Patent GB-777718-A (GB)
Title: New organic compounds containing phosphorus and process for making them
IPC: C07F9/40
Filed: 1954-04-13
Abstract: The invention comprises as new products organic compounds containing phosphorus having the formula <FORM:0777718/IV(b)/1> in which R to R4 represent alkyl, cycloalkyl, aralkyl, aryl, or heterocyclic residues which may contain substituents, and etherified or esterified derivatives thereof.  The alkyl residues may be straight or branched chain and may contain substituents, specified groups being methyl, ethyl, propyl, isopropyl, butyl, hexyl, 2-ethyl butyl, octyl, 2-butyloctyl, lauryl, octadecyl and 2-chloroethyl radicals, also alkyl groups substituted by thiocyano, cyano, or ester groups.  The residues R to R4 may be the same or different.  When they are aromatic residues they may be mononuclear or polynuclear and may contain nuclear substituents, specified aromatic residues being phenyl, 2- and 4-chlorophenyl, 2:4-dichlorophenyl, 4-methoxyphenyl, 4-nitrophenyl, naphthyl and 4-diphenyl groups.  Other residues specified are benzyl, cyclohexyl, and tetrahydrofurfuryl.  The products may be obtained by condensing a compound of the formula (R1O)(R2O)P(O).C(R)(O) with a compound of the formula H.P.(O)(OR3)(OR4) in the presence of an alkaline condensing agent, e.g. a tertiary amine such as triethylamine or tributylamine or an alkali metal or alkaline earth metal salt of a weak acid, e.g. potassium carbonate, barium acetate, or sodium acetate or an alkali metal alcoholate such as sodium methylate. Instead of using an alkaline condensing agent the compound H.P(O)(OR3)(OR4) may be used in the form of an alkali metal salt of the formula Me.P.(O)(OR3)(OR4) where Me is an alkali metal and the alcoholate first formed subsequently hydrolysed to the corresponding alcohol.  The hydrolysis may be effected by passing a stream of humid air through the reaction mixture.  When the radicals R1 to R4 are identical the products may be obtained by reacting two moles. of a compound of the formula (R1O)-(R2O)P(O)(Me where Me is a monovalent metal with one mole. of a carboxylic acid halide of the formula Hal.CO.R. and then hydrolysing the alcoholate first formed, e.g. with humid air, to the corresponding alcohol.  The reactions may be carried out in an inert solvent, e.g. benzene, toluene, ether, dioxane, hexane, or low boiling benzine.  Suitable reaction temperatures are 40-120 DEG  C. and the products can be distilled off under reduced pressure.  The hydroxyl group in the products may be converted to other groups, e.g. it may be esterified or etherified.  Examples are given for the production of compounds of the above formula in which R1 to R4 are ethyl groups and (1) R is CH3; (2) R is -CH2.CH3; (3) R is C6H5 and the benzoyl ester of this product; (4) R is Cl.CH2-; (5) R is Cl2CH-; and (6) R is CCl3-.  The product in which R1 to R4 are ethyl groups and R is CH3 is stated to have a strong inhibiting action on serum cholinesterase (see Group VI).  It is stated that some of the products may be used as additives to lubricants and that some of the products can be incorporated as active substances in preparation for combating pests.  The compounds of the formula (R1.O)(R2O)P(O).C(R)(O) may be obtained by reacting a compound of the formula (R1O)(R2O)P.OMe where Me is an atom of a monovalent metal with a carboxylic acid halide of the formula Hal-CO.R.ALSO:Some of the phosphorus-containing organic compounds corresponding to the general formula:-  <FORM:0777718/VI/1> in which R to R4 represent alkyl, cycloalkyl, aralkyl, aryl, or heterocyclic residues which may contain substituents, and etherified or esterified derivatives thereof (see Group IVb) may be incorporated as active substances in preparations for p  combating pests while others are stated to have utility in the pharmaceutical field, e.g. for inhibiting serum cholinesterase. The compound 1 : 1 - diphosphonic acid diethyl ester-ethanol, i.e. the compound of the above formula in which R1 to R4 are ethyl and R is CH3 on topical application to the eye strongly inhibits serum cholinesterase.  The alkyl residues in the products may be straight or branched chain and may contain substituents, specified groups being methyl, ethyl, propyl, isopropyl, butyl, hexyl, 2 - ethyl butyl, octyl, 2 - butyloctyl, lauryl, octadecyl and 2 - chloroethyl radicals, also alkyl groups substituted by thiocyana, cyano, or ester groups.  When the groups R to R4 are aromatic they may be mononuclear or polynuclear and may contain nuclear substituents, specified aromatic residues being phenyl, 2 - and - 4 - chlorophenyl, 2 : 4 - dichlorophenyl, 4 - methoxyphenyl, 4 - nitrophenyl, naphthyl and 4 - dipenyl groups.  Other residues specified are benzyl, cyclohexyl, and tetra-hydrofurfuryl.  Other products of the above general formula which are specified are those in which R1 to R4 are ethyl groups and (1) R - CH2, CH3; (2) R is C6 H5 and the benzoyl ester of this product; (3) R is Cl. CH2; (4) R is Cl2 CH-; and (5) is CCl3.