JP2012131724A - Method for producing cyclic disulfonic acid ester - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing cyclic disulfonic acid ester industrially advantageously in batch reaction in the same tank.SOLUTION: The method for producing the cyclic disulfonic acid ester under the presence of diphosphate pentoxide includes: a first step of dehydrating a disulfonic acid compound and a formaldehyde compound under the presence of diphosphorus pentaoxide; and a second step of adding 0.5-1.2 mol of water with regard to one mol of diphosphorus pentaoxide to a reaction mixture obtained in the first step and of extracting the reaction mixture from a reaction tank. The first and second steps are performed in a batch manner.

Description

  The present invention relates to an industrial process for producing a cyclic disulfonic acid ester compound.

  Cyclic disulfonic acid esters are useful as intermediates and functional materials for medicines and agricultural chemicals. For example, Patent Document 1 discloses that they are useful for treating cancer in mammals, and Patent Document 2 discloses electrolysis for secondary batteries. It is disclosed to be used as a liquid stabilizer.

As a method for producing a cyclic disulfonic acid ester, Patent Document 1 and Patent Document 3 disclose a method of reacting silver disulfonate with diiodomethane or dibromoethane (see Scheme 1).

Patent Document 4 discloses a method of reacting a dialkanesulfonic acid with methylene diacetate or the like (see Scheme 2).

Further, Patent Document 5 discloses a method of synthesizing an acyclic disulfonic acid ester using a sulfonic acid anhydride, and Patent Document 6 discloses a method of reacting a sulfonic acid compound and formaldehyde in the presence of a dehydrating agent to form an acyclic disulfonic acid. A method for obtaining an ester is disclosed.

JP 61-501089 A International Publication WO2005 / 057714 International Publication WO2007 / 148597 JP 2005-336155 A JP 2008-169162 A JP 2008-169161 A

  However, in the methods of Patent Document 1 and Patent Document 3, there is a problem that silver carbonate necessary for producing the raw material silver disulfonate and diiodomethane used for the reaction are expensive, and the reaction rate is slow. May not be obtained in a satisfactory yield. Further, the method of Patent Document 4 has a problem that it is difficult to obtain methylene diacetate to be used, and it is expensive. Either method is suitable for obtaining a target on a small scale, but it is not necessarily advantageous on a large scale on an industrial scale.

  On the other hand, in the method of Patent Document 6, since an inexpensive reagent such as diphosphorus pentoxide is used as a dehydrating agent, it can be manufactured at a lower cost than the above method.

However, in order to carry out the method of Patent Document 6 using a dehydrating agent in a batch-type reaction (hereinafter also simply referred to as “batch reaction”), it is essential to dry the reaction tank between batches. According to the Example of Patent Document 6, the cyclic disulfonic acid ester represented by the formula [2] is produced by the reaction represented by the following scheme 3.

  Although the reaction proceeds well in the above scheme, when water is added after the completion of the reaction and the target product is isolated by filtration, a yield similar to that of the patent literature can be obtained in the first batch, but it continues as it is. When the batch reaction is performed, the yield is significantly reduced (see Comparative Example 3). Therefore, if the reaction mixture after the reaction is extracted from the reaction vessel without adding water after the completion of the reaction of the above scheme, the reaction mixture is solidified (see Comparative Example 1). Further, when the target product is extracted with a solvent after completion of the reaction, a solid insoluble in the solvent is produced, resulting in difficulty in operation and a low yield (see Comparative Example 2). Thus, when performing the said scheme by batch reaction, since drying of a reactor becomes essential before performing the next batch, it is not necessarily industrially advantageous.

  Therefore, a method for producing a cyclic disulfonic acid ester industrially advantageously by a batch reaction in the same tank is required.

  The present inventors diligently studied, in a method for obtaining a cyclic disulfonic acid ester compound by reacting a disulfonic acid compound with a formaldehyde compound in the presence of niline pentoxide, by adding a specific amount of water to the reaction mixture, The problem has been solved.

  That is, this invention provides the manufacturing method of the cyclic | annular disulfonic acid ester compound containing the following invention [invention 1]-[invention 5].

[Invention 1]
Cyclic disulfonic acid ester represented by the formula [2] in the presence of niline pentoxide

(In the formula, X is an oxygen atom, a sulfur atom, and the formula [3].

