EP0639177A1 - Process for producing hydroxyalkane carboxylic acid amides - Google Patents

Process for producing hydroxyalkane carboxylic acid amides

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Publication number
EP0639177A1
EP0639177A1 EP93911742A EP93911742A EP0639177A1 EP 0639177 A1 EP0639177 A1 EP 0639177A1 EP 93911742 A EP93911742 A EP 93911742A EP 93911742 A EP93911742 A EP 93911742A EP 0639177 A1 EP0639177 A1 EP 0639177A1
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EP
European Patent Office
Prior art keywords
acid
general formula
carbon atoms
mol
chloride
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.)
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Application number
EP93911742A
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German (de)
French (fr)
Inventor
Stefan Scholz
Michael Harre
Hans-Jörg Vidic
Günter Neef
Gerald Kirsch
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Bayer Pharma AG
Original Assignee
Schering AG
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Publication of EP0639177A1 publication Critical patent/EP0639177A1/en
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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

The description relates to a process for producing hydroxyalkane carboxylic acid amides of the general formula (I), in which n is a whole number from 1 to 20 and R1 and R2 are alkyl groups with a maximum of 8 carbon atoms or together represent an alkylene group with 4 to 8 carbon atoms, possibly interrupted by an oxygen or a nitrogen atom, from hydroxyalkane carboxylic acids of the general formula (II): HO-CnH2n-COOH, in which n has the significance given above and amines of the general formula (III), in which R1 and R2 have the significance given above, characterized in that the hydroxylalkane carboxylic acid is heated with reflux in a one-pot reaction with 10 to 30 mol acetyl chloride per mol acid, the superfluous acetyl chloride is distilled off after acetylisation, the residue is heated with reflux with 1.5 to 5 mol thionyl chloride per mol acid, after the formation of acid chloride the thionyl chloride is distilled off, the residue is dissolved in a dialkyl ether with 4 to 8 carbon atoms, the solution obtained is added proportionately to an aqueous solution of the amine cooled to 0 to 10 °C and, after amide formation, the acetal group is separated off by treatment with aqueous sodium hydroxide solution at a reaction temperature of 10 to 30 °C.

