JP2008266176A - METHOD FOR PRODUCING alpha-PYRONE COMPOUND - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing the objective α-pyrone compound in high efficiency and yield. <P>SOLUTION: The method for producing a compound expressed by general formula (I) comprises the reaction of a ketone compound having a specific structure with an α,β-unsaturated ester compound having a specific structure and cyclizing the reaction product. In the formula, R<SB>1</SB>, R<SB>2</SB>and R<SB>3</SB>are each independently a hydrogen atom, an alkyl group or the like; and R<SB>4</SB>is a cyano group, a carbamoyl group or the like. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a method for producing an α-pyrone compound that is useful as a fluorescent material or an electroluminescent material and is known to have various physiological activities.

  Compounds having an α-pyrone skeleton are used in various fields. For example, as described in Patent Document 1, for use as a fluorescent pigment, and as described in Patent Document 2, for an optical recording medium. It is known as a useful skeleton for a very wide range such as as a dye of the above, or as a compound having an immunosuppressive action as described in Patent Document 3, and various methods are known for its production.

  For example, as shown in Patent Document 4, a method of adding an acrylate ester and an alkyne in the presence of a metal catalyst, and as shown in Patent Document 5, a nickel trialkylphosphine complex is present and 2-methyl-1 A method of reacting hexene-3-yne and carbon dioxide is known.

  However, with respect to α-pyrone having an electron-withdrawing group at the 3-position, it may be difficult to use the above method, and another method is known. For example, Non-Patent Document 1 describes a method in which an alkoxymethylene malonate and a ketone are added to form a keto ester, which is then closed to form α-pyrone, and Non-Patent Document 2 describes (N-methyl). A method is described in which a ketone is added to (N-phenyl) aminomethylenemalonic acid ester to form a ketoester, which is then cyclized to obtain α-pyrone. However, in the former case, an aromatic ketone such as acetophenone can obtain a pyrone with a good yield, but an aliphatic ketone often cannot obtain a pyrone with a satisfactory yield. In the latter, the yield of aliphatic ketone is slightly improved, but it requires a relatively high temperature when producing (N-methyl-N-phenyl) aminomethylene malonate, and requires heating and cooling. There were problems in terms of cost and cost.

JP 2003-183640 A JP 2005-71410 A International Publication WO95 / 6045 Pamphlet JP 2000-256344 A JP-A-6-92953 “Journal of Organic Chemistry”, 49, 4033 (1984) "Synthetic Communications", Vol. 21, No. 14, p. 1433 (1991)

  An object of the present invention is to provide a method for producing an α-pyrone compound, preferably an α-pyrone compound having an electron-withdrawing group at the 3-position, wherein the raw material ketone is an aromatic ketone or an aliphatic ketone. It is an object of the present invention to provide a method for efficiently obtaining a target product with any yield of any ketone.

The problems of the present invention have been solved as follows.
[1] A method for producing a compound represented by the following general formula (I), after reacting a compound represented by the following general formula (II) with a compound represented by the following general formula (III) A process for producing a compound represented by the general formula (I), wherein the compound represented by the general formula (I) is obtained by ring closure.

[Wherein, R ₁ , R ₂ and R ₃ each independently represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group or a heterocyclic ring. R ₁ and R ₂ may be bonded to each other to form a 4- to 8-membered ring. R ₄ represents a cyano group, a sulfonyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, a carbamoyl group, a trifluoromethyl group or a sulfamoyl group, and R ₃ and R ₄ are bonded to each other when possible to form 4 to 8 members. The ring may be formed. R ₅ represents an alkyl group or an aryl group. L represents an amino group represented by —NR ₆ R ₇ . Here, R ₆ and R ₇ independently represent hydrogen or an alkyl group. R ₆ and R ₇ may combine with each other to form a 4- to 8-membered heterocycle. ]
[2] The compound represented by the general formula (III) is a compound represented by the following general formula (IV) and HL (L represents an amino group represented by —NR ₆ R _7. Here, R ₆ and R ₇ independently represents hydrogen or an alkyl group, and R ₆ and R ₇ may be bonded to each other to form a 4- to 8-membered heterocyclic ring. After the reaction, the compound represented by the general formula (III) is allowed to react with the compound represented by the general formula (II) without isolation. A method for producing a compound represented by formula (I).
Formula (IV)

[Wherein represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group or a heterocyclic ring. R ₄ represents a cyano group, a sulfonyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, a carbamoyl group, a trifluoromethyl group or a sulfamoyl group, and R ₃ and R ₄ are bonded to each other when possible to form 4 to 8 members. The ring may be formed. R ₅ represents an alkyl group or an aryl group. R ₈ represents an alkyl group or an aryl group. ]

  By the method of the present invention, the target α-pyrone compound can be produced simply and in high yield.

