JP7653307B2 - Method for producing carboxylic acid thioester - Google Patents

Description

The present invention relates to a method for producing a carboxylic acid thioester.

Carboxylic acid thioesters are widely used as raw materials for the synthesis of sulfur-containing compounds used in functional materials such as pharmaceuticals, agricultural chemicals, and liquid crystals. A commonly known method for producing carboxylic acid thioesters is to react a carboxylic acid or a carboxylic acid derivative with a thiol.

For example, Patent Document 1 describes a method in which a carboxylic acid anhydride and a thiol are reacted in the presence of an equal amount of a carbonate ester and catalytic amounts of an alkali salt and an alkaline earth salt.

Patent Document 2 and Non-Patent Document 1 describe a method of reacting a carboxylic acid with a thiol in the presence of a catalytic amount of trifluorosulfonic acid or Nafion.

Non-Patent Document 2 describes a method of reacting a carboxylic acid with a thiol in the presence of a catalytic amount of hafnium (IV) chloride.

Non-Patent Document 3 describes a method of reacting a carboxylic acid with a thiol in the presence of a catalytic amount of a perfluoropyridinium salt.

Patent No. 6627653 Patent No. 3777324

Chemistry Communication, 2002, pp. 94-95 Tetrahedron, Vol. 58, No. 41, pp. 8179-8188 Green Chemistry, 2006, No. 8, pp. 1022-1027

However, in the manufacturing method described in Patent Document 1, because carboxylic anhydride is used as a raw material, an equal amount of carboxylic acid is produced as a by-product, and an equal amount of by-product derived from the activator carbonate ester is also produced. In the manufacturing process, the by-product needs to be removed, resulting in a large amount of waste, which is problematic from both an economic and environmental standpoint.

The manufacturing method described in Non-Patent Document 2 uses hafnium, a rare resource, and although details are unclear, there is no mention of recovering the hafnium catalyst, which poses problems from the perspective of sustainability.

The manufacturing methods described in Patent Document 2, Non-Patent Document 1, and Non-Patent Document 3 require a reaction termination step using an alkaline aqueous solution, etc., which poses problems in the manufacturing process.

The object of the present invention is to provide a method for producing carboxylic acid thioesters that is easy to operate, reduces waste, and is sustainable.

The present invention is a method for producing a carboxylic acid thioester, which comprises reacting a carboxylic acid with a thiol in the presence of a solid acid catalyst to produce a carboxylic acid thioester, wherein the solid acid catalyst is a non-particulate organic porous strongly acidic cation exchanger .

In the method for producing a carboxylic acid thioester, the cation exchange capacity of the strongly acidic cation exchange resin is preferably greater than 1 mg equivalent/g.

In the method for producing a carboxylic acid thioester, the non-particulate organic porous strongly acidic cation exchanger preferably comprises a continuous skeleton phase and a continuous pore phase, the thickness of the continuous skeleton being in the range of 1 to 100 μm, the average diameter of the continuous pores being in the range of 1 to 1000 μm, the total pore volume being in the range of 0.5 to 50 mL/g, the cation exchange capacity per weight in a dry state being in the range of 1 to 5 mg equivalents/g, and the cation exchange groups being distributed throughout the non-particulate organic porous strongly acidic cation exchanger.

The present invention provides a method for producing carboxylic acid thioesters that is simple to operate, reduces waste, and is sustainable.

1 is a SEM photograph of a first monolith morphology example. 1 is a SEM photograph of a second monolith morphology example. 13 is an SEM photograph of a third monolith morphology example. FIG. 4 is a transfer of the skeleton portion shown as a cross section in the SEM photograph of FIG. 3 . 11 is an SEM photograph of a fourth monolith embodiment; FIG. 13 is a schematic diagram of the co-continuous structure of the fourth monolith. 1 is a SEM photograph of an example of the morphology of the monolith intermediate (4). FIG. 4 is a schematic cross-sectional view of a protrusion. 5 is a SEM photograph of the monolith embodiment No. 5-1. 1 is a SEM photograph of a monolith intermediate obtained in an example. 1 is a SEM photograph of a monolith obtained in an example. 4 is an EPMA measurement result showing the distribution state of sulfur on the surface of the monolithic cation exchanger obtained in the example. 4 is an EPMA measurement result showing the distribution state of sulfur in the cross section of the framework of the monolithic cation exchanger obtained in the example.

The following describes an embodiment of the present invention. This embodiment is an example of implementing the present invention, and the present invention is not limited to this embodiment.

<Method of Producing Carboxylic Acid Thioester>
The method for producing a carboxylic acid thioester according to the present embodiment is a method for producing a carboxylic acid thioester by reacting a carboxylic acid with a thiol in the presence of a solid acid catalyst, where the solid acid catalyst is a strongly acidic cation exchange resin.

As a result of intensive research, the inventors have found that carboxylic acid thioesters can be obtained through simple manufacturing procedures by reacting carboxylic acids and thiols as raw materials with a strong acid cation exchange resin, a common solid material, as a catalyst. This method can reduce the amount of waste. In addition, this method is a sustainable method.

According to the method for producing a carboxylic acid thioester according to this embodiment, since carboxylic acid and thiol are used as raw materials, the by-product is water, and the carboxylic acid thioester can be obtained economically and with less environmental impact than conventional methods. In addition, the carboxylic acid thioester can be obtained by removing the strong acid cation exchange resin, which is a solid acid catalyst, after the reaction. Therefore, the carboxylic acid thioester can be obtained by a simple production operation without performing the reaction termination step and purification step required in conventional methods. In addition, since the strong acid cation exchange resin, which is a familiar resource, is used as a catalyst, the carboxylic acid thioester can be obtained by a highly sustainable method.

[Carboxylic acid]
The carboxylic acid used as the raw material is represented by the following general formula (I): In general formula (I), ^R1 represents an optionally substituted hydrocarbon group having 1 to 30 carbon atoms.
R ¹ -COOH (I)

Examples of the hydrocarbon group having 1 to 30 carbon atoms represented by ^R1 include saturated aliphatic hydrocarbon groups, unsaturated aliphatic hydrocarbon groups such as alkenyl groups and alkynyl groups, and aromatic hydrocarbon groups. The saturated aliphatic hydrocarbon group and the unsaturated aliphatic hydrocarbon group may be linear, branched, monocyclic, or polycyclic, and the aromatic hydrocarbon group may be condensed.

