WO2003045934A1 - Procede de production de 2 (5h)-furanone 5-substituee - Google Patents

Procede de production de 2 (5h)-furanone 5-substituee Download PDF

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Publication number
WO2003045934A1
WO2003045934A1 PCT/JP2002/011346 JP0211346W WO03045934A1 WO 2003045934 A1 WO2003045934 A1 WO 2003045934A1 JP 0211346 W JP0211346 W JP 0211346W WO 03045934 A1 WO03045934 A1 WO 03045934A1
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substituent
group
alkoxy
represented
general formula
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PCT/JP2002/011346
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English (en)
Japanese (ja)
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Takashi Sugioka
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Kuraray Co.,Ltd.
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Priority to AU2002344437A priority Critical patent/AU2002344437A1/en
Publication of WO2003045934A1 publication Critical patent/WO2003045934A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D307/60—Two oxygen atoms, e.g. succinic anhydride

Definitions

  • the present invention relates to a method for producing 2 (5H) -furanone in which the 5-position is substituted with an alkoxyl group or the like.
  • the 5-substituted 1-2 (5H) -furanone obtained according to the present invention for example, 5-ethoxy-12 (5H) -furanone, is useful as a synthetic intermediate for pharmaceuticals such as anti-inflammatory agents.
  • 5-alkoxy-2- (5H) -furanone and other 2- (5H) -furanones in which the 5-position is substituted with an alkoxyl group, etc. can be produced by (1) oxidizing furfural under light irradiation conditions. To obtain 5-hydroxy_2 (5H) -furanone and react it with alcohol [see Tetrahedron, Vol. 44, pp. 7213 (1988)], (2) A method of oxidizing acetylfuran or furan-2-furonic acid ester in an alcohol or acetate solvent under light irradiation conditions [Chemistry Express (Chemistry Ex ress), Vol. 1, pp.
  • the method (7) uses carbon tetrachloride as a solvent and has a problem that it has a large effect on the human body and the environment.
  • the reaction conditions are not efficient because an aqueous solution of potassium carbonate is used and the decomposition of 5-promo 2 (5H) -furanone derivative, which is unstable to water, occurs simultaneously. Therefore, these methods cannot be said to be industrially advantageous methods for producing 2 (5H) -furanone in which the 5-position is substituted with an alkoxyl group or the like.
  • An object of the present invention is to provide a method capable of producing a 5-monosubstituted 1-2 (5H) -furanone such as 5-alkoxy1-2 (5H) -furanone at low cost, efficiently and industrially advantageously. Is to do. Disclosure of the invention
  • the present invention provides a compound represented by the general formula (I):
  • R 1 represents a hydrogen atom, an alkyl group which may have a substituent, an aryl group which may have a substituent, or an aralkyl group which may have a substituent.
  • 2 (3H) -furanones (hereinafter referred to as 2 (3H) -furanones (I)) represented by the general formula (II)
  • R 2 OH (II) (wherein, R 2 is an alkyl group which may have a substituent, a cycloalkyl group which may have a substituent, or an aralkyl which may have a substituent. Represents a hydroxyl group. )
  • R 1 and R 2 are as defined above, and X represents a halogen atom.
  • 4-alkoxy-3-halogenobutyrolactone (hereinafter referred to as 4-alkoxy-13-halogenoabutyrolactone (III)] represented by the formula: General formula (IV) characterized by reacting a lactone (III) with a base
  • 5-alkoxy-12 (5H) -furanone a method for producing 5-alkoxy-12 (5H) -furanone [hereinafter referred to as 5-alkoxy-12 (5H) -furanone (IV)].
  • the present invention is a method for producing 5-alkoxy-12 (5H) -1-furanone (IV), comprising reacting 4-alkoxy-3-halogenoa-butyrolactone (III) with a base.
  • the present invention is 4-alkoxy-13-halogenoa-butyrolactone (III).
  • the present invention relates to a method for converting 2 (3H) monofuranones (I) into alcohols (II) and And a halogenating agent. 4.
  • alkyl group represented by R 1 and R 2 a linear or branched alkyl group having 1 to 6 carbon atoms is preferable, for example, a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group Group, isobutyl group, tert-butyl group, hexyl group and the like.
  • These alkyl groups may have a substituent.
  • substituents examples include an alkoxyl group such as a methoxy group, an ethoxy group, a propoxy group and a butoxy group; a tert-butyldimethylsilyloxy group and a tert-butyldiphenyl group. Trisubstituted silyloxy groups such as silyloxy groups; nitro groups and the like.
  • the cycloalkyl group represented by R 2 is preferably a cycloalkyl group having 3 to 8 carbon atoms, and examples thereof include a cyclopropyl group, a cyclopentyl group, a cyclohexyl group, and a cyclooctyl group.
  • These cycloalkyl groups may have a substituent, and examples of the substituent include alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and tert-butyl.
