WO1993022278A1 - Procede de fabrication d'amides d'acide hydroxy-alcane-carboxylique - Google Patents

Procede de fabrication d'amides d'acide hydroxy-alcane-carboxylique Download PDF

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Publication number
WO1993022278A1
WO1993022278A1 PCT/DE1993/000413 DE9300413W WO9322278A1 WO 1993022278 A1 WO1993022278 A1 WO 1993022278A1 DE 9300413 W DE9300413 W DE 9300413W WO 9322278 A1 WO9322278 A1 WO 9322278A1
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WO
WIPO (PCT)
Prior art keywords
acid
general formula
carbon atoms
mol
chloride
Prior art date
Application number
PCT/DE1993/000413
Other languages
German (de)
English (en)
Inventor
Stefan Scholz
Michael Harre
Hans-Jörg Vidic
Günter Neef
Gerald Kirsch
Original Assignee
Schering Aktiengesellschaft
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 Schering Aktiengesellschaft filed Critical Schering Aktiengesellschaft
Priority to EP93911742A priority Critical patent/EP0639177A1/fr
Priority to JP5518842A priority patent/JPH07506819A/ja
Priority to CA002127292A priority patent/CA2127292A1/fr
Publication of WO1993022278A1 publication Critical patent/WO1993022278A1/fr
Priority to FI945181A priority patent/FI945181A0/fi
Priority to NO944238A priority patent/NO944238L/no

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic 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
    • C07D295/16—Heterocyclic 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 acylated on ring nitrogen atoms
    • C07D295/18—Heterocyclic 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 acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
    • C07D295/182—Radicals derived from carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines

Definitions

  • the invention relates to a process for the preparation of hydroxyalkanecarboxamides of the general formula I.
  • n represents an integer from 1 to 20 and
  • R ⁇ and R 2 each represent alkyl groups with a maximum of 8 carbon atoms or together represent an alkylene group with 4 to 8 carbon atoms, optionally interrupted by an oxygen atom or a nitrogen atom, from hydroxyalkanecarboxylic acids of the general formula II
  • R ⁇ and R 2 have the abovementioned meaning, which is characterized in that the hydroxyalkanecarboxylic acid is heated under reflux with 10 to 30 moles of acetyl chloride per mole of acid in a one-pot reaction, the excess acetyl chloride is distilled off after acetylation, and the residue is 1.5 to 5 moles of thionyl chloride per mole of acid are heated under reflux, the thionyl chloride is removed by distillation after the formation of acid chloride, the residue is dissolved in a dialkyl ether having 4 to 8 carbon atoms, the solution obtained is cooled to 0 ° C. to 10 ° C.
  • the invention relates to the preparation of hydroxyalkanecarboxamides of the general formula I ## STR1 ## in which the group
  • R3 and R4 independently represent a hydrogen atom or a methyl group and X represents a methylene group an oxygen atom or an N-CH3 group.
  • hydroxyalkanecarboxamides of the general formula I are known to be valuable intermediates and / or pharmacologically active substances.
  • R5 represents a hydrogen atom or an alkyl group, valuable intermediates for
  • the process according to the invention is carried out in such a way that the hydroxyalkane carboxylic acid is dissolved or suspended in 10 to 30 moles of acetyl chloride per mole of acid and the reaction mixture is heated under reflux. After acetylation has taken place (recognizable by thin-layer chromatographic analysis, or by the fact that no more hydrogen chloride is produced), the excess acetyl chloride is distilled off, care being taken to remove the acetyl chloride as completely as possible by applying a vacuum.
  • dialkyl ether having 4 to 8 carbon atoms.
  • Suitable dialkyl ethers are, for example, diethyl ether, diisopropyl ether, dibutyl ether or, in particular, methyl tert-butyl ether.
  • the ethereal solution of the acid chloride is then introduced into a preferably stirred and, if appropriate, mixed with the same ether, cooled to 0 ° C. to 10 ° C., aqueous solution of preferably 2 to 5 mol of amine per mol of acid used, so that the reaction temperature is 10 ° C does not exceed.
  • the reaction mixture is then left to stand at room temperature for a further 20-60 minutes to complete the reaction, and an excess of aqueous or aqueous / alcoholic sodium hydroxide solution is added and the mixture is stirred at room temperature for 20-60 minutes.
  • the reaction mixture is prepared in a customary manner, for example by separating the organic phase, washing it, concentrating it and cleaning the residue by recrystallization.
  • a g of ⁇ -hydroxyalkanoic acid are suspended in b ml of acetyl chloride and heated under reflux and stirring for 30 minutes. Then the acetyl chloride is distilled off in vacuo, c ml of thionyl chloride is added to the residue and the mixture is heated at 60 ° C. for one hour. Then the thionyl chloride is distilled off in vacuo and the residue is dissolved in d ml of methyl tert-butyl ether.
  • e ml of 40% aqueous dimethylamine solution are mixed with f ml of methyl tert-butyl ether and cooled to 0 ° C. with stirring.
  • the ethereal acid chloride solution is then added dropwise to this mixture such that the reaction temperature does not exceed 10 ° C., stirring is continued for 30 minutes at room temperature, and a solution of mercury sodium hydroxide in a mixture of i ml methanol and k ml water is added to the reaction mixture and stirred for a further 30 minutes at room temperature.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Il est décrit un procédé de fabrication d'amides d'acide hydroxy-alcane-carboxylique, de formule générale (I), dans laquelle n désigne un nombre entier de 1 à 20, R1 et R2 désignent respectivement des groupes alkyle ayant au maximum 8 atomes de carbone ou représentent ensemble un groupe alkylène ayant 4 à 8 atomes de carbone, interrompu, le cas échéant, par un atome d'oxygène ou un atome d'azote, provenant d'acides hydroxy-alcane-carboxyliques de formule générale (II): HO-CnH2n-COOH où n a la signification précitée, et d'amines de formule générale (III), où R1 et R2 ont la signification précitée, caractérisé en ce qu'on chauffe à reflux en faisant réagir dans un seul pot l'acide hydroxy-alcane-carboxylique avec 10 à 30 moles de chlorure d'acétyle par mole d'acide, ou sépare par distillation, après acétylation, le chlorure d'acétyle en excès, on chauffe à reflux le résidu avec 1,5 à 5 moles de chlorure de thionyle par mole d'acide, on élimine par distillation le chlorure de thionyle une fois le chlorure d'acide formé, on dissout le résidu dans du dialkyléther ayant 4 à 8 atomes de carbone, on introduit proportionnellement la solution obtenue dans une solution aqueuse de l'amine refroidie à une température comprise entre 0 °C et 10 °C, et une fois l'amide formé, on sépare le groupe acétal par traitement par une solution aqueuse d'hydroxyde de sodium, à une température de réaction de 10 °C à 30 °C.
PCT/DE1993/000413 1992-05-07 1993-05-05 Procede de fabrication d'amides d'acide hydroxy-alcane-carboxylique WO1993022278A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
EP93911742A EP0639177A1 (fr) 1992-05-07 1993-05-05 Procede de fabrication d'amides d'acide hydroxy-alcane-carboxylique
JP5518842A JPH07506819A (ja) 1992-05-07 1993-05-05 ヒドロキシアルカンカルボン酸アミドの製法
CA002127292A CA2127292A1 (fr) 1992-05-07 1993-05-05 Procede d'obtention d'amides d'acide hydroxyalcanecarboxylique
FI945181A FI945181A0 (fi) 1992-05-07 1994-11-03 Menetelmä hydroksialkaanikarboksyylihappoamidien valmistamiseksi
NO944238A NO944238L (no) 1992-05-07 1994-11-07 Fremgangsmåte for fremstilling av hydroxyalkancarboxylsyreamider

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DEP4214895.2 1992-05-07
DE19924214895 DE4214895A1 (de) 1992-05-07 1992-05-07 Verfahren zur Herstellung von Hydroxyalkancarbonsäureamiden

Publications (1)

Publication Number Publication Date
WO1993022278A1 true WO1993022278A1 (fr) 1993-11-11