The substituent that may be substituted on the hydrocarbon group having 1 to 30 carbon atoms represented by ^R1 is not particularly limited as long as it does not inhibit the reaction, and examples thereof include an alkyl group having 1 to 30 carbon atoms, an alkenyl group having 2 to 30 carbon atoms, an alkynyl group having 2 to 30 carbon atoms, an alkoxy group having 1 to 30 carbon atoms, a nitro group, a cyano group, an amino group, etc. The alkyl group, alkenyl group, alkynyl group, and alkoxy group may be linear, branched, monocyclic, or polycyclic.

[Thiol]
The thiol used as the raw material is represented by the following general formula (II): In general formula (II), ^R2 has the same meaning as ^R1 in general formula (I).
R ² -SH (II)

[Strongly acidic cation exchange resin]
The strongly acidic cation exchange resin used as a catalyst is an ion exchange resin into which a sulfonic acid group, a phosphoric acid group, or the like is introduced as a cation exchange group. The strongly acidic cation exchange resin has a cation exchange capacity of more than 1 mg equivalent/g. The strongly acidic cation exchange resin preferably has a cation exchange capacity of more than 1 mg equivalent/g and less than or equal to 5 mg equivalent/g. If the cation exchange capacity is less than 1 mg equivalent/g, the resin does not function as a catalyst in the method for producing a carboxylic acid thioester according to the present embodiment. Even if the cation exchange capacity exceeds 5 mg equivalent/g, there are cases in which an improvement in production efficiency cannot be expected.

Types of strongly acidic cation exchange resins include particulate organic porous cation exchangers and non-particulate organic porous cation exchangers. In the case of particulate organic porous cation exchangers, there are no particular limitations as long as the cation exchange capacity is greater than 1 mg equivalent/g, but examples include Amberlyst (trademark) 16 WET, Amberlyst (trademark) 15 DRY, and Amberlite (trademark) XH2071H (all manufactured by Organo Corporation).

Strongly acidic cation exchange resins may be pretreated as necessary before use. Pretreatments include conversion to free acids (H form) and drying of the strongly acidic cation exchange resin.

The amount of strongly acidic cation exchange resin used is not particularly limited as long as it is an amount that can produce a carboxylic acid thioester, but for example, it is an amount of 10 to 1000% by mass based on the raw carboxylic acid. If it is less than 10% by mass based on the raw carboxylic acid, the production efficiency may decrease, and even if 1000% by mass or more is used, a significant improvement in effect may not be expected.

[Non-particulate organic porous strongly acidic cation exchanger]
A non-particulate organic porous cation exchanger is a monolithic organic porous material having a continuous framework phase and a continuous pore phase, in which a cation exchange group has been introduced. The monolithic organic porous material has a large number of communicating holes that serve as flow paths between the frameworks. In this specification, the term "monolithic organic porous material" is also referred to simply as "monolith", the term "monolithic organic porous cation exchanger" is also referred to simply as "monolithic cation exchanger", and the term "monolithic organic porous intermediate", which is an intermediate (precursor) in the production of a monolith, is also referred to simply as "monolith intermediate".

The structure of this non-particulate organic porous cation exchanger is disclosed in JP-A-2002-306976, JP-A-2009-007550, JP-A-2009-062512, JP-A-2009-067982, and JP-A-2009-108294.

The non-particulate organic porous cation exchanger preferably comprises a continuous framework phase and a continuous pore phase, the thickness of the continuous framework being in the range of 1 to 100 μm, the average diameter of the continuous pores being in the range of 1 to 1000 μm, the total pore volume being in the range of 0.5 to 50 mL/g, the cation exchange capacity per weight in the dry state being in the range of 1 to 5 mg equivalent/g, and the cation exchange groups being distributed in the organic porous cation exchanger. The continuous framework phase and the continuous pore phase are observed by SEM images.

The thickness of the continuous skeleton of the non-particulate organic porous cation exchanger in a dry state is preferably in the range of 1 to 100 μm. The thickness of the continuous skeleton of the non-particulate organic porous cation exchanger in a dry state is determined by SEM observation. If the thickness of this continuous skeleton is less than 1 μm or more than 100 μm, the contact between the treated liquid and the monolithic cation exchanger during the reaction may be insufficient, resulting in a decrease in cation exchange performance and a decrease in reaction efficiency.

The average diameter of the continuous pores in the non-particulate organic porous cation exchanger in a dry state is preferably in the range of 1 to 1000 μm. The average diameter of the continuous pores in the non-particulate organic porous cation exchanger in a dry state is measured by mercury intrusion porosimetry and refers to the maximum value of the pore distribution curve obtained by mercury intrusion porosimetry. If the average diameter of the continuous pores is less than 1 μm or exceeds 1000 μm, contact between the treated liquid and the monolithic cation exchanger during the reaction may be insufficient, resulting in a decrease in cation exchange performance and a decrease in reaction efficiency.

The total pore volume of the non-particulate organic porous cation exchanger in a dry state is preferably in the range of 0.5 to 50 mL/g. The total pore volume of the non-particulate organic porous cation exchanger in a dry state is measured by mercury intrusion porosimetry. If this total pore volume is less than 0.5 mL/g, the contact between the treated liquid and the monolithic cation exchanger during the reaction may be insufficient. If this total pore volume exceeds 50 mL/g, the mechanical strength of the non-particulate organic porous cation exchanger may decrease, and ease of operation may be impaired.

The cation exchange capacity per weight of the non-particulate organic porous cation exchanger in a dry state is preferably in the range of 1 to 5 mg equivalents/g. The cation exchange capacity per weight of the non-particulate organic porous cation exchanger in a dry state is measured by a method such as neutralization titration or precipitation titration. If this cation exchange capacity is less than 1 mg equivalent/g, the amount of cations that can be exchanged and supported decreases, and the reaction efficiency may decrease. If this cation exchange capacity exceeds 5 mg equivalent/g, the conditions for the cation exchange group introduction reaction become severe, and the oxidative deterioration of the monolith may progress significantly.

In the non-particulate organic porous cation exchanger, the cation exchange groups introduced are preferably distributed not only on the surface of the monolith but also inside the skeleton of the monolith, i.e., in the organic porous cation exchanger, and more preferably distributed uniformly. "Cation exchange groups are uniformly distributed in the organic porous cation exchanger" means that the cation exchange groups are distributed on the surface and inside the skeleton of the organic porous cation exchanger at least on the order of μm. The distribution of the cation exchange groups is confirmed by using an electron probe microanalyzer (EPMA). If the cation exchange groups are distributed not only on the surface of the monolith but also inside the skeleton of the monolith, the physical and chemical properties of the surface and inside of the monolith can be made almost uniform, improving the durability against swelling and shrinkage.

