KR20160102228A - Method for producing halogen-substituted phthalide - Google Patents

Abstract

A process for producing a halogen-substituted phthalide comprising the steps (A) and (B).
Step (A): A step of reacting halogen-substituted phthalic anhydride with sodium borohydride in at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent in the presence of water.
Step (B): A step of replacing part or all of at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent contained in the reaction mixture obtained in the step (A) with an aromatic hydrocarbon solvent.

Description

METHOD FOR PRODUCING HALOGEN-SUBSTITUTED PHTHALIDE BACKGROUND OF THE INVENTION [0001]

The present invention relates to a process for the preparation of halogen substituted phthalides.

Halogen substituted phthalides are compounds useful as raw materials, intermediates and substrates for pesticides. Patent Literature 1 discloses a method of reacting tetrachlorophthalic anhydride and sodium borohydride in the presence of 2-propanol, tetrahydrofuran or 1,2-dimethoxyethane, filtering out the obtained crystals, A process for producing 6,7-tetrachlorophthalide is described.

Japanese Laid-Open Patent Publication No. 2011-26295

There has been a demand for a process for producing a halogen-substituted phthalide at a good yield while recovering a solvent to be used.

The present invention provides the following inventions [1] to [7].

[1] A process for producing a halogen-substituted phthalide comprising the following steps (A) and (B).

Step (A): A step of reacting halogen-substituted phthalic anhydride with sodium borohydride in at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent in the presence of water.

Step (B): A step of replacing part or all of at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent contained in the reaction mixture obtained in the step (A) with an aromatic hydrocarbon solvent.

[2] The production process according to [1], wherein water is added to the reaction system before the step (B).

[3] A process for producing a halogen-substituted phthalide comprising the following steps (A) and (B).

Step (A): a step of reacting a halogen-substituted phthalic acid anhydride with sodium borohydride in the presence of at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent.

Step (B): Water is added to the reaction mixture obtained in the step (A), and part or all of at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent contained in the reaction mixture is reacted with an aromatic hydrocarbon solvent The process of substitution.

[4] The production method according to [1] to [3], which further comprises the following step (C).

Step (C): a step of mixing the mixture obtained in the step (B) with an acid.

[5] The production method according to [1] to [4], wherein the amount of water is 0.05 to 3 moles relative to 1 mole of sodium borohydride.

[6] The process according to [1] to [5], wherein the halogen-substituted phthalide is tetrahalogen-substituted phthalic anhydride.

[7] The process according to [1] to [6], wherein the halogen-substituted phthalide is tetrachlorophthalic anhydride.

≪ Process (A) >

The halogen-substituted phthalic anhydride is a phthalic anhydride in which at least one of the four hydrogen atoms of the phthalic anhydride is substituted with a halogen atom such as a fluorine atom, a chlorine atom or a bromine atom. Examples of the halogen-substituted phthalic anhydride include monohalogen-substituted phthalic anhydride, dihalogen-substituted phthalic anhydride, trihalogen-substituted phthalic anhydride and tetraloguan-substituted phthalic anhydride.

The monohalogen-substituted phthalic anhydride is an anhydrous phthalic acid in which one of the four hydrogen atoms of the phthalic anhydride is substituted with a halogen atom.

Examples of the monohalogen-substituted phthalic anhydride include 3-fluorophthalic anhydride, 4-fluorophthalic anhydride, 3-chlorophthalic anhydride, 4-chlorophthalic anhydride, 3-bromophthalic anhydride and 4- have.

The dihalogen-substituted phthalic anhydride is an anhydrous phthalic acid in which two of the four hydrogen atoms of the phthalic anhydride are substituted with a halogen atom.

Examples of the dihalogen-substituted phthalic anhydride include 3,4-difluorophthalic anhydride, 3,5-difluorophthalic anhydride, 3,6-difluorophthalic anhydride, 4,5-difluorophthalic anhydride, Dicarboxylic anhydride, 3,5-dicarboxylic anhydride, 4-dicarboxylic anhydride, 4-dicarboxylic anhydride, 4-dicarboxylic anhydride, Dicarboxylic anhydride, 3,6-dibromo phthalic acid, 4,5-dibromo phthalic acid, 3-chloro-4-fluorophthalic anhydride, 3-chloro- 3-bromo-4-fluorophthalic anhydride, 3-bromo-4-fluorophthalic anhydride, 3-bromo-5-fluorophthalic anhydride, 3- 4-bromo-5-fluorophthalic anhydride.

