UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

Mechanism of pyrolysis of 3,3,4,5-tetrasubstituted 1-pyrazolines. McKinley, James William 1969

Your browser doesn't seem to have a PDF viewer, please download the PDF to view this item.

Item Metadata

Download

Media
831-UBC_1970_A6_7 M34.pdf [ 4.62MB ]
Metadata
JSON: 831-1.0059988.json
JSON-LD: 831-1.0059988-ld.json
RDF/XML (Pretty): 831-1.0059988-rdf.xml
RDF/JSON: 831-1.0059988-rdf.json
Turtle: 831-1.0059988-turtle.txt
N-Triples: 831-1.0059988-rdf-ntriples.txt
Original Record: 831-1.0059988-source.json
Full Text
831-1.0059988-fulltext.txt
Citation
831-1.0059988.ris

Full Text

MECHANISM OF PYROLYSIS OF 3,3,4,5-TETRASUBSTITUTED 1-PYRAZOLINES BY J.W. McKINLEY B . S c , U n i v e r s i t y of B r i t i s h Columbia, 1967 A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF. SCIENCE i n the Department of CHEMISTRY We accept t h i s Thesis as conforming to the required standard THE UNIVERSITY OF BRITISH COLUMBIA December, 1969 In presenting this thesis in partial fulfilment of the requirements for an advanced degree at the University of British Columbia, I agree that the Library shall make it freely available for reference and study. I further agree tha permission for extensive copying of this thesis for scholarly purposes may be granted by the Head of my Department or by his representatives. It is understood that copying or publication of this thesis for financial gain shall not be allowed without my written permission. Depa rtment r The University of British Columbia Vancouver 8, Canada Date ABSTRACT A s e r i e s of t e t r a s u b s t i t u t e d 1-pyrazolines uniquely substituted at a l l three carbon centers has been prepared and decomposed thermally. The 1-pyrazolines i n which three of the substituents occupy a pseudo equatorial p o s i t i o n and the remaining substituent occupies a pseudo a x i a l p o s i t i o n give as the major product the cyclopropane with reten-t i o n of c o n f i g u r a t i o n . On the other hand,the 1-pyrazolines i n which two substituents are pseudo equatorial and two are pseudo a x i a l give a random d i s t r i b u t i o n of cyclopropanes. Evidence i s presented that the former set of pyrazolines have a larger degree of f o l d i n g between the two planes defined by C-3, C-4, C-5 and C-5, N-1, N-2, C-3. This suggests that the larger the degree of f o l d i n g i n the pyrazoline molecule the more s t e r e o s p e c i f i c i t y there i s . Two mechanisms are proposed to account f o r the cyclopropane formed with retention of configuration - one i n v o l v i n g a concerted mechanism and the other involv-ing an intermediate resembling a pyramidal d i r a d i c a l . In the case of one p a i r of C-5 isomeric pyrazolines, the pyrazoline i n which three substituents are pseudo equatorial and one i s pseudo a x i a l gave 99% cyclopropane products whereas the C-5 isomer i n which there are two substituents both equatorial and a x i a l gave 67% o l e f i n products. This supports the mechanism i n v o l v i n g concerted migration of the hydrogen at C-4 that i s trans to the leaving nitrogen. - i i i -TABLE OF CONTENTS Page I. INTRODUCTION . . 1 P y r o l y s i s of 1-Pyrazolines 1 a) 3-Acetyl and 3-Carbomethoxy-1-Pyrazolines 1 b) 3,5-Diaryl-l-Pyrazolines 13 c) 3-Cyano-3-Carbomethoxy-l-Pyrazolines 14 d) A l k y l Substituted 1-Pyrazolines 19 II . RESULTS AND DISCUSSION 36 Preparation and Product D i s t r i b u t i o n s 36 I d e n t i f i c a t i o n of Pyrazolines 45 I d e n t i f i c a t i o n of Cyclopropanes 49 I d e n t i f i c a t i o n of Olef i n s 52 Discussion 55 a) O l e f i n Formation 55 b) Cyclopropane Formation 60 I I I . EXPERIMENTAL 73 General Statement 73 N-Nitroso-N-ethyl Urea 73 Diazoethane 74 Benzaldehyde Hydrazone 74 Phenyl Diazomethane 74 3-Methyl-3-pentene-2-one, (Z)- (131) 75 3-Methyl-4-phenyl-3-butene-2-one, (E)- (132) 76 - i v -Page 3-Acetyl-3',4'-dimethyl-5-(and 5')-phenyl-l-pyrazolines (118 and 119) 7 6 a) Preparation and Enrichment 76 b ) P y r o l y s i s and Product I d e n t i f i c a t i o n 78 c) Product D i s t r i b u t i o n 80" 3'-Acetyl-3,4'-dimethyl-5-(and 5')-phenyl-l-pyrazolines (120 and 121) 8 1 a) Preparation and Enrichment 81 b ) P y r o l y s i s and Product I d e n t i f i c a t i o n 8 2 c) Product D i s t r i b u t i o n 8 ^ 3-Acetyl-3',4-(and3*,5')-dimethyl-4 1-phenyl-l-pyrazolines (122 and 123) 8 4 a) Preparation and Enrichment 8 4 b ) P y r o l y s i s and Product I d e n t i f i c a t i o n 8 ^ c) Product D i s t r i b u t i o n 8 7 Erythro- and threo-3-methyl-4-phenyl-5-hexene-2-one (134 and 135) . 8 8 Trimethyl a-phosphonopropionate 88 Methyl 3-methyl-3-benzyl-2-butenoate, (E)- (128) and (Z)- (129) . 89 3-Methyl-4-benzyl-3-pentene-2-one, (E)- (128) and (Z)- (129) 90 Methyl-2-methyl-3-phenyl-2-pentenoate, .(E)- (140) and (Z)- (141) 91 3-Methyl-4-phenyl-3-hexene-2-one, (E)- (136) and (Z)-. (158) 92 - V -Page BIBLIOGRAPHY 94 APPENDIX 97 Nomenclature 97 - v i -LIST OF TABLES Table I 3,3,4,5-Tetrasubstituted-l-pyrazolines II P y r o l y s i s Products f o r 1-Acetyl-l 1,2 1-dimethyl-3-(and 3')-phenyl-l-pyrazolines (118 and 119) and l ' - A c e t y l -l,2-dimethyl-3-(and 3 1)-phenyl-l-pyrazolines III P y r o l y s i s Products f o r 1-Acetyl-l',3-(and 1»,3')-dimethyl-2 1-phenyl-l-pyrazolines (122 and 123) IV N.m.r. Data f o r 3,3,4,5-Tetrasubstituted 1-Pyrazolines V N.m.r. Data f o r 1,1,2,3-Tetrasubstituted Cyclopropanes VI N.m.r. Data f o r Determination of Conformational Preferences of 3-Methyl-3-acetyl-l-pyrazolines VII Cyclopropane Products from 3,3,4,5-Tetrasubstituted-l-pyrazolines VIII D i s t r i b u t i o n of Cyclopropane Products f o r Pyrazolines with Electron Drawing Group at C-3 IX D i s t r i b u t i o n of Cyclopropane Products f o r 3,5-diaryl-1-pyrazolines and A l k y l Substituted 1-pyrazolines X D i s t r i b u t i o n of Products for the Pyr o l y s i s of D i f f e r -ent Ratios of the Pyrazolines 118 and 119  XI D i s t r i b u t i o n of Products f o r the Py r o l y s i s of D i f f e r -ent Ratios of the Pyrazolines 120 and 121  - V l l -Table Page XII D i s t r i b u t i o n of Products for the P y r o l y s i s of D i f f e r -ent Ratios of the Pyrazolines 122 and 123 8 7 - v i i i -LIST OF FIGURES Figure Page 1" Ionic mechanism for the p y r o l y s i s of 3,4-dimethyl-3-carbomethoxy-1-pyrazolines 2 2 O l e f i n formation from preferred conformations of 3,5-dimethyl-3-carbomethoxy-l-pyrazolines 5 3 Intermediate i n dihydrofuran formation 7 4 Preferred conformations of 3,5-dimethyl-3-acetyl-l-pyrazolines 7 5 T r a n s i t i o n states of the o l e f i n forming r e a c t i o n f o r c i s - and trans-3-methyl-4-ethy1-1-pyrazolines 9 6 K i n e t i c scheme for the 3-methyl-3-carbomethoxy-l-pyrazolines H 7 Radical mechanism for 3,5 - d i a r y l - l - p y r a z o l i n e s 15 8 T r a n s i t i o n state f o r the p y r o l y s i s of 3-cyano-3-carbo-methoxy-4-alkyl-4-aryl-l-pyrazolines 18 9 K i n e t i c scheme for p y r o l y s i s of a l k y l substituted 1-pyrazolines . .. 20 10 A l t e r n a t i v e k i n e t i c scheme f o r p y r o l y s i s of a l k y l s u bstituted 1-pyrazolines 21 11 Rate determining t r a n s i t i o n state f o r 3 - v i n y l - l -pyrazoline ... 22 - i x -Figure Page 12 ir-Cyclopropane intermediates 23 13 Concerted t r a n s i t i o n state f o r o l e f i n forming r e a c t i o n f o r c i s - and trans-4-deuterio-3-methyl-1-pyrazolines.. 25 14 Two trimethylene intermediates from c i s - and trans-3,4-dimethyl-1-pyrazoline 26 15 T r a n s i t i o n states and o l e f i n s expected on basis of concerted mechanism f o r p y r o l y s i s of c i s - and trans-3,4-dimethyl-5,5-d2-l-pyrazolines 27 16 K i n e t i c scheme for Z,3-d^- and 3,3,5,5-d^-l-pyrazolines 29 17 K i n e t i c scheme f o r 4-d^- and 4,4-d2~l-pyrazolines .... 30 18 Pyramidal d i r a d i c a l mechanism f o r decomposition of exo- and endo-5-methoxy-2,3-diazabicyclo[2.2.1]-2-heptene 33 19 T r a n s i t i o n state f o r concerted nitrogen e l i m i n a t i o n from exo-5,6-dideuterio-2, 3-diazabicyclo[2.2.1]-2-heptene 35 20 Favourable conformations of c i s - and trans-3,5-dimethyl-3-acetyl-l-pyrazolines 46 21 Conformational preferences of 5-(and 5')-phenyl-3 1,4 1 -dimethyl-3-acetyl-l-pyrazolines 47 22 Preferred conformations and C-5 chemical s h i f t values of some 3-methyl-3-acetyl-l-pyrazolines 48 - X -Figure Page 23 Thermal rearrangement of 1-acetyl-l 1,3-dimethyl-2 1 -phenyl-cyclopropane 51 24 Reaction sequence i n preparation of 3-methyl-4-phenyl-3- hexene-2-one, (E) and (Z) S3 ~> 25 3-Methyl-4-phenyl-3-hexene-2-one, (E) and (Z) assignment by n.m.r S3 26 Reaction sequence for preparation of 3-methyl-4-benzyl-3-pentene-2-one, (E) and (Z) 55 27 Preferred conformations of 3-acetyl-3',5- and (3',5')-4- phenyl-l-pyrazolines S6 28 Concerted mechanism for formation of cyclopropanes with retention of configuration 67 29 Pyramidal d i r a d i c a l mechanism f o r formation~of cy c l o -propanes with retention of configuration 67 30 Intermediate resembling a pyramidal d i r a d i c a l species i n p y r o l y s i s of endo-5-methoxy-2,3-diazabicyclo[2.2.1]-2-heptene 7 ^ - x i -ACKNOWLEDGEMENT I wish to thank Dr. D.E. McGreer f o r h i s h e l p f u l discussions and constant encouragement throughout t h i s research. } I. INTRODUCTION Pyro l y s i s of 1-Pyrazolines (a) 3-Acetyl and 3-Carbomethoxy-l-Pyrazolines von Auwers and Konig (1,2) studied the stereochemistry of the preparation of cyclopropanes by the addition of diazomethane to double bonds activ a t e d by electron-withdrawing groups, followed by thermal decomposition of the r e s u l t i n g pyrazolines. They concluded that when the intermediate pyrazolines are 1-pyrazolines, the cyclopropanes formed r e t a i n the geometry of the i n i t i a l o l e f i n s . Other studies by Jones (3-5) on 2-pyrazolines were based on the assumption that 1-pyrazolines decompose with retention of geometry. However, major errors i n the a n a l y t i c a l r e s u l t s of von Auwers and Konig have been demonstrated by McGreer and co-workers (6,7). In l a t e r work by Jones and T a i (8,9), they conclude that at best the r e a c t i o n i s p a r t i a l l y s t e r e o s p e c i f i c with respect to the three and four p o s i t i o n s of the pyrazoline. Rinehart and Van Auken (10,11) prepared and studied both the thermal and p h o t o l y t i c decompositions of the two isomeric pyrazolines, c i s - and trans -3,5-dimethy1-3-carbomethoxy-1-pyrazo1ines (1_ and 2). Py r o l y s i s of the s t e r e o c h e m i c a l ^ pure pyrazolines 1_ and 2_ gave four products i n c l u d i n g two cyclopropanes, i n d i c a t i n g the reaction gives products of mixed stereochemistry,although a s l i g h t degree of stereo-- 2 -C0 2CH 3 C0 2CH 3 C 0 2 C H 3 \ / / \ > ~ C 0 2 C H 3 rV N N 1 N = N 2 C0 2CH 3 18 12 66 C0 2CH 3 28 35 33 s e l e c t i v i t y i s noted. The r e s u l t s were explained by the i o n i c mechanism as shown i n Figure 1. I C0 2CH 3 i rC S T E P J I M ^ CH„ a 3 N N 1 or 2 C0 2CH 3 step b CH_ CH 3 3, 3 H ? — N 2 + step d C0 2CH 3 CH. step c CH cyclopropanes ^ .3 and 4 C0 2CH 3 CH. Figure 1 - Ionic mechanism f o r the p y r o l y s i s of 3,4-dimethyl-3-carbomethoxy-l-pyrazolines. - 3 -The C-3 N-2 bond i s f i r s t broken to give the i o n i c species 7_ i n which there i s competition between r o t a t i o n and loss of nitrogen. It i s expected that loss of nitrogen (step b) i s f a s t e r than r o t a t i o n , and thus the resonance forms 8^  and 9 would c y c l i z e immediately upon formation (step c) , r e s u l t i n g i n some s t e r e o s e l e c t i v i t y . Besides l o s i n g nitrogen (step b),the i o n i c species 1_ can also possibly give displacement of the diazonium group by backside attack of the C-3 carbanion (step d) . With larger groups present }any of these routes would p r e d i c t an increase i n s t e r e o s e l e c t i v i t y as a r e s u l t of more hindered r o t a t i o n . S i m i l a r l y , s t e r e o s e l e c t i v i t y should be reduced when the pyrazoline i s modified i n such a way as to increase the s t a b i l i t y , and hence the l i f e - t i m e , of the intermediates involved. The p o s s i b i l i t y that the pyrazolines themselves isomerize (reverse of step a) was ruled out since a f t e r p a r t i a l p y r o l y s i s none of the other isomeric pyrazoline could be detected. McGreer and co-workers (7,12,13) have investigated the p y r o l y s i s of 3-methyl-3-carbomethoxy-l-pyrazoline (10) and the two isomeric pyrazolines, c i s - and trans-3,5-dimethyl-3-carbomethoxy-1-pyrazolines (11 and 12). Py r o l y s i s of the three pyrazolines 10, 11, and L2 gave the following product d i s t r i b u t i o n s . 13 14 15 16 65 15 15 5 10 - 4 -3 4 17 18 19 -rY. 18 48 0 32 2 N== N 11 60 15 22 0 3 12 There are two important features from t h i s data. F i r s t of a l l , the a,B and B,y-unsaturated esters are formed e s s e n t i a l l y stereo-s p e c i f i c a l l y ; that i s , the o l e f i n 18_ from the pyrazoline 11 tand the o l e f i n 17_ from the pyrazoline 12_. An explanation i s possible assuming hydrogen migration i s concerted with nitrogen elimination, and assuming that the pyrazolines Y\_ and 1_2 e x i s t e n t i r e l y i n the conforma-tions as shown i n Figure 2. The r e s u l t s then suggest that the hydrogens designated as H m,which are trans to the leaving nitrogen,are migrating i n the olefin-forming r e a c t i o n . The second feature from the data i s the cyclopropane-forming r e a c t i o n i n which the c i s - p y r a z o l i n e 11 gives predominantly the trans-cyclopropane £,and the cyclopropane 5_ with the methyls c i s i s the predominant cyclopropane from the trans-pyrazoline 12. Thus the cyclopropane-forming r e a c t i o n i s not s t e r e o s e l e c t i v e and requires i n v e r s i o n e i t h e r at C-3 or C-5. The t r a n s i t i o n state may involve a d i r a d i c a l 9 or a d i p o l a r structure 7_ (Figure 1) but McGreer and - 5 -H 12 11 l i Figure 2 - O l e f i n formation from preferred conformations of 3,5-dimethyl-3-carbomethoxy-1-pyrazolines. ..co-workers favour a concerted process. The e f f e c t of solvent has been to r a i s e the proportion of the o l e f i n s i n the product as the d i e l e c t r i c constant of the solvent i s r a i s e d and t h i s suggests that the cyclopropane products are formed through a s l i g h t l y d i f f e r e n t t r a n s i t i o n state and presumably less polar than the o l e f i n s . To obtain i n v e r s i o n by a concerted process two extremes f o r nitrogen expulsion are considered. One i s loss of nitrogen i n theC-3,C-4 and C-5 plane,accompanied by formation of two p - o r b i t a l s at C-3 and C-5 which would bond to give product of retained configuration. The other i s loss of nitrogen perpendicular to the C-3,C-4 and C-5 plane giving two p - o r b i t a l s at C-3 and C-5 p a r a l l e l to each other. However,the groups at C-3 and C-5 would - 6 -b e s u f f i c i e n t l y c l o s e t o e a c h o t h e r t o c a u s e u n e q u a l s t r e t c h i n g o f t h e C-N b o n d s i n t h e t r a n s i t i o n s t a t e ? w h i c h w o u l d p e r m i t a t w i s t i n g o f t h e m o l e c u l e a n d e v e n t u a l l y l e a d t o i n v e r s i o n a t o n e c e n t e r . M c G r e e r e_t a l _ . ( 1 4 ) h a v e a l s o s t u d i e d t h e p y r o l y s i s o f t h e t h r e e p y r a z o l i n e s ; 3 - m e t h y l - 3 - a c e t y l - l - p y r a z o l i n e ( 2 0 ) a n d c i s - a n d 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 (Zl_ a n d 2 2 ) . P y r o l y s i s o f t h e p y r a z o l i n e 20. g a v e f i v e p r o d u c t s i n c l u d i n g 2 , 3 - d i m e t h y l - 4 , 5 - d i h y d r o -f u r a n ( 2 7 ) , a n d p y r o l y s i s o f t h e p y r a z o l i n e s 21_ a n d 22^ g a v e s i x p r o d u c t s i n c l u d i n g 2 , 3 , 5 - t r i m e t h y l - 4 , 5 - d i h y d r o f u r a n ( 3 3 ) . The formation of the dihydrofuran d e r i v a t i v e s i s explained assuming an intermediate 34 (Figure 3) i s formed with negative charge 3, products Figure 3 - Intermediate i n dihydrofuran formation. b u i l t up onC-3of the pyrazoline. As t h i s negative charge i s d e l o c a l i z e d i n t o the carbonyl oxygen, the oxygen w i l l be able to p a r t i c i p a t e i n a r i n g closure r e a c t i o n . The f a c t that the dihydrofuran d e r i v a t i v e 33_ i s formed e x c l u s i v e l y from the pyrazoline 21_ shows that s t e r i c factors present play an important r o l l . Assuming that the pyrazolines 21 and 22 e x i s t e n t i r e l y i n the conformations as shown i n Figure 4, then i t can Figure 4 - Preferred conformations of 3,5-dimethyl-3-acetyl-l-pyrazolines. be seen that i n 21_ the oxygen i s i n a more favourable p o s i t i o n f o r r i n g closure. The amount of dihydrofuran i s also influenced by the rea c t i o n medium. The percentage of the dihydrofuran isomer i s highest i n a non-polar solvent. There i s also an i n t e r e s t i n g c o r r e l a t i o n between the c i s - and - 8 -trans-3,5-dimethy1-3-acetyl-1-pyrazolines (21 and 22) and the c i s - and trans-3,5-dimethyl-3-carbomethoxy-1-pyrazolines (11 and 12). The two trans-pyrazolines 22 and 1__ give almost i d e n t i c a l product d i s t r i b u t i o n r a t i o s (cis-cyclopropane:trans-cyclopropane:olefin) of 60:15:25 and 61:17:22 r e s p e c t i v e l y . For the cis-pyrazolines,the product d i s t r i b u t i o n r a t i o s (cis-cyclopropane:trans-cyclopropane:olefin) are 18:48:34 f o r the 3-carbomethoxy pyrazoline H^and 16:24:37 plus 23% dihydrofuran f o r the 3-acetyl pyrazoline 21. I f the dihydrofuran portion i s added onto the trans-cyclopropane,the r a t i o becomes 16:47:37 f o r the pyrazoline ___ . which i s close to the r a t i o observed f o r the corresponding trans-3-carbomethoxy-pyrazoline 12_. This suggests that the dihydrofuran product i s being formed at the expense of the trans-cyclopropane during the p y r o l y s i s of the cj__-pyrazoline 21. McGreer and Wu (15) demonstrated s t e r e o s p e c i f i c o l e f i n formation by preparing and pyrolyzing the two isomeric pyrazolines. c i s - and trans-3-methyl-4-ethyl-3-carbomethoxy-l-pyrazolines (35 and 36). Each pyrazoline gave s t e r e o s p e c i f i c a l l y a d i f f e r e n t a,g-unsaturated ester. This s t e r e o s p e c i f i c i t y can be r e l a t e d to the structure of the pyrazoline through the requirement that loss of nitrogen must be from the side of the pyrazoline that i s trans to the migrating hydrogen at C-4. The product d i s t r i b u t i o n shows the same general trends as the corresponding 4-methyl pyrazolines 1_ and 2_. Pyrazolines 3_5 and 36_ do however show a greater proportion of cyclopropane product,and at the same time a greater tendency towards s t e r e o s p e c i f i c formation of the cyclopropanes. The mechanism based on concerted migration of hydrogen - 9 -CO„CH J \ 2 * . A < C0 2CH 3 C0 2CH 3 C,2 3 J \ / _ _ / ~ 37 N = N 35 C0 2CH 3 11 N = N 36 C0 2CH 3 72 13 / \ 38 39 40 41_ 9 0 56 4 from C-4 to C-5 trans to the leaving nitrogen can be applied i n t h i s case. The t r a n s i t i o n states 4_2 and 4_3 may be an t i c i p a t e d f o r the pyrazolines 35_ and 36 as i n Figure 5. H H C0 2CH 3 N 42 43 Figure 5 - T r a n s i t i o n states of the o l e f i n forming r e a c t i o n f o r c i s -and trans-3-methyl-4-ethyl-l-pyrazolines. Another example that i l l u s t r a t e s the concerted type o l e f i n formation i s the c i s , t r a n s - and cis,cis-3,4,5-trimethy1-3-carbomethoxy-1-pyrazolines (44 and 45). On the basis of the proposed o l e f i n forming - 10 -reaction,the a,8-unsaturated esters expected from the p y r o l y s i s of the pyrazolines 44 and 4_5 w i l l be the same i n both cases. N = N 45 McGreer and Masters (16) have determined the k i n e t i c s and product d i s t r i b u t i o n f o r the p y r o l y s i s of 3-methyl-3-carbomethoxy-l-pyrazoline (10) and i t s 4,4-d^ and 5,S-d^ analogues 50_ and _51_ i n t e t r a l i n , n-butyl phthalate, nitrobenzene and foramide. The k i n e t i c isotope e f f e c t s k^/k D f o r the 5,5-d2 pyrazoline 51_ of 1.22 and for the 4,4-d2 pyrazoline 50 of 1.36 are consistent with a mechanism invo l v i n g migration of the C-4 hydrogen concerted with loss of nitrogen. 