In the non-particulate organic porous cation exchanger, the material constituting the continuous skeleton is an organic polymer material having a crosslinked structure. It is preferable that the organic polymer material contains 0.1 to 30 mol % of crosslinked structural units, and more preferably 0.1 to 20 mol % of crosslinked structural units, based on the total structural units constituting the organic polymer material.

The type of organic polymer material is not particularly limited, and examples thereof include aromatic vinyl polymers such as polystyrene, poly(α-methylstyrene), polyvinyltoluene, polyvinylbenzyl chloride, polyvinylbiphenyl, and polyvinylnaphthalene; polyolefins such as polyethylene and polypropylene; poly(halogenated polyolefins) such as polyvinyl chloride and polytetrafluoroethylene; nitrile polymers such as polyacrylonitrile; and crosslinked polymers such as (meth)acrylic polymers such as polymethyl methacrylate, polyglycidyl methacrylate, and polyethyl acrylate. The organic polymer material may be a polymer obtained by copolymerizing a single vinyl monomer and a crosslinking agent, or a polymer obtained by polymerizing multiple vinyl monomers and a crosslinking agent, or may be a blend of two or more polymers. Among these organic polymer materials, crosslinked polymers of aromatic vinyl polymers are preferred because of the ease of forming a continuous structure, the ease of introducing cation exchange groups, high mechanical strength, and high stability against acids or alkalis. In particular, styrene-divinylbenzene copolymers and vinylbenzyl chloride-divinylbenzene copolymers are preferred materials.

The cation exchange groups introduced into the non-particulate organic porous cation exchanger include sulfonic acid groups, phosphoric acid groups, etc., but sulfonic acid groups are preferred because of the ease of their production method.

[First to fifth monolithic cation exchangers]
More specific embodiments of the non-particulate organic porous cation exchanger include, for example, the first monolithic organic porous cation exchanger (monolithic cation exchanger) to the fifth monolithic organic porous cation exchanger (monolithic cation exchanger) shown below. In the following description, the description of the same configuration as the above non-particulate organic porous cation exchanger is omitted.

(First monolith cation exchanger)
The first monolithic cation exchanger has a continuous macropore structure having interconnected macropores and common openings (mesopores) with an average diameter in the range of 1 to 1000 μm in the walls of the macropores, a total pore volume in the range of 1 to 50 mL/g, a cation exchange capacity per weight in a dry state in the range of 1 to 5 mg equivalent/g, and a cation exchange group distributed in the organic porous cation exchanger.

The first monolith cation exchanger is a continuous macropore structure having continuous macropores (fine pores) as shown in Figure 1. The first monolith cation exchanger and its manufacturing method are disclosed in JP 2002-306976 A.

The first monolith cation exchanger has interconnected macropores and common openings (mesopores) located within the walls of the macropores. The mesopores have overlapping portions where the macropores overlap. The overlapping portions of the mesopores preferably have an average diameter in the dry state of 1 to 1000 μm, more preferably in the range of 10 to 200 μm, and even more preferably in the range of 20 to 200 μm. The average diameter of the openings of the first monolith in the dry state is measured by mercury intrusion porosimetry and refers to the maximum value of the pore distribution curve obtained by mercury intrusion porosimetry.

Most of such first monolith cation exchangers have an open pore structure in which the voids formed by the macropores and mesopores serve as flow paths. If the average diameter of the overlapping parts of the mesopores in a dry state is less than 1 μm or exceeds 1000 μm, the contact between the treated liquid and the monolith cation exchanger during the reaction may be insufficient, resulting in a decrease in cation exchange performance and a decrease in reaction efficiency. The overlapping of macropores is, for example, 1 to 12 in one macropore, and in most cases 3 to 10. Since the first monolith cation exchanger is the above-mentioned continuous macropore structure, it is possible to form groups of macropores and groups of common pores almost uniformly, and it is possible to significantly increase the pore volume and specific surface area compared to particle agglomeration type porous bodies such as those described in JP-A-8-252579.

The total pore volume per weight of the first monolith cation exchanger in a dry state is preferably in the range of 1 to 50 mL/g, and more preferably in the range of 2 to 30 mL/g. If the total pore volume per weight in a dry state is less than 1 mL/g, the contact area per unit cross-sectional area may become small, resulting in a decrease in processing capacity. If the total pore volume per weight in a dry state exceeds 50 mL/g, the mechanical strength may decrease, resulting in a decrease in ease of operation.

The cation exchange capacity per weight in a dry state is as described above. In addition, the fact that "cation exchange groups are distributed in the organic porous cation exchanger" is as described above.

(Method for producing the first monolithic cation exchanger)
The first monolithic cation exchanger can be produced, for example, by the following method.

For example, an oil-soluble monomer not containing a cation exchange group, a surfactant, water, and optionally a polymerization initiator can be mixed to obtain a water-in-oil emulsion. This water-in-oil emulsion can then be polymerized to form a first monolith.

The oil-soluble monomer not containing a cation exchange group used in the production of the first monolith refers to a monomer that does not contain a cation exchange group, has low solubility in water, and is lipophilic. Examples of such monomers include styrene, α-methylstyrene, vinylbenzyl chloride, ethylene, propylene, acrylonitrile, and methacrylonitrile. These monomers can be used alone or in combination of two or more. However, it is preferable to select a crosslinkable monomer such as divinylbenzene as at least one component of the oil-soluble monomer and set its content in the range of, for example, 0.3 to 10 mol%, preferably 0.3 to 5 mol%, of the total oil-soluble monomers, in order to quantitatively introduce the cation exchange group in a later step and ensure sufficient mechanical strength for practical use.

The surfactant used in the production of the first monolith is not particularly limited as long as it can form a water-in-oil (W/O) emulsion when an oil-soluble monomer not containing a cation exchange group is mixed with water. Examples of the surfactant include non-cationic surfactants such as sorbitan monooleate, sorbitan monolaurate, and polyoxyethylene nonylphenyl ether; anionic surfactants such as potassium oleate, sodium dodecylbenzenesulfonate, and dioctyl sodium sulfosuccinate; cationic surfactants such as distearyl dimethyl ammonium chloride; and amphoteric surfactants such as lauryl dimethyl betaine. These surfactants can be used alone or in combination of two or more. A water-in-oil emulsion is an emulsion in which the oil phase is the continuous phase and water droplets are dispersed therein. The amount of surfactant added may be, for example, in the range of about 2 to 70% of the total amount of the oil-soluble monomer and the surfactant. In order to control the shape and size of the monolith's bubbles, alcohols such as methanol and stearyl alcohol; carboxylic acids such as stearic acid; hydrocarbons such as octane, dodecane, and toluene; and cyclic ethers such as tetrahydrofuran and dioxane can also be present in the system.

