WO2007020964A1

WO2007020964A1 - Method for producing 4-halocatechol compound

Info

Publication number: WO2007020964A1
Application number: PCT/JP2006/316149
Authority: WO
Inventors: Shigeyoshi Nishino; Akira Nakamura; Hiroyuki Oda; Yoji Omata
Original assignee: Ube Industries, Ltd.
Priority date: 2005-08-17
Filing date: 2006-08-17
Publication date: 2007-02-22
Also published as: CN101243030A; JP5338072B2; CN101243030B; JPWO2007020964A1

Abstract

Disclosed is a method for producing a 4-halocatechol compound, which is characterized in that a catechol compound is reacted with 1,3-dihalo-5,5-dimethylhydantoin. Also disclosed are a high-purity 4-chloromethylenedioxybenzene which is characterized in that the methylenedioxybenzene content is not more than 0.5% by mass and the 4,5-dichloromethylenedioxybenzene content is not more than 0.5% by mass, and a method for producing such a high-purity 4-chloromethylenedioxybenzene.

Description

Specification

4—Production of halocatechol compound

Technical field

[0001] The present invention relates to a novel method for producing a 4-halocatechol compound. The 4-halocatechol compound is a useful compound as a raw material for pharmaceuticals, agricultural chemicals, etc. and as a synthetic intermediate.

The present invention also relates to high-purity 4-chloromethylenedioxybenzene and a process for producing the same. High purity 4-chloromethylenedioxybenzene is a useful compound as a raw material for pharmaceuticals and agricultural chemicals and as a synthetic intermediate.

Background art

Conventionally, as a method for producing a 4-halocatechol compound such as 4-chloromethylenedioxybenzene from a catechol compound, for example, the following method has been disclosed.

(1) A method for producing 5_cloguchi-1,3-benzodioxole by reacting benzodioxol, aluminum trichloride and diphenylsulfide in the presence of sulfuryl chloride (for example, patent Reference 1).

(2) 1,2-methylenedioxybenzene and acetyl chloride are reacted with cetyl chloride in the presence of ceric ammonium nitrate to form 1-chloro-3,4-methylenedioxybenzene. (See Non-Patent Document 1, for example).

(3) A method for producing 1-chloro-or bromo-3,4-methylenedioxybenzene by reacting methylenedioxybenzene with N-chloro-or bromosuccinimide in an ionic liquid solvent. Law (see Non-Patent Document 2, for example).

However, in these methods, the reaction system is complicated, and gases such as chlorine gas, hydrogen chloride gas, sulfur dioxide disulfide, and other highly toxic and corrosive gases are generated. However, it is disadvantageous as an industrial 4-halocatechol compound manufacturing method.

In addition, when used as a raw material for pharmaceuticals and agricultural chemicals or as a synthetic intermediate, impurities such as methylenedioxybenzene as a residual raw material and 4,5-dichloromethylenedioxybenzene as a by-product are substantially eliminated. High purity 4-chloromethylenedioxybenzene not contained in Needless to say, the purity of 4-chloromethylenedioxybenzene obtained in any literature was not mentioned!

Patent Document 1: International Application WO02 / 16352A1 Pamphlet

Non-patent document 1: Synlett, 221 (2003)

Non-Patent Document 2: Adv. Synth. Catal., 346, 77 (2004)

Disclosure of the invention

Problems to be solved by the invention

[0003] An object of the present invention is to solve the above-mentioned problems and to obtain a 4-nitrocatechol compound in high yield by a simple method under mild conditions, which is industrially suitable. It is to provide a method for producing a 4-nocatechol compound.

The subject of the present invention is also a residual raw material such as methylenedioxybenzene and a by-product such as 4,5-dichloromethylenedioxybenzene, which are most suitable for use as raw materials for pharmaceuticals' agricultural chemicals and synthetic intermediates. The object is to provide a high-purity 4-chloromethylenedioxybenzene containing substantially no impurities and a process for producing the same.