13 C0 2CH 3 n-butyl-phthalate 10 14 68.9 14.7 15 12.3 16 4.1 D 2 C0 2CH 3 N = N 50 n-butyl-phthalate neat 78.2 77.8 9.6 8.9 10.2 10.5 2.0 2.8 N — N 51 C0 2CH 3 neat 63.8 14.6 16.2 5.4 Using the scheme i n Figure 6 ;the k i n e t i c isotope e f f e c t can be divi d e d i n t o a co n t r i b u t i o n from the o l e f i n forming r e a c t i o n and a (IV C0 2CH 3 . N = N o l e f i n s cyclopropane Figure 6 - K i n e t i c scheme for the 3-methyl-3-carbomethoxy-l-pyrazolines. - 12 -co n t r i b u t i o n from the cyclopropane forming r e a c t i o n by making use of the product d i s t r i b u t i o n s . For the pyrazoline 10 and i t s 4,4-d2 analogue 50: kH koH + kcH . k n k n + k n D oD cD koH 31.1 , koD 21 . 1 and k u 68.9 k _ 78.2 cH cD Thus - 1.94 and ^ =1.20 KoD cD For the pyrazoline ___ and i t s 5,5-^ analogue 5_1_: __H koH + kcH _ • „ KD KoD KcD koH 33.2 _____ 36.2 k „ = 66.8 k _ 63.8 cH cD Thus r^- =1.12 and ^ = 1.28 oD cD - 13 -A primary isotope e f f e c t f o r the hydrogen on C-4 i s expected with a magnitude of 1.41 to 2.36,based on studies by Sester and Rabinovitch (17a) and Blacks (17b) f o r the cyclopropane to o l e f i n isomerization. The isotope e f f e c t i n the cyclopropane to propylene r e a c t i o n has been a t t r i b u t e d to. a primary e f f e c t associated with the breaking of the migrating C-D bond. For the cyclopropane forming r e a c t i o n the isotope e f f e c t of 1.20 may be a t t r i b u t e d to a secondary isotope e f f e c t 3 2 r e l a t e d to the change of h y b r i d i z a t i o n from sp towards sp found i n cyclopropane. The k i n e t i c isotope e f f e c t of 1.22 found f o r the 5,5-^ pyrazoline 51_ was divided i n t o 1.12 and 1.28 for the o l e f i n and cyclopropane forming r e a c t i o n r e s p e c t i v e l y . This provides evidence that the C-5 N-1 bond i s breaking i n the t r a n s i t i o n state i n the o l e f i n forming r e a c t i o n . This also provides evidence that there i s a change of h y b r i d i z a t i o n at C-5 and the C-5 N-1 bond i s breaking i n the t r a n s i t i o n state of the cyclopropane forming r e a c t i o n . This secondary isotope e f f e c t i s i n l i n e with that found by S e l t z e r and co-workers (17a-c) for azoalkanes. Further mention w i l l be made of deuterium isotope e f f e c t s i n the discussion of deuterated a l k y l pyrazolines (19-23). (b) 3,5-Diary1-1-Pyrazolines Overberger and co-workers (25-28) have prepared a seri e s of 3,5-d i a r y l - l - p y r a z o l i n e s and determined the product r a t i o s and rates of thermal decomposition. The k i n e t i c studies on the 3 , 5 - d i a r y l - l - p y r a z o l i n e s indicated that e l e c t r o n i c contributions had l i t t l e e f f e c t since the rates and i • • - 14 -trans-cyclopropane cis-cyclopropane C 6 H 5 ""I^ V C 6 H 5 89 11 52 OMe £-0Me-C 6H 4 . . . .|^Y- C6H4-p_- 93.3 6.7 N = N 53 OMe £ - O M e - C 6 H 4 _ _ ^ N p C6H4-p_-57.0 43.0 N = N 54 E-; C 1- C6 H4 , , , ,| X Vlr C 6 H 4 - ^ C N = N 55 1 100 a c t i v a t i o n energies f o r the trans-pyrazolines 52, 53 and 55 were e s s e n t i a l l y the same. Electron spin resonance studies of the p h o t o l y t i c decomposition of pyrazoline _52_ indi c a t e d the presence of a free r a d i c a l . This suggested a mechanism in v o l v i n g a free r a d i c a l as i l l u s t r a t e d i n the scheme i n Figure 7. (c) 3-Cyano-3-Carbomethoxy-1-Pyrazolines A structure such as the i o n i c species 1_ i n Figure 1 suggests that p o s i t i v e charge i s b u i l t up at C-5 of the pyrazoline system i n the t r a n s i t i o n s t a t e . I f t h i s i s the case, rearrangements c h a r a c t e r i s t i c - 15 -N = N Ar / \ H H A r 1 H A r v 1 Ar A r H H A r F i g u r e 7 - R a d i c a l m e c h a n i s m f o r 3 , 5 - d i a r y l - l - p y r a z o l i n e s , o f c a r b o n i u m i o n s s h o u l d b e p o s s i b l e f o r t h e p y r a z o l i n e s y s t e m . M c G r e e r et_ al_ ( 2 9 ) h a v e p r e p a r e d a n u m b e r o f 4 , 4 - d i a l k y l - 3 - c y a n o -c a r b o m e t h o x y - l - p y r a z o l i n e s . CN C 0 2CH ^ 2 ^ 3 C 0 2 C H 3 N = N 56 C 0 2 C H 3 CN 59 39 _/ \ • 6 0 C N 39 / S 61 C N 22 CN C 0 2CH 3 C0„CH. y CN N — N C 0 2CH 3 62 15 6 3 ( c i s a n d t r a n s ) 85 57 - 16 -CO_CH 3 C 0 2 C H 3 C 0 2 C H 3 y \ / N s - S -\ CN CN ' CN C 0 2 C H 3 64 ( c i s a n d 65_ __6 ( c i s a n d t r a n s ) t r a n s ) N — N C N 25 35 4 0 The r e s u l t s o b t a i n e d f r o m t h e p y r o l y s i s o f t h e p y r a z o l i n e s 5 6 , 57 a n d 58_ a r e c o n s i s t e n t w i t h t h e d e v e l o p m e n t o f a p o s i t i v e c h a r g e at C - 5 o f t h e p y r a z o l i n e s y s t e m . I n a d d i t i o n , p r e l i m i n a r y s t u d i e s o n the r a t e o f p y r o l y s i s w e r e c a r r i e d o u t i n a v a r i e t y o f s o l v e n t s . The r e s u l t s s u g g e s t a t r a n s i t i o n s t a t e w h i c h i s m o r e p o l a r t h a n t h e s t a r t i n g m a t e r i a l . H a m e l i n a n d C a r r i e (30 a - e ) a n d M c G r e e r a n d W i g f i e l d (31) h a v e p r e p a r e d a n u m b e r o f 3 - c y a n o - 3 - c a r b o e t h o x y ( o r 3 - c a r b o m e t h o x y ) - 4 -a l k y l - 4 - a r y l - l - p y r a z o l i n e s a n d s t u d i e d t h e p y r o l y s i s r e a c t i o n . T y p i c a l p r o d u c t d i s t r i b u t i o n s a t 7 0 ° i n n i t r o b e n z e n e a r e s h o w n . CN • A r CN A r C ° 2 C H 3 N / N / A r S ___/ \ C 0 2 C H 3 CN ( c i s a n d t r a n s ) ( c i s a n d t r a n s ) ( c i s a n d t r a n s ) C 0 2 C H 3 C 0 2 C H 3 6 5 N — N 3 3 53 14 • • 67_ _ 5 8 ( 5 , 5 - d 2 ) 36 52 12 - 17 -N — N 69 *CN 1 0 0 C02CH3 p-OMe-C,H/ I ' 70 **1 ''CN 3 8 5 2 1 0 C02CH3 E-NO2-C6H;- - - CN 21 E-N02-C6H C02CH3 34 49 17 »*%| T"' 92 N=N C N 72 The c i s - p y r a z o l i n e s 69 and 72_ (carbomethoxy and a r y l c i s ) gave predominately the o l e f i n from a r y l migration,whereas the trans-pyrazolines 67, 70 and 71_ gave predominately the o l e f i n from methyl migration. A k i n e t i c study was also c a r r i e d out f o r the p y r o l y s i s r e a c t i o n and the value of the secondary deuterium k i n e t i c isotope e f f e c t of k^/k^ = 1.03 suggests that at the t r a n s i t i o n state there i s l i t t l e progress i n the bond breaking of the C-5 N-1 bond. This r e s u l t d i f f e r s considerably from the r e s u l t obtained by McGreer and Masters (16) who obtained an isotope e f f e c t of k^/k^ = 1.22 for 3-methyl-3-carbomethoxy-5,5-d.-l-n D 2 - 18 -p y r a z o l i n e . I t was a l s o f o u n d t h a t t h e r e i s n e g l i g i b l e e f f e c t o n t h e r a t e o n g o i n g f r o m p _ - m e t h o x y p h e n y l t o p h e n y l t o p _ - n i t r o p h e n y l . T h i s s u g g e s t s t h a t m i g r a t i o n o f t h e a r y l g r o u p a n d a n y r e s u l t i n g p a r t i c i p a t i o n h a s a l s o p r o g r e s s e d t o a n e g l i g i b l e d e g r e e i n t h e t r a n s i t i o n s t a t e . T h i s a g a i n d i f f e r s f r o m t h e 4 , 4 - d 2 - l - p y r a z o l i n e 50_ i n w h i c h i t was f o u n d t h a t t h e C - 4 h y d r o g e n was i n v o l v e d i n c o n s i d e r a b l e p a r t i c i p a t i o n i n t h e t r a n s i t i o n s t a t e . A n o t h e r i n t e r e s t i n g p i e c e o f i n f o r m a t i o n o b t a i n e d f r o m t h e same s t u d y i s t h e e n t r o p y o f a c t i v a t i o n v a l u e s . T h e n e g a t i v e v a l u e s a r e n o t c o n s i s t e n t w i t h t h o s e f o u n d b y M c G r e e r a n d M a s t e r s ( 1 6 ) a l t h o u g h t h e y a r e c o n s i s t e n t w i t h a d d i t i o n a l c o n s t r a i n t i n t h e d e g r e e s o f f r e e d o m o f t h e t r a n s i t i o n s t a t e c o m p a r e d t o t h e s t a r t i n g m a t e r i a l w h i c h i s o b s e r v e d i n r e a c t i o n s o c c u r r i n g v i a i o n i c t r a n s i t i o n s t a t e s i n p o l a r m e d i a . A n o t h e r f a c t d r a w n o u t b y s o l v e n t e f f e c t s i s t h a t t h e c h a n g e o f r a t e i n t e t r a l i n t o n i t r o b e n z e n e t o f o r m a m i d e was f o u n d t o b e 1 : 3 4 : 3 . 4 x 3 10 . S u c h a c h a n g e o f r a t e c a n b e a t t r i b u t e d t o a t r a n s i t i o n s t a t e m o r e p o l a r t h a n t h e s t a r t i n g m a t e r i a l . C o n s i d e r i n g a l l t h e r e s u l t s t o g e t h e r ( t h e 5 , 5 - d 2 i s o t o p e e f f e c t , a r y l g r o u p s o n r a t e s , e n t r o p y o f a c t i v a t i o n , s o l v e n t e f f e c t o n r a t e s ) t h e t r a n s i t i o n s t a t e 73_ may b e r e p r e s e n t e d a s i n F i g u r e 8 . A r . ^ ^ t ^ ^ ^ .CN CO CH_ 21 F i g u r e 8 - T r a n s i t i o n s t a t e f o r t h e p y r o l y s i s o f 3 - c y a n o - 3 - c a r b o m e t h o x y - 4 -a l k y l - 4 - a r y l - l - p y r a z o l i n e s . - 19 -( d ) A l k y l S u b s t i t u t e d - l - P y r a z o l i n e s C r a w f o r d a n d c o - w o r k e r s ( 1 9 a - c ) h a v e p r e p a r e d a n d s t u d i e d t h e k i n e t i c s o f a s e r i e s o f a l k y l s u b s t i t u t e d 1 - p y r a z o l i n e s . F i r s t o r d e r k i n e t i c s w e r e o b s e r v e d t o g r e a t e r t h a n 95% c o m p l e t i o n a n d t h e r a t e was f o u n d t o b e i n d e p e n d e n t o f p r e s s u r e . A s t h e n u m b e r o f m e t h y l g r o u p s a r e i n c r e a s e d o n t h e p y r a z o l i n e , t h e a c t i v a t i o n e n e r g i e s show a c o n t i n u o u s d e c r e a s e f r o m 4 2 . 4 K c a l / m o l e f o r 74_ t o 3 7 . 7 K c a l / m o l e f o r p y r a z o l i n e 82_. The d e c r e a s e p e r m e t h y l g r o u p o f a p p r o x i m a t e l y o n e K c a l / m o l e may b e d u e t o a n i n c r e a s e i n g r o u n d s t a t e e n e r g i e s . T h e e n t r o p y o f a c t i v a t i o n v a r i e s f r o m 1 1 . 2 e u f o r 74_ t o 4 . 6 e u f o r p y r a z o l i n e 82_,as i s e x p e c t e d i f t h e t r a n s i t i o n s t a t e m o r e c l o s e l y r e s e m b l e s t h e s t a r t i n g m a t e r i a l s o n p r o c e e d i n g f r o m p y r a z o l i n e 74 t o 8 2 . c y c l o p r o p a n e o l e f i n c y c l o p r o p a n e o l e f i n l ^ ^ l 8 9 . 2 1 0 . 8 N j X V ^ 3 3 . 2 c i s N ^ = N N N 6 6 . 1 t r a n s 0 . 7 74 79 j ^Y ' 9 3 . 3 6 . 7 ' ' { ^ Y N = N N = N 75 80 5 2 . 3 4 7 . 7 N — N N __N 76 81 7 2 . 6 c i s 2 . 0 2 5 . 4 t r a n s 9 9 . 3 6 0 . 6 4 - 20 -PS N — N 77 9 8 . 6 1 . 4 N N 82 9 9 . 7 5 0 . 2 5 ( ^ f \ 9 6 . 7 3 . 3 N 100 t r a c e N = N 7__ 83 I n t h e same w o r k . t h e C - 4 d e u t e r a t e d p y r a z o l i n e 84 was p r e p a r e d . A k i n e t i c i s o t o p e e f f e c t o f k ^ / k ^ = 1 . 0 7 was o b s e r v e d . F o l l o w i n g t h e p r o p o s e d r e a c t i o n s e q u e n c e i n F i g u r e 9 t h e i s o t o p e e f f e c t f o r t h e o l e f i n f o r m i n g r e a c t i o n may b e c a l c u l a t e d . x C D ) — 2 • I J > i n t e r m e d i a t e W A F i g u r e 9 - K i n e t i c s c h e m e f o r p y r o l y s i s o f a l k y l s u b s t i t u t e d 1 - p y r a z o l i n e s . A s s u m i n g k c H / k c D = 1 . 0 F r o m p r o d u c t d i s t r i b u t i o n s k y k ^ = 4 7 . 7 / 5 2 . 3 k n / k _ = 3 4 . 0 / 6 6 . 0 oD cD T h e n __H c oD = 1 . 8 0 Nr=N 74 21 -cyclopropane 52.3 o l e f i n 47.7 L N — N 84 66.0 34.0 The value of 1.80 i s close to the value observed f o r the isomer-i z a t i o n of deuterated cyclopropanes (17a,b). The a l t e r n a t i v e approach of assuming that the o l e f i n and cyclopropane come from d i f f e r e n t paths gives r i s e to the k i n e t i c scheme outlined i n Figure 10t CD) -N = N 74 or 84 H(D) jS~ CH, y H(D) A Figure 10 - A l t e r n a t i v e k i n e t i c scheme f o r p y r o l y s i s of a l k y l s u bstituted 1-pyrazolines. H k . + k .. oH cH k n + k n oD cD 1.07 ^oH 47.7 k „ 52.3 cH and oD  :cD 34.0 66.0 - 22 -Then oK = 1 . 5 0 a n d c H 0 . 8 4 T h e v a l u e o f 0 . 8 4 i m p l i e s t h a t s u b s t i t u t i o n o f d e u t e r i u m a t C - 4 i n c r e a s e s t h e r a t e o f c y c l o p r o p a n e b y 1 9 % , t h u s i n d i c a t i n g s u c h a s c h e m e ( F i g u r e 10) i s h i g h l y i m p r o b a b l e . I t was t h e r e f o r e c o n c l u d e d t h a t 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 i s f o r m e d a f t e r t h e r a t e d e t e r m i n i n g s t e p . F u r t h e r e v i d e n c e f o r a n i t r o g e n - f r e e i n t e r m e d i a t e i s f u r n i s h e d b y C r a w f o r d a n d C a m e r o n ( 2 1 ) b y t h e p y r o l y s i s o f 3 - v i n y l - l - p y r a z o l i n e ( 8 5 ) a n d 3 - v i n y l - 5 , 5 - d 2 " l - p y r a z o l i n e ( 8 6 ) . B e c a u s e t h e e n e r g y o f a c t i v a t i o n was 1 0 . 2 k c a l / m o l e l e s s t h a n t h e p a r e n t 1 - p y r a z o l i n e , t h i s s u g g e s t e d t h a t i n t h e r a t e d e t e r m i n i n g t r a n s i t i o n s t a t e , c o m p l e t e d e r e a l i z a t i o n i n v o l v i n g t h e v i n y l g r o u p i s a t t a i n e d a n d t h u s t h e C - 3 N - 2 b o n d i s a l m o s t c o m p l e t e l y b r o k e n . T h e s e c o n d a r y i s o t o p e e f f e c t o f k ^ / k ^ = 1 . 2 1 i s i n a g r e e m e n t w i t h t h e e x p e c t e d v a l u e ( 1 8 a - c ) . T h e c o n c l u s i o n i s t h a t b o t h c a r b o n - n i t r o g e n b o n d s a r e b r e a k i n g i n t h e r a t e d e t e r m i n i n g t r a n s i t i o n s t a t e a s r e p r e s e n t e d i n F i g u r e 11, w i t h t h e C - 3 N - 2 b o n d r u p t u r e f a r i n a d v a n c e o f t h e C - 5 N-1 b o n d . —N // N . . . . N /// N 85 F i g u r e 11 - R a t e d e t e r m i n i n g t r a n s i t i o n s t a t e f o r 3 - v i n y l - l - p y r a z o l i n e . - 2 3 -On the basis of the r e s u l t s obtained from deuterium isotope e f f e c t s , the nitrogen-free intermediate was thought of as a ir-cyclo-propane. Comparison of the r e s u l t s from pyrazolines 79_ and 80, c i s - and trans-3,5-dimethyl-1-pyrazolines r e s p e c t i v e l y , indicates that the two terminal carbons of the intermediate are not free of each other (or the l i f e t i m e of the intermediate i s short) so that equilibrium may be reached. I f an equilibrium could be reached,then the products from both pyrazolines 79_ and 80_ would be i d e n t i c a l . One p o s s i b i l i t y , to explain why the two terminal carbons are not f r e e , i s i n terms of pir-pir bonding as i n species 87. The conversion of a 1-pyrazoline i n t o a nitrogen-free intermediate with an antisymmetric s i n g l e t trimethylene Figure 12_ - ir-Cyclopropane intermediates. structure 88_ may also be considered. Such a structure as 88_ i s e s p e c i a l l y d e s i r a b l e since the immediate consequence of t h i s species i s that conrotation would be preferred to give the inverted stereo-chemistry,which i s i n agreement with experimental r e s u l t s obtained from the p y r o l y s i s of several 3,5-disubstituted-l-pyrazolines (11,13,14). Crawford and Erikson (22) have studied the thermolysis of c i s -and trans-4-deuterio-5-methyl-1-pyrazolines (89 and 90) T r e s u l t i n g i n - 24 -f u r t h e r e v i d e n c e f o r a 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 u c h a s t h e a n t i s y m -m e t r i c t r i m e t h y l e n e s i n g l e t 88_. T h e a d v a n t a g e o f p y r a z o l i n e __9 a n d 90_ i s t h a t t h e same t r i m e t h y l e n e s t r u c t u r e j _ l w i l l r e s u l t f r o m b o t h p y r a z o l i n e s a n d t h u s s h o u l d g i v e i d e n t i c a l p r o d u c t r a t i o s i n d e p e n d e n t o f t h e i n i t i a l s t e r e o c h e m i s t r y . c y c l o p r o p a n e c i s - 2 - b u t e n e t r a n s - 1 - b u t e n e 1 - b u t e n e T h e r e s u l t s a r e q u i t e c o n s i s t e n t w i t h t h e p r o p o s a l o f a n i n t e r -m e d i a t e f r e e o f n i t r o g e n , i n t h a t t h e p r o d u c t d i s t r i b u t i o n s a r e n e a r l y t h e same f o r b o t h _39 a n d 90_ a n d t h e r a t i o o f h y d r o g e n : d e u t e r i u m m i g r a t i o n f o r t h e o l e f i n s i s n e a r l y e q u a l f o r b o t h p y r a z o l i n e s . T h e r e s u l t s a l s o d o n o t a l l o w f o r t h e p o s s i b i l i t y o f a c o n c e r t e d m i g r a t i o n o f o n l y t h e h y d r o g e n t r a n s o i d t o t h e d e p a r t i n g n i t r o g e n a s s h o w n b y t h e i n t e r m e d i a t e 9 1 a a n d 91b i n F i g u r e 1 3 . I f a t r a n s o i d m e c h a n i s m w e r e o p e r a t i n g , o n l y t r a n s - 2 - b u t e n e 92_ i n w h i c h t h e h y d r o g e n m i g r a t e d j w o u l d - 25 -\ / / 9 2 89 F i g u r e 13 - C o n c e r t e d t r a n s i t i o n s t a t e f o r o l e f i n . f o r m i n g r e a c t i o n f o r c i s - a n d t r a n s - 4 - d e u t e r i o - 3 - m e t h y l - l - p y r a z o l i n e s . r e s u l t . S i m i l a r l y , o n l y c i s - 2 - b u t e n e 93 i n w h i c h d e u t e r i u m m i g r a t e d w o u l d r e s u l t . F u r t h e r s t u d i e s b y C r a w f o r d a n d A l i ( 2 3 ) h a v e g i v e n r e s u l t s c o n s i s t e n t w i t h t h e n i t r o g e n - f r e e i n t e r m e d i a t e p r o p o s e d a s s p e c i e s 8 8 , a n a n t i s y m m e t r i c t r i m e t h y l e n e s i n g l e t . T h e y p r e p a r e d a n d s t u d i e d t h e p y r o l y s i s o f c i s - a n d t r a n s - 3 , 4 - d i m e t h y l - 1 - p y r a z o l i n e s (94 a n d 9 5 ) a n d t h e i r 5 , 5 - d 2 a n a l o g u e s 9 6 a n d 97_. I s o t o p e e f f e c t s o f 1 . 