Tandem Aldol-Michael Reactions in Aqueous Diethylamine Medium: A Greener and Efficient Approach to Bis-Pyrimidine Derivatives

Abstract

A simple protocol, involving the green synthesis for the construction of novel bis-pyrimidine derivatives, 3a–i and 4a–e are accomplished by the aqueous diethylamine media promoted tandem Aldol-Michael reaction between two molecules of barbituric acid derivatives 1a,b with various aldehydes. This efficient synthetic protocol using an economic and environmentally friendly reaction media with versatility and shorter reaction time provides bis-pyrimidine derivatives with high yields (88%–99%).

Crystal structure of diethylammonium 1,3-dimethyl-2,4,6-trioxohexahydropyrimidin-5-ide, C10H19N3O3

“…In the meanwhile, barbituric acid has been found to be associated with important biological activities including anti-hypertensive, anti-in ammatory, antitumor, anticonvulsant and hypnotic drugs [1][2][3][4][5][6][7][8][9][10][11][12]. We have succeeded to separate the active species which can act as nucleophile generated by aqueous diethylamine medium.…”

“…The H atoms of the methyl groups were allowed to rotate with a xed angle around the C-C bond to best t the experimental electron density [1].…”

Crystal structure of 5-(3-fluorobenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione; C13H11FN2O3

“…Additionally, barbituric acid derivatives exhibit antifungal, antimicrobial, antiviral, potential mushroom tyrosinase inhibition, antituberculosos, radio-sensitization, anticancer with anti-in ammatory activities, inhibition for diaminopimelate aminotransferase, and anti-proliferative activity [1][2][3][4][5][6][7][8][9][10][11][12][13].…”

Crystal structure of 5-((4-bromophenyl)(2-hydroxy-6-oxocyclohex-1-en-1-yl)methyl)-6-hydroxy-1,3-dimethylpyrimidine-2,4(1H,3H)-dione, C19H19BrN2O5

“…The synthesis of 5-((4-bromophenyl)(2-hydroxy-6-oxocyc lohex-1-en-1-yl)methyl)-6-hydroxy-1,3-dimethylpyrimidine-2,4 (1H,3H)-dione prepared according to reported method by Barakat et al [1]. …”