Recent Developments in the Reactivity of the Biginelli Compounds

Mihaela      Matache; Cristian      Dobrota; Niculina      D. Bogdan; Daniel      P. Funeriu

Abstract

The synthesis of highly functionalized molecules using multicomponent reactions became increasingly important in organic and medicinal chemistry. The Biginelli reaction is a typically one-pot three-component cyclocondensation between an aldehyde, a β- ketoester and urea leading to multifunctionalized 3,4-dihydropyrimidin-2(1H)-ones (DHPMs), which provide various possibilities for transformation of the dihydropyrimidine core and the groups grafted on it. Over the years, the synthesis of DHPMs, also called the Biginelli compounds, has attracted considerable interest because of their interesting pharmacological and structural profiles. However, the chemistry of the Biginelli compounds was limited for a long time to their convenient synthesis via the multicomponent reaction, which was also successfully exploited for combinatorial purposes. Nevertheless, a growing number of studies published during the last decade described various transformations of adducts issued from the Biginelli multicomponent process. This paper focuses on recent developments concerning the reactivity of the Biginelli-type dihydropyrimidines. We present here an update in the chemistry of these compounds, in order to illustrate their potential for further functionalization through various reactions: N-alkylation or N-acylation, oxidation/ reduction, substitution/addition or annelation of the dihydropyrimidine ring.

Keywords: Biginelli, dihydropyrimidine, multicomponent reaction, nitrogen-based heterocycles, substituted pyrimidines, reactivity, organic, synthesis, compounds, chemistry