GB765591A - Esters of 4-amino-2-hydroxybenzoic acids mono-substituted at the nitrogen atom and aprocess for their production - Google Patents

Esters of 4-amino-2-hydroxybenzoic acids mono-substituted at the nitrogen atom and aprocess for their production

Info

Publication number
GB765591A
GB765591A GB24797/54A GB2479754A GB765591A GB 765591 A GB765591 A GB 765591A GB 24797/54 A GB24797/54 A GB 24797/54A GB 2479754 A GB2479754 A GB 2479754A GB 765591 A GB765591 A GB 765591A
Authority
GB
United Kingdom
Prior art keywords
amino
ester
hydroxybenzoic acid
methyl
diethylaminoethyl
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
GB24797/54A
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.)
Rheinpreussen AG fuer Bergbau und Chemie
Original Assignee
Rheinpreussen AG fuer Bergbau und Chemie
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 Rheinpreussen AG fuer Bergbau und Chemie filed Critical Rheinpreussen AG fuer Bergbau und Chemie
Publication of GB765591A publication Critical patent/GB765591A/en
Expired legal-status Critical Current

Links

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

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

Abstract

The invention comprises esters of a 4-amino-2-hydroxy-benzoic acid mono-substituted at the nitrogen atom having the general formula <FORM:0765591/IV(b)/1> in which X is an organic radical, Y is a straight or branched aliphatic carbon chain containing from 1 to 10 carbon atoms, and Z1 and Z2 are the same or different alkyl groups each of which contains from 1 to 6 carbon atoms, or Z1 is a hydrogen atom and Z2 is an alkyl group containing from 1 to 6 carbon atoms, or the grouping: <FORM:0765591/IV(b)/2> is a nitrogen containing heterocyclic radical. The radical X may be for example a methyl, ethyl, butyl, secondary amyl, benzyl, 3-(p-nitrophenyl) - propyl, p - tolyl, 3 - hydroxyphenyl -, b - dimethylaminoethyl, b - isopropyl-aminoethyl, 1 - methyl - 2 - methyl - 3 - diethyl-aminopropyl, b - piperidinoethyl or b - thiazolidinoethyl group; Z1 and Z2 may be groups such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl or hexyl or Z1, may be hydrogen and Z2 an alkyl group containing from 1 to 6 carbon atoms or the grouping: <FORM:0765591/IV(b)/3> may be the radical of a heterocyclic ring system, e.g. a piperidino, morpholino, thiazolidino or pyrrolidino group. The products of the invention may be obtained by reacting an ester of 4-amino-2-hydroxybenzoic acid in which the alcoholic ester component is one of the radicals defined under X, optionally in an anhydrous organic solvent such as isopropanol or secondary butanol and preferably in a non-polar solvent such as benzene, toluene or xylene, with an amino-substituted alkyl halide of the formula: <FORM:0765591/IV(b)/4> in which Hal is a halogen atom and Y, Z1 and Z2 are as defined above. Examples of amino-substituted alkyl halides mentioned include chloroethyldimethylamine, bromo- or chloroethyldiethylamine, 2 - chloro - 1 - dibutyl-amino - propane, 1 - bromo - 1 - methyl - 2-methyl - 3 - diethylamino - propane, 3 - isobutyl-amino-propyl chloride, piperidinoethyl iodide and morpholinoethyl iodide. When free 4-amino-2-hydroxybenzoic acids are reacted with an amino-substituted alkyl halide of the above kind and an organic solvent for both reactants is employed, e.g. isopropanol, the alkylaminoalkyl ester of the 4-amino-2-hydroxybenzoic acid is obtained together with the alkylaminoalkyl ester of 4 - (alkylaminoalkylamino) - 2 - hydroxybenzoic acid in which the ester group X is identical with the group: <FORM:0765591/IV(b)/5> The reactions are carried out by heating the reactants together under reflux or at elevated pressure. In examples: the methyl ester of 4 - (diethylaminoethylamino) - 2 - hydroxy benzoic acid is obtained by heating under reflux 4 - amino - 2 - hydroxy - benzoic acid methyl ester with diethylamino ethyl chloride in benzene, removing the benzene, extracting the product with dilute hydrochloric acid, adding