TWI648268B - Method for producing halogen substituted phthalide - Google Patents

Abstract

The method for producing a halogen-substituted azlactone of the present invention comprises the following steps (A) and (B).

Step (A): a step of reacting a 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 substituting a 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 azlactone

The present invention relates to a process for producing a halogen-substituted azlactone.

A halogen-substituted azlactone can be used as a raw material, an intermediate, and a drug substance of a pharmaceutical pesticide. In Patent Document 1, it is described that tetrachlorophthalic anhydride and sodium borohydride are reacted in the presence of 2-propanol, tetrahydrofuran or 1,2-dimethoxyethane, and the obtained crystal is separated by filtration. And a method for producing 4,5,6,7-tetrachlorodecalactone.

[Previous Technical Literature] Patent literature

[Patent Document 1] Japanese Patent Laid-Open Publication No. 2011-26295

At present, a method of producing a halogen-substituted azlactone in a high yield while recovering a solvent used is desired.

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

[1] A method for producing a halogen-substituted azlactone, which comprises the following steps (A) and (B); and step (A): in at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent. And a step of reacting a halogen-substituted phthalic anhydride with sodium borohydride in the presence of water, and step (B): at least a group selected from the group consisting of an ether solvent and an alcohol solvent contained in the reaction mixture obtained in the step (A) A step in which a part or all of a solvent is substituted with an aromatic hydrocarbon solvent.

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

[3] A method for producing a halogen-substituted azlactone, which comprises the following steps (A) and (B);

Step (A): a step of reacting a halogen-substituted phthalic 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): adding water to the reaction mixture obtained in the step (A), and 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, A step of an aromatic hydrocarbon solvent.

[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 mol with respect to 1 mol of sodium borohydride.

[6] The production method according to [1] to [5], wherein the halogen-substituted phthalic anhydride is a tetrahalogen-substituted phthalic anhydride.

[7] The production method according to [1] to [6] wherein the halogen-substituted phthalic anhydride is tetrachlorophthalic anhydride.

Embodiment of the invention

<Step (A)>

The halogen-substituted phthalic anhydride is at least one of four hydrogen atoms contained in the phthalic anhydride, and isocyanic acid anhydride substituted with a halogen atom such as a fluorine atom, a chlorine atom or a bromine atom. The halogen-substituted phthalic anhydride is, for example, a monohalogen-substituted phthalic anhydride, a dihalogen-substituted phthalic anhydride, a trihalogen-substituted phthalic anhydride, and a tetrahalogen-substituted phthalic anhydride.

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

The monohalogen-substituted phthalic anhydride is, for example, 3-fluorodecanoic anhydride, 4-fluorodecanoic anhydride, 3-chlorophthalic anhydride, 4-chlorophthalic anhydride, 3-bromophthalic anhydride, and 4-bromophthalic anhydride.

The dihalogen-substituted phthalic anhydride is an phthalic anhydride in which two of the four hydrogen atoms contained in the phthalic anhydride are replaced by a halogen atom.

The dihalogen substituted phthalic anhydride is, for example, 3,4-difluorophthalic anhydride, 3,5-difluorophthalic anhydride, 3,6-difluorophthalic anhydride, 4,5-difluorophthalic anhydride, 3,4-dichloro Anthracene anhydride, 3,5-dichlorophthalic anhydride, 3,6-dichlorophthalic anhydride, 4,5-dichlorophthalic anhydride, 3,4-dibromophthalic anhydride, 3,5-dibromophthalic anhydride, 3, 6-dibromophthalic anhydride, 4,5- Dibromophthalic anhydride, 3-chloro-4-fluorophthalic anhydride, 3-chloro-5-fluorophthalic anhydride, 3-chloro-6-fluorophthalic anhydride, 4-chloro-5-fluorophthalic anhydride, 3-bromo-4 - fluorophthalic anhydride, 3-bromo-5-fluorophthalic anhydride, 3-bromo-6-fluorophthalic anhydride and 4-bromo-5-fluorophthalic anhydride.