The trihalogen-substituted phthalic anhydride is an anhydrous phthalic acid in which three of the four hydrogen atoms of the phthalic anhydride are substituted with a halogen atom.

Examples of the trihalogen-substituted phthalic anhydride include 3,4,5-trifluorophthalic anhydride, 3,4,6-trifluorophthalic anhydride, 3,4,5-trichlorophthalic anhydride, 3,4,6-trichloro There may be mentioned phthalic anhydride, 3,4,5-tribromomethane phthalic acid, 3,4,6-tribromomethane phthalic acid, 3,4-dichloro-5-fluorophthalic anhydride, 3,4-dichloro-6- Include phthalic anhydride and 4,5-dichloro-3-fluorophthalic anhydride.

The tetrahalogen-substituted phthalic anhydride is an anhydrous phthalic acid in which all of the four hydrogen atoms of the phthalic anhydride are substituted with halogen atoms.

Examples of the tetrahalogen-substituted phthalic anhydride include tetrafluorophthalic anhydride, tetrachlorophthalic anhydride, tetrabromophthalic anhydride, 3,6-dichloro-4,5-difluorophthalic anhydride, 4,5-dichloro- -Difluorophthalic anhydride, 6-fluoro-3,4,5-trichloro anhydride, and 6-chloro-3,4,5-trifluorophthalic anhydride.

The monohalogen-substituted phthalic anhydride, the dihalogen-substituted phthalic anhydride and the trihalogen-substituted phthalic anhydride may further have a substituent which is inert to the reaction of the halogen-substituted phthalic anhydride with sodium borohydride.

Examples of the substituent which is inert to the reaction of halogen-substituted phthalic anhydride with sodium borohydride include alkyl groups having 1 to 12 carbon atoms such as methyl group, ethyl group and propyl group.

The halogen-substituted anhydrous phthalic acid is preferably tetrahalogen-substituted phthalic anhydride, more preferably tetrachlorophthalic anhydride.

Halogen-substituted phthalic acid can be obtained by a method of halogenating phthalic anhydride (see JP-A-6-329653), a method of reacting a halogen-substituted phthalic acid with thionyl chloride or the like to dehydrate (Japanese Patent Application Laid-Open No. 6-16656 ). ≪ / RTI >

The sodium borohydride may be commercially available or may be prepared by a known method such as reacting a boric acid ester with sodium hydride.

The amount of sodium borohydride to be used is preferably 0.5 mol or more, more preferably 0.5 to 3 mol, still more preferably 0.7 to 1.5 mol, particularly preferably 0.8 to 1 mol, per mol of halogen-substituted anhydrous phthalic acid. It is mall.

Examples of the ether solvent include diethyl ether, methyl tert-butyl ether, tetrahydrofuran, 1,4-dioxane, diisopropyl ether and 1,2-dimethoxyethane.

The ether solvent is preferably tetrahydrofuran or 1,2-dimethoxyethane, more preferably 1,2-dimethoxyethane.

As the ether solvent, commercially available ones can be used as they are, or they can be purified and used by refining means such as distillation.

The amount of the ether solvent to be used is preferably 0.1 to 100 parts by weight, more preferably 1 to 10 parts by weight based on 1 part by weight of the halogen-substituted phthalic anhydride.

Examples of the alcohol solvent include a compound having at least one hydroxyl group, specifically, methanol and an alcohol having 2 or more carbon atoms.

Examples of the alcohols having 2 or more carbon atoms include primary alcohols having 2 to 12 carbon atoms, secondary alcohols having 3 to 12 carbon atoms, and tertiary alcohols having 3 to 12 carbon atoms.

Examples of primary alcohols having 2 to 12 carbon atoms include alcohols such as ethanol, 1-propanol, 1-butanol, 2-methyl-1-propanol, 1-pentanol, Ethylene glycol monomethyl ether and ethylene glycol monoethyl ether.

Examples of secondary alcohols having 3 to 12 carbon atoms include 2-propanol, 2-butanol, 2-pentanol, 3-pentanol, cyclopentyl alcohol and cyclohexyl alcohol.

Examples of tertiary alcohols having 3 to 12 carbon atoms include 2-methyl-2-propanol, 2-methyl-2-butanol and 3-ethyl-3-pentanol.

The alcohol solvent is preferably methanol, a primary alcohol having 2 to 12 carbon atoms or a secondary alcohol having 3 to 12 carbon atoms, more preferably methanol, a primary alcohol having 2 to 6 carbon atoms or a tertiary alcohol having 3 to 6 carbon atoms Secondary alcohol, more preferably methanol or 2-propanol, and still more preferably 2-propanol.