Family

ID=6458253

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DE1993/000413 WO1993022278A1 (fr) 1992-05-07 1993-05-05 Procede de fabrication d'amides d'acide hydroxy-alcane-carboxylique

Country Status (9)

Country Link
EP (1) EP0639177A1 (fr)
JP (1) JPH07506819A (fr)
AU (1) AU4259493A (fr)
CA (1) CA2127292A1 (fr)
DE (1) DE4214895A1 (fr)
FI (1) FI945181A0 (fr)
HU (1) HUT68198A (fr)
NO (1) NO944238L (fr)
WO (1) WO1993022278A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0695738A1 (fr) * 1994-08-05 1996-02-07 Hoechst Aktiengesellschaft Procédé pour la préparation d'anilides de l'acide 0-acyl-glycollique
EP0753507A1 (fr) * 1995-07-10 1997-01-15 Hoechst Aktiengesellschaft Procédé pour la préparation d'anilides d'acide hydroxycarboxylique

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4420736C1 (de) * 1994-06-15 1995-08-10 Henkel Kgaa Pseudoceramide
US7541489B2 (en) 2004-06-30 2009-06-02 Sabic Innovative Plastics Ip B.V. Method of making halophthalic acids and halophthalic anhydrides
DE102008017213B4 (de) * 2008-04-04 2012-08-09 Clariant International Limited Kontinuierliches Verfahren zur Herstellung von Amiden aliphatischer Hydroxycarbonsäuren
WO2010108817A1 (fr) 2009-03-26 2010-09-30 Basf Se Procédé de préparation de dialkylamide d'acide n,n'-lactique au moyen de liquides ioniques
WO2010108814A1 (fr) 2009-03-26 2010-09-30 Basf Se Procédé de préparation de dialkylamide d'acide n,n'-lactique sous pression

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB868556A (en) * 1957-05-02 1961-05-17 Hoechst Ag Analeptically active ª--hydroxy-and ª--acyloxy-butyric acid alkyl-amides and a process for their manufacture
WO1990009373A1 (fr) * 1989-02-17 1990-08-23 Schering Aktiengesellschaft Derives d'acide carboxylique d'hydroxyalkane, leur fabrication et emploi

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB868556A (en) * 1957-05-02 1961-05-17 Hoechst Ag Analeptically active ª--hydroxy-and ª--acyloxy-butyric acid alkyl-amides and a process for their manufacture
WO1990009373A1 (fr) * 1989-02-17 1990-08-23 Schering Aktiengesellschaft Derives d'acide carboxylique d'hydroxyalkane, leur fabrication et emploi

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SYNTH. COMMUN. Bd. 22, Nr. 6, März 1992, NEW YORK (US) Seiten 859 - 869 S. E. KELLY, T. G. LACOUR 'A one pot procedure for the synthesis of .alpha.-hydroxy amides from the corresponding .alpha.-hydroxy acids' *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0695738A1 (fr) * 1994-08-05 1996-02-07 Hoechst Aktiengesellschaft Procédé pour la préparation d'anilides de l'acide 0-acyl-glycollique
US5705680A (en) * 1994-08-05 1998-01-06 Hoechst Aktiengesellschaft Process for the preparation of O-acylglycolanilides
EP0753507A1 (fr) * 1995-07-10 1997-01-15 Hoechst Aktiengesellschaft Procédé pour la préparation d'anilides d'acide hydroxycarboxylique
US5712414A (en) * 1995-07-10 1998-01-27 Hoechst Aktiengesellschaft Hydroxycarboxylic acid anilides

Also Published As

Publication number Publication date
JPH07506819A (ja) 1995-07-27
HU9401335D0 (en) 1994-08-29
CA2127292A1 (fr) 1993-11-11
DE4214895A1 (de) 1993-11-11
FI945181A (fi) 1994-11-03
HUT68198A (en) 1995-05-29
FI945181A0 (fi) 1994-11-03
NO944238D0 (no) 1994-11-07
AU4259493A (en) 1993-11-29
NO944238L (no) 1994-11-07
EP0639177A1 (fr) 1995-02-22

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