Means for solving the problem

[0004] The present invention relates to a general formula (1):

^[0005]

Wherein R ¹ and IT represent the same or different hydrocarbon groups,

R ³ , R ⁴ and R ⁵ represent a group not participating in the reaction, wherein R ¹ and R ² may be bonded to each other to form a ring,

And the general formula (2): [0007]

[0008] In the formula, x represents a halogen atom.

General formula (3), which is characterized by reacting with 1,3-dinoporin-5,5-dimethylhydantoin represented by formula (3):

[0010] where:

R ² , R ³ , R ⁴ , R ⁵ and X are as defined above,

It is related with the manufacturing method of 4-halocatechol compound shown by.

The present invention is also characterized in that the content power of methylenedioxybenzene is 0.5% by mass or less and the content of 4,5-dichloromethylenedioxybenzene is 0.5% by mass or less. -Relates to chloromethylenedioxybenzene.

The present invention further relates to a process for producing high-purity 4-chloromethylenedioxybenzene, which is obtained by reacting methylenedioxybenzene with a chlorinating agent and then purifying it by distillation.

The invention's effect

[0011] According to the present invention, a 4-halocatechol compound can be obtained in a high yield with a simple method under mild conditions. Can provide a manufacturing method.

In addition, according to the present invention, methylenedioxybenzene as a residual raw material and 4,5-dichloromethylenedioxybenzene as a by-product, which are most suitable for use as raw materials for pharmaceuticals' agricultural chemicals and synthetic intermediates, etc. Thus, it is possible to provide a high-purity 4-chloromethylenedioxybenzene and a process for producing the same, which are substantially free of impurities. Lead these compounds to pharmaceuticals, pesticides, etc. For example, WO 02/163521 A1 can be referred to.

BEST MODE FOR CARRYING OUT THE INVENTION

[0012] The catechol compound used in the reaction of the present invention is represented by the general formula (1). In the general formula (1), R ¹ and R ² represent a hydrogen atom or a hydrocarbon group which may be the same or different, and examples of the hydrocarbon group include a methyl group, an ethyl group, and a propyl group. Alkyl group having 1 to 10 carbon atoms such as butyl group, pentyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group; cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cyclo A cycloalkyl group having 3 to 8 carbon atoms such as a heptyl group or a cyclooctyl group; an aralkyl group in which an aryl group is bonded to an alkyl group having 1 to 6 carbon atoms such as a phenethyl group or a phenylpropyl group; a full group And aryl groups having 6 to 20 carbon atoms such as p-tolyl group, naphthyl group and anthryl group. These groups include various isomers. R ¹ and R ² may be bonded to each other to form a ring. Examples of the ring formed by bonding include a methylenedioxy ring and an ethylenedioxy ring containing an alkylene group having 1 to 3 carbon atoms. And propylenedioxy ring. In the present invention, among these, those in which R ¹ and R ² are bonded to each other to form a methylene group are particularly preferable.

[0013] R ³ , R ⁴ and R ⁵ each represent a group not involved in the reaction. Specifically, for example, a hydrogen atom, an alkyl group, a cycloalkyl group, an aralkyl group, an aryl group, a halogen atom, It represents a hydroxyl group, an alkoxyl group, an alkylthio group, a nitro group, a cyano group, a carboxylic group, an amino group or a carboxyl group.

[0014] Examples of the alkyl group include, for example, a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, a nonyl group, and a decyl group. Of the alkyl group. These groups include various isomers.

[0015] Examples of the cycloalkyl group include cycloalkyl groups having 3 to 8 carbon atoms, such as a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, and a cyclooctyl group. .

[0016] Examples of the aralkyl group include an aralkyl group in which an aryl group is bonded to an alkyl group having 1 to 6 carbon atoms such as a benzyl group, a phenethyl group, or a phenylpropyl group. It is done. These groups include various isomers.

[0017] Examples of the aryl group include aryl groups having 6 to 20 carbon atoms such as a phenyl group, a P-tolyl group, a naphthyl group, and an anthryl group. These groups include various foreign substances.

[0018] Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.

[0019] Examples of the alkoxyl group include an alkoxyl group having 1 to 10 carbon atoms such as a methoxyl group, an ethoxyl group, and a propoxyl group. These groups include various isomers.