Commercially available alcohol solvents may be used as they are, or they may be purified by distillation or other purification means.

When the alcohol solvent is methanol, the amount of the alcohol solvent to be used is preferably 1 to 50 mol based on 1 mol of sodium borohydride. When the alcohol solvent is an alcohol having 2 or more carbon atoms, it is preferably 0.1 to 100 parts by weight, more preferably 0.2 to 10 parts by weight based on 1 part by weight of halogen-substituted phthalic anhydride.

In the step (A), the reaction is carried out in the presence of a solvent which is inert to the reaction of the halogen-substituted phthalic anhydride and sodium borohydride as a solvent other than the ether solvent and the alcohol solvent (hereinafter may be referred to as an inert solvent) .

Examples of the inert solvent include aromatic hydrocarbon solvents, halogenated aromatic hydrocarbon solvents and aliphatic hydrocarbon solvents. Examples of the aromatic hydrocarbon solvent include toluene and xylene. Examples of the halogenated aromatic hydrocarbon solvent include chlorobenzene and dichlorobenzene. Examples of the aliphatic hydrocarbon solvent include pentane, hexane, heptane, octane, and cyclohexane. . The inert solvent is preferably an aromatic hydrocarbon solvent, more preferably an aromatic hydrocarbon solvent having 6 to 10 carbon atoms, and more preferably toluene.

As the inert solvent, commercially available ones can be used as they are, or they can be purified by means of purification means such as distillation.

The amount of the inert solvent to be used is preferably 0.05 to 10 parts by weight, more preferably 0.1 to 2 parts by weight based on 1 part by weight of at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent, Is 0.1 to 0.5 parts by weight.

Step (A) is carried out by mixing at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent, and halogen-substituted phthalic anhydride and sodium borohydride. As a mixing method, a method of mixing at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent and sodium borohydride, mixing the resultant mixture with a halogen-substituted anhydrous phthalic acid, an ether solvent and an alcohol solvent And a halogen-substituted phthalic anhydride are mixed, and sodium borohydride is mixed with the resultant mixture. It is preferable to mix at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent and halogen-substituted anhydrous phthalic acid, and to mix the resultant mixture with sodium borohydride. At least one solvent selected from the group consisting of sodium borohydride, an ether solvent and an alcohol solvent may be added in divided portions. When sodium borohydride is used in the preparation, it is also possible to prepare sodium borohydride in the resulting mixture by mixing at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent and halogen-substituted phthalic anhydride.

The reaction temperature of halogen-substituted phthalic anhydride and sodium borohydride is usually -20 to 200 占 폚, preferably -10 to 100 占 폚, and more preferably -5 to 80 占 폚.

The step (A) is carried out under atmospheric pressure, under reduced pressure or under pressure, and preferably under atmospheric pressure. The progress of the reaction can be confirmed by an analytical means such as gas chromatography or liquid chromatography.

≪ Process (B) >

The substitution is carried out by distilling off a solvent containing at least one selected from the group consisting of an ether solvent and an alcohol solvent from the reaction mixture obtained in the step (A) (hereinafter sometimes referred to as the mixture (A)), It is preferably carried out by adding a hydrocarbon solvent.

The solvent contained in the mixture obtained in the step (B) (hereinafter sometimes referred to as the mixture (B)) contains an aromatic hydrocarbon solvent. The solvent contained in the mixture (B) may contain at least one solvent or an inert solvent selected from the group consisting of an ether solvent and an alcohol solvent.

The content of at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent relative to the solvent contained in the mixture (B) is usually less than 10% by weight, preferably less than 5% by weight.

The content of the aromatic hydrocarbon solvent relative to the solvent contained in the mixture (B) is usually 90% by weight or more, and preferably 95% by weight or more.

When the mixture (A) contains an ether solvent, the content of the ether solvent with respect to the solvent contained in the mixture (B) is preferably 3% by weight or less.

When the alcohol (A) contains an alcohol solvent, the content of the alcohol solvent in the solvent contained in the mixture (B) is preferably 2% by weight or less.

Examples of the aromatic hydrocarbon solvent include toluene and xylene, preferably toluene.

The solvent removed by distillation is preferably recycled and used as at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent in the step (A). It is more preferable to perform refining operation such as rectification before reuse.

The addition of water to the reaction system may be performed before the step (A), during the step (A), or between the step (A) and the step (B). It is preferable to add water between the step (A) and the step (B).

