WO2003045934A1

WO2003045934A1 - Process for producing 5-substituted 2(5h)-furanone

Info

Publication number: WO2003045934A1
Application number: PCT/JP2002/011346
Authority: WO
Inventors: Takashi Sugioka
Original assignee: Kuraray Co.,Ltd.
Priority date: 2001-11-26
Filing date: 2002-10-31
Publication date: 2003-06-05
Also published as: AU2002344437A1

Abstract

A process for producing a 5-alkoxy-2(5H)-furanone represented by the general formula (IV), characterized by reacting a 2(3H)-furanone compound represented by the general formula (I) with an alcohol represented by the general formula (II) and a halogenating agent to obtain a 4-alkoxy-3-halogeno-Ϝ-butyrolactone represented by the general formula (III) and reacting the resultant 4-alkoxy-3-halogeno-Ϝ-butyrolactone with a base. (I) (II) (III) (IV) (In the formulae, R1 represents hydrogen, optionally substituted alkyl, optionally substituted aryl, or optionally substituted aralkyl; R2 represents optionally substituted alkyl, optionally substituted cycloalkyl, or optionally substituted aralkyl; and X represents halogeno.) Thus, a 5-substituted 2(5H)-furanone, such as a 5-alkoxy-2(5H)-furanone, can be industrially advantageously produced efficiently at low cost.

Description

Specification

Method for producing 5-substituted mono (5H) monofuranone

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. Background art

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. 475 (1989) ), (3) Method of oxidizing 2-silyloxyfuran derivatives with sodium benzene [Tetrahedron Letters, Vol. 30, pp. 31--19 (1989 See), (4) Dalioxylic acid and aldehyde Production of 5-Alkoxy-12 (5H) -furanones with a Substituent at the 4-Position by Mannich Reaction with and [Journal of Organic Chemistry (J. Org. Chem.), Vol. 46 , 488, 9 (1 (981 years)], (5) Heating 3-formylmethacrylic acid in hydrochloric acid to obtain 5-hydroxy-3-methyl-12 (5H) -furanone and reacting it with alcohol [ Journal of the Chemical Society (c) (see J. Chem. Soc., (C)), pp. 1984 (1966)], (6) .5—Promote 4-methoxy — 2 (5H) Method of Applying Alcohol to 1-Furanone [Journal of the Chemical Society, Parkin Transaction I (J. Chem. Soc, Perkin Trans. I), No. 7 17 Page (1 9

(1987)), (7) Bromination of 2 (5H) monofuranone derivative with N-bromosuccinimide in carbon tetrachloride to obtain 5-bromo-2 (5H) -furanone derivative, which was carbonated Reaction with phenol in the presence of an aqueous solution [Synthesis, page 760 (1

98 8) cf.] is known.

When the methods (1) and (2) are carried out on an industrial scale, the reaction equipment and energy for light irradiation become excessive. The 2-silyloxyfuran derivative and eodosobenzene used in the above method (3) are expensive. In the above method (4), the raw materials are expensive, and the obtained products are all 5-alkoxy-12 (5H) -furanone derivatives having a substituent at the 4-position, and thus lack versatility. In the method (5), the raw material is expensive and the yield is as low as 35%.

In the method (6), hydrogen bromide as a strong acid is produced as a by-product, and the hydrogen bromide acts on the product to cause a ring-opening reaction of the product. In addition, a reaction in which an alcohol is allowed to act in the presence of n-butyllithium is performed. However, in the present invention, 5-octanogeno-2 (5H) -furanone having no substituent at the 4-position is used. When alcohol is allowed to act in the presence of n-butyllithium, the selectivity is poor and the desired 5-alkoxy-2 (5H) -furanone Can only be obtained in low yields.

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. In addition, 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):

(In the formula, 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. )

The 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. )

(Hereinafter referred to as alcohol (I I)) and a halogenating agent to give a compound of the general formula (I I I)

(Wherein, 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

(Wherein, R ¹ and R ² are as defined above.)

And 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. A method for producing 4-alkoxy-13-c-geno-T-butyrolactone (III). BEST MODE FOR CARRYING OUT THE INVENTION

In the above general formula, as the 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. Examples of the substituent 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; 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.

Examples of the halogen atom represented by X include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.

First, a process for producing a 4-alkoxy-3-halogenoa-ptyloractone (III) by reacting a 2 (3H) -furanone (I) with an alcohol (II) and a halogenating agent will be described.

Examples of 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. Among them, it is preferable to use N-chlorosuccinic acid imid, N-bromosuccinic acid imid, 5,5-dimethyl-1,3-dibromohydantoin, trichloroisocyanuric acid and the like. Hachiguchi 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.

Examples of alcohol (II) 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. Among them, 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. When a large amount of alcohol (II) is used, 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.