The trihalogen-substituted phthalic anhydride is an phthalic anhydride substituted with a halogen atom by three of the four hydrogen atoms contained in the phthalic anhydride.

The trihalogen substituted phthalic anhydride is, for example, 3,4,5-trifluorophthalic anhydride, 3,4,6-trifluorophthalic anhydride, 3,4,5-trichlorophthalic anhydride, 3,4,6-trichloroanthracene. Anhydride, 3,4,5-tribromophthalic anhydride, 3,4,6-tribromophthalic anhydride, 3,4-dichloro-5-fluorophthalic anhydride, 3,4-dichloro-6-fluoroanhydride 4,5-Dichloro-3-fluorophthalic anhydride.

The tetrahalogen-substituted phthalic anhydride is an phthalic anhydride in which all of the four hydrogen atoms contained in the phthalic anhydride are replaced by a halogen atom.

The tetrahalogen substituted phthalic anhydride is, for example, tetrafluorophthalic anhydride, tetrachlorophthalic anhydride, tetrabromophthalic anhydride, 3,6-dichloro-4,5-difluorophthalic anhydride, 4,5-dichloro-3,6- Difluorophthalic anhydride, 6-fluoro-3,4,5-trichlorophthalic 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 contain a substituent which is inert in the reaction of the halogen-substituted phthalic anhydride with sodium borohydride.

The substituent which is inert in the reaction of the halogen-substituted phthalic anhydride with sodium borohydride may, for example, be an alkyl group having 1 to 12 carbon atoms such as a methyl group, an ethyl group or a propyl group.

The halogen-substituted phthalic anhydride is preferably a tetrahalogen-substituted phthalic anhydride, and tetrachloro phthalic anhydride is more preferable.

For the halogen-substituted phthalic anhydride, a method of halogenating phthalic anhydride (refer to Japanese Laid-Open Patent Publication No. Hei 6-329653), a method of dehydrating by reacting a halogen-substituted phthalic anhydride with sulfinium chloride or the like (refer to Japanese Patent Laid-Open) It is manufactured by the publication No. 6-16656.

Sodium borohydride may be commercially available or may be prepared by a generally known method such as a reaction of a boric acid ester with sodium hydride.

The amount of sodium borohydride used is preferably 1 mol or more, more preferably 0.5 to 3 mol, more preferably 0.7 to 1.5 mol, especially 0.8 to 1 mol, relative to the halogen-substituted phthalic anhydride 1 mol. Better yet.

The ether solvent is, for example, 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.

The ether solvent can be used as it is, or it can be used as a commercially available product, and it can also be used after purification, such as distillation.

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

The alcohol solvent is a compound containing at least one hydroxyl group, and specifically, for example, methanol and an alcohol having 2 or more carbon atoms.

The alcohol having 2 or more carbon atoms is, for example, an alcohol having 2 to 12 carbon atoms, an alcohol having 3 to 12 carbon atoms, and an alcohol having 3 to 12 carbon atoms.

The alcohol having 2 to 12 carbon atoms is, for example, ethanol, 1-propanol, 1-butanol, 2-methyl-1-propanol, 1-pentanol, 2,2-dimethyl-1-propanol Alcohol, benzyl alcohol, ethylene glycol, ethylene glycol monomethyl ether and ethylene glycol monoethyl ether.

The alcohol having a carbon number of 3 to 12 is, for example, 2-propanol, 2-butanol, 2-pentanol, 3-pentanol, cyclopentanol, and cyclohexanol.

The alcohol having a carbon number of 3 to 12 is, for example, 2-methyl-2-propanol, 2-methyl-2-butanol, and 3-ethyl-3-pentanol.

The alcohol solvent is preferably methanol, a carbon number of 2 to 12, or a carbon number of 3 to 12, and a methanol, a carbon number of 2 to 6 or a carbon number of 3 to 6 Preferably, methanol or 2-propanol is more preferred, and 2-propanol is more preferred.

The alcohol solvent can be used as it is in a commercially available product, and can also be used after purification by distillation or the like.