In addition, when water is already contained in the solvent in the step (A), the reaction may be carried out without adding water.

The amount of water added to the reaction system is preferably 0.05 to 3 moles relative to 1 mole of sodium borohydride.

When water is added to the reaction system before the step (A), the amount of water to be added is usually 0.05 to 1 mole, preferably 0.05 to 0.5 mole, more preferably 0.1 to 0.3 mole per mole of sodium borohydride to be.

When water is added to the reaction system in the step (A), the amount of water to be added is usually 0.05 to 1 mole, preferably 0.05 to 0.5 mole, more preferably 0.1 to 0.3 mole based on 1 mole of sodium borohydride .

When water is added to the reaction system between the steps (A) and (B), the amount of water to be added is usually 0.05 to 3 mol, preferably 0.1 to 1 mol, per mol of sodium borohydride, Is 0.2 to 0.6 mol.

Water may be added together with the aforementioned inert solvent.

The temperature of the reaction mixture at the time of adding water is usually -20 to 200 占 폚, preferably -20 to 80 占 폚, and more preferably -10 to 40 占 폚.

The production method of the present invention preferably includes steps (A), (B) and (C).

≪ Process (C) >

Examples of the acid include inorganic acids such as hydrogen chloride, hydrogen sulfide, and boric acid; Aliphatic carboxylic acids such as formic acid, acetic acid, trifluoroacetic acid, propionic acid, butanoic acid and oxalic acid; Aromatic carboxylic acids such as benzoic acid; Aliphatic sulfonic acids such as methanesulfonic acid, ethanesulfonic acid, and trifluoromethanesulfonic acid; And aromatic sulfonic acids such as benzenesulfonic acid and p-toluenesulfonic acid. The acid is preferably an inorganic acid, more preferably hydrogen sulfide.

Commercially available acids may be used, either alone or in combination with a solvent. Examples of the solvent to be mixed with the acid include water, the above-mentioned ether solvent, and the above-mentioned alcohol solvent. When an acid and a solvent are mixed, they may be used as a mixture of an acid and a solvent. The mixture may be sulfuric acid, which is a mixture of hydrogen sulfide and water. In the case of sulfuric acid, it is preferably 5 to 38% by weight of sulfuric acid, more preferably 20 to 38% by weight of sulfuric acid.

The amount of the acid to be used is usually 0.5 to 10 mol based on 1 mol of sodium borohydride.

The mixture of the mixture (B) and the acid may be carried out in the presence of a solvent. Examples of the solvent include the above-mentioned inert solvent, the above-mentioned ether solvent, and the above-mentioned alcohol solvent.

Examples of the method of mixing the mixture (B) and the acid include a method of mixing the solvent and the acid, adding the mixture (B) to the obtained acid solution, and a method of adding the acid to the mixture (B). The mixture (B) and the acid may be added in portions.

The mixing temperature of the mixture obtained in the step (B) and the acid is usually 10 to 70 ° C.

<Extraction Process>

The production method of the present invention preferably includes the steps (A), (B) and the extraction step, and more preferably includes the steps (A), (B), and (C) and the extraction step.

The extraction step is a step of extracting the halogen-substituted phthalide from the mixture (B) or the mixture obtained in the step (C).

The halogen-substituted phthalide may be extracted from the mixture obtained in the step (B) or the step (C), for example, by subjecting the mixture obtained in the step (B) or step (C) have. If necessary, neutralization, concentration, cooling, and the like may be performed before the solid-liquid separation. It is preferable to dry the halogen-substituted phthalide taken out.

<Purification step>

It is preferable to further purify the halogen-substituted phthalide obtained in the extraction step. The purification method includes, for example, washing, column chromatography, crystallization and the like. Examples of the crystallization method include a method of dissolving a halogen-substituted phthalide in a solvent to prepare a solution and cooling the resulting solution, a method of concentrating the solution, and a method of adding a poor solvent to the solution . It is preferable to add a poor solvent to the solution.

