Phosphorylation of Amino(aryl)methylphosphonates by the Atherton—Todd Reaction

Abstract

We were the first to perform phosphorylation of amino(aryl)methylphosphonates having a primary amino group under the Atherton–Todd reaction conditions. The reactions of amino(aryl)methylphosphonates Ia–Ie with diethyl phosphonate and carbon tetrachloride in the presence of triethylamine were carried out at room temperature, on heating at 110oC, and under microwave irradiation. The reactions under microwave irradiation were complete in 30–40 min, and the corresponding N-(α-phosphoryl)amidophosphates IIa–IIe were obtained in 63–93% yield. No reaction occurred at room temperature, whereas after heating for 24 h at 110°C compounds IIa–IIe were isolated in poor yields (15–20%) due to predominant formation of pyrophosphate on prolonged heating. The product structure was confirmed by their H, C, and P NMR spectra and elemental analyses. Compounds IIa–IIe displayed in the P NMR spectra doublet signals at δP 6.2–6.8 and 22.2–22.6 ppm with coupling constants of 40.2–42.7 Hz. In the H NMR spectra of IIa–IIe, the NCH proton characteristically resonated at δ 4.4–4.6 ppm, and the corresponding carbon signal appeared in the C NMR spectra as a doublet at δC 51.3–53.8 ppm (JPC = 153–156 Hz). Diethyl aryl(diethoxyphosphorylamino)methylphosphonates IIa–IIe (general procedure). Carbon tetrachloride, 20 mmol (3.08 g, 2.11 ml), triethylamine, 15 mmol (1.52 g, 1.08 ml), and aminophosphonate Ia–Ie, 10 mmol, were added in succession to 10 mmol (1.38 g, 1.29 ml) of diethyl phosphonate. The reaction was carried out in an open vessel under microwave irradiation (102 W, 115°C). The precipitate of triethylamine hydrochloride was filtered through a glass filter, the filtrate was cooled and evaporated on a rotary evaporator, and the residue was subjected to column chromatography on silica gel using chloroform–methanol (50 : 1) as eluent.