The amount of the alcohol solvent used is preferably from 1 to 50 moles per mole of sodium borohydride in the case where the alcohol solvent is methanol. 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, per part by weight of the halogen-substituted phthalic anhydride.

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

The inert solvent is, for example, an aromatic hydrocarbon solvent, a halogenated aromatic hydrocarbon solvent, and an aliphatic hydrocarbon solvent. The aromatic hydrocarbon solvent is, for example, toluene and xylene; the halogenated aromatic hydrocarbon solvent is, for example, chlorinated benzene and dichlorobenzene; and the aliphatic hydrocarbon solvent is, for example, pentane, hexane, heptane, octane, and cyclohexane. alkyl. 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.

The inert solvent may be used as it is, or may be used as a commercially available product, or may be purified by distillation or the like.

The amount of the inert solvent to be used is preferably 0.05 to 10 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. More preferably, it is 0.1 to 2 parts by weight, and more preferably 0.1 to 0.5 part by weight.

In the step (A), at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent may be mixed with a halogen-substituted phthalic anhydride and sodium borohydride. An example of the mixing method is a method in which at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent is mixed with sodium borohydride, and the resulting mixture is mixed with a halogen-substituted phthalic anhydride; At least one solvent selected from the group consisting of a solvent and an alcohol solvent is mixed with a halogen-substituted phthalic anhydride, and the resulting mixture is mixed with sodium borohydride. Further, a method in which at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent is mixed with a halogen-substituted phthalic anhydride, and the resulting mixture is mixed with sodium borohydride is preferred. Sodium borohydride and at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent may also be separately added. In the case of modulating sodium borohydride, at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent may be mixed with a halogen-substituted phthalic anhydride, and sodium borohydride may be prepared in the resulting mixture.

The temperature at which the halogen-substituted phthalic anhydride is reacted with sodium borohydride is usually -20 to 200 ° C, more preferably -10 to 100 ° C, still more preferably -5 to 80 ° C.

The step (A) can be carried out under normal pressure, under reduced pressure or under pressure, and is preferably carried out under normal pressure. The degree of the reaction can be determined by analytical procedures such as gas chromatography and liquid chromatography.

<Step (B)>

The substituent is obtained by distilling off at least one solvent 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)), and adding an aromatic hydrocarbon solvent. It is better to carry out.

The mixture obtained in the step (B) (hereinafter, sometimes referred to as a mixture (B)) The solvent contained in the solvent 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 is usually less than 10% by weight, preferably less than 5% by weight, based on the solvent contained in the mixture (B).

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

When the ether solvent is contained in the mixture (A), the content of the ether solvent is preferably 3% by weight or less based on the solvent contained in the mixture (B).

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

The aromatic hydrocarbon solvent is, for example, toluene and xylene, and toluene is preferred.

The solvent to be distilled off is preferably used in the step (A) as at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent. It is preferred to carry out a refining operation such as rectification before reuse.

The addition of water to the reaction system can be carried out before step (A), or in step (A), or between step (A) and step (B). It is preferred to add water between step (A) and step (B).

Further, 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 per mole of sodium borohydride.

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

When water is added to the reaction system in the step (A), the amount of water added is usually 0.05 to 1 mol with respect to sodium borohydride, preferably 0.05 to 0.5 mol, and more preferably 0.1 to 0.3 mol. .

When water is added to the reaction system between the step (A) and the step (B), the amount of water added is usually 0.05 to 3 moles relative to sodium borohydride, preferably 0.1 to 1 mole, 0.2. It is better to 0.6 moles.

Water may also be added simultaneously with the above inert solvent.

The temperature of the reaction mixture when water is added is usually -20 to 200 ° C, preferably -20 to 80 ° C, more preferably -10 to 40 ° C.

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

<Step (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, butyric acid, and oxalic acid; aromatic carboxylic acids such as benzoic acid; methanesulfonic acid and ethane; An aliphatic sulfonic acid such as sulfonic acid or trifluoromethanesulfonic acid; and an aromatic sulfonic acid such as benzenesulfonic acid or p-toluenesulfonic acid The acid is preferably an inorganic acid, and the hydrogen sulfide is more preferred.