  • Alkoxyl groups such as methoxy, ethoxy, propoxy and butoxy groups; trisubstituted silyloxy groups such as tert-butyldimethylsilyloxy group, tert-butyldiphenylsilyloxy group; phenyl group, p-methoxyphenyl group And aryl groups such as an enyl group.
  • the aralkyl group represented by R 1 and R 2 is preferably an aralkyl group having an alkyl group having 1 to 6 carbon atoms as an alkyl moiety and an aralkyl group having 6 to 10 carbon atoms as an aryl moiety, such as a benzyl group.
  • the one Examples include a naphthylmethyl group and a phenethyl group.
  • These aralkyl groups may have a substituent. Examples of the substituent include an alkyl group such as a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group and a tert-butyl group.
  • Trifluoromethyl group Trifluoromethyl group; alkoxyl group such as methoxy group, ethoxy group, propoxy group and butoxy group; trisubstituted silyloxy group such as tert-butyldimethylsilyloxy group and tert-butyldiphenylsilyloxy group; nitro group A aryl group such as a phenyl group and a p-methoxyphenyl group;
  • the aryl group represented by R 1 is preferably an aryl group having 6 to 10 carbon atoms, such as a phenyl group and a naphthyl group. These aryl groups may have a substituent. Examples of such a substituent include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isopropyl group, a tert-butyl group, and the like.
  • Alkoxy groups such as methoxy, ethoxy, propoxy and butoxy groups; trisubstituted silyloxy groups such as tert-butyldimethylsilyloxy group and tert-butyldiphenylsilyloxy group Groups; nitro groups; phenyl groups, aryl groups such as p-methoxyphenyl group and the like.
  • halogen atom represented by X examples include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
  • octalogenating agents include chlorine, bromine, sulfuryl chloride, N-chlorosuccinimide, N-bromosuccinimide, 5,5-dimethyl-1,3, -dibromohydantoin, pyridine dibumidamide hydropromide, and bromine-dioxane.
  • Promoted Trichloromethane, Trichloroisocyanur Acids and the like are used.
  • N-chlorosuccinic acid imid N-bromosuccinic acid imid, 5,5-dimethyl-1,3-dibromohydantoin, trichloroisocyanuric acid and the like.
  • the amount of the genating agent is preferably in the range of 0.1 to 10 mol, and more preferably in the range of 0.5 to 2 mol, per 1 mol of 2 (3H) monofuranone (I). Is more preferable.
  • alcohol (II) examples include methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, tert-butanol, 1-pentanol, 2-pentanol, 3 Aliphatic saturated alcohols such as pentanol, 1-hexanol, 2-hexanol, 3-hexanol, 1-octanol, 2-methoxyethanol, 2-ethoxyethanol, 3-ethoxy-1-propanol; benzyl Examples include aromatic alcohols such as alcohol, 1-phenylethanol, 1-naphthalenemethanol, 2-naphthylenemethanol, methylbenzyl alcohol, and methoxybenzyl alcohol.
  • methanol, ethanol, 11-propanol, 11-pentanol, 1-hexanol, 1-octanol and the like are preferably used.
  • the amount of the alcohol (II) to be used is preferably 1 mol or more, more preferably 1 to 100 mol, per 1 mol of 2 (3H) -furanones (I). preferable.
  • alcohol (II) also acts as a solvent.
  • the reaction is preferably performed in the presence of a solvent.
  • the solvent is not particularly limited as long as it does not adversely affect the reaction.
  • examples of the solvent include hydrocarbons such as pentane, hexane, heptane, octane, petroleum ether, and benzene; getyl ether, tetrahydrofuran, and diisopropyl ether.
  • Ethers such as ter, dioxane, dimethoxyethane, dibutyl ether; 1346 Nitriles such as tonitrile, propionitrile, benzonitrile; halogenated carbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,1-dichloroethane, trichloroethane, and cyclobenzene. Hydrogen; or a mixture thereof.
  • the amount of the solvent to be used is preferably in the range of 0.5 to 100 times the weight of the 2 (3H) -furanone (I).
  • the reaction temperature is preferably in the range of 50 to 200 ° C., more preferably in the range of ⁇ 20 to 100 ° C.
  • the reaction time varies depending on the type of 2 (3H) -furanone (I), halogenating agent, alcohol (II) and solvent, the amount used and the reaction temperature, but is in the range of 0.5 to 30 hours. It is preferred that
  • the reaction is preferably carried out by dissolving or suspending, for example, a 2 (3H) monofuranone (I), a halogenating agent and an alcohol (II) as necessary, and stirring the mixture at a predetermined temperature.
  • a 2 (3H) monofuranone (I) for example, a 2 (3H) monofuranone (I), a halogenating agent and an alcohol (II) as necessary, and stirring the mixture at a predetermined temperature.
  • isolating and purifying 4-alkoxy_3-halogenoa-ptyrolactone (III) from the above each can be subjected to the next step.
  • Isolation / purification of 4-alkoxy-3-halogenor-butyrolactone (III) from the reaction mixture can be carried out by a method generally used in the isolation / purification of organic compounds.