[0020] Examples of the alkylthio group include alkylthio groups having 1 to 10 carbon atoms such as a methylthio group, an ethylthio group, and a propylthio group. These groups include various isomers.

[0021] The 1,3-diha-5,5-dimethylhydantoin used in the reaction of the present invention is represented by the general formula (2). In the general formula (2), X is a halogen atom, and examples thereof include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom, and a chlorine atom and a bromine atom are preferable.

[0022] The amount of 1,3-diha-5,5-dimethylhydantoin used is preferably 0.4 to 1.3 mol, more preferably 0.45 to 1.15 mol, per 1 mol of the catechol compound.

[0023] The solvent used preferably in the presence of a solvent is not particularly limited as long as it does not inhibit the reaction. For example, water; formic acid, acetic acid, propionic acid Carboxylic acids such as methanol, ethanol, isopropyl alcohol, _t -butyl alcohol, etc .; Ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone; Ν, Ν-dimethylformamide, Ν, Ν-dimethylacetate Amides, amides such as Ν-methylpyrrolidone; Ureas such as Ν, Ν'-dimethylimidazolidinone; Sulfoxides such as dimethyl sulfoxide; Sulfones such as sulfolane; -Tolyls such as acetonitrile and propio-tolyl; Ethers such as jetyl ether, diisopropyl ether, tetrahydrofuran, dioxane; benzene, toluene Aromatic hydrocarbons such as ruene and xylene can be mentioned, but carboxylic acids are preferred, and acetic acid is more preferred. These organic solvents May be used alone or in admixture of two or more.

[0024] The amount of the solvent used is preferably 0.5 to 100 ml, more preferably 1 to 50 ml, relative to catechol compound lg.

[0025] The reaction of the present invention is carried out, for example, by a method of mixing a catechol compound, 1,3-diha-5,5-dimethylhydantoin and a solvent and reacting them with stirring. The reaction temperature at that time is preferably −20 to 200 ° C., more preferably 0 to 120 ° C., and the reaction pressure is not particularly limited.

[0026] The ability to obtain a 4-halocatechol compound by the reaction of the present invention. After completion of the reaction, for example, neutralization, extraction, filtration, concentration, distillation, recrystallization, crystallization, column chromatography, etc. The product is isolated and purified by a general production method.

[0027] It should be noted that the reaction of the present invention is particularly useful for producing a 4-halocatechol compound such as 4-halomethylenedioxybenzene from a weakly strong alcohol compound such as methylenedioxybenzene. This is an advantageous method.

[0028] The high-purity 4-chloro-methylenedioxy O carboxymethyl benzene of the invention, the content of methylenedioxy O carboxymethyl content of benzene in 0.5 ^_0/0 or less, and 4,5-dichloro-methylenedioxy O carboxymethyl benzene Force Indicates that 4-chloromethylenedioxybenzene is less than mass%. Contact Itewa the present invention, the following methylenedioxy O carboxymethyl content force 0.1 ^_0/0 of benzene, and 4,5-content of dichloromethylene di O carboxymethyl benzene preferably not more than 0.1 mass% instrument further preferred details, at a content of methylene di O carboxymethyl benzene 0.01 ^_0/0 or less, and the content of 4,5-dichloro-methylenedioxy O carboxymethyl benzene is 0.01 ^_0/0 or less.

[0029] The high purity 4-chloromethylenedioxybenzene of the present invention can be obtained by distillation purification after reacting a chlorinating agent with methylenedioxybenzene.

[0030] The distillation purification method is, for example, at least selected from the group consisting of Sulzer One Pack (registered trademark), Paul Ring, Merapack (registered trademark), Meracarbon (registered trademark), and Mellajour (registered trademark). One kind of packing is carried out by a method such as distillation purification by packing one or more in the distillation column of a distillation apparatus. The filler is preferably filled with two or more theoretical plates. There are no particular restrictions on the temperature or pressure during distillation purification. [0031] Examples of the chlorinating agent include sulfuryl chloride, 1,3-dichloro-5,5-dimethylhydantoin, trichloroisocyanuric acid, t-butyl hypochlorite, and the like. 3,3-Dichloro-5,5-dimethylhydantoin is used. These chlorinating agents may be used alone or in combination of two or more.

