Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
  • C07C303/02—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof
  • C07C303/04—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof by substitution of hydrogen atoms by sulfo or halosulfonyl groups
  • C07C303/08—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof by substitution of hydrogen atoms by sulfo or halosulfonyl groups by reaction with halogenosulfonic acids
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D327/00—Heterocyclic compounds containing rings having oxygen and sulfur atoms as the only ring hetero atoms

Definitions

• the present invention relates to a method for producing a methylene disulfonic acid compound using a carboxylic acid halide compound.
• Methylene disulfonic acid compounds are known as intermediates for synthesizing methylene disulfonate compounds useful in various fields such as pharmaceuticals such as animal leukemia therapeutic agents and additives for secondary battery electrolytes.
• a method for producing a methylene disulfonic acid compound sulfonation of dihalogenated methylene is known.
• a method for producing a methylene disulfonic acid compound by reacting an aqueous sodium sulfite solution with dibromomethane in the presence of potassium iodide and tetrabutylammonium bromide (Patent Document 1).
• the method (nonpatent literature 1) etc. which are manufactured by hydrolysis of thioacetic acid alkylester are known.
• Patent Document 2 there are known methods for obtaining alkanedisulfonic acid hydrates by adding an excess amount of water to alkanedisulfonyl halide, and methods for dehydrating alkanedisulfonic acid hydrates with a dehydrating agent (thionyl chloride).
• Non-Patent Document 1 a methylene disulfonic acid compound can be easily obtained.
• thioacetic acid alkyl ester as raw material, it is necessary to use odorous thioacetic acid, so it is necessary to take sufficient deodorizing measures. May be required.
• Patent Document 2 it is a method of producing a methylene disulfonic acid compound by adding an excess amount of water to the methylene disulfonyl chloride compound. Any water present must be removed. Furthermore, when obtaining the methylene disulfonyl chloride compound which is a raw material, the reaction using specific carboxylic acid, chlorosulfonic acid, and phosphoryl trichloride is used (nonpatent literature 2). In these reactions, an insoluble by-product is generated during the reaction, which causes poor stirring of the raw materials and clogging of the apparatus. Therefore, it is not preferable to industrially produce a methylene disulfonyl chloride compound.
• the conventional method for obtaining a methylene disulfonic acid compound has a problem that it is not preferable from an industrial point of view, such as complicated equipment and facilities and a long process. Furthermore, when manufacturing via a methylene disulfonyl chloride compound, since many poisonous substances, such as phosphoryl trichloride, are used at the time of manufacture of a methylene disulfonyl chloride compound, it improves on industrial implementation, such as an increase in waste water. There was a problem.
• the object of the present invention is to efficiently produce a methylene disulfonic acid compound by an industrially advantageous method.
• the present invention includes, for example, the subject matters described in the following sections.
• R 1 R 2 CHCOX (1) (Wherein R 1 and R 2 each independently represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms in which the hydrogen atom may be substituted with a halogen atom, and X represents a halogen atom).
• the following formula (3) including the step of reacting the carboxylic acid halide compound represented by) and chlorosulfonic acid, and the step of (B) mixing the reaction solution obtained in the step (A) and water:
• R 1 and R 2 are the same as R 1 and R 2 in formula (1), respectively).
• Item 2. The process for producing a methylene disulfonic acid compound according to Item 1, wherein in the step (A), the amount of chlorosulfonic acid used per 1 mol of the carboxylic acid halide compound represented by the formula (1) is 2 mol or more and 6 mol or less. Method.
• the amount of water used is 100 parts by mass or more and 1200 parts by mass or less with respect to 100 parts by mass of the carboxylic acid halide compound represented by the formula (1) used in the step (A).
• Item 3. A method for producing a methylene disulfonic acid compound according to Item 1 or 2.
• Item 4 The step of obtaining a methylene disulfonic acid compound represented by the formula (3) by the production method according to any one of items 1 to 3, and (C) a methylene disulfonic acid compound represented by the formula (3), Formula (4) including the step of mixing and reacting a dehydrating agent and at least one compound selected from the group consisting of formaldehyde, trioxane and paraformaldehyde:
• R 1 and R 2 are the same as R 1 and R 2 in formula (1), respectively).
• a reaction solution obtained by reacting a carboxylic acid halide compound and chlorosulfonic acid is further mixed with water in an industrially advantageous manner.
• the manufacturing method which can obtain a methylene disulfonic acid compound directly from a carboxylic acid halide compound can be provided.
