WO2001079192A1

WO2001079192A1 - Process for preparing 5-substituted-2(5h)-furanones

Info

Publication number: WO2001079192A1
Application number: PCT/JP2001/003225
Authority: WO
Inventors: Kuniaki Tatsuta
Original assignee: Kuraray Co., Ltd.
Priority date: 2000-04-19
Filing date: 2001-04-16
Publication date: 2001-10-25

Abstract

A process for preparing 5-substituted-2(5H)-furanones of the general formula (I) wherein R1 is hydrogen, optionally substituted alkyl, optionally substituted aryl, or optionally substituted aralkyl; and R2 is optionally substituted alkyl, optionally substituted alkenyl, or optionally substituted aralkyl, characterized by reacting a compound of the general formula (II) wherein R1 is as defined above; and X is halogeno with an alcohol of the general formula (III) wherein R2 is as defined above under nonaqueous conditions in the presence of a base selected from the group consisting of lithium carbonate, sodium carbonate, calcium carbonate, sodium hydrogencarbonate, and potassium hydrogencarbonate.

Description

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

The present invention relates to a method for producing 2 (5H) -furanone substituted at the 5-position with an alkoxyl group or the like. The 5-Okida 2 (5H) 1-furanone, for example, 5-ethoxy-12 (5H) 1-furanone, obtained by the present invention is useful as a synthetic intermediate for pharmaceuticals such as anti-inflammatory agents. Background art

2- (5H) monofuranone, in which the 5-position of 5-alkoxy-12 (5H) monofuranone is substituted by an alkoxyl group, etc., can be produced by (1) oxidation of furfural under light irradiation 5-Hydroxy-2 (5H) — a method of obtaining furanone and reacting it with alcohol [see Tetrahedron, Vol. 44, pp. 7213 (1988)], (2) acetylfuran or furan — 2-—Oxidation of carboxylic acid ester in alcohol or acetone solvent under light irradiation conditions [See Chemistry Ex press, vol. 1, p. 475 (1 986)], (3) 2— A method for oxidizing silyloxyfuran derivatives with odosobenzene [see Tetrahedron on Letters, vol. 30, p. 30 (1989)], (4) Mannich of glyoxylic acid and aldehyde By reaction , 4-Substituted 5-alkoxy 1 (511) —a method for producing furanone [Journal of Organic Chemistry (J. Or. Chem.), Vol. 46, p. 4889 (1998) (5) Heating 3-formylmethacrylic acid in hydrochloric acid to give 5-hydroxy-13-methyl-2 (511) -furanone, Method for reaction with alcohol [Journal of the Chemical Society (c) (see J. Chem. Soc., (C)), pp. 1984 (1966)], (6) 5—Promote 4-Methoxy _ 2 (5H) How to make alcohol act on one furanone [Journal of the Chemical Society, Parkin Transaction I (

J. Chem. Soc., Perkin Trans. 1), pp. 717 (1989)], (7) 2 (5H) monofuranone derivative in carbon tetrachloride, N— Bromination with bromosuccinimide to obtain a 5-bromo-2 (5H) monofuranone derivative, which is reacted with phenol in the presence of an aqueous solution of potassium carbonate [Synthesis, p. (1988)] is known.

When the methods (1) and (2) are performed on an industrial scale, the reaction equipment and energy for light irradiation are excessive. The 2-silyloxyfuran derivative and eodosobenzene used in the method (3) are expensive. In the above method (4), the raw materials are expensive and all the obtained products have 5-substituted alkoxy groups having a substituent at the 4-position.