The thus obtained reaction mixture containing 4-alkoxy-13-halogeno-leptin lactone (III) as it is, or after filtering or washing with water depending on the type of halogenating agent, or the reaction mixture After 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. For example, water is added to the reaction mixture to separate the organic layer and the aqueous layer, and the aqueous layer is mixed with a solvent such as getyl ether, ethyl acetate, toluene, methylene chloride, 1,2-dichlorobenzene, or the like. Extract, combine the extract and the organic layer, dry over anhydrous sodium sulfate and concentrate. Also, if necessary, the obtained crude product is recrystallized, distilled, silica gel The purity can be further increased by subjecting it to ordinary purification means such as column chromatography. Next, a process of producing 4-alkoxy-12 (5H) -1-furanone (IV) by reacting 4-alkoxy-13-halogeno T-butyrolactone (III) with a base will be described.

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. These bases may be used alone or as a mixture of two or more. Of the bases, 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. For example, 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. When a solvent is used, its use amount is not particularly limited, but it is preferably in the range of 0.5 to 100 times the weight of 4-alkoxy-3-octogenobutyrolactone (III).

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. For example, 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

Hereinafter, the present invention will be described specifically with reference to Examples, but the present invention is not limited to these Examples.

Example 1

5,61-Dimethyl-1,3-dibromohydantoin 2.86 1 g (1 Ommo 1) was placed in a 3-neck flask equipped with a thermometer and a magnetic stirrer and having a capacity of 5 Om 1, and ethanol 2 Om After adding 1 and purging the system with nitrogen, the system was cooled to 110 ° C. To this solution, 1.680 g (2 Ommo 1) of 2 (3H) -furanone was added dropwise while maintaining the internal temperature at 0 ° C or lower. After the reaction solution was concentrated under reduced pressure until ethanol did not evaporate, toluene 2 Om 1 and water 1 Om 1 were added at room temperature and stirred for 30 minutes. The organic layer and the aqueous layer are separated, and the organic layer is dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a brown liquid, 3-bromo 4-ethoxy-ethoxybutyrolactone 3.824 g (purity 94%, 17.2 mmo1, yield 86%).

One NMR (2 7 0MH z, CDC 1 3, TMS, p pm) 6: 5. 6 3 (s, 1 H), 4. 29 (d, 1 H, J = 6. 9Hz), 3. 8 7 (dq, 1 H, J = 6.9, 2.0 Hz) 3.66 (dq, 1 H, J = 6.9, 2.0 Hz), 3.33 (dd, 1 H, J = 6.9, 18.

8 Hz), 2.81 (d, 1 H, J = 18.8 Hz), 1.24 (t, 1 H, J = 6.9 Hz)

Example 2

Place 1.06 g (10 mmo1) of sodium carbonate in a three-necked flask equipped with a thermometer, Magnetics mixer and a dropping funnel and having a capacity of 500 ml, add 20 ml of water, and add water. It was purged with nitrogen and heated to 40 ° C. To this solution, 3.824 g (purity 94%, 17.2 mmo 1) of 3-promo 4--1-ethoxy r-butyrolactone obtained by the method of Example 1 was dissolved in toluene 2 Om 1 to obtain a solution. The resulting solution was added dropwise over 1 hour, and after completion of the addition, the mixture was stirred at 40 ° C for 3 hours. After cooling the reaction solution to room temperature, an organic layer and an aqueous layer were separated using a separating funnel. The aqueous layer was extracted once with 1 Om 1 of toluene, and the extract was combined with the organic layer, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product obtained was further purified using silica gel column chromatography (developing solvent: hexane / ethyl acetate = 4: 1 (volume ratio)) to obtain the following physical properties as a yellow transparent liquid. There was obtained 1.805 g (yield: 82%) of 5-ethoxy 2 (5H) monofuranone.

- NMR (2 7 0MH z, CD C 1 3> TMS, p pm) (5: 7. 2 1 (d, 1 H, J = 1 0. 9H z), 6. 23 (d, 1 H, J = 6.

9 Hz), 5.94 (s, 1 H), 4.00-38.8 (m, 1 H), 3.82-3.70 (m, 1 H), 1.29 (t 3 H, J = 6.9 Hz)

Boiling point: 7 6-7 8 ° C / 667 kPa

Example 3

In 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-τ-butyrolactone having the following physical properties (purity: 93%, 14.4 mmo1, yield: 72) %).

- NMR (27 0 MHz, CD C 1 3, TMS, p pm) δ: 5. 42 (s, 1 Η), 4. 33 (d, 1 Η, J = 5. 9 Η ζ), 3. 5 3 (s, 1Η), 3.16 (dd, 1Η, J = 6.9, 18.8Η), 2.68 (d, 1Η, J = 18.8 1) )

Example 4

In 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 5

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 τ-butyrolactone was used in Example 2, but the 3-chloro-4-methoxy alcohol obtained by the method of Example 3 was used. The reaction was carried out in the same manner except that 2.330 g (purity 93%, 14.4 mmo 1) of ptyrrolactone was used, and the obtained crude product was subjected to silica gel column chromatography (developing solvent: hexane / hexane). Purification with ethyl acetate = 4Z 1 (volume ratio)) gave 1.490 g (isolation yield 76%) of 5-methoxy-2-z 5H) -furanone having the following physical properties.