  The method for producing the compound represented by the general formula (I) of the present invention comprises a compound represented by the general formula (II) and a compound represented by the general formula (III) as shown in the following reaction scheme. After the reaction, ring closure is performed to obtain a compound represented by the general formula (I). Preferably, the compound represented by the general formula (III) is a compound obtained by reacting a compound represented by the general formula (IV) with an amine represented by HL. The compound represented by formula (II) is reacted with the compound represented by formula (II) without isolation.

First, each group in the compounds represented by the general formulas (I) to (IV) will be described.
R ₁ , R ₂ and R ₃ each independently represent a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group or a heterocyclic ring, and the alkyl group has 1 to 15 carbon atoms (more preferably 1 to 1 carbon atoms). 9) A linear or branched alkyl group and a cycloalkyl group having 3 to 15 carbon atoms (more preferably 3 to 12 carbon atoms) are preferable, and these alkyl groups may have a substituent. Examples include methyl group, ethyl group, isobutyl group, t-butyl group, hexyl group, octyl group, cyclopropyl group, cyclohexyl group, cycloheptyl group, 4-ethylcyclohexyl group, 4-propylcyclohexyl group, 4-butylcyclohexyl. Groups and the like. The alkenyl group is preferably a linear or branched alkenyl group having 2 to 15 carbon atoms (more preferably 2 to 10 carbon atoms), and a cyclic alkenyl group is also preferably used. Examples include vinyl group, allyl group, 2-buten-1-yl group, cyclopenten-1-yl group, cyclohexen-1-yl group and the like. The alkynyl group is preferably an alkynyl group having 2 to 15 carbon atoms (more preferably 2 to 10 carbon atoms). Examples include ethynyl group, propargyl group, 1-pentyn-1-yl group, and 4-butyn-1-yl. Groups and the like. As the aryl group, an aryl group having 6 to 18 carbon atoms (more preferably 6 to 14 carbon atoms) is preferable, and a phenyl group, a naphthyl group, an anthranyl group, and the like are preferable, and these aryl groups may have a substituent. Good. Substituents on the aryl group include halogen atoms (fluorine, chlorine, bromine or iodine), alkyl groups, aryl groups, cyano groups, carboxyl groups, alkoxycarbonyl groups, alkoxy groups, aryloxy groups, sulfanyl groups, hydroxyl groups, nitro Group, trifluoromethyl group, sulfonyl group, carbamoyl group, acylamino group, sulfonylamino group and the like are preferable. Specific examples include 4-ethylphenyl group, 3,4-difluorophenyl group, 2,3-difluorophenyl group, 4-butoxyphenyl group, 4-phenylphenyl group and the like. As an example of a heterocyclic ring, a C1-C15 4-8 membered heterocyclic ring is preferable, and a 5-6 membered heterocyclic ring is more preferable. A hetero atom forming a hetero ring is preferably a nitrogen atom, a sulfur atom, an oxygen atom or a boron atom, and may be an aromatic hetero ring or a non-aromatic hetero ring. Examples include 2-pyridyl group, 4-pyridyl group, 2-thienyl group, benzothiazol-2-yl group and the like.

R ₄ represents a cyano group, a sulfonyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, a carbamoyl group, a trifluoromethyl group or a sulfamoyl group, and more preferably a cyano group or an alkoxycarbonyl group.

R ₅ represents an alkyl group or an aryl group, and an alkyl group is more preferable.