As halogen substituted phthalides there may be mentioned 4-fluorophthalide, 5-fluorophthalide, 6-fluorophthalide, 7-fluorophthalide, 4- chlorophthalide, 5- Bromophthalide, 4-bromophthalide, 5-bromophthalide, 6-bromophthalide, 7-bromophthalide, 4,5-difluorophthalide, 4,6-difluorophthalide, 4,7-difluorophthalide, 5,6-difluorophthalide, 4,5-dichlorophthalide, 4,6-dichlorophthalide, 4,7- Dibromophthalide, 5,6-dichlorophthalide, 4,5-dibromophthalide, 4,6-dibromophthalide, 4,7-dibromophthalide, 5,6-dibromophthal Chloro-5-fluorophthalide, 4-chloro-6-fluorophthalide, 4-chloro-5- 5-fluorophthalide, 4-bromo-6-fluorophthalide, 4-bromo-7-fluorophthalide, Trifluorophthalide, 4,5,6-trichlorophthalide, 4,5,6-trichlorophthalide, 4,5,6-trichlorophthalide, 4,5,6-trichlorophthalide, 4,5,6- Tribromophthalide, 4,5,6-tribromophthalide, 4,5,7-tribromophthalide, 4,5-dichloro-6-fluorophthalide, 4,5- Dichloro-7-fluorophthalide, 5,6-dichloro-4-fluorophthalide, 4,5,6,7-tetrafluorophthalide, 4,5,6,7-tetrachlorophthalide, 4,5,6,7-tetrabromophthalide, 4,7-dichloro-5,6-difluorophthalide, 5,6-dichloro-4,7-difluorophthalide, 7-fluoro 4,5,6-trichlorophthalide, and 7-chloro-4,5,6-trifluorophthalide.

According to the present invention, halogen-substituted phthalides can be produced at a good yield while recovering at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent.

Example

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.

(Example 1)

60.1 g of tetrachlorophthalic anhydride, 150.2 g of 1,2-dimethoxyethane, 90.1 g of toluene and 18.8 g of 2-propanol were introduced into a separable flask at room temperature, and the resulting mixture was cooled to -5 DEG C with stirring. 7.9 g of sodium borohydride was added to the mixture in portions over about 1 hour, and the mixture was stirred at -5 캜 for 3 hours.

To the obtained mixture, 480.2 g of toluene and 1.1 g of water were added. As a result, the mixture was changed from yellow to yellowish white slurry with light foaming. The obtained slurry was stirred at 60 캜 for 24 hours to check the stability, and as a result, the content was not lowered.

Thereafter, 657.9 g of the solvent was distilled off under reduced pressure at 30 to 40 ° C. The composition of the distillation-removed solvent was 77.3% by weight of toluene, 21.9% by weight of 1,2-dimethoxyethane, 1.5% by weight of 2-propanol and 472 ppm by weight of water. The concentrated residue was improved in the lump shape to such an extent that the slurry became a low-viscosity slurry in the high-viscosity slurry and a slight degree of scaling occurred. The pumping property was good. 291.9 g of toluene was added to the obtained residue to obtain a mixture in which the solvent was substituted.

The obtained mixture was dropped into a separable flask charged with 120.2 g of toluene and 151.5 g of 20.6% by weight sulfuric acid at 40 DEG C over 30 minutes, and light foaming was observed. The resulting mixture was heated to 80 DEG C, and after standing still, the organic layer was washed with water and the liquid separation operation was carried out again.

To the obtained organic layer, 327.6 g of a solvent under atmospheric pressure was distilled off, 30.2 g of toluene was added, and 240.2 g of a 50% by weight 2-propanol toluene solution was added dropwise. Thereafter, the mixture was cooled to 70 deg. C for 2 hours and cooled to -5 deg. C over 3 hours to precipitate white crystals, and filtration was carried out. The filtered crystals were washed with 60.2 g of a 50% by weight 2-propanol-toluene solution and, after drying, 45.7 g of 4,5,6,7-tetrachlorophthalide was obtained as white crystals. The yield was determined by gas chromatography internal standard method.

Yield: 80.3% (based on tetrachlorophthalic anhydride)

(Example 2)

In a separable flask, 60.1 g of tetrachlorophthalic anhydride, 212.3 g of 1,2-dimethoxyethane, 28.1 g of toluene and 18.8 g of 2-propanol were introduced at room temperature, and the resulting mixture was cooled to -5 ° C with stirring. 8.0 g of sodium borohydride was added to the mixture in portions over about 1 hour, and the mixture was stirred at -5 캜 for 3 hours.

To the obtained mixture, 480.2 g of toluene and 1.9 g of water were added. As a result, the mixture was changed from yellow to yellowish white slurry with light foaming. The resulting slurry was stirred at 40 占 폚 for 138 hours to confirm the stability, and as a result, the content was not lowered.