1 9 a n d 1 . 2 1 were f o u n d f o r t h e c i s a n d t r a n s - p y r a z o l i n e s 94 a n d 95 A A 94 4 5 . 4 3 3 . 0 1 4 . 3 7 . 2 46.0 21.8 16.3 15.8 N = N 95 respectively,implying that the C-5 N-1 bond is breaking in the rate determining transition state. That the product distributions from 94 and 95_ are different can be explained by use of two discrete intermediates 98 and 99_ (Figure 14)}both being produced from each pyrazoline but in Figure 14 - Two trimethylene intermediates from cis- and trans-3,4-dimethy1-1-pyrazolines. different ratios^depending on the relative populations of the two conformations. The results are also indicative of non-stereospecific olefin formation as already shown by use of cis- and trans-4-deuterio-3-methyl-l-pyrazoline (23). For a transoid elimination of nitrogen,the olefins 100 and 101 in Figure 15 would be the expected products. Howeverjit was found that only 4% of 100 was formed from 96 and only N - 27 -W- N ,W.... v , _, l— M ; \ D 2 D N CD 0 H 96 2 100 2 N _____ •' 1 : N v CD 2 H // H...\ I /// N = < 6% i Z 2 101 F i g u r e 15 - T r a n s i t i o n s t a t e s a n d o l e f i n s e x p e c t e d o n t h e b a s i s o f c o n c e r t e d m e c h a n i s m f o r p y r o l y s i s o f c i s - a n d t r a n s - 3 , 4 -d i m e t h y l - 5 , 5 - d 2 - l - p y r a z o l i n e s . 6% o f 101 f r o m p y r a z o l i n e 9 7 . T h i s c a n b e e x p l a i n e d b y t h e s c h e m e i n F i g u r e 1 4 . a s s u m i n g t h a t t h e m a j o r i n t e r m e d i a t e f r o m t h e c i s -p y r a z o l i n e 94_ i s 9 9 , a n d t h e m a j o r i n t e r m e d i a t e f r o m t h e t r a n s - p y r a z o l i n e 9 5 i s 9 8 . I t i s s u g g e s t e d t h a t t h e s e c o n d m e t h y l g r o u p a t C - 4 l e a d s t o s t e r i c c r o w d i n g i n t h e r a t e d e t e r m i n i n g t r a n s i t i o n s t a t e . A l - S a d e r a n d C r a w f o r d ( 2 4 ) h a v e s t u d i e d t h e p r o d u c t r a t i o s a n d r a t e s o f a s e r i e s o f d e u t e r a t e d 1 - p y r a z o l i n e s . I s o t o p e e f f e c t s a t b o t h C - 4 a n d C - 5 w e r e d e t e r m i n e d f o r b o t h t h e o l e f i n a n d c y c l o p r o p a n e f o r m i n g r e a c t i o n . The.C-4 i s o t o p e e f f e c t i s l a r g e r t h a n e x p e c t e d , b u t h y p e r c o n j u g a t i v e i n t e r a c t i o n s may b e g i v i n g r i s e t o t h e e n h a n c e d 3 - d e u t e r i u m i s o t o p e e f f e c t s i n t h e r a t e d e t e r m i n i n g s t e p . N — N 74 c y c l o p r o p a n e p r o p y l e n e k t , A r > n V 8 8 . 4 3 1 1 . 5 7 1 . 0 0 - 28 -c y c l o p r o p a n e p r o p y l e n e ^ H ^ D n J>2 N = N 102 8 7 . 9 9 1 2 . 0 1 1 . 1 9 D 2 ^ D ; 1 0 3 H D 104 D 2 N = N 105 8 7 . 4 3 1 2 . 5 7 1 . 4 0 8 9 . 2 1 1 0 . 7 9 1 . 0 5 9 0 . 2 7 9 . 7 3 1 . 1 2 I t was f o u n d t h a t t h e r a t i o o f C D 2 H - C H = C H 2 a n d CD=CH-CH 3 f r o m t h e p y r o l y s i s o f p y r a z o l i n e 102 was 5 2 : 4 8 , g i v i n g a n i n v e r s e i n t r a m o l e c u l a r i s o t o p e e f f e c t o f k ° 1 0 2 / k ° 1 0 3 = 0 . 9 2 . The v a l u e o f 0 . 9 2 i s c o n s i s t e n t n D w i t h t h e i n c r e a s e i n o l e f i n o n g o i n g f r o m 102 t o 1 0 3 . The i n v e r s e i s o t o p e e f f e c t i s e x p l a i n e d b y t h e c h a n g e i n h y b r i d i z a t i o n o n g o i n g f r o m r 2 3 • ' ' sp to sp,. - 29 -N — N 74 2k 074 H - > i n t e r m e d i a t e c 9 7 y NIZ N 102 0 1 0 2 0 1 0 2 i n t e r m e d i a t e C102 s / :D2H N ~ N 103 2k 0 1 0 3 D i n t e r m e d i a t e C 1 0 3 ,CD2H F i g u r e 16 - K i n e t i c s c h e m e f o r 3 , 3 - d 2 ~ a n d 3 , 3 , 5 , 5 - d ^ - l - p y r a z o l i n e s . A s s u m i n g 0 7 4 ' (H 0 1 0 2 = 1 . 0 F r o m t h e p r o d u c t d i s t r i b u t i o n s -2k, 074 H 1 1 . 5 7 C77 8 8 . 4 3 , 0 1 0 2 0 1 0 2 H * KD _ 1 2 . 0 1 , C 1 0 2 " 8 7 . 9 9 T h e n C74 c C102 = 1 . 0 0 - 30 -. 0 1 0 2 k D S i m i l a r l y , b y a s s u m i n g 'Q_Q3 k D 1 . 0 0 T h e n C102 c C103 = 1 . 0 1 ^ , . . . C 7 4 . . C 1 0 2 . n n , . C 1 0 2 . . C 1 0 3 . The v a l u e s o f k / k = 1 . 0 0 a n d k / k = 1 . 0 1 s u g g e s t t h a t t h e r e i s l i t t l e o r n o c h a n g e i n t h e C - H o r C-D f o r c e c o n s t a n t s o f t h e t e r m i n a l m e t h y l e n e g r o u p s t o c y c l o p r o p a n e a n d p r o p y l e n e . A s c h e m e may a l s o b e d r a w n o u t f o r t h e C-4 d e u t e r a t e d p y r a z o l i n e s a s s h o w n i n F i g u r e 1 7 . N — N 104 0104 i n t e r m e d i a t e —Q 1 Q 4 — ^ y CH_D D D N ~ N 105 i n t e r m e d i a t e 0 1 0 5 y CH_D D „ D F i g u r e 17 - K i n e t i c s c h e m e f o r 4 - d ^ - a n d 4 , 4 - d 2 - l - p y r a z o l i n e s . F r o m t h e p r o p y l e n e a r r i v e d f r o m p y r a z o l i n e 104 >the r a t i o o f CH^= C D - C H 3 t o C H 2 = C H - C H 2 D was 2 : 1 , g i v i n g a n i s o t o p e e f f e c t o f k j j 1 0 4 / k p 1 0 4 1 . 5 0 . A s s u m i n g 074 0104 = 1 . 0 1 - 31 -F r o m t h e p r o d u c t d i s t r i b u t i o n s 074 Ji _ 1 1 . 5 7 , C 7 4 8 8 . 4 3 , 0 1 0 4 0104 KH + K D 1 0 . 7 9 , C 1 0 4 8 9 . 2 1 k T h e n k C 7 4 , C104 k = 1 . 1 3 k 0 1 0 4 S i m i l a r l y , b y a s s u m i n g 0 1 0 5 = 1 . 0 1 k D , C104 ™ e n 7 1 0 5 " 1 A 5 k T h u s d e u t e r i u m s u b s t i t u t i o n a t t h e C - 4 p o s i t i o n o f t h e p y r a z o l i n e m o l e c u l e s l o w s down t h e r a t e a t w h i c h t h e i n t e r m e d i a t e c y c l i z e s t o 3 2 c y c l o p r o p a n e . T h i s i s w h a t i s e x p e c t e d o n g o i n g f r o m s p t o s p h y b r i d i z a t i o n , k e e p i n g i n m i n d t h a t t h e C - H b o n d s i n c y c l o p r o p a n e c l o s e l y 2 r e s e m b l e s p h y b r i d i z a t i o n . I n s u m m a r y , t h e i s o t o p e e f f e c t s f o r t h e d e u t e r a t e d 1 - p y r a z o l i n e d e r i v a t i v e s a r e : F o r 3 - d _ d e u t e r i u m s u b s t i t u t i o n k ^ / k ^ = 0 . 9 2 Z M L ) - 32 -F o r 4 - c L d e u t e r i u m s u b s t i t u t i o n k[!/k!? = 1 . 5 0 i n u KS/ku = 1 - 1 3 R e c e n t l y , C r a w f o r d a n d M i s h r a ( 3 2 ) h a v e p r e p a r e d ( 3 R : 5 R ) - ( + ) - 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 ( 1 0 6 ) . On t h e r m o l y s i s . p y r a z o l i n e 106 g a v e 2 5 . 6 % o f t r a n s - 1 , 2 - d i m e t h y l c y c l o p r o p a n e ( 1 0 8 a a n d 108b) o f 23% o p t i c a l p u r i t y h a v i n g t h e S : S c o n f i g u r a t i o n ( 1 0 8 b ) , t h u s i n d i c a t i n g a n e x c e s s o f d o u b l e i n v e r s i o n . I f t h e t r i m e t h y l e n e s p e c i e s 107 ( F i g u r e 19) w e r e t h e i n t e r m e d i a t e , t h e n a r a c e m i c m i x t u r e o f 108 s h o u l d r e s u l t . I n o r d e r <U < t . .' < f 01efin 1 0 8 a 108b 73 25 23% o p t i c a l p u r i t y 106 o f 108b t o a c c o u n t f o r t h e 23% o p t i c a l p u r i t y , u s e i s made o f a p y r a m i d a l d i r a d i c a l i n t e r m e d i a t e p r o p o s e d b y A l l r e d a n d S m i t h ( 3 3 ) . I n t h e i r s y s t e m , u s i n g e x o - a n d e n d o - 5 - m e t h o x y - 2 , 3 - d i a z o b i c y c l o [ 2 . 2 . 1 ] - 2 -h e p t e n e ( 1 0 9 a n d 1 1 0 ) , t h e y h a v e a t t r i b u t e d i n v e r s i o n t o t h e f o r m a t i o n o f s t r u c t u r a l l y i n v e r t e d p y r a m i d a l d i r a d i c a l s 113 a n d 114 ( F i g u r e 18) T h e i n v e r s i o n was c o n s i d e r e d t o b e a c o n s e q u e n c e o f r e c o i l f r o m e n e r g y - 3 3 -^5 N N 109 ( e n d o ) C H , 0 . 111 3 7 - i C H 3 ° 112 6 3 6-r 94 N /' CH_0 1 1 « <• -> 3 110 ( e x o ) r e l e a s e d b y C - N b o n d b r e a k i n g . R i n g c l o s u r e b e f o r e c o m p l e t e e q u i l i b r a t i o n a c c o u n t s f o r t h e e x c e s s o f t h e 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 . C H 3 0 109 ( e x o ) N // C H , 0 113 111 N / / CH 0 N I 1 0 ( e n d o ) 3 t C H 3 0 114 CH^O 112 F i g u r e 18 - P y r a m i d a l d i r a d i c a l m e c h a n i s m f o r d e c o m p o s i t i o n o f e x o - a n d e n d o - 5 - m e t h o x y - 2 , 3 - d i a z a b i c y c l o [ 2 . 2 . 1 ] - 2 - h e p t e n e . - 34 -T h u s C r a w f o r d a n d M i s h r a s u g g e s t t h a t t h e s c h e m e t h a t b e s t f i t s the d a t a u t i l i z e s t h e p y r a m i d a l d i r a d i c a l . T h i s scheme w i l l r a t i o n a l i z e the e x c e s s o f d o u b l e i n v e r s i o n f o u n d f o r t h e t r a n s - c y c l o p r o p a n e . T h e r a c e m i c t r a n s - c y c l o p r o p a n e , t h e c i s _ - c y c l o p r o p a n e a n d o l e f i n s a r e b e l i e v e d t o a r i s e f r o m a t r i m e t h y l e n e i n t e r m e d i a t e . T h e d a t a t h u s f a r c a n n o t d i s t i n g u i s h i f 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 i s f o r m e d f r o m the p y r a z o l i n e o r f r o m t h e p y r a m i d a l d i r a d i c a l s t r u c t u r e o r f r o m b o t h . N e i t h e r c a n t h e d a t a t e l l i f t h e p y r a m i d a l d i r a d i c a l i s e q u i l i b r a t i n g . T h e f i r s t e x a m p l e o f a b i c y c l i c s y s t e m i n w h i c h t h e m a j o r p r o d u c t i s t h e o n e t h a t r e s u l t s f r o m d o u b l e i n v e r s i o n was r e p o r t e d b y R o t h a n d M a r t i n ( 3 4 ) . T h e p y r a z o l i n e e x o - 5 , 6 - d i d e u t e r i o - 2 , 3 - d i a z o b i c y c l o -D 116 117 25 [ 2 . 2 . 1 ] - 2 - h e p t e n e ( 1 1 5 ) g a v e a 3 : 1 m i x t u r e o f t r a n s - a n d c i 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 (116 a n d 117) . T h e p r e d o m i n a n t p r o d u c t was a t t r i b u t e d t o c o n c e r t e d 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 a c c o m p a n y -i n g b a c k - s i d e p - o r b i t a l o v e r l a p i n t h e t r a n s i t i o n s t a t e ( F i g u r e 1 9 ) . - 35 -N F i g u r e 19 - T r a n s i t i o n s t a t e f o r c o n c e r t e d n i t r o g e n e l i m i n a t i o n f r o m e x o - 5 , 6 - d i d e u t e r i o - 2 , 3 - d i a z a b i c y c l o T 2 . 2 . 1 ] - 2 - h e p t e n e . T h i s i n t r o d u c t i o n h a s t r e a t e d t w o m a i n a s p e c t s i n t h e p y r o l y s i s o f 1 - p y r a z o l i n e s - o n e t h e o l e f i n f o r m i n g r e a c t i o n , a n d t h e o t h e r t h e c y c l o p r o p a n e f o r m i n g r e a c t i o n . I n t h e c a s e o f a l k y l s u b s t i t u t e d 1 - p y r a z o l i n e s ( p a r t (d) o f " i n t r o d u c t i o n " ) , t h e r e i s c o n s i d e r a b l e e v i d e n c e f o r a t r i m e t h y l e n e i n t e r m e d i a t e , b o t h f o r o l e f i n a n d c y c l o -p r o p a n e f o r m a t i o n . I n t h e c a s e o f 3 - a c e t y l a n d 3 - c a r b o m e t h o x y p y r a z o l i n e s ( p a . r t ( a ) o f " i n t r o d u c t i o n " ) } a t r a n s o i d m e c h a n i s m i n w h i c h t h e s u b s t i t u e n t a t C - 4 o f t h e p y r a z o l i n e m i g r a t e s w i t h c o n c e r t e d l o s s o f n i t r o g e n h a s b e e n w e l l e s t a b l i s h e d . H o w e v e r , t h e r e i s v e r y l i t t l e known a b o u t t h e m e c h a n i s m o f f o r m a t i o n o f c y c l o p r o p a n e d e r i v a t i v e s f r o m 3 - a c e t y l o r 3 - c a r b o m e t h o x y p y r a z o l i n e s . I t i s t h e p u r p o s e o f t h i s r e s e a r c h t o f u r t h e r i n v e s t i g a t e t h e f o r m a t i o n o f c y c l o p r o p a n e d e r i v a t i v e s b y t h e p r e p a r a t i o n a n d p y r o l y s i s o f a s e r i e s o f 3 - m e t h y l - 3 - a c e t y l - l - p y r a z o l i n e s u n i q u e l y s u b s t i t u t e d a t a l l t h r e e c a r b o n c e n t e r s . I t was a l s o a n t i c i p a t e d t h a t t h e same s e r i e s o f p y r a z o l i n e s w o u l d g i v e r e s u l t s t h a t w o u l d e m p h a s i z e t h e i m p o r t a n c e o f t h e c o n f o r m a t i o n o f t h e s t a r t i n g 1 - p y r a z o l i n e i n t h e o l e f i n f o r m i n g r e a c t i o n . - 56 -I I . RESULTS AND DISCUSSION P r e p a r a t i o n a n d P r o d u c t D i s t r i b u t i o n s T h e 1 - p y r a z o l i n e s p r e p a r e d f o r t h e p r e s e n t w o r k a r e l i s t e d i n T a b l e I . The p y r a z o l i n e s w e r e p r e p a r e d b y t h e a d d i t i o n o f e i t h e r d i a z o e t h a n e o r p h e n y l d i a z o m e t h a n e t o t h e a p p r o p r i a t e a , 8 - u n s a t u r a t e d k e t o n e . TABLE I 3 , 3 , 4 , 5 - T e t r a s u b s t i t u t e d - 1 - P y r a z o l i n e s COCH 3 1 - P y r a z o l i n e R „ R , R. R . 2 3 4 5 118 H C H , C H r H o o b 119 H C H , H C , H C o o b 120 C H , H C £ H C H o o b 121 C H , . H H C H r 5 o b 122 H C , H C - C H , H o b 3 123 H C , H C H C H , o b 3 - 37 -Addition of phenyldiazomethane to 3-methyl-3-pentene-2-one, (E)-(24) gave the pyrazolines 118 and 119 i n about a 2:1 r a t i o r e s p e c t i v e l y . P u r i f i c a t i o n by column chromatography gave a mixture of the two C-5 isomeric pyrazolines as a c l e a r colourless l i q u i d . The pyrazolines could not be c r y s t a l l i z e d . I t was not p o s s i b l e to separate the isomeric pyrazolines i n order to obtain pure samples of each, e i t h e r by t . l . c . or by column chromato-graphy. However,the pyrazoline 118 was enriched to 85% and the pyra-z o l i n e 119 to 62% by successive column chromatography. The purpose of separating the pyrazolines was to e s t a b l i s h the product d i s t r i b u t i o n s from the p y r o l y s i s of each. An i n d i r e c t second method became a v a i l a b l e to determine the products of p y r o l y s i s from pyrazoline 118,as i t was discovered that when a mixture of the two pyrazolines i n ether s o l u t i o n was kept at room temperature over several weeks only 118 pyrolyzed. Investigation of the decomposition products by column chromatography revealed that none of the cyclopropane 127 was present. Thus cyclo-propane 127 must occur e x c l u s i v e l y from pyrazoline 119 and the decomposition products must therefore be representative of pyrazoline 118. Evidence that the pyrazoline 118 was decomposing e x c l u s i v e l y at room temperature i n ether s o l u t i o n i s the f a c t that the s t a r t i n g r a t i o 24 118 119 - 38 -o f 1 1 8 : 1 1 9 was a b o u t 2 : 1 r e s p e c t i v e l y a n d a f t e r s e v e r a l w e e k s t h e r a t i o a p p r o a c h e d 1 : 3 r e s p e c t i v e l y . I t i s a s s u m e d t h a t t h e d i f f e r e n c e o f p r o d u c t d i s t r i b u t i o n s i s n e g l i g i b l e f o r p y r a z o l i n e 118 i n e t h e r s o l u t i o n c o m p a r e d t o n e a t p y r o l y s i s . T h e p r o d u c t d i s t r i b u t i o n f o r 118 i s t h a t f o r t h e e t h e r s o l u t i o n a t r o o m t e m p e r a t u r e . The p r o d u c t d i s t r i b u t i o n f o r 100% 119 i s c a l c u l a t e d u s i n g t h e n e a t p y r o l y s i s o f a 2 5 : 7 5 r a t i o o f 1 1 8 : 1 1 9 r e s p e c t i v e l y a n d t h e n c o r r e c t i n g t o 100% 119 u s i n g t h e r e s u l t s f o r t h e d e c o m p o s i t i o n o f 118 i n e t h e r s o l u t i o n . F i v e p r o d u c t s w e r e i d e n t i f i e d , t h r e e c y c l o p r o p a n e s a n d t w o a , 6 - u n s a t u r a t e d k e t o n e s , a n d t h e p r o d u c t d i s t r i b u t i o n s a r e g i v e n i n T a b l e I I . T h e r e w e r e t w o m i n o r p r o d u c t s t h a t + 126 129 . 