Combination of the Suzuki-Miyaura cross-coupling and nucleophilic aromatic substitution of hydrogen (S N H) reactions as a versatile route to pyrimidines bearing thiophene fragments

Abstract

It has been shown that combination of the Suzuki-Miyaura cross-coupling and nucleophilic aromatic substitution of hydrogen is a versatile method for the synthesis of 4-(thiophen-2-yl)-, 5-(thiophen-2-yl)-, and 4,5-di(thiophen-2-yl) substituted pyrimidines from the commercially available 5-bromopyrimidine. The S N H (AE)- and S N H (AO)-reactions of 5-bromopyrimidine with thiophene and 2-bromothiophene have been studied by gas-liquid chromatography/mass-spectrometry. The structures of intermediate σ H-adducts, as well as thiophene-(thiophenyl)pyrimidine and bithiophene-(thiophenyl)pyrimidine dyads have first been established by X-ray crystallography analysis. © 2012 Elsevier Ltd. All rights reserved.