L represents an amino group represented by —NR ₆ R ₇ . Here, R ₆ and R ₇ independently represent a hydrogen atom or an alkyl group. R ₆ and R ₇ may combine with each other to form a 4- to 8-membered heterocycle. When R ₆ and R ₇ are an alkyl group, carbon number 1 to 10 are preferred, even more preferably 1-6. Examples include methyl, ethyl, n-propyl, butyl, isopropyl, isobutyl, 2-methoxyethyl and the like. When R ₆ and R ₇ are bonded to each other to form a heterocycle, the heterocycle is a 4- to 8-membered heterocycle, preferably a 5- to 6-membered ring. Examples thereof include pyrrolidine, piperidine, 4-ethylpiperazine, piperazine, morpholine and the like.

Next, a preferred embodiment of the present invention will be described.
First, a ketone represented by the general formula (II) and an α, β-unsaturated ester represented by the general formula (III) are subjected to an addition reaction (first step), and then this adduct is closed to obtain a pyrone. (Second step). The compound represented by the general formula (III) used in the first step in this embodiment has an amino group represented by L. As a method for producing the compound represented by the general formula (III), a method of reacting the compound represented by the general formula (IV) with an amine corresponding to L in the general formula (III) is general. By using the amine corresponding to the above L, the compound represented by the general formula (IV) requires almost no heating, and can be converted into the compound represented by the general formula (III) very easily and in a high yield. Can be converted. That is, when carrying out the reaction of the present invention, it is not always necessary to add the compound represented by the general formula (III) as a raw material. If there is a compound represented by the general formula (IV) and an amine, This means that a merit that can be easily generated in the reaction system has occurred. A method for generating the general formula (III) in the reaction system will be described later. Furthermore, unexpectedly, when the compound represented by the above general formula (III) is used, the yield of the target α-pyrone represented by the general formula (I) is also represented by L. Is an anilino group (the method described in Synthetic Communications, Volume 21 (14), page 1433 (1991)).

  In general, the first step can be performed using a base. Examples of the base include metal hydroxides (eg, sodium hydroxide, potassium hydroxide, lithium hydroxide, magnesium hydroxide, calcium hydroxide). , Amines (for example, triethylamine, diisopropylethylamine, pyridine, 2,6-dimethylpyridine, 1,8-diazabicyclo [5.4.0] -7-undecene, tetramethylguanidine, etc.), metal alkoxides (for example, sodium Methoxide, sodium ethoxide, potassium-t-butoxide, sodium-t-butoxide, sodium-t-amyloxide, lithium-t-butoxide, magnesium ethoxide, etc., organic metals (eg n-butyllithium, bromide) Ethyl magnesium, phenyl magnesium bromide Etc.), metal hydrides (eg sodium hydride, potassium hydride, lithium hydride, calcium hydride etc.), metal amides (eg sodium amide, lithium diisopropylamide, sodium hexamethyldisilane amide, potassium hexamethyl) Disilane amide, etc.) and metals (for example, sodium, potassium, lithium, etc.). In the present invention, metal hydroxides, amines, metal alkoxides, metal hydrides and metal amides are preferably used, and metal hydroxides, metal alkoxides and metal hydrides are most preferred.

  The equivalent of the base to the compound represented by the general formula (II) is preferably 0.5 to 4 equivalents, more preferably 0.8 to 3 equivalents, and most preferably 1.0 to 2.5 equivalents.

  The reaction solvent used in the first step can be any solvent as long as it is stable to the base used, but it must have sufficient solubility in both the raw material ketone and ester. preferable. Preferred solvents in the present invention are aromatic solvents (eg, toluene, xylene, mesitylene, chlorobenzene, dichlorobenzene, t-butylbenzene, tetrahydronaphthalene, etc.), alcohol solvents (eg, methanol, ethanol, isopropyl alcohol, t- Butyl alcohol, etc.), ethers (eg, diethyl ether, t-butyl methyl ether, tetrahydrofuran, tetrahydropyran, etc.), ester solvents (eg, ethyl acetate, methyl acetate, isobutyl acetate, etc.), hydrocarbon solvents (eg, n-pentane, n-hexane, n-heptane, cyclopentane, cyclohexane, etc.), amide solvents (for example, N, N-dimethylacetamide, N, N-dimethylformamide, N-methyl-2-pyrrolidone, etc.) Nitrile solvents (eg, acetonitrile, propionitrile, etc.), sulfoxide solvents (eg, dimethyl sulfoxide, etc.) can be used, and these can be used as a mixture as appropriate. In the present invention, aromatic solvents, Ether solvents, alcohol solvents, hydrocarbon solvents, amide solvents and sulfoxide solvents are more preferred, and aromatic solvents and ether solvents are most preferred.