608.6 g of the solvent was distilled off under reduced pressure at 30 to 40 ° C. The composition of the solvent from which the distillation was removed was 66.7% by weight of toluene, 31.7% by weight of 1,2-dimethoxyethane, 1.4% by weight of 2-propanol and 217 ppm by weight of water. The concentrated residue was improved in the lump shape to such an extent that the slurry became a low-viscosity slurry in the high-viscosity slurry and a slight degree of scaling occurred. The pumping property was good. 266.6 g of toluene was added to the obtained residue to obtain a mixture in which the solvent was substituted.

The obtained mixture was dropped into a separable flask charged with 124.9 g of toluene and 151.6 g of 20.6% by weight sulfuric acid at 40 DEG C over 30 minutes, and light foaming was observed. The temperature of the resulting mixture was raised to 80 DEG C, and the organic layer was washed with water after the liquid separation.

To the obtained organic layer, 309.6 g of a solvent under atmospheric pressure was distilled off, 27.6 g of toluene was added, and 240.0 g of a 50% by weight 2-propanol 2-propanol toluene solution was added dropwise. Thereafter, the mixture was cooled to 70 deg. C for 2 hours and cooled to 0 deg. C over 14 hours to precipitate white crystals and carry out filtration. The filtered crystals were washed with 120.2 g of a 50 wt% 2-propanol-toluene solution and dried to obtain 43.9 g of 4,5,6,7-tetrachlorophthalide as white crystals. The yield was determined by gas chromatography internal standard method.

Yield: 78.1% (based on tetrachlorophthalic anhydride)

(Example 3)

60.2 g of tetrachlorophthalic anhydride, 212.3 g of 1,2-dimethoxyethane, 28.0 g of toluene and 18.9 g of 2-propanol were introduced into a separable flask at room temperature, and the resulting mixture was cooled to -5 DEG C with stirring. 8.1 g of sodium borohydride was added portionwise thereto over a period of about 1 hour, and the mixture was stirred at -5 캜 for 3 hours.

To the obtained mixture, 480.2 g of toluene and 3.9 g of water were added. As a result, the mixture was changed from yellow to yellowish white slurry with light foaming. The obtained slurry was stirred at 40 DEG C for 67 hours to confirm the stability, and as a result, the content was not lowered.

611.5 g of the solvent was distilled off under reduced pressure at 30 to 40 ° C. The composition of the distillation-removed solvent was 64.8% by weight of toluene, 33.0% by weight of 1,2-dimethoxyethane, 2.1% by weight of 2-propanol and 706 ppm by weight of water. The concentrated residue was improved in bulkiness to such an extent that the slurry became a low-viscosity slurry in the high-viscosity slurry and a slight degree of scaling occurred. The pumping property was good. 220.9 g of toluene was added to the obtained residue to obtain a solvent-substituted mixture.

The resultant mixture was dropped into a separable flask charged with 122.0 g of toluene and 152.0 g of 20.6 wt% sulfuric acid at 40 DEG C over 30 minutes, and light foaming was observed. The temperature of the resulting mixture was raised to 80 DEG C, and the organic layer was washed with water after the liquid separation.

342.0 g of a solvent under atmospheric pressure was distilled off from the obtained organic layer, and 27.7 g of toluene and 240.5 g of a 50% by weight 2-propanol-toluene solution were added dropwise. Thereafter, the mixture was cooled to 70 deg. C for 2 hours and cooled to 0 deg. C over 14 hours to precipitate white crystals and carry out filtration. The filtered crystals were washed with 120.4 g of a 50% by weight 2-propanol toluene solution and, after drying, 45.3 g of 4,5,6,7-tetrachlorophthalide was obtained as white crystals. The yield was determined by gas chromatography internal standard method.

Yield: 80.3% (based on tetrachlorophthalic anhydride)

(Example 4)

60.1 g of tetrachlorophthalic anhydride, 212.5 g of 1,2-dimethoxyethane, 28.0 g of toluene and 15.0 g of 2-propanol were charged into the separable flask at room temperature, and the resulting mixture was cooled to -5 DEG C with stirring. 6.3 g of sodium borohydride was added to the mixture in portions over 10 hours, and the mixture was stirred at -5 DEG C for 3 hours.

To the obtained mixture, 480.9 g of toluene and 1.2 g of water were added. As a result, the mixture was changed from yellow to yellowish white slurry with light foaming.

600.5 g of the solvent was distilled off under reduced pressure at 30 to 40 ° C. The composition of the solvent from which the distillation was removed was 66.2% by weight of toluene, 32.5% by weight of 1,2-dimethoxyethane and 1.3% by weight of 2-propanol. The concentrated residue was improved in bulkiness to such an extent that the slurry became a low-viscosity slurry in the high-viscosity slurry and a slight degree of scaling occurred. The pumping property was good. 422.8 g of toluene was added to the obtained residue to obtain a mixture in which the solvent was substituted.

