Reaction of hydrazones derived from active methylene compounds with Vilsmeier–Haack reagent

Abstract

Reaction of hydrazones derived from active methylene compounds with the Vilsmeier–Haack reagent was studied. Compounds with sulfone, ester, nitrile, triphenylphosphonium, and phthalimide moieties were evaluated. It was found that electron-withdrawing and steric effects provided by the substituent at α position strongly influenced the regioselectivity of the reaction. Increasing mesomeric electron-withdrawing effect of this group favors the formation of functionalized 1,3,4-trisubstituted pyrazoles as compared to 1,3-disubstituted pyrazole-4-carbaldehydes. On the contrary, enhanced steric hindrance and lowered electron-withdrawing effect shift the balance toward 1,3-disubstituted pyrazole-4-carbaldehydes. Other factors such as substituent at the nitrogen atom of the hydrazone, as well as reagent ratio, can affect the outcome of the reaction dramatically, so that in certain cases acyclic products are obtained.