New bisphosphorothioates and bisphosphoroamidates: Synthesis, molecular modeling and determination of insecticide and toxicological profile

A series of new compounds, N,N′-bis(dialkylphosphoryl)diamines and S,S′-bis(dialkylphosphoryl)-1,3-propanedithiols were prepared by a Todd–Atherton like reaction of dialkylphosphites with symmetrical diamines and 1,3-propanedithiols in a biphasic system [F.R. Athertoon, H.T. Howard, A.R. Todd, J. Chem. Soc. (1948) 1106–1111; F.R. Athertoon, H.T. Openshaw, A.R. Todd, J. Chem. Soc. (1945) 660–663]. The structures were characterized by IR, 1H NMR, 13C NMR and mass spectrometry. Compounds with butoxy, isobutoxy and isopropoxy groups linked in the phosphorus atom showed the lowest LD50 values when tested against Musca domestica and Stomoxys calcitrans. The pharmacological and toxicological evaluation of N,N′-bis(diisobutylphosphoryl)-1,3-propylenediamine and S,S′-bis(diisobutylphosphoryl)-1,3-propanedithiol, which were very active against M. domestica and S. calcitrans, demonstrated that these compounds present no toxicological effects against mice in a concentration of 200 mg/kg. An explanation for the observed activity profile is presented based on results obtained in a molecular modeling study with insect and mammalian acetylcholinesterase models.