Patent GB-788915-A (GB)
Title: Improvements in or relating to diquaternary compounds
Inventor: ADAMSON DONALD WALLACE
IPC: C07D295/13
Filed: 1954-03-05
Abstract: The invention comprises compounds of the formula <FORM:0788915/IV (b)/1> wherein X is C=CH or CH.CH2, R1 and R2 are the same or different and are each a cycloalkyl 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), phenyl or lower alkyl groups having from 1 to 4 carbon atoms or lower alkoxy groups having from 1 to 4 carbon atoms, the total number of carbon atoms in the alkyl and/or alkoxy groups present on either of the phenyl groups not exceeding four; n is an integer from 1 to 9; +N1 is a quaternary nitrogen atom either carrying two alkyl groups together having up to 5 carbon atoms, preferably 2 or 3 carbon atoms, or forming part of a pyrrolidino, piperidino or morpholino ring; +N2 is a quaternary nitrogen atom carrying at least one alkyl group having from 1 to 4 carbon atoms and either carrying two further alkyl groups having a total of up to nine carbon atoms, preferably a total of 3 to 6 carbon atoms, or forming part of a pyrrolidino, piperidino or morpholino ring; Y is an alkylene chain having from 2 to 10 carbon atoms, preferably 2 to 6 carbon atoms, or +N1-Y-+N2 may be a piperazine ring in which +N1 is a quaternary nitrogen atom carrying one alkyl group having up to 4 carbon atoms and +N2 is a quaternary nitrogen atom carrying two alkyl groups having a total of up to 4 carbon atoms, the total number of carbon atoms in the alkyl groups not exceeding 6; and A- is an anion of an inorganic or organic acid which may be, for example, halide or alkyl sulphate.  Such compounds may be obtained by quaternisation of a diamine of the formula (II) R1R2X.(CH2)n-N3-Y-N4 in which N3 is a secondary, tertiary or quaternary nitrogen atom and N4 is a primary or tertiary or quaternary nitrogen atom when N3 is a secondary or tertiary nitrogen atom, or a primary or tertiary nitrogen atom when N3 is a quaternary nitrogen atom, the substituents provided by the quaternizing agent together with any substituents on N3 and N4 being such as will give the desired substituents in compound I.  Except in the case of the piperazine derivatives the products can also be obtained by reacting a compound of the formula Z-Y-N2.A- (where Z is halogen) with a compound of the general formula R1R2X(CH2)n.N5, where N5 is a tertiary nitrogen atom.  Compounds of formula I where X is C : CH may be prepared by dehydration of the products of Specification 788,914, for example by heating with dilute hydrochloric acid. Compounds of formula I where X is CH.CH2 can be obtained by hydrogenation of compounds of formula I, where X is C : CH2 in the presence of a catalyst such as palladized charcoal which does not promote hydrogenation of phenyl groups.  Compounds containing a particular anion A- may be converted to other salts, e.g. by treatment with silver chloride or by conversion to the hydroxide (using an ion-exchange resin) followed by salt formation.  Compounds of formula II where N4 is a primary nitrogen atom may be obtained by reaction of a compound of the formula Z(CH2)mCN (where m is an integer from 2 to 9) with the appropriate primary, secondary or tertiary amine, followed by reduction of the nitrile group.  Other compounds of formula II are obtainable by reacting a compound R1R2X(CH2)nBr with the appropriate diamine (or alkylation product thereof).  If N3 is a quaternary nitrogen atom and N4 is a tertiary nitrogen atom, compounds of formula II can be obtained by the reaction of compounds of the formula <FORM:0788915/IV (b)/2> and HNR6R7, where q is an integer from 2 to 10 and R6 and R7 are alkyl groups or NR6R7 is a pyrrolidino, piperidino or morpholino ring.  