1 2 8 127 r e m a i n e d u n i d e n t i f i e d . I t i s p o s s i b l e t h a t t h e u n i d e n t i f i e d p r o d u c t s w e r e t h e d i h y d r o f u r a n d e r i v a t i v e s 130 e x p e c t e d f r o m p y r a z o l i n e 1 1 9 . F o r m a t i o n o f d i h y d r o f u r a n p r o d u c t s was s h o w n t o b e c h a r a c t e r i s t i c o f 3 - a c e t y l - l - p y r a z o l i n e s ( 1 4 ) . I n o n e o f t h e c o n f o r m a t i o n s p o s s i b l e f o r p y r a z o l i n e 119 , t h e a c e t y l g r o u p w o u l d b e i n a f a v o u r a b l e p o s i t i o n f o r r i n g c l o s u r e t o o c c u r . - 39 -The peaks a t t r i b u t e d to the a,8-unsaturated ketones had the same re t e n t i o n times as 128 and 129 obtained by the independent synthesis and were i s o l a t e d i n about 10% p u r i t y along with 90% of the cycl o -propane 127. The 10% por t i o n was determined to be a mixture of the two o l e f i n s 128 and 129 on the basis of the c h a r a c t e r i s t i c benzylic hydrogen absorptions i n the n.m.r. spectrum. Only 129 i s expected from the p y r o l y s i s of 118 or 119 (15) and the low y i e l d of 128 and 129 makes the s i g n i f i c a n c e of t h i s r e s u l t uncertain. I t may be that thermal isomerization on the v.p.c. column has taken place as consid-erable overlap of the two peaks occurred, c h a r a c t e r i s t i c of such isomerization. Addition of phenyl diazomethane to 3-methyl-3-pentene-2-one, (Z) -(25) gave the pyrazolines 120 and 121 i n about a 2:1 r a t i o r e s p e c t i v e l y . . P u r i f i c a t i o n by column chromatography gave a mixture of the two C-5 isomeric pyrazolines as a white s o l i d . 120 121 - 40 -A s i n t h e c a s e o f t h e two p y r a z o l i n e s 118 a n d 1 1 9 , i t was n o t p o s s i b l e t o s e p a r a t e t h e i s o m e r i c p y r a z o l i n e s c o m p l e t e l y , e i t h e r b y t . l . c . o r c o l u m n c h r o m a t o g r a p h y . H o w e v e r , i t was p o s s i b l e t o e n r i c h 120 t o 80% a n d 121 t o 50% b y c o l u m n c h r o m a t o g r a p h y . I t was a l s o p o s s i b l e t o s e p a r a t e p a r t i a l l y t h e t w o p y r a z o l i n e s b y s l o w r e c r y s t a l -l i z a t i o n f r o m e t h e r - p e t r o l e u m e t h e r , w i t h s u b s e q u e n t s e p a r a t i o n o f t h e c r y s t a l s a c c o r d i n g t o s i z e . S a m p l e s e n r i c h e d t o 95% 120 a n d 75% 121 w e r e t h u s o b t a i n e d . T h e p r o d u c t d i s t r i b u t i o n s f o r 120 a n d 121 a r e c a l c u l a t e d u s i n g t h e p r o d u c t d i s t r i b u t i o n s f r o m t h e i r e n r i c h e d s a m p l e s . F o u r p r o d u c t s w e r e o b t a i n e d , t h r e e i s o m e r i c c y c l o p r o p a n e s a n d o n e a , 6 - u n s a t u r a t e d k e t o n e , a n d t h e c a l c u l a t e d d i s t r i b u t i o n s a r e g i v e n i n T a b l e I I . Two m i n o r p r o d u c t s w e r e n o t i d e n t i f i e d a l t h o u g h i t i s p o s s i b l e t h a t t h e f o r m a t i o n o f t h e d i h y d r o f u r a n d e r i v a t i v e 150 t o o k p l a c e , r e s u l t i n g f r o m r i n g c l o s u r e o f t h e p y r a z o l i n e 120 ( 1 4 ) . The o l e f i n 128 was i d e n t i f i e d s o l e l y o n t h e b a s i s o f c o m p a r i s o n o f r e t e n t i o n 120 121 125 C O C H , ( V H r 5 o b + 126 128 127 - 41 -times with authentic samples of 128 and 129. Only 128 i s expected i f a transoid concerted e l i m i n a t i o n of nitrogen (15) takes place. The other u n i d e n t i f i e d product was present i n less than one percent. The p o s s i b i l i t y that t h i s u n i d e n t i f i e d product was the cyclopropane 133 was excluded on the grounds that when a sample containing t h i s product was heated at 220° f o r 2 hours t h i s same product did not rearrange to the Y*6-isomers 134 and 135 tas would be expected i n the case of an ac e t y l group c i s to a methyl group i n a cyclopropane d e r i v a t i v e (35). The peak i n the v.p.c. assigned as the a,g-unsaturated ketone 128 also remained unchanged on heating to 220° f o r 2 hours. 133 134 and 135 (erythro and threo) To fur t h e r exclude cyclopropane 135 as a product,a sample containing both pyrazolines 120 and 121 was decomposed at 120-30° and the n.m.r. of the r e s u l t i n g products was run. C h a r a c t e r i s t i c peaks i n the n.m.r. expected f o r the C-3 methyl and a c e t y l methyl of cyclopropane 133 (Table V) were not observed. Also absent were any peaks a t t r i b u t e d to the Y > ^ - i s o m e r s po s s i b l e from the p y r o l y s i s of 133. Addition of diazoethane to 3-methyl-4-phenyl-3-butene-2-one, (E)-(132) gave the pyrazolines 122 and 123 i n a r a t i o of 90:10 r e s p e c t i v e l y . A f t e r three treatments of the o l e f i n with the diazo compound,the crude product was t r i t u r a t e d with petroleum ether to y i e l d white c r y s t a l s . - 42 -TABLE II Py r o l y s i s Products f o r 3-Acetyl-3',4'-dimethyl-5-(and 5')-phenyl-l-pyrazolines (118 and 119) and 3'-Acetyl-3',4-dimethyl-5-(and 5')-phenyl-1-pyrazolines (120 and 121). 1-Pyrazoline A 125 A 126 ct,B-E a,6-Z* 128 and 129 A 127 118 1 98 1 0 119 13 25 21(7:14) 41 - 120 91 6 0 3 121 26 22 7 45 * Geometrical assignment was not made. R e c r y s t a l l i z a t i o n from ether-petroleum ether yielded the pure pyrazoline 122. The mother l i q u o r , now co n s i s t i n g of about a 50:50 mixture of COCH- C 6 H 5 COCH, COCH 6"5^, - X + CH„CHN * - 1 f + /'"j f C 6 H 5 132 122 123 122 and 123, was seeded with pure c r y s t a l s of 122 and l e f t f o r one week. On removing the a d d i t i o n a l c r y s t a l s of 122, the mother l i q u o r was fr a c t i o n a t e d by column chromatography. Product data f o r the p y r o l y s i s of f r a c t i o n s containing 122 and 123 i n the r a t i o s of 28:72, 32:68 and - 43 -36:64 r e s p e c t i v e l y w e r e d e t e r m i n e d . T h e d a t a f r o m t h e 28:72 s a m p l e w i t h t h e d a t a f r o m p u r e 122 p e r m i t t e d c a l c u l a t i o n s o f t h e p r o d u c t c o m p o s i t i o n f r o m 123 g i v e n i n T a b l e I I I . C.H, C ° C H 3 C 6 H 5 COCH5 b 5/,„. / /,,. _/ COCH. A N / A N / C_H 5 / S 122 123 136 C,H_ COCH, \ n n n „ A^^ fJOCH 6"5v ^ " 3 + V-COCH^ / \ ™ 3 ' \ / S 138 137 125 • C 6 126 C 6 H 5 127 T A B L E I I I P y r o l y s i s P r o d u c t s f o r 3 - A c e t y l - 3 ' , 5 - ( a n d 3 * , 5 ' ) - d i m e t h y l - 4 ' - p h e n y l -1 - p y r a z o l i n e s (122 a n d 123) a , 8 - E 8.Y-Z A A A 1 - P y r a z o l i n e 136 137 138 139 125 126 u n . 127 122 0 0 0 • 0 79 t r a c e 1 20 123 28 371 2 0 21 5 1 6 * G e o m e t r i c a l a s s i g n m e n t b a s e d o n t r a n s o i d a l e l i m i n a t i o n (15) - 44 -TABLE I V N.m.r. Data^for 3,3,4,5-Tetrasubstituted-l-pyrazolines 2 3" Pyrazoline COCH C-3 methyl H-4 H-5 C-4 or J „ C-5 methyl 4 5 ,...N COCH, 7.58 8.82 8.08 5.32 8.97 10.4 118 C 6 H 5 C0CH3 / / N 7.76 8.52 . 7.29 4.63 9.65 8.5 119 C 6 H 5 z. C0CH3 / / N 120 C 6 H 5" COCH, L N N 121 7.96 8.31 8.4 5.10 9.03 9.8 7.58 8.68 7.7 4.69 9.82 7.5 C6H5...'js^ C0CH3 N // N 7.52 8.93 6.78 5.18 8.48 8.4 122 - 4 5 -TABLE I V ( C o n t i n u e d ) P y r a z o l i n e COCH 3 C - 3 m e t h y l H - 4 H - 5 C - 4 o r C - 5 m e t h y l J. 8 . 5 0 6 . 2 7 5 . 9 1 8 . 5 6 7 . 0 123 1 C h e m i c a l s h i f t v a l u e s i n T u n i t s . 2 D r a w n i n p r e f e r r e d c o n f o r m a t i o n . 3 u Hz u n i t s . S i x p r o d u c t s w e r e i d e n t i f i e d a n d o n e , c o n s i s t i n g o f a b o u t 1% o f t h e t o t a l was n o t . T h r e e o f t h e p r o d u c t s w e r e i s o m e r i c c y c l o p r o p a n e s , a n d t h e r e m a i n i n g p r o d u c t s w e r e c t , B - a n d B , y - u n s a t u r a t e d k e t o n e s . No e v i d e n c e f o r t h e B , y - u n s a t u r a t e d o l e f i n 3 - m e t h y l - 4 - p h e n y l - 4 -h e x e n e - 2 - o n e , ( Z ) - ( 1 3 9 ) was f o u n d . I d e n t i f i c a t i o n o f P y r a z o l i n e s T h e a s s i g n m e n t t o t h e 1 - p y r a z o l i n e s i s o m e r i c a t C - 5 was made p r i m a r i l y o n t h e b a s i s o f n . m . r . a n d t h e p e r t i n e n t d a t a i s g i v e n i n T a b l e I V . I n t h e f i v e membered p y r a z o l i n e r i n g t h e a n i s o t r o p y o f t h e -N=N- d o u b l e b o n d a f f e c t s t h e s u b s t i t u e n t s a t C - 3 , C - 4 , a n d C - 5 u n e q u a l l y . When t h e p y r a z o l i n e i s i n o n e o f i t s c o n f o r m a t i o n s , t h e p s e u d o a x i a l p o s i t i o n s a r e i n a s h i e l d i n g z o n e a n d t h u s t h e c h e m i c a l s h i f t s o f s u b s t i t u e n t s i n t h e s e p o s i t i o n s a r e s h i f t e d u p f i e l d ; w h e r e a s the pseudo equatorial positions are in a deshielding zone and thus the chemical shifts are lowered in value. For example, consider the two isomeric pyrazolines, cis- and trans-3,5-dimethyl-3-acetyl-l-pyrazolines (21 and 22) which are drawn i n their preferred conformation in Figure 20. The C-3 methyl of the trans-pyrazoline 22 is expected to be at higher field than the C-3 8.40 x 7.78 T trans-22 cis-21  Figure 20 - Favourable conformations of cis- and trans-3,5-dimethyl-l-pyrazolines and chemical shifts of C-3 substituents. methyl of the cis-pyrazoline 21. In other words, the C-3 methyl of the trans-pyrazoline is expected to spend more time in the shielding zone of the -N=N- group than the C-3 methyl of the cis-pyrazoline. A similar argument holds for the acetyl groups at C-3 (14). For the series of pyrazolines prepared in this work i t is necessary to differentiate between pairs of compounds isomeric at C-5,for example, pyrazolines 118 and 119. The conformation for pyrazoline 118 in which three groups are in the pseudo equatorial position is expected to be the preferred conformation; whereas pyrazoline 119 will have its two conformations more equally populated, since each isomer has two substituents in both the pseudo equatorial and pseudo axial positions (13-15). Hence the C-3 methyl, C-4 hydrogen and C-5 hydrogen of 118 are expected to be at higher field than the same three groups in - 4 7 -F i g u r e 21 - C o n f o r m a t i o n a l p r e f e r e n c e s o f 5 - ( a n d 5 ' ) - p h e n y l - 3 ' , 4 ' -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 (118 a n d 1 1 9 ) . p y r a z o l i n e 1 1 9 . L i k e w i s e , t h e a c e t y l g r o u p a n d t h e C - 4 m e t h y l a r e e x p e c t e d t o b e a t l o w e r f i e l d i n p y r a z o l i n e 1 1 8 . A s i m i l a r a r g u m e n t h o l d s f o r t h e r e l a t i v e c h e m i c a l s h i f t s o f t h e s u b s t i t u e n t s i n p y r a z o l i n e s 120 a n d 121 ( T a b l e I V ) . T h e c o r r e s p o n d i n g s u b s t i t u e n t s f o r p y r a z o l i n e s 122 a n d 123 - a c e t y l m e t h y l , C - 3 m e t h y l , C - 5 m e t h y l , C - 4 h y d r o g e n - h a v e c h e m i c a l s h i f t s w h i c h a r e c o n s i s t e n t w i t h t h e a b o v e r a t i o n a l i z a t i o n . H o w e v e r , t h e C - 5 h y d r o g e n s o f p y r a z o l i n e s 122 a n d 123 h a v e t h e o p p o s i t e r e l a t i v e c h e m i c a l s h i f t s f r o m w h a t i s e x p e c t e d . T h e c h e m i c a l s h i f t o f t h e C - 5 h y d r o g e n o f 123 i s a t 3 . 9 1 T o r 0 . 7 3 ppm h i g h e r t h a n t h e c h e m i c a l s h i f t o f t h e C - 5 h y d r o g e n o f 122 a t 5 . 1 8 T . S i n c e t h e C - 5 h y d r o g e n o f 123 i s e x p e c t e d t o b e a t l e a s t 0 . 3 ppm l o w e r a n d n o t 0 . 7 3 ppm h i g h e r t h a n t h e C - 5 h y d r o g e n o f 1 2 2 , t h e n e i t h e r t h e C - 5 h y d r o g e n o f 122 i s d e s h i e l d e d b y a b o u t 1 . 2 ppm o r t h e C - 5 h y d r o g e n o f 123 i s s h i e l d e d b y a b o u t 1 . 2 ppm - p r e s u m a b l y d u e t o t h e e f f e c t o f t h e p h e n y l g r o u p a t C - 4 . A n e x p l a n a t i o n f o r t h e p o s i t i o n o f t h e C - 5 h y d r o g e n c h e m i c a l s h i f t s i s n o t e v i d e n t . I t i s d i f f i c u l t t o d e t e r m i n e w h i c h o f t h e t w o - 48 -C - 5 h y d r o g e n s h a s t h e n o r m a l c h e m i c a l s h i f t , s i n c e c o m p a r i s o n s w i t h o t h e r 3 - a c e t y l - l - p y r a z o l i n e s ( F i g u r e 22) t e n d t o s u g g e s t t h a t t h e C - 5 h y d r o g e n o f 122 i s much l o w e r t h a n e x p e c t e d a n d t h e C - 5 h y d r o g e n o f 1 2 3 i s s l i g h t l y h i g h e r t h a n e x p e c t e d . On t h i s b a s i s , i t a p p e a r s t h a t t h e C O C H 3 C O C H 3 H . II N H 5 . 5 3 H 5 . 6 7 20 C , H / C 0 C H 3 F i g u r e 22 - P r e f e r r e d c o n f o r m a t i o n s a n d H - 5 c h e m i c a l s h i f t v a l u e s o f some 3 - m e t h y l - 3 - a c e t y l - l - p y r a z o l i n e s . p h e n y l g r o u p a t C - 4 i s d e s h i e l d i n g t h e h y d r o g e n w h i c h i s c i s a t C - 5 i n t h e p y r a z o l i n e 1 2 2 . . '• . , O t h e r v a l u a b l e i n f o r m a t i o n w h i c h a i d s i n t h e a s s i g n m e n t s t o t h e C - 5 i s o m e r i c 1 - p y r a z o l i n e s i s t h e m a g n i t u d e o f t h e v i c i n a l c o u p l i n g c o n s t a n t , w h i c h i s d e p e n d e n t o n t h e d i h e d r a l a n g l e ( 1 3 ) , s i m i l a r t o e t h a n e d e r i v a t i v e s ( 3 6 ) . O v e r b e r g e r e t a l _ ( 2 7 ) h a v e p r e p a r e d c i s -a n d t r a n s - 3 , 5 - b i s ( p - m e t h o x y p h e n y l ) - 1 - p y r a z o l i n e s (54 a n d 5 3 ) . T h e c i s -p y r a z o l i n e h a s a v i c i n a l t r a n s - ( a , a ) - c o u p l i n g o f 1 1 . 5 Hz c o m p a r e d t o t h e v i c i n a l c i s c o u p l i n g f o r t h e t r a n s - p y r a z o l i n e o f a b o u t 8 . 0 H z . S i m i l a r - 49 -coupling constants are observed f o r the C-5 isomeric 1-pyrazolines (Table IV) i n which the pyrazolines 118, 120 and 122 di s p l a y larger couplings than the respective pyrazolines 119, 121 and 123. Physical data that are consistent with the assignments to the 1-pyrazolines are the values. The R^ values of the three pyrazolines 118, 120 and 122 are less than t h e i r C-5 isomeric counterparts 119, 121 and 123 r e s p e c t i v e l y . The product d i s t r i b u t i o n s also support the s t r u c t u r a l assignments i n that the pyrazolines 118, 120 and 122 give as the major product from p y r o l y s i s the cyclopropane r e s u l t i n g from r e t e n t i o n of configuration, whereas the pyrazolines 119, 121 and 123 give a more random d i s t r i b u t i o n of products. I d e n t i f i c a t i o n of Cyclopropanes There are four p o s s i b l e cyclopropane products and these are presented i n Table V.- I d e n t i f i c a t i o n i s based on three aspects: the r e l a t i v e p o s i t i o n s of the chemical s h i f t s , the H-2 H-3 coupling constants, and the thermal rearrangement of cis-l-acetyl-3-methyl-cyclopropane d e r i v a t i v e s to y,6-unsaturated ketones. The r e l a t i v e p o s i t i o n s of the chemical s h i f t s of the 1-methyl and 1-acetyl groups provide important information i n determining the stereo-chemistry between C-l and C-2.* It i s expected that the substituent, i n t h i s case e i t h e r a c e t y l or methyl, c i s to the phenyl group w i l l be more shielded, r e l a t i v e to the group when i t i s trans. It i s found that i n cyclopropanes 125 and 127 the a c e t y l resonances are at 7.81 and 7.79 T r e s p e c t i v e l y , well within the normal range of 7.4-7.9 T. * C-2 i s always taken as the carbon bearing the phenyl group. - 50 -TABLE V N . m . r . D a t a ^ o r 1 , 1 , 2 , 3 - T e t r a s u b s t i t u t e d C y c l o p r o p a n e s C y c l o p r o p a n e C 0 C H 3 C^CH^ C 2 - H C 3 - H C 3 ~ C H 3 J H _ H ( H z ) C6VA/°C H3 126 8 . 2 0 8 . 5 1 7 . 9 9 7 . 6 6 8 . 7 6 7 . 0 C H L 6 5 127 COCH 3 7 . 7 9 8 . 8 8 7 . 1 9 8 . 2 8 . 9 5 9 . 8 A c O C H 3 7 . 8 1 8 . 9 2 7 . 1 5 8 . 6 8 . 8 8 6 . 4 C 6 H 5 * 125 c6\AJOCH-133 8 . 2 8 . 5 * C h e m i c a l s h i f t v a l u e s i n x u n i t s . 2 A p p r o x i m a t e e x p e c t e d v a l u e s . T h e r e s p e c t i v e C - l m e t h y l s o f 125 a n d 127 a p p e a r a t 8 . 9 2 a n d 8 . 8 7 T. H o w e v e r , i n t h e c a s e o f c y c l o p r o p a n e 1 2 6 , t h e a c e t y l r e s o n a n c e i s s h i f t e d b y a b o u t 0 . 4 ppm t o h i g h e r f i e l d a t 8 . 2 0 x a n d t h e C - l m e t h y l i s a b o u t 0 . 4 ppm l o w e r a t 8 . 5 1 x . T h u s t h e p h e n y l g r o u p s i g n i f i c a n t l y s h i e l d s t h e a c e t y l g r o u p a n d m u s t b e c i s i n c y c l o p r o p a n e 1 2 6 . R o b e r t s e_t al_. ( 3 7 ) h a v e s t u d i e d t h e a b s o l u t e m a g n i t u d e s o f t h e n . m . r . c o u p l i n g c o n s t a n t s f o r s e v e r a l c y c l o p r o p a n e d e r i v a t i v e s a n d - 51 -have found that in general J . > J. > J . I n particular, values & cis trans gem r of J . were found to be in the range of 8.0 - 11.2 Hz and J. in cis b trans the range of 5.2 - 7.0 Hz. For the cyclopropanes 125 and 126?the ^-Hj coupling constants of 6.4 and 7.0 Hz respectively are consistent with trans coupling. For the remaining cyclopropane 127 ,the coupling of 9.8 Hz is attributed to cis coupling. The H-2 H-3 coupling constant establishes the stereochemistry between C-2 and C-3. The third check used in the identification of the cyclopropanes was the expectation that the cyclopropanes, in which the acetyl and C-3 methyl are cis, would rearrange thermally to the y>6"-unsaturated ketones (35). Thus on heating cyclopropane 123 at 227° for 3.5 hours, complete rearrangement took place to the erythro- and threo-y,5-unsatur-ated ketones 134 and 135 in a ratio of 2:1 respectively. Identification of the erythro- and threo-isomers was based on the fact that the substituent - methyl or acetyl - which is cis to the phenyl group in the most stable conformation will be shielded (38). Neither cyclopropane 126 or 127 rearranged under similar reaction conditions. C,H 6 5 125 COMe H H C=C C6 H5 erythro-134 H, ^'Hv H H COCH, C=C C6 H5 threo-135 Figure 23 - Thermal rearrangement of 1-acetyl-l',3-dimethyl-2'-phenyl-cyclopropane. - 52 -Thus there are three pieces of evidence,all of which are i n t e r n a l l y consistent and providing an unambiguous assignment to the three isomeric cyclopropanes 125, 126 and 127. I d e n t i f i c a t i o n of Ol e f i n s The thermal decomposition of pyrazoline 125 gave 3-methyl-4-phenyl-3-hexene-2-one, (E)- (136) and 3-methyl-4-phenyl-4-hexene-2-one, (E)- (137) i n 28 and 37% r e s p e c t i v e l y . The corresponding Z_ isomer of 136, that i s , 3-methyl-4-phenyl-3-hexene-2-one, (Z)- (138) was detected i n about 2%. The corresponding Z_- 139 isomer of 157 was not detected at a l l (Table I I I ) . According to the transoid nitrogen elimination (15),the exp-and 8,Y-unsaturated ketones 136 and 137 are expected to be the major o l e f i n s from the p y r o l y s i s of pyrazoline 123. Since the v.p.c. re t e n t i o n times of the o l e f i n s from the p y r o l y s i s of 123 are almost i d e n t i c a l , i t was necessary to i s o l a t e them together. Peaks i n the n.m.r. are c l e a r l y resolved f o r 136 and 137. However, several smaller peaks, p o s s i b l y due to the o l e f i n 138 and other impurities were also present i n the n.m.r. In order to confirm the structure of the a,B-unsaturated ketone 136 and the presence of 138, a mixture of the a,g-unsaturated o l e f i n s 136 and 138 were synthesized f o r comparison. A modified W i t t i g (39), using propiophenone and trimethyl a-phosphonopropionate gave methyl-2-methyl-3-phenyl-2-pentenoate, (E)-(140) and (Z)- (141) i n a 1:2 r a t i o r e s p e c t i v e l y . Hydrolysis of the esters gave the corresponding acids 142 and 143 i n about a 1:2 r a t i o r e s p e c t i v e l y . Subsequent r e a c t i o n of the acids with methyl l i t h i u m (40) yi e l d e d a mixture of the o l e f i n s 136 and 138 i n a r a t i o of 1:9 - 53 -r e s p e c t i v e l y . 