  The amount of the solvent is a capacity corresponding to 1 to 50 times the mass of the total mass of the compounds of the general formula (II) and general formula (III), more preferably a capacity corresponding to 2 to 20 times the mass, It is more preferable to use a capacity corresponding to 2 to 10 times the mass.

Although reaction temperature changes with bases and solvents to be used, it is usually preferably -20 ° C to 120 ° C, more preferably 0 ° C to 100 ° C, and most preferably 10 ° C to 60 ° C. When heat is generated by the reaction, it is preferable to carry out the reaction with appropriate cooling.
The reaction may be added in any order, but (a) a compound of the general formula (II), a compound of the general formula (III), a base order, (b) a compound of the general formula (III), The order of the compound of the general formula (II) and the base, (c) the order of the compound of the general formula (II), the base and the compound of the general formula (III) are preferable.
The reaction molar ratio of the compound of the general formula (II) and the compound of the general formula (III) is preferably 1: 0.7 to 1: 2 for the compound of the general formula (II): the compound of the general formula (III). 0.9 to 1: 1.3 is more preferable.
The amount of the base used is preferably 1: 1 to 1: 5, more preferably 1: 1 to 1: 3 in terms of the compound of the general formula (II): base (molar ratio).

  The ketone represented by the general formula (II) may be either an aromatic ketone or an aliphatic ketone, and specific examples include, but are not limited to, acetone, 2-butanone, 1-cyclohexyl. Examples include -1-ethanone, acetophenone, 1- (4-ethylphenyl) -1-ethanone, 3-methyl-2-butanone, 1-cyclopropyl-1-ethanone, and the like.

  Specific examples of the α, β-unsaturated ester represented by the general formula (III) include, but are not limited to, (diethylaminomethylene) malonic acid diethylester, (morpholinomethylene) malonic acid diethylester, Examples include diethylaminomethylene) ethyl cyanoacetate and ethyl (dimethylaminomethylene) acetoacetate.

  The first step is a step in which the ketone represented by the general formula (II) and the α, β-unsaturated ester represented by the general formula (III) are subjected to an addition reaction. As described above, the general formula (III) The compound represented by general formula (IV) and the amine HL corresponding to L in the general formula (III) can also be generated in the system. A method for generating the compound represented by the general formula (III) in the system will be described.

  As the solvent for the reaction of the compound represented by the general formula (IV) and the amine represented by HL, the solvent used in the first step can be used as it is. When using a solvent that is different from the solvent used in the first step, it is preferably carried out in a low boiling point solvent that can be easily distilled off. This reaction can be performed by adding the amine compound represented by the above HL to the compound represented by the general formula (IV). The reaction temperature is preferably 0 ° C. to 60 ° C. so that heating and cooling do not take time.

  The post-treatment of the reaction in the first step may be performed after the solvent is distilled off (or without distilling off), followed by extraction with an organic solvent that is not miscible with water, such as ethyl acetate, and water, or You may move to a 2nd process only by distilling off the solvent used at the 1st process. If possible, distillation purification may be performed. Further, it is possible to add only the reagent for the second step without distilling off the solvent in the first step.

The second step is a reaction for cyclization of the adduct of the compounds of general formula (II) and general formula (III) produced in the first step, and is a step for obtaining the target α-pyrone compound.
This ring closure reaction can generally be carried out under acidic conditions. The solvent for this reaction can also serve as an acid. For example, acetic acid, propionic acid, butyric acid and the like are preferable. An acid anhydride can also be used as a solvent, and acetic anhydride, propionic anhydride, or the like can be used. Furthermore, an acid halide can also be used as a preferable solvent, and examples thereof include acetyl chloride and propionyl chloride. It is also preferable to use these solvents in an appropriate mixture. In addition to the above-mentioned solvents, ordinary solvents can be used. In addition to sulfonic acids, sulfuric acid, hydrochloric acid, hydrobromic acid, Lewis acids such as aluminum chloride and zinc chloride can be used as the acids mentioned in the first step. In addition.