In the manufacture of the first monolith, when forming a monolith by polymerization, a polymerization initiator that is used as necessary is preferably a compound that generates radicals when exposed to heat and light. The polymerization initiator may be water-soluble or oil-soluble, and examples include azobisisobutyronitrile, azobisdimethylvaleronitrile, azobiscyclohexanenitrile, azobiscyclohexanecarbonitrile, benzoyl peroxide, potassium persulfate, ammonium persulfate, hydrogen peroxide-ferrous chloride, sodium persulfate-acidic sodium sulfite, and tetramethylthiuram disulfide. However, in some cases, there are systems in which polymerization proceeds only by heating or exposure to light without the addition of a polymerization initiator, and in such systems, it is not necessary to add a polymerization initiator.

In the production of the first monolith, the polymerization conditions for polymerizing the water-in-oil emulsion can be selected from various conditions depending on the type of monomer, initiator system, etc. When azobisisobutyronitrile, benzoyl peroxide, potassium persulfate, etc. are used as the polymerization initiator, for example, the polymerization can be carried out by heating in a sealed container under an inert atmosphere at 30 to 100°C for 1 to 48 hours. When hydrogen peroxide-ferrous chloride, sodium persulfate-acidic sodium sulfite, etc. are used as the polymerization initiator, the polymerization can be carried out in a sealed container under an inert atmosphere at 0 to 30°C for 1 to 48 hours. After the polymerization is completed, the contents are removed and subjected to Soxhlet extraction with a solvent such as isopropanol to remove unreacted monomers and residual surfactants, thereby obtaining the first monolith.

Methods for introducing cation exchange groups into the first monolith include, for example, the following methods (1) and (2). (1) Instead of a monomer that does not contain a cation exchange group, a monomer that contains a cation exchange group, for example, the oil-soluble monomer that does not contain the above-mentioned cation exchange group, can be polymerized with a monomer into which a cation exchange group has been introduced, to produce a monolith cation exchanger in one step. (2) A monomer that does not contain a cation exchange group can be polymerized to form the first monolith, and then a cation exchange group can be introduced.

There are no particular limitations on the method for introducing cation exchange groups into the first monolith, and known methods such as polymer reactions and graft polymerization can be used. For example, a method of reacting a monolith of a styrene-divinylbenzene copolymer with concentrated sulfuric acid, or a method of reacting a monolith of a styrene-divinylbenzene copolymer with chlorosulfonic acid in an organic solvent can be used.

(Second Monolith Cation Exchanger)
The second monolith cation exchanger is a monolith cation exchanger in which organic polymer particles having an average particle size in the range of 1 to 50 μm are aggregated to form a three-dimensionally continuous skeleton, the skeleton having three-dimensionally continuous pores having an average diameter in the range of 20 to 100 μm between the skeletons, a total pore volume in the range of 1 to 10 mL/g, a cation exchange capacity per weight in a dry state in the range of 1 to 5 mg equivalent/g, and cation exchange groups distributed in the organic porous cation exchanger.

The second monolith cation exchanger is a particle aggregate structure formed by agglomerating particles, as shown in Figure 2. The second monolith cation exchanger and its manufacturing method are disclosed in JP 2009-007550 A.

The second monolith cation exchanger has a three-dimensionally continuous skeleton formed by the aggregation of organic polymer particles having crosslinked structural units and an average particle diameter in the dry state of preferably 1 to 50 μm, more preferably 1 to 30 μm. The second monolith cation exchanger has three-dimensionally continuous pores (continuous pores) between the continuous skeletons, the average diameter in the dry state of preferably 20 to 100 μm, more preferably 20 to 90 μm. An SEM photograph is taken of an arbitrarily selected portion of the cross section of the second monolith cation exchanger in a dry state, the diameters of the organic polymer particles of all the particles in the SEM photograph are measured, and the average value of these is taken as the average particle diameter. The average diameter of the continuous pores in the dry state is determined by mercury intrusion porosimetry, as in the first monolith cation exchanger.

If the average particle diameter of the organic polymer particles is less than 1 μm in a dry state, the average diameter of the continuous pores between the skeletons may become small, less than 20 μm in a dry state. If the average particle diameter of the organic polymer particles exceeds 50 μm, the contact between the treated liquid and the monolith cation exchanger during the reaction may be insufficient, resulting in a decrease in cation exchange performance and a decrease in reaction efficiency. In addition, if the average diameter of the aforementioned continuous pores is less than 20 μm or exceeds 100 μm in a dry state, the contact between the treated liquid and the monolith cation exchanger during the reaction may be insufficient, resulting in a decrease in cation exchange performance and a decrease in reaction efficiency.

The total pore volume per weight of the second monolith cation exchanger in a dry state is preferably in the range of 1 to 10 mL/g. If the total pore volume is less than 1 mL/g, the contact amount per unit cross-sectional area will be small, and the processing capacity may decrease. If the total pore volume exceeds 10 mL/g, the mechanical strength will decrease, and ease of operation may be impaired.

The cation exchange capacity per weight in a dry state is as described above. In addition, the fact that "cation exchange groups are distributed in the organic porous cation exchanger" is as described above.

(Method for producing the second monolithic cation exchanger)
The second monolithic cation exchanger can be prepared, for example, by the following method.

For example, the second monolith can be obtained by mixing a vinyl monomer, a specific amount of a cross-linking agent, an organic solvent, and a polymerization initiator, and polymerizing the mixture in a stationary state.

The vinyl monomer used in producing the second monolith is the same as the monomer used in producing the first monolith.

The crosslinking agent used in the production of the second monolith preferably contains at least two polymerizable vinyl groups in the molecule and is highly soluble in an organic solvent. Examples of the crosslinking agent include divinylbenzene, divinylbiphenyl, and ethylene glycol dimethacrylate. These crosslinking agents can be used alone or in combination of two or more. Preferred crosslinking agents are aromatic polyvinyl compounds such as divinylbenzene, divinylnaphthalene, and divinylbiphenyl, from the viewpoints of high mechanical strength and stability against hydrolysis. The amount of crosslinking agent used relative to the total amount of vinyl monomer and crosslinking agent ({crosslinking agent/(vinyl monomer+crosslinking agent)}×100) is, for example, in the range of 1 to 5 mol%, preferably in the range of 1 to 4 mol%.

The organic solvent used in the production of the second monolith is an organic solvent that dissolves the vinyl monomer and the crosslinking agent but hardly dissolves the polymer produced by polymerization of the vinyl monomer, in other words, it is a poor solvent for the polymer produced by polymerization of the vinyl monomer. For example, when the vinyl monomer is styrene, this organic solvent is an alcohol such as methanol, butanol, octanol, etc.; a chain ether such as diethyl ether, ethylene glycol dimethyl ether, etc.; a chain saturated hydrocarbon such as hexane, octane, decane, etc.

