EP1494987A1 - Procede de production d'acide 2,4,5-trimethyle-phenyle-acetique - Google Patents

Procede de production d'acide 2,4,5-trimethyle-phenyle-acetique

Info

Publication number
EP1494987A1
EP1494987A1 EP03745691A EP03745691A EP1494987A1 EP 1494987 A1 EP1494987 A1 EP 1494987A1 EP 03745691 A EP03745691 A EP 03745691A EP 03745691 A EP03745691 A EP 03745691A EP 1494987 A1 EP1494987 A1 EP 1494987A1
Authority
EP
European Patent Office
Prior art keywords
acid
trimethylphenyl
isomeric
ethanone
pseudocumene
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.)
Withdrawn
Application number
EP03745691A
Other languages
German (de)
English (en)
Inventor
Thomas Himmler
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.)
Bayer CropScience AG
Original Assignee
Bayer CropScience AG
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 Bayer CropScience AG filed Critical Bayer CropScience AG
Publication of EP1494987A1 publication Critical patent/EP1494987A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
    • C07C45/46—Friedel-Crafts reactions
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
    • C07C49/80—Ketones containing a keto group bound to a six-membered aromatic ring containing halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/093—Preparation of carboxylic acids or their salts, halides or anhydrides by hydrolysis of —CX3 groups, X being halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
    • C07C51/377—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups

Definitions

  • the present invention relates to a new process for the preparation of 2,4,5-trimethylphenylacetic acid.
  • 2,4,5-Trimethylphenylacetic acid is a well-known compound (for example from: J. Prakt. Chem. 80 (1909) 193; J. Amer. Chem. Soc. 58 (1936) 629-35).
  • the preparation can be carried out, for example, starting from 2,4,5-trimethylphenyl acetophenone by an illgerodt-Kindler reaction.
  • this method produces large amounts of sulfur-containing waste.
  • highly odorous, volatile sulfur compounds can occur.
  • Another method is based on 2,4,5-trimethylbenzyl bromide. It is used e.g. the corresponding nitrile with sodium cyanide, which is then saponified (J. Amer. Chem. Soc. 58 (1936) 629-35; DE-A 19 602 524).
  • This nitrile can also be obtained by reacting durol (1,2,4,5-tetramemylbenzene) with cyanogen chloride at above 600 ° C. (DE-A 2 854210); however, the high toxicity of cyanogen chloride is disadvantageous.
  • the 2,4,5-trimethylbenzyl bromide required can in turn be produced by bromination of durol with N-bromo-succmimide (see, for example, J. Amer. Chem. Soc. 92 (1970) 994-8).
  • it is disadvantageous here that experience has shown that such brominations also lead to multi-brominated products, so that complex cleaning steps are necessary.
  • 2,4,5-trimethylphenylacetic acid can be obtained in high yield and isomer purity by firstly producing pseudocumene with dichloroacetyl chloride in a Friedel-Crafts reaction to give 2,2-dichloro-l- (2,4,5 -trimethylphenyl) -ethanone is converted, the 2,4,5-trimethylmandelic acid is produced from it using an alkali metal hydroxide and is then finally used
  • Dichlorinated acetophenones can also be prepared in a two-stage process by Friedel-Craf s acylation of the corresponding aromatics with acetyl chloride and subsequent chlorination.
  • the present invention accordingly also relates to the new connection
  • the 2,4,5-trimethylphenylacetic acid can be prepared in a simpler manner, in better selectivity and in a better yield than in the previously known processes by the process according to the invention.
  • 2,2-dichloro-l- (2,4,5-trimethylphenyl) ethanone is prepared by the first step of the process according to the invention by reacting pseudocumene with dichloroacetyl chloride in the presence of a Friedel-Crafts catalyst.
  • aluminum chloride, iron (III) chloride, tin tetrachloride or zeolites can be used as Friedel-Crafts catalysts in the process according to the invention.
  • Aluminum chloride is preferably used as the Friedel-Crafts catalyst.
  • the amount of Friedel-Crafts catalyst to be used in the process according to the invention is not critical. For example, 0.8 to 1.2 moles of catalyst can be used per dichloroacetyl chloride. 0.9 to 1.1 moles of dichloroacetyl chloride per mole of dichloroacetyl chloride are preferred.
  • Solvents for the Friedel-Crafts reaction are largely inert solvents such as nitrobenzene, carbon disulfide, methylene chloride, 1,2-dichloroethane or pseudocumene itself are used in the process according to the invention. Carbon disulfide, 1,2-dichloroethane and pseudocumene are preferred.
  • Pseudocumol is particularly preferred.
  • the amount of dichloroacetyl chloride to be used by the process according to the invention is not critical and can be varied within wide limits.
  • 0.8 to 1.2 moles of dichloroacetyl chloride can be used per mole of pseudocumene.
  • 0.9 to 1.1 moles of dichloroacetyl chloride per mole of pseudocumol are preferred.
  • the first step of the process according to the invention can be carried out at temperatures between -20 and + 60 ° C. Temperatures between - 10 and + 30 ° C are preferred.
  • reaction times of the first step of the process according to the invention are between 1 and 24 hours.
  • NaOH, KOH and CsOH can be used as alkali metal oxide in the second step of the process according to the invention.
  • NaOH and KOH are preferred; NaOH is particularly preferred.
  • the amount of alkali hydroxide is 3 to 7 moles per mole of 2,2-dichloro-1 - (2,4,5-trimethylphenyl) ethanone. 4 to 6 moles per mole of 2,2-dichloro-1- (2,4,5-trimethylphenyl) ethanone are preferably used.
  • Water is used as the solvent for the second step of the process according to the invention.
  • the second step of the process according to the invention can be carried out at temperatures between -20 and + 120 ° C. Temperatures between +20 and + 110 ° C are preferred.
  • reaction times of the second step of the process according to the invention are between 1 and 24 hours.
  • the reduction of 2,4,5-trimethylmandelic acid in the third step of the process according to the invention can be carried out by various fundamentally known methods for reducing mandelic acids, for example using hydrogen on suitable catalysts or using red phosphorus.
  • the reduction is preferably carried out with red phosphorus.
  • the red phosphorus is in the third step of the process according to the invention in
  • Amounts of 0.67 to 3 moles per mole of 2,4,5-trimethylmandelic acid are used. 1 to 2 moles per mole of 2,4,5-trimethylmandelic acid are preferred. Excess red phosphorus can be recovered and reused.
  • hydrogen iodide, KJ or NaJ is used as the iodide source.
  • iodine can also be used. NaJ or KJ is preferably used.
  • the amount of iodide is 1 to 30 mole percent (based on 2,4,5-trimethylmandelic acid); 5 to 20 mole percent are preferably used.
  • Suitable solvents in the third step of the process according to the invention are formic acid, acetic acid, propionic acid, etc., mixtures of these solvents, or 70 to 85% aqueous phosphoric acid. 70 to 85% aqueous phosphoric acid and acetic acid are preferred; acetic acid is particularly preferred.
  • conc. Sulfuric acid, conc. Hydrochloric acid or 80 to 85% aqueous phosphoric acid are used.
  • the third step of the method according to the invention can be carried out at temperatures between +20 and + 120 ° C. Temperatures between +60 and + 110 ° C are preferred.
  • reaction times of the third step of the process according to the invention are between 1 and 24 hours.
  • A1C1 3 146.6 g of A1C1 3 are introduced in portions into a mixture of 333 g of pseudocumene and 147.7 g of dichloroacetyl chloride at 0-5 ° C. in the course of 2-3 hours. The mixture is then stirred at 0-5 ° C for 2 hours and allowed to come to room temperature. The reaction mixture is concentrated in 3300 ml of ice water with 66.7 g. Hydrochloric acid stirred in. It is extracted with once 350 ml and twice 500 ml of ethyl acetate. The combined organic phases are first shaken with 165 ml of water and then 85 ml of saturated aqueous NaCl solution, dried and concentrated (up to 70 ° C. bath / 1 mbar).
  • Target product isomers 5.32%; i.e. the ratio of ZP to isomers is approximately 94: 6.
  • reaction mixture is mixed with 400 ml of water at 45 ° C. and with 400 ml of MTBE at room temperature, the phases are separated, the aqueous phase is shaken again with 300 ml of MTBE, then acidified with sulfuric acid and the precipitated solid is suctioned off. This is washed three times with 50 ml of water and then dried. This gives 102.4 g of white solid which, according to GC, is 91.9%
  • Example 5 2,4,5-trimethylphenylacetic acid
  • a mixture of 69.9 g of 2,4,5-trimethylmandelic acid, 38.3 g of 36% hydrochloric acid, 11.2 g of red phosphorus and 6 g of KJ in 270 ml of glacial acetic acid is heated to 100 ° C. for 16 hours. It is then diluted with 150 ml of glacial acetic acid at room temperature. The excess phosphorus is filtered off and washed with three times 50 ml of glacial acetic acid. The filtrate is mixed with 150 ml of water and the acetic acid at 50 ° C bath. / 60 mbar largely spun off. The remaining suspension is adjusted to pH 1 with 5 ml of 20% sulfuric acid and the solid is filtered off with suction.
  • A1C1 3 are introduced in portions into a mixture of 60 g of pseudocumene and 7.85 g of acetyl chloride within 1-2 hours. The mixture is then stirred at 0-5 ° C for 2 hours and allowed to come to room temperature. The reaction mixture is concentrated in 340 ml of ice water with 7 g. Hydrochloric acid stirred in. It is extracted with 35 ml once and twice 50 ml of ethyl acetate. The combined organic phases are first shaken with 20 ml of water and then 10 ml of saturated aqueous ⁇ aCl solution, dried and concentrated (up to 70 ° C. bath / 1 mbar).

