Direct Synthesis of 2,4,6‐Trisubstituted Pyrimidines via Base‐Mediated One‐Pot Multicomponent Reaction

Abstract

A base‐mediated strategy was adopted to synthesize 2,4,6‐trisubstituted pyrimidines from amidine hydrochlorides, aldehydes and acetylacetone. The starting materials were widely available and could tolerate various functional groups, and the produced 2,4,6‐trisubstituted pyrimidines had moderate to good yields. The construction of C−C and C−N bonds was achieved under transition metal‐free conditions. Unlike previous approaches, the present approach utilizes a multicomponent reaction and is a new protocol for the construction of 2,4,6‐trisubstituted pyrimidines from raw materials that do not require further preparation.

A review on pyrimidine‐based derivatives: Synthesis and their biological application

“…Pyrimidines are common structural motifs in nature and can be found in many different types of molecules, such as antibiotics, vitamins, alkaloids, and nucleotides (Figure 2) [26][27][28]. The diverse biological activities of numerous substituted pyrimidines further emphasize the importance of the marked pyrimidine medications [10,29]. However, due to its incorporation in a various F I G U R E 2 Chart of the pyrimidine incorporated natural products (source of pyrimidine shown in parenthesis) [26][27][28] bioactive chemical compounds, pyrimidine has diversified into a substantial heterocyclic system during many years of active research.…”

“…The expanding research interest on heterocyclic molecules is driven by their wide synthetic exploration and functional versatility [3][4][5], also serving as a key component in understanding structure-activity relationships [6,7]. However, pyrimidine is an essential six-membered heterocyclic compound that is present in various biologically active compounds and functional materials [8][9][10]. These are extracted from various natural compounds such as nucleic acids, alkaloids, and vitamins B1.…”

“…Later, Kossel and Neumann isolated and characterized two important pyrimidine compounds, thymine, and cytosine, from calf thymus in 1893 and 1894, respectively [12]. The heterocyclic compounds having two nitrogen atoms in the ring are known as diazines, which are classified into three types based on the position of the nitrogen atoms, namely pyridazine (1, 2-diazine), pyrimidine (1, 3-diazine), and pyrazine (1, 4-diazine) (Figure 1) [8][9][10]. Among these isomers, pyrimidines are the most regularly found diazine isomer and the focus of this review.…”