ammonia to the extract and extracting the desired ester with isopropyl chloride, the hydrochloride and picrate are referred to (1); the n - propyl ester of 4 - (diethylaminoethyl-amino) - 2 - hydroxybenzoic acid is similarly prepared from the n-propyl ester of 4-amino-2-hydroxybenzoic acid and diethylaminoethyl chloride and the product is converted to the hydrochloride with ethanolic hydrochloric acid (2); the n-butyl ester of 4-(diethylaminoethyl-amino)-2-hydroxybenzoic acid is similarly prepared by heating the n-butyl ester of 4-amino-2-hydroxybenzoic acid in butyl acetate with diethylaminoethyl chloride and is converted into the hydrochloride (3); the b -diethylaminoethyl ester of 4-(diethyl aminoethylamino-2-hydroxybenzoic acid is similarly prepared by (a) heating the b -diethylaminoethyl ester of 4-amino-2-hydroxybenzoic acid with diethylamino ethyl chloride in benzene uder reflux, the mixture of esters obtained being converted to the corresponding hydrochlorides, the unchanged 4-amino - 2 - hydroxybenzoic acid b - diethyl-amino ethyl ester hydrochloride separated by fractional crystallization from water and the dihydrochloride of the desired product is obtained by concentrating the aqueous mother liquor and adding isopropanol; or (b) by boiling 4 - amino - 2 - hydroxybenzoic acid with diethylaminoethyl chloride and isopropanol under reflux, adding ammonia, extracting with isopropyl chloride, converting the extracted products to hydrochlorides and separating as described under (a) (4).ALSO:A pharmaceutical composition comprises an ester of 4-amino-2-hydroxy-benzoic acid mono-substituted at the nitrogen atom and having the general formula <FORM:0765591/VI/1> in which X is an organic radical, Y is a straight or branched aliphatic carbon chain containing from 1 to 10 carbon atoms, and Z1 and Z2 are the same or different alkyl groups each of which contains from 1 to 6 carbon atoms, or Z1 is a hydrogen atom and Z2 is an alkyl group containing from 1 to 6 carbon atoms or the grouping <FORM:0765591/VI/2> is a nitrogen-containing heterocyclic radical. The ester may be present in the form of a salt of an acid, e.g. a mono- or dihydrochloride. The radical X may be methyl, ethyl, butyl, secondary amyl, benzyl, 3-(p-nitrophenyl)-propyl, p-tolyl, 3-hydrophenyl, beta-dimethylaminoethyl, beta-diethylaminoethyl, beta - ethalaminoethyl, beta - isopropylaminoethyl, 1-methyl-2-methyl-3-diethylaminopropyl, beta - piperidinoethyl and beta-thiazolindinoethyl groups. Z1 and Z2 may be alkyl or isoalkyl groups. When the grouping <FORM:0765591/VI/3> is a heterocyclic group this may be piperidino, morpholino, thiazolino or pyrnolidino. Aqueous solutions of alkyl esters of 4-(diethylaminoethylamino) - 2 - hydroxybenzoic acid in which the alkyl group of the ester contains not more than 4 carbon atoms, and the beta-dimethyl- and beta-diethylaminoethyl esters of 4-(diethyl-aminoethylamino)-2-hydroxybenzoic acid or salts thereof are employed as local anaesthetics.
GB24797/54A 1953-09-03 1954-08-25 Esters of 4-amino-2-hydroxybenzoic acids mono-substituted at the nitrogen atom and aprocess for their production Expired GB765591A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE765591X 1953-09-03

Publications (1)

Publication Number Publication Date
GB765591A true GB765591A (en) 1957-01-09

Family

ID=6673149

Family Applications (1)

Application Number Title Priority Date Filing Date
GB24797/54A Expired GB765591A (en) 1953-09-03 1954-08-25 Esters of 4-amino-2-hydroxybenzoic acids mono-substituted at the nitrogen atom and aprocess for their production

Country Status (1)

Country Link
GB (1) GB765591A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3211609A (en) * 1961-09-29 1965-10-12 Merck & Co Inc Anticoccidial compositions and method of using same

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3211609A (en) * 1961-09-29 1965-10-12 Merck & Co Inc Anticoccidial compositions and method of using same

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