WO1997047582A1 - Procede pour la preparation de cycloalkylcetones substituees - Google Patents

Procede pour la preparation de cycloalkylcetones substituees Download PDF

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Publication number
WO1997047582A1
WO1997047582A1 PCT/EP1997/002765 EP9702765W WO9747582A1 WO 1997047582 A1 WO1997047582 A1 WO 1997047582A1 EP 9702765 W EP9702765 W EP 9702765W WO 9747582 A1 WO9747582 A1 WO 9747582A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
process according
coor
alkyl
substituted cycloalkyl
Prior art date
Application number
PCT/EP1997/002765
Other languages
German (de)
English (en)
Inventor
Joachim Komoschinski
Nikolaus Müller
Original Assignee
Bayer 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 Bayer Aktiengesellschaft filed Critical Bayer Aktiengesellschaft
Priority to JP10501119A priority Critical patent/JP2000511911A/ja
Priority to EP97925960A priority patent/EP0906266A1/fr
Priority to HU0100108A priority patent/HUP0100108A2/hu
Publication of WO1997047582A1 publication Critical patent/WO1997047582A1/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
    • C07C67/333—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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/74—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring
    • C07C69/757—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety

Definitions

  • the present invention relates to a process for the preparation of cycloalkyl ketones mono- and di-substituted in the ⁇ -position.
  • Substituted cycloalkyl ketones can, for example, by the known
  • Dieckmann condensation can be produced.
  • a necessary prerequisite for this type of condensation reaction is the presence of an activated methylene group and of keto ester functions in the ⁇ and ⁇ positions.
  • R is C j -C jQ alkyl or C 6 -C 10 aryl, each optionally with 1 to 3 substituents from the group of the C, -C 6 alkyl, C, -C 6 alkoxy and sulfone groups and C 6 -C ] 0 -aryl can optionally also be substituted with halogen and
  • n an integer from 1 to 8
  • R 2 has the same scope as R 1 and can be the same or different from R,
  • Z and Z 1 are the same or different and each represents chlorine or bromine and
  • R 1 has the meaning given for formula (I) and
  • R 3 represents Na, K or R 2 ,
  • R 2 has the meaning given for formula (I),
  • alkyl radicals including those in alkoxy radicals, can be straight-chain or branched
  • Halogen can be, for example, fluorine, chlorine or bromine
  • Substituted cycloalkyl ketones of the formula (I) are preferably prepared in which X is COOR 2 or H, R 1 and R 2 are the same and are unsubstituted straight-chain or branched C, -C 4 -alkyl or unsubstituted phenyl, in particular for methyl or ethyl stand, and m represents an integer from 2 to 5, wherein the corresponding carboxylic acid halides of the formula (II) and the corresponding malonic ester derivatives of the formula (III) are reacted with one another
  • the components can be used, for example in a molar ratio of (II) to (III), from 1 1 to 1 3. This ratio is preferably from 1 1 to 1 2
  • Suitable bases for the process according to the invention are, for example, alkali metal and alkaline earth metal alcoholates, t ⁇ alkylamines and aromatic amines, where t ⁇ alkylamines and aromatic amines are to be used in combination with magnesium chloride. At least 1 mole of magnesium chloride is used in relation to 1 mol of t ⁇ alkylamine or aromatic amine Preferably 1 to
  • the alkali and alkaline earth metal alcoholates can contain, for example, alkyl groups with 1 to 8 carbon atoms in the alcoholate part.
  • Sodium and potassium methylate, ethylate, isopropoxide, n-butoxide and t-butoxide are preferred.
  • the trialkylamines can be, for example, those of the formula (IV)
  • R 4 to R 6 are the same or different and each represents C, -C 8 alkyl
  • At least one of the three radicals R 4 to R 6 is a C r C 4 alkyl radical
  • T ⁇ methyl-, T ⁇ ethyl-, T ⁇ propyl- and T ⁇ butylamine are particularly preferred
  • aromatic amines examples include Py ⁇ din, Picohn and Colhdin
  • the base can be used, for example, in amounts of 0.5 to 3 mol, based on 1 mol of the compound of the formula (II). This amount is preferably
  • organic solvent examples include methylene chloride, acetic acid esters, in particular ethyl acetate and ethyl acetate and acetonitrile. Acetonitrile is preferred.
  • the implementation according to the invention can e.g. in the temperature range from -15 to + 20 ° C. -10 to + 15 ° C are preferred.
  • the method according to the invention can e.g. perform so that one
  • Heating should be intercepted by cooling so that the carboxylic acid halide can then be metered in if possible at -15 to + 20 ° C.
  • the reaction according to the invention is generally ended shortly after the addition of the last amounts of carboxylic acid halide. If necessary, you can still stir, e.g. 1 to 15 hours at e.g. +10 to + 30 ° C.
  • reaction mixture can e.g. so that it is first concentrated, then an organic, water-immiscible solvent, e.g. Methylene chloride or toluene, and water is added, whereupon two phases form and finally isolate the substituted cycloalkyl ketone of the formula (I) prepared from the organic phase by removing the solvent.
  • an organic, water-immiscible solvent e.g. Methylene chloride or toluene
  • the process according to the invention permits the preparation of substituted cycloalkyl ketones of the formula (I) in a simple manner and with good yields. It is particularly advantageous that cycloalkyl ketones of the formula (I) can be prepared in a one-step process according to the invention. This is particularly surprising because from J. Org. Chem. 50, 2622 (1985) it is only known that one can acylate with alcoholates or a base system consisting, for example, of triethylamine, magnesium chloride and acetonitrile, diethyl malonate with carboxylic acid chlorides. In the method according to the invention, an unforeseeable intramolecular ring closure takes place at the same time.
  • reaction mixture was concentrated on a rotary evaporator, 522 g of a light yellow, viscous residue being obtained. 750 ml of methylene chloride were added to this, then 500 ml of water were added dropwise with stirring. Two well-separated phases formed. The organic phase was separated off, dried and concentrated on a rotary evaporator. 210 g of cyclopentanone-2,2-dicarboxylic acid di ethyl ester were obtained in this way

