Design, Synthesis and Characterization of New Aroyl thioureas, Iminothiazolidinones, Azo-iminothiazoles and Azo-thiohydantoins For Various Applications

Abstract

This research work reports the design, synthesis and characterization of novel aroyl thioureas and nitrogen, Sulphur containing heterocyclic compounds Iminothiazolidinones, azo-iminothiazoles and azo-thiohydantoins hybrid compounds. Part 1 of the research was the expedient synthesis of aroyl thioureas (1-aroyl-3-(3-chloro-2-methylphenyl) thiourea). The intended compounds were synthesized by the conversion of aromatic acids into corresponding acid chlorides followed by reaction with potassium thiocyanate to obtain reactive intermediates isothiocyanates, the latter was treated with 2-Me-3-Chloroaniline to afford the title (1-aroyl-3-(3-chloro-2-methylphenyl) thiourea). Part 2 of the current research was the catalyst free synthesis of new potentially pharmaceutically important Iminothiazolidinones. For this purpose the novel synthesized 1-aroyl-3-(3-chloro-2-methylphenyl) thioureas were cyclized through diethyl acetylene dicarboxylate in dry DCM on stirring at room temperature for 24 hours, without using any catalyst resulted in desired (Z)-ethyl 2-((Z)-2-arylamido-3-(3-chloro-2-methylphenyl)-4-oxothiazolidin-5-ylidene) acetates. Part 3 of this research work comprises the design of hybrid structures by the incorporation of different bioactive moieties into the single structure to enhance their potential as pharmacophores. Keeping in view, two schemes were designed to synthesize two types of hybrid structures azo-iminothiazoles and azo-thiohydantoins. For this purpose first of all diazonium salts were prepared which were coupled with salicylaldehyde to get azo-compounds. Azo- compounds in the next step treated with thiosemicarbazide which resulted in the formation of azo-thiosemicarbazones. All the synthesized derivatives of azo-thiosemicarbazones were new. These azo-thiosemicarbazones were cyclized in two schemes to afford the desired compounds. Scheme 1 explores the cyclization of azo-thiosemicarbazones with 2,4’-Dibromoacetophenone and fused sodium acetate refluxed in ethanol resulted in azo-iminothiazoles hybrid structures equipped with bioactive moieties azo, hydrazone moiety and thiazole group. In scheme 2 azo-thiosemicarbazones were cyclized by ethyl chloroacetate and fused sodium acetate refluxed in ethanol to get azo-thiohydantoins hybrid compounds having azo, imine and hydantoin moieties in single structure .