0 yx'Z ~ 6 ^ 5 ; " 2 ~ " 3 II C O - , C H „ C , H r C O „ C H ^ C 6 " 5 C Q 2 C H 3 i 4 £ 141 ( 1 : 2 ) C 0 2 H C 6 H 5 C 0 2 H COCHj c H C 0 C H / + \ / > "~\ / \ / • \ \ / \ \ i i i H I 6 5 136 138 ( 1 : 2 ) ( 1 : 9 ) F i g u r e 24 - R e a c t i o n s e q u e n c e i n p r e p a r a t i o n o f 3 - m e t h y l - 4 - p h e n y l - 3 -h e x e n e - 2 - o n e , ( E ) - ( 1 3 6 ) a n d , ( Z ) - ( 1 3 8 ) . A s s i g n m e n t o f s t r u c t u r e s t o t h e c t , 3 - u n s a t u r a t e d k e t o n e s 136 a n d 138 i s made b y c o m p a r i s o n o f t h e a c e t y l a n d C - 3 m e t h y l r e s o n a n c e s i n t h e n . m . r . T h e E- 136 i s o m e r g i v e s a n o r m a l a c e t y l p e a k a t 7 . 9 5 T w h e r e a s t h e Z- 138 i s o m e r , w i t h t h e a c e t y l a n d p h e n y l c i s , h a s t h e a c e t y l p e a k s h i f t e d u p f i e l d b y a b o u t 0 . 5 ppm t o 8 . 5 1 x . A s i m i l a r s h i f t o f t h e C - 3 m e t h y l d u e t o t h e p h e n y l g r o u p i s o b s e r v e d ( F i g u r e 2 5 ) . 7 . 9 5 x C O C H , C , H o 4 \ C 6 H 5 8 . 3 4 x — \ 8 . 5 1 x C O C H , 8 . 1 0 x 136 138 F i g u r e 25 - 3 - M e t h y l - 4 - p h e n y l - 3 - h e x e n e - 2 - o n e , ( E ) - ( 1 3 6 ) a n d ( Z ) - ( 1 3 8 ) a s s i g n m e n t s b y n . m . r . - 54 -A u t h e n t i c s a m p l e s o f 157 a n d 139 w e r e n o t a v a i l a b l e f o r c o m p a r i s o n a n d t h e r e f o r e a s s i g n m e n t o f s t r u c t u r e 137 i s b a s e d e n t i r e l y o n t h e t r a n s o i d n i t r o g e n e l i m i n a t i o n m e c h a n i s m ( 1 5 ) . S u c h a m e c h a n i s m w o u l d p r e d i c t t h a t t h e C - 5 m e t h y l a n d p h e n y l g r o u p s a r e c i s , a s t h e y a r e i n t h e s t a r t i n g p y r a z o l i n e 1 2 3 . T h e m a j o r a , B - u n s a t u r a t e d k e t o n e p r o d u c t i s c o n s i s t e n t w i t h t h e t r a n s o i d e l i m i n a t i o n m e c h a n i s m . 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 p y r a z o l i n e s 121 a n d 119 g a v e t h e a , 8 - u n s a t u r a t e d k e t o n e s 3 - m e t h y l - 4 - b e n z y l - 3 - p e n t e n e - 2 - o n e , ( E ) - ( 1 2 8 ) a n d ( Z ) - ( 1 2 9 ) . T h e e x p e c t e d 8 , y - u n s a t u r a t e d k e t o n e s w e r e n o t d e t e c t e d I d e n t i f i c a t i o n o f t h e t w o k e t o n e s 128 a n d 129 was b a s e d o n t h e p r e s e n c e of b e n z y l i c h y d r o g e n a b s o r p t i o n s i n t h e n . m . r . a n d b y c o m p a r i s o n o f r e t e n t i o n t i m e s w i t h t h o s e o b t a i n e d f r o m a n a u t h e n t i c m i x t u r e . A m o d i f i e d W i t t i g ( 3 9 ) , u s i n g p h e n y l a c e t o n e a n d t r i m e t h y l a -p h o s p h o n o p r o p i o n a t e g a v e m e t h y l 3 - m e t h y l - 3 - b e n z y l - 2 - b u t e n o a t e , ( E ) -( 1 4 4 ) a n d ( Z ) - ( 1 4 5 ) . C o n v e r s i o n o f t h e e s t e r s t o t h e c o r r e s p o n d i n g a c i d s 146 a n d 147 a n d s u b s e q u e n t r e a c t i o n o f t h e a c i d s w i t h m e t h y l l i t h i u m ( 4 0 ) g a v e t h e t w o k e t o n e s 128 a n d 129 i n a 1 : 2 r a t i o r e s p e c t i v e F i f t y p e r c e n t o f t h e r e a c t i o n p r o d u c t was o n e o f t h e B , y - u n s a t u r a t e d k e t o n e i s o m e r s . I t was n o t p o s s i b l e t o d e t e r m i n e t h e s t e r e o c h e m i s t r y o f t h e i s o m e r i c 3 - m e t h y l - 4 - b e n z y l - 3 - p e n t e n e - 2 - o n e s ( E ) - ( 1 3 6 ) a n d ( Z ) - ( 1 3 8 ) b y u s i n g t h e c h e m i c a l s h i f t s o f t h e b e n z y l i c h y d r o g e n s . N o r m a l l y t h e C - 5 h y d r o g e n s o f an a , 8 - u n s a t u r a t e d k e t o n e t h a t a r e c i s t o t h e a c e t y l g r o u p a r e a t l o w e r f i e l d i n t h e n . m . r . ; h o w e v e r , t h e r e a r e a t l e a s t , t w o e x c e p t i o n s . One i s t h e k e t o n e s 3 - m e t h y l - 3 - p e n t e n e - 2 - o n e ( E ) - ( 2 4 ) - 55 -CO CH . c * H c - V •CO. CH_ C H C 0 2 C H 3 6 5 1 4 4 145 + g,Y-isomer > corresponding acids 146 and 147 + 3 , Y _ a c i d 6 5 ^ ' + y ^ + g,Y-isomer / C > C H 3 C 6 H 5 - / ^ C 0 C H 3 Figure 26 - Reaction sequence f o r preparation of 3-methyl -4-benzyl -3 -pentene -2-one, (E)- (128) and (Z)- (129). and (Z_)- (25) i n which the C-5 hydrogens resonate at 8.18 and 8.19 r e s p e c t i v e l y (14). The other i s two ketones from t h i s work, 3-methyl-4-phenyl -3-pentene -2-one (E)- (136) and (Z)- (138), with both the C-5 and C-6 hydrogens of the E_ isomer appearing at higher f i e l d than the corresponding peaks of the !_ isomer. Discussion (a) O l e f i n Formation Part (a) of the d i s c u s s i o n w i l l be concerned with o l e f i n formation from the p y r o l y s i s of 1-pyrazolines. The main feature concerning the o l e f i n forming r e a c t i o n from the p y r o l y s i s of the t e t r a s u b s t i t u t e d 1-pyrazolines i n t h i s work i s that pyrazoline 122 gives only cyclopropane products, whereas the C-5 isomeric pyrazoline 123 gives 67 percent a,8- and B,y-unsaturated ketones and 33 percent cyclopropane products (Table I I I ) . This r e s u l t demonstrates the dependence of the o l e f i n - 56 -forming reactions on the conformation of the s t a r t i n g 1-pyrazoline and supports the mechanism in v o l v i n g concerted loss of nitrogen from the side of the pyrazoline that i s trans to the migrating hydrogen at C-4 (13-15)". That o l e f i n formation r e s u l t e d from pyrazoline 123 and not from pyrazoline 122 depends on the fac t that pyrazoline 122 must populate e n t i r e l y the conformation i n which three groups ( a c e t y l , C-5 methyl, phenyl) occupy pseudo equatorial p o s i t i o n s and the remaining group (C-3 methyl) occupies a pseudo a x i a l p o s i t i o n ; whereas pyrazoline 123 populates both conformations (Figure 27). COCH C 6 H 5 123 H <?6H5 N s I COCH3 / / / and COCH,/// COCH. 136 N _ / « H s 137 COCH, Figure 27 - Preferred conformations of 3-acetyl-3',5-(and 3',5')-4-phenyl-1-pyrazolines (122 and 123). - 57 -That pyrazoline 122 occupies only one conformation and that pyrazoline 123 occupies both conformations i s derived from n.m.r. studies. It has been established by McGreer and co-workers (13-15) that a substituent at C-4 or C-5 prefers to occupy a pseudo equatorial p o s i t i o n . I t i s therefore expected that pyrazoline 122 prefers the conformation with three of i t s substituents pseudo equatorial and one pseudo a x i a l . Pyrazoline 123 i s expected to occupy more equally both conformations, with the conformation avoiding the 3,5-diaxial (methyl and methyl) i n t e r a c t i o n being the major contributor (Figure 27). Thus the pyrazoline 123 should more r e a d i l y y i e l d o l e f i n products. A d d i t i o n a l evidence f o r conformational preference based on n.m.r. i s obtained from chemical s h i f t values, i n p a r t i c u l a r , the C-3 and ac e t y l methyl resonances (Table VI). Representative values f o r a pyrazoline that occupies both conformations equally are obtained from 3-methyl-3-acetyl-l-pyrazoline (20). That both conformations of pyrazoline 20_ are equally populated i s based on two f a c t o r s . One i s that the C-5 hydrogens have i d e n t i c a l chemical s h i f t values and the other i s that the two isomeric a,6-unsaturated ketones are formed equally (14) Chemical s h i f t values of pyrazolines that occupy only one conformation may be obtained from c i s - and trans-3,5-dimethyl-3-acetyl-1-pyrazolines (21 and 22). It appears that the conformational preference of a 3-methyl-3-acetyl-l-pyrazoline may be decided upon eit h e r by the p o s i t i o n of the C-3 and ac e t y l methyl resonances or by the d i f f e r e n c e between the two values (Table.VI). Thus the C-3 and a c e t y l methyl chemical s h i f t s of 21_ and 22_ should give an i n d i c a t i o n of values expected f o r other C-3 methyl and C-3 ac e t y l 1-pyrazolines that have - 58 -TABLE VI N . m . r . D a t a f o r D e t e r m i n a t i o n o f C o n f o r m a t i o n a l P r e f e r e n c e s o f 3 - M e t h y l - 3 - a c e t y l - 1 - p y r a z o l i n e s P y r a z o l i n e 1 3 - m e t h y l ( x ) a c e t y l m e t h y l ( x ) A(ppm) 1 . 4 1 1 . 1 0 0 . 9 8 0 . 8 4 - 59 -TABLE VI (Continued) Pyrazoline 3-methyl(x) a c e t y l methyl(x) A(ppm) 0.76 0.75 0.62 0.35 120 Drawn i n preferred conformation. Influenced by C-4 phenyl group. - 60 -a preference f o r one conformation over the other (Table VI). That pyrazolines 21_ and 22_ occupy only one conformation i s based on the s t e r e o s p e c i f i c formation of an a,g-unsaturated ketone from each. The values of the C-3 methyl resonance at 8.49 T and the C-3 a c e t y l methyl at 7.75 x f o r pyrazoline 123 f a l l between the respective values f o r pyrazolines 20 and 21, i n d i c a t i n g population of both conformations, with the one i n which the two methyls are pseudo equatorial being preferred. On the other hand the values of the C-3 and a c e t y l methyl resonances f o r pyrazoline 122 are more extreme than expected on comparison to pyrazoline 22_. This not only in d i c a t e s a strong preference for one conformation but also may i n d i c a t e a larger degree of f o l d i n g i n pyrazoline 122 compared to _22_. This l a t t e r point w i l l be dealt with i n more d e t a i l i n part (b) of the di s c u s s i o n , concerning the formation of cyclopropanes from 1-pyrazolines. The point being made from the comparison of the products from the C-5 isomeric pyrazolines 122 and 125 i s that the C-4 hydrogen must be pseudo equatorial before i t can migrate e i t h e r to C-5 or C-5. Since pyrazoline 122 e x i s t s i n only one conformation (Figure 27),the C-4 hydrogen i s always pseudo a x i a l and thus i s never i n a favourable p o s i t i o n to migrate trans to the leaving nitrogen. However, pyrazoline 125, occupying both conformations, now has a C-4 hydrogen pseudo equatorial i n one of the conformations. It i s through t h i s conformation that the formation of 6 7 percent o l e f i n takes place. (b) Cyclopropane Formation Part (b) of the dis c u s s i o n w i l l be concerned with cyclopropane formation from the p y r o l y s i s of 1-pyrazolines. Stereochemical aspects - 61 -of cyclopropane formation have been studied by McGreer and co-workers (12-15) f o r both 3,4- and 3,5-dialkyl-3-acetyl-(and 3-carbomethoxy)-1-pyrazolines (Table V I I I ) . Other studies have been made on 3,5-diaryl-1-pyrazolines by Overberger and co-workers (25-28),and on 3 ,4 - and 3,5-disubstituted-1-pyrazolines by Crawford and co-workers (19a-c,22,23,32) (Table IX). It i s the purpose of the present study to extend the understanding of cyclopropane formation by studying the p y r o l y s i s of pyrazolines uniquely substituted at a l l three carbon centers. The most s i g n i f i c a n t feature i n the p y r o l y s i s of the 1-pyrazolines i n t h i s work (Table VII) i s the f a c t that the pyrazolines 118, 120 and 122 - i n which three of the substituents are pseudo equatorial and the other pseudo a x i a l - give the cyclopropane r e s u l t i n g from r e t e n t i o n at both C-3 and C-5 as the major product; whereas the pyrazolines 119, 121 and 123 - i n which two of the substituents are pseudo equatorial and the other two pseudo a x i a l - give a random d i s t r i b u t i o n of cyclo-propanes. In the l a t t e r case, the major product may or may not be the cyclopropane r e s u l t i n g from r e t e n t i o n at both C-3 and C-5. This r e s u l t suggests that there i s a d i s t i n c t d i f f e r e n c e between the two sets of pyrazolines - on one hand 118, 120 and 122 - and on the other hand 119, 121 and 123. It i s the former set of pyrazolines that appear to be abnormal since other 3,5-disubstituted 1-pyrazolines with an e l e c t r o n withdrawing group at C-3 give as the major cyclopropane the one r e s u l t i n g from in v e r s i o n at e i t h e r C-3 or C-5 (13,14). T y p i c a l examples from Table VIII and c i s - and trans-3,5-dimethyl-3-acetyl-l-pyrazolines (____ and 22) . The most obvious di f f e r e n c e s - using pyrazolines 122 and 123 as an - 62 -TABLE V I I C y c l o p r o p a n e P r o d u c t s 1 f r o m 3 , 3 , 4 , 5 - T e t r a s u b s t i t u t e d - l - p y r a z o l i n e s 1 - P y r a z o l i n e C 6 H J_?l 126 127 133 / C O C H . C . H / C O C H , C O C H , C ^ H * " ' t O C H , o o o 0 3 6 5 3 COCH_ i L N C 6 H 5 ^ i' l» 9 8 ° i5 ° i3 ,5 118 1 T • N C f i H K ( / 91 6 . , 3 0 6 N i 3 ^ 1 3 , 5 ° i 5 120 6 5 \ T N 122 z _ - N 7 7 9 °i3 • 2 ° i 5 — N , C O C H , / / C 6 H 5 4 _ ^ L ; / l 3 i 3 , 5 » i 5 C 6 H 5 \ 119 .COCH JL ! N // 1 2 1 ~ ~ C 6 H 5 ^ _ _ N 2 6 i 5 2 2 i 3 , 5 4 5 i 3 i 3 I N C O C H , / / 9 1 _ 3 " 2 1 . 5 . , _ 6 0 . N 1 5 i 3 , 5 u i 3 123 I n v e r s i o n r e q u i r e m e n t s a t C - 3 ; i 5 - i n v e r s i o n f o l l o w c y c l o p r o p a n e p e r c e n t a g e s : i 3 - i n v e r s i o n a t C - 5 ; i 3 , 5 - i n v e r s i o n a t C - 3 a n d C - 5 . - 63 -TABLE V I I I D i s t r i b u t i o n o f C y c l o p r o p a n e P r o d u c t s f o r P y r a z o l i n e s w i t h E l e c t r o n W i t h d r a w i n g G r o u p s a t C - 3 P y r a z o l i n e c i s - A t r a n s - A o t h e r r e f . C 0 2 C H 3 22 N = N N — N CO C H 3 C 0 2 C H 3 35 •  ~; C 0 2 C H 3 36 C , 6 H 5 18 1 2 i 3 70 (11) 2 8 i 3 35 27 (11) I ' w C 0 2CH 3 60 16 ^ 24. 1 3 or s 60 (14} 6 1 i 3 o r 5 17 22 ( 1 4 ) 31 9 i 3 60 ( 1 5 ) H i 3 72 17 ( 1 5 ) C ° 2 C H 3 2 9 - 6 7 0 - 4 ( 3 1 ) 146 f^C'^Z-"^ » i 3 N ~ N - 64 -TABLE I X D i s t r i b u t i o n o f C y c l o p r o p a n e P r o d u c t s f o r 3 , 5 - D i a r y l - l - p y r a z o l i n e s a n d A l k y l S u b s t i t u t e d 1 - P y r a z o l i n e s P y r a z o l i n e c i s - A t r a n s - A O t h e r R e f . C 6 H S ^ . C 6 H 5 N — N " ' ' n i 3 o r 5 8 9 0 C 2 8 ) p _ - a n i s y } ( p _ - a n i s y l 5 3 , | = J, 6 . 7 i 3 o r 5 9 3 . 0 0 ( 2 8 ) £ - a n i s y l £ - a n i s y l — . 1 1 4 3 . 0 5 7 . 0 . ^ n T . _ 0 ( 2 8 ) C 1 - C , H „ , C - H . - C I 6 4 / ' # , / \ ^ » 6 4 • 5 5 79 80 89 N — N 0 i 3 o r 5 1 0 0 0 ( 2 8 ) N = N 3 3 - 2 ^ i S o r S ° ' 7 ( " J 7 2 • ^ 3 o r 5 2 5 ' 4 2 - 0 ( 1 9 ) N ZZ N D r V 1 _ 1 50 5 0 . 4 . 9 ( 2 2 ) N = N 1 3 D 2°_ P T 50 50 5 . 3 ( 2 2 ) N — N 1 3 ~  94 [ I 45.4 3 3 , 0 i 3 2 1 - 6 ( 2 3) ~ N —- N 21 I ' 4 6 . 0 . _ 2 1 . 8 2 2 . 2 ( 2 3 ) N = : N 13 . - 6 5 -e x a m p l e - i s t h a t p y r a z o l i n e 122 e x i s t s i n o n l y o n e c o n f o r m a t i o n } w h e r e a s p y r a z o l i n e 125 o c c u p i e s b o t h c o n f o r m a t i o n s . T h i s p o i n t c o n c e r n i n g c o n f o r m a t i o n a l p r e f e r e n c e s o f 122 a n d 123 h a s b e e n d i s c u s s e d p r e v i o u s l y i n p a r t ( a ) o f t h e d i s c u s s i o n . T h e e x p l a n a t i o n c h o s e n t o e x p l a i n t h e f a c t t h a t f r o m p y r a z o l i n e s 1 1 8 , 120 a n d 122 t h e m a j o r c y c l o p r o p a n e i s t h e o n e i n w h i c h r e t e n t i o n i s o b s e r v e d a t b o t h C - 3 a n d C - 5 , w h e r e a s p y r a z o l i n e 1 1 9 , 1 2 1 , a n d 123 g i v e a r a n d o m s e l e c t i o n o f c y c l o p r o p a n e s d o e s n o t d e p e n d o n t h e o b v i o u s d i f f e r e n c e b e t w e e n c o n f o r m a t i o n a l p o p u l a t i o n s . I n s t e a d , i t i s p r o p o s e d t h a t i t i s t h e d i f f e r e n c e b e t w e e n t h e d e g r e e o f f o l d i n g i n t h e p y r a z o l i n e m o l e c u l e , w h e r e t h e d e g r e e o f f o l d i n g i s d e f i n e d a s t h e a n g l e b e t w e e n t h e p l a n e o f a t o m s C - 3 , C - 4 , C - 5 a n d t h e p l a n e o f a t o m s C - 3 , N - 2 , N - 1 , C - 5 . M c G r e e r _3_t a l _ ( 1 3 ) h a v e e s t i m a t e d t h e c i s - d i h e d r a l a n g l e a n d t h e t r a n s - ( a , a ) - d i h e d r a l a n g l e t o b e a b o u t 2 5 ° a n d 1 4 5 ° r e s p e c t i v e l y f o r c i s - a n d t r a n s - 3 , 5 - d i m e t h y l - 1 - p y r a z o l i n e s (11 a n d 1 2 ) . T h i s e s t i m a t i o n was b a s e d o n t h e o b s e r v e d c o u p l i n g c o n s t a n t s o f a b o u t 8 . 