JP5338072B2 - Preparation of 4-halocatechol compounds - Google Patents

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

The present invention relates to a novel process for producing 4-halocatechol compounds. The 4-halocatechol compound is a useful compound as a raw material for pharmaceuticals and agricultural chemicals and 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 a synthetic intermediate.

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-chloro-1,3-benzodioxole by reacting benzodioxole, aluminum trichloride and diphenyl sulfide in the presence of sulfuryl chloride (see, for example, Patent Document 1).
(2) A method for producing 1-chloro-3,4-methylenedioxybenzene by reacting 1,2-methylenedioxybenzene and acetyl chloride in acetonitrile in the presence of seric ammonium nitrate (for example, Non-patent document 1).
(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 (for example, non-patented) Reference 2).
However, in these methods, the reaction system is complicated, and toxic and corrosive gases such as chlorine gas, hydrogen chloride gas, and sulfur dioxide are generated, and the post-treatment of the reaction solution becomes complicated. There was a problem and it was disadvantageous as an industrial 4-halocatechol compound production method.
In addition, when used as a raw material for pharmaceuticals and agricultural chemicals or as a synthetic intermediate, it substantially contains impurities such as methylenedioxybenzene as a residual raw material and 4,5-dichloromethylenedioxybenzene as a by-product. Needless to say, high purity 4-chloromethylenedioxybenzene is not useful, but the purity of 4-chloromethylenedioxybenzene obtained in any literature is not mentioned.
International application WO02 / 16352A1 brochure Synlett, 221 (2003) Adv.Synth.Catal., 346,77 (2004)

An object of the present invention is to solve the above-mentioned problems and obtain a 4-halocatechol compound in a high yield in a simple manner under mild conditions, and an industrially suitable 4-halocatechol compound It is to provide a manufacturing method.
The subject of the present invention is also suitable for use as a raw material for pharmaceuticals and agricultural chemicals and synthetic intermediates, such as methylenedioxybenzene as a residual raw material and 4,5-dichloromethylenedioxybenzene as a by-product. An object of the present invention is to provide a high-purity 4-chloromethylenedioxybenzene substantially free from impurities and a process for producing the same.

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

In the formula, R ¹ and R ² may be the same or different and each represents a hydrocarbon group,
R ³ , R ⁴ and R ⁵ represent groups not involved in the reaction, wherein R ¹ and R ² are
They may combine with each other to form a ring,
A catechol compound represented by the general formula (2):

In the formula, X represents a halogen atom.
A general formula (3) characterized by reacting 1,3-dihalo-5,5-dimethylhydantoin represented by the following formula:

In the formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ and X are as defined above.
To a method for producing a 4-halocatechol compound represented by the formula:
The present invention is also characterized in that the content of methylenedioxybenzene is 0.5% by mass or less and the content of 4,5-dichloromethylenedioxybenzene is 0.5% by mass or less. It relates to chloromethylenedioxybenzene.
The present invention further relates to a process for producing high-purity 4-chloromethylenedioxybenzene, in which methylenedioxybenzene is reacted with a chlorinating agent and then purified by distillation to obtain high-purity 4-chloromethylenedioxybenzene.

According to the present invention, a 4-halocatechol compound can be obtained in a high yield with a simple method under mild conditions, and an industrially suitable method for producing a 4-halocatechol compound can be provided.
In addition, according to the present invention, impurities such as methylenedioxybenzene as a residual raw material and 4,5-dichloromethylenedioxybenzene as a by-product, which are optimal for use as raw materials for pharmaceuticals and agricultural chemicals and synthetic intermediates, can be used. It is possible to provide a high purity 4-chloromethylenedioxybenzene which is substantially not contained and a method for producing the same. In order to lead these compounds to pharmaceuticals, agricultural chemicals and the like, for example, WO 02/1635 2A 1 can be referred to.

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 may be the same or different and each represents a hydrogen atom or a hydrocarbon group. Examples of the hydrocarbon group include a methyl group, an ethyl group, a propyl group, C1-C10 alkyl groups such as butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl; cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclo A cycloalkyl group having 3 to 8 carbon atoms such as an octyl 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 and a phenylpropyl group; a phenyl group, a p-tolyl group, and a naphthyl group And aryl groups having 6 to 20 carbon atoms such as a group and an 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 containing an alkylene group having 1 to 3 carbon atoms, An ethylene dioxy ring, a propylene dioxy ring, etc. are mentioned. 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.

