1,3-disubstituted thioureas: Versatile building blocks for the construction of heterocycles

Abstract

(A) Synthesis of Thiazolidene-2-imines: 1,3-Disubstituted thioureas react with an enolizable ketone and 1,1-(ethane-1,2-diyl)dipyridinium bistribromide (EDPBT) in the presence of triethylamine to give thiazolidene-2-imine derivatives.4 The unsymmetrical thiourea gives a regioisomeric mixture of products and the regioselectivity is dependent on the pKa values of the corresponding amines attached to the thiourea moiety.5 (B) Synthesis of 2-Imino-4-thiazolidinones: A facile, general and high-yielding protocol for the synthesis of novel 2-imino-4-thiazolidinone has been described utilizing 1,3-disubstituted thiourea and chloroacetylchloride in solvent-free conditions at room temperature. C) Synthesis of 1,3-Thiazolidin-2-imines: The reaction of 1,3-disubstituted thiourea with epichlorohydrin in DMF gives 2-arylimino- 3-aryl-1,3-thiazolidine.7 In this reaction, Yb(OTf)3 has been used as the catalyst and inversion of configuration was observed at the chiral center of the epoxide. D) Synthesis of N-Substituted 2-Amino Benzimidazoles and Benzoxazoles: N-substituted 2-amino benzimidazoles and benzoxazoles have been prepared using suitable desulfurizing agent, such as CuCl or diacetoxyiodobenzene (DIB), starting from in situ generated N-(2-amino/hydroxy aryl)thioureas. (E) Synthesis of Substituted 2-Mercapto Benzimidazoles and 2-Amino Benzothiazoles by Catalytic Approaches: Substituted 2-mercapto benzimidazoles have been synthesized from their corresponding 1,3-disubstituted thioureas through S-alkylation followed by copper-catalyzed intramolecular N-arylation.10 In a similar strategy Castillon and co-workers have reported the synthesis of 2-amino benzothiazoles by a palladium-catalyzed cyclization of o-bromophenylthioureas. 11 These types of heterocycles have immense importance in medicinal chemistry. (F) Synthesis of N,N'-Disubstituted Thiobarbituric Acids: 1,3-Disubstituted 2-thiobarbituric acids have been prepared in excellent yield from 1,3-disubstituted thioureas, via an acylation-cyclization strategy.12 These heterocycles have pharmaceutical importance as anticonvulsants, immunotropic, anti-inflammatory, and antineoplastic agents as well as in the synthesis of other biologically active compounds. (G) Synthesis of Triazoles: Chorev and co-workers have reported a thiophile-promoted synthesis of disubstituted 4H-[1,2,4]-triazol-3- ylamines.13 When 1,3-disubstituted thiourea was reacted with formic hydrazide and mercury(II) acetate as thiophile, the reaction mixture produced acyl hydrazide adduct, which was cyclized to the corresponding [1,2,4]triazole under acidic conditions.