The resulting mixture was dropped into a separable flask charged with 151.8 g of 20.6 wt% sulfuric acid at 40 DEG C over 30 minutes, resulting in mild foaming. The temperature of the resulting mixture was raised to 80 DEG C, and the organic layer was washed with water after the liquid separation.

389.6 g of a solvent under atmospheric pressure was distilled off from the obtained organic layer, and 33.4 g of toluene and 266.7 g of a 45% by weight 2-propanol toluene solution were added dropwise. Thereafter, the mixture was cooled to 0 deg. C over 14 hours to precipitate white crystals, and filtration was carried out. The filtered crystals were washed with 60.6 g of a 45% by weight 2-propanol-toluene solution and, after drying, 46.1 g of 4,5,6,7-tetrachlorophthalide was obtained as white crystals. The yield was determined by gas chromatography internal standard method.

Yield: 81.1% (based on tetrachlorophthalic anhydride)

(Example 5)

60.0 g of tetrachlorophthalic anhydride, 212.4 g of 1,2-dimethoxyethane, 28.1 g of toluene, 15.0 g of 2-propanol and 1.3 g of water were charged into a separable flask at room temperature, and the resulting mixture was cooled . 6.3 g of sodium borohydride was added portionwise to the mixture over 5 hours, and the mixture was stirred at -5 캜 overnight.

480.5 g of toluene and 1.2 g of water were added to the obtained mixture, and 597.0 g of a solvent was distilled off under reduced pressure at 30 to 40 ° C. As a result, the solvent composition of the distillate was 64.6% by weight of toluene, 32.8% by weight of 1,2-dimethoxyethane %, And 1.9 wt% of 2-propanol. The concentrated residue was improved in bulkiness to such an extent that the slurry became a low-viscosity slurry in the high-viscosity slurry and a slight degree of scaling occurred. The pumping property was good. 403.8 g of toluene was added to the obtained residue to obtain a reaction mixture in which the solvent was substituted.

The obtained mixture was dropped into a separable flask charged with 151.4 g of 20.6 wt% sulfuric acid at 40 DEG C over 30 minutes, resulting in mild foaming. The temperature of the resulting mixture was raised to 80 DEG C, and the organic layer was washed with 120.2 g of water and the liquid separation operation was carried out again.

To the obtained organic layer, 358.1 g of a solvent under atmospheric pressure was distilled off, 13.4 g of toluene was added, and 266.8 g of a 45% by weight 2-propanol-toluene solution was added dropwise. Thereafter, the mixture was cooled to 0 deg. C over 14 hours to precipitate white crystals, and filtration was carried out. The filtered crystals were washed with 60.3 g of a 45 wt% 2-propanol-toluene solution and dried to obtain 42.6 g of 4,5,6,7-tetrachlorophthalide as white crystals. The content of 4,5,6,7-tetrachlorophthalide in crystals, filtrate and wash liquor was determined by gas chromatography internal standard method, and the yield was determined.

Yield: 75.1% (based on tetrachlorophthalic anhydride)

(Example 6)

60.2 g of tetrachlorophthalic anhydride, 212.4 g of 1,2-dimethoxyethane, 28.1 g of toluene, 15.2 g of 2-propanol and 0.8 g of water were charged into a separable flask at room temperature, and the resulting mixture was cooled . 6.3 g of sodium borohydride was added portionwise to the mixture over 5 hours, and the mixture was stirred at -5 캜 overnight.

To the resulting mixture was added 480.3 g of toluene and 653.3 g of a solvent was distilled off under reduced pressure at 30 to 40 ° C. As a result, the solvent composition of the distillate was 67.5% by weight of toluene, 31.0% by weight of 1,2-dimethoxyethane, And 1.5% by weight of propanol. The concentrated residue was improved in bulkiness to such an extent that the slurry became a low-viscosity slurry in the high-viscosity slurry and a slight degree of scaling occurred. The pumping property was good. To the obtained residue was added 502.7 g of toluene to obtain a mixture in which the solvent was substituted.

The resultant mixture was dropped into a separable flask charged with 151.3 g of sulfuric acid having a concentration of 20.6 wt% at 40 DEG C over 30 minutes, resulting in mild foaming. The temperature of the resulting mixture was raised to 80 DEG C, and the organic layer was washed with 120.3 g of water and the liquid separation operation was carried out again.