R ³ , R ⁴ and R ⁵ represent groups 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, a hydroxyl group, An alkoxyl group, an alkylthio group, a nitro group, a cyano group, a carbonyl group, an amino group, or a carboxyl group is shown.

  Examples of the alkyl group include alkyl groups having 1 to 10 carbon atoms such as 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. It is done. These groups include various isomers.

  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.

  As said aralkyl group, the aralkyl group which the aryl group couple | bonded with C1-C6 alkyl groups, such as a benzyl group, a phenethyl group, a phenylpropyl group, is mentioned, for example. These groups include various isomers.

  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 isomers.

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

  As said alkoxyl group, C1-C10 alkoxyl groups, such as a methoxyl group, an ethoxyl group, a propoxyl group, are mentioned, for example. These groups include various isomers.

  As said alkylthio group, C1-C10 alkylthio groups, such as a methylthio group, an ethylthio group, a propylthio group, are mentioned, for example. These groups include various isomers.

  The 1,3-dihalo-5,5-dimethylhydantoin used in the reaction of the present invention is represented by the above 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.

  The amount of the 1,3-dihalo-5,5-dimethylhydantoin used is preferably 0.4 to 1.3 mol, more preferably 0.45 to 1.15 mol, relative to 1 mol of the catechol compound.

  The reaction of the present invention is desirably carried out in the presence of a solvent, and the solvent used is not particularly limited as long as it does not inhibit the reaction. For example, water; carboxylic acids such as formic acid, acetic acid, 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 N, N-dimethylformamide, N, N-dimethylacetamide and N-methylpyrrolidone Ureas such as N, N'-dimethylimidazolidinone; sulfoxides such as dimethyl sulfoxide; sulfones such as sulfolane; nitriles such as acetonitrile and propionitrile; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran and dioxane; Benzene, toluene, key Although aromatic hydrocarbons such as alkylene are exemplified, preferably a carboxylic acid is more preferably used acetic acid. In addition, you may use these organic solvents individually or in mixture of 2 or more types.

  The amount of the solvent to be used is preferably 0.5 to 100 ml, more preferably 1 to 50 ml, with respect to 1 g of the catechol compound.

  The reaction of the present invention is carried out, for example, by a method of mixing a catechol compound, 1,3-dihalo-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.

  A 4-halocatechol compound is obtained by the reaction of the present invention, and this is performed after completion of the reaction, for example, by a general production method such as neutralization, extraction, filtration, concentration, distillation, recrystallization, crystallization, column chromatography, etc. Isolated and purified by

  The reaction of the present invention is a particularly advantageous method for producing, for example, a 4-halocatechol compound such as 4-halomethylenedioxybenzene from an acid-sensitive catechol compound such as methylenedioxybenzene.

  The high-purity 4-chloromethylenedioxybenzene of the present invention has a methylenedioxybenzene content of 0.5% by mass or less and a 4,5-dichloromethylenedioxybenzene content of 0.5% by mass or less. -Indicates chloromethylenedioxybenzene. In the present invention, the content of methylenedioxybenzene is preferably 0.1% by mass or less and the content of 4,5-dichloromethylenedioxybenzene is preferably 0.1% by mass or less, more preferably methylenedioxybenzene. The oxybenzene content is 0.01% by mass or less, and the 4,5-dichloromethylenedioxybenzene content is 0.01% by mass or less.

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

  The distillation purification method includes, for example, at least one selected from the group consisting of Sulzer Pack (registered trademark), Pole Ring, Merapack (registered trademark), Meracarbon (registered trademark), and Merajour (registered trademark). One or a plurality of packing materials are packed in a distillation column of a distillation apparatus and purified by distillation. The filling is preferably filled with at least two theoretical plates. The temperature and pressure at the time of distillation purification are not particularly limited.

  Examples of the chlorinating agent include sulfuryl chloride, 1,3-dichloro-5,5-dimethylhydantoin, trichloroisocyanuric acid, t-butyl hypochlorite, and the like, preferably 1,3-dichloro- 5,5-dimethylhydantoin is used. In addition, you may use these chlorinating agents individually or in mixture of 2 or more types.

  The amount of the chlorinating agent used is preferably 0.4 to 1.3 mol, more preferably 0.45 to 1.15 mol, per 1 mol of methylenedioxybenzene.

