US3100223A - Ammoniumaliphatic esters of carbamic acids - Google Patents

Ammoniumaliphatic esters of carbamic acids Download PDF

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Publication number
US3100223A
US3100223A US41025A US4102560A US3100223A US 3100223 A US3100223 A US 3100223A US 41025 A US41025 A US 41025A US 4102560 A US4102560 A US 4102560A US 3100223 A US3100223 A US 3100223A
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Prior art keywords
acid
compound
chloride
butynyl
acids
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US41025A
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Inventor
Hopkins Thomas Robert
James H Rea
Roszkowski Adolph Peter
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Spencer Chemical Co
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Spencer Chemical Co
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Priority to US41025A priority Critical patent/US3100223A/en
Priority to FR869584A priority patent/FR1330M/fr
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids

Definitions

  • Aryl radicals suitable as R substituents in the above general formula include the monoand di-nuclear aromatic carbocyclic aryl radicals such as phenyl, to-lyl or naphthyl.
  • Substituents in these aromatic nuclei may be, for example, lower alkyl such as methyl, ethyl, propyl, butyl or pentyl; halo such as chloro, fluoro, iodo or bromo; amino, particularly tertiary amino, such as dilower alkyl amino for example, dimethyl, diethyl, or dibutylamino; or amino-lower alkoxy groups, for example dimethylaminoethoxy.
  • Heterocyclic substituents on the aryl nuclei may be those containing from four to five carbon atoms, interrupted, if desired, by oxygen, nitrogen or sulfur linkages as for example, pyrrolidino, piperidino, morpholino, thiamorpholino, piperazino, etc.
  • Substituents depicted by M in the above general formula may be lower alkyl radicals such as for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, etc.
  • the anion Y in the above formula is more particularly a therapeutically useful anion of an acid such as that of an inorganic acid for example a hydrohalic acid, i.e., hydrochloric, hydrobromic or hydriodic acid, sulphuric acid, phosphoric acid, nitric acid or thiocyanic acid; or an organic carboxylic acid such as, for example, acetic, acetoacetic, prop-ionic, beta-cyclopentylpropionic, oxalic, malonic, succinic, maleic, fuman'c, malic, citric, tartaric, benzoic, phenylacetic, beta-phenylpropionic, salicylic acid, acetylsal-icylic, or para-aminosalicylic acid; an organic sulphonic or sulphuric acid such as, for example, paratoluenesulphonic acid, methanesulphonic acid, ethanesulphonic acid, or methyl or
  • the compounds of the present invention affect the autonomic nervous system and are therefore useful in reversing tensive states. For example, certain of the compounds stimulate autonornic ganglia and thereby raise the blood pressure from a hypotensive to a normal tensive level. Others depress autonomic ganglia and are useful in loweding blood pressure from hypertensive to normal tensive levels. For this purpose they may be administered orally or intraperitoneally. The dose may be varied widely depending upon the route of administration chosen, i.e., from five to one hundred milligrams per kilogram United States Patent ice body weight intnapenitoneally, or from about two to about twenty micrograms per kilogram body weight intravenously.
  • the compounds may be formulated into preparations which contain these compounds in admixture with suitable pharmaceutical organic or inorganic, solid or liquid carriers appropriate for oral or parenteral administration.
  • suitable pharmaceutical organic or inorganic, solid or liquid carriers appropriate for oral or parenteral administration.
  • substances which may be employed are, for example, water, gelatin, lactose, starches, magnesium stearate, talc, vegetable oils, benzyl alcohols, gums, polyalkylene glycols, cholesterol, or any other known carrier commonly used in the preparation of medicaments.
  • the pharmaceutical preparations may be in the form of tablets, capsules or in liquid form such as solutions, suspensions or emulsions. If desired, they may contain auxiliary substances such as preserving agents, stabilizing agents, wetting agents, emulsifying agents, salts for varying osmotic pressure or buffers.
  • novel quaternary ammonium alkyl carbamates are preparedby reacting a compound of the formula:
  • novel carbamates may be prepared by reacting a compound of the formula:
  • R and X substituents are as defined above and M is hydrogen or lower alkyl, with a reactive ester of an alcohol such as those with strong inorganic acids, for example hydrohalic acids, e.g., hydrochloric, hydrobromic, hydriodic or sulphuric acid; with strong onganic sulphonic acids such as, for example, aryl sulphonic acids, e.g., para-toluenesulphonic, or alky-lsulphonic acids, e.g., methanesulphonic or ethanesulphonic acid, or with strong organic sulphuric acids, for example methyl or ethyl sulphuric acid halt ester.
  • preparation of the novel quaternary ammonium carbam-ates may be accomplished by reacting the appropriate 4-dialkylamino-2-alkynyl-N- (2-haloaryl) carbarnate with an alkyl halide.
  • the quaternizing reactions such as outlined above are performed according to standard procedures, that is to say, in the presence or absence of a solvent at room temperature or at :an elevated temperature or under cooling at atmospheric pressure or in a closed vessel under pressure.
  • Suitable solvents are, more particularly, enzene, the lower alkanols such as methanol, ethanol, prop-anol, isopropanol or amyl alcohol or organic acid amides such as formamide or dimethylformamide.
  • fonmamide or dimethylformamide may be used as solvents and the reaction is advantageously run in a closed vessel under pressure.
  • Introduction of the amine into the starting material may be in the form of a gas or in the form of a liquid, whichever is appropriate.
  • Quaternary ammonium alkyl canbamates such as those obtained by the process of the invention may be converted into corresponding quaternary ammonium hydroxides, for example by reaction of the quaternary ammonium halides with silver oxide, or by reaction of the sulfates with barium hydroxide, or by treating the quatertherapeutically suitable quaternary ammonium salts by reaction with the acids, for example with inorganic acids such as hydrohalic acids, e.g., hydrochloric, hydrobromic or hydriodic, sulphuric, phosphoric acids, nitric acid or thiocyanic acid; or organic acids such as acetic, acetoa-cetic, propion-ic, di-lbeta-cyclopentylpropionic, oxalic, malonic, succinic, maleic, iumaric, malic, citric, tartaric, benzoic, phenylacetic, betaphenylpropionic, salicylic,
  • quaternary ammonium salts obtained may also be converted into other quaternary salts directly without conversion into the quaternary hydroxide.
  • a quaternary ammonion iodide maybe reacted with freshly prepared silver chloride to yield the quaternary ammonium chloride.
  • Example I 12.9 parts by weight of 4-chloro-2butynyl-N-(2-chlorohenyDcarbamate is dissolved in 200 parts by volume of benzene. Trimethyl-amine gas is passed slowly into the solution for about three hours. The solid precipitate which forms is removed by filtration and recrystallized from an ethanol-ether mixture. 9.1 parts by weight of 4-'[N-(2-ehlorophenyl) carbarnoyloxy]-2-butynyl-trimethylammonium chloride is obtained. Analysis.-Ca1cu.lated for C H Cl N O Ionic Cl, 11.22. Found, 11.28.
  • Example [I 20.8 parts by weight of 4-chloro-2-butenyl-N-(3-chloropheny1)carb amate, 150 parts by volume of benzene and 15.2 parts by weight of triethylamine is stirred at ambient temperature for about forty hours. The precipitate which forms is removed by filtration and dried in a desiccator over P A total of 11.5 parts by weight of 4-[N-(3- chlorophenyhcarbamoyloxy] -2 butenyl triethylammonium chloride is obtained.
  • Example III A mixture of 16 parts by weight of 4-dietl1y1amino-2- butynyl-N-(Z-chlorophenyl)carbamate, 16.35 parts of ethyl bromide and 250 parts by volume of benzene is mixed and stirred at ambient temperature for forty hours. The precipitate which forms is removed by filtration and dried under reduced pressure over P 0 A total of 5.7 parts by weight of 4-[N-(Z-chlorophenyDcarbamoyloxy] -2 butynyl-trielthylammonium bromide is obtained. Analysis-Calculated for CHHMBI'CINZOZ. Ionic Br, 19.77. Found, 19.62.
  • bamoyloxy -2-butynyltrimethyl ammonium chloride bamoyloxy -2-butynyltrimethyl ammonium chloride.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
US41025A 1960-07-06 1960-07-06 Ammoniumaliphatic esters of carbamic acids Expired - Lifetime US3100223A (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US41025A US3100223A (en) 1960-07-06 1960-07-06 Ammoniumaliphatic esters of carbamic acids
FR869584A FR1330M (fr) 1960-07-06 1961-07-31 Composé d'ammonium quaternaire.