The acid can be used as a commercially available product, and it can be used singly or in combination with a solvent. The solvent which can be mixed with an acid may, for example, be water, the above ether solvent, or the above alcohol solvent. When the acid is mixed with a solvent, a mixture of an acid and a solvent may be used, and the mixture may be sulfuric acid such as a mixture of hydrogen sulfide and water. In the case of sulfuric acid, preferably 5 to 38% by weight of sulfuric acid, 20 to 38 weight The amount of sulfuric acid is better.

The amount of acid used is usually from 0.5 to 10 moles relative to 1 mole of sodium borohydride.

Mixing of the mixture (B) with an acid can also be carried out in the presence of a solvent. Examples of the solvent include the above-mentioned inert solvent, the above ether solvent, and the above alcohol solvent.

The method of mixing the mixture (B) with an acid may, for example, be a method in which a solvent is mixed with an acid, a method in which the mixture (B) is added to the obtained acid solution, and a method in which an acid is added to the mixture (B). The mixture (B) and the acid can be added separately.

The temperature at which the mixture obtained in the step (B) is mixed with an acid is usually from 10 to 70 °C.

<Separation step>

The production method of the present invention preferably comprises the steps (A), (B) and the separation step, and the step (A), (B), (C) and the separation step are more preferred.

The separation step is a step of separating the halogen-substituted azlactone from the mixture obtained in the mixture (B) or the step (C).

A method for separating a halogen-substituted azlactone from a mixture obtained in the mixture (B) or the step (C), which may be a mixture of the mixture obtained by filtering the mixture (B) or the step (C), and then separating the solid liquid by decantation or the like. Methods. It may be neutralized, concentrated, cooled, etc. before the solid liquid is separated, depending on its needs. It is preferred to dry the azlactone substituted with the separated halogen.

<Refining step>

The halogen-substituted azlactone obtained by the separation step is preferably further purified. The purification method can be mentioned as follows: cleaning, column chromatography, crystallization Wait. The method of crystallization may be a method in which a halogen-substituted azlactone is dissolved in a solvent to prepare a solution, and the obtained solution is cooled; a method of concentrating the solution; a method of adding a poor solvent to the solution; It is preferred to add a poor solvent to the solution.

Examples of the halogen-substituted azlactone include 4-fluorodecalactone, 5-fluorodecalactone, 6-fluorodecalactone, 7-fluorodecalactone, 4-chlorodecalactone, 5-chloro Azlactone, 6-chlorolactone, 7-chlorolactone, 4-bromodecanolactone, 5-bromodecanolactone, 6-bromodecanolactone, 7-bromodecanolide, 4,5- Difluorodecalactone, 4,6-difluorodecalactone, 4,7-difluorodecalactone, 5,6-difluorodecalactone, 4,5-dichlorodecanolide, 4,6- Diclosan, 4,7-dichlorodecanolide, 5,6-dichlorodecanolide, 4,5-dibromodecanolide, 4,6-dibromodecanolide, 4,7- Dibromopyrone lactone, 5,6-dibromodecanolide, 4-chloro-5-fluorodecanolactone, 4-chloro-6-fluorodecanolactone, 4-chloro-7-fluorodecanolactone, 5 -chloro-6-fluorodecanolide, 4-bromo-5-fluorodecanolactone, 4-bromo-6-fluorodecanolactone, 4-bromo-7-fluorodecanolactone, 5-bromo-6-fluoro Azlactone, 4,5,6-trifluorodecanolide, 4,5,7-trifluorodecanolactone, 4,5,6-trichlorodecanolide, 4,5,7-trichloropurine Ester, 4,5,6-tribromodecanolide, 4,5,7-tribromodecanolide, 4,5-dichloro-6-fluorodecanolactone, 4,5-dichloro-7-fluoro Azlactone, 5,6-dichloro-4-fluorodecanolactone, 4,5,6,7-tetrafluorodecalactone, 4,5,6,7-tetrachlorodecanolide, 4,5, 6,7-tetrabromodecanolactone, 4,7-Dichloro-5,6-difluorodecalactone, 5,6-dichloro-4,7-difluorodecalactone, 7-fluoro-4,5,6-trichlorodecanolide and 7-Chloro-4,5,6-trifluorodecanolactone and the like.

