WO2004007420A1 - Procede de production d'$g(a)-methyl-$g(b)-cetoester - Google Patents

Procede de production d'$g(a)-methyl-$g(b)-cetoester Download PDF

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Publication number
WO2004007420A1
WO2004007420A1 PCT/JP2003/008847 JP0308847W WO2004007420A1 WO 2004007420 A1 WO2004007420 A1 WO 2004007420A1 JP 0308847 W JP0308847 W JP 0308847W WO 2004007420 A1 WO2004007420 A1 WO 2004007420A1
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WO
WIPO (PCT)
Prior art keywords
formula
ketoester
producing
reaction
methyl
Prior art date
Application number
PCT/JP2003/008847
Other languages
English (en)
Japanese (ja)
Inventor
Toshio Nishizuka
Hiroshi Kurihara
Original Assignee
Meiji Seika Kaisha, Ltd.
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 Meiji Seika Kaisha, Ltd. filed Critical Meiji Seika Kaisha, Ltd.
Priority to AU2003280975A priority Critical patent/AU2003280975A1/en
Priority to JP2004521195A priority patent/JP4316499B2/ja
Publication of WO2004007420A1 publication Critical patent/WO2004007420A1/fr

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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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
    • B01J23/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals
    • B01J23/40—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals of the platinum group metals
    • B01J23/44—Palladium
    • 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
    • C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
    • C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J21/00—Catalysts comprising the elements, oxides, or hydroxides of magnesium, boron, aluminium, carbon, silicon, titanium, zirconium, or hafnium
    • B01J21/18—Carbon

