Alkynes Pechmann pyrazole synthesis

The 1,3-dipolar cycloaddition between diazoalkanes and alkynes resulting in pyrazole formation is known as the Pechmann pyrazole synthesis. ... 

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. 

Ethyldiazoacetate (EDAC) has become a commonly utilized 1,3-dipole in the Pechmann pyrazole synthesis. In efforts toward the rational design of growth inhibitors of Mycobacterium tuberculosis, Kozikowski and co-workers utilized this strategy for the synthesis of the pyrazole ester. Treatment of a mixture of alkyne and EDAC under microwave conditions resulted in the preparation of the pyrazole ester as a mixture of H and 2H tautomers. The pyrazole ester proved inactive in the anti-TB assay, thereby proving the importance of an isoxazole moiety for anti-TB activity, as previous work by these authors suggested. ... 

The Pechmann pyrazole synthesis features a 1,3-dipolar [3 + 2] cycloaddition between a diazoalkane and an alkyne followed by tautomerization, presumably via a 1,5-hydride shift, to give the pyrazole (1). 

A common dipolarophile for the Pechmann pyrazole synthesis is dimethyl acetylene dicarboxylate (DMAD, 41), a highly electron-deficient alkyne. Spring and co-workers used the 1,3-dipolar cycloaddition between DMAD and a fluorous-tagged diazoacetate (40) as part of studies aimed at production of structurally diverse scaffolds. As expected, the reaction proceeded efficiently to produce 42 in high yield. 

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