(5H) —Furanone derivative, lacking versatility. In the method (5), the raw materials are expensive and the yield is as low as 35%. In the above method (6), hydrogen bromide which is 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, although a reaction in which an alcohol is reacted in the presence of n-butyllithium is performed, n-butylyllithium is added to 5-halogeno 2 (5H) monofuranone having no substituent at the 4-position in the present invention. When an alcohol is allowed to act in the presence of a compound, the selectivity is poor and the desired 5-alkoxy-12 (5H) -furanone is obtained only in low yield. 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, aqueous potassium carbonate solution is used], and the reaction conditions are not efficient because the decomposition of 5-promo 2 (5H) monofuranone derivative, which is unstable to water, occurs simultaneously. Therefore, none of these methods can 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.

It is an object of the present invention to provide 5-substituted-2 (511) -furanone-like 5H) To provide an inexpensive, efficient, and industrially advantageous method for producing monofuranone. Disclosure of the invention

According to the present invention, the above object is

① General formula (II)

(Wherein, 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, X Represents a halogen atom.) [Hereinafter, this is abbreviated as “halolactone (II)”], under non-aqueous conditions, lithium carbonate, sodium carbonate, calcium carbonate, sodium hydrogencarbonate and hydrogencarbonate. In the presence of a base selected from the group consisting of potassium, the general formula (

I I I)

R ² OH (III)

(Wherein, R ² represents an alkyl group which may have a substituent, an alkenyl group which may have a substituent, or an aralkyl group which may have a substituent.) Alcohol (hereinafter abbreviated as alcohol (III)).

(The formulas B, R ¹ and R ² are as defined above.) 5 -substituted _ 2 (5)) 1 furanone [Hereinafter, this is abbreviated as 5-year old xylactone (I)] Manufacturing method And

② General formula (IV)

(Wherein R ¹ is as defined above) (hereinafter abbreviated as lactone (IV)) with a halogenating agent to give halolactone (II). The halogenolactone (II) is converted to an alcohol (III) under non-aqueous conditions in the presence of a base selected from the group consisting of lithium carbonate, sodium carbonate, calcium carbonate, sodium bicarbonate and hydrogen bicarbonate. This is achieved by providing a method for producing 5-oxylactone (I), which is characterized by reacting BEST MODE FOR CARRYING OUT THE INVENTION

In the above general formula, the alkyl ¾ represented by R ¹ and R ² is preferably a linear or branched alkyl group having 1 to 8 carbon atoms, for example, methyl ¾, ethyl ½, propyl, isopropyl, butyl. Group, isobutyl group, tertiary butyl group, hexyl group, octyl group and the like. These alkyl groups may have a ίί ′ exchange S, and examples of such substituents include an alkoxyl group such as a methoxy group, an ethoxy group, a propoxy group and a butoxy group; a tert-butyldimethylsilyloxy group; trisubstituted silyloxy groups such as tert-butyldiphenylsilyloxy group; nitro group and the like.

The aralkyl group represented by R ′ and R ² is preferably an aralkyl group having an alkyl group having 1 to 8 carbon atoms as an alkyl moiety and having an aralkyl group having 6 to 10 carbon atoms as an aryl moiety. Group, 11-naphthylmethyl group, phenethyl group and the like. These aralkyls may have a substituent such as methyl, ethyl: propyl, isopropyl !; butyl, isobutyl, and tort-butyl ^. ¾; Trifluoro chill チル; Alkoxyl groups such as ethoxy, propoxy and butoxy groups; trisubstituted silyloxy groups such as tert-butyldimethylsilyloxy group and tert-butyldiphenylsilyloxy group; nitro groups; phenyl groups and p-methoxyphenyl. Groups such as aryl groups.

The aryl group represented by R ¹ is preferably an aryl group having 6 to 10 carbon atoms, and examples thereof include a phenyl group and a naphthyl group. These aryl 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, butoxy group; trisubstituted silyloxy group such as tert-butyldimethylsilyloxy group and tert-butyldiphenylsilyloxy group; nitro group; phenyl group And p-aryl groups such as a methoxyphenyl group.

