A simple method of β-aminophosphonates synthesis

Abstract

We developed a simple two-stage synthesis of aminophosphonates containing an unsubstituted amino group, whose synthesis by other methods was a complex problem [1, 2]. Diethyl methylphosphonate was treated by butyllithium in THF, after which it was reacted with nitriles to form β-enaminophosphonates Ia–Id in high yields as we have described previously [3]. Then βenaminophosphonates I were reduced with calcium borohydride in the THF-isopropanol or THF-aqueous ethanol mixture to give β-aminophosphonate II in high yield. Calcium borohydride was obtained by the reaction of sodium borohydride with calcium chloride in THF. In the mixture THF-aqueous ethanol this reaction proceeded more rapidly. However, besides aminophosphonate, ketophosphonate admixture formed (~10%), which was easily separated by extraction with ethyl acetate after acidification of the reaction mixture by hydrochloric acid where the aminophosphonate exists as hydrochloride. Free aminophosphonate was isolated after the reaction mixture was neutralized with alkali. Aminophosphonates were purified by vacuum distillation, and they were isolated as colorless viscous liquids. Purity and structure of aminophosphonates II were confirmed by TLC, Н, F, and Р NMR spectroscopy. In the P NMR spectrum the chemical shifts δP were displaced to 30 ppm. The Н NMR spectra contain a doublet signal of the two protons of PCH2 group; protons of amino group appear as a broad signal at 2.5 ppm.