Pivalic Acid Promoted Aqueous Synthesis of Pyrimido-Quinolinediones and Coumaryl-Pyrimidinediones with Antivenom Activity

Abstract

A pivalic acid-promoted aqueous multicomponent reaction involving 4-aminocoumarin or aniline with aromatic aldehyde and 1,3-dimethylbarbituric acid, giving pyrimido-quinolinediones or coumaryl-pyrimidinediones respectively as products is reported. Reactions involving 4-aminocoumarin proceeded at room temperature, however the aniline reaction required heating at 60 degrees C. These methods give 52 percent - 98 percent yield and avoid tedious work-up procedures and chromatographic purification. 7 new pyrimido-quinolinediones and 6 new coumaryl-pyrimidinediones are prepared. Single-crystal XRD studies gave further insights into the mechanistic studies of the reaction and the product structure. The three compounds, i.e., coumaryl-pyrimidinedione and chloro-substituted coumaryl-pyrimidinediones 2a, 2d, and 2e, possess both in vitro and in vivo antivenom activity against Vipera russellii snake venom.