Or an organic group represented by formula [4]

R ¹ in the organic group of the formula [3] is a hydrogen atom, a fluorine atom, a linear or branched alkyl group having 1 to 8 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, A linear or branched haloalkyl group having 1 to 8 carbon atoms, a halocycloalkyl group having 3 to 8 carbon atoms, or an unsubstituted or substituted phenyl group; R ² in the alkylene chain of the formula [4] And R ³ are each independently a hydrogen atom, a fluorine atom, a linear or branched alkyl group having 1 to 8 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, a straight chain having 1 to 8 carbon atoms, or A branched haloalkyl group, a halocycloalkyl group having 3 to 8 carbon atoms, or an unsubstituted or substituted phenyl group is shown, and m is an integer of 1 to 4. )
A method of manufacturing
Disulfonic acid compound represented by formula [1]

(In the formula, X is the same as in formula [2].)
And a formaldehyde compound are subjected to a dehydration reaction in the presence of niline pentoxide, and a first step, and
A second step of adding 0.5 to 1.2 mol of water to 1 mol of niline pentoxide to the reaction mixture obtained in the first step, and extracting the reaction mixture from the reaction vessel;
A method for producing a cyclic disulfonic acid ester, characterized in that the first step and the second step are performed in a batch system.

[Invention 2]
The method for producing a cyclic disulfonic acid ester according to the invention 1, wherein the temperature of the reaction mixture is 80 ° C or higher when water is added to the reaction mixture in the second step.

[Invention 3]
The method for producing a cyclic disulfonic acid ester according to the invention 1 or 2, wherein the temperature of the reaction mixture is 60 ° C or higher when the reaction mixture is extracted from the reaction vessel in the second step.

[Invention 4]
The method for producing a cyclic disulfonic acid ester according to any one of the inventions 1 to 3, wherein the first step and the second step are continuously performed after the reaction mixture is extracted from the reaction vessel in the second step. .

[Invention 5]
The method for producing the cyclic disulfonic acid ester according to any one of Inventions 1 to 4, wherein the disulfonic acid compound is any one of imidodisulfonic acid, methanedisulfonic acid, and ethanedisulfonic acid.

  When the method of the present invention is used, the target cyclic disulfonic acid ester compound can be efficiently produced with good reproducibility in batch production using the same tank.

  Hereinafter, the present invention will be described in detail.

First, the reaction in the first step will be described. The disulfonic acid compound used as a raw material for the reaction is a compound represented by the formula [1],

In the formula, X is an oxygen atom, a sulfur atom, and the formula [3]

Or an organic group represented by the formula [4]

An alkylene chain represented by

R ¹ in the organic group of the formula [3] is a hydrogen atom, a fluorine atom, a linear or branched alkyl group having 1 to 8 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, or a linear chain having 1 to 8 carbon atoms. Or a branched haloalkyl group, a halocycloalkyl group having 3 to 8 carbon atoms, or an unsubstituted or substituted phenyl group, among which a hydrogen atom, a methyl group, and an ethyl group are preferable, and a methyl group is more preferable. preferable. The substituent substituted on the phenyl group includes a fluorine atom, a linear or branched alkyl group having 1 to 8 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, a linear haloalkyl group having 1 to 8 carbon atoms, Or a C3-C8 halocycloalkyl group is mentioned, Especially, a methyl group and an ethyl group are preferable and a methyl group is more preferable.

R ² and R ³ in the alkylene chain of the formula [4] are each independently a hydrogen atom, a fluorine atom, a linear or branched alkyl group having 1 to 8 carbon atoms, or a cycloalkyl group having 3 to 8 carbon atoms. Represents a linear or branched haloalkyl group having 1 to 8 carbon atoms, a halocycloalkyl group having 3 to 8 carbon atoms, or a phenyl group having no substituent or a substituent, and among them, a hydrogen atom or 1 to 1 carbon atoms 4 alkyl groups and haloalkyl groups having 1 to 4 carbon atoms are preferable, and among them, a hydrogen atom, a methyl group, and a trifluoromethyl group are more preferable. The substituent substituted on the phenyl group includes a fluorine atom, a linear or branched alkyl group having 1 to 8 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, a linear haloalkyl group having 1 to 8 carbon atoms, Or a C3-C8 halocycloalkyl group is mentioned, Especially, a methyl group and an ethyl group are preferable and a methyl group is more preferable. m represents an integer of 1 to 4, and in particular, m is preferably 1 or 2, and m is particularly preferably 1.

