Patent GB-1233286-A (GB)
IPC: C07F9/655
Filed: 1969-05-12
Abstract: 1,233,286. (Cis - -1,2 - epoxypropyl)phosphonic acid salts and esters. MERCK & CO. Inc. 12 May, 1969 [15 May, 1968], No. 23977/69. Heading C2C. A salt or ester of (cis-1,2-epoxypropyl) phosphonic acid is obtained by irradiating with ultraviolet light a solution containing a salt or ester of (trans 1,2-epoxypropyl) phosphonic acid. The salt may be a mono- or di-salt and the ester may be a mono- or di-ester and the salt or ester may be racemic, either optical isomer, or a mixture of the (+) and (-) enantiomers. The ultra-violet light may be that produced by a mercury vapour lamp and the solution of the trans material may be sensitised to u.v. light before the irradiation is carried out by the addition of about 10% (based on the weight of the starting material) or a photo-sensitizing agent such as benzophenone or acetophenone. Suitable solvents are C 1 -C 6  alkanols, dioxane, acetonitrile and tributylamine or aqueous mixtures thereof. On completion of the isomerization the cis salt products may be isolated by concentrating the reaction mixture in vacuo and separating any unreacted trans isomer by repeated crystallization using an alcohol: water mixture. In the case of the cis ester products isolation may be effected by use of vapour phase chromatography. When a mono- or di-ester of the trans acid is used as starting material the ester may be converted to a salt of the cis acid by carrying out the irradiation in a basic medium, e.g. in the presence of a tertiary amine or an amine salt, e.g. pyridine or trimethylammonium carbonate, in which case the product is an amine salt of the cis form. The ester group or groups in the trans starting material may be hydrocarbyl or substituted hydrocarbyl groups, e.g. a C 1 -C 7  alkyl, C 2 -C 7  alkenyl or alkynyl, or an aryl or aralkyl group and the salt starting materials may be e.g. alkali metal or alkaline earth metal salts, or ammonium or amine salts, e.g. salts with C 1 -C 6  alkyl amines, arylamines, e.g. phenylamine, or aralkylamines, e.g. benzylamine and phenylethylamine, or cyclohexylamine. () And (-) (cis 1,2-epoxy propyl) phosphonic acid and salts thereof are useful antimicrobial agents. The ammonium salt of () (trans.1,2-epoxypropyl) phosphonic acid is obtained by reacting diisopropyl (2-chloropropyl) phosphonate with KOH in ethanol to form trans propenyl phos. phonic acid, treating the latter with NH 4 OH to form its ammonium salt, and then epoxidizing with H 2 O 2  in the presence of sodium tungstate. Other salts of the trans acid may be obtained by passing a solution of the NH 4  salt through a column containing a strong ion exchange resin adjusted to the H<SP>+</SP> cycle into an appropriate base e.g. benzylamine, KOH or NaOH. Esters of the trans acid may be obtained by treating the Na salt with an equivalent amount of silver nitrate to form the silver salt and reacting the latter with an alkyl, alkenyl, alkynyl or aralkyl halide at about 60 C. in dimethoxyethane. Aryl esters may be obtained by treating trans propenyl phosphonic acid with thionyl chloride and pyridine in benzene, reacting the acid chloride thus formed with phenol or a substituted phenol and then epoxidizing the resulting aryl propenyl phosphonate using H 2 O 2  and sodium tungstate.