Patent GB-802870-A (GB)
Title: Improvements in and relating to diquaternary compounds and the manufacture thereof
Inventor: BILLINGHURST JOHN EVLYN WARNER
IPC: C07D295/12
Filed: 1955-06-30
Abstract: The invention comprises compounds of the general formula <FORM:0802870/IV (b)/1> wherein R1 and R2 are the same or different and are each a cyclo-alkyl group, for example a cyclohexyl group or a phenyl group which may carry one or more substituents, said substituents being halogen atoms, for example chlorine or bromine atoms or lower alkyl groups defined as alkyl groups containing not more than four carbon atoms, for example methyl groups; n is an integer from two to ten; N+1 is a quaternary nitrogen atom carrying two alkyl groups together having up to five carbon atoms, preferably two or three carbon atoms; N+2 is a quaternary nitrogen carrying at least one alkyl group having from one to four carbon atoms and either carrying two further alkyl groups giving a total of up to nine carbon atoms, preferably a total of three to six carbon atoms, or forming part of a pyrrolidino, piperidino or morpholino ring; Y is an alkylene chain having from two to ten carbon atoms, preferably two to six carbon atoms; or N+1-Y-N+2 may be a piperazine ring in which N+1 is a quaternary nitrogen atom carrying one alkyl group having up to four carbon atoms and N+2 is a quaternary nitrogen atom carrying two alkyl groups having a total of up to four carbon atoms, the total number of carbon atoms in the alkyl groups not exceeding six; and A- is an equivalent of the anion of an inorganic or organic acid which may be, for example, halide or alkyl sulphate.  The above compounds are produced by treating a diamine of the general formula <FORM:0802870/IV (b)/2> with a quaternizing agent such as a lower alkyl halide or lower dialkyl sulphate, R1, R2, Y and n have the meanings given above, N3 and N4 are tertiary nitrogen atoms or N3-Y-N4 is a piperazine ring, the substituents provided by the quaternizing agent, together with any substituents on N3 and N4 being such as will give the desired substitution in the compound of the first formula above.  Examples relate to the preparation of N1-(2-benzhydroloxyethyl)-N2 : N2 - diethyl - N1 : N1 : N2 - trimethylethylene - 1 : 2 - diammonium di - iodide (1); N1 - (3 - benzhydryloxypropyl) - N2 : N2 - diethyl - N1 : N1 : N2 - trimethylethylene - 1 : 2 diammonium di - iodide (2); N1 - (3 - benzhydryloxypropyl) - N1 : N1 : N2 - trimethylethylene - 1 - ammonium - 2 - piperidinium di-iodide (3); N1-(4-benzhydryloxybutyl)-N2-trimethylpiperazinium di-iodide (4); N1-(4-benzhydryloxybutyl) - N2 : N2 - di - n - butyl-N1 : N1 : N2 - trimethylethylene - 1 : 2 - diammonium di-iodide (5); N1-(4-benzhydryloxybutyl) - N1 : N1 : N2 - trimethylethylene - 1 - ammonium - 2 - pyrrolidinium di - iodide (6); N1 - (4 - benzhydryloxybutyl) - N1 : N1 : N2-trimethylethylene - 1 - ammonium - 2 - piperidinium di - iodide (7); N1 - benzhydryloxybutyl - N1 : N1 : N2 - trimethylethylene - 1 - ammonium - 2 - morpholinium di - iodide (8); N2 : N2 - diethyl - N1 : N1 : N2 - trimethyl - N1-[4 - di - (4 - methylphenyl) methoxybutyl] - ethylene - 1 : 2 - diammonium diiodide (9); N2 : N2 - diethyl - N1 : N1 : N2 - trimethyl - N1-[4 - di - (2 - methylphenyl) methoxybutyl]-ethylene - 1 : 2 - di - ammonium di - iodide (10); N1 - (4 - benhydryloxybutyl) - N1 : N1 : N2\h - trimethylhexamethylene - 1 - ammonium - 6 - morpholinium di-iodide (11); N1-(3-benzhydryloxypropyl) - N1 : N1 : N2 - trimethylethylene-1-ammonium-2-morpholinium dichloride (12); N1 - (4 - benzhydryloxybutyl) - N2 : N2 - diethyl - N1 : N1 : N2 - trimethylethylene - 1 : 2 diammonium diiodide (13); N1-[6-(4-methylphenyl) 6-phenyl-5-oxahexyl]-N1 : N1 : N2-trimethylethylene - 1 - ammonium - 2 - morpholinium di-iodide monohydrate (14); N1-[4-di - (4 - chlorophenyl) methoxybutyl] - N1 : N1 : N2 - trimethylethylene-1 - ammonium-2 - piperidinium di - iodide (15); N2 : N2 - diethyl - N1 - (4 - dicyclohexylmethoxybutyl) - N1 : N1 : N2 - trimethylethylene - 1 : 2 - diammonium di-iodide (16); N1-(3-benzhydryloxypropyl) - N1 : N1 : N2 - trimethyltrimethylene-1 - ammonium - 3 - morpholinium di - iodide (17); N1-(4-benzhydryloxybutyl)-N1 : N1 : N2-trimethyltrimethylene - 1 - ammonium - 3 - morpholinium diiodide and dichloride (18); and N1 - (4 - benzhydryloxybutyl) - N1 : N2 : N2 : N2 - tetraethyl - N1 - methylethylene - 1 : 2-diammonium di-iodide (19).  Benzhydryl compounds employed as starting materials are obtained either by reacting appropriate benzhydrols and chlorohydrins to prepare benzhydryl chloroalkyl ethers and reacting the latter with appropriately substituted diamines or by reacting appropriate benzhydryl amino alkyl ethers with amino alkyl halides.  4 - (N - 2 - diethylaminoethyl - N - methyl) amino butyl dicyclohexylmethyl ether is obtained by catalytic hydrogenation of the corresponding diphenyl compound.