• the methylene disulfonate compound can be obtained in a high yield by an industrially advantageous method (particularly, without using phosphoryl trichloride).
• the production method of the present invention comprises: (A) A step of reacting the carboxylic acid halide compound represented by the formula (1) with chlorosulfonic acid, and (B) a step of mixing the reaction solution obtained in the step (A) and water.
• the step of reacting the carboxylic acid halide compound represented by the formula (1) and chlorosulfonic acid is the step (A), the step of mixing the reaction solution obtained in the step (A) and water (B ) Process.
• R 1 and R 2 are the same as R 1 and R 2 in formula (1), respectively).
• the reaction liquid containing the chlorosulfonyl methylene sulfonic acid compound represented by this can be obtained.
• R 1 R 2 CHCOX (1) (Wherein R 1 and R 2 each independently represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms in which the hydrogen atom may be substituted with a halogen atom, and X represents a halogen atom). ) It is a compound represented by these.
• the alkyl group having 1 to 4 carbon atoms may be linear or branched. Specific examples include a methyl group, an ethyl group, an n-propyl group, an n-butyl group, and an isopropyl group.
• the hydrogen atom of the alkyl group may be substituted with a halogen atom.
• the halogen atom is preferably a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom, more preferably a chlorine atom.
• the number of hydrogen atoms substituted with halogen atoms is preferably 1, 2, 3, or 4, more preferably 1 or 2.
• an unsubstituted or monosubstituted product in which one of R 1 and R 2 is hydrogen and the other is an alkyl group having 1 to 4 carbon atoms which may be substituted with hydrogen or a halogen atom is preferable.
• the alkyl group having 1 to 4 carbon atoms which may be substituted with a monosubstituted halogen atom is preferably a linear alkyl group such as a methyl group, an ethyl group, an n-propyl group or an n-butyl group.
• examples of the halogen atom represented by X include a chlorine atom, a bromine atom and an iodine atom.
• a chlorine atom is preferable from the viewpoints of easy availability and safety.
• carboxylic acid halide compound of the formula (1) include chlorides such as acetic acid chloride, propionic acid chloride, butyric acid chloride, valeric acid chloride, isobutyric acid chloride, and isovaleric acid chloride; and acetic acid bromide and propione.
• chlorides such as acetic acid chloride, propionic acid chloride, butyric acid chloride, valeric acid chloride, isobutyric acid chloride, and isovaleric acid chloride
• acetic acid bromide and propione examples include bromides such as acid bromide, butyric acid bromide, valeric acid bromide, isobutyric acid bromide, and isovaleric acid bromide.
• chlorides are preferable from the viewpoint of availability, safety, and the like, more preferably acetic acid chloride, propionic acid chloride, and butyric acid chloride, and particularly preferable are acetic acid chloride and propionic acid chloride.
• carboxylic acid halide compounds By using these carboxylic acid halide compounds, methylene disulfonic acid compounds can be obtained with high yield.
• carboxylic acid halide compound Commercially available products may be used as the carboxylic acid halide compound. Moreover, you may use what was manufactured in accordance with the conventional method, for example, what was manufactured by making carboxylic acid, thionyl chloride, or thionyl bromide react can be used.
• the amount of the chlorosulfonic acid used is preferably 2 mol or more and 6 mol or less with respect to 1 mol of the carboxylic acid halide compound. , More preferably 2 mol or more and 4 mol or less.
• the amount used is 6 mol or less, generation of sulfuric acid due to side reaction can be suppressed, so that decomposition of the chlorosulfonylmethylenesulfonic acid compound by sulfuric acid can be suppressed.
• the said usage-amount is 2 mol or more, reaction advances efficiently and the yield of the said chlorosulfonyl methylene sulfonic acid compound can be improved more.
• the method of mixing the carboxylic acid halide compound and chlorosulfonic acid is not particularly limited, and examples thereof include a method of adding chlorosulfonic acid to the carboxylic acid halide compound.
• the method of dripping chlorosulfonic acid from a viewpoint of safety etc. is preferable.
• the temperature at the time of dropping is preferably 0 to 20 ° C. If a reaction liquid is 20 degrees C or less, the production
• the dropping time is preferably 0.5 to 3.0 hours. By dropping over 0.5 hours or more, heat generation can be suppressed and a rapid temperature rise of the reaction solution can be prevented, so that the reaction can be performed more safely. In addition, if the dropping time is 3.0 hours or less, the heat generated by dropping can be used efficiently, so that the time required for temperature rise can be saved during subsequent heating, which is economical for industrialization. .
