Selective cyclization of S-substituted pyrimidinethione: Synthesis and antimicrobial evaluation of novel polysubstituted thiazolopyrimidine and thiazolodipyrimidine derivatives

The synthetic strategy is based on alkylation of 4-aryl-N-(4-chlorophenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide derivatives IV a-g, with some alkyl halides and alpha-haloketones, namely, methyl iodide, chloroacetonitrile, and phenacyl bromide to give the corresponding S-substituted derivatives Va-c. Treatment of IVa-c with ethyl bromoacetate in ethanol under reflux in the presence of potassium hydroxide solution led to the formation of N-(4-chlorophenyl)-7-methyl-3-oxo-5-(aryl)-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidine-6-carboxamide derivative VIII a-c in a single-step synthesis. On the other hand, compound IVa reacted with alpha-halo carbonitriles, namely, chloro acetonitrile, and monobromo malononitrile, to produce directly thiazolo[3,2-a]pyrimidine derivatives Xa and Xb, respectively, Compound Xb also reacted with each of formic acid, formamide, and ammonium thiocyanate to form thiazolodipyrimidine derivatives XI-XIII, respectively. Compound VIIIa-c coupled with arenediazonium salts in pyridine to give the corresponding 2-arylhydrazo derivatives XVIa-e. Compounds IV a-g and VIIIa-c were resynthesized under microwave irradiation. Some of the newly synthesized compounds were tested for their antimicrobial activities.