0 Hz f o r b o t h t h e c i s - a n d t r a n s - ( a , a ) - c o u p l i n g . T h e c a l c u l a t e d d i h e d r a l a n g l e s o f 2 5 ° a n d 1 4 5 ° g i v e s a f o l d i n g o f a b o u t 2 5 ° b e t w e e n t h e t w o p l a n e s i n t h e p y r a z o l i n e s 1_1 a n d 1_2. A s s u m i n g t h a t t h e t r a n s - ( a , a ) - c o u p l i n g , c o n s t a n t i n c r e a s e s a s t h e a x i a l - a x i a l d i h e d r a l a n g l e i n c r e a s e s ( 3 6 ) , t h e n t h e p y r a z o l i n e s 1 1 8 , 120 a n d 122 h a v e a l a r g e r d e g r e e o f f o l d i n g t h a n u s u a l . T h e H - 4 H - 3 t r a n s - c o u p l i n g o b s e r v e d a r e 1 0 . 4 , 9 . 8 a n d 8 . 4 Hz r e s p e c t i v e l y . I t i s p o s s i b l e t h a t t h i s l a r g e r d e g r e e o f f o l d i n g i n t h e p y r a z o l i n e r i n g s y s t e m a c c o u n t s f o r t h e m a j o r p r o d u c t f r o m p y r a z o l i n e s 1 1 8 , 120 a n d 1 2 2 being the cyclopropane formed with r e t e n t i o n at both C-3 and C-5. I f the a x i a l - a x i a l coupling constant i s proportional to the degree of f o l d i n g then i t i s expected that the f o l d i n g decreases from pyrazolines 1 1 8 to 120 to 122 with trans-couplings of 10.4, 9.8, and 8.4 Hz r e s p e c t i v e l y . This order also c o r r e l a t e s with the degree of stereo-s p e c i f i c i t y o f 98 to 91 to 79 percent f o r pyrazolines 118, 120 and 1 2 2 r e s p e c t i v e l y . The s t e r e o s p e c i f i c i t y r e f e r s to the percentage of the cyclopropane formed with the same con f i g u r a t i o n as the s t a r t i n g p y r a z o l i n e . Another i n d i c a t i o n of the degree of f o l d i n g i s obtained from the chemical s h i f t values o f the C-3 and a c e t y l methyl resonances, or t h e i r d i f f e r e n c e , i n the n.m.r. (Table VI). However, the resonances of the resp e c t i v e groups f o r pyrazolines 118, 120 and 122 have more extreme values than expected on comparison to c i s - and trans-3,5-dimethyl-3-a c e t y l - l - p y r a z o l i n e s (21 and 22) which occupy only one conformation (14) (Figure 4). The more extreme values i n the n.m.r. spectrum can be a t t r i b u t e d to increased f o l d i n g of the pyrazoline molecule. Increased f o l d i n g places the substituents at C-3 (or C-5) i n a more intense s h i e l d i n g (equatorial) or deshielding ( a x i a l ) zone of the -N=N- double bond. On the b a s i s of the preceding explanation of the r e s u l t s , two mechanisms are proposed to account f o r the large degree of r e t e n t i o n i n the formation of cyclopropanes from pyrazolines 118, 120 and 122. One mechanism i s that as the pyrazoline i s e x p e l l i n g nitrogen, there i s at the same time some overlap of the p o t e n t i a l bonding o r b i t a l s between 67 -C-3 and C-5 and thus a cyclopropane with retention of configuration i s formed i n a concerted process (Figure 28). How much bonding there i s between the C-3 and C-5 po s i t i o n s of the pyrazoline i n the t r a n s i t i o n s tate i s dependent on the degree of f o l d i n g i n the s t a r t i n g pyrazoline molecule. COCH, COCH. C 6 H 5 3 — 7 N / /// I N COCH. 118 126 Figure 28 - Concerted mechanism f o r formation of cyclopropanes with re t e n t i o n of confi g u r a t i o n . An a l t e r n a t i v e explanation, which allows f o r an intermediate, u t i l i z e s the formation of a pyramidal d i r a d i c a l (Figure 29) as described by A l l r e d and Smith (33) (Figure 18). However, the pyramidal d i r a d i c a l i s not "inverted" at C-3 and C-5, where inv e r s i o n was a consequence of r e c o i l from the energy released by the C-N bond breaking (33), but i s formed merely from the expulsion of nitrogen without r e c o i l (Figure 29). Upon the formation of t h i s pyramidal d i r a d i c a l , immediate r i n g closure r e s u l t s i n a cyclopropane with r e t e n t i o n at C-3 and C-5. It may be that a true pyramidal d i r a d i c a l i s not produced but that the H , . u ^ COCH3 N C,H 6"5 118 COCH. C 6 H 5 COCH. 126 Figure 29 - Pyramidal d i r a d i c a l mechanism for;, formation of cyclopropanes with r e t e n t i o n of configuration. - 68 -back lobes have some development. This would give an intermediate between the pyramidal d i r a d i c a l and a trimethylene species where the p - o r b i t a l s are f u l l y developed. The more the intermediate resembles a pyramidal d i r a d i c a l , t h e more cyclopropane with retention of configura-t i o n . Thus the l a r g e r the degree of f o l d i n g i n the pyrazoline molecule the more the intermediate w i l l resemble the pyramidal d i r a d i c a l . Exactly why a greater f o l d i n g i n the pyrazoline molecule should allow f o r greater overlap of the developing bond between C-3 and C-5 (mechan-ism 1) or should make the intermediate resemble more strongly a pyramidal d i r a d i c a l (mechanism 2) i s not understood. Thus a mechanism invo l v i n g e i t h e r a concerted process or an intermediate resembling a pyramidal d i r a d i c a l i s proposed to play an important part i n the formation of cyclopropanes i n which retention of configuration i s observed. The degree to which a pyrazoline gives a cyclopropane with r e t e n t i o n of configuration appears dependent on the degree of f o l d i n g i n the pyrazoline molecule. In a pyrazoline such as 118,the degree of f o l d i n g i s large and p y r o l y s i s gives 98 percent of the cyclopropane 126 r e s u l t i n g from retention at C-3 and C-5. In pyrazolines such as c i s - and trans-3,5-dimethyl-3-acetyl-l-pyrazoline (21 and 22) and the analogous 3-carbomethoxy-l-pyrazolines 10_ and 11, the cyclopropane with the same stereochemistry as the s t a r t i n g pyrazoline varies from 15 to 18 percent (Table V I I I ) . This i s consistent with the le s s e r degree of f o l d i n g i n pyrazolines 10, 11, 21 and 22 as indicated by n.m.r. However,the degree of f o l d i n g may be to such a l e s s e r degree i n pyrazolines 10, 11, 21 and 2_2 compared to 118, 120 and 122 that the cyclopropanes with retention of stereochemistry may not be formed - 69 -at a l l through e i t h e r of the above two mechanisms but rather through some a l t e r n a t i v e route. Another feature of the r e s u l t s i s that cyclopropane 133 was never observed as a product of p y r o l y s i s from any of the s i x pyrazolines i n t h i s study (Table V I I ) . It was an t i c i p a t e d that pyrazoline 121 would give to some extent cyclopropane 133, since the pyrazoline and cycl o -propane have the same stereochemistry about the carbon atoms. Such was the case with the analogous pyrazolines 119 and 123 as cyclopropanes with r e t e n t i o n of configuration were formed from both pyrazolines. The chemical s h i f t values (Table VI) of the ac e t y l and C-3 methyls of pyrazoline 121 in d i c a t e that the molecule occupies e n t i r e l y the conformation i n which the C-3 ac e t y l group and the C-5 phenyl group are pseudo e q u a t o r i a l ; whereas the n.m.r. of the analogous pyrazolines 119 and 123 ind i c a t e s that both conformations are occupied, with the conforma-t i o n most highly populated being the one i n which the 3,5-diaxial i n t e r a c t i o n i s avoided. This suggests that f o r 3,5-diaxial i n t e r a c t i o n s , phenyl and a c e t y l (pyrazoline 121) i s much greater than e i t h e r phenyl and methyl (pyrazoline 119) or methyl and methyl (pyrazoline 123). Such a severe i n t e r a c t i o n of a phenyl and a c e t y l may also be i n d i c a t i v e of an equally severe i n t e r a c t i o n i n the t r a n s i t i o n s t a t e . However, such an i n t e r a c t i o n between an a c e t y l and phenyl group cannot be the main f a c t o r which explains the lack of formation of cyclopropane 133 since cyclo-propane 126, with a phenyl and a c e t y l c i s , i s formed s u b s t a n t i a l l y from each of the pyrazolines 119, 121, and 123. The a d d i t i o n a l f a c t o r must there f o r e be due to the presence of the C-4 methyl group which i s c i s to both the a c e t y l group at C-3 and the methyl group at C-5 i n the - 70 -s t a r t i n g pyrazoline 121, and which gives r i s e to s t e r i c crowding i n the t r a n s i t i o n s t a t e . Before continuing on to the next point concerning double i n v e r s i o n at C-3 and C-5,it i s f i r s t necessary to comment b r i e f l y on the formation of bicyclo[2.1.0]pentane derivatives from the correspond-ing 2,3-diazobicyclo[2.2.1]-2-heptene (33,34). A l l r e d and Smith (33) have proposed an inverted pyramidal d i r a d i c a l formed from the consequences of r e c o i l from energy released by C-N bond breaking. Ring closure before complete e q u i l i b r a t i o n accounts f o r the excess of the product of inverted structure (Figure 18). However, the product of inverted structure may also be r a t i o n a l i z e d using the second mechanism (Figure 29) from t h i s work i n v o l v i n g an intermediate resembling a pyramidal diradical,which accounted f o r the large degree of retention i n the formation of cyclopropane products from pyrazolines 118, 120 and 122 (Table VII). Expulsion of nitrogen from the b i c y c l i c pyrazoline without r e c o i l and double in v e r s i o n would r e s u l t i n an intermediate (Figure 30) resembling a pyramidal d i r a d i c a l i n which the back lobes are p a r t i a l l y developed. The d i s t i n c t d i f f e r e n c e between the intermediates from 118, 120 and 122 Figure 30 - Intermediate resembling a pyramidal d i r a d i c a l species i n p y r o l y s i s of endo-5-methoxy-2,3-diazabicyclo[2.2.1]-2-heptene. - 71 -and the intermediate from 109 and 110 is that in the former case the larger front lobes are pointing towards each other; however, in the latter case the strain of the five membered ring results in the back lobes pointing towards each other. Taking into consideration the bonding in bicyclo[2.1.0]pentane (46),the back lobes are in a favourable geometric position to bond as opposed to the front lobes. Allred and Smith (33) have suggested that the pyramidal diradical in their case can equilibrate, although not entirely, before ring closure occurs. However,in the second mechanism in this work the intermediate resembling a pyramidal diradical ring closes immediately upon formation. Similar work by Roth and Martin (34) has indicated predominance of double inversion in the pyrolysis of exo-5,6-dideuterio-2,3-diazobicyclo-[2.2.1]-2-heptene (115) (Figure 19). Their proposed mechanism involving concerted elimination of nitrogen with accompanying backside p-orbital overlap in the transition state seems equally improbable from a geometrical point of view since the developing backside p-orbitals are directed away from each other. The feature in the present study concerning double inversion is the substantial contribution of the cyclopropane in which inversion has taken place at both C-3 and C-5 of the starting pyrazolines 119, 121 and 12 3 (Table VII). There are several mechanisms which can explain double inversion, two of which have been mentioned in the preceding two paragraphs. As pointed out, the use of an "inverted" pyramidal diradical by Allred and Smith (33) is not necessary from the point of view that an intermediate resembling a pyramidal diradical can equally explain the predominance of the double inverted product. The other mechanism by Roth and Martin (34) seemed unlikely from a - 72 -geometrical point of view. Thus a t h i r d mechanism may be required to explain the considerable amount of double inverted cyclopropane product formed from the p y r o l y s i s of the 1-pyrazolines 119, 121 and 123. One such mechanism would involve a trimethylene intermediate, i n which a symmetrical trimethylene on d i s r o t a t i o n , would give cyclopropanes with retention or inv e r s i o n at both C-3 and C-5. However ,to t h i s date there i s no conclusive evidence that a trimethylene intermediate p a r t i c i p a t e s i n the p y r o l y s i s of 1-pyrazolines with an electron withdrawing group at C-3, although the existence of a trimethylene intermediate i s quite well established i n the p y r o l y s i s of a l k y l substituted 1-pyrazolines (19-24,32). As pointed out i n part (a) of the Introduction,very l i t t l e i s known about the formation of cyclopropane d e r i v a t i v e s from the p y r o l y s i s of 1-pyrazolines that have an electron-withdrawing group, such as a c e t y l or carbomethoxy, at the C-3 p o s i t i o n . A concerted mechanism (Figure 28) or a mechanism in v o l v i n g an intermediate resembling a pyramidal d i r a d i c a l (Figure 29) has been proposed to account f o r the formation of cyclopropanes that have the same stereochemistry as the s t a r t i n g pyra-z o l i n e . However,additional experimental data are required i n order to further the understanding of cyclopropanes formed by an inv e r s i o n at ei t h e r C-3 or C-5 or by a double i n v e r s i o n at C-3 and C-5. I I I . EXPERIMENTAL General Statement Melting points (m.p.) and b o i l i n g points (b.p.) are uncorrected. Infrared ( i . r . ) - s p e c t r a were recorded on a Perkin-Elmer model 137 spectrophotometer. A l l spectra were measured as a l i q u i d f i l m using sodium c h l o r i d e p l a t e s . The 60 MHz nuclear magnetic resonance (n.m.r.) spectra were recorded on e i t h e r a Varian Associates Model A-60 spectrometer or a J e l c o Model C-60 spectrometer by Miss P. Watson. The 100 MHz nuclear magnetic resonance spectra were recorded on a Varian Associates Model HR-100 spectrometer by Mr. R. Burton. The spectra were run as solutions e i t h e r i n carbon t e t r a c h l o r i d e or deuteriochloroform (Merck, Sharp and Dohm) with Tetramethylsilane as the i n t e r n a l reference. The vapour-phase chromatography (v.p.c.) u n i t s used were an Aerograph Model A-90-P and an Aerograph Model A-90-P3. A l l columns used were 10' x 1/4" unless otherwise in d i c a t e d . The elemental microanalyses were performed by Mr. P. Borda. Petroleum ether r e f e r s to the f r a c t i o n b o i l i n g between 30-60°. N-Nitroso-N-ethyl Urea N-Nitroso-N-ethyl urea was prepared according to the procedure given by Chiu (41). - 74 -Diazoethane Diazoethane was prepared from N-nitroso-N-ethyl urea according to the procedure given by Chiu (41). Benzaldehyde Hydrazone A procedure similar to that of Curtius (42) was used in the prepar-ation of benzaldehyde hydrazone. Into a 250 ml round bottom flask equipped with a mechanical stirrer was placed 1.5 g of barium oxide and 50 g (1.0 mole) of hydrazine hydrate. Over a period of one hr 95 g (0.90 mole) of freshly distilled benzaldehyde (Analar) was added. The reaction mixture was stirred vigourously at 100° for 6 hr. Before completion of the reaction a considerable amount of solid was formed,but during the course of the reaction the solution again became clear. The reaction mixture was cooled, diluted with ether, and filtered. The ether layer was dried with sodium sulphate and concentrated with a rotatory evaporator. The crude reaction product was distilled under vacuum to yield 90 g (0.74 mole) of a clear pale yellow liquid: yield 82%; b.p. 138-40° (14 mm); n.m.r. 4.08 T (broad singlet) nitrogen protons, 2.43 x (singlet) benzylic hydrogen, 2.40 and 2.74 x (multiplets' with areas of 2 and 3 respectively) ^2^5 system of aromatic hydrogens. Phenyl Diazomethane A procedure similar to Standinger (43),with yellow mercuric oxide (AC) as the oxidant,was used in the preparation of phenyl diazomethane. Into a 250 ml Erlenmeyer was placed 12 g (0.1 mole) of benzaldehyde hydrazone, 70 ml of petroleum ether and 1 ml of saturated potassium hydroxide alcoholic (ethanol) solution. The flask was placed in an - 75 -ice-water bath and over a period of 20 min 21.6 g (0.1 mole) of mercuric oxide was added to the magnetically s t i r r e d s o l u t i o n . The mixture was allowed to s t i r f o r an a d d i t i o n a l 10 min and the decanted petroleum ether layer was f i l t e r e d . The r e s u l t i n g red s o l u t i o n was made up to 100 ml with petroleum ether and used immediately. The preparation was c a r r i e d out i n a fume hood. Based on the reaction with 0.1 molar q u a n t i t i e s of methyl isopropenyl ketone, methylmethacrylate, and m e t h a c r y l o n i t r i l e , the y i e l d of phenyl diazomethane va r i e d between 50 and 65%. 3-Methyl-3-pentene-2-one, (Z)- (25) I r r a d i a t i o n of 12 g (0.12 mole) of 3-methyl-3-pentene-2-one, (E)-(24) (Aldrich) i n 100 ml of ether f o r 16 hr i n a s i l i c a tube using a o Hanovia 450 W lamp (2537 A) r e s u l t e d i n approximately 25% conversion to the desired _Z isomer 25_ as determined by v.p.c. (didecyl phthalate, 138°, 120 ml per min). The r e t e n t i o n .times f o r the Z_ and E isomers were 8.6 and 11.0 min r e s p e c t i v e l y ( l i t . (14): b.p. 124° and 147° r e s p e c t i v e l y ) . The ether was removed and a simple d i s t i l l a t i o n gave a f r a c t i o n b o i l i n g between 131-136° which consisted of a 50:50 mixture of the Z_ and E_ isomers. The 50:50 mixture was then f r a c t i o n a l l y d i s t i l l e d using a Nester and Faust s t a i n l e s s s t e e l spinning-band apparatus. The f r a c t i o n between 124-30° was c o l l e c t e d and consisted of a 90:10 r a t i o of the Z_ and E_ isomers r e s p e c t i v e l y . Since the spinning-band d i s t i l -l a t i o n f a i l e d to p u r i f y the Z_ isomer s u f f i c i e n t l y , 1.8 g (0.18 mole) was c o l l e c t e d using the v.p.c. r e s u l t i n g i n greater than 95% p u r i t y . - 76 -3-Methyl-4-phenyl-3-butene-2-one, (E)- (132) The o l e f i n 132 was prepared according to the procedure of Noyce (44). Into a 500 ml round bottom f l a s k was placed 106 g (1.0 mole) of benzaldehyde and 72 g (1.0 mole) of methyl ethyl ketone together with 3 ml of concentrated sulphuric acid and 100 ml of a c e t i c a c i d . The mixture was s t i r r e d at 75-85° f o r 3 hr. The rea c t i o n was monitored by v.p.c. (SE 30, 210°, 120 ml per min). The r e a c t i o n mixture was poured onto 650 g of i c e and water and extracted with ether. The ether was extracted with saturated sodium c h l o r i d e s o l u t i o n , 10% sodium carbonate, and again with saturated sodium c h l o r i d e . The s o l u t i o n was dried over sodium sulphate, concen-t r a t e d using a rotatory evaporator, and vacuum d i s t i l l e d to c o l l e c t the f r a c t i o n between 100-105° at 0.5 mm. The product was r e c r y s t a l l i z e d from ether-petroleum ether (1:1) to give white c r y s t a l s : y i e l d 23%; m.p. 37-40°; n.m.r. 7.97 x (doublet J = 1.5 Hz) C-3 methyl, 7.60 x (s i n g l e t ) a c e t y l methyl, 2.54 x (multiplet) v i n y l hydrogen, 2.65 x (si n g l e t ) aromatic hydrogens. 