Highly effective, rapid and convenient one-pot synthesis of O,O’-dialkyl-N,N-dialkylphosphoramidates from trialkyl phosphites

Abstract

Verification of Chemical Weapon Convention (CWC) related chemicals necessitates proper synthesis of reference chemicals for their ­unambiguous identification during off-site analysis. O,O’-dialkyl-N,N-dialkylphosphoramidates are listed in Annex 2.B.6 of CWC as precursor of highly toxic nerve agent ‘Tabun’ (Schedule 1.A.2). Existing ­methods for synthesis of O,O’-dialkyl-N,N-dialkylphosphoramidates (DADAP’s) rely on utilization of hazardous chlorinating agents in the intermediate stage for chlorination purposes. Herein, we report novel one-pot synthesis of CWC related O,O’-dialkyl-N,N-dialkylphosphoramidates from trialkylphosphites by using iodine and appropriate secondary amines as per convention requirement. Reaction was performed in hexane using iodine as a catalyst. Both hexane and iodine were relatively safe, inexpensive and easy to handle. The developed method was tolerated for the synthesis of various O,O’-dialkyl-N,N-dialkylphosphoramidates (1a–1y). Optimized method gives 88–96% product yield within 15 min at 25 °C. All products were characterized by GC-MS, LC-MS,¹H NMR and ³¹P{¹H} NMR techniques.