The alkenyl group represented by R ² is preferably a linear or branched alkenyl group having 2 to 8 carbon atoms, for example, a vinyl group, a propenyl group, a methallyl group, a butenyl group, a prenyl group, and an octenyl group. And the like. These alkenyl groups may have a substituent. Examples of such a substituent include a trifluoromethyl group; an alkoxyl group such as a methoxy group, an ethoxy group, a propoxy group and a butoxy group; and iert monobutyldimethylsilyloxyl. Groups, tert-butyltriphenylsilyloxy groups and other trisubstituted silyloxy groups; nitro groups; phenyl groups and aryl-groups such as ρ-methoxy phenyl groups.

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 halactone (II) by reacting lactone (IV) with a halogenating agent will be described.

Examples of the halogenating agent include chlorine, bromine, sulfuryl chloride, chloro-succinic acid imid, bromo-succinic acid imid, 5,5-dimethyl-1.3-dibromohydant , Pyridine dibumid hydropromide, bromine-dioxane, bromotrichloromethane and the like are used. The amount of the halogenating agent to be used is preferably in the range of 0.1 to 10 mol, more preferably in the range of 0.5 to 2 mol, per 1 mol of lactone (IV).

The halogenating agent is preferably used in the presence of a radical initiator, from the viewpoint of allowing the reaction to proceed smoothly. As such a radical initiator, for example, dibenzoyl peroxide, azobisisobutyronitrile, ditert-butylperoxide, dicumylperoxide, tert-butyl perbenzoate and the like are used. When a radical initiator is used, the amount thereof is not particularly limited, but is preferably in the range of 0.01 to 1 mol per mol of the halogenating agent, and is preferably 0.01 to 1 mol. More preferably, it is in the range of 0.01 mole.

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, and benzene; getyl ether, tetrahydrofuran, and diisopropyl ether Ethers such as dioxane, dimethyloxetane and dibutyl ether; ditolyls such as acetonitrile, propionitrile and benzonitrile; methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,1-dichloroethane Halogenated hydrocarbons such as loroethane, trichloroethane, and benzene; and mixtures thereof. Although there is no particular limitation on the use of the solvent, it is preferably in the range of 0.5 to 100 times by weight the lactone (IV).

The reaction temperature is preferably in the range of 0 to 200 ° C, more preferably in the range of 50 to 100 ° C. The reaction time varies depending on the type of the lactone (IV), the halogenating agent and the solvent, the ratio 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 halogenating agent, lactone (IV) and, if necessary, a radical initiator in a solvent at a predetermined temperature. The thus-obtained halolactone (II) can be isolated and purified by a method generally used for isolation and purification of an organic compound. For example, water is added to the reaction mixture to separate an organic layer and an aqueous layer, 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 organic layers are combined, dried over anhydrous sodium sulfate, etc., and concentrated. However

Since halolactone (II) is unstable to water and tends to decompose, it is desirable to perform the extraction operation in a short time. Further, if necessary, the purity of the obtained crude product can be further increased by subjecting it to ordinary purification means such as recrystallization, distillation and silica gel column chromatography.

Next, a process for producing 5-oxylactone (I) by reacting halolactone (II) with alcohol (III) under non-aqueous conditions in the presence of a base will be described.

As a base, it is necessary to use lithium carbonate, sodium carbonate, calcium carbonate, sodium hydrogencarbonate or hydrogencarbonate. These may be used alone or as a mixture of two or more. When lithium carbonate, sodium carbonate or calcium carbonate is used as the base, the amount thereof is preferably in the range of 0.5 to 50 mol per mol of halolactone (II), and 0.5 to 50 mol. More preferably, 5 to 5 moles: When using sodium bicarbonate or hydrogen carbonate bicarbonate, the amount used is preferably in the range of 1 to 50 mol, and preferably 1 to 5 mol, per mol of halolactone (II). More preferably, it is within the range.