The polymerization initiator used in the production of the second monolith is preferably a compound that generates radicals by heat and light irradiation. The polymerization initiator is preferably oil-soluble. Examples of the polymerization initiator include 2,2'-azobis(isobutyronitrile), 2,2'-azobis(2,4-dimethylvaleronitrile), 2,2'-azobis(2-methylbutyronitrile), 2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile), 2,2'-azobisisobutyric acid dimethyl, 4,4'-azobis(4-cyanovaleric acid), 1,1'-azobis(cyclohexane-1-carbonitrile), benzoyl peroxide, lauroyl peroxide, potassium persulfate, ammonium persulfate, and tetramethylthiuram disulfide. The amount of polymerization initiator used relative to the total amount of vinyl monomer and crosslinker ({polymerization initiator/(vinyl monomer+crosslinker)}×100) is, for example, in the range of about 0.01 to 5 mol%.

When using, for example, 2,2'-azobis(isobutyronitrile), 2,2'-azobis(2,4-dimethylvaleronitrile), benzoyl peroxide, lauroyl peroxide, potassium persulfate, or the like as a polymerization initiator in the production of the second monolith, the polymerization can be carried out, for example, by heating in a sealed container under an inert atmosphere at 30 to 100°C for 1 to 48 hours. After the polymerization is completed, the contents are removed and extracted with a solvent such as acetone to remove unreacted vinyl monomer and organic solvent, to obtain the second monolith.

In the production of the second monolith, organic polymer particles with an average particle size of 1 to 50 μm can be aggregated by adjusting the polymerization conditions, such as increasing the amount of crosslinking agent, increasing the monomer concentration, and increasing the temperature. By using a specific amount of crosslinking agent relative to the total amount of vinyl monomer and crosslinking agent, three-dimensionally continuous pores with an average diameter of 20 to 100 μm can be formed between the skeletons. By polymerizing under conditions in which the amount of organic solvent used relative to the total amount of organic solvent, monomer, and crosslinking agent used ({organic solvent/(organic solvent + monomer + crosslinking agent)} x 100) is in the range of, for example, 30 to 80% by weight, preferably 40 to 70% by weight, the total pore volume of the monolith can be set to 1 to 5 mL/g.

The method for introducing cation exchange groups into the second monolith is the same as the method for introducing cation exchange groups into the first monolith.

(Third monolith cation exchanger)
The third monolith cation exchanger is a monolith cation exchanger having a continuous macropore structure in which bubble-like macropores overlap each other and the overlapping portions form openings with an average diameter in the range of 30 to 300 μm, a total pore volume in the range of 0.5 to 10 mL/g, a cation exchange capacity per weight in a dry state in the range of 1 to 5 mg equivalent/g, cation exchange groups distributed in the organic porous cation exchanger, and in an SEM image of a cut surface of the continuous macropore structure, the area of the framework portion appearing on the cross section is in the range of 25 to 50% of the image area.

As shown in FIG. 3, the third monolith cation exchanger has a continuous macropore structure, similar to the first monolith cation exchanger. The third monolith cation exchanger and its manufacturing method are disclosed in JP 2009-062512 A.

The continuous pores have overlapping portions where macropores overlap each other. In the dry state, the overlapping portions preferably have an average diameter in the range of 30 to 300 μm, more preferably in the range of 30 to 200 μm, and even more preferably in the range of 40 to 100 μm. This average diameter is measured by mercury intrusion porosimetry and refers to the maximum value of the pore distribution curve obtained by mercury intrusion porosimetry. If the average diameter of the openings in the dry state is less than 30 μm or exceeds 300 μm, contact between the treated liquid and the monolith cation exchanger during the reaction will be insufficient, reducing the cation exchange performance and reaction efficiency.

In the third monolith cation exchanger, in an SEM image of a cut surface of the continuous macropore structure in a dry state, the area of the skeleton portion appearing on the cross section is, for example, in the range of 25 to 50% of the image area, and preferably in the range of 25 to 45%. If the area of the skeleton portion appearing on the cross section is less than 25% of the image area, the skeleton becomes thin, the mechanical strength decreases, and ease of operation may be impaired. If the area of the skeleton portion appearing on the cross section is more than 50% of the image area, the skeleton becomes too thick, and contact between the treated liquid and the monolith cation exchanger during the reaction may be insufficient, resulting in a decrease in reaction efficiency.

The conditions for obtaining an SEM image may be such that the skeletal portion appearing on the cross section of the cut surface is clearly visible, for example, a magnification of 100 to 600 and a photographic area of about 150 mm x 100 mm. SEM observation is preferably performed using three or more images taken at different cut locations or photographed locations at any location on any cut surface of the third monolith cation exchanger, eliminating subjectivity. The third monolith cation exchanger to be cut is in a dry state. The skeletal portion of the cut surface in the SEM image will be explained with reference to Figures 3 and 4. In Figures 3 and 4, the part that is roughly irregular and appears on the cross section is the "skeletal portion appearing on the cross section (reference number 12)," the circular pores appearing in Figure 3 are openings (mesopores), and those with a relatively large curvature or curved surface are macropores (reference number 13 in Figure 4). The area of the skeletal portion appearing on the cross section of Figure 4 is 28% of the rectangular image area 11.

In SEM images, methods for measuring the area of the skeleton appearing in the cross section of the cut surface include a method in which the skeleton is identified by known computer processing or the like, and then a calculation is performed automatically using a computer or the like, or a manual calculation is performed. An example of a manual calculation is a method in which irregular shapes are replaced with an aggregate of squares, triangles, circles, trapezoids, etc., and these are stacked to determine the area.

The total pore volume per weight of the third monolith cation exchanger in a dry state is preferably in the range of 0.5 to 10 mL/g, more preferably in the range of 0.8 to 8 mL/g. If the total pore volume is less than 0.5 mL/g, the amount of permeating fluid per unit cross-sectional area will be small, and the processing capacity may decrease. If the total pore volume exceeds 10 mL/g, the mechanical strength may decrease, and the ease of operation may be impaired. Furthermore, the contact efficiency between the treated liquid and the monolith cation exchanger during the reaction may decrease.

The cation exchange capacity per weight in a dry state is as described above. In addition, the fact that "cation exchange groups are distributed in the organic porous cation exchanger" is as described above.

(Third method for producing monolithic cation exchanger)
The third monolithic cation exchanger can be produced, for example, by the following method.