  Specific examples of the disulfonic acid compound include imidodisulfonic acid, N-methylimidodisulfonic acid, methanedisulfonic acid, 1,2-ethanedisulfonic acid, 1,3-propanedisulfonic acid, 1,4-butanedisulfonic acid 1,1. -Difluoromethane-disulfonic acid, 1,1,2,2-tetrafluorodisulfonic acid, 1,1,2,2,3,3-hexafluorodisulfonic acid, 1,1-dimethylmethanedisulfonic acid, 2,2- Examples thereof include propanedisulfonic acid, among which imide disulfonic acid, methanedisulfonic acid, and ethanedisulfonic acid are preferable, and methanedisulfonic acid is particularly preferable.

Commercially available disulfonic acid compounds may be used, and the formula [5]

(Wherein X is the same as the above formula [1], X ′ represents a halogen atom) and obtained by a method of reacting water with a disulfonyl halide represented by the formula (for example, JP-A-2005-336155). You may also use a new one.

  Examples of the formaldehyde compound used in the present invention include paraformaldehyde, anhydrous formaldehyde, and trioxane. These paraformaldehyde compounds can be used individually or in combination of 2 or more types.

  The amount of niline pentoxide used in the first step is usually in the range of 0.6 to 10 mol, particularly in the range of 0.8 to 3.0 mol, with respect to 1 mol of the disulfonic acid compound. preferable.

  Although the reaction temperature of this reaction changes with compounds to be used, it is 0-200 degreeC normally, Preferably it is 50-150 degreeC. Moreover, although reaction time changes with reaction temperature and the compound to be used, it is 0.1 to 10 hours normally. These should be examined appropriately according to the conditions.

  If necessary, a solvent may be used for this reaction, and the solvent that can be used is only required to be inert to the reaction. Specifically, hydrocarbon solvents such as toluene, xylene, monochlorobenzene, dichlorobenzene, trichlorobenzene, hexane, heptane, decane, ether solvents such as diethyl ether, ethylene glycol dimethyl ether, diisopropyl ether, diphenyl ether, tetrahydrofuran, dioxane, Ketone solvents such as acetone and methyl ethyl ketone, amide solvents such as dimethylformamide and hexamethylphosphoric triamide, acetate solvents such as ethyl acetate, nitrile solvents such as acetonitrile, sulfoxide and sulfone solvents such as dimethyl sulfoxide and sulfolane, etc. Can be mentioned. Or you may use the pyrophosphoric acid produced | generated by reaction as a solvent. However, since the reaction in the first step proceeds satisfactorily without a solvent, it can be said that it is industrially advantageous when no solvent is used.

Next, the second step will be described in detail. It is considered that metaphosphoric acid is generated in the reaction mixture by the reaction in the first step (see Scheme 4).

The metaphosphoric acid produced is an arbitrary polymer (simply described as (HPO ₃ ) _{n in the} scheme), and this polymer is considered to cause a decrease in operability. In the present invention, it is assumed that by adding a specific amount of water to the reaction mixture obtained in the first step, the produced metaphosphoric acid is converted to pyrophosphoric acid and the operability is improved. When an excessive amount of water is added, metaphosphoric acid is converted to phosphoric acid, so that the operability is considered to be further improved. However, the acidity of the reaction mixture becomes high, and the reaction vessel may be corroded at high temperatures. Therefore, problems such as the need to use an acid-resistant reaction tank arise on an industrial scale where temperature control is difficult, and it is not industrially advantageous (see Scheme 5).

  The amount of water added to the reaction mixture is preferably 0.5 to 1.5 mol with respect to 1 mol of niline pentoxide used in the first step. Furthermore, 0.8 to 1.2 mol is more preferable. If the amount of water is less than 0.5 mol, pyrophosphoric acid cannot be sufficiently prepared. Therefore, the reaction mixture cannot be withdrawn even at 80 ° C. If it is more than 1.2 mol, the acidity of the reaction mixture This is not preferable because the degree is high, or the yield is reduced when the next batch reaction is performed in the same tank.