Examples of the alcohol (III) include methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, tert-butanol, 1-pentanol, and 2-pentanol. Fats such as 3-pentanol, 1-hexanol, 2-hexanol, 3-hexanol, 1-octanol, 2-methoxyethanol, 2-ethoxyethanol, 3-ethoxy-11-propanol Group-saturated alcohols: allylic alcohol, 2-butene-l-ol, 3-butene-l-l-ol, 2-pentene-l-l-ol, 3-penten-l-l-ol, 4-pentene-l-l-ol, 4-l-pentene-l-l . Aliphatic unsaturated alcohols include aromatic alcohols such as benzyl alcohol, 1-phenylethanol, 1-naphthylenemethanol, 2-naphthylenemethanol, methylbenzyl alcohol and methoxybenzyl alcohol. Among them, methanol, ethanol, 1-propanol, 1-pentanol, 1-hexanol, 1-year-old ketanol and the like are preferably used. The amount of the alcohol (III) to be used is preferably 1 mol or more, more preferably 1 to 1,000 mol, per 1 mol of the halolactone (II).

The reaction must be carried out under non-aqueous conditions, because the presence of water degrades halactolone (II). The reaction can be performed in the presence or absence 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; getyl ether, tetrahydrofuran Ethers such as diisopropyl ether, dioxane, dimethoxyethane and dibutyl ether; nitriles such as acetate nitrile, propionitrile and benzonitrile; methylene chloride, chloroform, carbon tetrachloride, dichloroethane, trichloroethane Halogenated hydrocarbons such as ethane; aprotic polar solvents such as dimethyl sulfoxide and N, N-dimethylformamide; and mixtures thereof. When a solvent is used, the use thereof is not particularly limited, but is preferably in the range of 0.5 to 1,000 times the amount of halolactone (II).

The reaction temperature is preferably in the range of 20 to 200 ° C, more preferably in the range of 40 to 100 ° C ffl. The reaction time varies depending on the type of the halolactone (I 1), the base and the alcohol (I I I), 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 preferably carried out at a predetermined temperature, for example, by suspending a base in alcohol (III) and, if necessary, in a solvent, and then adding halolactone (II) to the mixture. The 5-oxylactone (I) 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 filtered to remove solids, water is added to the filtrate to separate the organic layer from the aqueous layer, and the aqueous layer is separated into getyl ether, ethyl acetate, toluene, methylene chloride, 1,2-dichloroethane, etc. The extract is combined with an organic solvent, and the extract and the organic layer are combined, dried over anhydrous sodium sulfate, etc., and concentrated.The crude product obtained is recrystallized, distilled, or purified by silica gel column chromatography if necessary. Purify.

The lactone (IV) used in the present invention can be prepared, for example, by a method of oxidizing furfural with hydrogen peroxide [The Organic Preparation and Procedures International, Inc. (The O r g a n i c P r e p a ra n a tio n a n d

Procedures International), vol. 28, p. 15 (1996)], a method of reacting an acetylene derivative with carbon monoxide in the presence of a rhodium catalyst or a palladium catalyst to form a cyclic carbonylation [ Organometallics (Organome ta lics), Vol. 10, pp. 2493 (1991); Journal of the American Chemical Society (J. Am. Chem. So), Vol. 88 , P. 128 (1966)]. Hereinafter, the present invention will be described differently with reference to examples, but the present invention is not limited to the examples.

Example 1

In a three-necked flask equipped with a thermometer and a magnetic stirrer and having a capacity of 1 000 m 1, 2 (5H) -furanone 25.20 g (300 mmo 1), 5,5-dimethyl-1- 1, 3-Dibromohydantoin 42.89 g (15 Ommo I) and 0.73 g of dibenzoyl peroxide were added, 300 ml of acetate nitrile was added as a solvent, and the system was replaced with nitrogen. The temperature was raised to ° C, and the mixture was heated and stirred for 3 hours. The reaction solution was cooled to 40 ° C or lower, concentrated under reduced pressure at the same temperature or lower until no acetone nitrile distilled, and then 300 ml of toluene and 300 ml of water were added at room temperature. In addition, they were stirred for 30 minutes. ^ Separate 機 'and Water 1' The organic layer is dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give a brown liquid, 5_bromo-2 (5H) monofuranone 38.6 1 g (purity 95%) having the following physical properties. 225 mmo yield 75%).

