Patent GB-1239159-A (GB)
IPC: C07F9/655
Filed: 1969-05-12
Abstract: 1,239,159. (Cis -1,2-epoxypropyl) phosphonic acid and its salts and esters. MERCK & CO. Inc. 12 May, 1969 [15 May, 1968], No. 23979/69. Heading C2C. (Cis - 1,2 - epoxypropyl) phosphonic acid or an ester or salt thereof is obtained by eliminating CO 2 , SO 2 , SO 3  or N 2  from (cis-5-methyl-2-oxo- 1,3 - dioxolan - 4 - yl) phosphonic acid, (cis- 5 - methyl - 1,3,2 - dioxathiol - 4 - yl) phosphonic acid S-oxide, (cis-5-methyl-1,3,2-dioxathiol-4- yl) phosphonic acid S,S-dioxide or (cis-4-methyl- 1,2,3-oxadiazolin-5-yl) phosphonic acid or from an ester or salt of said acids. The starting materials have the general formula: where Z is an -O-C(O)-, -O-S(O)-, -O-S(O)(O)-, or -N=N group and R is H or a substituted or unsubstituted hydrocarbyl or heterocyclic radical or an equivalent of an organic or inorganic salt-forming cation, the two R's being the same or different. The compounds I and the resulting products are preferably in the form of their racemates. Specified salt-forming cations are Na, K, Ca, Mg, Ag, Fe, NH<SP>4</SP> and cations derived from amines. The elimination of CO 2 , SO 2 , SO 3  or N 2  may be effected by heating, e.g. by pyrolysis at temperatures above 80 C. depending on the particular type of starting material I. The heating may be carried out in a mineral oil, e.g. white oil or in a high boiling solvent such as dichlorobenzene, diphenylether, dodecyl benzene or cumene. In another method elimination is effected by irradiating a solution or suspension of the starting material with U.V. light, the solution or suspension containing, if desired, a photo-sensitizing agent such as benzo-phenone or acetophenone. The irradiation is usually conducted at from - 10 C. to 50 C. The compounds of Formula I in which Z is -N=N- may be formed and simultaneously decomposed to form the (cis-1,2-epoxypropyl) phosphonic acid compound by reacting a formyl phosphonate ester (RO) 2 P(O)CHO with diazoethane at or below room temperature, the formyl phosphonate ester being obtained by the ozonization of a vinyl phosphonate ester. The compounds I in which Z is -N=N- may also be prepared by reacting a (cis-1-propenyl) phosphonic acid or ester or salt thereof with nitrous oxide at high temperature, e.g. 150 to 350 C., usually under pressure and generally in an inert solvent and are simultaneously converted to the (cis-1,2- epoxypropyl) phosphonic acid compound. When the product is an ester of (cis-1,2-epoxypropyl)- phosphonic acid it can be converted to the free acid or to a mono- or di-salt thereof by hydrolysis or reductive removal of the ester group. It is preferred to use a salt of the acid I but if the free acid is used the product is preferably isolated as a salt, e.g. as a sodium or benzylammonium salt. When the products formed are racemic mixtures the latter may be resolved into their optically active forms and if the starting material I is a cis/trans mixture the cis/trans mixture formed may be separated into the cis and trans isomers of the desired product. Alternatively the mixture of cis/trans isomers (I) may be separated before the decomposition step. Any trans isomer present in the final product may be converted to the cis isomer by U.V. light treatment The compounds of Formula I in which Z is -O-C(O), can be prepared by reacting a 1,2- dihydroxy propyl phosphonic acid, ester or salt with phosgene or a combination of carbonate cyclizing agents such as ethyl chlorocarbonate, diethyl carbonate or ethylene carbonate plus anhydrous K 2 CO 3 . The cyclic sulphites I in which Z is -O-S(O) may be obtained by reacting 1,2-dihydroxypropyl phosphonic acid or an ester or salt thereof with a molar amount of a sulphite cyclizing agent, e.g. thionyl chloride, bromide or fluoride, in the presence of a hydrogen halide acceptor, e.g. a tertiary amine. The cyclic sulphate I in which Z is -O-S(O)(O)- may be obtained similarly to the cyclic sulphite but using sulphuryl chloride, bromide or fluoride instead of the thionyl halide.