  The amount of the solvent is a capacity corresponding to 1 to 50 times the mass of the total mass of the compounds of the general formula (II) and general formula (III), more preferably a capacity corresponding to 2 to 20 times the mass, It is more preferable to use a capacity corresponding to 2 to 10 times the mass.

  The reaction temperature varies depending on the solvent and acid used, but is preferably about room temperature to 150 ° C, more preferably 50 ° C to 130 ° C.

  The α-pyrone compound represented by the general formula (I) produced by the method of the present invention is not limited, but is preferably an α-pyrone compound having an electron withdrawing group at the 3-position. Preferred electron withdrawing groups include acyl groups, alkoxycarbonyl groups, carbamoyl groups, cyano groups, and sulfonyl groups.

  EXAMPLES Hereinafter, although this invention is demonstrated in detail based on an Example, this invention is not limited to these.

Example 1
Preparation of 6- (4-ethylphenyl) pyrone-3-carboxylic acid ethyl ester 22.0 g of ethoxymethylenemalonic acid diethyl ester was dissolved in 120 mL of tetrahydrofuran / toluene = 2/1, and 8.9 g of morpholine was added to room temperature. And 14.8 g of 4′-ethylacetophenone was added to the reaction. Subsequently, 22.0 g of potassium t-butoxide was added little by little while keeping the temperature at 30 ° C. or lower. After 5 hours, the precipitated crystals were collected by filtration and washed with toluene. 150 mL of acetic acid was added to the crystals and heated under reflux for 5 hours. After cooling, water was added and the precipitated crystals were collected by filtration and recrystallized from ethyl acetate and hexane to obtain the desired product. Yield 23.3 g, Yield 85.6%, mp 94-96 ° C.
NMR spectrum (CDCl ₃ ): 8.30 (1H, d), 7.83 (2H, d), 7.32 (2H, d), 6.75 (1H, d), 4.40 (2H, q) ), 2.71 (2H, q), 1.39 (3H, t), 1.29 (3H, t)

Comparative Example 1
The same operation as in Example 1 was carried out except that morpholine was not added to obtain the target compound. Yield 21.0 g, Yield 77.1%, Melting point 94-96 ° C.

Example 2
Preparation of 6- (1-benzylcyclopropyl) pyrone-3-carboxylic acid ethyl ester 22.0 g of ethoxymethylenemalonic acid diethyl ester was dissolved in 120 mL of tetrahydrofuran, 8.9 g of morpholine was added, and the mixture was stirred at room temperature for 1 hour. 17.4 g of 1-benzyl-1- (acetyl) cyclopropane was added to the reaction. To this mixed solution, 23.0 g of potassium t-butoxide was slowly added while being kept at 30 ° C. or lower and stirred overnight. Crystals precipitated, but the solvent was distilled off under reduced pressure to dryness.
To this residue, 100 mL of acetic acid and 20 mL of acetic anhydride were added and heated to reflux for 5 hours. After completion of the reaction, the solvent was distilled off under reduced pressure, extraction was performed by adding water and ethyl acetate, and the organic phase was dried over anhydrous magnesium sulfate and concentrated. The residue was crystallized from ethyl acetate and hexane to obtain the desired product. Yield 20.5 g, Yield 68.7%, melting point 132-134 ° C.
NMR spectrum _{(CDCl 3): 8.03 (1H} , d), 7.30-7.15 (5H, m), 6.02 (1H, d), 4.31 (2H, q), 3.08 (2H, s), 1.48 (2H, t), 1.30 (3H, t), 1.04 (2H, t)

Comparative Example 2-1
The same operation as in Example 2 was carried out except that morpholine was not added to obtain the target compound. Yield 9.0g, 30.2%

Comparative Example 2-2
22.0 g of ethoxymethylenemalonic acid diethyl ester was dissolved in 120 mL of tetrahydrofuran, 10.9 g of N-methylaniline was added, and the mixture was heated to reflux for 6 hours. Thereafter, the same operation as that after the step of adding 1-benzyl-1 (acetyl) cyclopropane in Example 2 was performed to obtain the target compound. Yield 18.8 g, Yield 63.0%