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US41025A US3100223A (en) 1960-07-06 1960-07-06 Ammoniumaliphatic esters of carbamic acids

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FR (1) FR1330M (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3621048A (en) * 1968-03-14 1971-11-16 Colgate Palmolive Co Quaternary ammonium compounds
US4007281A (en) * 1971-04-16 1977-02-08 Colgate-Palmolive Company Pharmaceutical compositions containing quaternary ammonium compounds

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1894162A (en) * 1930-05-08 1933-01-10 Dalmer Otto New choline derivative and process for making same
GB734745A (en) * 1953-10-27 1955-08-03 Bofors Ab Improvements relating to anaesthetics
US2772289A (en) * 1953-03-26 1956-11-27 Searle & Co Basic esters of n-aralkyl-n-aryl-carbamic acids and the manufacture thereof
US2794810A (en) * 1952-03-08 1957-06-04 Searle & Co Aminoalkyl cycloalkylcarbamates
US2967880A (en) * 1957-10-21 1961-01-10 Boehringer Sohn Ingelheim Carbamic acid glycol esters
US2973385A (en) * 1958-03-10 1961-02-28 Searle & Co Dialkylaminoalkyl chlorocarbanilates and process

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1894162A (en) * 1930-05-08 1933-01-10 Dalmer Otto New choline derivative and process for making same
US2794810A (en) * 1952-03-08 1957-06-04 Searle & Co Aminoalkyl cycloalkylcarbamates
US2772289A (en) * 1953-03-26 1956-11-27 Searle & Co Basic esters of n-aralkyl-n-aryl-carbamic acids and the manufacture thereof
GB734745A (en) * 1953-10-27 1955-08-03 Bofors Ab Improvements relating to anaesthetics
US2967880A (en) * 1957-10-21 1961-01-10 Boehringer Sohn Ingelheim Carbamic acid glycol esters
US2973385A (en) * 1958-03-10 1961-02-28 Searle & Co Dialkylaminoalkyl chlorocarbanilates and process

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3621048A (en) * 1968-03-14 1971-11-16 Colgate Palmolive Co Quaternary ammonium compounds
US4007281A (en) * 1971-04-16 1977-02-08 Colgate-Palmolive Company Pharmaceutical compositions containing quaternary ammonium compounds

Also Published As

Publication number Publication date
FR1330M (fr) 1962-05-28

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