Synthesis of Some New 1,2,3,4-Tetrahydropyrimidine-2-thione and Their Thiazolo[3,2-a]pyrimidine, Thiazino and Benzothiazepine Derivatives

Abstract

The starting N‐(2‐pyridyl)‐6‐methyl‐4‐phenyl‐2‐thioxo‐1,2,3,4‐tetrahydropyrimidine‐5‐carboxamide (4) was used as a key intermediate for the synthesis of new 1,2,3,4‐tetrahydropyrimidine‐2‐thione and their thiazolo[3,2‐a]pyrimidine, thiazino and benzothiazipen derivatives. The reaction of 4 with haloketones in ethanol catalyzed by base afforded the corresponding thiophenopyrimidine and pyrimidothiazipine derivatives 5, 6, 7, 8, 9, 10. Methylation and formylation of 4 led to the pyrimidine derivatives 15 and 16, respectively. The preventative compounds were established on the basis of elemental and spectral data.

Synthesis and anticonvulsant activity of 6-methyl-2-((2-oxo-2-arylethyl)thio)pyrimidin-4(3 H)-one derivatives and products of their cyclization

“…In the literature (Danelet al 1998;Fadda et al 2013;Abdel Moty et al 2016) there is evidence that the reaction formed product 3 may be subject to intramolecular cyclization with the nitrogen N 1 and N 3 atoms, and it is difficult to stop the reaction at the stage of the formation of S-derivatives. This is precisely what happened in our attempt to get compound 3.…”

“…Danel et al (1998) found that the N 3 atom is more reactive than N 1 due to the influence of the neighbouring carbonyl group, therefore we assumed that the reaction products are compounds of type 3 and 5. In addition, a group of authors (Fadda et al 2013) argues that boiling under the above conditions, 6-methyl-thiouracy 1 with phenacyl bromide 2 precisely results in the formation of 7-methyl-3-phenyl-5H-thiazolo[3,2-a] pyrimidine 5.1. However, by analyzing the 1 H NMR spectra, the expected singlet signal of the proton at position 2 of the thiazole ring of compound 5.1 in the region characteristic of aromatic protons was not found.…”

Transformations of Di‐ and Tetrahydropyrimidine Derivatives into Condensed Heterocycles with Retention of their Partially Saturated Structure

“…In particular, these compounds have been used as precursors for the synthesis of some condensed derivatives. For example, the conversion of 3,4‐dihydropyrimidin‐2(1 H )‐thione derivatives 77 into the corresponding 3‐oxo‐3,5‐dihydro‐2 H ‐thiazolo[3,2‐ a ]pyrimidines 78 has been widely described (Scheme ).…”

“…As condensing agents for this cyclization were used halogen‐derived doubly electrophilic building blocks such as chloroacetyl chloride , methyl chloroacetate , ethyl chloroacetate , ethyl bromoacetate , chloroacetic acid , bromoacetic acid , and 2‐haloacetamides (Scheme ). Carrying out this reaction in the presence of aromatic aldehydes afforded 2‐arylidene‐2,3‐dihydro‐ 5H ‐thiazolo[3,2‐ a ]pyrimidines 79 .…”

“…A variety of traditional synthetic methods for the preparation of 3‐substituted 5‐aryl‐5 H ‐thiazolo[3,2‐ a ]pyrimidines are based on the annulation of 3‐bromopentane‐2,4‐dione , chloroacetone , bromoacetophenones with 3,4‐dihydropyrimidin‐2(1 H )‐thione derivatives. The selective intramolecular reaction of in situ generated α‐brominated ketones with 4‐aryl‐3,4‐dihydropyrimidin‐2(1 H )‐thiones 77 was observed via linked C2–N3 centers .…”