ABSTRACT

Background: we reported in this paper another part of our investigations concerning the preparation of diethyl (2-benzoylamino-2-(phenylsulfanyl) methyl) phosphonate and diethyl (2-benzoylamino-2-(4-chloro- phenylsulfanyl) methyl) phosphonate 2-3, with the aim to have access to new active biomolecules with a good yield through S-alkylation reaction. Objectives: α-Amino esters possess a broad range of applications ranging from agrochemistry to medicine. We developed a simple, efficient, and environmentally benign method for the Synthesis of new racemic phosphonic α-amino esters by S-alkylation of diethyl (2-azido-2-benzoylaminomethyl) phosphonate with aromatic thiols (thiophenol and 4-chloro thiophenol). The structures of the newly synthesized compounds were supported by ¹H NMR, ¹³C-NMR and mass spectral data. This method has advantages of mild condition, no environmental pollution, and simple work-up procedures. Most importantly, compounds of α-phosphonic aminoesters are obtained in acceptable to moderate yields by this methodology. Methods: The S-alkylation of diethyl (2-azido-2-benzoylaminomethyl) phosphonate with aromatic thiols (thiophenol and 4-chloro thiophenol) are performed in different solvents (acetone and acetonitrile) for 48 h at room temperature in the presence of various bases (Et₃N and DIEPA). Results: The products 2-3 synthesized with a satisfactory yields were characterized by nuclear magnetic resonance and mass spectrometry. Conclusions: we have developed an environmentally friendly, mild condition protocol and convenient procedure for the preparation of new phosphonic α-aminoesters derivatives starting from the appropriate azide derivative 1. The nucleophilic substitution of azide with different thiols (thiophenol and 4-chloro thiophenol) occurred under very mild conditions and led after a reaction time of about 48 hours to the desired products with a satisfactory yields.
Keywords: α-amino ester, S-alkylation, thiophenol, diethyl (2-azido-2-benzoylaminomethyl) phosphonate.