[0032] The amount of the chlorinating agent used is preferably 0.

The amount is 4 to 1.3 mol, more preferably 0.45 to 1.15 mol.

[0033] The reaction of methylenedioxybenzene and chlorinating agent is preferably carried out in the presence of a solvent, and is not particularly limited as long as it does not inhibit the reaction. , Water; carboxylic acids such as formic acid, acetic acid and propionic acid; alcohols such as methanol, ethanol, isopropyl alcohol and t-butyl alcohol; ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone; Amides such as formamide, Ν, Ν-dimethylacetamide, Ν-methylpyrrolidone; Ureas such as Ν, Ν'-dimethylimidazolidinone; Sulfoxides such as dimethyl sulfoxide; Sulfones such as sulfolane; Acetonitrile, Propio -Tolyls such as -tolyl; jetyl ether, diisopropyl ether, tetrahydrofuran, dio Examples include ethers such as xane; aromatic hydrocarbons such as benzene, toluene, and xylene. In addition, you may use these organic solvents individually or in mixture of 2 or more types.

[0034] The amount of the solvent used is preferably 0.5 to 100 ml, more preferably 1 to 50 ml based on methylenedioxybenzene lg.

[0035] The reaction between the methylenedioxybenzene and the chlorinating agent is performed by, for example, a method of mixing methylenedioxybenzene, a chlorinating agent and a solvent and reacting them while stirring. The reaction temperature at that time is preferably −20 to 200 ° C., more preferably 0 to 120 ° C., and the reaction pressure is not particularly limited.

Example

Next, the ability to specifically explain the present invention with reference to examples The scope of the present invention is not limited to these.

Example 1 (Synthesis of 4-chloromethylenedioxybenzene)

To a 1000 ml glass flask equipped with a stirrer, thermometer and reflux condenser, Under an argon atmosphere, 244.2 g (2.0 mol) of methylenedioxybenzene and 122 g of acetic acid were removed, and the liquid temperature was raised to 55 ° C. Next, while maintaining the liquid temperature at 60 to 90 ° C, 216.7 g (l.lmol) of 1,3-dichloro-5,5-dimethylhydantoin was added little by little, and the mixture was stirred at 70 ° C with stirring. The reaction was performed for a time. After completion of the reaction, the reaction solution was cooled to room temperature, 245 ml of hexane and 245 ml of water were added to the reaction solution and stirred, and then the organic layer was separated. The obtained organic layer was washed with a 10% aqueous sodium hydroxide solution and a 10% aqueous sodium chloride solution, and then dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and then the concentrated solution was distilled under reduced pressure (85 ° C, 1067 to 1333 Pa) to obtain 227.3 g of 4_chloromethylenedioxybenzene as an colorless liquid (isolation yield) 72.6%).

The physical properties of 4-chloromethylenedioxybenzene were as follows.

[0038] EI-MS (m / e); 156 (M), 158 (M + 2)

^ -NMRCDMSO-d, δ (ppm)); 7.05 (lH, dd, J = 2.0,0.5Hz), 6.93 (lH, dd, J = 8.3,0.5Hz), 6.

6

87 (lH, dd, J = 8.3,2.0Hz), 6.07 (2H, s)

Example 2 (Synthesis of 4-chloromethylenedioxybenzene)

Under a argon atmosphere, add 1.22 g (10 mmol) of methylenedioxybenzene and 1.22 g of acetic acid to a glass flask with an internal volume of 25 ml equipped with a stirrer, thermometer and reflux condenser, and bring the liquid temperature to 60 ° C. The temperature rose. Next, while maintaining the liquid temperature at 60 to 90 ° C, 1.13 g (5.5 mmol) of 1,3-dichloro-5,5-dimethylhydantoin was added little by little, and the mixture was stirred at 70 ° C with stirring. The reaction was allowed for hours. After completion of the reaction, the reaction solution was analyzed by high performance liquid chromatography (absolute quantification method). As a result, .34 g of 4-chloromethylenedioxybenzene force was generated (reaction yield; 85.6%).