^{X H-NMR (270 MHz,} CDC 1 3, TMS, p pm) (5:. 7. 62 (d, 1 H, J = 4 9Hz), 6. 95 (s, 1H), 6. 24 (d , 1 H, J = 4

. 9 H z)

Reference example 1

In Example 1, stirring was continued at 25 ° C without separating the organic layer and the aqueous layer, and the residual ratio was measured by gas chromatography in order to observe the stability of 5-promo 2 (5H) monofuranone. It was measured using a graph. 5-Promo 2 (5H) monofuranone decomposed at a rate of about 3% / hour.

Example 2

In a three-necked flask equipped with a thermometer, a magnetic stirrer, and a dropping funnel and having a capacity of 50 Om1, 39.90 g (540 mmo1) of lithium carbonate was placed, and 27 Om1 of ethanol was added to purge the system with nitrogen. Heated to 80 ° C. To this solution, 46.46 g (purity 95%, 270 mMol) of 5-bromo-2 (5H) monofuranone obtained by the method of Example 1 was added dropwise over 3 hours, and after the addition was completed. The mixture was stirred at 80 ° C for 7 hours. After the reaction solution was cooled to room temperature, insolubles were removed by filtration, and the filtrate was concentrated under reduced pressure. 25 Om1 of ethyl acetate and 25 Om1 of water were added to the obtained residue, and the organic layer and the aqueous layer were separated. The aqueous layer was extracted twice with 100 ml of ethyl acetate, and the extract was dried over anhydrous sodium sulfate in accordance with the previous organic calendar, and then concentrated under reduced pressure. The obtained crude product was further purified by distillation to obtain 27-65 g (yield 80%) of 5-ethoxy-2 (5H) -furanone having the following physical properties as a colorless and transparent liquid.

^{] H-NMR (270 MHz,} CDC 1 3, TMS, m) (5:.. 7. 2 1 (d, 1 H, J = 1 0. 9Hz), 6. 23 (d 1 II J = 6. 9 II z), 5.94 (s.1 I-1) '4.00-3.88 (m.1H), 3.82--3.70 (m.1H), 1.29 (t, 3H, J = 6.9 Hz)

Boiling point: 7 6—7 8 ° C / 6 67 kPa

Example 3

The reaction and post-treatment were carried out in the same manner as in Example 2 except that 54.00 g (54 Ommo 1) of calcium carbonate was used instead of 39.90 g of lithium carbonate, to give 5-ethoxy-2 (5H). — 2.68 g of furanone (isolation yield 83%) was obtained.

Example 4

The reaction was carried out in the same manner as in Example 2 except that methanol 27 Om 1 was used instead of ethanol 270 ml, and the obtained crude product was subjected to silica gel column chromatography (developing solvent: hexane Z acetic acid). (10: 1 (volume ratio)) to give 26.16 g (85% isolated yield) of 5-methoxy-2 (5H) -furanone having the following physical properties. .

^{J H-NMR (2 7 0MH} z, CDC 1 3, TMS, p pm) δ 7. 2 3 (d, 1 Η, J = 5. 9 Η ζ), 6. 24 (dd, 1 Η, J = 5. 9, 2.ΟΗ ζ), 5. 8 7

(d, 1Η, J = 2.ΟΗΟΗ), 3.59 (s, 3Η)

Example 5

The reaction and post-treatment were carried out in the same manner as in Example 2 except that 57.23 g (54 Ommo 1) of sodium carbonate was used instead of 39.90 g of lithium carbonate. H) 16.33 g of monofuranone (isolation yield: 72%) was obtained.

