Patent GB-819735-A (GB)
Title: Quaternary ammonium salts of dialkylaminoalkyl thiophosphate esters
IPC: C07F9/165
Filed: 1956-05-09
Abstract: The invention comprises quaternary ammonium halides and sulphates of dialkylaminoalkyl thiophosphates of the formula <FORM:0819735/IV (b)/1> wherein R, R1 and R2 are alkyl groups, R3 is hydrogen, alkyl, or substituted alkyl (e.g. dialkylaminoalkyl), X is sulphur or oxygen, at least one X being sulphur, and n is 1, 2, or 3.  They may be obtained by treating a dialkylamino alkyl thiophosphate ester of the above formula dissolved in a suitable solvent with an alkyl halide, e.g. methyl iodide or a dialkyl sulphate, e.g. dimethyl sulphate in accordance with methods known for the conversion of tertiary bases into quaternary ammonium salts.  If the quaternary salt is soluble in the solvent used it may be precipitated by the addition of a non-solvent.  Quaternary salts of esters in which R3 in the formula is H may also be obtained by causing a b -halogenoethanol or an alkali metal salt thereof to react with a thionophosphoryl halide and reacting the resulting b -halogenoethyl ester with a trialkylamine to give a quaternary ammonium halide salt.  The basic esters used to form the quaternary salts may be obtained by causing an alkali metal salt of a b -dialkylaminoethanol or of an appropriately substituted b -dialkylaminoethanol to react with a thionophosphoryl halide.  The alkali metal salt may be dissolved or suspended in an inert solvent such as benzene or toluene and an excess of the b -dialkylaminoethanol may be used in some cases to aid in solution of the alkali metal salt.  The thionophosphoryl halide may be the trihalide, a monoalkoxy thionophosphoryl dihalide or a dialkoxythionophosphoryl monohalide to give products containing three, two, or one b -dialkylaminoethyl (or substituted ethyl) ester groups, respectively.  Crude mixtures of monoalkoxy thionophosphoryl dihalides and dialkoxy thionophosphoryl monohalides obtained by reacting a thionophosphoryl trihalide with an alcohol or alkali metal alcohoholate may also be employed.  The thionophosphates obtained will generally contain greater or lesser amounts of the isomeric thiolphosphates.  The thiol esters may also be prepared by reacting an alkali metal salt of a dialkylaminoethyl (or appropriately substituted ethyl) mercaptan with a phosphoryl halide (or alkoxy halide) or thionophosphoryl halide (or alkoxy halide) or by reacting a dialkylaminoethyl (or appropriately substituted substituted ethyl) halide with an appropriate thiolothionophosphate ester, the products of the last two methods being the thiolthiono phosphate esters. Examples are given for the production of (1) (CH3)2NCH2CH2OP(S) (OC2H5)2, its acid oxalate salt, its methomethylsulphate, and its methiodide, methobromide and methochloride; (2) (CH3)2NCH2CH2SP(O) (OC2H5)2, its acid oxalate salt and its methiodide; (3) (CH3)2 NCH2CH2OP(S)(OCH3)2 and its methiodide; (4) (CH3)2NCH2CH2OP(S) (OC3H7)2, its acid oxalate and its methiodide; (5) (CH3)2NCH2 CH2OP(S)(OCH(CH3)2)2 and its methiodide; (6) (CH3)2NCH2CH2OP(S) (OC4H9)2, its acid oxalate and methiodide; (7) (CH3)2NCH2 CH2SP(O)(OC4H9)2, its acid oxalate and methiodide; (8) (CH3)2NCH2CH(CH3)OP(S) (OC2H5)2 its acid oxalate and methiodide; (9) [(CH3)2 NCH2]2CHOP(S)(OC2H5)2 its di-acid oxalate and dimethiodide; (10) [(CH3)2NCH2CH2O]2 P(S)OC2Hr, its di-acid oxalate and dimethiodide; (11) [(CH3)2NCH2CH2O]2P(S) OC7H18 and its dimethiodide; (12) [(CH3)2NCH2CH2O]3 P(S), its tri-acid oxalate and trimethiodide; (13) (C2H5)2NCH2CH2OP(S) (OC2H5)2 and its methomethyl sulphate; (14) the acid oxalate and methomethyl sulphate of (C2H5)2NCH2CH2 SP(O)(OC2H5)2; (15) (CH3)2NCH2CH2OP(S) (OC2H4)(OC5H9) its acid oxalate and methiodide; (16) (CH3)2NCH2CH2SP(S) (OC2H5)2, its acid oxalate and methiodide; and (17) (CH3)2NCH2CH2SP(S) [OCH(CH3)2]2, its acid oxalate and methiodide. The quaternary ammonium salt products are stated to show a prolonged inhibition of cholinesterase and to be suitable for topical application to the eye.  They are also useful as insecticidal agents.  Specifications 738,839 and 740,563 are referred to.