In examples: (1) N1-3-hydroxy-3 : 3-diphenylpropyl-N2-methylpiperazine is heated in a mixture of acetic and hydrochloric acids to give N2-methyl - N1 - 3 : 3 - diphenylprop - 2 - enyl-piperazine, which is quaternated with methyl iodide to form N1 : N2 : N2-trimethyl-N1-(3 : 3-diphenylprop - 2 - enyl) piperazinium diiodide; (4) N1 : N1 : N2 - trimethyl - N1 - (3 : 3 - diphenylprop - 2 - enyl) - ethylene - 1 - ammonium - 2 - pyrrolidinium diiodide is prepared either by a method analogous to that of Example (1) or by dehydration of N1-(3-hydroxy-3 : 3-diphenylpropyl) - N1 : N1 : N2 - trimethyl-ethylene - 1 - ammonium - 2 - pyrrolidinium diiodide; (10) 6 - (N - 2 - diethylaminoethyl - N - methyl) amino - 1 : 1 - diphenylhex - 1 - ene is prepared by dehydration of the appropriate carbinol or by reacting 6-bromo-1 : 1-diphenyl-hex - 1 - ene with N - (2 - diethylaminoethyl) - N-methylamine and is then quaternated with methyl iodide; (32) 3-(N-3-diethylaminopropyl-N-methyl)-amino-1 : 1-diphenylprop-1-ene (prepared by reacting 3-methylamino-1 : 1-diphenylprop - 1 - ene, 3 - bromo - 1 - diethylamino - propane hydrobromide and triethylamine) is quaternated by reaction with methyl iodide; (35) N1 : N2 : N2 - trimethyl - N1 - (3 : 3 - diphenylpropyl) piperazinium diiodide is prepared by quaternation with methyl iodide of the corresponding base (prepared from N-methyl-piperazine and 3 : 3-diphenylpropyl chloride; (36) 3-bromo-1 : 1-diphenylpropane and N-(2-diethylaminoethyl)-N-methylamine are reacted to give 3-(N-2-diethylaminoethyl-N-methyl)-amino - 1 : 1 - diphenylpropane which is quaternated with methyl iodide; (37) N-2-bromoethyl - N : N - dimethyl - N - 3 : 3 - diphenylpropylammonium bromide and triethylamine are reacted to give N2 : N2 : N2 - triethyl-N1 : N1 - dimethyl - N1 - (3 : 3 - diphenylpropyl) ethylene - 1 : 2 - diammonium dibromide; (39) N1 : N1 : N2 - trimethyl - N1 - (3 : 3 - diphenylpropyl) ethylene - 1 - ammonium - 2 - piperidinium di-iodide is prepared either by quaternation of the corresponding base (obtained by hydrogenation of the corresponding prop-1-ene derivative) or by reacting N-2-bromethyl-N : N-dimethyl - N - 3 : 3 - diphenylpropylammonium bromide (from 3-dimethylamino-1 : 1-diphenylpropane and ethylene dibromide) with piperidine; (59) 5-(N-2-diethylaminoethyl-N-methyl) amino - 1 - cyclohexyl - 1 - phenylhexane (from the catalytic hydrogenation of 6-(N-2-diethylaminoethyl - N - methyl) - amino - 1 : 1 - diphenylhex-1-ene) is quaternated with methyl iodide; (61) N1 : N1 : N2 : N2 : N2-pentamethyl-N1 - (3 : 3 - diphenylpropyl) - trimethylene - 1 : 3-diammonium diiodide is prepared by reacting 3-dimethylamino - 1 : 1 - diphenylpropane with 3 - chloropropyltrimethylammonium bromide; (62) N2 : N2 : N2 - trimethyl - N1 - (6 : 6 - diphenylhexyl) - trimethylene - 3 - ammonium - 1-pyrrolidinium dichloride is prepared by hydrogenation of the corresponding hex-5-ene derivative; (64) 5-bromovaleronitrile and 3-methylamino - 1 : 1 - diphenylpropane (from 3 - bromo - 1 : 1 - diphenylpropane and methylamine) are reacted to give 3-(N-4-cyanobutyl-N-methyl) amino-1 : 1-diphenyl propane.  This is reduced with lithium aluminium hydride to 3 - (N - 5 - amino - pentyl - N - methyl) - 1 : 1 - diphenylpropane, quaternation of which gives N1 : N1 : N2 : N2 : N2 - pentamethyl - N1 - (3 : 3 - diphenylpropyl) pentamethylene - 1 : 5 - diammonium diiodide; (66) 1-bromo-6-diethylaminohexane and 3 - methylamino - 1 : 1 - diphenylpropane are reacted to give 3-(N-6-diethylaminohexyl - N - methyl) amino - 1 : 1 - diphenylpropane which is then quaternated with methyl iodide. Additional examples illustrate the preparation of similar compounds containing radicals corresponding to those present in the carbinols prepared in the examples of Specification 788,914. Specifications 682,160 and 683,950 also are referred to.