Description

Verfahren zur Herstellung von Hydroxyalkancarbonsäureamiden Process for the preparation of hydroxyalkane carboxamides
Die Erfindung betrifft ein Verfahren zur Herstellung von Hydroxyalkancarbonsäureamiden der allgemeinen Formel IThe invention relates to a process for the preparation of hydroxyalkanecarboxamides of the general formula I.
HO-Cn-H2n-CON XHO-C n -H 2n -CON X
XR2 (I), XR 2 (I),
worin n eine ganze Zahl von 1 bis 20 darstellt undwherein n represents an integer from 1 to 20 and
R^ und R2 jeweils Alkylgruppen mit maximal 8 Kohlenstoffatomen oder gemeinsam eine gegebenenfalls durch ein Sauerstoffatom oder ein Stickstoffatom unterbrochene Alkylen- gruppe mit 4 bis 8 Kohlenstoffatomen bedeuten, aus Hydroxyalkancarbonsäuren der allgemeinen Formel IIR ^ 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
HO-CnH2n-COOH (II), worin n die oben genannte Bedeutung besitzt und Aminen der allgemeinen Formel IIIHO-C n H 2n -COOH (II), in which n has the meaning given above and amines of the general formula III
, Rι, Rι
HNV R2 (III), worinHN V R 2 (III), wherein
R^ und R2 die obengenannte Bedeutung besitzen, welches dadurch gekennzeichnet ist, daß man in einer Eintopfreaktion die Hydroxyalkancarbonsäure mit 10 bis 30 Mol Acetylchlorid je Mol Säure unter Rückfluß erhitzt, das überschüssige Acetylchlorid nach erfolgter Acetylierung abdestilliert, den Rückstand mit 1,5 bis 5 Mol Thionylchlorid pro Mol Säure unter Rückfluß erhitzt, das Thionylchlorid nach erfolgter Säurechlorid-Bildung durch Destillation entfernt, den Rückstand in einem Dialkylether mit 4 bis 8 Kohlenstoffatomen löst, die erhaltene Lösung in eine auf 0 °C bis 10 °C gekühlte wässrige Lösung des Amins anteilig einträgt und nach erfolgter Amidbildung die Acetatgruppe durch Behandeln mit wässriger Natriumhydroxid-Lösung bei einer Reaktionstemperatur von 10 °C bis 30 °C abspaltet. Insbesondere betrifft die Erfindung die Herstellung von Hydroxyalkancarbonsäureamiden der allgemeinen Formel I worin die GruppeR ^ 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. in an aqueous solution of the Entered amine proportionally and after the amide formation, the acetate group is split off by treatment with aqueous sodium hydroxide solution at a reaction temperature of 10 ° C to 30 ° C. In particular, the invention relates to the preparation of hydroxyalkanecarboxamides of the general formula I ## STR1 ## in which the group
eine Dialkylaminogruppe mit jeweilsl bis 4 Kohlenstoffatomen in den Alkylresten, oder die Gruppierunga dialkylamino group each having 1 to 4 carbon atoms in the alkyl radicals, or the grouping
worin R3 und R4 unabhängig voneinander ein Wasserstoffatom oder eine Methylgruppe darstellen und X eine Methylengruppe ein Sauerstoffatom oder eine N-CH3 Gruppe bedeuten.wherein 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.
Die Hydroxyalkancarbonsäureamide der allgemeinen Formel I sind bekanntlich wertvolle Zwischenprodukte und/oder pharmakologisch wirksame Substanzen.The hydroxyalkanecarboxamides of the general formula I are known to be valuable intermediates and / or pharmacologically active substances.
So sind zum Beispiel Hydroxyalkancarbonsäureamide der allgemeinen Formel IaFor example, hydroxyalkanecarboxamides of the general formula Ia
R5 - CH - CON^ (Ia),R 5 - CH - CON ^ (Ia),
OH ^R2 OH ^ R 2
worinwherein
R5 ein Wasserstoffato oder eine Alkylgrappe darstellt, wertvolle Zwischenprodukte zurR5 represents a hydrogen atom or an alkyl group, valuable intermediates for
Herstellung von Herbiziden (DE-A 3038 598).Production of herbicides (DE-A 3038 598).
Hydroxyalkancarbonsäureamide der allgemeinen Formel IbHydroxyalkanecarboxamides of the general formula Ib