For example, first, a water-in-oil emulsion is prepared by stirring a mixture of an oil-soluble monomer not containing a cation exchange group, a surfactant, and water. Next, the third monolith can be obtained by carrying out the following steps I, II, and III. In step I, the water-in-oil emulsion is polymerized to obtain a monolithic organic porous intermediate (hereinafter also referred to as monolith intermediate (3)) having a continuous macropore structure with a total pore volume in the range of 5 to 16 mL/g. In step II, a mixture is prepared containing a vinyl monomer, a crosslinking agent having at least two or more vinyl groups in one molecule, an organic solvent that dissolves the vinyl monomer and the crosslinking agent but not the polymer produced by polymerization of the vinyl monomer, and a polymerization initiator. In step III, the mixture obtained in step II is left to stand and polymerized in the presence of the monolith intermediate (3) obtained in step I to obtain a third monolith having a skeleton thicker than that of the monolith intermediate (3).

Step I is the same as the manufacturing method of the first monolith cation exchanger.

The monolith intermediate (3) obtained in step I has a continuous macropore structure. When this is present in a polymerization system, a porous structure with a sturdy skeleton can be formed using the structure of the monolith intermediate (3) as a model. The crosslink density of the polymer material is preferably in the range of, for example, 0.3 to 10 mol %, and preferably 0.3 to 5 mol %, of crosslinked structural units relative to the total structural units constituting the polymer material of the monolith intermediate (3).

The total pore volume per weight of the monolith intermediate (3) obtained in step I in a dry state is, for example, in the range of 5 to 16 mL/g, preferably in the range of 6 to 16 mL/g. In order to bring the total pore volume of the monolith intermediate (3) into the above numerical range, the ratio of monomer to water may be, for example, in the range of approximately 1:5 to 1:20.

The monolith intermediate (3) obtained in step I has an average diameter of the openings (mesopores) where the macropores overlap, in the dry state, for example, in the range of 20 to 200 μm.

Step II is a step of preparing a mixture containing a vinyl monomer, a crosslinking agent having at least two vinyl groups in one molecule, an organic solvent that dissolves the vinyl monomer and the crosslinking agent but not the polymer produced by polymerization of the vinyl monomer, and a polymerization initiator. Note that the order of steps I and II may be any.

The vinyl monomer used in step II may be any lipophilic vinyl monomer that contains a polymerizable vinyl group in the molecule and has high solubility in organic solvents, and it is preferable to select a vinyl monomer that produces the same or similar polymer material as the monolith intermediate (3) that is coexistent in the polymerization system. Specific examples of these vinyl monomers are the same as the vinyl monomers used in the production of the first monolith.

The amount of vinyl monomer used in step II is, for example, 3 to 50 times, and preferably 4 to 40 times, by weight relative to the monolith intermediate (3) that is allowed to coexist during polymerization.

The cross-linking agent used in step II is the same as the cross-linking agent used in the production of the second monolith.

The organic solvent used in step II is the same as the organic solvent used in the production of the second monolith. It is preferable to use the organic solvent in such an amount that the concentration of the vinyl monomer is, for example, 30 to 80% by weight.

The polymerization initiator used in step II is the same as the polymerization initiator used in the production of the second monolith.

In step III, for example, the mixture obtained in step II is left to stand and polymerized in the presence of the monolith intermediate (3) obtained in step I, to obtain a third monolith having a skeleton thicker than that of the monolith intermediate (3). When the monolith intermediate (3) having a continuous macropore structure is present in the above polymerization system, the third monolith can be obtained.

In step III, for example, the monolith intermediate (3) is placed in a reaction vessel in a state where it is impregnated with the mixture (solution). The mixture obtained in step II and the monolith intermediate (3) may be mixed in a ratio, for example, such that the amount of vinyl monomer added is in the range of 3 to 50 times, preferably 4 to 40 times, by weight, relative to the monolith intermediate (3). In the reaction vessel, the vinyl monomer and crosslinking agent in the mixture are adsorbed and distributed to the skeleton of the stationary monolith intermediate, and polymerization proceeds within the skeleton of the monolith intermediate (3).

In step III, various polymerization conditions are selected depending on the type of monomer, the type of polymerization initiator, etc. For example, when 2,2'-azobis(isobutyronitrile), 2,2'-azobis(2,4-dimethylvaleronitrile), benzoyl peroxide, lauroyl peroxide, potassium persulfate, etc. are used as the polymerization initiator, the polymerization may be carried out, for example, at 30 to 100°C for 1 to 48 hours in a sealed container under an inert atmosphere. By the thermal polymerization, the vinyl monomer and crosslinking agent adsorbed and distributed to the skeleton of the monolith intermediate (3) are polymerized within the skeleton, making the skeleton thicker. After the polymerization is completed, the contents are removed, and the third monolith can be obtained by extraction with a solvent such as acetone to remove the unreacted vinyl monomer and organic solvent.

The third monolith cation exchanger can be obtained, for example, by carrying out step IV in which a cation exchange group is introduced into the third monolith obtained in step III. The method for introducing a cation exchange group into the third monolith is the same as the method for introducing a cation exchange group into the first monolith.

(Fourth monolith cation exchanger)
The fourth monolith cation exchanger is a bicontinuous structure consisting of a three-dimensionally continuous skeleton having a thickness in the range of 1 to 60 μm and composed of an aromatic vinyl polymer containing crosslinked structural units in the range of 0.1 to 5.0 mol % of all structural units into which cation exchange groups have been introduced, and three-dimensionally continuous pores having an average diameter in the range of 10 to 200 μm between the skeletons, the total pore volume being in the range of 0.5 to 10 mL/g, and the cation exchange capacity per weight in a dry state being in the range of 1 to 5 mg equivalent/g, and the cation exchange groups being distributed in the organic porous cation exchanger.

As shown in Figures 5 and 6, the fourth monolith cation exchanger has a continuous skeleton phase 1 (continuous skeleton) and a continuous pore phase 2 (continuous pores), which are intertwined to form a bicontinuous structure 10 that is three-dimensionally continuous. Compared to the first and second monoliths described above, the pore phase 2 is highly continuous and has almost no deviation in size. The fourth monolith cation exchanger is considered to have high mechanical strength because of its thick skeleton. The fourth monolith cation exchanger and its manufacturing method are disclosed in JP 2009-067982 A.