• the temperature at which the reaction solution is heated and reacted after mixing the carboxylic acid halide compound and chlorosulfonic acid is preferably 70 to 140 ° C., more preferably 90 to 120 ° C.
• the reaction temperature is 70 ° C. or higher, the reaction proceeds at an appropriate reaction rate and the efficiency is good. Moreover, if it is 140 degrees C or less, the production
• the reaction time is usually 10 to 20 hours.
• reaction may be performed without a solvent, but a solvent may be used as necessary.
• reaction is performed in an inert atmosphere such as nitrogen or argon as necessary.
• chlorosulfonylmethylenesulfonic acid compound represented by the formula (2) include, for example, chlorosulfonylmethylenesulfonic acid, 1,1-chlorosulfonylethylenesulfonic acid, 1,1-chlorosulfonylpropanesulfonic acid, 1 1,2-chlorosulfonylbutanesulfonic acid, 2,2-chlorosulfonylpropanesulfonic acid, 2-methyl-1,1-chlorosulfonylpropanesulfonic acid, and the like.
• chlorosulfonylmethylenesulfonic acid, 1,1-chlorosulfonylethylenesulfonic acid, and 1,1-chlorosulfonylpropanesulfonic acid are preferable, and chlorosulfonylmethylenesulfonic acid and 1,1-chlorosulfonylethylenesulfonic acid are particularly preferable.
• the methylene disulfonic acid compound can be industrially advantageously obtained by mixing (preferably mixing and heating) the reaction solution obtained in the process (A) and water.
• the reaction solution obtained in the step (A) is not limited to a reaction solution obtained by reacting a carboxylic acid halide compound and chlorosulfonic acid, but a carboxylic acid halide compound and chlorosulfonic acid.
• a concentrated reaction liquid obtained by further concentrating the reaction liquid obtained by the reaction by distillation or the like is also included.
• the resulting methylene disulfonic acid compound has the following formula (3):
• R 1 and R 2 are the same as R 1 and R 2 in formula (1), respectively). It is a methylene disulfonic acid compound represented by these.
• R 1 and R 2 in the formula (3) include those exemplified in R 1 and R 2 in Formula (1).
• methylene disulfonic acid compound of the formula (3) include, for example, methane disulfonic acid, ethane-1,1-disulfonic acid, propane-1,1-disulfonic acid, butane-1,1-disulfonic acid, propane -2,2-disulfonic acid, 2-methyl-propane-1,1-disulfonic acid and the like.
• methanedisulfonic acid, ethane-1,1-disulfonic acid, and propane-1,1-disulfonic acid are preferable, and methanedisulfonic acid and ethane-1,1-disulfonic acid are particularly preferable.
• the amount of water used is 100 parts by mass of the carboxylic acid halide compound.
• the amount is preferably 100 to 1200 parts by mass, and more preferably 400 to 600 parts by mass.
• the amount of water used is 100 parts by mass or more, the reaction proceeds efficiently, the chlorosulfonylmethylene sulfonic acid compound does not become unreacted, and the reaction proceeds with higher yield. Moreover, if it is 1200 mass parts or less, the removal of the excess water is easier and efficient.
• the method of mixing the reaction solution obtained in the step (A) and water is not particularly limited.
• water is charged in a flask and obtained in the step (A) while bathing in an ice bath.
• the reaction solution (preferably a concentrated reaction solution obtained by concentrating the reaction solution obtained in the above reaction) is added, and then the temperature is raised.
• produce when adding a reaction liquid the method of dripping a reaction liquid from a safety viewpoint etc. is preferable.
• the temperature at the time of dropping is preferably 0 to 20 ° C., and the dropping time is preferably 0.5 to 3.0 hours. Heat generation can be suppressed by dripping within a predetermined time. If it is within 3.0 hours, the time required for production can be shortened, which is economical in the case of industrialization.
• the temperature for heating and reacting the mixture is preferably 70 to 100 ° C., more preferably 90 to 100 ° C. If reaction temperature is 70 degreeC or more, it will prevent that an unreacted chlorosulfonyl methylene sulfonic acid compound remains, and reaction will progress with a sufficient yield.
• the reaction time is usually 1 to 2 hours.
• the production method of the present invention may include additional steps as long as the effects of the present invention are not impaired.
• Examples of the additional step include a step of removing excess chlorosulfonic acid as shown below.
