Patent GB-787279-A (GB)
Title: Improvements in and relating to diquaternary compounds and the manufacture thereof
Inventor: BILLINGHURST JOHN EVLYN WARNER
IPC: C07D295/12
Filed: 1955-06-08
Abstract: The invention comprises diquaternary compounds of the general formula <FORM:0787279/IV (b)/1> wherein R1 and R2 are the same or different and are each a cycloalkyl group or a phenyl group which may optionally be substituted by one or more halogen, lower alkyl or lower alkoxy substituents ; X is (CH2)n or (CH2)2.O.(CH2)2, n being an integer from 2 to 10 ; N+1 is a quaternary nitrogen atom carrying two alkyl groups having together up to 5 carbon atoms, preferably 2 or 3 carbon atoms, or which together form part of a pyrrolidino, piperidino or morpholino ring; N+2 is a quaternary nitrogen atom carrying at least one alkyl group of 1 to 4 carbon atoms and either two further alkyl groups of a total of up to 9 carbon atoms, preferably 3 to 6 carbon atoms, or forming part of a pyrrolidino piperidino or morpholino ring ; Y is an alkylene chain of 2 to 10, preferably 2 to 6, carbon atoms, or N+1-Y-N+2 is a piperazine ring in which N+1 is a quaternary nitrogen atom carrying an alkyl group of up to 4 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 6, and A- is the anion of an inorganic or organic acid which may be, for example, a halide or alkyl sulphate.  The compounds are made by treating a diamine of the formula <FORM:0787279/IV (b)/2> wherein N3 is a secondary or tertiary nitrogen atom and N4 is a primary, tertiary or quaternary nitrogen atom, with a quaternizing agent such as an alkyl halide or dialkyl sulphate. Preferred products include the di-quaternary salts, e.g. di-iodides, of N1-(5-cyano-5 : 5-diphenylpentyl) - N1:N1:N2 - trimethyl - ethylene - 1 - ammonium - 2 - morpholine ; N1 - (6 - cyano - 6 : 6 - diphenylhexyl) - N1:N1:N2 - trimethylethylene - 1 - ammonium - 2 - morpholine ; N1-(6 - cyano - 6 : 6 - diphenyl - 3 - oxahexyl) - N1 : N1 : N2 - trimethyl - ethylene - 1 - ammo nium - 2 - morpholine ; N1 - (3 - cyano - 3 : 3 - diphenylpropyl) - N1:N1:N2 - trimethyl -ethylene - 1 - ammonium - 2 - morpholine and N1-(5 - cyano - 5 : 5 - diphenylpentyl) - N1:N1:N2-trimethyl - trimethylene - 1 - ammonium - 3 - morpholine. Examples describe the preparation of many compounds of formula I in which R1 and R2 are chosen from phenyl, p-methylphenyl, p-chlorophenyl, p-methoxyphenyl and cyclohexyl radicals, X is a propane, butane, pentane, hexane, heptane, octane or 3-oxahexane residue, Y is an ethane, propane or hexane residue, or N+1-Y-N+2 forms a piperazine ring, and the quaternary nitrogen atoms carry substituents as defined above.  Starting materials.  Compounds of the formula II, where N3 is a secondary or tertiary nitrogen atom and N4 is a tertiary nitrogen atom are made by treating a halo-alkyl acetonitrile of the formula <FORM:0787279/IV (b)/3> wherein Z is a halogen atom, with a diamine of the formula N5-Y-N4, where N5 is a primary or secondary nitrogen atom.  Compounds of the formula II, wherein Y represents two or three or six to ten methylene groups, may be prepared by reaction of an aminonitrile of the formula <FORM:0787279/IV (b)/4> with a halogenoamine of the formula Z-Y-N4. Specified diamines include, for example, N1-3-cyano - 3 : 3 - diphenyl - N2 - methylpiperazine, 5 - (N - 2 - di - n - butylaminoethyl - N - methyl) amino - 1 - cyano - 1 : 1 - diphenylpentane, 1 - cyano - 5 - (N - methyl - N - 2 - piperidinoethyl) amino - 1 : 1 - diphenylpentane, 1 - cyano - 5 - (N - methyl - N - 2 - morpholinoethyl) amino - 1 : 1 - diphenylpentane, 1 - cyano - 6 - (N - 2 - diethylaminoethyl - N - methylamino - 1 : 1 - diphenylhexane and many other diamines of the general formula II. Haloalkyl acetonitriles of the formula III are made by treating an acetonitrile of the formula R1(R2)CH.CN with a polymethylene a :o -dihalide Z-X-Z.  Specified haloalkylacetonitriles include 5-chloro-1-cyano-1 : 1 - diphenylpentane, 6 - chloro - 1 - cyano - 1 : 1 - diphenylhexane, 3 - bromo - 1 - cyano - 1 : 1-diphenylpropane, 4 - chloro - 1 - cyano - 1 : 1 - diphenylbutane, 5 - chloro - 1 - cyano - 1 - (4 - methylphenyl) - 1 - phenylpentane, 5 - chloro - 1 - cyclohexyl - 1 - phenylpentane and 6 - chloro - 1 - cyano - 1 : 1 - diphenyl - 4 - oxahexane.  N1-2-Chloroethyl - N2 - methylpiperazine hydrochloride is made by treating N1-2-hydroxyethyl-N2-methylpiperazine with thionyl chloride. 1-Bromo-6-piperidinohexan is made by treating 1-phenoxy-6-piperidinohexane with hydrobromic acid.