Dihydropyrazoles, formation

The problems are due to the electrophilicity of the metal-carbene intermediates in these transformations, and to competitive, fast dihydropyrazole formation resulting from uncatalyzed thermal [3 + 2] cycloaddition of the diazo compound to the alkene furthermore, o , -unsaturated nitriles often yield 2-vinyloxazoles under the reaction conditions. 

The reaction of disubstituted diacetylenes with hydrazine hydrate was reported by Darbinyan et al. (70AKZ640). In the first stage the addition of hydrazine to the terminal carbon atom of the diacetylene system is analogous to that of primary amines to diacetylene (69ZC108 69ZC110). With monosubstituted diacetylenes (R = H), hydrazine adds to the terminal triple bond. This leads to the formation of vinylacetylenic hydrazine 22 which cyclizes to dihydropyrazole 23 subjected to further isomerization to the pyrazole 25. It is possible that hydrazine 22 undergoes hydration to the ketone 24 which can easily be cyclized to the pyrazole 25... 

Photoelimination of nitrogen from the tetrazole 429 results in the formation of the dihydropyrazole 430, presumably via intramolecular addition of the photochemically generated nitrile imine 431.358 Other examples of this type of behavior have been reported.359... 

Photolytic decomposition of a diethyl ether solution of 3-methyl-3-phenyldiazirine (7) in the presence of A -methylmaleimide afforded cyclopropanated products 9 and 10 via an alkylcar-bene intermediate 8 by direct extrusion of nitrogen." Phenyldiazomethane was involved as an intermediate when the photolytic decomposition of 3-methyl-3-phenyldiazirine was carried out in the absence of solvent as shown by the formation of dihydropyrazoles as side products, in addition to cyclopropanated products. 

Using diazoalkanes results in the formation of isomeric mixtures of cycloadducts.Unlike some reactants (phenyl azide, tosyl azide and diphenylnitrilimine), benzonitrile oxide, diazomethane, and A-phenylbenzylideneamine A-oxide underwent [3 4- 2] cycloaddition on mixing with lumisantonin using A -phenylbenzylideneamine A-oxide, however, gave the product cycloadduct in 8% yield.Dihydropyrazoles were obtained in some cases.Furthermore, pyrrole derivatives were obtained in low yield by intramolecular addition of an azomethine ylide to an a- and / -monocyclopropyl acrylate moiety. 

The 5,6-dihydro-477-l,2,6-thiadiazine 1,1,2-trioxides (162) described in Section 6.16.9.2.3.1 are susceptible to nucleophilic attack at sulfur, which promotes heterolytic cleavage of the heterocyclic ring and formation of )S-hydroxyaminosulfamic acid derivatives (163) as outlined in Scheme 15 <90LA775>. However, with a primary amine as the attacking nucleophile the sulfamides (163) so formed undergo base-catalysed ring closure to the 4,5-dihydropyrazoles (164) in yields of 72-90%. 

In general, photolytic azo-extrusion from 4,5-dihydro-3/f-pyrazoles is superior to thermolysis. Photolysis was introduced as a method for synthesis by Jeger s group (Kocsis et al., 1960). The configurations of the products in the thermolysis, in the direct photolysis, and in the sensitized photolysis are often quite different. Cyclopropanation for the synthesis of alkyl cyclopropanes via dihydropyrazoles is preferred to the direct route via carbenes, because, in the latter, the C - H insertion of the carbene into the alkyl group is faster than the cyclopropanation. The dihydro-pyrazole pathway was used in particular for the formation of highly strained bicyclo[1.1.0]butanes (Franck-Neumann, 1967 Komendantov and Bekmukhametov, 1971 6.89) and bicyclo[2.1.0]pentanes (Vogelbacher et al., 1984 6.90). 

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