Synthesis and Spectral Characterization of Novel N-(2,2,2-Trichloro-1-(3-Arylthioureido)Ethyl)Pivalamides

One of the directions of modern pharmaceutical chemistry is the structural modification of biologically active compounds aimed at optimizing their physicochemical and pharmacological properties. The introduction of specific functional groups into the structure of potential drug candidates is an effective strategy for regulating lipophilicity, membrane permeability, and other parameters that determine their pharmacokinetic profile. Such modifications can improve bioavailability, selectivity, and the therapeutic efficacy of potential drug candidates. Among the promising structural motifs, the pivaloyl moiety has attracted attention due to its ability to favorably modify the physicochemical properties of drug molecules and enhance their pharmacokinetic characteristics.

In the present study, we report the synthesis of novel N-(2,2,2-trichloro-1-(3-arylthioureido)ethyl)pivalamides. These compounds combine thiourea, trichloroethyl, and pivaloyl fragments within a single molecular framework, making them promising candidates for the development of new biologically active compounds. The target thioureas were synthesized by the reaction of N-(2,2,2-trichloro-1-isothiocyanatoethyl)pivalamide with p-toluidine, o- and p-chloroaniline, as well as o- and p-bromoaniline. The reactions were carried out by refluxing equimolar amounts of the starting materials in acetonitrile for 1-2 min, followed by standing at room temperature for 24 h. The precipitated products were isolated by filtration and purified by recrystallization from acetonitrile. The proposed synthetic approach is straightforward, proceeds under mild reaction conditions, and affords the desired products in high yields (82–86%). The structures of the synthesized compounds were unequivocally confirmed by ¹H and ¹³C NMR spectroscopy. The obtained derivatives represent promising scaffolds for the development of novel biologically active compounds.