  The reaction between the methylenedioxybenzene and the chlorinating agent is preferably carried out in the presence of a solvent, and the solvent used is not particularly limited as long as it does not inhibit the reaction. For example, water; formic acid, acetic acid Carboxylic acids such as propionic acid; alcohols such as methanol, ethanol, isopropyl alcohol and t-butyl alcohol; ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone; N, N-dimethylformamide, N, N-dimethylacetamide, Amides such as N-methylpyrrolidone; Ureas such as N, N'-dimethylimidazolidinone; Sulfoxides such as dimethyl sulfoxide; Sulfones such as sulfolane; Nitriles such as acetonitrile and propionitrile; Diethyl ether and diisopropyl Ether, tetrahydrofuran, dioxane, etc. Ether like; benzene, toluene, aromatic hydrocarbons such as xylene. In addition, you may use these organic solvents individually or in mixture of 2 or more types.

  The amount of the solvent used is preferably 0.5 to 100 ml, more preferably 1 to 50 ml, with respect to 1 g of methylenedioxybenzene.

  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.

  Next, the present invention will be specifically described with reference to examples, but the scope of the present invention is not limited thereto.

Example 1 (Synthesis of 4-chloromethylenedioxybenzene)
Under an argon atmosphere, 244.2 g (2.0 mol) of methylenedioxybenzene and 122 g of acetic acid were added to a glass flask having an internal volume of 1000 ml equipped with a stirrer, a thermometer and a reflux condenser, and the liquid temperature was raised to 55 ° C. . Next, 216.7 g (1.1 mol) of 1,3-dichloro-5,5-dimethylhydantoin was added little by little while maintaining the liquid temperature at 60 to 90 ° C., and the mixture was reacted at 70 ° C. for 1 hour with stirring. 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 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.

EI-MS (m / e); 156 (M), 158 (M + 2)
¹ H-NMR (DMSO-d ₆ , δ (ppm)); 7.05 (1H, dd, J = 2.0,0.5 Hz), 6.93 (1H, dd, J = 8.3,0.5 Hz), 6.87 (1H, dd, J = 8.3, 2.0Hz), 6.07 (2H, s)

Example 2 (Synthesis of 4-chloromethylenedioxybenzene)
Under an argon atmosphere, 1.22 g (10 mmol) of methylenedioxybenzene and 1.22 g of acetic acid were added to a glass flask having an internal volume of 25 ml equipped with a stirrer, a thermometer and a reflux condenser, and the liquid temperature was raised to 60 ° C. . Next, 1.13 g (5.5 mmol) of 1,3-dichloro-5,5-dimethylhydantoin was added little by little while maintaining the liquid temperature at 60 to 90 ° C., and the mixture was reacted at 70 ° C. for 1 hour with stirring. After completion of the reaction, the reaction solution was analyzed by high performance liquid chromatography (absolute quantification method). As a result, 1.34 g of 4-chloromethylenedioxybenzene was formed (reaction yield; 85.6%).

Comparative Example 1 (Synthesis of 4-chloromethylenedioxybenzene)
To a glass flask having an internal volume of 500 ml equipped with a stirrer, a thermometer and a reflux condenser, 244.2 g (2.0 mol) of methylenedioxybenzene was added under an argon atmosphere, and the temperature of the solution was kept at 30 to 35 ° C. Sulfuryl 405.0 g (3.0 mol) was gently added dropwise, followed by reaction at 30 ° C. for 4 hours with stirring. After completion of the reaction, the reaction solution was cooled to room temperature, 200 ml of hexane was added to the reaction solution, and the obtained organic layer was washed twice with 200 g of 32% sodium thiosulfate aqueous solution and with 200 g of 10% sodium hydrogen carbonate aqueous 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 192.1 g of 4-chloromethylenedioxybenzene (isolated yield) as a colorless liquid. ; 59.7%).

Example 3 (Synthesis of 4-bromomethylenedioxybenzene)
To a glass flask having an internal volume of 500 ml equipped with a stirrer, a thermometer and a reflux condenser, 61.1 g (0.5 mol) of methylenedioxybenzene and 30 g of acetic acid were added under an argon atmosphere, and the liquid temperature was raised to 60 ° C. . Next, 78.6 g (0.275 mol) of 1,3-dibromo-5,5-dimethylhydantoin was added little by little while maintaining the liquid temperature at 60 to 90 ° C., and the mixture was reacted at 70 ° C. for 1 hour with stirring. 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.

