We present a multicomponent reaction strategy to synthesize a (dihydro-1H-benzo[d]imidazole)phosphonate family of compounds, using benzimidazoles, diethyl chlorophosphate and aliphatic amines as starting reactants. Giving its simplicity, our procedure involves reaction times of only few hours and avoid the usage of any catalyst agent. All the newly synthesized compounds were characterized by Nuclear Magnetic Resonance spectroscopy (¹H, ¹³C and ³¹P) and mass spectrometry by the DART method.

We present a new single-step multicomponent reaction strategy for the synthesis of symmetric and (novel) asymmetric bisphosphoramidate and bisphosphoramidothioate derivatives. Reactions proceed under routine experimental conditions, do not require the aid of any catalyst, and provide moderate yields after a short time. We synthesized 18 different compounds, 10 of them for the first time. The cytotoxic activity of our adducts was assessed by measuring their inhibitory capacity (IC₅₀) against two different cell lines, the A549 (lung cancer cells) and the SW1353 (chondrosarcoma cells). Graphical Abstract

A fast, safe and accessible multicomponent reaction procedure is reported for the synthesis of symmetric and nonsymmetric benzyl-bisphosphoramidate derivatives. Our key reagents were 1,3-phenylenedimethanamine 3 conjointly with the five different phosphorous chlorides, O, O′-diethyl chlorothiophosphate 1, diphenyl phosphoryl chloride 2, diethyl chlorophosphate 5, N, N, N ′, N′-tetramethylphosphorodiamidic chloride 7 and O, O′-dimethyl chlorothiophosphate 9. A total of seven products were obtained, five of them none reported before. As far as we know, our work constitutes the first approach for the synthesis of nonsymmetric benzyl-bisphosphoramidate derivatives. The presence of our adducts were always confirmed by NMR spectroscopy (¹H, ¹³C and ³¹P) and mass spectrometry. Graphical Abstract