The continuous skeleton is composed of a vinyl polymer (such as an aromatic vinyl polymer) containing 0.1 to 5.0 mol% of crosslinked structural units among all structural units into which cation exchange groups have been introduced, and the thickness of the continuous skeleton is three-dimensionally continuous, for example, in the range of 1 to 60 μm, preferably in the range of 3 to 58 μm, in a dry state. If the crosslinked structural units are less than 0.1 mol%, the mechanical strength may be insufficient, and if they exceed 5.0 mol%, the structure of the porous body may easily deviate from the co-continuous structure. If the thickness of this continuous skeleton is less than 1 μm or more than 60 μm in a dry state, the contact between the treated liquid and the monolithic cation exchanger during the reaction may be insufficient, resulting in a decrease in cation exchange performance and a decrease in reaction efficiency.

The continuous pores are three-dimensionally continuous between the continuous skeletons, with an average diameter in the range of 10 to 200 μm, preferably 15 to 180 μm, in a dry state. If the average diameter of these continuous pores is less than 10 μm or exceeds 200 μm in a dry state, contact between the treated liquid and the monolith cation exchanger during the reaction will be insufficient, resulting in reduced cation exchange performance and reduced reaction efficiency.

The aforementioned average diameter is measured by mercury intrusion porosimetry and refers to the maximum value of the pore distribution curve obtained by mercury intrusion porosimetry. The thickness of the continuous skeleton in a dry state is determined by SEM observation of the fourth monolith cation exchanger in a dry state. Specifically, SEM observation of the fourth monolith cation exchanger in a dry state is performed at least three times, the thickness of the skeleton in the obtained image is measured, and the average value of these is taken as the thickness of the continuous skeleton. Note that the skeleton is rod-shaped and has a circular cross-sectional shape, but may also include ones with different cross-sections such as elliptical cross-sectional shapes. In this case, the thickness is the average of the minor axis and major axis.

The total pore volume per weight of the fourth monolith cation exchanger in a dry state is, for example, in the range of 0.5 to 10 mL/g. If the total pore volume is less than 0.5 mL/g, the amount of permeating fluid per unit cross-sectional area will be small, and the processing capacity may decrease. If the total pore volume exceeds 10 mL/g, the mechanical strength may decrease, and ease of operation may be impaired. Furthermore, the contact efficiency between the treated liquid and the monolith cation exchanger during the reaction may decrease.

Examples of vinyl polymers (aromatic vinyl polymers) that constitute the continuous backbone include polystyrene, poly(α-methylstyrene), polyvinylbenzyl chloride, and the like. The above polymers may be polymers obtained by copolymerizing a single vinyl monomer and a crosslinking agent, or polymers obtained by polymerizing multiple vinyl monomers and a crosslinking agent, or may be blends of two or more types of polymers. Among these organic polymer materials, styrene-divinylbenzene copolymers and vinylbenzyl chloride-divinylbenzene copolymers are preferred because of the ease of forming a co-continuous structure, the ease of introducing cation exchange groups, high mechanical strength, and high stability against acids or alkalis.

The cation exchange capacity per weight in a dry state is as described above. In addition, the fact that "cation exchange groups are distributed in the organic porous cation exchanger" is as described above.

(Fourth method for producing monolithic cation exchanger)
The fourth monolithic cation exchanger can be produced, for example, by the following method.

For example, the fourth monolith can be obtained by preparing a water-in-oil emulsion and then carrying out the following steps I to III. In step I, for example, the water-in-oil emulsion can be polymerized to obtain a monolithic organic porous intermediate (hereinafter, monolith intermediate (4)) having a continuous macropore structure with a total pore volume of, for example, more than 16 mL/g and 30 mL/g or less. In step II, for example, a mixture is prepared containing an aromatic vinyl monomer, a crosslinking agent in the range of, for example, 0.3 to 5 mol % of the total oil-soluble monomer having at least two or more vinyl groups in one molecule, an organic solvent that dissolves the aromatic vinyl monomer and the crosslinking agent but not the polymer produced by polymerization of the aromatic vinyl monomer, and a polymerization initiator. In step III, for example, the mixture obtained in step II is left to stand and polymerized in the presence of the monolith intermediate (4) obtained in step I to obtain the fourth monolith.

Step I in the fourth monolith manufacturing method is the same as the first monolith cation exchanger manufacturing method.

The monolith intermediate (4) obtained in step I is, for example, an organic polymer material having a crosslinked structure, preferably an aromatic vinyl polymer. The crosslink density of this polymer material is, for example, in the range of 0.1 to 5 mol %, preferably 0.3 to 3 mol %, of crosslinked structural units relative to the total structural units constituting the polymer material.

The type of polymer material of the monolith intermediate (4) is the same as the type of polymer material of the monolith intermediate (3) in the third monolith manufacturing method.

The total pore volume per weight of the monolith intermediate (4) obtained in step I in a dry state is, for example, more than 16 mL/g and not more than 30 mL/g, preferably more than 16 mL/g and not more than 25 mL/g. As shown in FIG. 7, the monolith intermediate (4) has a skeleton that is close to a rod shape. When this is allowed to coexist in a polymerization system, a porous body with a cocontinuous structure can be formed using the structure of the monolith intermediate (4) as a mold.

The monolith intermediate (4) obtained in step I has an average diameter of the openings (mesopores) where the macropores overlap, in the dry state, for example, in the range of 5 to 100 μm.

Step II in the fourth monolith manufacturing method is a step of preparing a mixture containing, for example, an aromatic vinyl monomer, a crosslinking agent in the range of, for example, 0.3 to 5 mol % of all oil-soluble monomers having at least two or more vinyl groups in one molecule, an organic solvent that dissolves the aromatic vinyl monomer and the crosslinking agent but not the polymer produced by polymerization of the aromatic vinyl monomer, and a polymerization initiator. Note that the order of steps I and II may be any.

The aromatic vinyl monomer used in step II is not particularly limited as long as it is an aromatic vinyl monomer that contains a polymerizable vinyl group in the molecule and is lipophilic and highly soluble in an organic solvent, but it is preferable to select a vinyl monomer that produces the same or similar polymer material as the monolith intermediate (4) that is coexisted in the polymerization system. Specific examples of these vinyl monomers include styrene, α-methylstyrene, vinyltoluene, vinylbenzyl chloride, vinylbiphenyl, vinylnaphthalene, etc. These monomers can be used alone or in combination of two or more. The aromatic vinyl monomers that are preferably used are styrene, vinylbenzyl chloride, etc.

The amount of aromatic vinyl monomer used in step II is, for example, in the range of 5 to 50 times, and preferably in the range of 5 to 40 times, by weight, the amount of monolith intermediate (4) that is allowed to coexist during polymerization.

