From Pyrazolines

From Pyrazolines. The mechanistic details of the thermal decomposition of pyrazolines to cyclopropanes continue to intrigue the organic chemist. Bergman has now cast serious doubts on the previously suggested routes from studies with the chiral cis- and frans-pyrazolines (120) and (121), and his observations overshadow 

Optical purity, and predominantly double retention of configuration). With the singly deuteriated analogues, (121) exhibits a deuterium isotope effect of about 10% on the optical purity of the products, while a real, but somewhat smaller, effect is observed with (122). The large fraction of optically active material from (120) shows that the percentage of products which must have resulted from chiral intermediates, by a route which avoids a planer 0,0-diradical, has been previously under-estimated, and this conclusion is supported by the observed deuterium isotope effect. The possibility of competitive mechanisms, though unlikely, remains, and the precise nature of the process will only be revealed by further painstakingly careful examinations. 

Bicyclo[3,l,0]alkenes are obtained from pyrazolines (124). The thermal reaction 

While pyrazolines derived from tropone and diazo-alkanes are stable only to -10°C, their analogues produced from iron-co-ordinated tropone are stable to 80 °C, at which temperature decomposition ensues and, after demetallation, an exo-endo mixture of homotropones (126) is obtained in high ( 90%) yield. The CIS- and trans-divinylpyrazolines (127) are also thermally labile, and at temperatures 

Although decomposition of (134) does give cyclopropane, the major product of reaction is believed to be the a-D-threo-isomer of (135), which results from radical 

From Pyrazolines.—Investigations of the mechanisms of pyrazoline decomposition continue. A mixture of cis- and trans-3,5-divinyl-l-pyrazoline was synthesized by cycloaddition of vinyldiazomethane to butadiene. Kinetics of the thermolysis in diphenyl ether at 35—65 °C, studied by measuring the rate of nitrogen evolution, gave data which, when compared with those for 1-pyrazoline and 3-vinyl-l-pyrazoline, led to the conclusion that both C—N bonds are broken in the rate-determining step. Thus, substituted 1-pyrazolines decompose concertedly, whereas the parent cyclic azoalkane does not.  

A number of steroidal pyrazolines have been prepared. Unlike the parent compounds (125 = H) and (126 R = R = H) which decompose photo- 

The triple bond of conjugated en-l-ynes is the preferred, or even exclusive, site of cycloaddition of diazoalkanes, but if the acetylene function is disubstituted the double bond becomes the preferred site of attack. The orientation of addition is generally unique.  

The pyrazolines (128 R = Ph, 1-cyclohexen-l-yl R R = H, Me X = Cl or F) are obtained by diazoalkane cycloaddition to tetrahalogenated cyclobutenes and lose nitrogen to give bicyclo[2,l,0]pentanes, generally in good yields. Further transformations of the bicycloalkanes were also reported.  

The thermal decomposition of pyrazoline (129) proceeds with predominant inversion of configuration to the bicyclohexene (130 = H, = Me), whereas 

From Pyrazolines. —The decomposition of A -pyrazolines to cyclopropanes may be photochemically or thermally induced and the mechanisms of both processes are still under active investigation. Both trans- and cis-3,4-dimethyl-A -pyrazolines (90a) and (90b) give trans- and ds-l,2-dimethylcyclopropanes 

The evidence appears to be consolidating against a di-n-methane mechanism for the thermal conversion of pyrazolines into cyclopropanes. From 2,3-diaza-bicyclo[3,2,0]hept-2-ene (94a), six products were obtained, and their relative yields changed with temperature. This suggested that all six were not obtained from a single common intermediate. By this thermolytic method, 

The addition of diazomethane to methyl a-acetamidoacrylate (99) followed by pyrolysis is the basis of a newly reported preparation of 1-aminocyclo-propanecarboxylic acid derivatives. Diazomethane adds to olefins (1(X)) and, when X or Y = acetyl, thermal isomerization to A -acetyl-A -pyrazolines occurs as well as other side-reactions and cyclopropane formation. Neither from these, nor by thermolysis of 3-acyl-3-alkoxycarbonyl-A -pyrazolines, were the yields of cyclopropanes good. From thermolysis of 4-vinyT3,3-di-(alkoxycarbonyl)pyrazolines, cyclopropanes were undetected. 

The substituted pyrazolines obtained by cycloaddition of the diazoalkanes (101) to norbornene and norbornadiene have been photolysed to give the corresponding cyclopropane compounds. The configurations of the adducts 

Danion-Bougot and R, Carri6, Bull. Soc. chim. France, 1972, 3511. R. Danion-Bougot and R. Carri6, Bull. Soc. chim. France, 1972, 3521. 

Miyashi, T. Sugiyama, T. Nakajo, and T. Mukai, Tetrahedron Letters, 1976, 3903. 

