Eco-Friendly Modification of Fused Pyrimidine Derivatives via Lemon Juice Catalyzed Biginelli Reaction

Abstract

Biginelli reaction is one of the most important one-pot multicomponent organic reactions which used to afford especial type of heterocyclic compounds represented by pyrimidine derivatives via acidic conditions. Pyrimidine have been shown a wide and diverse applications in medical, pharmaceutical, biological and industrial fields. In this work our target is to prepare fused pyrimidine derivatives via Biginelli reaction with replacement the metallic acid catalyst by lemon juice as a natural acid catalyst with multiplier effect. First of all, the sulfathiazole underwent the diazotization reaction to give the diazonium salt (1) followed by reaction with malononitrile to obtained the aryl hydrazine propanedinitrile (2) which then reacted with hydrazine hydrate (98%) to afford 2,5-diamino pyrazole derivative (3). Finally , the last one underwent Biginelli reaction with dimedone and aromatic aldehydes in acidic media from lemon juice to achieve poly Biginelli products (4-7,) which illustrated by 1H-NMR, FT-IR and GC-Mass spectroscopy in addition to the theoretical biological study using the molecular Docking program.