Synthesis and Antimicrobial Evaluation of Some New Tetrahydropyrimidine Derivatives

Abstract

The utility of 1,2,3,4-tetrahydropyrimidine-5-carboxylate (1a,b), and 1,2-dihydropyrimidine-5-carboxylate (2) in the synthesis of some new functionalized pyrimidine derivatives such as 6-(2-(dimethylamino)vinyl)-1,2,3,4tetrahydropyrimidine, 6-(1-cyano-2-(phenylamino)-2-thioxoethyl)-1,2,3,4-tetrahydropyrimidine and 4,6-distyryl-1,2-dihydropyrimidine derivatives is reported. Antimicrobial evaluation of some selected examples from the synthesized products was carried out and showed promising results. Pyrimidine derivatives are reported to possess antibacterial, antifungal anticancer, antiinflammatory, and cardioprotective effects. In addition, certain pyrimidine derivatives are known to display antimalarial, antifilarial and antileshmainal activities. Also, pyrimidine nucleus is considered as one of the most important classes of chemotherapeutic drugs. Many pyrimidine derivatives are used for thyroid drugs and leukemia. In view of the these results and as an extension of our recent work concerned with the synthesis of heterocycles of interested biological activity we decided to synthesize some new pyrimidine derivatives starting from the readily obtainable 1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives 1a, 1b, and dihydropyrimidine 2 as highly versatile and useful building blocks for the synthesis of a wide variety of pyrimidine derivatives and to test their antimicrobial activity. 1,2,3,4-Tetrahydropyrimidine 1a was found to react readily with dimethylformamide dimethyl acetal (DMF-DMA) to produce ethyl 6-(2-(dimethylamino)vinyl)-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine5-carboxylate (3) (Scheme 1). The IR spectrum of the product 3 showed absorption bands at, 1624, 1701, 3117, 3244 cm due to two carbonyl groups, and two imino functions, respectively. Its H NMR spectrum showed a triplet signal at  1.11 (J = 6.9 Hz) due to CH3 protons, singlet signal at  2.85, characteristics for two methyl protons, a quartet signal at  3.96 (J = 6.9 Hz) due to CH2 protons, a doublet signal at  5.17 (J = 3.6 Hz) due to CH proton, two doublets at  6.18 and  7.48 (J = 14.1 Hz) due to two olefinic protons, and two D2O-exchangeable signals at  7.52 and 8.61 corresponding to two NH protons, in addition to an aromatic multiplet in the region  7.22-7.29. The value of the coupling constant for the ethylenic protons indicates that the pyrimidine 3 exists exclusively in the E-configuration.