The pyrazoline (133) affords only bicyclo[3,l,0]hex-2-ene on thermolysis, but on photolysis this and hexa-l,3,5-triene are obtained. In the vapour phase at pressures below lOTorr the -triene (134) is obtained (8-10%), but at pressures higher than 50Torr the Z-isomer (135) ensues. The formation of triene is thought to proceed in a 

The full details of oxa-bis- and oxa-tris-a/ic-homobenzene syntheses, cw-aza-bis-and cis-aza-tris-a-homobenzene and cis-aza-tris-a-homotropilidene synthesis, and the decomposition of spiro[fluorene-9,3 -indazole] have become available, and there have been a number of routine applications of pyrazoline decomposition for cyclopropane synthesis.  

Kocor and W. KroszczyAski, Synthesis, 1976, 813 G.-I. Tsuchihashi, S. Mitamura, and K. Ogura, Tetrahedron Letters, 1976, 855. 

Dimethylsulphoxonium methylide continues to be used for olefin cyclopropana-tion, but the reagent appears to be of little use with -substituted styrenes since an alternative pathway which results in a 2-isoxazoline N-oxide is frequently followed. The diylide (144) undergoes condensation with electron-deficient olefins to give the 

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It was demonstrated (83) that the reaction of dinitrostyrenes (28) with aryl diazo compounds RR CN2 afford nitronates (24 g) in good yields. These products contain the nitro group at the C-4 atom in the trans position with respect to the substituent at C-5 (if R =H). Since the reaction mechanism remains unknown, the direct formation of cyclic nitronates (24 g) from pyrazolines A without the intermediate formation of cyclopropanes also cannot be ruled out. 

Extrusion of N2 from Pyrazolines. Pyrazoles, and Triazolines Azo-extrusion... 

Diazo compounds have been extensively used in the preparation of three-membered carbocycles either as carbene sources or as precursors for 1-pyrazolines or 3//-pyrazoles. Nitrogen extrusion from pyrazolines is particularly valuable for the synthesis of alkylcy-clopropanes, since the direct carbene route is impractical, as a matter of fact, owing to rapid intramolecular processes in alkylcarbenes. The cycloaddition of diazo compounds to unsaturated bonds to give 1-pyrazolines and 3/f-pyrazoles usually proceed in a concerted manner, and hence is stereospecific. In the subsequent nitrogen extrusion from the adducts,... 

After a brief historical recapitulation, the substantial body of experimental and theoretical work on these thermal epimerization reactions reported over the past 40 years is summarized. Of primary concern here are examples of stereomutations involving monocyclic, stereochemically unconstricted and minimally substituted molecules. Experimental studies of more heavily substituted cyclopropanes attempts to generate trimethylene diradical intermediates from pyrazolines " and the fascinating and still incompletely understood thermal chemistry of bicyclo[2.1.0]pentanes, 2-methylenebi-cyclop.l.OJpentanes", bicyclo[3.1.0]hex-2-enes and related reactions such as the pyrolysis of cyclopropane at 1200 °C to give products such as cyclopentadiene and toluene are neglected, in spite of obvious mechanistic interrelationships. 

VI is that of II minus an HCN fragment. It is also of importance to recognize that cyclopropanation is indeed an excellent method to incorporate a methylene unit into I. Then, one is led to believe that II ought to be the cyclopropane derivative VIII, produced in all probability from pyrazoline intermediate VII (see Scheme 45.2). 

Numerous unsuccessful attempts to synthesize cyclopropanethione have been reported. Thermal or photochemical generation of the C3H4S species from different sources always leads to allene episulfide. Some representative experiments include (a) in vacuo pyrolysis of the sodium salt of 2,2,4,4-tetramethylthietanone tosylhydrazone (4) into the stable tetramethylallene episulfide (S), (b) pyrolytic extrusion of nitrogen from perfluorinated thiadiazoline 6, (c) in vacuo pyrolysis of spiro compound 8 into methylenethiirane (3), (d) the flash vacuum pyrolysis-microwave spectroscopic approach applied to spiro compounds 9 and 10, (e) pyrolysis of anthracene adduct 11 and tosylhydrazide salt 12, (f) thermolytic nitrogen extrusion from pyrazoline-4-thione 13, thermolysis of tetramethylallene episulfide (5) or pyrazoline 13 in dig-lyme solution, and photolytic nitrogen extrusion from pyrazoline 13, ° (g) thionation of methylenecyclopropanone 15, and (h) reaction of donor-acceptor substituted allenes 18 with elemental sulfur. ... 

Without additional reagents Cyclopropane ring from pyrazoline ring... 

Irradiation (s. a. under lithium salt) Cyclopropanes from -pyrazolines... 

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