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention concerne un nouveau procédé de production d'acide 2,4,5-triméthyle-phényle-acétique. Ce procédé consiste à faire réagir du pseudocumol avec du dichloracétylchlorure dans une réaction de Friedel-Crafts pour obtenir 2,2-dichloro-1-(2,4,5-triméthylphényle)-éthanone, à partir duquel on produit l'acide 2,4,5-triméthylmandélique à l'aide d'un hydroxyde de métal alcalin puis on réduit cet acide pur obtenir de l'acide 2,4,5-triméthyle-phényle-acétique.
EP03745691A 2002-04-08 2003-03-27 Procede de production d'acide 2,4,5-trimethyle-phenyle-acetique Withdrawn EP1494987A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10215294 2002-04-08
DE10215294A DE10215294A1 (de) 2002-04-08 2002-04-08 Verfahren zur Herstellung von 2,4,5-Trimethylphenylessigsäure
PCT/EP2003/003180 WO2003084914A1 (fr) 2002-04-08 2003-03-27 Procede de production d'acide 2,4,5-trimethyle-phenyle-acetique

Publications (1)

Publication Number Publication Date
EP1494987A1 true EP1494987A1 (fr) 2005-01-12

Family

ID=28458618

Family Applications (1)

Application Number Title Priority Date Filing Date
EP03745691A Withdrawn EP1494987A1 (fr) 2002-04-08 2003-03-27 Procede de production d'acide 2,4,5-trimethyle-phenyle-acetique

Country Status (9)

Country Link
US (1) US7019166B2 (fr)
EP (1) EP1494987A1 (fr)
JP (1) JP2005522475A (fr)
KR (1) KR20040102068A (fr)
CN (1) CN1659129A (fr)
AU (1) AU2003226720A1 (fr)
DE (1) DE10215294A1 (fr)
IL (1) IL164437A0 (fr)
WO (1) WO2003084914A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101298416B (zh) * 2008-06-10 2012-05-02 中国科学院广州化学研究所 一种由天然茴香脑制备对甲氧基苯乙酸的方法
CN101353296B (zh) * 2008-09-02 2011-09-21 中国科学院广州化学研究所 一种以可再生天然植物资源为原料制备(z)-3＇-羟基-3,4,4＇,5-四甲氧基二苯乙烯的方法

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3658923A (en) * 1969-12-29 1972-04-25 Phillips Petroleum Co Halomethylation of trimethylbenzenes
DE2854210C2 (de) * 1978-12-15 1984-08-09 Degussa Ag, 6000 Frankfurt Verfahren zur Herstellung von aromatisch oder heteroaromatisch substituierten Acetonitrilen
MX9710373A (es) * 1995-06-28 1998-07-31 Bayer Ag Fenilcetoenoles 2,4,5-trisubstituidos para el empleo como pesticidas y herbicidas.
CN1215390A (zh) * 1996-04-02 1999-04-28 拜尔公司 取代的苯基酮烯醇杀虫剂及除草剂

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO03084914A1 *

Also Published As

Publication number Publication date
KR20040102068A (ko) 2004-12-03
DE10215294A1 (de) 2003-10-23
AU2003226720A1 (en) 2003-10-20
US20050182274A1 (en) 2005-08-18
IL164437A0 (en) 2005-12-18
JP2005522475A (ja) 2005-07-28
WO2003084914A1 (fr) 2003-10-16
CN1659129A (zh) 2005-08-24
US7019166B2 (en) 2006-03-28

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