^{X H-NMR (27 0MH z} , CDC 1 3, TMS, p pm) δ: 7. 23 (d, 1 H, J = 5.9 Hz), 6.24 (dd, 1 H, J = 5.9, 2.0 Hz), 5.87 (d, 1 H, J = 2.0 H z), 3.59 (s, 3 H)

Example 6

The reaction and work-up were carried out in the same manner as in Example 2, except that 1.06 g (1 Ommo 1) of sodium carbonate and 2.04 g (2 Ommo 1) of triethylamine were used in place of water 2 Om1. There were obtained 1.519 g (yield: 69%) of 5-ethoxy-2 (5H) monofuranone.

Example 7

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.

Example 8

In a 50 ml 3-neck flask equipped with a thermometer, a dropping funnel and a magnetic stirrer, 20 ml of toluene, 1.380 g of ethanol (3 Ommo 1) and 5,5-dimethyl-1,3-dibromohydantoin were added. 2. 861 g (1 Ommo 1) was added, the system was purged with nitrogen, and then cooled to 110. 1.680 g (2 Ommo 1) of 2 (3 H) -furanone was added dropwise to this solution while maintaining the internal temperature at 0 ° C or less, and after the addition was completed, the mixture was further stirred at 0 or less for 30 minutes. did. To the obtained reaction solution, 0.22 g (2 mmo 1) of triethylamine was added so that the internal temperature was kept at 0 ° C. or lower. Next, 40 g of a 5% aqueous sodium carbonate solution was added dropwise using a dropping funnel while keeping the internal temperature at 0 or lower, and after the addition was completed, the mixture was further stirred for 5 hours. The reaction solution was separated into an organic layer and an aqueous layer using a separatory funnel, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. As a clear liquid, 2.109 g of 5-ethoxy-2 (5H) -furanone (purity 95%, total yield from 2 (3H) -furanone 78%) was obtained. Industrial applicability

According to the present invention, 5-alkoxy_2 (5H) -furanone (IV) can be produced inexpensively, efficiently, and industrially advantageously.

Claims

The scope of the claims

1. General formula (I)

2 (3 H) -furanones represented by the general formula (II)

R ² OH (II)

(In the formula, R ² represents an alkyl group which may have a substituent, a cycloalkyl group which may have a substituent, or an aralkyl group which may have a substituent.)

By reacting with an alcohol represented by the formula (I) and a halogenating agent,

(Wherein, R ¹ and R ² are as defined above, and X represents a halogen atom.)

A general formula (IV) characterized in that 4-alkoxy-3-halogenoa-butyrolactone represented by the following formula is obtained, and the obtained 4-alkoxy-3-halogeno-r-butyrolactone is reacted with a base.

(Wherein, R ¹ and R ² are as defined above.)

Method for producing 5-alkoxy-1 2 (5H) 1-furanone represented by

2. General formula (I I I)

(Wherein, R ¹ is 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. R ² represents an alkyl group which may have a substituent, an alkyl group which may have a substituent or an aralkyl group which may have a substituent, and X represents a halogen atom. Represents.)

A general formula (IV) characterized by reacting a 4-alkoxy-13-halogenoa-ptyrolactone represented by the formula with a base:

(Wherein, R ¹ and R ² are as defined above.)

A method for producing 5-alkoxy-2 (5H) monofuranone represented by the formula:

3. The production method according to claim 1, wherein an alkali metal or alkaline earth metal carbonate, hydrogen carbonate or hydroxide, or a tertiary amine is used as the base.

4. The method according to claim 1, wherein a tertiary amine is used as the base.

5. The production method according to claim 1, wherein a mixed system of a tertiary amine and an aqueous solution of an inorganic base selected from the group consisting of a metal carbonate, a metal bicarbonate, and a metal hydroxide is used as the base.

6. The reaction with a base is performed at a temperature in the range of _50 to 100 ° C.

The production method according to 1 or 2.

7. The process according to claim 2, wherein the reaction with the base is carried out at a temperature in the range of 20 ° C. to 30 ° C.

8. General formula (I I I)

(Wherein, R ¹ is 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. R ² represents an alkyl group which may have a substituent, a cycloalkyl group which may have a substituent or an aralkyl group which may have a substituent, and X represents a halogen atom. Represents.)

4-alkoxy-3-halogenoa-ptyrolactone represented by

9. General formula (I)

(Wherein, R ¹ represents a hydrogen atom, an alkyl group which may have a substituent, an aryl group which may have a substituent or a substituent: Represents a alkyl group. )

The 2 (3H) monofuranones represented by the general formula (II)

R ² 0H (II)

A general formula (I I I) characterized by reacting with an alcohol and a halogenating agent represented by

(Wherein, R ¹ and R ² are as defined above, and X represents a halogen atom.)

A method for producing a 4-alkoxy-3-halogenoa-ptylolactone represented by the formula: