An experimental and computational study of new spiro-barbituric acid pyrazoline scaffolds: restricted rotation vs. annular tautomerism

Abstract

A regioselective [3+2] cycloaddition (32CA) reaction to synthesize unsymmetric spiro-barbituric pyrazolines containing a chromone or phenolic pyrazole moiety was achieved, providing good to excellent yields. These rigid spiro-barbiturates exhibited good functional group tolerance, and they remained stable in the presence of an excessive amount of hydrazine. Spectral data and DFT calculations demonstrated the predominance of restricted rotation about a single C–C bond over annular tautomerism. The proposed one-pot sequential synthetic strategy allows for the efficient regio- and chemoselective preparation of new spiro-barbiturate scaffolds containing a locked phenolic pyrazole moiety, offering a much broader scope for obtaining stable drug functionalities under green conditions.