GB788915A - Improvements in or relating to diquaternary compounds - Google Patents

Improvements in or relating to diquaternary compounds

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Publication number
GB788915A
GB788915A GB648654A GB648654A GB788915A GB 788915 A GB788915 A GB 788915A GB 648654 A GB648654 A GB 648654A GB 648654 A GB648654 A GB 648654A GB 788915 A GB788915 A GB 788915A
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GB
United Kingdom
Prior art keywords
carbon atoms
nitrogen atom
methyl
formula
compounds
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
GB648654A
Inventor
Donald Wallace Adamson
John Evlyn Warner Billinghurst
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Wellcome Foundation Ltd
Original Assignee
Wellcome Foundation Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Wellcome Foundation Ltd filed Critical Wellcome Foundation Ltd
Priority to GB648654A priority Critical patent/GB788915A/en
Publication of GB788915A publication Critical patent/GB788915A/en
Expired legal-status Critical Current

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D295/00Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/12Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
    • C07D295/125Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/13Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

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.
GB648654A 1954-03-05 1954-03-05 Improvements in or relating to diquaternary compounds Expired GB788915A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
GB648654A GB788915A (en) 1954-03-05 1954-03-05 Improvements in or relating to diquaternary compounds

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB648654A GB788915A (en) 1954-03-05 1954-03-05 Improvements in or relating to diquaternary compounds

Publications (1)

Publication Number Publication Date
GB788915A true GB788915A (en) 1958-01-08

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GB648654A Expired GB788915A (en) 1954-03-05 1954-03-05 Improvements in or relating to diquaternary compounds

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GB (1) GB788915A (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999051578A1 (en) * 1998-04-02 1999-10-14 Janssen Pharmaceutica N.V. Biocidal benzylbiphenyl derivatives
EP1433775A2 (en) * 2002-12-26 2004-06-30 Mitsubishi Gas Chemical Company, Inc. Modified chain aliphatic polyamine
US20140194640A1 (en) * 2012-05-30 2014-07-10 Luz Amalia Rios Vasquez Quaternary n-(halomethyl) ammonium salts as therapeutic agents

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6440440B1 (en) 1998-02-04 2002-08-27 Lieven Meerpoel Biocidal benzylbiphenyl derivatives
WO1999051578A1 (en) * 1998-04-02 1999-10-14 Janssen Pharmaceutica N.V. Biocidal benzylbiphenyl derivatives
EP1433775A2 (en) * 2002-12-26 2004-06-30 Mitsubishi Gas Chemical Company, Inc. Modified chain aliphatic polyamine
EP1433775A3 (en) * 2002-12-26 2004-07-21 Mitsubishi Gas Chemical Company, Inc. Modified chain aliphatic polyamine
US7473806B2 (en) 2002-12-26 2009-01-06 Mitsubishi Gas Chemical Company, Inc. Modified chain aliphatic polyamine
US20140194640A1 (en) * 2012-05-30 2014-07-10 Luz Amalia Rios Vasquez Quaternary n-(halomethyl) ammonium salts as therapeutic agents
US9145352B2 (en) * 2012-05-30 2015-09-29 Universidad De Caldas Quaternary N-(halomethyl) ammonium salts as therapeutic agents

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