Dihydropyrimidinones Lab Report

Good Essays
3.3. Synthetic methodologies for dihydropyrimidinones 3.3.1. Classical method Scheme-1: The conventional method for the synthesis of DHPMs is the one-pot three-component reaction of benzaldehyde, ethyl acetoacetate and urea in the presence of an acid catalyst. The product of this novel one-pot, three components synthesis that precipitated on cooling of the reaction mixture was identified as 3,4-dihydropyrimidin-2(1H)-one and this reaction came to be known as “Biginelli reaction”, or “Biginelli condensation”, or “Biginelli dihydropyrimidine synthesis” after the name of its inventor “Pietro Biginelli”.1 Mechanism Forty years after Biginelli’s initial report, the first mechanism for the synthesis of DHPMs was conducted by Folkers and Johnson…show more content…
This has led to the recent disclosure of several improved reaction protocols for the synthesis of DHPMs, either by modification of the classical one-pot Biginelli approach itself or by the development of novel, but more complex multistep strategies. 3.3.2. Alternative multistep…show more content…
One noticeable exception is the so-called “Atwal modification” of the Biginelli reaction. In this scheme, an enone(a) is first condensed with a suitable protected urea or thiourea derivative(b) under almost neutral conditions. Deprotection of the resulting 1,4-dihydropyrimidine(c) with HCl or TFA leads to the desired DHPMs.20 Scheme-3: Shutalev et al described another approach to DHPMs synthesis. This synthesis is based on the condensation of readily available R-tosylated (thio)ureas(a) with the enolates of acetoacetates or 1,3-dicarbonyl compounds. The resulting hexahydropyrimidines(b) need not to be isolated and can be converted directly into DHPMs. This method works particularly well for aliphatic aldehydes and thiourea and produces high overall yields of the desired compound.21 Scheme-4: There are several combinatorial approaches towards DHPMs have been advanced using solid phase. In the solid-phase modifications of the Biginelli condensation, the urea component is linked to the solid support via the amide nitrogen, which invariably leads to the formation of N1-functionalized
Get Access