EI-MS (m / e); 200 (M), 202 (M + 2)
¹ H-NMR (DMSO-d ₆ , δ (ppm)); 7.16 (1H, d, J = 1.9 Hz), 7.00 (1H, dd, J = 8.3,2.2 Hz), 6.88 (1H, d, J = 8.3Hz), 6.06 (2H, s)

Example 4 (Synthesis of 4-bromoveratrol (4-bromo-1,2-dimethoxybenzene))
Veratrol 13.8 g (100 mmol) and acetic acid 21.0 g (350 mmol) were added to a glass flask having an internal volume of 100 ml equipped with a stirrer and a thermometer, and the liquid temperature was cooled to 10 to 20 ° C. under an argon atmosphere. Next, over the course of 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 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 the toluene layer, and acetic acid was removed into the aqueous layer. 25 ml of water was added to the obtained toluene extract, and after combining with the second fraction of the filtrate, extraction operation was performed in the same manner to obtain a toluene extract. Repeat the same procedure for the remaining two fractions, and all the filtrates are separated. The resulting toluene extract is washed twice with 25 ml of water, once with 20 ml of saturated aqueous sodium bicarbonate solution, and finally. Washed once with 35 ml of saturated saline. The obtained toluene extraction solution was analyzed by high performance liquid chromatography (absolute quantification method), and as a result, 19.8 g (yield 91.6%) of 4-bromoveratrol was contained. After concentrating the toluene extract, the obtained concentrated solution (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)
¹ H-NMR (CDCl ₃ , δ (ppm)); 7.03 (1H, dd, J = 2.4,8.5 Hz), 6.98 (1H, d, J = 2.4 Hz), 6.74 (1H, d, J = 8.5 Hz) ), 3.87 (3H, s), 3.86 (3H, s)

Example 5 (Synthesis of high purity 4-chloromethylenedioxybenzene)
To a glass flask having an internal volume of 2000 ml equipped with a stirrer, a thermometer and a reflux condenser, 488.4 g (4.0 mol) of methylenedioxybenzene and 240 g of acetic acid were added under an argon atmosphere, and the liquid temperature was raised to 60 ° C. . Subsequently, 433.4 g (2.2 mol) of 1,3-dichloro-5,5-dimethylhydantoin was added little by little while maintaining the liquid temperature at 60 to 90 ° C., and the mixture was reacted at 70 ° C. for 1 hour with stirring. 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 subjected to vacuum distillation (84 ° C., 1067 to 1200 Pa) using a distillation apparatus in which three throughzer packs (55 mmH × 25 mmφ) were packed in a distillation column to obtain a colorless liquid. Thus, 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 quantification method). As a result, 4-chloromethylenedioxybenzene remained in 4-chloromethylenedioxybenzene with respect to 4-chloromethylenedioxybenzene. The raw material contained only 0.17% by mass of methylenedioxybenzene, and only 0.35% by mass of by-product 4,5-dichloromethylenedioxybenzene.

Example 6 (Synthesis of high purity 4-chloromethylenedioxybenzene)
Under an argon atmosphere, 244.2 g (2.0 mol) of methylenedioxybenzene and 122 g of acetic acid were added to a glass flask having an internal volume of 1000 ml equipped with a stirrer, a thermometer and a reflux condenser, and the liquid temperature was raised to 55 ° C. . Next, 216.7 g (1.1 mol) of 1,3-dichloro-5,5-dimethylhydantoin was added little by little while maintaining the liquid temperature at 60 to 95 ° C., and the mixture was reacted at 70 ° C. for 1 hour with stirring. 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 100% (0.25 mol) aqueous solution of 10% sodium hydroxide and 100 g of 10% aqueous solution of sodium chloride , and then dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the concentrate was distilled under reduced pressure (84 ° C., 1067-1200 Pa) using a distillation apparatus packed with three sulzer packs (55 mmH × 25 mmφ) into a distillation column, and colorless. As a liquid, 227.3 g of distilled and purified 4-chloromethylenedioxybenzene was obtained (isolation yield: 72.6%). As a result of analysis in the same manner as in Example 5, in 4-chloromethylenedioxybenzene, 0.03% by mass of the remaining raw material methylenedioxybenzene relative to 4-chloromethylenedioxybenzene was a by-product. 4,5-dichloromethylenedioxybenzene contained only 0.01% by mass or less.

