Microwave-Enhanced Synthesis of Phosphonoacetamides

Abstract

An efficient microwave protocol is described for the Michaelis–Arbuzov synthesis of secondary and tertiary N-aryl (and alkyl) (diethylphosphono)acetamides 1, by reaction of chloro- and bromoacetamides with triethyl phosphite in the presence of catalytic amounts of sodium iodide. Remarkable acceleration of the reaction (minutes vs. several hours) over conventional heating was achieved, together with improved product yields and purity, when bromoacetamides were employed as the substrates. Chloroacetamides were comparatively less reactive, leading to satisfactory yields only when a high excess of the reagent was employed.

GRAPHICAL ABSTRACT

Keywords:

• Michaelis–Arbuzov reaction
• microwaves
• phosphonoacetamides
• phosphorus compounds
• sodium iodide

ACKNOWLEDGMENTS

This work was supported by the Universidad de Buenos Aires (B-096) and by CONICET (PIP 11420090100286). We thank Lic. Ignacio L. Berlanga for some preliminary experiments.

Notes

^a Yields correspond to pure compound 1a.

^b Conventional heating at 110 °C.

^c Reactants were supported on neutral Alumina.

^d 5 mmoles of the substrate and 7.5 mmoles of the reagent were employed.

^a Yields correspond to pure compounds.

^b DME was employed as the solvent.