GB1204448A - Production of cis-propenylphosphonic acid and salts and esters thereof - Google Patents

Abstract

1,204,448. Preparing cis-propenyl phosphonic acid and derivatives thereof. MERCK & CO. Inc. 24 Oct., 1968 [30 Oct., 1967; 15 May, 1968], No. 50637/68. Heading C2C. The ( + ) isomer, or a mixture containing ( + ) and ( - ) isomers, of (cis-1,2-epoxypropyl)- phosphonic acid or a salt or ester thereof is reacted with a de-epoxidizing agent to produce cis-propenyl phosphonic acid or a salt or ester thereof. The de-epoxidizing agent may be a reducing metal salt, preferably chromous chloride or acetate, hydrogen iodide or compounds which form hydrogen iodide in solution, e.g. NaI or KI, phosphorus compounds, e.g. triaryl phosphines, tri-(C 1 -C 7 alkyl)-phosphines or -phosphites, or a phosphonium halide, e.g. a phosphonium iodide, a sulphur compound, e.g. (C 1 -C 7 alkyl) xanthates such as Na or K-nbutyl xanthates and thiocyanate salts, e.g. Na-, K- or ammonium thiocyanates, a potassium iron carbonyl compound, e.g. KHFe(CO) 4 , K 2 Fe(CO) 4 or K 2 Fe(CO) 8 , or potassium selenocyanide. De-epoxidation is generally carried out in a solvent and the reaction conditions and solvent used depend on the particular type of de-epoxidizing agent used. The cis-propenyl phosphonic acid may be epoxidized to form a racemic mixture of (cis1,2-epoxypropyl)-phosphonic acid and the latter then resolved to form the pure ( - ) isomer which is useful as an antibiotic. The ester derivatives may be mono- or di-esters, e.g. aryl or aralkyl esters or C 1 -C 7 alkyl, C 2 -C 7 alkenyl or C 2 -C 7 alkynyl esters and the alkyl or aryl groups present may be substituted. The salts may be mono- or di-salts and may be metal salts or ammonium or organosubstituted ammonium salts, including the mono - benzylammonium, mono - cyclohexylamine, phenylamine, bis-hexylamine and isopropyl phenethylammonium ester salt. Di - n - butyl - cis - propenylphosphonate is obtained by selectively reducing the corresponding propynyl ester and is hydrolysed to the free acid (cis-propenyl phosphonic acid) by means of conc. HCl, the free acid is neutralized with NH 4 OH and epoxidized with H 2 O 2 in the presence of sodium tungstate to form the ammonium salt of (Œ)(cis-1,2-epoxypropyl)-phosphonic acid which is then resolved by use of quinine in methanol to yield the ammonium salt of the ( - ) isomer and the ammonium salt of a mixture of the ( + ) isomer and a small amount of the ( - ) isomer, the latter salt mixture being converted to the ( - ) α-phenylethylamine salt of the ( + ) isomer and the latter converted to the diammonium salt of the (+) isomer which may be converted to the monobenzylammonium salt or to various esters of the ( + ) isomer by passage through a strongly acid ion exchange resin and either treating the eluate with benzylamine or with NaOH followed by reaction with an alkyl, alkenyl, or alkynyl halide or benzyl chloride. Aryl trans-propenyl phosphonates may be obtained by dissolving trans-propenyl phosphonic acid (obtained from its monobenzylammonium salt), thionyl chloride and pyridine in benzene and then reacting with phenol or a substituted phenol and may be epoxidized.