In the present invention, a halogen-substituted phthalic anhydride can be produced in a high 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 by way of examples, but the invention is not limited thereto.

(Example 1)

In a separable flask, 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 added at room temperature, and the resulting mixture was Cool to -5 ° C with stirring. Thereafter, 7.9 g of sodium borohydride was separately added to the mixture over about 1 hour, followed by stirring at -5 ° C for 3 hours.

After adding 480.2 g of toluene and 1.1 g of water to the obtained mixture, foaming was gradually carried out, and the slurry was converted from yellow to yellowish white. The obtained slurry was further stirred at 60 ° C for 24 hours to confirm its stability, and as a result, no reduction in content was observed.

Thereafter, 657.9 g of a solvent was distilled off under reduced pressure at 30 to 40 °C. The composition of the solvent to be distilled off was 77.3 wt% of toluene, 21.9% by weight of 1,2-dimethoxyethane, 1.5 wt% of 2-propanol, and 472 ppm by weight of water. The concentration of the concentrated residue, which is converted from a high-viscosity slurry to a low-viscosity slurry, is only slightly occurred, so that an improvement in the properties of the substance is observed. And its transportability is also good. Further, when 291.9 g of toluene was further added to the obtained residue, a solvent-substituted mixture was obtained.

Thereafter, the obtained mixture was dropped into a separable flask containing 120.2 g of toluene and 151.5 g of sulfuric acid of 20.6% by weight at 40 ° C for 30 minutes, and foaming was observed slowly. Thereafter, the obtained mixture was heated to 80 ° C, and after standing to stand for liquid separation, the organic layer was washed with water and subjected to a liquid separation operation.

Then, the obtained organic layer is sequentially subjected to distillation under normal pressure. 327.6 g, 30.2 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 ° C over 2 hours, cooled to -5 ° C over 3 hours to precipitate white crystals, and filtered. The filtered crystals were washed with 60.2 g of a 50% by weight 2-propanol-toluene solution and dried to obtain 45.7 g of white crystals of 4,5,6,7-tetrachlorodecanolide. The yield was then determined by gas chromatography using an 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 charged at room temperature, and the resulting mixture was further mixed. Cool to -5 ° C with stirring. Thereafter, 8.0 g of sodium borohydride was separately added to the mixture over about 1 hour, followed by stirring at -5 ° C for 3 hours.

After adding 480.2 g of toluene and 1.9 g of water to the obtained mixture, the slurry was gradually converted from yellow to yellowish white while gradually foaming. The obtained slurry was stirred at 40 ° C for 138 hours to confirm its stability, and as a result, no reduction in content was observed.

Thereafter, 608.6 g of a solvent was further distilled off under reduced pressure at 30 to 40 °C. The composition of the solvent to be distilled off was 66.7 wt% of toluene, 31.7% by weight of 1,2-dimethoxyethane, 1.4 wt% of 2-propanol, and 217 ppm by weight of water. The concentration of the concentrated residue, which is converted from a high-viscosity slurry to a low-viscosity slurry, is only slightly occurred, so that an improvement in the properties of the substance is observed. And its transportability is also good. When 266.6 g of toluene was further added to the obtained residue, a solvent-substituted mixture was obtained.

Thereafter, the obtained mixture was dropped into a separable flask containing 124.9 g of toluene and 151.6 g of sulfuric acid of 20.6% by weight at 40 ° C for 30 minutes, and foaming was observed slowly. Thereafter, the obtained mixture was heated to 80 ° C, and after standing to stand for liquid separation, the organic layer was washed with water and subjected to a liquid separation operation.

