Patent GB-761107-A (GB)
Title: Carbamic acid ester compounds and a process of producing the same
IPC: C07C271/06
Filed: 1954-06-18
Abstract: A process of producing new polymethylene-and phenylene-bis-carbamie acid ester derivatives of the general formula <FORM:0761107/IV(b)/1> wherein R1 and R2 are alkyl radicals of 1 to 4 carbon atoms, cyclohexyl or benzyl radicals, A is an ethylene radical or phenylene radical and B is a polymethylene radical with more than 2 and preferably 4 to 10 CH2 groups or a phenylene radical, comprises reacting an organic diisocyanate of the polymethylene series or of phenylene isomers of the formula O = C = N.B.N = C = O or polymethylene or phenylene dicarboxylic acid diazides or dicarbamic acid dichlorides with compounds of the general formula R1R2N.A.OH. The products can be converted to the corresponding bis-quaternary compounds of the formula <FORM:0761107/IV(b)/2> where R3 is an alkyl radical of 1 to 4 carbon atoms, a cyclohexyl radical or a benzyl radical and X is an anion by reaction with R3X.  The organic di-isocyanates correspond to the formula O = C = N(CH2)yN = C = O or O : C : N.C6H4 N : C : O, the diazides to the formul  N3.OC. (CH2)y.CO.N3 and N3.OC.C6H4.CO.N3 and the dicarbamic acid chlorides have the formul  Cl.CO.NH(CH2)yNH.CO.Cl and Cl.CO.NH.C6H4.NH.CO.Cl. The amino-alcohols include dimethyl or diethylamino-ethanol, cyclohexyl alkyl aminoethanol, benzyl alkylamino ethanol, cyclohexyl benzyl aminoethanol, dicyclohexyl aminoethanol and dibenzyl aminoethanol. Tertiary aminophenols may be substituted by alkyl, cyclohexyl or benzyl radicals.  Lists are given of such starting materials and of chlorides, sulphates and sulphonic acid esters for use as quaternating agents, additional to those shown in the Examples. In Example (1) tetramethylene di-isocyanate and b -dimethylamino ethanol are reacted to form tetramethylene bis-(carbamic acid-b -dimethylamino ethyl ester) which on reaction with methyl iodide gives tetramethylene bis-(carbamic acid chloline iodide ester).  In similar examples there are prepared (2) octamethylene bis-(carbamic acid-b -dimethylamino ethyl ester); (4) the corresponding diethylamino ester; (5) decamethylene bis-(carbamic acid-b -dimethylaminoethyl ester); (6) octamethylene bis-(carbamic acid m-dimethylamino phenylester; (7) p-phenylene bis-(carbamic acid-b -dimethylamino ethyl ester); (8) hexamethylene bis-(carbamic acid-b -dimethylamino ethyl ester); (12) tetramethylene bis-(carbamic acid-b -diethylamino ethyl ester; (14) hexamethylene bis-(carbamic acid-b -diethylamino ethyl ester); (15) p-phenylene-bis-(carbamic acid-b -diethylamino ethyl ester); (17) m-phenylene bis-(carbamic acid-b -dimethylamino ethyl ester); (18) m-phenylene bis-(carbamic acid-b -diethylaminoethyl ester); (19) tetramethylene bis-(carbamic acid-m-dimethylamino phenyl ester); (20) hexamethylene bis-(carbamic acid-m-dimethylaminophenyl ester); (22) decamethylene bis-(carbamic acid-m-dimethylamino phenyl ester); (24) hexamethylene bis-(carbamic acid - b  - dicyclohexylamino ethyl ester); (25) tetramethylene bis-carbamic acid-b -di-n-butylamino ethyl ester).  The quaternation of such compounds is described either as part of the above examples or as separate examples.  The quaternation of the above products is effected variously with methyl iodide, methyl chloride, methyl bromide, ethyl bromide, ethyl iodide and ethyl or methyl p-toluene sulphonates.  The quaternary compounds are muscle relaxants.ALSO:Compounds of the formula:-<FORM:0761107/VI/1> in which R1, R2 and R3 are alkyl radicals with 1 to 4 carbon atoms, cyclohexyl or benzyl radicals, A is an ethylene radical or a phenylene radical and B is a polymethylene radical with more than 2 and preferably 4 to 10 CH2 groups or a phenylene radical and X is an anion are used as muscle relaxants. They may be used as solutions in isotonic aqueous solutions.  For intravenous injection a solution of hexamethylene bis - carbamic acid choline bromide ester) was mixed with a solution of thiopentone sodium no precipitation of the barbiturate taking place. The preparation of the quaternary compounds and corresponding tertiary bases is described (see Group IV(b)).