• the reaction liquid containing the chlorosulfonylmethylenesulfonic acid compound obtained in the step (A) usually contains an excess of chlorosulfonic acid together with the chlorosulfonylmethylenesulfonic acid compound represented by the formula (2). Therefore, it is preferable to remove excess chlorosulfonic acid from the reaction solution.
• Examples of the method for removing excess chlorosulfonic acid from the reaction solution include a method of concentrating the reaction solution by a method such as distillation before the subsequent step (B) to remove the excess chlorosulfonic acid.
• the mixture is reacted with water as it is in the step (B) to hydrolyze the excess chlorosulfonic acid to obtain sulfuric acid.
• the method for removing sulfuric acid after hydrolysis include a method for removing barium sulfate by adding barium chloride and water.
• chlorosulfonic acid When chlorosulfonic acid is removed from the reaction solution by distillation or the like, it may be performed after the step (A) and before the step (B). When the chlorosulfonic acid is hydrolyzed and then removed as sulfuric acid, it may be carried out after the step (B). These methods may be performed alone or in combination.
• barium chloride When removing excess chlorosulfonic acid as sulfuric acid, after heating and reacting the mixture of the reaction solution and water, barium chloride is added and filtered to remove sulfuric acid as barium sulfate.
• the temperature in this operation is not limited, but after adding barium chloride, it is preferable to keep the temperature once at 70 to 90 ° C. and then cool to 0 to 20 ° C. and then filter.
• the amount of barium chloride used is not limited, but for example, it is preferably about 0.9 to 1.2 mol with respect to 1 mol of sulfuric acid present in the mixed solution.
• the quantification of sulfuric acid present in the mixed solution is not particularly limited, and examples thereof include an ion chromatographic method because it is simple and can be analyzed in a small amount.
• the ion chromatograph method used in the present invention may be a commercially available ion chromatograph apparatus, and the column used is not particularly limited.
• the measurement conditions such as the measurement temperature and elution conditions may be set appropriately as long as the objective is achieved.
• the methylene disulfonic acid compound represented by the formula (3) contains an excess amount of water. Therefore, a methylene disulfonic acid compound with a low water content can be obtained by distilling off excess water.
• the methylene disulfonic acid compound represented by the formula (3) is usually considered to form hydrogen bonds with water molecules. Since an excessive amount of water is reacted in the above production method, the obtained methylene disulfonic acid compound is considered to form hydrogen bonds with water molecules. Although this state is sometimes described as the formation of a hydrate of a methylene disulfonic acid compound, it is described in this specification that water is present in the methylene disulfonic acid compound.
• Water in the methylene disulfonic acid compound may inhibit the dehydration condensation reaction particularly in the reaction of synthesizing the methylene disulfonate compound by the steps described below. Therefore, it is desirable to remove water from the methylene disulfonic acid compound according to the present invention as much as possible.
• the content of water in the methylene disulfonic acid compound is preferably about 5% by mass or less. More preferably, it is 4 mass% or less.
• water can be efficiently removed by bringing the obtained methylene disulfonic acid compound to a high temperature (for example, about 120 ° C. or higher) under reduced pressure conditions.
• Water contained in the methylene disulfonic acid compound can be removed by a simple method.
• the water content in the methylene disulfonic acid compound can be reduced to about 5% by mass or less by adjusting the temperature to 140 ° C. and 5 mmHg or less.
• water when the method of the present invention is used, water can be sufficiently distilled off only by distilling off water from the obtained methylenedisulfonic acid compound under heating and reduced pressure conditions.
• a polar organic solvent preferably an aprotic polar organic solvent such as dimethyl sulfoxide, sulfolane, methylpyrrolidine, dimethylformamide, etc.
• the polar organic solvent can be used as it is as a solvent when a methylene disulfonate compound is synthesized by the steps described below.
• a cyclic methylene disulfonate compound can be synthesized from the methylene disulfonic acid compound represented by the above formula (3) produced by the above-described method by a known method.
• the known method for example, the method described in International Publication No. WO2007 / 125736 is preferably exemplified. Specifically, it is a method of synthesizing a cyclic methylene disulfonate compound by reacting a methylene disulfonic acid compound and a formaldehyde compound in the presence of a dehydrating agent.
• R 1 and R 2 are the same as R 1 and R 2 in formula (1), respectively).
• the methylene disulfonate compound represented by these can be manufactured.
• R 1 and R 2 in Formula (4) include those exemplified in R 1 and R 2 in Formula (1).
