Diazomethane Pechmann pyrazole synthesis

PECHMANN PYRAZOLE SYNTHESIS. Formation of pyrazoles from acetylenes and diazomethane. The analogous addition of diazoacetic esters to the triple bond yields pyrazolecarboxylic acid derivatives. 

The original reaction discovered by Pechmann involved the cycloaddition of diazomethane and acetylene. Although a better understanding of the reaction has led to the common use of more electron-deficient alkynes, diazomethane continues to be synthetically useful. A recent elegant example of the use of diazomethane as the 1,3-dipole was demonstrated in the preparation of 2,3-benzodiazepine derivatives as potential non-competitive AMPA antagonists. " Beginning with the alkyne, the pyrazole moiety could be incorporated into the benzodiazepine structure, using the Pechmann pyrazole synthesis, to produce the 2,3-benzodiazepines. 

In a number of studies, the Pechmann pyrazole synthesis has found utility in the synthesis of fluorinated heterocycles.As an example, the cyclization between 13 and diazomethane resulted in the efficient preparation of trifluoroalkyl pyrazole 14. As is the case with the majority of isolated pyrazoles, the product 14 is in equilibrium with the other N-H tautomer. 

Buchner accomplished the first synthesis of pyrazole by a cycloaddition in 1889, but not by the direct reaction of diazomethane and ethyne, but with methyl diazoacetate and an electron-deficient dipolarophile, ethynedicarboxylate (see Sect. 6.2). Unsubstituted ethene and ethyne were considered for a very long time to be not sufficiently reactive for synthetic purposes, although von Pechmann (1898 b) had reported a 50 0 yield of pyrazole from diazomethane and ethyne shortly after the discovery of diazomethane. The knowledge of diazomethane being explosive is probably the reason that the obvious advantage of a reaction under pressure in order... 

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