Comparative Example 1 (Synthesis of 4-chloromethylenedioxybenzene)

To a 500 mL glass flask equipped with a stirrer, thermometer and reflux condenser, add 244.2 g (2.0 mol) of methylenedioxybenzene in an argon atmosphere to maintain the liquid temperature at 30 to 35 ° C. While slowly adding 405.0 g (3.0 mol) of sulfuryl chloride, the mixture was reacted at 30 ° C. for 4 hours with stirring. After completion of the reaction, the reaction solution was cooled to room temperature, and 200 ml of hexane was added to the reaction solution, and then the obtained organic layer was washed twice with 200 g of 32% aqueous sodium thiosulfate solution and 200 g of 10% aqueous sodium bicarbonate solution. And dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and then the concentrated solution was distilled under reduced pressure (80 to 85 ° C, 933 to 1067 Pa) to obtain 192. lg of 4-chloromethylenedioxybenzene as a colorless liquid (single Separation yield; 59.7%).

Example 3 (Synthesis of 4-bromomethylenedioxybenzene)

In a glass flask equipped with a stirrer, thermometer and reflux condenser, add 61.1 g (0.5 mol) of methylenedioxybenzene and 30 g of acetic acid in an argon atmosphere to a liquid temperature of 60 ° C. The temperature rose. Next, while maintaining the liquid temperature at 60 to 90 ° C, 78.6 g (0.275 mol) of 1,3-dibromo-5,5-dimethylhydantoin was added little by little, and the mixture was stirred at 70 ° C with stirring. The reaction was allowed for hours. After completion of the reaction, the reaction solution was cooled to room temperature, and 200 g (1.0 mol) of 20% aqueous sodium hydroxide solution was added to the reaction solution and stirred. Next, the reaction solution was filtered to separate the organic layer, and then the organic layer was distilled under reduced pressure (93 ° C., 1200 Pa) to obtain 71.2 g of 4-bromomethylenedioxybenzene as a colorless liquid (isolated product). Rate; 70.8%).

The physical properties of 4-bromomethylenedioxybenzene were as follows.

[0042] EI— MS (m / e); 200 (M) ゝ 202 (M + 2)

^ -NMRCDMSO-d, δ (ppm)); 7.16 (lH, d, J = 1.9Hz) ゝ 7.00 (lH, dd, J = 8.3,2.2Hz), 6.88 (1

6

H, d, J = 8.3Hz), 6.06 (2H, s)

Example 4 (Synthesis of 4 bromoveratrol (4 bromo 1,2 dimethoxybenzene)) 13.8 g (100 mmol) of veratrol under argon atmosphere in a 100 ml glass flask equipped with stirrer and thermometer Then, 21.0 g (350 mmol) of acetic acid was cooled to a temperature of 10-20 ° C. Then, after 30 minutes, 17.2 g (60 mmol) of 1,3-dibromo-5,5-dimethylhydantoin was added little by little, and then reacted at 10 to 20 ° C. for 1 hour. After completion of the reaction, 25 ml of toluene was added and the mixture was stirred at 10 to 20 ° C. for 30 minutes, and the precipitated hydantoin and monobromohydantoin solids were separated by filtration. The filtrate was divided into four parts, the first fraction was added to a mixed solvent of toluene (50 ml) _water (25 ml), the target product was extracted into a toluene layer, and acetic acid was removed into the aqueous layer. 25 ml of water was added to the obtained toluene extract, and subsequently combined with the second fraction of the filtrate, and then the extraction operation was carried out in the same manner to obtain a toluene extract. Repeat the same procedure for the remaining two fractions, and then separate all the filtrates. The resulting toluene extract is twice with 25 ml of water, once with 20 ml of saturated aqueous sodium hydrogen carbonate solution, and finally. And washed once with 35 ml of saturated saline. The obtained Toru When the extracted solution was analyzed by high performance liquid chromatography (absolute quantification method), it contained 19.8 g (yield 91.6%) of 4 bromoveratrol. After concentrating the toluene extract, the resulting concentrate (crude 4 bromoveratrol) was distilled under reduced pressure (5 mmHg, bp 99-100 ° C) to obtain 15.8 g of 4 bromoveratrol as a pale yellow liquid ( Isolated yield 72.9%).

