Patent GB-1236956-A (GB)
Title: Epoxypropylphosphonic and thiophosphonic acid derivatives
Inventor: CHRISTENSEN BURTON GRANT
IPC: C07F9/6587
Filed: 1968-10-24
Abstract: 1,236,956.  (cis 1,2 - Epoxypropyl) - phosphonic acid derivatives. MERCK & CO. Inc. 24 Oct., 1968 [15 May, 1968], No. 50634/68. Heading C2C. The invention comprises a mixture of the (+) and (-) enantiomers of (cis 1,2-epoxypropyl)-phosphonic acid compounds of the formula in which X is O or S, Y is -OR, -SR, -NR 1 R 2  or halogen and Z is -OR, -SR, -NR 1 R 2  or halogen, with the proviso that at least one of Y and Z is other than -OR when X is oxygen, R is H or a substituted or unsubstituted hydrocarbyl or heterocyclic radical and each of R 1  and R 2  is H, a substituted or unsubstituted hydrocarbyl or heterocyclic radical or an acyl radical or NR 1 R 2 represents a heterocyclic amino group, also the cyclic derivatives of such compounds in which Y and Z are joined together by a divalent radical, e.g. polymethylene or arylene, and salts of such compounds in which at least one of Y and Z is -OH or -SH. The invention also comprises ( ) cis compounds of the formula or or in which X and Z are as defined above, A is -O-, -S- or -NR-, R 1  and R 2  when present in Z being a substituted or unsubstituted hydrocarbon or heterocyclic radical or an acyl radical, R 3  is H, an alkali or alkaline earth metal or C 1 -C 6  alkyl, with the proviso that at least one of X, Z and A is other than oxygen or an oxygen-containing radical. The compounds (I) may be obtained by the epoxidation of a compound of the formula with an oxidizing agent and compounds of Formul  (II), (III) and (IV) may be prepared by treating a compound of the formula or or with an oxidizing agent. Several suitable oxidizing agents are specified, the preferred agents being peroxy compounds such as H 2 O 2 , an inorganic or organic per acid (including optically active organic per acids), an organic hydroperoxide or peroxyimidic acid which may be formed in situ from H 2 O 2  and a nitrile. The compounds may also be obtained by reacting the corresponding cis-propenyl phosphonous acid derivatives with an oxidizing agent as above so as to convert the phosphorus atom from P<SP>III</SP> to P<SP>v</SP> and to epoxidize the olefinic double bond in the one reaction. The products when they are other than salts may be converted to salts, e.g. the Na, Ca, Mg, piperazine, ethylenediamine, benzylamine or phenethylamine salts. The cis-propenyl phosphonic compounds used as starting materials may be obtained from the cis-propenyl phosphonic (or thiophosphonic)-dichloride by reacting with an alcohol, thiol or amine, the reaction being carried out with more than one such reactant and in more than one stage as appropriate and when X in the products is sulphur the latter may be replaced by oxygen by treatment with peroxy-trifluoroacetic acid or with bromine water. The ( )(cis - 1,2 - epoxypropyl)-phosphonic acid and its salts and labile esters have antibacterial properties and may be administered orally, e.g. as capsules or tablets or in an orally administratable liquid solution or suspension. The formulations may be prepared from diluents, granulating agents, preservatives, binders, flavouring agents and coating agents. The agents may also be administered parenterally by injection in a sterile vehicle.