HO-(CH2)m-CON (Ib), worin m die Ziffern 7 bis 18 bedeutet sind beispielsweise zur Herstellung von Arzneimitteln für die lokale Behandlung von Erkrankungen der Haut oder Schleimhaut geeignet (WO 90/09373) oder können als Zwischenprodukte zur Herstellung von Detergentien verwendet werden (US- A 2,936,325). Die Synthese dieser Hydroxyalkancarbonsäureamide ist aber in der Regel recht aufwendig und die Ausbeute und Reinheit der erhaltenen Produkte oft unbefriedigend. Demgegenüber bietet die erfindungsgemäße Eintopfreaktion sowohl ökologische und ökonomische Vorteile. Sie ist im Vergleich zu den vorbekannten Verfahren relativ einfach durchführbar und liefert die Verfahrensprodukte in überraschend hoher Ausbeute und Reinheit.HO- (CH 2 ) m -CON (Ib), where m is the numbers 7 to 18 are, for example, suitable for the production of medicaments for the local treatment of diseases of the skin or mucous membrane (WO 90/09373) or can be used as intermediates for the production of detergents (US Pat. No. 2,936,325). However, the synthesis of these hydroxyalkanecarboxamides is generally quite complex and the yield and purity of the products obtained are often unsatisfactory. In contrast, the one-pot reaction according to the invention offers both ecological and economic advantages. It is relatively easy to carry out in comparison to the previously known processes and delivers the process products in surprisingly high yield and purity.
Das erfindungsgemäße Verfahren wird in der Weise durchgeführt, daß man die Hydroxy¬ alkancarbonsäure in 10 bis 30 Mol Acetylchlorid pro Mol Säure löst oder suspendiert und das Reaktionsgemisch unter Rückfluß erhitzt. Nach erfolgter Acetylierung (erkennbar durch dünnschichtchromatographische Analyse, oder daran, daß keine Chlorwasserstoff- Entwicklung mehr erfolgt) wird das überschüssige Acetylchlorid abdestilliert, wobei man durch Anlegen von Vakuum für eine möglichst vollständige Entfernung des Acetylchlorids Sorge trägt.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.
Der erhaltene Rückstand wird dann mit 1,5 bis 5 Mol Thionylchlorid pro Mol eingesetzter Säure versetzt und das erhaltene Gemisch unter Rückfluß erhitzt. Nach der erfolgten Säurechlorid-Bildung wird das Thionylchlorid in gleicher Weise möglichst vollständig ent¬ fernt wie zuvor das Acetylchlorid und der erhaltene Rückstand in einem Dialkylether mit 4 bis 8 Kohlenstoffatomen gelöst. Als Dialkylether eignet sich beispielsweise der Diethylether, der Diisopropylether, der Dibutylether oder insbesondere der Methyl-tert.-butylether.The residue obtained is then mixed with 1.5 to 5 moles of thionyl chloride per mole of acid used and the mixture obtained is heated under reflux. After the formation of acid chloride has taken place, the thionyl chloride is removed as completely as possible in the same way as the acetyl chloride and the residue obtained are dissolved in a 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.
Die etherische Lösung des Säurechlorids wird dann in eine vorzugsweise gerührte und gegebenenfalls mit dem gleichen Ether versetzte, auf 0 °C bis 10 °C gekühlte, wässrige Lösung von vorzugsweise 2 bis 5 Mol Amin pro Mol eingesetzter Säure anteilig so eingetragen, daß die Reaktionstemperatur 10 °C nicht übersteigt. Dann läßt man die Reaktionsmischung zur Vervollständigung der Umsetzung noch 20 - 60 Minuten bei Raumtemperatur stehen und versetzt sie mit einem Überschuß an wässriger oder wässrig/alkoholischer Natriumhydroxid-Lösung und rührt sie 20 - 60 Minuten lang bei Raumtemperatur. Die Aufbereitung der Reaktionsmischung erfolgt in üblicher Weise, indem man beispielsweise die organische Phase abtrennt, wäscht, einengt und den Rückstand durch Umkristallisation reinigt.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.