The physical properties of 4 bromoveratrol were as follows.

EI — MS (m / e); 216 (M), 218 (M + 2)

^ -NMRCCDCl, δ (ppm); 7.03 (lH, dd, J = 2.4,8.5Hz) ゝ 6.98 (lH, d, J = 2.4Hz), 6.74 (lH, d

Three

, J = 8.5Hz) ゝ 3.87 (3H, s) ゝ 3.86 (3H, s)

Example 5 (Synthesis of high purity 4-chloromethylenedioxybenzene)

To a glass flask with an internal volume of 2000 ml equipped with a stirrer, thermometer and reflux condenser, 488.4 g (4.0 mol) of methylenedioxybenzene and 240 g of acetic acid were added in an argon atmosphere, and the liquid temperature was raised to 60 ° C. Warm up. Next, while maintaining the liquid temperature at 60 to 90 ° C, 433.4 g (2.2 mol) of 1,3-dichloro-5,5-dimethylhydantoin was added little by little, and then stirred at 70 ° C for 1 hour. It was made to react between. After completion of the reaction, the reaction solution was cooled to room temperature, and 1000 g (6.25 mol) of 25% aqueous sodium hydroxide solution was added to the reaction solution and stirred. Next, after separating the organic layer, the organic layer was distilled under reduced pressure (84 ° C, 1067-1200Pa) using a distillation apparatus packed with 3 pieces of Sulzer Pack (55mmH x 2.5mm) in a distillation column, and then a colorless liquid As a result, 420.7 g of 4-chloromethylenedioxybenzene purified by distillation was obtained (isolation yield; 67.2%). The obtained 4-chloromethylenedioxybenzene was analyzed by high performance liquid chromatography (absolute quantitative method). As a result, 4-chloromethylenedioxybenzene contained 4-chloromethylenedioxybenzene with respect to 4-chloromethylenedioxybenzene. methylenedioxy O carboxymethyl benzene residual feedstock 0.17 mass ^_0/0, the by-product 4,5-Jikurorome Chi range O carboxymethyl benzene contained only 0.35 wt ^_0/0.

Example 6 (Synthesis of high purity 4-chloromethylenedioxybenzene)

In a 1000 mL glass flask equipped with a stirrer, thermometer and reflux condenser, 244.2 g (2.0 mol) of methylenedioxybenzene and 122 g of acetic acid were calored in an argon atmosphere, and the liquid temperature was increased to 55 ° C. The temperature rose. Next, 216.7 g (l.lmol) of 1,3-dichloro-5,5-dimethylhydantoin was added little by little while maintaining the liquid temperature at 60 to 95 ° C., and then stirred at 70 ° C. with stirring. The reaction was performed for a time. After completion of the reaction, the reaction solution is cooled to room temperature, and 245 ml of hexane is added to the reaction solution. After adding 245 ml of water and stirring, the organic layer was separated. The obtained organic layer was washed with 10% sodium hydroxide 100 g (0.25 mol) aqueous solution and 10% sodium chloride aqueous solution 100 g (0.25 mol), and then dried over anhydrous magnesium sulfate. After filtration, the filtrate is concentrated under reduced pressure, and the concentrate is distilled under reduced pressure (84 ° C, 1067-1200Pa) using a distillation apparatus packed with 3 pieces of Sulzer Pack (55mmH x 2.5mmφ) in a distillation column. As a colorless liquid, 227.3 g of 4-chloromethylenedioxybenzene purified by distillation was obtained (isolation yield; 72.6%). As a result of analysis in the same manner as in Example 5, in 4-chloromethylenedioxybenzene, the remaining raw material methylenedioxybenzene was 0.03 mass% with respect to 4-chloromethylenedibenzene. The by-product 4,5-dichloromethylenedioxybenzene contained only 0.01% by mass or less.

