Synthetic Routes to 1,4,5,6-Tetrahydropyrimidines: An Overview and Recent Advances

Partially reduced heterocyclic compounds such as 1,4,5,6-tetrahydropyrimidines are often found to possess interesting pharmacological properties. Yet, the synthetic routes towards such systems are less developed than their fully aromatic counterparts. In this review article, the biological significance of 1,4,5,6-tetrahydropyrimidines is discussed and the existing literature reports describing various preparative routes to access 1,4,5,6-tetrahydropyrimidine derivatives have been categorically described. The focus has been expanded to present an overview of the chronological development of the traditional synthetic routes as well as the contemporary approaches to 1,4,5,6-tetrahydropyrimidines that generally include: (i) condensation reactions of diamines with various appropriate counterparts such as carbonyl compounds, imino ethers, amidines or nitriles, condensation of amidines with 1,3-dibromopropane and α,β-unstaurated carbonyl compounds, condensation of amino alcohols; (ii) selective reduction of pyrimidines; (iii) ring expansion chemistry of cyclopropanes, aziridines, and azetidines; and (iv) miscellaneous examples such as various multicomponent reactions.