  The temperature of the reaction mixture when adding water is preferably 80 ° C. or higher, more preferably 90 ° C. or higher. When the temperature is lower than 80 ° C., coagulation of metaphosphoric acid starts, which is not preferable because operability is lowered.

  The reaction mixture to which water has been added is desirably sufficiently stirred, but the time required for stirring may be appropriately determined depending on the amount of water added and the temperature of the reaction mixture.

  When extracting the reaction mixture from the reaction vessel, the temperature of the reaction mixture is preferably 60 ° C. or higher, more preferably 70 ° C. or higher. When the temperature at the time of extraction is lower than 60 ° C., coagulation of pyrophosphoric acid starts, which is not preferable because operability is lowered.

  The tank after extraction may be washed and dried before the first step of the next batch, but by omitting the washing and drying operation, it is not necessary to use a washing solvent, so the operation becomes simple. It is industrially advantageous to carry out batch reaction continuously without drying.

  The target substance contained in the extracted reaction mixture is purified by applying a known method. For example, after cooling the reaction mixture extracted from the reaction vessel to room temperature, water is added and stirred, and the precipitate is filtered. Separately, crystals of the target cyclic disulfonic acid ester can be easily obtained.

  Next, the present invention will be described in detail based on examples. In addition, this invention is not limited to this Example.

(First batch, first step and second step)
To a 100 ml four-necked flask, 5.0 g (28.4 mmol) of methanedisulfonic acid and 4.0 g (28.4 mmol) of niline pentoxide were added, and 0.85 g (28.4 mmol) of paraformaldehyde was added with stirring. After completion of the addition, the mixture was stirred at 120 ° C. for 1 hour and then cooled to 80 ° C. After slowly adding 0.5 g of water to the reaction mixture and stirring for 10 minutes, it was taken out into a 100 ml eggplant flask at 65 ° C., and it was confirmed that the reaction mixture could be transferred. The reactor after the transfer was used as it was in the next batch. The reaction mixture taken out into the eggplant flask was cooled to room temperature, and 35 g of water was further added. After stirring for 30 minutes, insoluble matters were filtered off to obtain white crystals. The obtained crystals were dried at 40 ° C. and 10 mmHg for 6 hours to obtain 2.4 g (yield 45%) of the target methylenemethane disulfonate.

(2nd batch 1st process and 2nd process)
To a 100 ml four-necked flask used in the first batch (one that was not washed and dried after the reaction mixture was taken out from the first batch), 5.0 g (28.4 mmol) of methanedisulfonic acid and niline pentoxide. 0 g (28.4 mmol) was added, and 0.85 g (28.4 mmol) of paraformaldehyde was added with stirring. After completion of the addition, the mixture was stirred at 120 ° C. for 1 hour and then cooled to 80 ° C. To this reaction mixture, 0.5 g of water was slowly added and stirred for 10 minutes, and then taken out into a 100 ml eggplant flask at 65 ° C. The reaction mixture taken out into the eggplant flask was cooled to room temperature, and 35 g of water was further added. After stirring for 30 minutes, insoluble matters were filtered off to obtain white crystals. The obtained crystals were dried at 40 ° C. and 10 mmHg for 6 hours to obtain 2.5 g (yield 47%) of the target methylenemethane disulfonate.

  From the results of the examples, by adding a specific amount of water from the reaction vessel to the dehydrating agent in the second step, good yield with good reproducibility without performing washing and drying of the reaction vessel between batches. It was found that a cyclic disulfonic acid ester compound was obtained.

[Comparative Example 1]
To a 100 ml four-necked flask, 2.9 g (16.46 mmol) of methanedisulfonic acid and 2.3 g (16.46 mmol) of niline pentoxide were added, and 0.49 g (16.46 mmol) of paraformaldehyde was added with stirring. After completion of the addition, the mixture was stirred at 120 ° C. for 1 hour, and then the reaction mixture was tried to be extracted at 70 ° C., but could not be extracted at all due to the solidification of the reaction mixture.