Definitions

  • the present invention relates to a method for producing ⁇ -methyl-
  • 3-ketoesters typified by ethyl acetate, are useful compounds as raw materials for producing pyrin-type antipyretics and sulfonamide-type agricultural chemicals, and are widely used.
  • Japanese Patent Publication No. 49-34661 discloses that a / 3-ketoester such as ethyl acetate is condensed with formaldehyde and the resulting alkylidene compound is hydrogenated in the presence of a palladium catalyst.
  • a method for producing a 1-methyl-3-ketoester has been disclosed. However, in this production method, the yield of the target compound is usually
  • ethyl 2-acetoxymethyl-acetoacetate is formed by condensing ethyl acetate with formaldehyde in the presence of acetic anhydride.
  • a production method is disclosed in which hydrogenolysis is carried out in the presence of a radium catalyst to obtain the desired ethyl 2-methylacetoacetate.
  • a pressure of 50 atm is applied, and solid paraformaldehyde is
  • One method is to heat the mixture to 80 ° C or more and thermally decompose it to form gaseous formaldehyde, which is then introduced into the reaction solution in gaseous form.
  • treating a compound that is highly carcinogenic and irritating in a gaseous state should be avoided as an industrial-scale production method.
  • the present inventors have now used inexpensive) 3-ketoester as a starting material, dissolve solid paraformaldehyde in] 3-ketoester and acetic anhydride without thermally decomposing paraformaldehyde, and present the presence of a lower alcohol. It has been found that by performing the following reaction and then subjecting to hydrogenolysis, it is possible to obtain hexamethyl-1- ⁇ -ketoester in a good yield.
  • an object of the present invention is to provide a production method capable of obtaining a monomethyl_-ketoester in good yield and safely.
  • the production method according to the present invention is a production method of the following general formula (I) monomethyl ketoester:
  • R 1 represents an optionally substituted straight-chain or branched-chain — 6 alkyl group or a cycloalkyl group
  • —R 2 represents a straight-chain or branched-chain C 4 alkyl group .
  • R 1 and R 2 are as defined above.
  • R 1 and R 2 are as defined above.
  • An object of the production method according to the present invention is a monomethyl-
  • R 1 represents a Ct- 6 alkyl group or a cycloalkyl group, and the alkyl group may be linear or branched.
  • the alkyl group may be substituted with one or more substituents. Examples of the substituent include a halogen atom (for example, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom), a hydroxyl group, and a Examples include branched alkyl groups c
  • the cycloalkyl group represented by R 1 is preferably a C-cycloalkyl group.
  • R 2 represents a linear or branched -4 alkyl group.
  • the compound represented by the formula (I) is useful as an intermediate for synthesizing various useful compounds.
  • a 6-t-butyl-8-fluoroquinoline derivative disclosed in WO 01/9223 31 is a compound having excellent control activity against agricultural and horticultural diseases.
  • the compounds of the formula (I) are used. That is, 41-t-butyl-2-fluoroaerin or a salt thereof was prepared by the method described in WOO 1/922331, J. Chem. Soc., (C). 2426 (1970) or Tetrahedron Lett., 4945 (1968).
  • a mixture of 3-ketoester and acetic anhydride is prepared.
  • the ratio of the compound of the formula (II) to acetic anhydride is not limited as long as the paraformaldehyde added next can be dissolved, but is preferably about 1:10 to 10: 1 (weight ratio), more preferably It is about 1: 5 to 5: 1 (weight ratio).
  • paraformaldehyde is added to and dissolved in the mixture of the compound of the formula (II) and acetic anhydride.
  • the use of formaldehyde as a gas in the reaction is disadvantageous or desired to be avoided in industrial production processes.
  • paraformaldehyde is dissolved in a mixture of the compound of the formula (II) and acetic anhydride, so that handling thereof is extremely easy.
  • paraformaldehyde is preferably used in an amount of 1 to 10 equivalents, more preferably about 1 to 3 equivalents, based on the formula (II).
  • reaction of the compound of formula (II) with acetic anhydride and paraformaldehyde is carried out in the presence of a hydrous lower alcohol.
  • the lower alcohol is preferably a 6 -valent alcohol, more preferably ethyl alcohol.
  • the lower alcohol contains water. The amount is 0.1-1.5% by weight alcohol /. And preferably from 0.3 to 0.8% by weight, most preferably 0.5% by weight.
  • the amount of the water-containing lower alcohol present in the reaction system may be appropriately determined, but is preferably about 2 to 50% by weight, more preferably about 2 to 50% by weight based on the total amount of the compound of the formula (II), acetic anhydride, and paraformaldehyde. Is about 3 to 30% by weight.
  • the reaction of the compound of formula (II), acetic anhydride and paraformaldehyde in the presence of a hydrous lower alcohol is carried out under heating.
  • the temperature and the reaction time may be determined as appropriate while taking into account the formation of by-products, the yield, etc., but are generally from room temperature to about 100 ° C., preferably from 35 to 50 ° C. ° C, most preferably about 40 ° C, and the reaction time is generally about 5 to 100 hours, preferably 7 to 80 hours.
  • R 1 and R 2 are as defined above.
  • the compound of the formula (III) is subjected to hydrogenolysis to obtain a thiomethylketoester represented by the formula (I).
  • This hydrogenolysis may be appropriately determined as long as the compound of the formula (I) is obtained.
  • the hydrogenolysis is carried out by contact with hydrogen under a palladium-carbon catalyst (for example, the reaction of hydrogen with hydrogen). It is preferable to pass the mixture directly or place the reaction mixture in a hydrogen atmosphere).
  • the reaction conditions may be determined as appropriate, but the hydrogen pressure is preferably about 1 to 50 atm, more preferably about 1 to 20 atm.
  • the reaction time is 5 to preferably about 100 hours, c palladium and more preferably about 7-80 hours - abundance of carbon May be appropriately determined, but is preferably about 0.01 to 0.2% by weight, more preferably about 0.02 to 0.1% by weight, based on the compound of the formula (III).
  • a step of producing a compound of the formula (III) by reacting the compound of the formula (II) with acetic anhydride and paraformaldehyde, and hydrogenating the compound of the formula (II I) the reaction conditions for the decomposition reaction one can be carried out continuously in a reaction system c at this time, about the hydrogen pressure to 50 atm, more preferably from about 1 to 20 atmospheres, a temperature from room temperature to The reaction temperature is preferably about 100 ° C., more preferably about 35 to 50 ° C., and the reaction time is preferably about 5 to 100 hours, more preferably about 7 to 80 hours.
  • the resulting compound of formula (I) is then isolated from the reaction system, for example
  • AD 10% palladium-carbon catalyst
  • a paraformaldehyde pellet (4.60 g, 1 mol) was added to a mixture of ethyl acetate (1.0 g, 0.768 mol) and acetic anhydride (8.60 g, 0.845 mol). .5 4 mol) was dissolved.
  • 99.5% ethanol water content: 0.5% by weight
  • 45 OmL 45 OmL
  • 50 Omg of 5% palladium-carbon catalyst (0.5% by weight based on the substrate weight
  • Kawaken Fine Chemicals AD 5% Pd / C

Landscapes

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

Abstract

L'invention concerne un procédé de production efficace d'un α-méthyl-β-cétoester à partir d'un β-cétoester en tant que matière de départ sans utiliser de réactif toxique ou sans que ce soit dans des conditions très difficiles. Ledit procédé consiste à dissoudre du paraformaldéhyde dans un mélange liquide d'un β-cétoester et d'anhydride acétique, à ajouter un alcool inférieur aqueux, et à mener à bien l'hydrolyse dans une atmosphère d'hydrogène à l'aide d'un catalyseur au palladium-carbone.
PCT/JP2003/008847 2002-07-11 2003-07-11 Procede de production d'$g(a)-methyl-$g(b)-cetoester WO2004007420A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU2003280975A AU2003280975A1 (en) 2002-07-11 2003-07-11 PROCESS FOR PRODUCING Alpha-METHYL-ss-KETO ESTER
JP2004521195A JP4316499B2 (ja) 2002-07-11 2003-07-11 α−メチル−β−ケトエステルの製造法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2002-202214 2002-07-11
JP2002202214 2002-07-11

Publications (1)

Publication Number Publication Date
WO2004007420A1 true WO2004007420A1 (fr) 2004-01-22

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ID=30112611

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Application Number Title Priority Date Filing Date
PCT/JP2003/008847 WO2004007420A1 (fr) 2002-07-11 2003-07-11 Procede de production d'$g(a)-methyl-$g(b)-cetoester

Country Status (5)

Country Link
JP (1) JP4316499B2 (fr)
CN (1) CN1318379C (fr)
AU (1) AU2003280975A1 (fr)
TW (1) TW200403221A (fr)
WO (1) WO2004007420A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009020211A1 (fr) * 2007-08-08 2009-02-12 Meiji Seika Kaisha, Ltd. Nouveau procédé de production d'un alpha-méthyl-bêta-cétoester
CN107188807A (zh) * 2017-07-10 2017-09-22 济南大学 阿拉伯糖制备乙酰丙酸乙酯的方法

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110483290B (zh) * 2019-08-09 2022-05-31 上海应用技术大学 一种铜催化合成β-酮酸酯的方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4567004A (en) * 1983-07-23 1986-01-28 Bayer Aktiengesellschaft Process for the preparation of monomethyl-substituted methylene compounds

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH560176A5 (en) * 1972-04-24 1975-03-27 Lonza Ag Ethyl alpha-methyl-aceto-acetate prodn. - from formaldehyde gas and acetoacetic ester contg. acetic anhydride and hydrogenation

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4567004A (en) * 1983-07-23 1986-01-28 Bayer Aktiengesellschaft Process for the preparation of monomethyl-substituted methylene compounds

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009020211A1 (fr) * 2007-08-08 2009-02-12 Meiji Seika Kaisha, Ltd. Nouveau procédé de production d'un alpha-méthyl-bêta-cétoester
JP5275235B2 (ja) * 2007-08-08 2013-08-28 Ｍｅｉｊｉ Ｓｅｉｋａファルマ株式会社 α−メチル−β−ケトエステルの新規製造法
CN107188807A (zh) * 2017-07-10 2017-09-22 济南大学 阿拉伯糖制备乙酰丙酸乙酯的方法

Also Published As

Publication number Publication date
JP4316499B2 (ja) 2009-08-19
TWI310031B (fr) 2009-05-21
TW200403221A (en) 2004-03-01
AU2003280975A1 (en) 2004-02-02
CN1318379C (zh) 2007-05-30
JPWO2004007420A1 (ja) 2005-11-10
CN1735586A (zh) 2006-02-15

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