Then, the obtained organic layer was subjected to an operation of distilling off a solvent (309.6 g) under normal pressure, adding 27.6 g of toluene, and dropping a 50 wt% 2-propanol-toluene solution (240.0 g). Thereafter, the mixture was cooled to 70 ° C over 2 hours, cooled to 0 ° C over 14 hours to precipitate white crystals, and filtered. The filtered crystals were washed with 120.2 g of a 50% by weight 2-propanol-toluene solution and dried to obtain 43.9 g of white crystals of 4,5,6,7-tetrachlorodecanolide. The yield was then determined by gas chromatography using an internal standard method.

Yield: 78.1% (based on tetrachlorophthalic anhydride)

(Example 3)

In a separable flask, 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 added at room temperature, and the resulting mixture was further Cool to -5 ° C with stirring. Thereafter, 8.1 g of sodium borohydride was separately added to the mixture over about 1 hour, and then stirred at -5 ° C for 3 hours.

To the obtained mixture, 480.2 g of toluene and 3.9 g of water were added, and the slurry was converted from yellow to yellowish white while gradually foaming. The obtained slurry was stirred at 40 ° C for 67 hours to confirm its stability, and as a result, no reduction in content was observed.

Thereafter, 611.5 g of a solvent was distilled off under reduced pressure at 30 to 40 °C. The composition of the solvent for the distillation is 64.8 wt% of toluene and 1,2-dimethoxyethane. 33.0% by weight, 2.1% by weight of 2-propanol, and 706 ppm by weight of water. The concentration of the concentrated residue, which is converted from a high-viscosity slurry to a low-viscosity slurry, is only slightly occurred, so that an improvement in the properties of the substance is observed. And its transportability is also good. When a further 220.9 g of toluene was added to the obtained residue, a solvent-substituted mixture was obtained.

Then, the obtained mixture was dropped into a separable flask containing 122.0 g of toluene and 152.0 g of sulfuric acid of 20.6% by weight at 40 ° C for 30 minutes, and foaming was observed slowly. Thereafter, the obtained mixture was heated to 80 ° C, and after standing to stand for liquid separation, the organic layer was washed with water and subjected to a liquid separation operation.

Then, the obtained organic layer was subjected to an operation of distilling off 342.0 g of a solvent under normal pressure, adding 27.7 g of toluene, and dropping 240.5 g of a 50 wt% 2-propanol-toluene solution. Thereafter, the mixture was cooled to 70 ° C for 2 hours, cooled to 0 ° C over 14 hours to precipitate white crystals, and filtered. The filtered crystals were further washed with 120.4 g of a 50% by weight 2-propanol-toluene solution, and dried to obtain 45.3 g of 4,5,6,7-tetrachlorodecanolide as white crystals. The yield was then determined by gas chromatography using an internal standard method.

Yield: 80.3% (based on tetrachlorophthalic anhydride)

(Example 4)

In a separable flask, 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 added at room temperature, and the resulting mixture was stirred. Cool down to -5 °C. Thereafter, 6.3 g of sodium borohydride was separately added to the mixture for about 10 hours, followed by stirring at -5 ° C for 3 hours.

After adding 480.9 g of toluene and 1.2 g of water to the obtained mixture, it is gentle The slurry is converted from yellow to yellowish white while slowly foaming.

The obtained slurry was subjected to distillation of 600.5 g of a solvent under reduced pressure at 30 to 40 °C. The composition of the solvent to be distilled off was 66.2% by weight of toluene, 32.5% by weight of 1,2-dimethoxyethane, and 1.3% by weight of 2-propanol. The concentration of the concentrated residue, which is converted from a high-viscosity slurry to a low-viscosity slurry, is only slightly occurred, so that an improvement in the properties of the substance is observed. And its transportability is also good. When 422.8 g of toluene was further added to the obtained residue, a solvent-substituted mixture was obtained.

Thereafter, the obtained mixture was dropped into a separable flask containing 20.6 wt% of sulfuric acid 151.8 g at 40 ° C for 30 minutes, and foaming was observed slowly. Thereafter, the obtained mixture was heated to 80 ° C, and after standing to stand for liquid separation, the organic layer was washed with water and subjected to a liquid separation operation.