  • Examples of the base include carbonates and hydrogen carbonates of alkali metals or alkaline earth metals such as lithium carbonate, sodium carbonate, calcium carbonate, sodium hydrogen carbonate and potassium hydrogen carbonate; sodium hydroxide, potassium hydroxide, Hydroxides of alkali metals or alkaline earth metals such as calcium hydroxide and aluminum hydroxide; tertiary amines such as trimethylamine, triethylamine, triptylamine, trioctylamine, triethanolamine, pyridine, quinoline, etc. Is mentioned.
  • the above-mentioned carbonate, hydrogencarbonate and hydroxide of alkali metal or alkaline earth metal are preferably used in the form of an aqueous solution.
  • bases may be used alone or as a mixture of two or more.
  • tertiary amines are preferably used, and a mixed system of tertiary amines and an aqueous solution of an inorganic base selected from the group consisting of metal carbonates, metal hydrogencarbonates and metal hydroxides is particularly preferable.
  • the amount used is preferably in the range of 0.2 to 50 mol, and more preferably in the range of 0.5 to 5 mol, per 1 mol of 4-alkoxy-3-halogeno-butyrolactone (III). It is better to have one.
  • the reaction is preferably performed in the presence of a solvent.
  • the solvent is not particularly limited as long as it does not adversely affect the reaction.
  • hydrocarbons such as pentane, hexane, heptane, octane, petroleum ether, benzene, toluene, xylene, cumene; Ter, tetrahydrofuran, TJP02 / 11346 Ethers such as diisopropyl ether, dioxane, dimethoxyethane and dibutyl ether; nitriles such as acetonitrile, propionitrile and benzonitrile; halogens such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane and trichloroethane Aprotic polar solvents such as dimethyl sulfoxide and N, N-dimethylformamide; and mixtures thereof.
  • a solvent When a solvent is used, its use
  • the reaction temperature is preferably in the range of 50 ° C to 100 ° C, more preferably in the range of 20 ° C to 30 ° C.
  • the reaction time varies depending on the type of 4-alkoxy-3-halogenoa-ptyrolactone (III), the type of base and solvent, the ratio of the amounts used and the reaction temperature, but is preferably in the range of 0.5 to 30 hours. .
  • the reaction is carried out, for example, by dissolving or suspending a base in a solvent as necessary to a predetermined temperature, adding 4-alkoxy-3-halogeno-butyrolactone (III) to the mixture, and performing the reaction with stirring, or It is preferable that 4-alkoxy-13-halogeno-butyrolactone (III) is dissolved in a solvent, if necessary, to a predetermined temperature, and a base is added to the mixture, followed by stirring.
  • the 5-alkoxy-1 2 (5H) -furanone (IV) thus obtained can be isolated and purified by a method generally used in the isolation and purification of organic compounds.
  • the reaction mixture is separated into an organic layer and an aqueous layer using a separatory funnel, and the aqueous layer is extracted with a solvent such as getyl ether, ethyl acetate, toluene, methylene chloride, 1,2-dichloroethane, and the like.
  • the liquid and organic layers are combined, dried over anhydrous sodium sulfate, etc., and concentrated. Purify the crude product obtained by recrystallization, distillation, silica gel column chromatography, etc. as necessary.
  • the 2 (3H) monofuranones (I) used in the present invention can be obtained, for example, by a method of oxidizing furfural with hydrogen peroxide [The Organic Preparation and Procedures International (The Organic Preparation and Procedures). I nternational), Vol. 28, pp. 2 15 (1996)].
  • Example 1 The Organic Preparation and Procedures International (The Organic Preparation and Procedures). I nternational), Vol. 28, pp. 2 15 (1996)].
  • Example 1 5,5-dimethyl-1,3-dibromohydantoin TJP02 / 11346 Use 1.564 g (6.67 mmo 1) of trichloroisocyanuric acid instead of 2.861 g (10 mmol), and use 10 ml of methanol instead of 20 ml of ethanol The reaction and post-treatment were carried out in the same manner except for the following, and 3.330 g of 3-chloro-4-methoxy- ⁇ -butyrolactone having the following physical properties (purity: 93%, 14.4 mmo1, yield: 72) %).
  • Example 1 N-bromosuccinimide 3.560 g (2 Ommo 1) was used instead of 5,5-dimethyl-1,3-dibromohydantoin 2.861 g (10 mmo 1). The reaction and post-treatment were carried out in the same manner as described above, to give 3.90 g of 3-bromo-4-ethoxy-butyrolactone (purity: 96%, 17.8 mmo1, yield: 89%).
  • Example 2 The same procedure as in Example 2 was repeated, except that 3.824 g (purity 94%, 17.2 mmo 1) of 3-promo 4_ethoxy ⁇ -butyrolactone was used in Example 2, but the 3-chloro-4-methoxy alcohol obtained by the method of Example 3 was used.
  • Example 2 was repeated in the same manner as in Example 2 except that 1.06 g (1 Ommo 1) of sodium carbonate and 2.04 g (20 mmo 1) of triethylamine were used instead of 20 ml of water and the reaction temperature was 0 ° C. The reaction and post-treatment were carried out to obtain 2.095 g (yield 93%) of 5-ethoxy-2 (5H) monofuranone.
  • 5-alkoxy_2 (5H) -furanone (IV) can be produced inexpensively, efficiently, and industrially advantageously.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

