r. (CC1 ) T 5.39 4  C-l H), 8.01  (d, 2, =CH ), 6.39 2  (ester C=0),  1655 cm"  1  ( , 3, COOCHj), 6.94 s  (m, 4, C-3 and C-6 H's), 8.52  (C=C);  (m, 1,  (m, 4, C-4 and C-5 H's).  The other peak, r e t . time 41 min was due to the following two compounds:  The r a t i o of the two were estimated from the integrations of the carbomethoxy peaks i n the n.m.r. spectrum.  IX•  Product studies of l-carbomethoxy-2,3-diazabicyclo(5.5.0)dec-2-ene. The pyrazoline was decomposed i n 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 c o l l e c t e d o f f the gas  chromatograph  and t h e i r n.m.r. spectra recorded. The f i r s t peak, r e t . time 28 min, was due to the following o l e f i n :  - 100 -  n.m.r. (CC1 ) T 5.14 (s, 2, =CH ), 6.37 ( , 3., COOCH ), 6.94 (m, 1, 4  2  s  3  C-l H), 8.10 (m, 10, C-3, C-4, C-5, C-6, C-7 H's). The other peak, r e t . time 34 min, was due to the following two compounds:  C00CH  3  The r a t i o of the two were estimated from the integration o f the carbomethoxy peaks .in the n.m.r. spectrum.  X.  3-Methyl-3-carbo-tert-butyl-l-pyrazoline. The pyrazoline was made from commercial tert-butyl  and diazomethane.  methacrylate  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 using a bulb-to-bulb d i s t i l l a t i o n apparatus; bath temp.: (0.03 mm). (60).  65-70°  Its properties were i d e n t i c a l to those reported by Snyder  n.m.r. (CC1 ) T 5.42 (m, 2, C-5 H's), 7.89 (m, 1, C-4 H), 4  8.56 (s, 12, (CH ) C + CH_ on C-3). 3  3  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 cyclopropane angelate tiglate  XI.  = = = =  4.50 74.13 11.45 9.94  ± ± ± ±  0.32% 0.77% 0.31% 0.22%  r e t . time  8.6 min 10.5 " 12.0 " 15.0 11  Preparation of c i s - and trans-3-methyl-4-alkyl-3-carbomethoxy pyrazolines,  cis  trans  CH HH R  = = =  R  3  £cOOCH iso-propyl iso-butyl tert-butyl  H ^1  3  189 191 1_93  COOCH  3  hCH  3  190 192 194  The preparation of pyrazolines followed the usual procedure i n which the a , 3 - o l e f i n i c esters were treated with diazomethane solution at room temperature.  i n ether  It i s worth noting that the size of  the a l k y l group has a profound effect on the rate of cycloaddition. When R = iso-propyl, i t requires 2 treatments i n two weeks, when R = t e r t -b u t y l i t takes 4-5 treatments i n 5 months to achieve 8590% conversion of the Z o l e f i n s .  The E isomers are somewhat more  reactive. It was anticipated from the beginning that a few s t e r e o s p e c i f i c a l l y deuterated pyrazolines would also be required to study k i n e t i c isotope effects.  Consequently such synthetic sequences were chosen which  could provide starting materials f o r both deuterated and undeuterated  - 102 -  a,B-olefinic esters.  The dehydration of 8-hydroxy esters, which could  be obtained i n good y i e l d by the Reformatsky reaction, were favored over other p o s s i b i l i t i e s f o r the preparation of o l e f i n i c esters because t h e i r oxydation to 6-keto esters and reduction with NaBD^ followed by dehydration could give the required B-deutero o l e f i n i c esters.  (a)  General procedure for the preparation of B-hydroxy esters.  Into a three necked flask equipped with a mechanical s t i r r e r , reflux condenser topped with a C a C ^ drying tube and a pressure equilibrating-  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 s t i r r e d 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 o f 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 p r e c i p i t a t e 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 f l a s h -  - 103 -  evaporated.  The r e s i d u e 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 t h e B-hydroxy e s t e r s came o v e r between 100-135° (25-30 mm).  1.  M e t h y l 2 , 4 - d i m e t h y l - 3 - h y d r o x y p e n t a n o a t e from i s o b u t y r a l d e h y d e and m e t h y l  a-bromopropionate  CH_—CH—CH—CH—COOCH.  I l l  CH Yield:  OH  3  3  CH  25_5  3  78.8%; n °D 1.4349; i r 3520 c m 2  (OH), 1735 cm"  - 1  1  ( e s t e r C=0); n.m.r. (CC1 ) -x 6.36 ( s , 3, C00CH_ ), 6.18 (m, 1, 4  3  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 ) . A n a l . C a l c d . f o r C H,^0,: o  o  lb o  C, 59.97; H, 10.06.  Found:  C, 59.67; H, 10.31.  2.  M e t h y l 2,5-dimethyl-3-hydroxyhexanoate from i s o v a l e r a l d e h y d e and methyl  a-bromopropionate  CH,—CH—CH„—CH—CH—COOCH  I  3  2  CH  3  Yield:  I  I  OH  CH  256^  3  67.1%; n_ °D 1.4351; i r 3500 cm" 2  1  (OH), 1760 cm"  1  ( e s t e r C=0); n.m.r. (CC1 ) x 6.36 ( s , 3, C00CH ), 7.65 (m, 1, 4  3  C-3 H ) , 8.70 (m, 2, C-2 H and OH), 8.90 ( d , 3, C H  3  on C-2), 9.12  (dd, 6, CHI on C-5). Anal. Calcd. f o r C H 0 : 9  l g  3  C, 62.04, H, 10.41.  Found:  C, 61.94; H, 10.46. 3.  M e t h y l 2 , 4 , 4 - t r i m e t h y l - 3 - h y d r o x y p e n t a n o a t e from p i v a l d e h y d e and m e t h y l  a-bromopropionate  CH_  I  CH —C 7  3  CH—CH—COOCH,  CH, OH  CH,  257  - 104 -  Yield:  70.0%; n °D 1.4380; i r 355 cm" 2  1  (OH), 1725 cm"  1  ( e s t e r C=0); n.m.r. (CC1 ) T 6.32 ( s , 3, C 0 0 C H ) , 6.40 (m, 1, 4  3  C-3 H ) , 7.40 (m, 2, C-2 H and OH), 8.73 ( d , 3, CH_ on C - 2 ) , 3  9.02 ( s , 9,  CH ) C). 3  3  A n a l . C a l c d . f o r CgH^O.^  C, 62.04; H, 10.41.  Found:  C, 61.81; H, 10.45.  (b)  General procedure f o r t h e p r e p a r a t i o n o f o l e f i n i c  esters.  The d e h y d r a t i o n o f t h e 3-hydroxy e s t e r s was e f f e c t e d by t r i p h e n y phosphine and carbon t e t r a c h l o r i d e which s e r v e d as reagent and s o l v e n t . I n t o a 1 l i t e r round bottom f l a s k equipped w i t h a condenser w i t h a d r y i n g t u b e , 0.2 m o f 3-hydroxy e s t e r , 0.22 m t r i p h e n y l and 400 ml o f d r y carbon t e t r a c h l o r i d e were p l a c e d . r e f l u x e d f o r 24 h o u r s .  phosphine  The s o l u t i o n was  The excess C C l ^ and t h e formed CHC1  e v a p o r a t e d on a r o t a r y e v a p o r a t o r .  topped  3  were  The semi s o l i d mass was worked up  w i t h 200 ml o f p e t r o l e u m e t h e r (30-60).  A f t e r k e e p i n g a t 0° f o r a  few h o u r s , t h e 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 t h e cake washed w i t h 50-70 ml o f i c e c o l d p e t r o l e u m e t h e r . ether provided a yellowish o i l s t i l l  c o n t a i n i n g some s o l i d  The p u r i f i c a t i o n o f t h e crude o l e f i n s lation.  The e v a p o r a t i o n o f p e t r o l e u m material.  was a c h i e v e d by vacuum d i s t i l -  The o l e f i n i c p r o d u c t s came over between 80-120° a t 25-30 mm.  The E and Z isomers as w e l l as t h e 3 , y - o l e f i n i c b y p r o d u c t s were s e p a r a t e d and c o l l e c t e d by gas chromatography  u s i n g a 25' l o n g 3/4" d i a m e t e r  copper column packed w i t h 20% carbowax 4000 monostearate. The i n d i v i d u a l o l e f i n s a r e , a s  follows:  - 105 -  1.  