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WO2001036366A1 - Procede de production d'esters d'acide phenylacetique - Google Patents

Procede de production d'esters d'acide phenylacetique Download PDF

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Publication number
WO2001036366A1
WO2001036366A1 PCT/EP2000/010322 EP0010322W WO0136366A1 WO 2001036366 A1 WO2001036366 A1 WO 2001036366A1 EP 0010322 W EP0010322 W EP 0010322W WO 0136366 A1 WO0136366 A1 WO 0136366A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
acid
hydrogenation
alkyl radical
esterification
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.)
Ceased
Application number
PCT/EP2000/010322
Other languages
German (de)
English (en)
Inventor
Karlheinz Niederreiter
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.)
Patheon Austria GmbH and Co KG
Original Assignee
DSM Fine Chemicals Austria Nfg GmbH and Co KG
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 DSM Fine Chemicals Austria Nfg GmbH and Co KG filed Critical DSM Fine Chemicals Austria Nfg GmbH and Co KG
Priority to AU12739/01A priority Critical patent/AU1273901A/en
Publication of WO2001036366A1 publication Critical patent/WO2001036366A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/317—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups

Definitions

  • Phenylacetic acid esters such as 4-hydroxyphenylacetic acid methyl ester, are required, inter alia, in the production of 4-hydroxyphenylacetamide, an important building block for the synthesis of the ⁇ -blocker atenolol.
  • Inhibitors, antihistamines, polymerization catalysts, diagnostic agents or liquid crystals are used
  • the phenylacetic acid esters have hitherto been prepared by hydrogenating the corresponding mandelic acid or the salt with hydrogen in the presence of a catalyst in glacial acetic acid / water mixtures, for example according to US Pat. No. 4,337,355, and subsequent esterification in the corresponding alcohol as solvent to the corresponding ester
  • J Mol Catal 75 (1992), 169-178 and 78 (1993), 9-20 describes a process variant for the preparation of phenylacetic acid esters, the phenylacetic acid esters being hydrogenated and esterified at the same time with the corresponding mandelic acid derivative with carbon monoxide in the presence of a Pd / C-HCI catalyst system can be obtained in ethanol and benzene as an additional solvent.
  • Pd / C is only a highly active catalyst in combination with HCI, so that poor results are achieved in the absence of HCI.
  • the additional solvent benzene is also according to These references are crucial for a high yield.
  • the invention accordingly relates to a process for the preparation of phenylacetic acid derivatives of the formula
  • Ar is a phenyl radical RH or C 1 -C 4 -alkyl radical which is mono- or polysubstituted by OR, NR 2 or halogen and R 'is a C 1 -C 4 -alkyl radical, by simultaneous hydrogenation and esterification of the corresponding substituted mandelic acids formula
  • phenylacetic acid esters of the formula (I) are prepared.
  • Ar denotes a phenyl radical which is mono- or polysubstituted.
  • OR or NR 2 are suitable as substituents, where R is H or —CC alkyl, or Halogen, such as F, Cl or Br.
  • the substituents can be in the o-, m- or p-position, the phenyl radical preferably having a maximum of 2 substituents and particularly preferably only one substituent.
  • Preferred substituents are the hydroxyl radical and the alkoxy radical, in which Alkoxy radical of methoxy and ethoxy rest preferred are particularly preferred, the phenyl radical is substituted only in the p-position by OH or OR or in the p-position by OH and in the m-position by OR
  • R ' in the formula (I) denotes a dC 4 -alkyl radical, a C 1 -C 2 -alkyl radical being preferred
  • Phenylacetic acid esters which can be prepared by the process according to the invention are, for example, 4-hydroxy-3-methoxyphenyless ⁇ gsauremethyl- or ethyl ester, 4-
  • Methyl or ethyl methoxyphenylacetate Preferably, methyl or ethyl 4-hydroxyphenylacetate, particularly preferably methyl 4-hydroxyphenylacetate, is prepared
  • correspondingly substituted mandelic acid compounds of the formula (II) or suitable salts thereof serve as the starting compound.
  • suitable salts thereof serve as the starting compound.
  • Na, K or NH 4 salts are suitable as salts
  • the corresponding almond acid compound of the formula (II) or its salt is hydrogenated and esterified at the same time.
  • the alcohol ROH which leads to the desired ester in the end product, is used as the solvent.
  • Methanol, ethanol, propanol or butanol are therefore preferred as alcohols methanol or ethanol are used, particularly preferably methanol is used as the solvent
  • the alcohol serves both as a solvent and as an esterifying agent, it is used in excess, based on the starting material, preferably in an amount of 2 mol to 60 mol per mol of starting material, particularly preferably from 10 to 40 mol per mol of starting material, used
  • Sulfuric acid is also required as an adjuvant for the process according to the invention.
  • the amount of sulfuric acid added depends on the starting material used, and in the case of starting material salts the excess sulfuric acid, based on the starting material, is used.
  • the preferred amount is dependent on the starting material used - educt, 0.3 to 3 mol of sulfuric acid per mol of educt. 0.5 to 2 mol of sulfuric acid per mol of educt are particularly preferably used
  • Suitable hydrogenation catalysts are conventional hydrogenation catalysts, such as transition metals from group 8 of the periodic table, such as Ni, Fe, Co, Pd or Pt catalysts or their salts, oxides or complexes, and elements from groups Ib, IIb, III , IV, V, VIb or VI Ib of the periodic table or their salts, oxides or complexes. Transition metals from group 8 of the periodic table are preferably used, a Pd catalyst, for example PdCl 2 , Pd / C, PdCl 2 -PPh3 etc. is particularly preferred, A Pd / C catalyst is particularly preferred.
  • the catalyst is added in customary amounts of about 1-10% by weight, based on the starting material
  • activated carbon can be added to the reaction mixture to facilitate the isolation of the catalyst after the end of the reaction, approximately in the amount of the catalyst
  • the process according to the invention is carried out at a hydrogen pressure of 2-10 bar, preferably at 3-6 bar and a reaction temperature of 70-150 ° C, preferably at 80-140 ° C and particularly preferably at 100-120 ° C
  • reaction mixture is constantly stirred
  • the catalyst, the sulfate formed when using a commercial acid salt and any activated carbon present are separated from the reaction solution, for example by simple filtration.
  • the remaining sulfuric acid solution is then removed by adding suitable bases, for example NaOH, KOH or NH 3 adjusted to a pH of 2 to 8, preferably 5 to 7, and filtered again.
  • suitable bases for example NaOH, KOH or NH 3 adjusted to a pH of 2 to 8, preferably 5 to 7, and filtered again.
  • the solvent, ie the alcohol is separated off from the filtrate obtained, which contains the desired phenyl acid acetic ester. This can be done, for example, by distillation or on a rotary evaporator respectively