L'invention concerne un procédé de production d'une 5-alcoxy-2- (5H) furanone représentée par la formule générale (IV), qui consiste à faire réagir un composé 2 (3H)-furanone représenté par la formule générale (I) avec un alcool représenté par la formule générale (II) et un agent d'halogénation pour obtenir une 4-alcoxy-3-halogéno-η-butyrolactone représentée par la formule générale (III) et à faire réagir la 4-alcoxy-3-halogéno-η-butyrolactone qui en résulte avec une base. (Dans ces formules, R1 représente hydrogène, éventuellement alkyle substitué, éventuellement aryle substitué, ou éventuellement aralkyle substitué; R2 représente éventuellement alkyle substitué, éventuellement cycloalkyle substitué, ou éventuellement aralkyle substitué; et X représente halogéno). Ainsi, sur le plan industriel, la production de 2- (5H) furanone 5-substituée, par exemple une 5-alcoxy-2- (5H) furanone, peut être avantageuse et efficace à moindre un coût.
PCT/JP2002/011346 2001-11-26 2002-10-31 Procede de production de 2 (5h)-furanone 5-substituee WO2003045934A1 (fr)

Priority Applications (1)

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JP2001-358886 2001-11-26

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102187866A (zh) * 2010-03-03 2011-09-21 刘广发 一种高效二溴海因助溶剂
RU2558210C1 (ru) * 2014-04-16 2015-07-27 Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Кубанский государственный технологический университет" (ФГБОУ ВПО "КубГТУ") Способ повышения посевных качеств семян яровой пшеницы

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
FERINGA BEN L., DE LANGE BEN: "Asymmetric 1,4-additions to 5-alkoxy-2(5H)-furanones. An efficient synthesis of (R)- and (S)- 3,4-epoxy-1-butanol", TETRAHEDRON, vol. 44, no. 23, 1988, pages 7213 - 7222, XP002961008 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102187866A (zh) * 2010-03-03 2011-09-21 刘广发 一种高效二溴海因助溶剂
RU2558210C1 (ru) * 2014-04-16 2015-07-27 Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Кубанский государственный технологический университет" (ФГБОУ ВПО "КубГТУ") Способ повышения посевных качеств семян яровой пшеницы

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