M e t h y l ( E ) - and ( Z ) - 2 , 4 - d i m e t h y l p e n t e n - 2 - o a t e from 255. Y i e l d : 65.0% CH CH,—CH—CH=C  COOCH,  j  J  S  CH (E) - 258_ (Z) - 259 ( E ) - i s o m e r ; b.p.: 163.3°; n C=0), 1650 cm"  1  D 1.4395; i r 1730 cm  (ester  (C=C); n.m.r. (CC1 ) x 3.56 ( d , 1, o l e f i n i c , J : 4  4.4 H z ) , 6.34 ( s , 3, C00CH_ ), 7.50 (m, 1, C-4 H) , 8.22 ( d , 3, CH_ 3  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 ) - i s o m e r ; b.p.: (C=0), 1650 c m  - 1  150.1°, n  D 1.4345; i r 1740 cm  (ester  (C=C, v e r y s m a l l ) ; n.m.r. (CC1 ) x 4.29 ( d , 1, 4  o l e f i n i c J = 3.8 H z ) , 6.33 ( s , 3, C00CH ), 6.75 (m, 1, C-4 H z ) , 3  8.17  ( s , 3, C H  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:  H, 9.89. 2.  M e t h y l ( E ) - and (Z)-2,5-dimethylhexen-2-oate  CH_—CH—CH_ — C H = C 3 | 2 C H  3  (E) - 260_ (Z) - 261  COOCH, 3  from 256.  C, 67.87;  - 106 -  (E)-isomer; b.p.: 189.1°; i r 1725 cm"  1  (C=C); n.m.r. (CC1 ) x 3.36 ( t , 4  (ester C=0), 1655 cm"  1, o l e f i n i c ) , 6.33 f s , 3, C00CH ), 3  8.00 (m, 2, C-4 H's), 8.13 ( , 3, CH s  3  on C-2), 8.49 (m, 1, C-5 HO,  9.05 (d, 6, ( C H ) ) . 3  2  Anal. Calcd. f o r 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 c m  -1  (C=C); n.m.r. (CC1 ) x 4.11 ( t , 1, o l e f i n i c ) , 6.31 (s, 3, C00CH ), 4  3  6.76 (m, 2, C-4 H's), 8.15( s, 3, CH_ on C-2), 8.36 (m, 1, C-5 H), 3  9.10 (d, 6, ( C H ) ) . 3  2  Anal. Calcd. f o r  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  CH — C CH Yield:  CH=C  COOCH  from 257.  (E) - 262_ (Z) - 263  3  80.0%  (E)-isomer; b.p.: 180.6?; n D 1.4458; i r 1720 cm" 20  (C=0), 1645 cm"  1  1  (ester  (C=C); n.m.r. (CC1 ) x 3.37 (m, 1, o l e f i n i c ) , 4  6.37 (s, 3, C00CH ), 8.10 (s, 3, CH_ on C-2), 8.80 (s, 9, (CH_ ) C). 3  Anal. Calcd. f o r C-H^O 69.33; H, 10.06.  3  • C, 69.23; H, 10.25.  3  Found:  C,  3  - 107 -  (Z)-isomer; b.p.: 162.3°; n/ D 1.4322, i r 1740 era" (ester u  C=0), 1660 cm"  1  1  (C=C); n.m.r. (CC1 ) T 4.60 (m, 1. o l e f i n i c ) , 6.33 4  (s, 3, C00CH ), 8.19 (d, 3, CHj on C-2 J = 1.6 Hz), 8.91 (s, 9, 3  (CH ) C). 3  3  Anal. Calcd. f o r CgH^Oy  C, 69.23; H, 10.24.  Found:  C, 69.55; H, 9.98. (c) 1.  Pyrazolines. cis-3-Methyl-4-isopropyl-3-carbomethoxy-1-pyrazoline. A l i q u i d which s o l i d i f i e s on long standing at low temperature  (-5°); i r 1762 cm"  1  T  (ester C=0), 1550 cm"  (N=N); n.m.r. (CC1 )  1  5.23 (dd, 1, pseudoequatorial C-5 H, J  T  R  4  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, —cis ' -gem r  6.23 (s, 3, COOCH_ ), 8.20 (m, 2, C-4 H and CH-(CH ) ), 8.81 (s, 3, 3  CH  3  3  2  on C-3), 9.13 (d, 6, (CH_ ) -CH). 3  Anal. Calcd. for  c 9  ^  1 (  ^  0 2  2  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, —cis ' -gem 6.30 (s, 3, C00CH ), 8.66(m, 2, C-4 H and CH-(CH ) ) , 9.05 (d, r  3  6, (CH ) -CH), 8.30 (s, 3, CHj on C-3). Anal. Calcd. for C_H.,N 0 : y io / i o  C, 58.78; H, 8.90.  o  C, 58.67; H, 8.75. Found:  - 108 -  3.  cis-3-Me thy1-4-i sobuty1-3-carbomethoxy-1-pyraz o1 ine. Liquid; i r 1760 cm"  1  (CC1 ) 4  T  (ester C=o), 1550 cm"  (N=N); n.m.r.  1  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 —cis  —  = 17.6 Hz), 6.21 ( s , 3, C00CH_ ) , 7.72 (m, 1, C-4 H), 8.79 3  ( s , 3, CH on C-3), 9.14 (m, 9, (Cii^-CJi-CH^-) . 3  Anal. Calcd. f o r C H N.0_: in  C, 60.51; H, 9.14. Found:  lo  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"  (N=N); n.m.r.  1  (CC1 ) T 5.19 (dd, 1, pseudoequatorial C-5 H, £ 4  = 8.4 Hz,  t r a n s  J = 16.4 Hz), 6.10 (dd, 1, pseudoaxial C-5 H, J . = 9.8 Hz, — gem —cis J^  = 16.4 Hz), 6.33 ( , .3, C00CH_ ), 8.16 (m, 1, C-4 H), 8.40  e m  s  3  ( s , 3, CH_ on C-3), 9.12 (m, 9, (CH_ ) ~CH-CH ). 3  3  2  2  Anal. Calcd. f o r C H N 0 • C, 60.51; H, 9.14. Found: i n  1U  1 o  o  lo 2  2  C, 60.8; H, 9.20. 5.  cis-3-Methyl-4-tert-butyl-3-carbomethoxy-l-pyrazoline. Liquid; i r 1760cm"  (CC1 ) 4  T  1  (ester C=0), 1550 c m  5.29 (dd, 1, pseudo equatorial C-5 H,  (N=N),; n.m.r.  - 1  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 ' -cis ' r  ^gem  =  1 7  ' ° ^> HZ  6  -  2 2  ( > ' > C00CH ), 8.76 ( s , 3, CH_) , 9.12 ( s , 9, (CH^C; s  3  3  Anal. Calcd. f o r C H. N.0 : 1U l o 2 2 in  C, 60.52; H, 9.00.  o  o  3  C, 60.51; H, 9.14. Found:  - 109 -  6.  trans-3-Methyl-4-tert-butyl-3-carbomethoxy-l-pyrazoline. Liquid; i r 1740 cm"  (ester C=0),  1  (CC1 )  1550 cm  -1  (N=N); n.m.r.  5.28 (dd, 1, pseudoequatorial C-5 H, J  = 8.7 Hz,  J—gem = 17.0 Hz), 5.98 (dd, 1, pseudoaxial C-5 H, ** > J — c i.s = 11.8 Hz, J  = 17.0 Hz), 6.40 (s, 3, COOCH ), 8.29 (s, 3, CH_ on C-3), O  §6111  9.09  j  ( , 9, (CH ) C). s  3  3  Anal. Calcd. for C H N 0 : i n  l o  o  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-3hydroxypentanoate which was oxidized to the corresponding B-keto ester by means o f RiX^/NalO^: CH_ CH_ I I CH_—C CH--CH--COOCH, 3 257  j C H  3 °  j H  r  3  CH_ CH_ Ru0 | | „ ^ * CH --C---C---CH--C00CH, 2  T  NalO^  | C H  ||  3 °  264  Into a 1 l i t e r three-necked round-bottom f l a s k equipped with a mechanical s t i r r e r (preferably with a large s t i 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 i n 200 ml of carbon tetrachloride and 200 mg RuO^ were placed.  The solution o f 27 g of sodium metaperiodate i n  400 ml of water was added over a period of 4 hours to the s t i r r e d  - 110 -  reaction mixture.  To control the pH of the mixture during the reaction  80 ml of 10% NaHCO^ solution was also added i n small portions. the  After  addition of sodium metaperiodate the mixture was s t i r r e d for 2 hours,  100 mg of RuC^ was added and warmed to 70° f o r 2 hours.  The organic  phase showed a blackish-yellow colour indicating the presence of the  end of reaction.  RuO^,  After cooling i t to room temperature, the excess  oxidizing agent was destroyed by addition of isopropanol.  The separated  organic phase was dried (MgS0 ) and d i s t i l l e d giving 12.8 g (82%) 4  b.p.:  115-119° (0.5 mm).  gas chromatography  The quality of the product was checked by  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 s t a r t i n g 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. (CC1 ) T 6.17 4  (CH ) C), 8.93 3  3  (q, 1, C-2 H), 6.37  s  3  ( , 9, s  (d, 3, CH_ on C-2). 3  Anal. Calcd. f o r CgH^Cy H,  ( , 3, C00CH ), 8.83  C, 62.71; H, 9.36.  Found:  C, 62.40;  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% i s o l t o p i c p u r i t y ) , 0.1 ml of 30% NaOD i n D^O were placed. cooled to -10° and 0.55 g of NaBD  4  was only p a r t i a l l y dissolved.)  This mixture was  (isotopic p u r i t y 98%).  (The NaBD  To this mixture 8.3 g methy 2,4,4-  trimethyl-3-ketppentanoate was added slowly and s t i r r e d  (magnetic)  4  - Ill -  overnight.  The reaction product was taken up i n 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 -  l a t i o n (140-150° at 10-15 mm) provided 7.2 g (85%) product; n.m.r. (CC1 ) 4  T 6 . 3 2 ( S , 3, C00CH ), 7.40 (m, : 2, C-2 H and OH), 8.73 (d, 3, CH on 3  3  C-2), 9.02 (s, 9, (CH ) C), peak at T 6.40 was absent. 3  3  Anal. Calcd. f o r 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-2oate-3di.  The same procedure was used as f o r the non deuterated compounds. The o l e f i n i c 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  (ester C=0), 1645 cm"  -1  1  (C=C); n.m.r.  (CC1 ) T 6.37 (s, 3, C00CH ), 8.10 ( s , 3, CH_ on C-2), 8.80 (s, 9, 4  3  3  (CH^j^D), the peak at 3.37 due to the o l e f i n i c proton was absent. Anal. Calcd. f o r C H D 0 : g  C, 68.99; H, 10.15.  15  2  C, 68.79; H, 10.67.  Found:  - 112 -  2.  (Z)-isomer; i t contained 1-2% (E)-isomer; i r 1740 cm  (C=0), 1660 cm"  1  1  (ester  (C=C); n.m.r. (CC1 ) T 6.33 (s, 3, C00CH_ ), 8.19 4  3  (s, 3, CH on C-2), 8.91 (s, 9, ( C R ^ C ) , the peak at T 4.60 due 3  to the o l e f i n i c proton was absent. Anal. Calcd. f o r 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-3carbomethoxy-l-pyrazoline-4d^.  1.  cis-3-Methyl-4-tert-butyl-3-carbomethoxy-l-pyrazoline-4d-| . The treatment of 1.6 g ( E ) - o l e f i n with diazomethane i n ether  provided 1.82 g crude pyrazoline which was p u r i f i e d by vacuum d i s t i l l a t i o n (see the procedure for the undeuterated  compound).  n.m.r. (CC1 ) x 5.28 (d, 1, pseudoequatorial C-5 H), 6.08 (d, 1, 4  pseudoaxial C-5 H), 6.10 ( , 3, C00CH_ ), 8.69 (s, 3, CH s  3  3  on C-2),  9.00 (s, 9, (CH ) C). 3  3  Anal. Calcd. f o r C H 1Q  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 o f 1.3 g o l e f i n with diazomethane i n ether  solution gave 1.25 g crude product which was p u r i f i e d by the same way as the undeuterated:  n.m.r. (CC1 ) x 5.35 (d, 1, pseudoequatorial 4  C-5 H), 6.01 (d, 1, pseudoaxial C-5 H), 6.40 (s, 3, COOCH,),  - 113 -  8.29  ( , 3, CH on C-3), 9.09 (s, 9, ( C H ^ C ) . s  3  Anal. Calcd. f o r  c  H 1 0  i7  D N  2°2  :  C  ' - > > 6 0  2 6  H  9  6 1  -  Found:  C, 60.50; H. 944.  XIII. Preparation o f 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 p u r i t y ) .  Its n.m.r. spectrum was i d e n t i c a l with those  reported by Fowells et a l . , indicating the presence of 10% undeuterated compound.  The crude ester was treated with diazomethane and p u r i f i e d  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 bath temp.: 5.82  apparatus,  55° (0.05 - 0.1 mm); n.m.r. (CC1 ) x 5.48 (d, 2, C-5 H's), 4  (q, 2, ester -CH ), 8.08 (m, 1, C-4 H), 8.48 (s, 3, CH on C-2), 2  3  8.77 (t, 3, ester CH ). 3  XIV. Product studies o f trans-3-methyl-3-carbethoxy-l-pyrazoline-4dj.  (a)  Thermal decomposition of trans-3-methyl-5-carbethoxy-lpyrazoline-4dj.  The products of the thermolysis of trans-3-methyl-3-carbethoxy-lpyrazoline-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. on the n.m.r. spectra.  The s t r u c t u r a l assignments were based  - 114 -  The following compounds were i d e n t i f i e d : 1.  Ethyl 2-methylbuten-2-oate-d ,  3,y-olefinic ester, r e t . time:  1  12.4 min.  The quite complex n.m.r. spectrum indicates the presence  of the following three compounds: CH  I  CH =CH—CD—COOCH —CH 2  2  3  212_  3  211_  3  265_  CH  I CH =CD—CH—COOCH —CH CH, 2  2  CH =CH—CH—COOCH —CH 2  2  n.m.r. (CC1 ) T 4.96 (m, 2, CH_ =), 5.95 (q, 2 ester CH_ ), 7.00 4  2  2  (m, C-3 H), 8.75 (m, ester CH , CH_ on C 3  2.  3  2  and C-2 H) .  l-Methyl-l-carbethoxycyclopropane-2dj, r e t . time:  16.6 min.  n.m.r. (CC1 ) T 6.03 (q, 2, ester CH ), 8.80 f s , 3, CH_ ), 8.81 4  2  3  ( t r . ester CH_ overlapping with the cyclopropane hydrogens), 3  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  H  CONH-NH-  CH,  H  C0NH— NH,  D  CH:  267 50%  - 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_ ), 8.19 (.S.l, CH_ 2  and CJH^D), 8.77  ( t , 3, e s t e r CH^).  3  (Due t o s e p a r a t i o n  difficulties  o n l y a s m a l l amount o f compound c o u l d be c o l l e c t e d , c o n s e q u e n t l y t h e i n t e g r a t i o n was hampered by a l a r g e n o i s e t o s i g n a l r a t i o . However, t h e shape and t h e i n t e g r a t i o n o f t h e m e t h y l s i g n a l s c l e a r l y showed t h a t t h e d e u t e r i u m was i n c o r p o r a t e d group a t t a c h e d  4.  t o t h e g-carbon.  E t h y l t i g l a t e - S d j , r e t . time:  x 3.39 (broad,  on t h e methyl  25.5 m i n , n.m.r. (CC1 ) 4  0.10 - 0.2 due t o t h e u n d e u t e r a t e d 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 t h e l a r g e n o i s e t o s i g n a l r a t i o ) , 5.85 ( q , 2, e s t e r CH_ ), 8.23 ( s , 6, C H ' s ) , 8.73 2  3  ( t , 3, e s t e r  CH ). 3  (b)  Direct photolysis of  trans-3-methyl-3-carbethoxy-l-pyrazoline-  Three grams 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 o f i s o p e n t a n e and 3100  i r r a d i a t e d f o r 15 hours i n a Rayonet P h o t o c h e m i c a l r e a c t o r A lamps.  The c a r e f u l e v a p o r a t i o n  using  o f the isopentane y i e l d e d a  p r o d u c t m i x t u r e c o n t a i n i n g t h e f o l l o w i n g components: Ethyl methacrylate-Sd! g,Y-olefin-dj C y c l o p r o p a n e prod-dj^ Ethyl angelate-dj Ethyl tiglate-dj  14.2% r e t . t i m e 5.7% 71.0% 4.4% 4.7%  TABLE IX Photoproducts o f trans-3-methy1-3-carbethoxyl-pyrazoline-4d^  10.5 min. 12.4 min. 16.6 min. 18.6 min. 25.2 min.  - 116 -  The analysis was performed under the same condition described e a r l i e r for the analysis of the product mixture obtained from thermolysis. Only the ethyl methacrylate-Sdj and the 1-methyl-l-carbethoxycyclopropane2d^ were collected o f f the gas chromatograph, the l a t t e r was transformed into i t s hydrazid and the n.m.r. spectra of both were recorded. The n.m.r. spectrum of the i s o l a t e d ethyl methacrylate-Sd^ showed a considerable change 0.26; 0.74 i n the r e l a t i v e areas of the two peaks at T 3.96 and 4.54 with respect to the starting material i n which the areas had been 0.1; 0.9.  (A detailed description of the n.m.r. spectrum  of the ethyl (Z-)methacrylate-3d  1  i s given  l-Methyl-l-hydrazidocyclopropane-2d  1  by Fowells et_ al_. (68). (CC1 ) x 6.20 (broad, 3, NH-NH_), 4  2  8.70 (s, 3, CH_ ), 8.25 (m, 1.35 cycloprop), 9.43 (m, 1.65, cycloprop). 3  The r e l a t i v e areas indicated that the following two isomers were present.  D  H  CO-NH—NH  266  CH  2  3  ~55% XV.  H  C0-NH-NH  D  CH  26J  2  3  -45%  Preparation of 3-methyl-3-carbethoxy-l-pyrazoline. Commercial ethyl methacrylate was treated with diazomethane i n 20  ether.  The workup was s i m i l a r to other pyrazolines.  n.m.r. (CC1 ) x 5.50 4  D 1.4492;  ( t , 2, C-5 H's), 5.81 (q, 2, ester CH_ ), 8.02 2  (m, 1, C-4 H), 8.50 ( s , 3, CH_ on C-3), 8.76 3  Anal. Calcd. for C H N Oy ?  H, 7.66.  n  12  ( t , 3, ester CH ).  C, 53.82; H, 7.68.  3  Found:  C, 53.64;  - 117 -  The products of thermal decomposition were analysed on the same column, on the same  day, under the same conditions as described  e a r l i e r f o r i t s analogous-4d^.  The separated components with the  exception o f ethyl angelate also served as components  f o r 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%) y i e l d reported by Fowells ejt al_. ( 6 8 ) by the d i r e c t preparation.  Sixteen grams  of crude ethyl ester was saponified with 100 ml o f M sodium hydroxyde solution at room temperature.  ,The solution was f i l 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 a c i d i f i e d with 65 ml of 2 m HC1. The acid was extracted with three 50 ml portions of ether, dried (MgSO^) and e s t e r i f i e d with diazomethane.  Its n.m.r. spectrum was  i d e n t i c a l with that reported by Fowells e_t al_. (68 ).  They claimed  on the basis of the expanded peak at T 3.96 with r e l a t i v e 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 i r r a d i a t i o n which resulted i n a coalesce of the s i x peaks (doublet of a quartet) into a doublet with J  „ = 1.8 Hz. Identical coupling constant was obtained from the 1 2 experiment done with simple methyl methacrylate. u  H  H  - 118 -  The crude ester was treated with diazomethane i n ether and p u r i f i e d by vacuum d i s t i l l a t i o n ; n.m.r. ( C C i p x 5.43 (d, 1, C-5 H), 5.55 (d, 1, C-5), 6.32 (s, 3, COOCH_ ), 8.55 (s, 3, CH ), 8.61 (m, 1, C-4 H). 3  3  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 c o l l e c t e d o f f  the gas chromatograph and t h e i r n.m.r. spectra were recorded. 1.  B,Y-01efinic ester;  r e t . time:  8.2 min; n.m.r. (CCl^)  x 4.88 (broad, 2, =CH ), 5.06 (m ^ 0.2, =CH), 6.35 (s, 3, C00CH_ ), 2  3  6.74 (m, ^ 0.7 - .8, C-2 H), 8.75 (s, 3, CH_ ).  The integration of  3  the peaks indicated that the sample consisted of two compounds D  CH,  .H  I I  CH =C—CH—C00CH , 2  3  200 major component.  CH_  I I  3  CH =C—CD—C00CH 2  3  201 (The accuracy of the integration was reduced  by the large signal to noise r a t i o . )  2.  l-Methyl-l-carbomethoxycyclopropane-2d^; r e t . time:  11.4  min; n.m.r. (CC1 ) x 6.41 (s, 3, C00CH_ ), 8.74 (s, 3, CH_ ), 4  3  3  8.92 (s, 1.5, cyclopropane H's c i s 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.  H  202  COOCH:  H  CH  D  3  -50% 3.  COOCH:  203  CH  3  -50%  Methyl angelate-4d ; r e t . time: 12.5 min; n.m.r. (CC1 ) 1  4  x 4.00 (broad, 1, o l e f i n i c ) , 6.30 ( s , 3, C00CH_ ), 8.16 ( s + 3  shoulder, ^ 5, CH,, C ^ D ) . The n.m.r. spectrum c l e a r l y indicated that the deuterium was on C-4 whose hydrogens appeared at somewhat lower f i e l d s due to the deshielding e f f e c t of the carbomethoxy group.  4.  Methyl tiglate-3d^; r e t . time:  17.3 min; n.m.r. (CCl^)  T 3.33 (broad, very small, due to the undeuterated isomer), 6.31 ( s , 3, C00CH ), 8.20 ( s , 6, the two CH_ ). 3  (b)  3  Direct photolysis of trans-3-methy1-3-carbomethoxy-1pyrazoline-4di.  The photolysis was carried out i n a Rayonet Photochemical reactor in isopentane solution using 3100 X lamps. to that described  The workup was similar  e a r l i e r for the ethyl ester.  No quantitative analysis  was done on the product mixture and only the cyclopropane product was  - 120 -  collected.  (c)  The n.m.r. spectrum indicated a 45:55 mixture of 202 and 203.  Sensitized photolysis of  trans-3-methyl-3-carbomethoxy-l-  pyrazoline-4di. Three grams of benzophenone and 0.3 g pyrazoline was i n 30 ml isopentane and photolyzed using 3500 A lamps.  dissolved  The workup  followed a r e p e t i t i o n of an e v a p o r a t i o n - c o o l i n g - f i l t r a t i o n cycle  till  about 0.5 - 0.6 ml yellowish l i q u i d was obtained s t i l l containing some benzophenone.  The decomposition products were d i s t i l l e d o f f  the benzophenone i n a bulb-to-bulb apparatus (bath temp.: and separated by gas chromatography.  140-150°)  Only the cyclopropane derivative  was c o l l e c t e d 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 i n B-bromo methacrylic acid could be replaced by hydrogen using copper-activated Zn-dust i n 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 s t i r r e r and a condenser 10 g of dry sodium (Z)B-bromomethacrylate, 30 ml of CH -0D, 4 ml of D 0 3  in D„0 were added and s t i r r e d f o r 10 minutes.  2  and 5 ml of 38% DC1  Ten grams of predried  - 121 -  Zn dust and 0.05 g C ^ C ^ were added at once. and s t i r r e d for 24 hours.  The s l u r r y was refluxed  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 e s t e r i f i e d with diazomethane. Yield:  3.1 g (62%) estimated by gas chromatography.  C a t a l y t i c reduction o f sodium (E)-3-bromomethacrylate i n 0^0 i n the presence of equivalent amounts o f NaOD or Et^N also gave ( E ) - and (Z)-methacrylic acid -3d^.  The r a t i o of the E and Z isomers present  i n the product mixture was dependent on the a c t i v i t y and the amount of catalyst used.  By applying only a small amount (0.5 - 1.0% of the  sodium s a l t ) of catalyst, 5% Pd or Pt on charcoal product mixtures were obtained containing 95 - 98% E isomer.  The methods drawback i s  the r e l a t i v e l y long reaction time of 2-3 days. some polymerization has also taken place. that described for the Zn reduction.  During the reaction  The workup was similar to  Yields varied between 25 - 40%;  n.m.r. (CCl^) x 3.98 (q, 1, o l e f i n i c H c i s to the carbomethoxy), 4.54 (broad, small, o l e f i n i c H trans to the carbomethoxy), 6.32 ( s , 3, COOCH,,), 8.12 (d, 3, CH_ ). 3  The o r i g i n o f the small peak at x 4.54  was attributed to the Z isomer on the basis o f n.m.r. studies. The methyl group was decoupled by i r r a d i a t i o n with the r e s u l t that the s i x peaks (doublet of a quartet) at x 4.54 collapsed into a s i n g l e t . The ester was treated with diazomethane i n ether.  The evaporation  of ether resulted i n a yellowish l i q u i d , the crude pyrazoline which was d i s t i l l e d i n vacuum; n.m.r. (CCl ) x 5.30 ( s , 1, C-5 H), 5.41 ( s , d  - 122 -  1, C-5 H), 6.19 ( , 3, C O O Q y ,  7.49 ( t t , 1, C-4 H), 8.41 ( s , 3, CH_ ). 3  s  XIX. P r o d u c t s t u d i e s o f c i s - 3 - m e t h y l - 3 - c a r b o m e t h o x y - l - p y r a z o l i n e . (a)  Thermal d e c o m p o s i t i o n .  I t was done i n t h e same way d e s c r i b e d e a r l i e r f o r t h e t r a n s - i s o m e r . Q u a n t i t a t i v e p r o d u c t a n a l y s i s has n o t been done and t h e c y c l o p r o p a n e p r o d u c t was c o l l e c t e d o n l y .  I t s n.m.r. spectrum i n d i c a t e d t h a t t h e  sample c o n s i s t e d o f t h e two isomers  (b)  Sensitized photolysis.  I t was done i n t h e same way as d e s c r i b e d f o r t h e t r a n s - i s o m e r . The r e s u l t s were a l s o  XX.  identical.  Product s t u d i e s o f c i s - and t r a n s - 3 - m e t h y l - 4 - a l k y l - 3 - c a r b o m e t h o x y 1-pyrazolines. 1.  Thermal d e c o m p o s i t i o n .  General procedure.  I n 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 p l a c e d and h e a t e d i n an o i l b a t h a t an a p p r o p r i a t e temperature f o r a p e r i o d t e n h a l f l i f e t i m e . The r e s u l t i n g p r o d u c t m i x t u r e was a n a l y s e d by gas  chromatography.  The s t r u c t u r e assignment o f t h e 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 .  spectra.  I n some cases t h e r e 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 t o t h e low y i e l d s and r e t e n t i o n  - 123 -  times were used f o r i d e n t i f i c a t i o n . The thermal decomposition of c i s - and trans-3-methyI-4-alkyl-3carbomethoxy-1-pyrazolines produced a mixture consisting of c i s - and trans-cyclopropane derivatives of (E) and (Z) o l e f i n i c esters (a,3) and 3,y-olefinic esters.  