Example 7 (Synthesis of high purity 4-chloromethylenedioxybenzene)
Under an argon atmosphere, 122.1 g (2.0 mol) of methylenedioxybenzene and 122 g of acetic acid were added to a glass flask having an internal volume of 500 ml equipped with a stirrer, a thermometer and a reflux condenser, and the liquid temperature was raised to 55 ° C. . 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 reacted at 70 ° C. for 1 hour with stirring. 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 100% (0.25 mol) aqueous solution of 10% sodium hydroxide and 100 g of 10% aqueous solution of sodium chloride , 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 25 mmφ) into a colorless liquid. As a result, 97.1 g of 4-chloromethylenedioxybenzene purified by distillation was obtained (isolation yield: 61.6%). As a result of analysis in the same manner as in Example 5, in 4-chloromethylenedioxybenzene, the remaining raw material methylenedioxybenzene was 0.01% by mass or less with respect to 4-chloromethylenedioxybenzene. The product 4,5-dichloromethylenedioxybenzene contained only 0.01% by mass or less.

Example 8 (Synthesis of high purity 4-chloromethylenedioxybenzene by distillation purification of crude 4-chloromethylenedioxybenzene)
0.96 wt% of methylenedioxybenzene remaining material, by-products of 4,5-dichloro-methylenedioxybenzene 1.84 wt% including crude 4-chloro-methylenedioxybenzene 594.86g a Sulzer pack (55mmH × 25 mmφ) Distillation under reduced pressure (80 to 81 ° C., 933 to 1066 Pa) using a distillation apparatus in which two were packed in a distillation column gave 365.59 g of distilled and purified 4-chloromethylenedioxybenzene as a colorless liquid. As a result of analysis in the same manner as in Example 5, in 4-chloromethylenedioxybenzene, the residual raw material methylenedioxybenzene was 0.10% by mass relative to 4-chloromethylenedioxybenzene, by-product. The product 4,5-dichloromethylenedioxybenzene contained only 0.09% by mass.

Example 9 (Synthesis of high purity 4-chloromethylenedioxybenzene by distillation purification of crude 4-chloromethylenedioxybenzene)
Crude 4-chloromethylenedioxybenzene (142.74 g) containing 6.41% by mass of residual methylenedioxybenzene and 1.22% by-product of 4,5-dichloromethylenedioxybenzene as a by-product (55 mmH x 25 mmφ) Distillation under reduced pressure (85 ° C., 1333 Pa) using a distillation apparatus in which three were packed in a distillation column gave 104.03 g of distilled and purified 4-chloromethylenedioxybenzene as a colorless liquid. As a result of analysis in the same manner as in Example 5, in 4-chloromethylenedioxybenzene, the remaining raw material methylenedioxybenzene was 0.01% by mass or less with respect to 4-chloromethylenedioxybenzene. The product 4,5-dichloromethylenedioxybenzene contained only 0.01% by mass or less.

The present invention relates to a novel process for producing 4-halocatechol compounds. The 4-halocatechol compound is a useful compound as a raw material for pharmaceuticals and agricultural chemicals and 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 a synthetic intermediate.

Claims (9)

General formula (1):

Wherein R ¹ and R ² combine with each other to form a methylene group ;
R ^{3, R 4} and ^{R 5} are tables to a group that does not participate in the reaction,
A catechol compound represented by the general formula (2):

In the formula, X represents a halogen atom.
A general formula (3) characterized by reacting 1,3-dihalo-5,5-dimethylhydantoin represented by general formula (3):

In the formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ and X are as defined above.
The manufacturing method of 4-halocatechol compound shown by these.   The process for producing a 4-halocatechol compound according to claim 1, wherein the carboxylic acid is acetic acid.   The method for producing a 4-halocatechol compound according to claim 1 or 2, wherein the catechol compound is methylenedioxybenzene.   The method for producing a 4-halocatechol compound according to any one of claims 1 to 3, wherein X is a chlorine atom or a bromine atom.   5. The method according to claim 1, wherein 1,3-dihalo-5,5-dimethylhydantoin is used in an amount of 0.4 to 1.3 mol relative to 1 mol of the catechol compound. -Production method of halocatechol compounds.   5. The method according to claim 1, wherein 1,3-dihalo-5,5-dimethylhydantoin is used in an amount of 0.45 to 1.15 mol per mol of the catechol compound. -Production method of halocatechol compounds.   The method for producing a 4-halocatechol compound according to any one of claims 1 to 6, wherein the reaction is carried out at a temperature of -20 to 200 ° C.   The method for producing a 4-halocatechol compound according to any one of claims 1 to 6, wherein the reaction is carried out at a temperature of 0 to 120 ° C.   The method for producing a 4-halocatechol compound according to any one of claims 1 to 8, wherein the 4-halocatechol compound is 4-chloromethylenedioxybenzene or 4-bromomethylenedioxybenzene.