Example 7 (Synthesis of high purity 4-chloromethylenedioxybenzene)

In a glass flask equipped with a stirrer, thermometer and reflux condenser, add 122.1 g (2.0 mol) of methylenedioxybenzene and 122 g of acetic acid under argon atmosphere, and bring the liquid temperature to 55 ° C. The temperature rose. Next, 108.4 g (0.55 mol) of 1,3-dichloro-5,5-dimethylhydantoin was added little by little while maintaining the liquid temperature at 60 to 75 ° C., and the mixture was stirred at 70 ° C. with stirring. The reaction was allowed for hours. After completion of the reaction, the reaction solution was cooled to room temperature, 120 ml of hexane and 120 ml of water were added to the reaction solution and stirred, and then the organic layer was separated. The obtained organic layer was washed with 10% aqueous sodium hydroxide solution 100 g (0.25 mol) and 10% aqueous sodium chloride solution 100 g (0.25 mol), and then dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the concentrate was distilled under reduced pressure (86 ° C, 1333 Pa) using a distillation apparatus packed with three Sulzer packs (55 mmH x 2.5 mmφ) in a distillation column, and colorless. As a liquid, 97. lg of 4_chloromethylenedioxybenzene purified by distillation was obtained (isolation yield; 61.6%). Incidentally, was analyzed in the same manner as in Example 5, 4-in-chloro methylenedioxy O carboxymethyl benzene, 4-chloro-methylenedioxy O respect carboxymethyl benzene, methylene di O carboxymethyl benzene residual feedstock 0.01 ⁰ / ₀ or less, by-product 4,5-dichloromethylenedioxybenzene contained only 0.01% by mass or less o

Example 8 (Synthesis of high purity 4-chloromethylenedioxybenzene by distillation purification of crude 4-chloromethylenedioxybenzene) 0.96 mass methylenedioxy O carboxymethyl benzene residual feedstock ^_0/0, Suruza one pack byproducts 4,5 Jikuroromechi range O carboxymethyl benzene 1.84 mass ^_0/0 containing crude 4-chloromethylene-di O carboxymethyl benzene 594.86g (55mmH x 2.5mm) 4_chloromethylenedioxybenzene distilled and purified as a colorless liquid by vacuum distillation (80-81 ° C, 933-1066Pa) using a distillation apparatus packed with 2 pieces in a distillation column 365.59g was obtained. As a result of analysis in the same manner as in Example 5, in 4-chloromethylenedioxybenzene, the remaining raw material methylenedioxybenzene was 0.10 mass relative to 4-chloromethylenedioxybenzene. ^_0/0, the by-product 4,5-dichloro b methylenedioxy O carboxymethyl benzene contained only 0.09 wt ^_0/0.

Example 9 (Synthesis of high purity 4-chloromethylenedioxybenzene by distillation purification of crude 4-chloromethylenedioxybenzene)

Methylene residual feedstock di O carboxymethyl benzene 6.41 mass ^_0/0, Suruza one pack 4,5 Jikuroromechi range O carboxymethyl benzene 1.22 mass ^_0/0 containing crude 4-chloromethylene-di O carboxymethyl benzene 142.74g byproducts (55mmH X 2.5mm φ) Distillation under reduced pressure (85 ° C, 1333 Pa) using a distillation apparatus packed with 3 pieces in a distillation column to obtain 104.03 g of distilled and purified 4-chloromethylenedioxybenzene as a colorless liquid It was. As a result of analysis in the same manner as in Example 5, in 4-chloromethylenedioxybenzene, the remaining raw material methylenedioxybenzene was 0.01 mass relative to 4-chloromethylenedioxybenzene. ^_0/0 or less, the by-product 4,5 Jikuroromechire Nji O carboxymethyl benzene contained only 0.01 wt%.

Industrial applicability

[0049] The present invention relates to a novel method for producing a 4-halocatechol compound. The 4-halocatechol compound is a useful compound as a raw material for pharmaceuticals, agricultural chemicals, etc. and as a synthetic intermediate.