R  CH:  COOCH:  COOCH:  CH:  CIS  trans  268  269  R  CH  R  3  COOCH  H CH  3  X C O O C H 3  3  CH  E 270  CH  3  3  Z C H  R — C—  II  CH  3 CH—COOCH,  271  3 2  272_  In order to determine the stereochemistry of the l-methyl-2alkyl-l-carbomethoxy cyclopropanes i t was necessary to f i n d out whether the two a l k y l groups, i . e . R and methyl, were c i s or trans to each other.  The assignment was based on the comparison between the f i r s t  - 124 -  and the l a s t member of a series and the assumption that i f they showed s i m i l a r patterns i n n.m.r. spectroscopy, rate of saponification and gas chromatographic chemistry.  retention times they should have s i m i l a r stereo-  The n.m.r. spectra of the c i s isomers showed a proton  signal around T 9.6 due to the cyclopropane hydrogen while the trans isomer exhibits no signal i n t h i s region.  The rate of saponification  of the c i s isomers are higher than for the trans ones due to stereochemical 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 o l e f i n i c ester. unsuccessful attempt has been made to add methyl  One  generated by the  method of Simons-Smith to both; methyl(E)- and (Z)-2,4,4trimethylpentene-2-oate. The amount of B,y-olefinic esters  i n the product mixtures  are quite small, i n most cases n.m.r. spectroscopy was used to i d e n t i f y them. The stereochemical assignment  for the a,B-olefinic esters was  based on n.m.r. spectroscopy and retention times. group i s c i s to the carbomethoxy  When the methyl  i t s signal tends to appear at  lower f i e l d because of the deshielding effect o f 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, r e t . time:  8.1 min was due to methyl .2—  methyl-3-isopropylbuten-3"-oate;  n.m.r. (CC1 ) T 4.57 (broad, 4  2, =CH ), 6.37 ( s , 3, C00CH_ ) , 7.00 (q, 1, C-2 H), 8.64 (d, 3, 2  3  CH_ on C-2), 9.24 (m, 7, CH(CH ) ) . 3  2  2.  trans-1-Methyl-2-isopropyl-1-carbomethoxycyc1opropane;  r e t . time:  1.2 min; n.m.r. (CC1 ) T 6.39 (s, 3, C00CH ), 4  8.74 ( s , 3, CH  3  3  on e y e ) , 8.97 (m, 10, CH(CH_ ) and cyclopropyl 3  2  H's). 3.  cis-1-Methyl-2-isopropyl-1-carbomethoxycyclopropane;  time:  ret.  15.0 min; n.m.r. (CC1 ) T 6.40 ( s , 3, C00CH_ ), 8.73 ( s , 4  3, CH  3  3  on c y c l p r . ) , 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; r e t . time:  19.4 min;  n.m.r. (CC1 ) T 6.40 ( s , 3, COOCj^), 9.19 (m, 1, C-4 H), 8.22 4  ( s , 6, CH 's on C-2 and C-3), 9.09 (d, 6, )CH_ ) 3  3  2  C) .  - 126 -  (b)  trans-3-Methyl-4-isopropyl-3-carbomethoxy-l-pyrazoline.  It was decomposed at 150°.  The r e s u l t i n g 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; r e t .  time: 2.  11.2 min; i t s n.m.r. spectrum was described e a r l i e r . cis-1-Methyl-2-isopropyl-l-carbomethoxycyclopropane; r e t .  time: 3.  15.0 min; i t s n.m.r. spectrum was described e a r l i e r .  Methyl (Z)-2,3,4-trimethylpenten-2-oate; r e t . time:  16.5  min; n.m.r. (CC1 ) x 6.32 (s, 3, COOCi^), 6.70 (m, 1, C-4 H), 4  8.19  (s, 3, CH  3  on C-2), 8.37 (s, 3, CH  on C-3), 9.00 (d, 6,  5  (CH ) CH). 3  2  (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 i d e n t i f i e d :  1.  Methyl 2,5-dimethyl-3-methylenehexen-3-oate; r e t . time:  13.8 min; n.m.r. (CC1 ) x 5.15 (d, 2, CH_ =), 6.38 (s, 3, C00CH_ ), 4  2  3  8.10 (m, 1, C-2 H), 8.78 (s, 3, CH_ on C-2), 9.10 (m, 9, ( C H ^ 3  CH-CH ). 2  - 127 -  2.  cis-1-Methy1-2-i sobuty1-1-carbomethoxy eye1opropane; r e t .  time:  18.6 min; n.m.r. (CC1 ) T 6.39 (s, 3, C00CH ), 8.73 (m, 4  2, CH_ -CH), 8.78 (s, 3, CH 2  3  3  on cycloprop.), 9.08 (d, 6, (CH_ ) D, 3  2  J_ = 6.0 Hz), 9.68 (d (unresolved), 1, cyclopropane H). 3.  Methyl E-2,3,5-trimethylhexen-3-oate;  r e t . time:  21.0 min;  n.m.r. (CC1 ) T 6.33 (s, 3, C00CH_ ), 8.07 (m, 5, CH_ on C-2 and 4  3  C-4 H's), 8.17 (s, 3, CH  3  on C-3), 9.08 (d, 7, (CHg) CH, J =  3  8.0 Hz).  (d)  trans-3-Methyl-4-isobutyl-3-carbomethoxy-l-pyrazoline.  It was decomposed and the r e s u l t i n g product mixture analysed i n the same way as f o r the product mixture of the c i s isomer. 1.  The f i r s t peak, r e t . time:  14.0 min, was due to trans-1-  methyl-2-isobutyl-l-carbomethoxycyclopropane;  n.m.r. (CC1 ) 4  T 6.21 ( s , 3, C00CH ), 8.60 ( s , 3, CH_ on cyclopr.), 9.00 (m, 3  12 (CH ) CH-CH 3  2.  2  3  and cyclopropane H's).  2  Methly (Z)-2,3,5-trimethylhexen-3-oate; r e t . time:  17.8 min;  n.m.r. (CC1 ), (due to poor separation the sample also contained 4  c i s -1-methyl - 2- isobutyl-1 -carbomethoxy cyclopropane); (s,  T 6.37  3, C00CH ), 8.24 (complex, 6, CH_*s on C-2 and C-3), 9.05 3  3  (complex, 9, (CH_ ) -CH-CH ~). 3  2  2  - 128 -  3.  cis_-l-Methyl-2-isobutyl-l-carbomethoxy cyclopropane.  It  was described e a r l i e r .  (e)  cis-3-Methyl-4-tert-butyl-3-carbomethoxy-1-pyrazoline.  It was decomposed at 155° giving only one product, tert-butyl-l-carbomethoxycyclopropane;  l-methyl-2-  b.p. 190.3°; n.m.r. (CCl^)  T 6.38 (s, 3, C00CH_ ), 8.76 (s, 3, CH_ on cyclopr.), 8.95 (s, 11, 3  3  (CH ) C and cyclopropr. H's), 9.40 (d, 1, cyclopropyl H). 3  3  Anal. Calcd f o r C  iri  H 0 • C, 70.48; H, 10.65. 1o  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-butyl1-carbomethoxycyclopropane;  b.p. 173.7°; n.m.r. (CCl^) T 6.40 (s, 3,  C00CH_ ), 8.75 (s, 3, CH_ on cyclopr.), 9.08 (s, 11, (CH ) C and 3  3  3  3  cycloprop. H). Anal. Calcd f o r C , „ H 0 •. C, 70.48; H, 10.65. lo  IU  Found:  C, 70.22;  l o 1.  H, 10.67.  2.  Photodecompositions  The d i r e c t and benzophenone sensitized photolyses of c i s - and trans-3-methy1-4-tert-butyl-1-carbomethoxy-1-pyrazolines  gave only  c i s - and trans-l-methyl-2-tert-butyl-l-carbomethoxycyclopropanes respectively.  The procedures  described e a r l i e r .  f o r photolyses and work-up have been  KINETIC MEASUREMENTS  The r a t e s o f d e c o m p o s i t i o n o f p y r a z o l i n e s were d e t e r m i n e d by v o l u m e t r i c measurements o f t h e e v o l v e d n i t r o g e n u s i n g a s l i g h t l y modified  a p p a r a t u s d e s c r i b e d by P e t e r s o n and coworkers  (69).  The  r e a c t i o n f l a s k was immersed i n a c o n s t a n t t e m p e r a t u r e b a t h made by the Haake Company.  The t h e r m o s t a t c o u l d m a i n t a i n t h e d e s i r e d  t e m p e r a t u r e w i t h i n ±0.02 - 0.05°C under 155° as c l a i m e d by t h e m a n u f a c t u r e r b u t above t h a t t h e 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 r e a g e n t grade was d i s t i l l e d t w i c e a t reduced  pressure.  For k i n e t i c runs s t a n d a r d s o l u t i o n o f p y r a z o l i n e s were p r e p a r e d so t h a t 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 o f nitrogen.  