Patent GB-1238422-A (GB)
IPC: C07F9/655
Filed: 1969-05-12
Abstract: 1,238,422. Preparing  (cis 1,2-epoxypropyl) phosphonic acid and its salts and esters. MERCK & CO. Inc. 12 May, 1969 [15 May, 1968], No. 23971/69. Heading C2C.  (Cis 1,2-epoxypropyl) phosphonic acid or an ester or salt thereof is obtained by treating an ester or salt of 1-propynyl phosphonic acid with an epoxidizing agent and hydrogenating the reaction product in situ in the presence of a hydrogenation catalyst comprising a metal or a metallic compound. In an alternative method the reduction of the epoxidized product is carried out by means of di-imide (NH=NH) formed in situ, e.g. by oxidation of hydrazine with H 2 O 2  in the presence of copper sulphate. Suitable ester starting materials include mono- and di - (C 1 -C 8  alkyl), mono- and di (C 2 -C 8  alkenyl), mono- and di- (C 2 -C 8  alkynyl), mono - and di - (C 3 -C 8  cycloalkyl) esters and mono - and di - aryl, aralkyl or alkaryl esters of 1-propynyl phosphonic acid and suitable salts include alkaline earth metal salts, mono- and dialkali metal salts and ammonium or organic amine salts. The epoxidizing agent may be a perorganic acid or may be hydrogen peroxide in the presence of a neutral tungstic acid salt catalyst. Typical hydrogenation catalysts are copper, nickel, palladium and platinum catalysts and Raney metal catalysts e.g. Raneynickel, -cobalt, -iron and -copper catalysts. The epoxidation is generally carried out in a solvent and the resulting 1,2-epoxypropenyl phosphonic acid ester or salt is subjected directly to the hydrogenation treatment without isolation, the hydrogenation being effected, after addition of the hydrogenation catalyst, until saturation of the olefinic bond is complete. When the ester starting material is an aralkyl, alkenyl or alkynyl ester the ester group is removed during the hydrogenation and the resulting cis 1,2- epoxypropyl phosphonic acid may be isolated from the reaction medium in the form of a salt. When the products are esters they may be converted to the free phosphonic acid or salt thereof by a variety of methods according to the nature of the ester group, e.g. by U.V. irradiation, basic hydrolysis, acid hydrolysis, enzymolysis, treatment with ionic salts, reduction, or ester interchange followed by one of the above methods. Any 1,1,2,2-diepoxy propyl phosphonic acid ester or salt which might be formed in the epoxidation reaction mixture may be converted to the corresponding (1,2-epoxypropenyl) phosphonate by adding triphenyl phosphine to the reaction mixture and heating at about 150 to 170 C. for 20 to 60 minutes. The triphenyl phosphine oxide formed is then removed by filtration, and the mixture then catalytically hydrogenated to form the desired product. The () (Cis, 1,2-epoxypropyl) phosphonic acid and its salts have antibiotic properties. 1 - Propynyl phosphonic acid is obtained by refluxing dibenzyl 1-propynyl phosphonate with conc. HCl and is converted to its monosodium salt by addition of aqueous sodium bicarbonate solution to a pH of 5À5 to 6 or to the di-salt by addition of further base to pH 8 to 9. Other specified bases which may be used to form salts are potassium bicarbonate, CaCO 3 , MgCO 3 , NH 4 OH and benzylamine.