Synthesis of Some New Pyrimidine Derivatives of Expected Antimicrobial Activity

Abstract

2-(2-Arylvinyl)-6-methyl-4-mercapto-5-acetylpyrimidine derivatives 3 _{a − d} , were synthesized form the reaction of the appropriate isothiocyanate derivatives 1 with α, β -unsaturated aminoketone 2 . Compound 3 was alkylated with methyl iodide, ethyl chloroacetate and/or bromosugar to afford 6 , 9 , and 22 _{a − c} respectively. Cyanoethylation of 3 _b afforded 6 _b which upon cyclization with hydrazine hydrate gave pyrazolopyrimidine 7 . Bromination of 6 _b gave dibromo compound 8 . Thieno[2,3-d]pyrimidines 10 and 12 were obtained by ring closure of the alkylated product 9 with TEA/EtOH and/or through cyclization of the hydrazide 11 with NaOEt/EtOH. While, Thieno[2,3-d]pyrimidine 14 was obtained directly by alkylation of 3 _b with chloroacetone in both TEA/EtOH and Na₂CO₃ solution. The cycloaddition products 15 and 16 were obtained by reaction of 3b with diethylmaleate and/or maleic anhydride. Formation of 1,3,4-oxadiazole 17 , pyrazoles 18 and 19 where obtained by treating the hydrazide 11 with carbon disulphide, triethyl orthoformate and acetylacetone respectively. While, reaction of 11 with p-chlorobenzaldehyde resulted in the Schiff's base 20 which, cyclizes with thioglycolic acid to afford thiazolidone 21 . Hydrolysis of 22 _{a − c} in TEA/MeOH afforded the free sugar 23 _{a − c} .

The structures of all the new compounds were confirmed using IR, ¹ H, and ¹³ C NMR spectra and microanalysis. Selected members of the synthesized compound were screened for antimicrobial activity.

Keywords:

• Pyrazolopyrimidine
• thieno[2,3-d]pyrimidines
• thiazolidone and bromosugar

Acknowledgments

We gratefully to Dr. Hasan Abd El-Salam Assistant Prof. Of microbiology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt for performance of the biological assay. Also, we are indebted to the Faculty of Chemistry, University of Konstanz, Germany, for carrying out all the analysis and spectra involved in this manuscript.