Then, the obtained organic layer was subjected to an operation of distilling off 389000 g of a solvent under normal pressure, adding 33.4 g of toluene, and dropping 266.7 g of a 45 wt% 2-propanol-toluene solution. Thereafter, it was cooled to 0 ° C over 14 hours to precipitate white crystals, which were filtered. The filtered crystals were further washed with 60.6 g of a 45 wt% 2-propanol-toluene solution, and dried to obtain 46.1 g of 4,5,6,7-tetrachlorodecalactone as a white crystal. The yield was then determined by gas chromatography using an internal standard method.

Yield: 81.1% (based on tetrachlorophthalic anhydride)

(Example 5)

In a separable flask, 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 added at room temperature. The mixture was further cooled to -5 ° C with stirring. Then, 6.3 g of sodium borohydride was added separately in the mixture for about 5 hours, and then at -5 ° C. Stir for one night.

To the obtained mixture, 480.5 g of toluene and 1.2 g of water were added, and when 597.0 g of a solvent was distilled off under reduced pressure at 30 to 40 ° C, the composition of the solvent to be distilled off was 64.6 wt% of toluene and 1,2-di. Methoxyethane was 32.8 wt% and 2-propanol was 1.9% by weight. The concentration of the concentrated residue, which is converted from a high-viscosity slurry to a low-viscosity slurry, is only slightly occurred, so that an improvement in the properties of the substance is observed. And its transportability is also good. When 403.8 g of toluene was further added to the obtained residue, a solvent-substituted mixture was obtained.

Thereafter, the obtained mixture was dropped into a separable flask containing 20.6 wt% of sulfuric acid in 151.4 g at 40 ° C for 30 minutes, and foaming was observed slowly. Thereafter, the obtained mixture was heated to 80 ° C, and after standing to stand for liquid separation, the organic layer was further washed with water 120.2 g and subjected to a liquid separation operation.

Then, the obtained organic layer was subjected to an operation of distilling off 358.1 g of a solvent under normal pressure, adding 13.4 g of toluene, and dropping 266.8 g of a 4 wt% 2-propanol-toluene solution. Thereafter, it was cooled to 0 ° C over 14 hours to precipitate white crystals, which were filtered. The filtered crystals were further 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-tetrachlorodecanolide as a white crystal. Then, the content of 4,5,6,7-tetrachlorodecanolide in the crystal, the filtrate, and the washing liquid was determined by gas chromatography using an internal standard method to determine the yield.

Yield: 75.1% (based on tetrachlorophthalic anhydride)

(Example 6)

In a separable flask, 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 water were added at room temperature. 0.8 g, the resulting mixture was cooled to -5 ° C with stirring. Thereafter, 6.3 g of sodium borohydride was added separately in the mixture over about 5 hours, followed by stirring at -5 ° C overnight.

To the obtained mixture, 480.3 g of toluene was added, and when the solvent was distilled off under a reduced pressure of 653.3 g at 30 to 40 ° C, the composition of the solvent to be distilled off was 67.5 wt% of toluene and 1,2-dimethoxyB. The alkane was 31.0% by weight and the 2-propanol was 1.5% by weight. The concentration of the concentrated residue, which is converted from a high-viscosity slurry to a low-viscosity slurry, is only slightly occurred, so that an improvement in the physical properties thereof is observed. And its transportability is also good. When 502.7 g of toluene was further added to the obtained residue, a solvent-substituted mixture was obtained.

Thereafter, the obtained mixture was dropped into a separable flask containing 20.6 wt% of sulfuric acid 151.3 g at 40 ° C for 30 minutes, and foaming was observed slowly. Thereafter, the obtained mixture was heated to 80 ° C, and after standing to stand for liquid separation, the organic layer was further washed with water 120.3 g and subjected to a liquid separation operation.

Then, the obtained organic layer was subjected to an operation of distilling off 395.4 g of a solvent under normal pressure, adding 2.3 g of toluene, and dropping a solution of 267.0 g of a 4 wt% 2-propanol-toluene solution. Thereafter, it was cooled to 0 ° C over 14 hours to precipitate white crystals, which were filtered. The filtered crystals were further washed with 60.2 g of a 45 wt% 2-propanol-toluene solution, and dried to obtain 45.2 g of white crystals of 4,5,6,7-tetrachlorodecanolide. Then, the content of 4,5,6,7-tetrachlorodecanolide in the crystal, the filtrate, and the washing liquid was determined by gas chromatography using an internal standard method to determine the yield.