[Comparative Example 2]
To a 100 ml four-necked flask, 2.9 g (16.46 mmol) of methanedisulfonic acid and 2.3 g (16.46 mmol) of niline pentoxide were added, and 0.49 g (16.46 mmol) of paraformaldehyde was added with stirring. After completion of the addition, the mixture was stirred at 120 ° C. for 1 hour. Thereafter, the reaction mixture was cooled to room temperature, and 50 g of methylene chloride was added, followed by stirring for 1 hour. The filtrate obtained by filtering insolubles was concentrated, and the obtained crystals were dried at 40 ° C. and 10 mmHg for 6 hours to obtain 0.59 g (yield 19%) of the target methylenemethane disulfonate. Thus, when solvent extraction was performed using methylene chloride, a large amount of solid insoluble in methylene chloride was precipitated, so that extraction could not be performed sufficiently and the yield was low.

[Comparative Example 3]
(First batch)
To a 100 ml four-necked flask, 5.0 g (28.4 mmol) of methanedisulfonic acid and 4.0 g (28.4 mmol) of niline pentoxide were added, and 0.85 g (28.4 mmol) of paraformaldehyde was added with stirring. After completion of the addition, the mixture was stirred at 120 ° C. for 1 hour and then cooled to room temperature. To this reaction mixture, 35 g of water was slowly added, and after stirring for 30 minutes, insoluble matters were filtered off to obtain white crystals. The obtained crystals were dried at 40 ° C. and 10 mmHg for 6 hours to obtain 2.4 g (yield 45%) of the target methylenemethane disulfonate.

(2nd batch)
The 100 ml four-necked flask used in the first batch was used as it was, and 5.0 g (28.4 mmol) of methanedisulfonic acid and 4.0 g (28.4 mmol) of niline pentoxide were added again, and 0.85 g of paraformaldehyde was stirred. (28.4 mmol) was added and reacted at 120 ° C. for 1 hour. After completion of the reaction, the reaction mixture was cooled to room temperature and 35 g of water was slowly added. After stirring for 30 minutes, insoluble matters were filtered off to obtain white crystals. The obtained crystals were dried at 40 ° C. and 10 mmHg for 6 hours to obtain 1.7 g (yield 31%) of the desired product methylenemethane disulfonate.

  The cyclic disulfonic acid ester compound obtained by the production method of the present invention can be suitably used as an intermediate or functional material for agricultural chemicals.

Claims (5)

Cyclic disulfonic acid ester represented by the formula [2] in the presence of niline pentoxide

(In the formula, X is an oxygen atom, a sulfur atom, and the formula [3].

Or an organic group represented by formula [4]

R ¹ in the organic group of the formula [3] is a hydrogen atom, a fluorine atom, a linear or branched alkyl group having 1 to 8 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, A linear or branched haloalkyl group having 1 to 8 carbon atoms, a halocycloalkyl group having 3 to 8 carbon atoms, or an unsubstituted or substituted phenyl group; R ² in the alkylene chain of the formula [4] And R ³ are each independently a hydrogen atom, a fluorine atom, a linear or branched alkyl group having 1 to 8 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, a straight chain having 1 to 8 carbon atoms, or A branched haloalkyl group, a halocycloalkyl group having 3 to 8 carbon atoms, or an unsubstituted or substituted phenyl group is shown, and m is an integer of 1 to 4. )
A method of manufacturing
Disulfonic acid compound represented by formula [1]

(In the formula, X is the same as in formula [2].)
And a formaldehyde compound are subjected to a dehydration reaction in the presence of niline pentoxide, and a first step, and
A second step of adding 0.5 to 1.2 mol of water to 1 mol of niline pentoxide to the reaction mixture obtained in the first step, and extracting the reaction mixture from the reaction vessel;
A method for producing a cyclic disulfonic acid ester, characterized in that the first step and the second step are performed in a batch system.   The method for producing a cyclic disulfonic acid ester according to claim 1, wherein the temperature of the reaction mixture is 80 ° C or higher when water is added to the reaction mixture in the second step.   The method for producing a cyclic disulfonic acid ester according to claim 1 or 2, wherein the temperature of the reaction mixture is 60 ° C or higher when the reaction mixture is extracted from the reaction vessel in the second step.   The cyclic disulfonic acid ester according to any one of claims 1 to 3, wherein the first step and the second step are continuously performed after the reaction mixture is extracted from the reaction vessel in the second step. Method. The method for producing a cyclic disulfonic acid ester according to any one of claims 1 to 4, wherein the disulfonic acid compound is any one of imidodisulfonic acid, methanedisulfonic acid, and ethanedisulfonic acid.