Example 6

The reaction and post-treatment were carried out in the same manner as in Example 2 except that sodium hydrogencarbonate 45.37 g (54 Ommo 1) was used in place of lithium carbonate 39.90 g, to give 5 monoethoxy-2 ( 5 H) 19.50 g of monofuranone (86% isolated yield) was obtained.

Example 7

In the same manner as in Example 2, except that potassium hydrogen carbonate 54.06 g (540 mm () 1) was used instead of lithium carbonate 39.90 g, k reaction and after-treatment fl! — Ethoxy_2 (5H) monofuranone 17.01 g (isolation yield 75%) was obtained.

Comparative Example 1

In Example 2, the mixture was heated and stirred under ethanol reflux for 3 hours without adding lithium carbonate. When this reaction solution was analyzed by gas chromatography, a peak corresponding to 5-ethoxy-2 (5H) -furanone was not detected, and a complex mixed system was obtained. Comparative Example 2

The reaction and work-up were carried out in the same manner as in Example 2, except that 74.63 g (54 Ommo 1) of potassium carbonate was used instead of 3.990 g of lithium carbonate. (5H) — No complex corresponding to furanone was detected.

Comparative Example 3

Contents equipped with a thermometer, a magnetics mixer and a dropping funnel ^ In a 3-neck flask of 10 Om 1, add 0.276 g (6 mmo 1) of absolute ethanol and 3 Om 1 of anhydrous tetrahydrofuran to the system. Was replaced with nitrogen and cooled to 0 ° C. To this solution, 3.75 ml (1.6 mol Z liter) of a hexane solution of n-butyllithium (6 mmo 1) was added dropwise at 5 ° C or less, and further at 5 for 10 minutes or less. Stirred. To this solution was added 0.85 58 g (purity 95%, 5 mmo1) of 5-promo 2 (5 II) -furanone obtained by the method of Example 1 over 15 minutes at 5 ° C or less. And after dripping,

The mixture was returned to room temperature and stirred for 12 hours. The reaction solution was concentrated under reduced pressure, 30 ml of water and 3 OmI of ethyl acetate were added to the residue, and the organic layer and the aqueous layer were separated. The aqueous solution was extracted twice with 15 ml of ethyl acetate, and the extract was combined with the organic layer, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product obtained was purified by silica gel column chromatography (extension | solvent: hexane / ethyl acetate = 41 (volume ratio)) to give 5-ethoxy-1 2 (5 II)-furanone 0. 0 96 g (yield 15%) was obtained. Industrial applicability According to the present invention, 5-oxylactone (I) represented by 5-alkoxy-12 (5H) -furanone can be produced inexpensively, efficiently and industrially advantageously.

Claims

The scope of the claims

-General formula (II)

(Wherein, 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, X Represents a halogen atom.)

Under non-aqueous conditions in the presence of a base selected from the group consisting of lithium carbonate, sodium carbonate, calcium carbonate, sodium bicarbonate and hydrogen carbonate bicarbonate, under the general formula (III)

R ² OH (III)

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

General formula (I) characterized by reacting with an alcohol represented by

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

For producing 5-substituted 2 (5H) furanone represented by

2. General formula (IV)

(I V)

R ¹ 1 0

(Formula, R ¹ is a hydrogen atom, alkyl optionally substituted with S ^ And represents an aryl group or an aralkyl group which may have a substituent. The compound represented by the general formula (II)

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

A compound selected from the group consisting of lithium carbonate, sodium carbonate, calcium carbonate, sodium hydrogencarbonate and potassium hydrogencarbonate under non-aqueous conditions is obtained by obtaining the compound represented by the general formula (II). In the presence of the general formula (III)

R ² 0H (III

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

General formula (I) characterized by reacting with an alcohol represented by

(I

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

For producing 5-substituted mono 2 (5H) monofuranone represented by