Die nachfolgenden Ausführungsbeispiele dienen zur näheren Erläuterung des erfindungsgemäßen Verfahrens. The following exemplary embodiments serve to explain the method according to the invention in more detail.
Allgemeine Vorschriften zur Darstellung von ω-Hvdroxyalkancarbonsäureamiden der allgemeinen Formel IGeneral regulations for the preparation of ω-hydroxyalkane carboxamides of the general formula I
a g ω-Hydroxyalkansäure werden in b ml Acetylchlorid suspendiert und 30 Minuten lang unter Rückfluß und Rühren erhitzt. Dann destilliert man das Acetylchlorid im Vakuum ab, versetzt den Rückstand mit c ml Thionylchlorid und erhitzt die Mischung eine Stunde lang bei 60 °C. Dann wird das Thionylchlorid im Vakuum abdestilliert und der Rückstand in d ml Methyl-tert.-butylether gelöst.a g of ω-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 40 %ige wässrige Dimethylaminlösung werden mit f ml Methyl-tert.-butylether versetzt und unter Rühren auf 0 °C gekühlt. Dann tropft man in dieses Gemisch die etherische Säurechlorid-Lösung so ein, daß die Reaktionstemperatur 10 °C nicht übersteigt, rührt noch 30 Minuten bei Raumtemperatur, setzt der Reaktionsmischung eine Lösung von h g Natriumhydroxid in einem Gemisch aus i ml Methanol und k ml Wasser zu und rührt weitere 30 Minuten bei Raumtemperatur.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.
Dann wird die Mischung mit Wasser und Methyl-tert.-butylether verdünnt, die organische Phase abgetrennt, gewaschen und im Vakuum eingeengt. Der Rückstand wird aus Essigsäure- ethylester/Hexan umkristallisiert und man erhält 1 g ω-Hydroxyalkansäuredimethylamid vom Schmelzpunkt m °C (= p % d. Th.)The mixture is then diluted with water and methyl tert-butyl ether, the organic phase is separated off, washed and concentrated in vacuo. The residue is recrystallized from ethyl acetate / hexane and 1 g of ω-hydroxyalkanoic acid dimethylamide with a melting point of m ° C. (= p% of theory) is obtained.
Beispiel 1:Example 1:
13-Hydroxytridecansäure-dimethylamid aus 13-Hydroxytridecansäure13-hydroxytridecanoic acid dimethylamide from 13-hydroxytridecanoic acid
C15H31NO2 (257.42) Ber. C 69.99 H 12,14 N 5.44C 15 H 31 NO 2 (257.42) calc. C 69.99 H 12.14 N 5.44
Gef. C 70.38 H 11.98 N 5,43 Beispiel 2: 11-Hydroxyundecansäure-dimethylamid aus 11-HydroxyundecansäureFound C 70.38 H 11.98 N 5.43 Example 2: 11-hydroxyundecanoic acid dimethylamide from 11-hydroxyundecanoic acid
C16H33NO2 (2271.44) Ber. C 68,08 H 11,87 N 6,11C 16 H 33 NO 2 (2271.44) calc. C 68.08 H 11.87 N 6.11
Gef. C 68,45 H 11,76 N 6,13 Beispiel 3:Found C 68.45 H 11.76 N 6.13 Example 3:
14-Hydroxytetradecansäure-dimethylamid aus 14-Hydroxytetradecansäure14-hydroxytetradecanoic acid dimethylamide from 14-hydroxytetradecanoic acid
C13H27NO2 (229.36) Ber. C 70,80 H 12,25 N 5,16C 13 H 2 7NO 2 (229.36) calc. C 70.80 H 12.25 N 5.16
Gef. C 71,16 H 12,27 N 5,20 Beispiel 4:Found C 71.16 H 12.27 N 5.20 Example 4:
15-Hydroxypentadecansäure-dimethylamid aus 15-Hydroxypentadecansäure15-hydroxypentadecanoic acid dimethylamide from 15-hydroxypentadecanoic acid
C17H35NO2 (285.4 Ber. C 71.53 H 12,36 N 4,91C 17 H 3 5NO 2 (285.4 calc. C 71.53 H 12.36 N 4.91
Gef. C 71,65 H 12,19 N 4,93 Beispiel 5:Found C 71.65 H 12.19 N 4.93 Example 5:
4-(13-Hydroxy-l-oxotridecyl)morpholin aus 13-Hydroxytridecansäure4- (13-hydroxy-l-oxotridecyl) morpholine from 13-hydroxytridecanoic acid
C17H33NO3 (299.45) Ber. C 68,19 H 11,11 N 4,68C17H33NO3 (299.45) calc. C 68.19 H 11.11 N 4.68
Gef. C 68,16 H 11,03 N 4,74Found: C 68.16 H 11.03 N 4.74
Beisp. mEx. M
22,4190 67 26,9 69-7186,022.4190 67 26.9 69-7186.0
17,7151 53 17,757-5880,017.7151 53 17.757-5880.0
11,799 35 14,370-7183,111.799 35 14.370-7183.1
8,1 69 24 10,473-7482,6 2,8 24 8 2,875-7662,1 8.1 69 24 10.473-7482.6 2.8 24 8 2.875-7662.1

