Novel N-(2,2,2-Trichloro-1-(3-arylthioureido)ethyl)nonanamides: Synthesis and Characterization

The incorporation of lipophilic structural fragments into biologically active molecules is a widely employed strategy in medicinal chemistry to improve their physicochemical properties and pharmacokinetic profile. Fatty acid amides are of particular interest because they can increase molecular hydrophobicity, improve membrane permeability, and influence interactions with biological targets. In this context, the nonanamide fragment represents a promising structural motif for the design of new functional molecules. Its combination with thiourea and trichloroethyl pharmacophoric units may provide compounds with valuable biological potential. In this work, a series of novel N-(2,2,2-trichloro-1-(3-arylthioureido)ethyl)nonanamides was synthesized and characterized. The target compounds were obtained by the reaction of N-(2,2,2-trichloro-1-isothiocyanatoethyl)nonanamide with substituted aromatic amines, including 4-fluoroaniline, 2-bromoaniline, methyl 2- and 4-aminobenzoate, butyl 4-aminobenzoate and 2,4-dichloroaniline. Equimolar amounts of the reagents were refluxed in acetonitrile for 1–2 min and subsequently allowed to stand at ambient temperature for 24 h to complete product formation. The resulting precipitates were collected by filtration and purified by recrystallization from acetonitrile. The developed synthetic protocol provides a convenient and efficient route to the desired thiourea derivatives under mild reaction conditions. The target compounds were isolated in good yields and exhibited satisfactory purity after recrystallization. Their structures were established by ¹H and ¹³C NMR spectroscopy, confirming the successful formation of the thiourea framework. The synthesized nonanamide derivatives expand the library of trichloroethyl-containing thioureas and constitute promising molecular scaffolds for further investigations aimed at the discovery of biologically active compounds with improved physicochemical characteristics.