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

Abstract

L'invention concerne des cycloalkylcétones substituées de la formule (I) dans laquelle les symboles utilisés ont la notation donnée dans la description. Pour préparer ces composés, on fait réagir un halogénure d'acide carboxylique de la formule (II), dans laquelle les symboles utilisés ont la notation donnée dans la description, avec un dérivé ester d'acide malonique de la formule (III), dans laquelle les symboles utilisés ont la notation donnée dans la description, en présence d'une base. Ce procédé donne de bons rendements et un bonne sélectivité, s'effectue en une étape et permet de préparer aisément des cycloalkylcétones substituées qui le sont deux fois en position α.
PCT/EP1997/002765 1996-06-10 1997-05-28 Procede pour la preparation de cycloalkylcetones substituees WO1997047582A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
JP10501119A JP2000511911A (ja) 1996-06-10 1997-05-28 置換シクロアルキルケトンの製造法
EP97925960A EP0906266A1 (fr) 1996-06-10 1997-05-28 Procede pour la preparation de cycloalkylcetones substituees
HU0100108A HUP0100108A2 (hu) 1996-06-10 1997-05-28 Eljárás szubsztituált cikloalkil-keton-származékok előállítására

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19623063.2 1996-06-10
DE19623063A DE19623063A1 (de) 1996-06-10 1996-06-10 Verfahren zur Herstellung substituierter Cycloalkylketone

Publications (1)

Publication Number Publication Date
WO1997047582A1 true WO1997047582A1 (fr) 1997-12-18

Family

ID=7796501

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1997/002765 WO1997047582A1 (fr) 1996-06-10 1997-05-28 Procede pour la preparation de cycloalkylcetones substituees

Country Status (7)

Country Link
EP (1) EP0906266A1 (fr)
JP (1) JP2000511911A (fr)
KR (1) KR20000016482A (fr)
CN (1) CN1221400A (fr)
DE (1) DE19623063A1 (fr)
HU (1) HUP0100108A2 (fr)
WO (1) WO1997047582A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116023263A (zh) * 2022-11-17 2023-04-28 苏州汉德创宏生化科技有限公司 一种中间体3-(3,5-二氯苯基)-3-氧代丙酸乙酯的合成方法

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
GÉRARD LHOMMET ET AL.: "Synthèse du gamma-chlorobutyrylacétate d'éthyle", COMPTES RENDUS HEBDOMADAIRES DES SEANCES DE L'ACADEMIE DES SCIENCES, SERIE C: SCIENCES CHIMIQUES, vol. 279, no. 6, 5 August 1974 (1974-08-05), MONTREUIL FR, pages 263 - 266, XP002040465 *
GLENN S. SKINNER ET AL.: "The Relative Instability of a C5-Spirobarbituric Acid", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 72, no. 4, 19 April 1950 (1950-04-19), DC US, pages 1648 - 1649, XP002040466 *
MICHEAL W.RATHKE ET AL.: "Procedures for the Acylation of Diethyl Malonate and Ethyl Acetoacetate with Acid Chlorides Using Tertiary Amine Bases and Magnesium Chloride", JOURNAL OF ORGANIC CHEMISTRY, vol. 50, no. 15, 26 July 1985 (1985-07-26), EASTON US, pages 2622 - 2624, XP002040464 *

Also Published As

Publication number Publication date
KR20000016482A (ko) 2000-03-25
JP2000511911A (ja) 2000-09-12
CN1221400A (zh) 1999-06-30
DE19623063A1 (de) 1997-12-11
HUP0100108A2 (hu) 2001-06-28
EP0906266A1 (fr) 1999-04-07

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