ES367094A1 - Preparation of (cis-1,2-epoxypropyl)phosphonic acid and salts and esters thereof - Google Patents

Abstract

(cis - 1,2 - Epoxypropyl)phosphonic acid or an ester or salt thereof is obtained by eliminating nitrogen from a cis azo phosphonic compound of the formula wherein each R is a hydrogen atom or a substituted or unsubstituted hydrocarbyl or heterocyclic radical, or from an organic or inorganic salt of such compound in which at least one R is a hydrogen atom. The elimination of nitrogen may be effected by irradiating a solution of the azo compound with U.V. light preferably in the presence of a photo-sensitizing agent, e.g. benzophenone or acetophenone, or by heating the azo compound, generally at above 80 C., e.g. from 100 to 300 C., the heating being carried out directly or with the azo compound suspended or dissolved in an appropriate suspending agent, e.g. a mineral oil, or inert solvent, e.g. toluene, pyridine, chloroform, cumene or xylene. Suitable solvents for use in the U.V. light treatment include water, C 1 -C 6 alkanols, dioxane, acetonitrile or tributyl amine, or aqueous mixtures thereof. If the starting material contains any of the trans isomer the latter can be separated or the cis/trans mixture can be converted by the defined process to a mixture of cis- and trans-1,2-epoxy propyl phosphonic and the trans isomer then separated and if desired converted to the cis isomer by irradiation with U.V. light. If the free phosphonic acid is used in the process it is preferred to isolate the product as a salt, e.g. the sodium or benzyl ammonium slat and if the starting material is an ester the ester product may be converted to the free acid or salt thereof by hydrolysis or reductive removal of the ester group. The end products are generally racemic mixtures which can be resolved into their optically active (+) and (-) forms. The ( )(cis - 1,2 - epoxypropyl)phosphonic acid and salts thereof have antimicrobial properties. The starting materials I may be prepared by the following reaction scheme: In these reactions the compounds V are converted to I by epoxidation and the compounds VI are converted to I by oxidation with mercuric oxide. The phosphonic reactants and products may be in the form of the free acids, esters or salts. Compounds IV or their salts are obtained by reacting chlorophosphonic acid or ester or salt thereof with hydrazine hydrate at low temperature, generally below 0 C. and in an inert solvent. Compounds II can be obtained by the following reaction scheme: The salt, ester or free acid of the phosphorus acid may be used (a salt being shown) and compounds VIII are converted to 1,2-epoxy-2- chloro-ethyl phosphonic acid or salt or ester thereof by treatment with water, this being followed by treatment with methylhydrazine to form compounds IX which are finally treated with mercuric oxide to form II.