395.4 g of a solvent under atmospheric pressure was distilled off from the obtained organic layer, and 2.3 g of toluene and 267.0 g of a 45% by weight 2-propanol toluene solution were added dropwise. Thereafter, the mixture was cooled to 0 deg. C over 14 hours to precipitate white crystals, and filtration was carried out. The filtered crystals were washed with 60.2 g of a 45 wt% 2-propanol-toluene solution and, after drying, 45.2 g of 4,5,6,7-tetrachlorophthalide was obtained as white crystals. The content of 4,5,6,7-tetrachlorophthalide in crystals, filtrate and wash liquor was determined by gas chromatography internal standard method, and the yield was determined.

Yield: 79.2% (based on tetrachlorophthalic anhydride)

(Reference Example 1)

In a separable flask, 60.1 g of tetrachlorophthalic anhydride, 212.3 g of 1,2-dimethoxyethane, 28.0 g of toluene and 18.8 g of 2-propanol were charged at room temperature, and the resulting mixture was cooled to -5 캜 with stirring. 8.0 g of sodium borohydride was added to the mixture in portions over about 1 hour, and the mixture was stirred at -5 캜 for 3 hours.

To the resulting mixture, 480.6 g of toluene was added, and the mixture was stirred at 40 DEG C for 21 hours to check the stability. As a result, the content was confirmed to be decreased (retention rate: about 95% by weight). 568.1 g of the solvent was distilled off under reduced pressure at 30 to 40 ° C. The composition of the solvent from which the distillation was removed was 65.1% by weight of toluene, 30.8% by weight of 1,2-dimethoxyethane and 0.6% by weight of 2-propanol. The concentrated residue becomes a high viscosity slurry, and it is difficult to transfer the entire amount due to a large amount of scaling. Further, even when 227.3 g of toluene was added to this concentrated residue, no significant improvement was observed. Toluene was added to the obtained residue to obtain a mixture in which the solvent was substituted.

120.2 g of toluene and 151.3 g of 20.6% by weight sulfuric acid were added dropwise to the separable flask at 40 占 폚 over 30 minutes, resulting in mild foaming. The temperature of the resulting mixture was raised to 80 DEG C, and the organic layer was washed with 120.0 g of water and the liquid separation operation was carried out again.

To the obtained organic layer, 335.6 g of a solvent under atmospheric pressure was distilled off, and 27.1 g of toluene was added and 240.2 g of a 50 wt% 2-propanol-toluene solution was added dropwise. Thereafter, the mixture was cooled to 70 deg. C for 2 hours and cooled to 0 deg. C over 14 hours to precipitate white crystals and carry out filtration. The filtered crystals were washed with 120.2 g of a 50% by weight 2-propanol-toluene solution and, after drying, 37.2 g of 4,5,6,7-tetrachlorophthalide was obtained as white crystals. The content of 4,5,6,7-tetrachlorophthalide in crystals, filtrate and wash liquor was determined by gas chromatography internal standard method, and the yield was determined.

Yield: 65.6% (based on tetrachlorophthalic anhydride)

According to the present invention, a halogen-substituted phthalide can be produced at a good yield while recovering at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent.

Claims (7)

A process for producing a halogen-substituted phthalide comprising the steps (A) and (B).
Step (A): A step of reacting halogen-substituted phthalic anhydride with sodium borohydride in at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent in the presence of water.
Step (B): A step of replacing part or all of at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent contained in the reaction mixture obtained in the step (A) with an aromatic hydrocarbon solvent. The method according to claim 1,
Wherein the water is added to the reaction system before the step (B). A process for producing a halogen-substituted phthalide comprising the steps (A) and (B).
Step (A): a step of reacting a halogen-substituted phthalic acid anhydride with sodium borohydride in the presence of at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent.
Step (B): Water is added to the reaction mixture obtained in the step (A), and part or all of at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent contained in the reaction mixture is reacted with an aromatic hydrocarbon solvent The process of substitution. The method according to claim 2 or 3,
And further comprising the following step (C).
Step (C): a step of mixing the mixture obtained in the step (B) with an acid. The method according to claim 2 or 3,
Wherein the amount of water is 0.05 to 3 moles relative to 1 mole of sodium borohydride. The method according to claim 2 or 3,
Wherein the halogen-substituted phthalide is tetrahalogen-substituted phthalic anhydride. The method according to claim 2 or 3,
Wherein the halogen-substituted phthalide is tetrachlorophthalic anhydride.