3-Acetyl-3',4'-dimethyl-5-phenyl-l-pyrazoline* (118) and 3-Acetyl-3 1,4 1 -dimethyl-5 1-phenyl-l-pyrazoline (119) (a) Preparation and Enrichment To an ether s o l u t i o n of 9.8 g (0.1 mole) of 3-methyl-3-pentene-2-, one, (E)- (124) was added phenyl diazomethane (from 12 g (0.1 mole) of benzaldehyde hydrazone). The s o l u t i o n was l e f t at -5° f o r 10 days. Pyrazoline formation was in d i c a t e d by use of n.m.r. The r a t i o of the * See Appendix f o r nomenclature - 77 -two pyrazolines 119 and 118 was estimated i n the crude r e a c t i o n mixture as 1:2 r e s p e c t i v e l y . The pyrazolines 118 and 119 were stored as a s o l u t i o n i n ether-petroleum ether at -5°. Column chromatography ( s i l i c a g e l , ether-petroleum ether, 5:95 to 10:90) on the crude reaction mixture gave two main f r a c t i o n s , the second of which y i e l d e d together the pure pyrazolines 118 and 119 as c l e a r c o l o u r l e s s l i q u i d s . By determining the r a t i o of the pyrazolines i n successive f r a c t i o n s , i t was found that the pyrazoline 119 had the larger R^- value. For the pyrazoline 118: n.m.r. 8.82 and 7.58 x ( s i n g l e t s ) C-3 and a c e t y l methyls r e s p e c t i v e l y , 8.97 x (doublet J = 7.0 Hz) C-4 methyl, 5.32 x (doublet J = 10.4 Hz) C-5 hydrogen, 8.08 x (multiplet) C-4 hydrogen, 2.7 x (multiplet) aromatic hydrogens. For the pyrazoline 119: n.m.r. 8.52 and 7.76 x ( s i n g l e t s ) C-3 and a c e t y l methyl r e s p e c t i v e l y , 9.65.x (doublet J = 7.5 Hz) C-4 methyl, 4.63 x (doublet J = 8.5 Hz) C-5 hydrogen, 7.29 x (multiplet) C-4 hydrogen, 2.7 x (multiplet) aromatic hydrogens. Anal. Calcd. f o r C.,H.,0N„ (as a mixture of 118 and 119): C, 13 16 2. 72.19; H, 7.46; N, 12.95. Found: C, 72.29; H, 7.36; N, 13.11. „ It was not p o s s i b l e to obtain pure samples of 100% 118 or 100% 119 by t . l . c . or by column chromatography. However, the pyrazoline 118 was enriched to 85% and the pyrazoline 119 to 62% by successive columns. A second method was used to enrich the pyrazoline 118. Although the p r e f e r e n t i a l decomposition of one pyrazoline over the other was unsuccessful at 55°, i t was discovered that over a period of several weeks slow decomposition of the pyrazoline 118 took place - 78 -at room temperature, thus enriching 119. Using column chromatography as described previously i t was po s s i b l e to determine the decomposition products from 100% 118 from the f i r s t f r a c t i o n , and the decomposition products from a mixture of 118 and 119 i n the r a t i o 25:75 r e s p e c t i v e l y from the second f r a c t i o n . Evidence that 118 decomposed e x c l u s i v e l y at room temperature i n ether-petroleum ether s o l u t i o n r e s u l t e d from the f a c t that the f i r s t f r a c t i o n from column chromatography contained none of the cyclopropane 127. Thus the cyclopropane 127 must occur e x c l u s i v e l y from the decomposition of the other pyrazoline 119. (b) P y r o l y s i s and Product I d e n t i f i c a t i o n The p y r o l y s i s of the pyrazolines 118 and 119 was c a r r i e d out e i t h e r as a neat sample at 100-120° or as a neat sample pyrolyzed i n the i n j e c t o r of the v.p.c. The v.p.c. (FFAP, 218°, 120 ml per min) showed 6 peaks A, B, C, D, E, and F with r e t e n t i o n times 8.6, 12.2, 13.6, 16.4, 17.6, and 20.0 min r e s p e c t i v e l y . Peak A was not i s o l a t e d or i d e n t i f i e d as i t was present i n only trace amounts. Peak B was i s o l a t e d and i d e n t i f i e d as a mixture of the cyclopropane 125 and the rearranged y,6-isomers 134 and 135 on the basis of n.m.r. Peak C was i s o l a t e d and i d e n t i f i e d as the compound 1-acetyl-l',3'-dimethyl-2-phenyl cyclopropane (126): i . r . 1695 cm * (carbonyl s t r e t c h i n g frequency); n.m.r 8.20 and 8.51 x (sin g l e t s ) a c e t y l and C- l methyls r e s p e c t i v e l y , 8.76 x (doublet J = 6.2 Hz) C-3 methyl, 7.99 x (doublet J = 7.0 Hz) C-2 hydrogen, 7.66 x (multiplet of approximately 5 l i n e s ) C-3 hydrogen, 2.8 x (broadened s i n g l e t ) aromatic hydrogens. - 79 -A n a l . C a l c d . f o r C , _ H . . , 0 : C , 8 2 . 9 3 ; H , 8 . 5 7 . F o u n d : C , 8 3 . 0 6 ; io io H, 8 . 5 5 • P e a k s D a n d E w e r e n o t i s o l a t e d i n p u r e f o r m s i n c e t h e y w e r e n o t p r e s e n t i n l a r g e a m o u n t s a n d s i n c e t h e i r r e t e n t i o n t i m e s w e r e c l o s e t o t h a t o f t h e m a j o r p e a k F. P a r t i a l s e p a r a t i o n g a v e a n a p p r o x i m a t e D a n d E toF r a t i o o f 1 0 : 9 0 r e s p e c t i v e l y . By c o m p a r i s o n o f t h e b e n z y l i c h y d r o g e n s i n t h e n . m . r . a n d r e t e n t i o n t i m e s w i t h a u t h e n t i c s a m p l e s , p e a k s D a n d E w e r e a s s i g n e d t h e s t r u c t u r e s 3 - m e t h y l - 4 - b e n z y l - 3 - p e n t e n e - 2 - o n e , ( E ) -( 1 2 8 ) a n d , ( Z ) - ( 1 2 9 ) . A l t h o u g h o n l y o n e o f t h e s e o l e f i n s i s e x p e c t e d ( 1 3 , 1 5 ) f r o m t h e p y r a z o l i n e s 118 a n d 1 1 9 , i t i s p o s s i b l e t h a t t h e o l e f i n s r e a d i l y i s o m e r i z e t h e r m a l l y o n t h e v . p . c . c o l u m n . C o n s i d e r a b l e o v e r l a p p i n g o f t h e t w o p e a k s D a n d E was o b s e r v e d . E v i d e n c e f o r b o t h o l e f i n s b e i n g p r e s e n t l i e s i n t h e f a c t t h a t t h e n . m . r . d i s p l a y s t w o b r o a d s i n g l e t s f o r t h e b e n z y l i c h y d r o g e n s i n t h e a p p r o p r i a t e r e g i o n . A d d i t i o n a l e v i d e n c e i s t h a t t h e p e a k s D a n d E h a v e s i m i l a r r e t e n t i o n t i m e s a s t h e a u t h e n t i c s a m p l e s t h a t w e r e s y n t h e s i z e d . P e a k F was i s o l a t e d a n d i d e n t i f i e d a s t h e compound 1 - a c e t y l - l ' , 3 ' -d i m e t h y l - 2 ' - p h e n y l c y c l o p r o p a n e ( 1 2 7 ) : i . r . 1690 cm 1 ( c a r b o n y l s t r e t c h i n g f r e q u e n c y ) ; n . m . r . ( 1 0 0 MHz) 7 . 7 9 a n d 8 . 8 8 x ( s i n g l e t s ) a c e t y l a n d C - l m e t h y l s r e s p e c t i v e l y , 8 . 9 5 x ( d o u b l e t J = 6 . 4 H z ) C - 3 m e t h y l , 7 . 1 9 x ( d o u b l e t J = 9 . 8 H z ) C - 2 h y d r o g e n , 8 . 2 x ( m u l t i p l e t ) C - 3 h y d r o g e n , 2 . 9 x ( b r o a d e n e d s i n g l e t ) a r o m a t i c h y d r o g e n s . A n a l . C a l c d . f o r C , , H 0 : C , 8 2 . 9 3 ; H , 8 . 5 7 . F o u n d : C , 8 2 . 8 9 ; H , 8 . 7 5 . - 80 -(c) Product D i s t r i b u t i o n TABLE X 1 2 D i s t r i b u t i o n of Products f or the Py r o l y s i s of D i f f e r e n t Ratios of the Pyrazolines 118 and 119 R a t i o 3 of 118:119 125 126 129 127 100:0 4 1 98 1 0 85:15 5 2 91 1 6 74:26 5 2 86 3 9 51:49 5 6 66 7 21 38:62 5 8 54 13 25 4 25:75 10 43 16 31 0:100 6 13 25 21 41 Average of three runs by v.p.c. D i s t r i b u t i o n of products from neat and v.p.c. P y r o l y s i s are i d e n t i c a l . Average of three integrations of C-5 hydrogens. P r e f e r e n t i a l decomposition of pyrazolines 118 and 119 at r . t . Successive f r a c t i o n a t i n g by column chromatography. Correction to 100% using r e s u l t s of p r e f e r e n t i a l decomposition r e s u l t s . - 81 -3'-Acetyl-3,4'-dimethyl-5-phenyl-l-pyrazoline (120) and 3'-Acetyl-3,4'-dimethyl-5 1-phenyl-l-pyrazoline (121) (a) Preparation and Enrichment To an ether s o l u t i o n of 1.8 g (0.18 mole) of 3-methyl-3-pentene-2-one, (Z)- (25) was added phenyl diazomethane (from 3.2 g (0.27 mole) of benzaldehyde hydrazone). The s o l u t i o n was l e f t at -5° f o r 2 weeks. Pyrazoline formation was indic a t e d by use of n.m.r. The r a t i o of the two pyrazolines 121 and 120 was estimated i n the crude r e a c t i o n mixture as 1:2 r e s p e c t i v e l y . The pyrazolines 120 and 121 were stored as a s o l u t i o n i n ether-petroleum ether at -5°. Column chromatography ( s i l i c a g e l , ether-petroleum ether, 5:95 to 10:90) on the crude r e a c t i o n mixture gave two main f r a c t i o n s , the second of which y i e l d e d together the pure pyrazolines 120 and 121 as white s o l i d s . By determining the r a t i o of the pyrazolines i n successive f r a c t i o n , i t was determined that the pyrazoline 121 had the larger value. For the pyrazoline 120: n.m.r. 8.31 and 7.96 T (sing l e t s ) C-3 and a c e t y l methyl r e s p e c t i v e l y , 9.03 T (doublet J = 6.8 Hz) C-4 methyl, 5.10 T (doublet J = 9.8 Hz) C-5 hydrogen, 8.4 x (multiplet C-4 hydrogen, 2.7 x (sin g l e t ) aromatic hydrogens. For the pyrazoline 121: n.m.r. 8.68 and 7.58 x (sing l e t s ) C-3 and a c e t y l methyl r e s p e c t i v e l y , 9.82 x (doublet J = 7.4 Hz) C-4 methyl, 4.69 x (doublet J = 7.5 Hz) C-5 hydrogen, 7.7 x (multiplet C-4 hydrogen, 2.7 x (sin g l e t ) aromatic hydrogens. Anal. Calcd. f o r C 1 3 H 1 6 0 N 2 (as a mixture of 120 and 121) : C, 72.19; H, 7.46; N, 12.95. Found: C, 72.40; H, 7.40; N, 12.70. - 82 -As i n the case of the pyrazolines 118 and 119, i t was not pos s i b l e to obtain pure samples of the pyrazolines 120 and 121 by t . l . c . or by column chromatography. However,pyrazoline 120 could be enriched to 80% and pyrazoline 121 to 50% by one run using column chromatography. As a r e s u l t of combining several f r a c t i o n s obtained from column chromatography and r e c r y s t a l l i z i n g f o r microanalysis i t was discovered that two d i f f e r e n t types of c r y s t a l s slowly developed. The pyrazolines were r e c r y s t a l l i z e d from ether-petroleum ether (10:90) and l e f t at -5° fo r two weeks. By separating the c r y s t a l s according to s i z e , samples enriched to 95% and 75% i n 120 and 121 r e s p e c t i v e l y were obtained. (b) P y r o l y s i s and Product I d e n t i f i c a t i o n The p y r o l y s i s of pyrazolines 120 and 121 was c a r r i e d out neat at 130-140°. The products of p y r o l y s i s were analyzed using the v.p.c. (FFAP, 218°, 120 ml per min) which showed 6 peaks, A, B, C, D, E, and F with r e t e n t i o n times 8.4, 12.2, 13.6, 16.4, 18.6 and 20.0 min re s p e c t i v e l y . Peak A was not i s o l a t e d and i d e n t i f i e d as i t was present i n only trace amounts. Peak B was i s o l a t e d and i d e n t i f i e d as a mixture of the cyclopropane 125 and the rearranged Y > < 5 - l s o m e r s 134 and 135 on the basis of n.m.r. Peak C was i s o l a t e d as a mixture with peak B and i d e n t i f i e d as the cyclopropane 126 on the basis of n.m.r. and comparison of re t e n t i o n times. Peak D was present i n only small amounts and therefore could not be i s o l a t e d . Its re t e n t i o n time does however,fall into the same - 83 -region as one of the two a,6-unsaturated ketones 128 and 129. Because of the small amount of peak D present i t was d i f f i c u l t to t e l l i f isomerization, as suggested i n the section dealing with the two ketones 128 and 129 from the p y r o l y s i s of the pyrazolines 118 and 119, was occurring. More important i s the f a c t that on heating the products of p y r o l y s i s at 220° f o r 2 hours, the peak D did not decrease i n s i z e . Thus peak D could not be the cyclopropane 133 which under these conditions would rearrange to the Y j ^ - o l e f i n s 134 and 135. Peak E was also present i n very small amounts and therefore was not i s o l a t e d or i d e n t i f i e d . Peak F was i s o l a t e d and i d e n t i f i e d as the cyclopropane 127 on the basis of n.m.r. and ret e n t i o n times. (c) Product D i s t r i b u t i o n TABLE XI D i s t r i b u t i o n * of Products f o r the Py r o l y s i s of D i f f e r e n t Ratios of the Pyrazolines 120 and 121 2 Ratio of 120:121 125 126 128 127 25:75 42 18 5 35 58:42 65 12 1 22 95:5 88 7 trace 5 100:0 3 91 6 0 3 0:100 3 . 26 22 7 45 Average of three runs by v.p.c. Integration of n.m.r. spectra. Correction to 100% using 25:75 and 95:5 r a t i o s of 120 and 121 r e s p e c t i v e l y . - 84 -3-Acetyl-3',5-dimethyl-4'-phenyl-l-pyrazoline (122) and 3-Acetyl-3',5'-dimethyl-4'-phenyl-l-pyrazoline (123) ' (a) Preparation and Enrichment To an ether s o l u t i o n o f 11.2 g (0.07 mole) of 3-methyl-4-phenyl-3-butene-2-one, (E)- (132) was added diazoethane (from 23.4 g (0.20 mole) of N-nitroso-N-ethyl urea). The s o l u t i o n was l e f t f o r one week at -5° and became c l e a r and c o l o u r l e s s . Pyrazoline formation was indicated by use of n.m.r. The r a t i o of the two pyrazolines 122 and 123 was estimated i n the crude r e a c t i o n mixture as 90:10 r e s p e c t i v e l y . The f i r s t treatment of the o l e f i n 132 with diazoethane r e s u l t e d i n about 35% formation of pyrazoline products. The o l e f i n 132 was then treated twice more with diazoethane with a one week i n t e r v a l between the second and t h i r d treatment. The pyrazolines 122 and 123 were stored as a s o l u t i o n i n ether-petroleum ether at -5°. Two weeks a f t e r the t h i r d treatment the solvent was removed with a rotatory evaporator. The crude r e a c t i o n product was t r i t u r a t e d with petroleum ether to give white c r y s t a l s . R e c r y s t a l l i z a t i o n from petroleum ether-ether (95:5) y i e l d e d the pure pyrazoline 122 as a white s o l i d : m.p. 65-68° dec 107°; n.m.r. 8.93 and 7.52 x (si n g l e t s ) C-3 and a c e t y l methyls r e s p e c t i v e l y , 8.48 x (doublet J = 7.0 Hz) C-5 methyl, 6.78 x (doublet J = 8.4 Hz) C-4 hydrogen, 5.18 x (multiplet) C-5 hydrogen, 2.8 x (multiplet) aromatic hydrogens. Anal. Calcd. f o r C^H^ON.: C, 72.19; H-, 7.46; N, 12.95. Found: C, 71.96; H, 7.61; io 16 I N, 12.95. The mother l i q u o r from the above r e c r y s t a l l i z a t i o n was approximated by n.m.r. as a 50:50 mixture of the two pyrazolines. The solvent was - 85 -removed from the mother l i q u o r and then d i l u t e d with 10 ml of petroleum ether-ether (95:5) and seeded with pure c r y s t a l s of the pyrazoline 122. . The s o l u t i o n was l e f t f o r one week at -5°, a f t e r which i t was observed that not only a d d i t i o n a l c r y s t a l s of 122 were present but also a l i q u i d , presumably the pyrazoline 123. A f t e r the removal of the s o l i d white c r y s t a l s , the mother l i q u o r was then f r a c t i o n a t e d by column chromatography ( s i l i c a g e l , petroleum ether-ether, 95:5 to 90:10). Three f r a c t i o n s were used f o r the product d i s t r i b u t i o n study. The r a t i o of the two pyrazolines 123 and 122 i n the three f r a c t i o n s , as determined by the i n t e g r a t i o n of the two acetyl peaks, was 72:28, 68:32, and 64:36 r e s p e c t i v e l y . By considering successive f r a c t i o n s , i t was found that the pyrazoline 123 had the larger value. It was not p o s s i b l e to c r y s t a l l i z e any of the f r a c t i o n s and thus the pyrazoline 123 must be a l i q u i d . For the pyrazoline 123: n.m.r. 8.50 and 7.75 T ( s i n g l e t s ) C-3 and a c e t y l methyls r e s p e c t i v e l y , 8.56 T (doublet J = 7.0 Hz) C-5 methyl, 6.27 T (doublet J = 7.0 Hz) C-4 hydrogen, 5.9 T (multiplet) C-5 hydrogen, 2.8 T (multiplet) aromatic hydrogens; no microanalysis was performed on the mixture of the two pyrazolines 122 and 123. (b) P y r o l y s i s and Product I d e n t i f i c a t i o n The pyrazolines 122 and 123 were decomposed neat at 140-145°. The product d i s t r i b u t i o n was determined by v.p.c. (FFAP, 208°, 120 ml per min) which showed f i v e peaks A, B, C, D, and E with r e t e n t i o n times 12.2, 13.4, 14.0, 21.0, and 23.5 min r e s p e c t i v e l y . Peak A was i s o l a t e d and found to consist of two major products (>95%). The f i r s t compound i d e n t i f i e d was 3-methyl-4-phenyl-3-hexene-- 86 -2-one, (E)- (136): i . r . 1685 cm"1 (carbonyl s t r e t c h i n g frequency); n.m.r. (100 MHz) 7.93 T ( s i n g l e t ) a c e t y l methyl, 8.35 T (multiplet showing long range coupling) alpha methyl, 9.11 T ( t r i p l e t J = 7.3 Hz) C-6 hydrogens, 7.60 T (quartet showing long range coupling J = 7.3 Hz) C-5 hydrogens, 2.8 T (multiplet) aromatic hydrogens. The second compound was i d e n t i f i e d as 3-methyl-4-phenyl-4-hexene-2-one, (__)- (137) i . r . 1715 cm"1; n.m.r. (100 MHz) 7.78 T ( s i n g l e t ) a c e t y l methyl, 8.88 T and 8.45 x (doublets J = 7.0 Hz) C-3 and C-5 methyl r e s p e c t i v e l y , 6.65 (quartet J = 7.0 Hz) C-5 hydrogen, 4.43 T (quartet J = 7.0 Hz) v i n y l hydrogen, 4.43 T (quartet J = 7.0 Hz) v i n y l hydrogen, 2.8 T (multiplet) aromatic hydrogens. The n.m.r. of peak A also i n d i c a t e d the presence of the other a,3-unsaturated ketone 3-methyl-4-phenyl-3-hexene-2-one, (Z)- (138). Peaks i n the n.m.r. (100 MHz) assigned to the o l e f i n 138 by comparison with an authentic sample were: 8.10 T ( s i n g l e t ) a c e t y l methyl, 8.50 T ( s i n g l e t ) alpha methyl, 9.07 T ( t r i p l e t J = 7.5 Hz). It was not poss i b l e to conclude i f any of the remaining extraneous peaks i n the n.m.r. were due to the other B,y-isomer 3-methyl-4-phenyl-4-hexene-2-one, (Z)- (159) since an authentic sample was not a v a i l a b l e f o r comparison. Anal. Calcd. f o r C^H^O (peak A): C, 82.93; H, 8.57. Found: C, 83.10; H, 8.71. Peaks B and C were i s o l a t e d and i d e n t i f i e d together. Peak B was assigned as having consisted of the cyclopropane 125 and the rearranged Y,6-olefins 134 and 155. Peak C was assigned as having consisted of the cyclopropane 125 on the basis of r e t e n t i o n times and c h a r a c t e r i s t i c peaks i n the n.m.r.: 8.32 and 8.55 T ( s i n g l e t s ) C-l and a c e t y l methyls r e s p e c t i v e l y . The peak B was c o l l e c t e d by v.p.c. f o r i . r . , - 87 -n.m.r. and microanalysis. For the compound 1-acetyl-l',3-dimethyl-2 1 -phenyl cyclopropane 125: i . r . 