G e n e r a l P r o c e d u r e f o r K i n e t i c Runs F o r t y - n i n e ml o f d i - ( n - b u t y l ) - p h t h a l a t e was preheated a t t h e approp r i a t e t e m p e r a t u r e , 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 m i n u t e s , t h e n when t h e n i t r o g e n b u b b l i n g s t o p p e d 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 t o a l 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 t h e p y r a z o l i n e was  i n j e c t e d by a s y r i n g e t h r o u g h a r u b b e r septum.  A l l runs were f o l l o w e d  - 130 -  up to 80% completion and then kept f o r 10 h a l f l i v e s i n the bath to obtain the f i n a l volume. volumes were within ± 2%.  The experimental and the calculated f i n a l The barometric pressure changes were also  monitored during the k i n e t i c runs. The k i n e t i c runs with deuterated compounds were done immediately a f t e r the corresponding nondeuterated pyrazolines. The rate constants were calculated on Hewett-Packard's desk calculator using the method o f least  squares.  Since the deuteration o f the trans-3-methy1-3-carbomethoxy-1pyrazoline-4d^ and the trans-3-methyl-3-carbethoxy-l-pyrazoline-4d^ was only 90% correction had to be made i n the rate of decomposition. The corrections were based on the assumption of the pyrazolines and t h e i r analogous  that the decompositions  -4d^ are concurrent reactions,  then the rate constants f o r the mixtures can be expressed as follows:  D meas  CD  = 0.1 k„ + 0.9 k, D  The measured o v e r - a l l deuterium k i n e t i c isotope effect i s given by eqn.  (2).  k, D meas  D  (2)  - 131 -  I f we assume that the i n d i v i d u a l processes involved i n pyrazoline decompositions are p a r a l l e l reactions we can calculate 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 for each separate pathway from the o v e r - a l l k i n e t i c isotope e f f e c t and the product d i s t r i b u t i o n s . The rate constant  for the thermolysis of a pyrazoline can be  expressed as follows:  k  H  =  k  lH  +  k  2H  +  ••••  Similarly, the rate constant deuterated  +  k  nH  ( 3 )  for the thermal decomposition of a  pyrazoline can be given as  k  D  =  k  lD  +  k  2D  +  ••••  +  k  nD  ( 4 )  where k , k „ , k „ are the rate constants for the i n d i v i d u a l IH 2H nH reactions involved i n the decomposition of a pyrazoline and 1u  K  1D'  k  u  2D'  k  nD  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  1H  "dt  -  =  k  lH H C  '  ( 5 )  - 132 -  nH ~dt~ dC  d C  =  k  nH H  '  =  k  lD D  >  =  k  C  ( 6 )  lD  -ardC  C  w  '  n D  ~dt~  nD D C  ( 8 )  where C , C „ are the concentration of products and C,~, C IH nH ID nD 1LJ  c  concentration of the deuterated  are the  products.  Dividing eqn. (5) by eqn. (6), and eqn. (7) by eqn. (8) we obtain,  m  dc  k  nD  nH  k  (  '  nD  The integration of eqn. (9) and eqn. (10), assuming that C , C-„, in Zn , C and C , C_ , C _ = 0 at t = 0, yields the r e s u l t s , 1 U  in  n  nH  ^  nD  nH  •  ^ nD  K  C12J  - 133 -  It follows that,  C  1H 2H  C  lD  : C  : C  : >  , : C  2D """ :  nH  : C  nD  =  The d i v i s i o n of eqn. (3) by k  1 u  K  1H 2H '  k  lD 2D ---" nD  :K  ' nH  :  : k  : ,  : k  and eqn. (4) by k  In  IH  k  =  1  • K  ^ 1D  ( 1 4 )  iri  yields,  ID  IH  lD  ^  :k  IH  •  ....  * K  ^ 1D  =  B  (16)  Dividing eqn. (15) by eqn. (16) we get,  k  H  k  lH  A  k  D  B  k  lD  (17)  The rearrangement and substitution of D f o r _H  give,  *D~  k  lH  k  lD  _  BD  (18)  A  The values of A and B are obtained from product studies and D from kinetic measurements.  - 134 -  I.  Rate c o n s t a n t s , a c t i v a t i o n parameters  and o v e r a l l d e u t e r i u m  isotope e f f e c t of 3-methyl-3-carbomethoxy-l-pyrazoline  kinetic  and t r a n s -  3-methy1-3-carbomethoxy-1-pyrazoline-4d  (a)  Rate  constants. 3  Name o f compound  t'  kx]L0-  3-methyl-3-carbomethoxy1-pyrazoline  122,.85 122,.85 124,.85 124. ,85 127..27 127,.26  3,.43 3.,25 4.,31 4.,54 5..37 5..36  AH = 33,.45 k c a l AS = 9,.52 e.u.  90% t r a n s - 3 - m e t h v l - 3 carbomethoxy-1-pyrazoline4d + 10% u n d e u t e r a t e d isomer  122.,85 124. ,85 127. ,32  2..91 3.,87 4..65  AH = 33.,60 k c a l AS = 9,.61 e.u.  l s  (b)  4  O v e r a l l deuterium k i n e t i c i s o t o p e e f f e c t s . ,  3.43  Ji k  D  , k„  n  k  =  2.91 4.31 _  D  H  x  IO"  =  1.15  4  -4 x 10 in  1.14 x  10"  + 5.36 2 4.65  -4  1 0  Z  5.37 -  in X  + 4.54 =  3.87  , k  + 3.25 2  x 10  4  1A X  -4  -4  1 0  1.16  - 135 -  (c)  C o r r e c t e d o v e r a l l deuterium  1.  H ~ D  k i n e t i c isotope  effects,  k  =  1.18  k  2.  k  H  R  3.  1.16  ^  1.17  D  =  H k  k  1  -  1 8  (d)  S p e c i f i c deuterium  1.  Deuterium k i n e t i c i s o t o p e e f f e c t = kg,Y  4.5  =  k ,Y  !  +  «L1  +  9^  V H  22.14  k  k  27.62  k  f o r 3,y-olefin 16di 4.5  =  =  2  ?  2 2  -  6  .  formation:  1 4  2  3.5  H  Y  k  effects.  17,7  +  3.5  D  +  4.5  3.5  3  2.  Mil + M l  i +  H  -V  k i n e t i c isotope  D  H , k'D  -  r  1.17  -  0.80  1.46  6' D Y  Deuterium k i n e t i c i s o t o p e e f f e c t  k  H  kcyc  =  4.5  +  . 1  +  64.4  It  14.3  +  64.4  f o r cyclopropane  16.5  , =1.55 r r  64.4  H k  D  kcyc  = D  3.5 69.3  +  . 1  +  9.7 69.3  +  17.7 69.3  =  1  1.46  formation:  - 136 -  kcyc  H  1.55  1.17  1.46  1.06  =  1.10  kcyc  Dueterium k i n e t i c i s o t o p e e f f e c t  f o r methyl  angelate  formation:  k  H  =  kang„ n  4.5  64.4  +  14.3  =  kang  hi  +  14.3  *L1  +  9.7  k  . 1  +  16.5  =  6.95  14.3  +  :  17V7  +  9.7  =  1 0  _  3 2  9.7  H  k a n g  k  H  =  =  10.32  D  kang  6.95  1.17  k  =  ? 4  0.673  D  Deuterium k i n e t i c i s o t o p e e f f e c t f o r methyl t i g l a t e f o r m a t i o n  k  H  ktig  k  =  ktig  = D  +  16.5  H  D  4.5  3.5 17.7  64.4  +  16.5  +  69.3 17.7  14.3  +  , 1  =  , 6.04  +  . 1  =  _ ^ 5.66  16.5  +  9.7 17.7  - 137  ktig.  -  k, _H  6.04  1.17  5.66 ktig  II.  1.09  1.07  r  Rate c o n s t a n t s , a c t i v a t i o n parameters and o v e r a l l d e u t e r i u m k i n e t i c i s o t o p e e f f e c t o f 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 t r a n s - 3 -  methyl-3-carbethoxy-l-pyrazoline-4d (a)  Rate c o n s t a n t s .  Name o f compound  t°  kxlO  3-methyl-3-carbethoxy1-pyrazoline  117, .89 117, .89 119, .81 119, .81 122, ,95 127, .01 126, ,95  1 .74 1 .83 2 .11 2..21 3 .14 4 .71 4,.63  AH AS  = =  33..20 k c a l 8,.67 e. u.  trans-3-methy1-3carbethoxy-1-pyrazoline-  117. ,89 117. ,89 119. ,81 122. 95 126. 95 127. 01  1..65 1,.67 1,.98 2,.82 4..18 4,.30  AH AS  := :=  32,,37 k c a l 6. 14 e .u.  4  " l d  (b)  O v e r a l l deuterium k i n e t i c isotope  1.  (1-74  + 1-83)  (1.65 + 1.67)  x 10" x  4  10"  = 4  1 > 0 ?  effect.  - 138 -  (2.11 + 2.21) 2 =  1.98  3.14 x 1 0 "  4  2.82 x 1 0 "  4  4.63 x 1 0 "  4  4.18 x 1 0 "  4  4.71 x 10  1.09  1.11  1.11  4  4.30 x 1 0 "  1.09 4  Corrected overall deuterium k i n e t i c isotope effects, 1.78 = 0.178  H —  + 0.9  K  1.070  Q  k  k  =  1.08  D  ^  - i.i:  H —  =  k  k  ^ 1. l.>  D  — k  1  D  =  1.13'  a,  1.12  - 139 -  5.  k —  (d)  =  1.10  S p e c i f i c deuterium k i n e t i c isotope  1.  effects.  Deuterium k i n e t i c i s o t o p e e f f e c t f o r 8 , Y - o l e f i n f o r m a t i o n :  1  =  k ,Y g  Y  g J  4.2  !  +  1^1  12L0  +  4.2  +  3.6  D  k  k  12,6  +  H  =  k  +  =  2  3  8  6  4.2  Ihl =  8^ 3.6  +  27.81  3.6  H  g' H  23.86  k  27.81  T  D  k  H k  1.12  1.30  0.858  Q  V D Y  2.  Deuterium k i n e t i c i s o t o p e e f f e c t  f o r cyclopropane  formation: k  H  kcyc  =  4.2  +  1  70.4  H  +  12.6  +  13.0  70.4  70.4  8.9 74.4  13.2 = 74.4  =  . 1.424  k D kcyc  =  Q  3.6 74.4  +  +  +  1.345  - 140 -  H  k C y C  k  1.424  -  k  1.345  D  kcyc  H — k  -  1.12  =  1.06  1.058  D  D  Deuterium k i n e t i c i s o t o p e e f f e c t f o r e t h y l  _Y  =  kang  k  H  D  _  kang  ±1  Z^l  +  12.6  3.6  k  1  13^0  +  12.6  7JL4  +  8.9  D  +  =  _  y  angelate  formation  9 5  12.6  +  1  1^2  +  8.9  =  n  >  2  4  7  8.9  H  k a n g  k  H  _ —  7.95 11.247  D  k  —  H k  1.12 —  —  0.707  D  1 .bo  ' ang • k  D  Deuterium k i n e t i c i s o t o p e e f f e c t  k  H  4.2  =  ktig  +  13.0  u  70.4  +  13.0  12.6  f o r ethyl  t i g l a t e formation:  +  . 1  =  , 7.704  +  1  =  7.583  n n A  13.0  n k  H  ktig  3.6  =  13.2  D  k  +  74.4 13.2  +  8.9 13.2  H H  k t l g  k  7,704 7.583 !  D  ktig  =  D  =  k  D  U 2 _  =  1.015  1  1 Q  - 141 -  Rate c o n s t a n t s and a c t i v a t i o n parameters  o f c i s - and t r a n s - 3 -  methyl-4-akyl-3-carbomethoxy-1-pyrazolines.  Name o f compound  t°  kxlO  sec  cis-3-methyl-4-isopropyl-3-carbomethoxy-1pyrazoline  141.0 147.0 151.0 151.3  1.61 2.74 4.40 4.79  AH AS  = 3 6 . 6 0 k c a l mol = 11.75 e.u.  trans-3-methyl-4-isopropyl-3-carbomethoxy-lpyrazoline  156.5 160.5 164.5 169.6  1.59 2.71 4.41 5.77  AH AS  = 3 4 . 5 0 k c a l mol = 3.91 e.u.  cis-3-methyl-4-isobutyl-3-carbomethoxy1-pyrazoline  144.5 147.0 154.5  2.14 2.80 5.85  AH AS  = 3 5 . 3 0 k c a l mol = 8.55 e.u.  trans-3-methy1-4-isobutyl-3-carbomethoxy1-pyrazoline  144.5 147.1 150.0 152.5  0.78 0.94 1.36 1.68  AH AS  = 35.00 k c a l mol = 5.76 e.u.  Rate c o n s t a n t s , a c t i v a t i o n parameters  and d e u t e r i u m  kinetic  isotope e f f e c t o f cis-3-methy1-4-tert-butyl-3-carbomethoxy-1p y r a z o l i n e and i t s analogue-4d Name o f compound cis-3-methy1-4-tertbuty1-3-carbomethoxy1-pyrazoline  3  t'  141,.00 147,.00 151,.00 151,.39 151..49 154,.20 154,.50  -4 f kxlO s e i 2.02 3.73 5.17 5.39 5.51 6.97 7.57  1  AH AS  = 35.67 k c a l m o l = 9.90  - 1  - 142 -  Name o f compound cis-3-methyl-4-tertbutyl-3-carbomethoxyl-pyrazoline-4-d  (a) Deuterium  k  H  k  -4 -1 kxlO sec  151.39 151.49 154.20 154.50  4.49 5.01 6.44 6.89  AH AS  = 3 6 . 3 6 k c a l mol' = 11.32 e.u.  k i n e t i c isotope effects.  5.39 x 1 0 "  =  t°  4  4.94 x 1 0 "  1.091 4  D 2.  S\ k  =  5.51 x 10  4  1.099  5.01 x 1 0 "  D  4  = k _H k  6.97 x 10  =  k _H k  -4 1.082  6.44 x 1 0 "  Q  =  7.57 x 10  1.093 ± 0.008  4  -4  6.89 x 1 0 "  1.098 4  D Rate c o n s t a n t s , a c t i v a t i o n parameters  and d e u t e r i u m  kinetic  isotope e f f e c t o f trans-3-methyl-4-tert-butyl-3-carbomethoxy1 - p y r a z o l i n e and i t s Name o f compound trans-3-methy1-4tert-butyl-3-carbomethoxy-l-pyrazoline  analogue-4d t°  kxlO s e c  148.70 148.84 150.96 153.30 154.00  1.28 1.31 1.59 1.97 2.30  AH AS  = 3 6 . 2 0 k c a l mol = 8.80 e.u.  - 143 -  Name o f compound  t°  trans-3-methyl-4tert-butyl-3-carbomethoxy-l-pyrazoline4d  kxl0~ sec ' 4  148.84 150.96 153.30  1.20 1.48 1.89  AH AS  = 36.67 k c a l mol' = 9.74 e.u.  r  (a) Dueterium k i n e t i c i s o t o p e e f f e c t s . 1.  k  H k  1.31 x 10"  = 1.091 4  D  1.20 x 1 0 "  H  1.59 x 1 0 "  4  k D.  1.48 x 1 0 "  4  1.97 x 1 0 "  4  1.89 x 1 0 "  4  k  n  =  k  D n  1.074  * 1.069 ± 0.024  1.042  Rate c o n s t a n t s , a c t i v a t i o n parameters and o v e r a l l d e u t e r i u m k i n e t i c isotope effect o f l-carbomethoxy-2,3-diazabicyclo(3.3.0) oct-2-ene and i t s analogue-5d^.  Name o f compound  t°  kxlO  4  1-carbomethoxy-•2,3d i a z a b i c y c l o ( 3 . 3.0) oct-2-ene  127..75 128..74 129..74 131..74 132..74  7,.82 8..45 9.,40 11.,22 12.,01  AH AS  = 28. 30 k c a l mol = -2 .62 e.u.  1-carbomethoxy-•2,3d i a z a b i c y c l o ( 3 . 3.0)oct-2-ene-5d^  127.,75 128.,74 129.,74 131.,74 132.,74  6.,20 6.,64 7.,53 9.,27 10.,06  AH AS  = 32.40 k c a l mol = 7 .17 e.u.  - 144 -  (a) O v e r a l l d e u t e r i u m k i n e t i c i s o t o p e  k  H  k  7.82 x 10  — k  4  =  6.20 x 10"  D  -  8  -  x 10"  4 5  1.26  4  4  6.64 x 10"  D  effect.  1.27  4  ^ 3.  9.40 x 10" k  4.  •k _H k  5  -  7.53 x 10"  D  1.122 x 10  — k  = 1.25  4  _  1.21  9.27 x 10"  D  -  1-201 x 10"  4  3  1.006 x 10"  Q  = 3  (b) S p e c i f i c d e u t e r i u m k i n e t i c i s o t o p e 1.  Deuterium k i n e t i c i s o t o p e e f f e c t  _A. k ,Y g  3  H  Y  D  V D Y  34,3  =  9.78  10.2  S*A  +  __  1 3  _  3 2 3  7.5  H  V H k  +  effects.  f o r B,y o l e f i n  +  7.5  D  k  ILi  +  10.2  1 k ,Y  l  =  1.24  4  „  =  _^78_ 13.323  =  0  >  ?  3  4  ^  =  k  Q  1  >  6  8  formation:  - 145 -  2.  Deuterium k  H  _  kc7c~ H k  D  10.2  19.6  ^  .  +  1  7.0  34.3  5  kc  — $  =  k  T 7 T ~ T "  58.1  34.3  y°u  19.6  +  7.5  =  kcTc^"  k i n e t i c isotope e f f e c t f o r cyclopropane formation:  09  =  5.09  2.91  k  =  2.91  D  =  1.745  u  _»  =  k [ )  0.71 _  kcyc  D  3.  Deuterium  k H  k  k i n e t i c isotope e f f e c t f o r a,B-olefin formation:  1 0  D  _  k,e a  2  •  7.5  +  1 9  "  +  6  344  +  1  =  1.4257  ^  1  58.1 58.1  D  k  -  H  k k ,e  -  R  ^257. 1.72  =  0.83 — -  ^  =  F  1.49  D  n  a  VII.  D  Rate c o n s t a n t s and a c t i v a t i o n parameters  o f 1-carbomethoxy-  2,5-diazabicyclo(4.3.0)non-2-ene. Name o f compound l-carbomethoxy-2,3diazabicyclo(3.3.0)non-2-ene  t  °  128.74 131.74 132.74  kxlO  4  8.21 10.81 11.81  AH AS  = 29.5 k c a l =0.13 e.u.  mol"  1  -IH  -  REFERENCES  1.  E. Buchner and H. Dessauer, B e r . , 26, 2S8 (1893).  2..  K. von Auwers and J . K o n i g , Ann., 496, 27 (1932).  3.  K. von Auwers and J . K o n i g , i b i d . , 496, 252 (1932).  4.  R. H u i s g e n , Angew Chem., 75, 604 (1963).  5.  R. H u i s g e n , Angew Chem., 75_, 742 (1963).  6.  E.M. Kosower:  An I n t r o d u c t i o n t o P h y s i c a l O r g a n i c C h e m i s t r y , John  W i l e y and Sons I n c . , New York, 1968, p. 209. 7.  W.E. Parkam, C. S e r r e s , J r . , P.R. O'Connor, J . Am. Chem. S o c , 87, 4119  (1965).  8.  H. P a u l , I . Lange  and A. Kausman, B e r . , 98, 1789 (1965).  9.  M.P. S c h n e i d e r and R.J. C r a w f o r d , Can. J . Chem., £8, 628 (1969).  10.  P.B. C o n d i t and R.G. Bergman, Chem. Comm., 4 (1971).  11.  G.W. C o w e l l and A. 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C l o s s , L.R. Kaplan and V . I . B e n d a l l , i b i d . , 89, 3376 (1967).  48.  G.L. C l o s s and L.R. Kaplan, i b i d . , 91_, 2168 (1969).  49.  J.C. Hinshaw and E . I . A l l r e d , Chem. Comm., 72 (1969).  50.  A.B. E v n i n , D.R. A r n o l d , L.A. K a r n i s c h k y and E. Strom, J . Am. Chem. Soc,  51.  92_, 6218 (1970).  D.E. McGreer, N.W.K. C h i u , M.G. V i n j e and C K . Wong, Can. J . Chem., 43, 1407 (1964).  52.  