Claims

PatentanspruchClaim
Verfahren zur Herstellung von Hydroxyalkancarbonsäureamiden der allgemeinen Formel IProcess for the preparation of hydroxyalkanecarboxamides of the general formula I
/Rι/ R ι
HO-Cn-H^-CON^HO-Cn-H ^ -CON ^
SR2 (I), SR 2 (I),
worin n eine ganze Zahl von 1 bis 20 darstellt undwherein n represents an integer from 1 to 20 and
R]_ und R2 jeweils Alkylgruppen mit maximal 8 Kohlenstoffatomen oder gemeinsam eine gegebenenfalls durch ein Sauerstoffatom oder ein Stickstoffatom unterbrochene Alkylen- gruppe mit 4 bis 8 Kohlenstoffatomen bedeuten, aus Hydroxyalkancarbonsäuren der allgemeinen Formel IIR] _ and R 2 each denote alkyl groups with a maximum of 8 carbon atoms or together an alkylene group with 4 to 8 carbon atoms which may be interrupted by an oxygen atom or a nitrogen atom, from hydroxyalkanecarboxylic acids of the general formula II
HO-CnH2n-COOH (II), worin n die oben genannte Bedeutung besitzt und Aminen der allgemeinen Formel IIIHO-CnH 2n -COOH (II), in which n has the meaning given above and amines of the general formula III
HNχ R2 (HI), worinHN χ R2 (HI), where
Rl und R2 die obengenannte Bedeutung besitzen, dadurch gekennzeichnet, daß man in einer Eintopftreaktion die Hydroxyalkancarbonsäure mit 10 bis 30 Mol Acetylchlorid je Mol Säure unter Rückfluß erhitzt, das überschüssige Acetylchlorid nach erfolgter Acetylierung abdestilliert, den Rückstand mit 1,5 bis 5 Mol Thionylchlorid pro Mol Säure unter Rückfluß erhitzt, das Thionylchlorid nach erfolgter Säurechlorid-Bildung durch Destillation entfernt, den Rückstand in einem Dialkylether mit 4 bis 8 Kohlenstoffatomen löst, die erhaltene Lösung in eine auf 0 °C bis 10 °C gekühlte wässrige Lösung des Amins anteilig einträgt und nach erfolgter Amidbildung die Acetatgruppe durch Behandeln mit wässriger Natriumhydroxid-Lösung bei einer Reaktionstemperatur von 10 °C bis 30 °C abspaltet. Rl and R 2 have the abovementioned meaning, characterized in that the hydroxyalkanecarboxylic acid is heated under reflux with 10 to 30 mol of acetyl chloride per mol of acid in a one-pot reaction, the excess acetyl chloride is distilled off after acetylation, and the residue is distilled with 1.5 to 5 mol of thionyl chloride heated under reflux per mole of acid, the thionyl chloride is removed by distillation after formation of the acid chloride, the residue is dissolved in a dialkyl ether having 4 to 8 carbon atoms, and the resulting solution is partially introduced into an aqueous solution of the amine which is cooled to 0 ° C. to 10 ° C. and after the amide formation has taken place, the acetate group is split off by treatment with aqueous sodium hydroxide solution at a reaction temperature of 10 ° C. to 30 ° C.
EP93911742A 1992-05-07 1993-05-05 Process for producing hydroxyalkane carboxylic acid amides Withdrawn EP0639177A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE4214895 1992-05-07
DE19924214895 DE4214895A1 (en) 1992-05-07 1992-05-07 Process for the preparation of hydroxyalkane carboxamides
PCT/DE1993/000413 WO1993022278A1 (en) 1992-05-07 1993-05-05 Process for producing hydroxyalkane carboxylic acid amides

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EP0639177A1 true EP0639177A1 (en) 1995-02-22

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EP (1) EP0639177A1 (en)
JP (1) JPH07506819A (en)
AU (1) AU4259493A (en)
CA (1) CA2127292A1 (en)
DE (1) DE4214895A1 (en)
FI (1) FI945181A (en)
HU (1) HUT68198A (en)
NO (1) NO944238L (en)
WO (1) WO1993022278A1 (en)

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Publication number Priority date Publication date Assignee Title
US7732559B2 (en) 2004-06-30 2010-06-08 Sabic Innovative Plastics Ip B.V. Method of making halophthalic acids and halophthalic anhydrides

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NO944238D0 (en) 1994-11-07
DE4214895A1 (en) 1993-11-11
WO1993022278A1 (en) 1993-11-11
FI945181A0 (en) 1994-11-03
HU9401335D0 (en) 1994-08-29
HUT68198A (en) 1995-05-29
CA2127292A1 (en) 1993-11-11
FI945181A (en) 1994-11-03
JPH07506819A (en) 1995-07-27
NO944238L (en) 1994-11-07
AU4259493A (en) 1993-11-29

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