1690 cm * (carbonyl s t r e t c h i n g frequency); n.m.r. (100 MHz) 8.92 and 7.81 T (si n g l e t s ) C-l and a c e t y l methyls r e s p e c t i v e l y , 8.88 T (doublet J = 6.4 Hz) C-3 methyl, 7.15 T (doublet J = 6.4 Hz) C-2 hydrogen, 8.6 x (multiplet) C-3 hydrogen, 2.9 x (singlet) aromatic hydrogens. Anal. Calcd. f o r C^H^O (mixture of 125, 134 and 135): C, 82.93; H, 8.57. Found: C, 82.83; H, 8.78. Peak D was not i s o l a t e d as i t was present i n only a small quantity. It was i d e n t i f i e d as cyclopropane 126 only on the basis of i t s retention time. Peak E was i s o l a t e d and i d e n t i f i e d as the cyclopropane 127. Its re t e n t i o n time and n.m.r. were i d e n t i c a l to the same cyclopropane i s o l a t e d from the decomposition of the pyrazolines 119, 120 and 121. (c) Product D i s t r i b u t i o n TABLE XII D i s t r i b u t i o n * of Products f o r the P y r o l y s i s of D i f f e r e n t Ratios of the Pyrazolines 122 and 123 2 Ratio of 122:123 o l e f i n s 125 126 unid. 127 100:0 3 0 79 trace 1 20 36:64 45 41 2 1 11 32:68 46 39 3 1 11 28:72 48 37 4 1 10 0:100 4 67 21 5 1 6 Average of three runs by v.p.c. Average of three integrations of a c e t y l hydrogens. From pure Pyrazoline 122. Corrected to 100% using 100:0 and 28:72 r a t i o s of 122 and 123 re s p e c t i v - 88 -Rearrangement of 1-acetyl-l 1,3-dimethyl-2'-phenyl to erythro- and threo-3-methyl-4-phenyl-5-hexene-2-one (134 and 135) Four 50 mg samples of the cyclopropane 125 already containing some of the Y>5-olefins were sealed i n pyrex tubes (2 mm diam) and placed i n a furnace maintained at 227° f o r 3.5 hours. The v.p.c. (DC 550, 210°, 120 ml per min) indicated that the cyclopropane 125 had completely rearranged to the y,6-olefins 134 and 135. The r a t i o of the threo 135 to erythro 134 isomer was estimated by n.m.r. at 2:1. It was not po s s i b l e to separate the two Y>6-isomers by v.p.c. The rearranged products could however be c o l l e c t e d as a mixture on the v.p.c. as a c l e a r colourless l i q u i d : i . r . 1723 cm * (carbonyl s t r e t c h i n g frequency); n.m.r. (100 MHz) 7.95 and 8.25 x (si n g l e t s ) a c e t y l methyls of 135 and 134 r e s p e c t i v e l y , 9.16 and 8.92 x (doublets J = 6.9 Hz) C-3 methyls of 135 and 134 r e s p e c t i v e l y , 6.60 x ( t r i p l e t J = 9.0 Hz) C-5 hydrogens, 7.17 x (multiplet of 8 l i n e s ) C-3 hydrogens, 4.12 x (complex m u l t i p l e t 40 Hz wide of area one) and 5.03x(complex m u l t i p l e t 32 Hz wide of area two) v i n y l hydrogens. Anal. Calcd. for C^H^O: C, 82.93; H, 8.57. Found: C, 8.71; H, 8.75. Assignment of a c e t y l methyls and the C-3 methyls was made on the basis that the function, i n t h i s case methyl or a c e t y l , that i s c i s to the phenyl group w i l l be shielded (38) i n the most stable conformation. Trimethyl q-phosphonopropionate Trimethyl a-phosphonopropionate was prepared according to the procedure given by K i n s t l e (39). The r e s u l t i n g r e a c t i o n mixture was ' d i s t i l l e d to give a 31% y i e l d of product b o i l i n g between 93-100° at 0.3 mm. "I - 89 -Methyl 3-methyl-3-benzyl-2-butenoate, (E)- (144) and Methyl 3-methyl-3-benzyl-2-butenoate, (Z)- (145) The procedure according to Kinstle (39) was used. To a slurry of 4.32 g (0.18 mole) of sodium hydride (Ventron) in 200 ml of dry 1,2-dimethoxyethane maintained at 15° was added dropwise in one hour 35.3 g (0.18 mole) of trimethyl a-phosphonopropionate. After the addition,the grey solution was stirred for one hr at room temperature and for 5 min at 35°. The solution was cooled to 15° and 24.1 g (0.18 mole) of freshly distilled phenyl acetone (Eastman) was added dropwise in 20 min with rapid stirring. The mixture was warmed to room tempera-ture and stirred vigorously for 15 min and then 20 min at 65°. Ice (300 g) was added with stirring. The mixture was extracted with five 100 ml portions of ether. The combined ether extracts were washed with two 100 ml portions of water to remove the glyme. The ether layer was dried over sodium sulphate and the ether was removed to give 20.8 g (54%) of crude product. The v.p.c. (Ap J, 222°, 120 ml per min) showed at least three products A, B, and C with retention times 18.6, 19.6 and 21.1 min with A and B overlapping considerably. The n.m.r. •indicated the presence of both a,g- and B,Y-isomers in approximately a 70:30 ratio respectively. For the a,8- 144 and 145 and 3 , Y -unsaturated esters: i . r . 1715-1740 cm 1 (overlapping carbonyl stretch-ing frequencies); n.m.r. 8.68 T (doublet J = 7.2 Hz) C-2 8,y-methyl, 8.0-8.4T(multiplets) vinyl methyls, 6.80 x (quartet J = 7.2 Hz) C-2 B,y-hydrogen, 6.54 T (broad singlet) a ,8-benzylic hydrogens, 6.3-6.4 T carbomethoxy methyls, 3.65 x (broad singlet) 3,Y - Vinyl hydrogen, 2.8-2.9 x aromatic hydrogens. Anal. Calcd. for C-.-H-.-O^  - 90 -(mixture of peaks A, B, and C): C, 76.43; H, 7.90. Found: C, 76.20; H , 8.10. 3-Methyl-4-benzyl-3-pentene-2-one, (E)- (128) and 3-Methyl-4-benzyl-3-pentene-2-one, (Z) - (129) The general procedure according to Vogel (45) was used i n the conversion of the esters 144 and 145 to t h e i r corresponding acids 146 and 147. In a 100 ml f l a s k was refluxed 6 g of the crude esters 144 and 145 i n 50 ml of 20% sodium hydroxide f o r 2.2 hours. The crude rea c t i o n mixture was cooled and extracted twice with ether and then a c i d i f i e d with hydrogen c h l o r i d e . The r e s u l t i n g s o l u t i o n was extracted twice with ether which was dr i e d with magnesium sulphate. Removing the ether gave 2.1 g of a white s o l i d containing the crude acids 146 and 147. The conversion of the acids to the corresponding methyl ketones was done according to the procedure of DePuy (40) . Into a 50 ml 3 necked round bottom f l a s k equipped with a condenser, mechanical s t i r r e r , and nitrogen was placed 2.1 g (0.011 mole) of the crude acids 146 and 147 and 25 ml of anhydrous ether. Methyl l i t h i u m i n ether (0.022 mole) was added dropwise. A f t e r the addition,saturated ammonium chlo r i d e was added dropwise to destroy the excess methyl l i t h i u m . Two c l e a r layers r e s u l t e d and the ether layer was separated and washed with a saturated ammonium chloride s o l u t i o n , twice with water, and dried over magnesium sulphate. The ether was removed to y i e l d 1.0 g of crude ketone. Bulb to bulb d i s t i l l a t i o n y i e l d e d 0.8 g (0.004 mole). The y i e l d from the acids was 38% and from phenyl acetone was 8%. The y i e l d - 91 -o f t h e a c i d s f r o m p h e n y l k e t o n e was 2 0 % . T h e v . p . c . ( F F A P , 2 1 8 ° , 120 m l p e r m i n ) s h o w e d t h r e e m a i n p e a k s A , B,. a n d C w i t h r e t e n t i o n t i m e s o f a p p r o x i m a t e l y 1 5 . 8 , 1 6 . 3 , a n d 1 7 . 6 m i n a n d w i t h a n a r e a r a t i o o f 3 : 1 : 2 r e s p e c t i v e l y . P e a k s A a n d B o v e r l a p p e d c o n s i d e r a b l y , T h e a , 8 t o 8 , y r a t i o i n t h e c r u d e r e a c t i o n m i x t u r e was e s t i m a t e d a t 5 0 : 5 0 b y n . m . r . T h u s p e a k A was a s s i g n e d a s t h e 8 , y - i s o m e r a n d p e a k s B a n d C a s t h e a , 0 - u n s a t u r a t e d k e t o n e s 128 a n d 1 2 9 . T h e p e a k s B a n d C h a v e t h e same r e t e n t i o n t i m e s a s p e a k s D a n d E f r o m t h e p y r o l y s i s o f p y r a z o l i n e s 118 a n d 1 1 9 . F o r t h e a , B - u n s a t u r a t e d k e t o n e s 128 a n d 1 2 9 : i . r . 1 6 8 0 a n d 1 6 8 5 cm" ( o v e r l a p p i n g c a r b o n y l s t r e t c h i n g f r e q u e n c i e s ) ; n . m . r . ( 1 0 0 MHz) 7 . 8 1 a n d 7 . 8 2 x ( s i n g l e t s ) a c e t y l m e t h y l s , 8 . 2 5 a n d 8 . 2 6 x ( s i n g l e t s ) C - 3 m e t h y l s , 6 . 5 4 a n d 6 . 5 9 x ( b r o a d s i n g l e t s o f a r e a s 1 : 2 r e s p e c t i v e l y ) b e n z y l i c h y d r o g e n s . F o r t h e 8 , Y - u n s a t u r a t e d k e t o n e : i . r . 1710 cm 1 ( c a r b o n y l s t r e t c h i n g f r e q u e n c y ) ; n . m . r . ( 1 0 0 MHz) 7 . 9 1 x ( s i n g l e t ) a c e t y l m e t h y l , 8 . 8 0 x ( d o u b l e t J = 6 . 9 H z ) C - 3 m e t h y l , 6 . 7 7 x ( q u a r t e t J = 6 . 9 H z ) C - 3 h y d r o g e n , 3 . 5 8 x ( b r o a d s i n g l e t ) v i n y l h y d r o g e n . M u l t i p l e t s a t 8 . 0 8 , 8 . 1 4 a n d 8 . 4 1 x w e r e a s s i g n e d t o t h e t w o B - m e t h y l s o f t h e a , 0 - i s o m e r s a n d t o t h e a - m e t h y l o f t h e 8 , Y - i s o m e r s . A n a l . C a l c d . f o r C ^ H ^ O ( m i x t u r e o f p e a k s A , B , a n d C) : C , 8 2 . 9 3 ; H , 8 . 5 7 . F o u n d : C , 8 2 . 5 1 ; H , 8 . 6 6 . M e t h y l - 2 - m e t h y l - 3 - p h e n y l - 2 - p e n t e n o a t e , ( E ) - ( 1 4 0 ) a n d M e t h y l - 2 - m e t h y l - 3 -p h e n y l - 2 - p e n t e n o a t e , ( Z ) - ( 1 4 1 ) T h e p r o c e d u r e a c c o r d i n g t o K i n s t l e ( 3 9 ) was u s e d a s p r e v i o u s l y d e s c r i b e d f o r t h e p r e p a r a t i o n o f t h e e s t e r s 144 a n d 1 4 5 . A b u l b t o b u l b - 92 -d i s t i l l a t i o n of the crude re a c t i o n product gave a c l e a r colourless l i q u i d whose v.p.c. (FFAP 212°, 120 ml per min) showed one peak with r e t e n t i o n time 10.7 minutes. The n.m.r. indicated that the peak consisted of the two expected a,8-unsaturated esters 140 and 141 i n a 2:1 r a t i o r e s p e c t i v e l y . For the esters 140 and 141: i . r . 1725 and 1735 cm"1 (overlapping carbonyl s t r e t c h i n g frequencies); n.m.r. 6.29 and 6.77 T ( s i n g l e t s ) carbomethoxy methyls r e s p e c t i v e l y , 8.32 and 8.00 T (singlets) alpha methyls r e s p e c t i v e l y , 9.05 T ( t r i p l e t J = 3.8 Hz) C-5 hydrogens, 6.5-6.6 T (overlapping quartets) C-4 hydrogens, 2.9 x aromatic hydrogens. Anal. Calcd. f o r C^H-,0 • C, 76.43; H, 7.90. Found: C, 76.02; H, 7.91. 3-Methyl-4-phenyl-3-hexene-2-one, (E)- (136) and 3-Methyl-4-phenyl-3-hexene-2-one, (Z)- (138) A procedure, s i m i l a r to the conversion of the methyl esters 144 and 145 to t h e i r corresponding acids 146 and 147, was used except that i t was necessary to r e f l u x the reaction mixture f o r 24 hours. The n.m.r. i n d i c a t e d a 72:28 mixture of the acids with the E_ isomer predominating. For the acids 142 and 143: n.m.r. 7.96 and 8.30 x (sin g l e t s ) alpha methyls, 9.06 x ( t r i p l e t J = 3.8 Hz) C-5 hydrogens, 7.26 and 7.52 x (quartets) C-4 hydrogens, -0.95 x (broad s i n g l e t ) a c i d proton. The conversion of the acids 142 and 143, derived from the methyl esters 140 and 141, was c a r r i e d out according to the procedure of DePuy (40) and i s s i m i l a r to that described f o r the preparation of the ketones 128 and 129. The y i e l d of 136 and 138 from t h e i r corresponding acids was 8.0%, and from propiophenone 0.6%. The y i e l d of the acids - 93 -from propiophencme was 7.5%. The v.p.c. (FFAP 215°, 120 ml per min) showed as the major product two overlapping peaks A and B with r e t e n t i o n times 9.0 and 9.4 minutes. The n.m.r. indic a t e d that the two ketones 138 and 136 were present i n a r a t i o of 90:10 although the i n i t i a l corresponding acids were i n a r a t i o of 72:28 r e s p e c t i v e l y . For the ketones 136 and 138: i . r . 1680-90 cm 1 (overlapping carbonyl s t r e t c h i n g frequencies); n.m.r. (100 MHz) 7.95 and 8.51 T (si n g l e t s ) acetyl methyls r e s p e c t i v e l y , 8.34 and 8.10 T (multiplets alpha methyls r e s p e c t i v e l y , 9.00 and 9. 1 0 T ( t r i p l e t s J = 7.4 Hz) C-6 hydrogens, 7.53 x (quartet J = 7.4 Hz) C-5 hydrogens of 138. Anal. Calcd. f o r C 1 T H 1 £ 0 : C, 82.93; H, 8.57. Found: C, 83.05; H, 8.58. io ib - 94 -BIBLIOGRAPHY 1. K. von Auwers and F. Konig. Ann. 496, 27 (1932). 2. . K. von Auwers and F. Konig. Ann. 496, 252 (1932). 3. W.M. Jones. J . Am. Chem. Soc. 8_0, 6687 (1958). 4. W.M. Jones. J . Am. Chem. Soc. 81_, 5153 (1959). 5. W.M. Jones. J . Am. Chem. Soc. 82_, 3136 (1960). 6. D.E. McGreer. J . Org. Chem. 25, 852 (1960). 7. D.E. McGreer, W. Wai and G. Carmichael. Can. J . Chem. _5_8, 2410 (1960). 8. W.M. Jones and W.T. T a i . J . Org. Chem. 27_, 1030 (1962). 9. W.M. Jones and W.T. T a i . J . Org. Chem. Z7, 1324 (1962). 10. K.L. Rinehart and T.V. Van Auken. J . Am. Chem. Soc. 8_2, 5251 (1960) 11. T.V. Van Auken and K.L. Rinehart. J . Am. Chem. Soc. 84_, 3736 (1962) 12. D.E. McGreer, P. Morris and G. Carmichael. Can. J . Chem. 41, 726 (1963). 13. D.E. McGreer, N.W.K. Chiu, M.G. Vinje and K.C.K. Wong. Can. J . Chem. 43, 1407 (1965). 14. D.E. McGreer, N.W.K. Chiu and M.G. Vi n j e . Can. J . Chem. 43, 1398 (1965). 15. D.E. McGreer and W.S. Wu. Can. J . Chem. 4J5, 461 (1967). 16. I.M. Masters, Ph.D. Thesis, U n i v e r s i t y of B r i t i s h Columbia, 1968. 17. a) D.W. Setser and B.S. Rabinovitch. J . Am. Chem. Soc. 86, 565 (1964). b) A.T. Blades Can. J . Chem. 39, 1401 (1961). 18. a) S. S e l t z e r and F.T. Dunne. J . Am. Chem. Soc. 87_, 2628 (1965) . _b) S. S e l t z e r . J . Am. Chem. Soc. 85_, 14 (1963). c) S. Se l t z e r . J . Am. Chem. Soc. 83, 2625 (1961). > - 95 -19. a) R.J. Crawford, R.J. Dummel and A. Mishra. J . Am. Chem. Soc. 87_, 3023 (1965). b) R.J. Crawford, A. Mishra and R.J. Dummel. J . Am. •Chem. Soc. 88, 3959 (1966). c) R.J. Crawford and A. Mishra. J . Am. Chem. Soc. 88, 3963 (1966). 20. R.J. Crawford and D.M. Cameron. J . Am. Chem. Soc. 88, 2589 (1966). 21. R.J. Crawford and D.M. Cameron. Can. J . Chem. 45_, 691 (1967). 22. R.J. Crawford and G.L. Erikson. J . Am. Chem. Soc. 89, 3907 (1967). 23. R.J. Crawford and L.H. A l i . J . Am. Chem. Soc. 89_, 3908 (1967). 24. B.H. Al-Sader and R.J. Crawford. Can. J . Chem. 46, 3301 (1968). 25. C.G. Overberger and J.P. Anselme. J . Am. Chem. Soc. 86_, 658 (1964) 26. C.G. Overberger, J.P. Anselme and N. Weinshenker. J . Am. Chem. Soc. 86, 5364 (1964). 27. C.G. Overberger, N. Weinshenker and J.P. Anselme. J . Am. Chem. Soc. 87, 4119 (1965) . 28. C.G. Overberger, R.E. Zangaro and J.P. Anselme. J . Org. Chem. 31_, 2046 (1966). 29. D.E. McGreer, R.S. McDaniel and M.G. Vinje. Can. J . Chem. 43_, 1389 (1965). 30. a) J . Hamelin and R. C a r r i e . Compte. Rend. 261, 5345 (1965). b) J . Hamelin and R. C a r r i e . Compte. Rend.260, 3102 (1965). c) J . Hamelin and R. C a r r i e . B u l l . Soc. Chim. Fr. 2162 (1968). d) J . Hamelin and R. C a r r i e . B u l l . Soc. Chim. Fr. 2513 (1968). e) J . Hamelin and R. C a r r i e . C u l l . Soc. Chim. Fr. 2521 (1968). 31. Y.Y. Wi g f i e l d , Ph.D. Thesis, U n i v e r s i t y of B r i t i s h Columbia, 1969. 32. A. Mishra and R.J. Crawford. Can. J . Chem. 47, 1515 (1969). 33. E.L. A l l r e d and R.L. Smith. J . Am. Chem. Soc. 89, 7133 (1967). - 96 -34. W.R. Roth and M. Martin. Ann. 702, 1 (1967). 35. D.E. McGreer and N.W.K. Chiu. Can. J . Chem. 46, 2217 (1968). 36. .M. Karplus. J . Chem. Phys. 30, 11 (1959). "37. D.J. P a t e l , M.E.H. Howden and J.D. Roberts. J . Am. Chem. Soc. 85_, 3218 (1963). 38. G.H. Schmid. Can. J . Chem. 46, 3415 (1968). 39. T.H. K i n s t l e , Ph.D. Thesis, U n i v e r s i t y of I l l i n o i s , 1963. 40. C H . DePuy, G.M. Dappen, K.L. E i l e r s and R.A. K l e i n . J . Org. Chem. 29, 2813 (1964). 41. N.W.K. Chiu, M.Sc. Thesis, U n i v e r s i t y of B r i t i s h Columbia, 1964. 42. T. Curtius and L. Pflu g . J . pr. Chem. 44_, 535 (1892); Chem. Soc. Abst. 456 (1892). 43. H. Staudinger and A. Gaule. Ber. 4£, 1906 (1916). 44. D.S. Noyce and W.L. Reed. J . Am. Chem. Soc. 81_, 624 (1959). 45. A.I. Vogel, " P r a c t i c a l Organic Chemistry", Longmans Green and Co. Ltd., New York, N.Y., 1943, page 921. 46. M. Pomerantz and E.W. Abrahamson. J . Am. Chem. Soc. 88, 3970 (1966). - 97 -APPENDIX Nomenclature The main purpose of the following system of nomenclature i s to unambiguously assign the stereochemistry about the three carbon skeleton of cyclopropanes and 1-pyrazolines that are uniquely substituted at a l l three carbon centers. A "prime" used as a superscript on the carbon number indicates substituents on one side of the r i n g system whereas the lack of a superscript indicates substituents on the other s i d e . For example, pyrazoline 118 becomes 3-acetyl-3 1,4'-dimethyl-5-phenyl-l-pyrazoline and the C-5 isomer 119 becomes 3-acetyl-3',4'-dimethyl-5'-phenyl-l-pyrazoline. Cyclopropane 126 i s c a l l e d 1 - a c e t y l - l 1 , 3 ' dimethyl-2-phenyl cyclopropane. 

Cite

Citation Scheme:

        

Citations by CSL (citeproc-js)

Usage Statistics

Share

Embed

Customize your widget with the following options, then copy and paste the code below into the HTML of your page to embed this item in your website.
                        
                            <div id="ubcOpenCollectionsWidgetDisplay">
                            <script id="ubcOpenCollectionsWidget"
                            src="{[{embed.src}]}"
                            data-item="{[{embed.item}]}"
                            data-collection="{[{embed.collection}]}"
                            data-metadata="{[{embed.showMetadata}]}"
                            data-width="{[{embed.width}]}"
                            async >
                            </script>
                            </div>
                        
                    
IIIF logo Our image viewer uses the IIIF 2.0 standard. To load this item in other compatible viewers, use this url:
http://iiif.library.ubc.ca/presentation/dsp.831.1-0059988/manifest

Comment

Related Items