Example 3
Preparation of 6- (cyclohexyl) pyrone-3-carboxylic acid ethyl ester 42.8 g of ethoxymethylenemalonic acid diethyl ester was dissolved in 250 mL of tetrahydrofuran, and 14.8 g of diethylamine was added and stirred. After 1 hour, the disappearance of ethoxymethylenemalonic acid diethyl ester was confirmed by TLC, and 25.0 g of cyclohexyl methyl ketone was added. Under water cooling, 52.0 g of potassium-t-butoxide was added little by little and stirred for 4 hours. The solvent was distilled off under reduced pressure to dryness, 250 mL of acetic acid was added, and the mixture was heated to reflux for 6 hours.
After evaporating the solvent under reduced pressure, extraction was performed by adding ethyl acetate and water, and the organic phase was concentrated and purified by silica gel column chromatography to obtain the desired product as an oil. Yield 40.1g, Yield 80.9%
NMR spectrum (CDCl ₃ ): 8.07 (1H, d), 6.10 (1H, d), 4.35 (2H, q), 2.48 (1H, m), 1.97 (2H, dd) ), 1.85 (2H, dd), 1.73 (2H, m), 1.40 (2H, m), 1.34 (3H, t), 1.30 (2H, m)

Comparative Example 3-1
A target compound was obtained in the same manner as in Example 3 except that diethylamine was not added. Yield 20.8 g, Yield 42.0%

Comparative Example 3-2
42.8 g of ethoxymethylenemalonic acid diethyl ester was dissolved in 250 mL of tetrahydrofuran, 21.7 g of N-methylaniline was added in place of diethylamine, heated under reflux for 5 hours, and cooled to room temperature. Thereafter, the same operation as that after the step of adding cyclohexyl methyl ketone in Example 3 was carried out to obtain the target compound. Yield 32.0 g, Yield 64.6%

Comparative Example 4
The same reaction as in Example 4 was carried out except that diethylamine was not added to obtain the target compound. Yield 5.0 g, Yield 38.5%

  By comparing the above Examples and Comparative Examples, it can be seen that the method of the present invention provides the target product efficiently and in high yield.

Claims (2)

A method for producing a compound represented by the following general formula (I), comprising: reacting a compound represented by the following general formula (II) with a compound represented by the following general formula (III); And producing a compound represented by the general formula (I), wherein the compound represented by the general formula (I) is obtained.

[Wherein, R ₁ , R ₂ and R ₃ each independently represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group or a heterocyclic ring. R ₁ and R ₂ may be bonded to each other to form a 4- to 8-membered ring. R ₄ represents a cyano group, a sulfonyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, a carbamoyl group, a trifluoromethyl group or a sulfamoyl group, and R ₃ and R ₄ are bonded to each other when possible to form 4 to 8 members. The ring may be formed. R ₅ represents an alkyl group or an aryl group. L represents an amino group represented by —NR ₆ R ₇ . Here, R ₆ and R ₇ independently represent hydrogen or an alkyl group. R ₆ and R ₇ may combine with each other to form a 4- to 8-membered heterocycle. ] The compound represented by the general formula (III) is a compound represented by the following general formula (IV) and HL (L represents an amino group represented by -NR ₆ R ₇ , where R ₆ and R ₇ are Each independently represents hydrogen or an alkyl group, and R ₆ and R ₇ may be bonded to each other to form a 4- to 8-membered heterocyclic ring). After the reaction, the compound represented by the general formula (III) is reacted with the compound represented by the general formula (II) without isolating the compound represented by the general formula (III). The manufacturing method of the compound represented by these.
Formula (IV)

[Wherein R ₃ represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group or a heterocyclic ring. R ₄ represents a cyano group, a sulfonyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, a carbamoyl group, a trifluoromethyl group or a sulfamoyl group, and R ₃ and R ₄ are bonded to each other when possible to form 4 to 8 members. The ring may be formed. R ₈ represents an alkyl group or an aryl group. R ₆ represents an alkyl group or an aryl group. ]