One-Pot Multicomponent Synthesis of Thiourea Derivatives in Cyclotriphosphazenes Moieties

Abstract

In this study, hexasubstituted thiourea was carried out via reaction of isothiocyanato cyclophosphazene intermediates with a series of aromatics amines and amino acids in a one-pot reaction system. The reaction was not as straightforward as typical thiourea synthesis. Six unexpected thiourea derivatives3a–fwere formed in the presence of cyclotriphosphazene moieties in good yields (53–82%). The structures of3a–fwere characterized by elemental analysis and FTIR,1H,13C, and31P NMR spectroscopies. The occurrence of reverse thioureas formation in a one-pot reaction system is discussed. The possible binding interaction of the synthesised thiourea3a-bin comparison to the predicted phenyl thiourea5a-band the targeted4awith enzyme enoyl ACP reductase (FabI) is also discussed. Molecular docking of the targeted hexasubstituted thiourea4ais able to give higher binding affinity of −7.5 kcal/mol compared to5a-b(−5.9 kcal/mol and −6.3 kcal/mol) and thiourea3a-b(−4.5 kcal/mol and −4.7 Kcal/mol).