Claims

The scope of the claims

[1]-General formula (1)

In the formula, R ¹ and R ² represent the same or different hydrocarbon groups, R ³ , R ⁴ and R ⁵ represent groups not involved in the reaction, wherein R ¹ and R ² are , You can combine with each other to form a ring.

And the general formula (2):

In the formula, X represents a halogen atom.

It is characterized by reacting with 1,3-dinoyokuguchi-5,5-dimethylhydantoin represented by the general formula (3):

Where

R ² , R °, R ⁴ , R ⁵ and X are as defined above,

A process for producing 4-nocatechol compounds shown in

[2] The process for producing a 4-halocatechol compound according to claim 1, wherein the reaction is carried out in an organic solvent

[3] The 4-halocatechol compound according to claim 2, wherein the organic solvent is a carboxylic acid. Manufacturing method.

[4] The process for producing a 4-halocatechol compound according to claim 3, wherein the carboxylic acid is acetic acid

[5] The process for producing a 4-halocatechol compound according to any one of claims 1 to 4, wherein the catechol compound is methylenedioxybenzene.

[6] The process for producing a 4-halocatechol compound according to any one of claims 1 to 5, wherein X is a chlorine atom or a bromine atom.

[7] 1,3-Dihaguchi-5,5-dimethylhydantoin is used in an amount of 0.4 to 1.3 mol per mol of the catechol compound. A method for producing a 4-norocatechol compound described in 1.

[8] 1,3-dihaguchi-5,5-dimethylhydantoin is used in an amount of 0.45 to 1.15 mol per mol of the catechol compound 1. A method for producing the 4-halocatechol compound described in the paragraph.

[9] The process for producing a 4-halocatechol compound according to any one of claims 1 to 8, wherein the reaction is carried out at a temperature of -20 to 200 ° C.

[10] The process for producing a 4-halocatechol compound according to any one of claims 1 to 8, wherein the reaction is carried out at a temperature of 0 to 120 ° C.

[11] The 4-halocatechol according to any one of claims 1 to 10, wherein the 4-halocatechol compound is 4-chloromethylenedioxybenzene or 4-bromomethylenedibenzene. Compound preparation.

[12] The content of the methylenedioxy O carboxymethyl benzene in 0.5 ^_0/0 or less, and the content of 4,5-dichloromethylene Jiokishibenzen is equal to or less than 0.5 wt%, high purity 4-black port Methylenedioxybenzene.

[13] methylenedioxy O carboxymethyl content force .1 mass ^_0/0 less benzene, and 4,5-content of dichloromethylene Jiokishibenzen range of paragraph 12, wherein claims more than 0.1 wt% high purity 4 -Chloromethylenedioxybenzene.

[14] in a content of methylene di O carboxymethyl benzene 0.01 ^_0/0 or less, and 4,5 Jikuroromechire Nji O content of carboxymethyl benzene according Claim 12 or less 0.01 mass% high Purity 4-chloromethylenedioxybenzene.

[15] The high-purity 4-chloromethylene according to claim 12, wherein methylenedioxybenzene is reacted with a chlorinating agent and then purified by distillation to obtain high-purity 4-chloromethylenedioxybenzene. Dioxybenzene production method.

[16] The distillation purification of 4-chloromethylenedioxybenzene is carried out through a distillation apparatus filled with at least one packing selected from the group consisting of a through-the-pack, a pole ring, a melapack, a melacarbon, and a melajoule force. A process for producing high-purity 4-chloromethylenedioxybenzene according to claim 15.

[17] The following methylenedioxy O carboxymethyl content force .1 weight of benzene ^_0/0, and, 4,5 Jikuroromechire Nji O range paragraph 15 of carboxymethyl claims benzene content is less than 0.1 wt%, or 16 A process for producing high-purity 4-chloromethylenedioxybenzene as described in the item.

[18] in a content of methylene di O carboxymethyl benzene 0.01 ^_0/0 or less, 4,5 Jikuroromechire Nji O range 15 of claims content of carboxymethyl benzene is less than 0.01% by mass or 16 A process for producing high-purity 4-chloromethylenedioxybenzene as described in the item.