D.E. McGreer and Weh-Sai Wu, Can. J . Chem., 45_, 461 (1967).  53.  J.A. Berson and S.S. O l i n , J . Am. Chem. S o c , 91_, 777 (1969).  54.  E.L. A l l r e d , J.C. Hinshaw and A.L. Johnson, i b i d . , 91_, 3382 (1969).  55.  H. T a n i d a and S. T e r a t a k e , T e t r a . L e t t . ,  56.  E. A l l r e d and A.L. Johnson, J . Am. Chem. S o c , 93, 1300 (1971).  57, 4991 (1970).  -  149 -  57.  B.M. T r o s t  a n d R.M.  Cory,  ibid.,  9 3 , 5572  (1971).  58.  B.M. T r o s t  a n d R.M.  Cory,  ibid.,  9 3 , 5573  (1971).  59.  E.L. A l l r e d  60.  H.R.  61.  I.M.E. M a s t e r s ,  62.  D.F. E a t o n , 1351  and K . J . V o o r h e e r s ,  Snyder,  Ph.D. T h e s i s ,  Boston  Ph.D. T h e s i s ,  R.G.  Bergman  i b i d . , 9_5, 620 University,  University  (1973).  1958.  of British  a n d G.S. Hammond, J . Am.  Columbia,  1965.  Chem. S o c , 9 4 ,  (1972).  63.  P.G. Gassman  a n d K.T. M a n s f i e l d ,  64.  C. R u c h a r d t ,  Angew. Chem.  65.  W.  66.  S. I n a g a k i a n d K. F u k u i ,  67.  R. M o o r e , A. M i s h r a  Schmidt, Helv.  J . O r g . Chem., 65_, 950  Internat.  Chim. A c t a . , Bull.  Edit.,  54, 862  9_, 830  (1970).  (1971).  Chem. S o c . J a p a n ,  and R . J . C r a w f o r d ,  (1967).  45_, 824  (1972).  C a n . J . Chem., 4 6 , 3305  (1968). 68.  W.  Fowells,  C. S c h u e r c h ,  F.A. B o v e y a n d F . P . Hood, J . Am.  Chem.  S o c . , 89_, 1396 (1967) . 69.  P.E. P e t e r s o n a n d J . E . Duddey, J . Am.  70.  H. G l u c k s m a n n , Mon. t u e r  71.  R.R.  72.  Beilstein,  Fraser,  Chem.,  Chem. S o c , 88_, 4990  10, 771  C a n . J . Chem., 38, 549  Handbuch d e r O r g a n i s c h e n  (1966).  (1889).  (1960). C h e m i e . , H., V o l . IX, 22, 44.  - 150 -  APPENDIX  T h i s appendix  i s aimed a t c o r r e c t i n g a d e f i c i e n c y i n t h e t h e s i s i n  t h e o m i s s i o n o f e r r o r l i m i t s f o r much o f t h e d a t a . Many s t u d i e s have been r e p o r t e d i n t h i s t h e s i s and t h a t o f M a s t e r s (61) on t h e r a t e o f d e c o m p o s i t i o n o f 3 - m e t h y l - 3 - c a r b o m e t h o x y - l - p y r a z o l i n e . The average e r r o r i s as h i g h as 5% b u t i n s p i t e o f c h a n g i n g o p e r a t o r s and equipment t h e v a l u e s r e p o r t e d a t 127° were t h e same w i t h i n t h e e r r o r limits.  I t i s f e l t t h a t t h e major s o u r c e o f e r r o r i s i n o u r i n a b i l i t y  t o r e p r o d u c e and m a i n t a i n t h e t e m p e r a t u r e  at a given value.  The  v a r i a n c e i n d a t a can be reduced t o 1% by d o i n g a s e r i e s o f c o n s e c u t i v e runs w i t h o u t a l t e r i n g t h e t e m p e r a t u r e t u r e bath.  c o n t r o l s on t h e c o n s t a n t tempera-  F o r t h i s reason runs f o r d e t e r m i n i n g t h e k i n e t i c i s o t o p e  e f f e c t were done one a f t e r t h e o t h e r 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 s o u r c e o f e r r o r s comes from combining r a t e d a t a and p r o d u c t c o m p o s i t i o n d a t a as was n e c e s s a r y t o i s o l a t e t h e d e u t e r i u m isotope effects f o r individual reactions.  I t s h o u l d be noted t h a t t h e  i s o t o p e e f f e c t f o r c y c l o p r o p a n e f o r m a t i o n from t h e 4 - t e r t - b u t y l  deriva-  t i v e s i s n o t s u b j e c t t o t h e s e q u a l i f i c a t i o n s as i n t h e s e cases t h e o n l y p r o d u c t was a c y c l o p r o p a n e p r o d u c t . To i l l u s t r a t e t h e e f f e c t , o f e r r o r s i n t h e p r o d u c t m i x t u r e a n a l y s i s on t h e d e r i v e d i s o t o p e e f f e c t s we w i l l c o n s i d e r one s e t o f d a t a w h i c h  - 151 -  l e a d s t o t h e a p p a r e n t l y anomalous i n v e r s e i s o t o p e e f f e c t f o r t h e c y c l o propane f o r m a t i o n from ene (164) (see p. 143).  l-carbomethoxy-2,3-diaza-bicyclo(3.3.0)oct-2The  d a t a g i v e n on page 53 a r e d e r i v e d from  t h e f o l l o w i n g r e s u l t s o f vapor c h r o m a t o g r a p h i c  a n a l y s e s a t 160° (see  p. 9 2 ) .  P e r c e n t p r o d u c t 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 w i t h average d e v i a t i o n s  cyclopropane  165  a,3-olefin  166  B,y-olefin  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 p r o d u c t d i s t r i b u t i o n from of  cyclopropane  164-5d,.  58.0  34.7  57.5  33.8  59.2  34.6  58.4  34.2  57.3  34.2  57.3  34.4  59.6  ±  8,Y-olefin  ct,B-olefin 182  181  34.7  34.4  pyrolysis  58.2  0.3  ±  •  •  167  7.2 7.7 7.0 7.0 8.4 8.4 7.1  7.5  0.7  ±  0.5  C l e a r l y the l a r g e s t r e l a t i v e e r r o r i s i n the minor component. T h e s e d a t a were used the  isotope  effect for  c y c l o p r o p a n e d e r i v a t i v e on p. 143 and y i e l d e d a v a l u e f o r k^/  kjj o f  0.71.  deviation) error  I f we make use o f p r o b a b l e e r r o r s c a r r y the e r r o r s through  i n the s p e c i f i c deuterium  H kcyc  _  k  1.  t o c a l c u l a t e the deuterium  H  10.2 19:6  ± 0.8 ± 0.8  the c a l c u l a t i o n s  isotope  +  (0.845 x  e f f e c t can be  average  *theprobable calculated.  70.1 ± 1.3 19.6 ± 0.8"  F. D a n i e l s , Mathematical P r e p a r a t i o n McGraw H i l l , 1956, p. 224.  f o r Physical  Chemistry,  - 155 -  = .52 ± 0.05  D kcyc k  k  D  H/  /ku n  ± 0.16  7.5 34.4  ± 0.4 ± 0.3  . 58.2 + 1 + 34.4  ±  0.22  ± 0.1  + 1 + 1.09  ± 0.03  .  D  k c / C  X  + 1 + 3.57  5.09  ± 0.16  kc7c7H 2.91 ± 0.03  ^k c y c  =  =  D  1.75  ±t nnl 0.06  = 175  =  = 5.09  ±  0.16  = 2.91  ±  0.03  ±0.7 0.3  .__  . _  ~ °-°  +  °'  71  6  ./  ± ' 0  0 3  or  ±4%  A s u r v e y o f the d a t a suggest t h a t i n g e n e r a l t h e p r o b a b l e  error  i s w i t h i n 5% except i n the cases o f c a l c u l a t i o n s on minor components. F o r example, t h e B , y - o l e f i n 167 g i v e s a s p e c i f i c k^Ap or  o f 1.68  ±  6%. F i n a l l y t h e v a l u e s o f AH* and AS* which a r e d e r i v e d from  rate  d a t a a t v a r i o u s t e m p e r a t u r e s 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 . we assume 5% a c c u r a c y i n the r a t e c o n s t a n t s and a t e m p e r a t u r e of  0.10  10°C,  t h e maximum e r r o r i n AH*  If  interval  can be e s t i m a t e d by t h e e q u a t i o n  2 g i v e n by Wiberg •p  6 =  2.  iY  2R , _ T  1  T  K.B. Wiberg, p. 378.  a  " P h y s i c a l Organic Chemistry", McGraw-Hill,  1940,  - 154 -  a i s the f r a c t i o n a l  error i n the r a t e  constant  6 i s t h e maximum e r r o r i n AH*. By u s i n g t e m p e r a t u r e s  o f 130 and 140°C we f i n d  6 = 3.3 k c a l / m o l e o r ±10% F o r t h e maximum e r r o r i n AS* t h e f o l l o w i n g e q u a t i o n can be used  T  +  2T'T  6 = 8.3 e.u. C l e a r l y t h e v a l u e s o f AH^ and AS* measured from a 10° i n t e r v a l have t o o l a r g e a  p r o b a b l e e r r o r t o be used i n any d e f i n i t i v e way.  

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