• the dehydrating agent used here is not particularly limited, and examples thereof include phosphorus pentoxide, phosphorus pentachloride, phosphorus oxychloride, thionyl chloride, acetyl chloride, and acetic anhydride. Among these, phosphorus pentoxide is preferable from the viewpoint of high reactivity.
• These dehydrating agents can be used singly or in combination of two or more.
• the amount of the dehydrating agent to be used is not particularly limited, but is preferably 0.6 to 10 mol, more preferably 0.8 to 3 mol with respect to 1 mol of the methylene disulfonic acid compound.
• the amount of at least one compound selected from the group consisting of formaldehyde, trioxane, and paraformaldehyde is not particularly limited, but is equivalent to formaldehyde with respect to 1 mole of methylene disulfonic acid compound. And preferably 0.2 to 10 mol, more preferably 0.3 to 3 mol.
• the reaction temperature is not particularly limited, but is preferably 0 to 200 ° C., more preferably 50 to 150 ° C., for example.
• the reaction time varies depending on the reaction temperature, but is about 0.1 to 15 hours, for example.
• the methylene disulfonate compound represented by the formula (4) obtained as described above is separated from the reaction mixture by a conventional separation means and purified.
• separation and purification means include distillation, recrystallization, column chromatography, ion exchange chromatography, gel chromatography, affinity chromatography, preparative thin layer chromatography, solvent extraction, and the like. it can.
• Example 1 A 100 mL four-necked flask equipped with a stirrer, condenser, thermometer and dropping funnel was charged with 27.8 g (0.30 mol) of propionic acid chloride under a nitrogen stream and cooled to 5 ° C. by bathing in an ice bath. did. 69.6 g (0.60 mol) of chlorosulfonic acid was added dropwise over 30 minutes while maintaining the temperature at 10 ° C. with a dropping funnel. Next, the temperature of the reaction solution was raised to 110 ° C. over an hour using an oil bath. The reaction solution was kept at 110 ° C. for 10 hours.
• This reaction solution was distilled off under reduced pressure at 100 ° C./3 mmHg, and the resulting concentrated solution was charged with 120.0 g of water charged in a 200 mL four-necked flask equipped with a stirrer, a condenser, a thermometer and a dropping funnel. The solution was added dropwise at 5 ° C. for 0.5 hours while cooling in an ice bath. After dropping, the temperature was raised to 100 ° C. by an oil bath and kept for 1 hour. When this reaction solution was quantified by ion chromatography, 0.12 mol of sulfate ion was present.
• Example 2 In the same manner as in Example 1 except that 104.4 g (0.90 mol) of chlorosulfonic acid was used instead of 69.6 g (0.60 mol) of chlorosulfonic acid, ethane-1, 11.6 g (0.06 mol, water content 3.8% by mass) of 1-disulfonic acid was obtained. The yield was 20.4%.
• Example 3 In Example 1, instead of 27.8 g (0.30 mol) of propionic acid chloride, 23.6 g (0.30 mol) of acetic acid chloride was used in the same manner as in Example 1, except that methanedisulfonic acid. 8 g (0.05 mol, moisture content 3.2% by mass) was obtained. The yield was 16.6%.
• Comparative Example 1 A 500 mL four-necked flask equipped with a stirrer, condenser, thermometer and dropping funnel was charged with 184.0 g (1.20 mol) of phosphoryl trichloride under a nitrogen stream and cooled to 5 ° C. by bathing in an ice bath. did. 76.9 g (0.66 mol) of chlorosulfonic acid was added dropwise over 30 minutes while maintaining the temperature at 10 ° C. with a dropping funnel. Further, 22.2 g (0.30 mol) of propionic acid was added dropwise over 30 minutes while maintaining at 10 ° C. Next, the temperature of the reaction solution was raised to 110 ° C. over an hour using an oil bath.
• Table 1 summarizes the conditions and results of the above Examples and Comparative Examples.
• Example 4 A 300 mL four-necked flask equipped with a stirrer, a condenser and a thermometer was charged with 18.6 g (0.098 mol) of ethane-1,1-disulfonic acid and 77.6 g of sulfolane under a nitrogen stream. The temperature was raised to 100 ° C. After the temperature increase, 4.1 g of paraformaldehyde (0.136 mol in terms of formaldehyde) and 27.8 g of diphosphorus pentoxide (0.196 mol) were added, and the temperature was kept for 12 hours.

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