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 further mixed. Cool to -5 ° C with stirring. Thereafter, 8.0 g of sodium borohydride was separately added to the mixture over about 1 hour, followed by stirring at -5 ° C for 3 hours.

To the obtained mixture, 480.6 g of toluene was added, and the mixture was stirred at 40 ° C for 21 hours to confirm the stability. As a result, it was confirmed that the content was reduced (retention rate was about 95% by weight). Thereafter, 568.1 g of a solvent was distilled off under reduced pressure at 30 to 40 °C. The composition of the solvent to be distilled off 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 was observed to have a high proportion of conversion to a high-viscosity slurry, thus making it difficult to transport the entire amount. At the same time, the addition of 227.3 g of toluene to the concentrated residue did not significantly improve. To the obtained residue, toluene is added to obtain a solvent-substituted mixture.

The obtained mixture was dropped into a separable flask containing 120.2 g of toluene and 151.3 g of sulfuric acid of 20.6% by weight at 40 ° C for 30 minutes, and foaming was observed slowly. Thereafter, the obtained mixture was heated to 80 ° C, and after standing to stand for liquid separation, the organic layer was further washed with water 120.0 g and subjected to a liquid separation operation.

Then, the obtained organic layer was subjected to an operation of distilling off 335.6 g of a solvent under normal pressure, adding 27.1 g of toluene, and dropping 240.2 g of a 50 wt% 2-propanol-toluene solution. Thereafter, the mixture was cooled to 70 ° C over 2 hours, cooled to 0 ° C over 14 hours to precipitate white crystals, and filtered. The filtered crystals were further washed with 120.2 g of a 50% by weight 2-propanol-toluene solution and dried. Thereafter, 37.2 g of 4,5,6,7-tetrachlorodecanolide was obtained as white crystals. Then, the content of 4,5,6,7-tetrachlorodecanolide in the crystal, the filtrate, and the washing liquid was determined by gas chromatography using an internal standard method to determine the yield.

Yield: 65.6% (based on tetrachlorophthalic anhydride)

[Possibility of industrial use]

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

Claims (5)

A method for producing a halogen-substituted azlactone, comprising the steps of: (A): substituting a halogen in at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent in the presence of water a step of reacting an acid anhydride with sodium borohydride, wherein the amount of water is 0.05 to 1 mol relative to 1 mol of sodium borohydride; and step (B): distilling from the reaction mixture obtained in the step (A) a step of replacing at least one solvent of the ether solvent and the alcohol solvent with a part or all of the solvent into an aromatic hydrocarbon solvent; and step (C): a step of mixing the mixture obtained in the step (B) with an acid; And the step of removing the halogen-substituted azlactone from the mixture obtained in the step (C). The production method according to the first aspect of the invention, wherein the water is added to the reaction system before the step (B). A method for producing a halogen-substituted azlactone, comprising the steps of: (A): halogen-substituted phthalic anhydride and boron in the presence of at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent a step of reacting sodium hydride; a step (B): adding water to the reaction mixture obtained in the step (A), and distilling from the reaction mixture at least one solvent selected from the group consisting of an ether solvent and an alcohol solvent, Part or all of the solvent, replaced by aromatic a step of aroma hydrocarbon solvent, wherein the amount of water is 0.05 to 3 moles relative to sodium borohydride 1 mol; step (C): a step of mixing the mixture obtained in step (B) with an acid; The step of removing the halogen-substituted azlactone from the mixture obtained in the step (C). The production method according to the first or third aspect of the invention, wherein the halogen-substituted phthalic anhydride is a tetrahalogen-substituted phthalic anhydride. The production method according to the first or third aspect of the invention, wherein the halogen-substituted phthalic anhydride is tetrachlorophthalic anhydride.