PHOSPHONOMETHYLATION OF AMINOALKANOLS PREPARATION OF 4-(PHOSPHONOMETHYL)-2-HYDROXY-2-OXO-1,4,2-OXAZAPHOSPHORINANES1

Abstract

Treatment of aminoalkanols 1 with phosphorous acid and formaldehyde in presence of conc. hydrochloric acid gave mixtures of (2-hydroxy alkyl)imino] dimethylene diphosphonic acids 3 and 4-(phosphonomethyl)-2-hydroxy-2-oxo-1,4,2-oxazaphosphorinanes 2 from which 2 were isolated as crystalline solids. Similar treatment of 2-amino-2-methyl-1,3-propanediol 8 gave a complex mixture from which dimethylene diphosphonic acid of 5-amino-5-methyl-1,3-dioxane 9 was isolated. 2-Aminoethanethiol, when subjected to phosphonomethylation. gave an unexpected novel quarternary nitrogen product 11. N-Alkylaminoalkanols 4 on phosphonomethylation gave 3:1 mixtures of N-alkyl-N-(2-hydroxyalkyl)amino] methane phosphonic acid 6 and N-alkyl-2-hydroxy-2-oxo-1,4,2-oxazaphosphorinane 5. Treatment of the crude mixtures of 5 and 6 with aqueous sodium hydroxide gave disodium salts of N-alkyl-N-(2-hydroxyalkyl)amino] methanephosphonic acid 7. The ratio of the cyclic to the open chain structures obtained as well as the formation of any unexpected novel products is dependent on the structure of the aminoalkanol that is phosphonomethylated. The ¹H, ¹³C and ³¹P spectra are reported for all new compounds.