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

Abstract

L'invention concerne un procédé de production de dérivés d'acide phénylacétique de la formule Ar-CH2COOR' (I) où Ar représente un reste phényle substitué au moins une fois par OR, NR2 ou un atome d'halogène ; R représente H ou un reste alkyle en C1-C4 et R' représente un reste alkyle en C1-C4, par hydrogénation et estérification simultanées des acides mandéliques substitués correspondants de la formule Ar-CHOHCOOH (II) où Ar a la signification susmentionnée ou représente un de ses sels adaptés. L'hydrogénation et l'estérification simultanées sont effectuées dans un alcool R'OH, où R' est un reste alkyle en C1-C4, comme solvant, en présence d'acide sulfurique, d'un catalyseur d'hydrogénation et d'hydrogène.
PCT/EP2000/010322 1999-11-17 2000-10-20 Procede de production d'esters d'acide phenylacetique Ceased WO2001036366A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU12739/01A AU1273901A (en) 1999-11-17 2000-10-20 Method for producing phenylacetic acid esters

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ATA1935/99 1999-11-17
AT193599 1999-11-17

Publications (1)

Publication Number Publication Date
WO2001036366A1 true WO2001036366A1 (fr) 2001-05-25

Family

ID=3524212

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2000/010322 Ceased WO2001036366A1 (fr) 1999-11-17 2000-10-20 Procede de production d'esters d'acide phenylacetique

Country Status (2)

Country Link
AU (1) AU1273901A (fr)
WO (1) WO2001036366A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007009590A1 (fr) * 2005-07-18 2007-01-25 Dsm Ip Assets B.V. Procede de preparation de composes phenoliques

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4337355A (en) * 1980-06-20 1982-06-29 Nippon Gohsei Kagaku Kogyo Kabushiki Kaisha Process for preparing 4-hydroxyphenylacetic acid
WO1997038963A1 (fr) * 1996-04-18 1997-10-23 E.I. Du Pont De Nemours And Company Procede de fabrication d'alkyl 2-(6-methoxy-naphtyl)propionates

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4337355A (en) * 1980-06-20 1982-06-29 Nippon Gohsei Kagaku Kogyo Kabushiki Kaisha Process for preparing 4-hydroxyphenylacetic acid
WO1997038963A1 (fr) * 1996-04-18 1997-10-23 E.I. Du Pont De Nemours And Company Procede de fabrication d'alkyl 2-(6-methoxy-naphtyl)propionates

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007009590A1 (fr) * 2005-07-18 2007-01-25 Dsm Ip Assets B.V. Procede de preparation de composes phenoliques

Also Published As

Publication number Publication date
AU1273901A (en) 2001-05-30

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