The crosslinking agent used in step II preferably contains at least two polymerizable vinyl groups in the molecule and is highly soluble in an organic solvent. Examples of crosslinking agents include divinylbenzene, divinylnaphthalene, divinylbiphenyl, ethylene glycol dimethacrylate, trimethylolpropane triacrylate, butanediol diacrylate, etc. These crosslinking agents can be used alone or in combination of two or more. The amount of crosslinking agent used is, for example, in the range of 0.3 to 5 mol% relative to the total amount of vinyl monomer and crosslinking agent (total oil-soluble monomer), and particularly in the range of 0.3 to 3 mol%. It is preferable to use the crosslinking agent in an amount that is approximately equal to the crosslink density of the monolith intermediate (4) that is coexistent during the vinyl monomer/crosslinking agent polymerization. If the amounts of the two are too far apart, the crosslink density distribution in the produced monolith will be biased, and when a cation exchange group is introduced, cracks may be more likely to occur during the cation exchange group introduction reaction.

The organic solvent used in the II step is, for example, an organic solvent in which the aromatic vinyl monomer and the crosslinking agent dissolve but not the polymer produced by polymerization of the aromatic vinyl monomer, in other words, a poor solvent for the polymer produced by polymerization of the aromatic vinyl monomer. For example, when the aromatic vinyl monomer is styrene, the organic solvent is alcohols such as methanol, butanol, octanol, etc.; chain (poly)ethers such as diethyl ether, polyethylene glycol, polypropylene glycol, etc.; chain saturated hydrocarbons such as hexane, heptane, octane, etc.; esters such as ethyl acetate, isopropyl acetate, ethyl propionate, etc. In addition, even if it is a good solvent for polystyrene such as dioxane, THF, or toluene, it can be used as an organic solvent when it is used together with the poor solvent and the amount used is small. The amount of these organic solvents used can be such that the concentration of the aromatic vinyl monomer is, for example, 30 to 80% by weight. If the amount of organic solvent used deviates from the above range and the aromatic vinyl monomer concentration is less than 30% by weight, the polymerization rate may decrease or the monolith structure after polymerization may deviate from the range of the fourth monolith. On the other hand, if the aromatic vinyl monomer concentration exceeds 80% by weight, polymerization may proceed too far.

The polymerization initiator used in step II in the fourth monolith manufacturing method is the same as the polymerization initiator used in step II in the third monolith manufacturing method.

Step III in the fourth monolith manufacturing method is, for example, a step in which the mixture obtained in step II is left to stand and polymerized in the presence of the monolith intermediate (4) obtained in step I, to change the continuous macropore structure of the monolith intermediate (4) to a co-continuous structure, thereby obtaining a fourth monolith that is a co-continuous structure monolith.

In step III, for example, the monolith intermediate (4) is placed in a reaction vessel in a state of being impregnated with the mixture (solution). As described above, the mixture obtained in step II and the monolith intermediate (4) may be mixed in such a ratio that the amount of aromatic vinyl monomer added is, for example, in the range of 5 to 50 times, preferably in the range of 5 to 40 times, by weight, relative to the monolith intermediate (4). This makes it possible to obtain a fourth monolith with a bicontinuous structure in which pores of appropriate size are three-dimensionally continuous and a thick skeleton is three-dimensionally continuous. In the reaction vessel, the aromatic vinyl monomer and crosslinking agent in the mixture are adsorbed and distributed to the skeleton of the stationary monolith intermediate (4), and polymerization proceeds within the skeleton of the monolith intermediate (4).

The polymerization conditions for step III in the fourth monolith manufacturing method are the same as those described for step III in the third monolith manufacturing method. The fourth monolith cation exchanger can be obtained by carrying out step IV to introduce a cation exchange group into the fourth monolith obtained in step III. The method for introducing a cation exchange group into the fourth monolith is the same as the method for introducing a cation exchange group into the first monolith.

(Fifth monolithic cation exchanger)
The fifth monolith cation exchanger is a monolith cation exchanger which comprises a continuous framework phase and a continuous pore phase, the framework having a plurality of particulate bodies with diameters in the range of 4 to 40 μm fixed to the surface or a plurality of protrusions with sizes in the range of 4 to 40 μm formed on the framework surface of the organic porous body, the average diameter of the continuous pores being in the range of 10 to 200 μm, the total pore volume being in the range of 0.5 to 10 mL/g, the cation exchange capacity per weight in a dry state being in the range of 1 to 5 mg equivalent/g, and the cation exchange groups being distributed in the organic porous cation exchanger.

The fifth monolith cation exchanger is a composite structure having an organic porous body with a continuous skeletal phase and a continuous pore phase, and further having a plurality of particle bodies or a plurality of protrusions, and is a composite structure having a large number of particle bodies or a large number of protrusions. The fifth monolith cation exchanger and a method for producing it are disclosed in JP 2009-108294 A.

The multiple particulate bodies are fixed to the skeletal surface of the organic porous body, and their diameters are, for example, in the range of 4 to 40 μm. The multiple protrusions are formed on the skeletal surface of the organic porous body, and their size in a dry state is, for example, in the range of 4 to 40 μm. The diameter of the particulate bodies or the size of the protrusions is preferably in the range of 4 to 30 μm, and more preferably in the range of 4 to 20 μm. In this specification, "particulate bodies" and "protrusions" are collectively referred to as "particulate bodies, etc.".

The average diameter of the interconnected pores in a dry state is preferably in the range of 10 to 200 μm.

The continuous skeletal phase and continuous pore phase of the fifth monolith cation exchanger are observed in SEM images. The basic structure of the fifth monolith cation exchanger includes a continuous macropore structure and a co-continuous structure. The skeletal phase of the fifth monolith cation exchanger appears as a continuous columnar structure, a continuous concave wall structure, or a composite of these, and has a shape that is clearly different from particulate or protruding shapes.

The fifth monolith cation exchanger includes the fifth monolith cation exchanger and the fifth monolith cation exchanger. The fifth monolith cation exchanger is a continuous macropore structure in which bubble-like macropores overlap each other, and the overlapping portions form openings with an average diameter of, for example, 10 to 120 μm in a dry state. The fifth monolith cation exchanger is a bicontinuous structure consisting of a three-dimensionally continuous skeleton with a continuous skeleton thickness of, for example, 0.8 to 40 μm in a dry state, and three-dimensionally continuous pores with an average diameter of, for example, 8 to 80 μm in a dry state between the skeletons. The monoliths of the fifth monolith cation exchangers before the introduction of the cation exchange groups are called the fifth monoliths. The aforementioned average diameter and the thickness of the continuous skeleton in a dry state are determined by the same measurement method as for the fourth monolith cation exchanger.

As shown in (A) to (E) in FIG. 8, the protrusions protruding from the skeleton surface 21 are the protrusions 22a to 22e. As shown in (A), the protrusion 22a has a shape close to a granule. As shown in (B), the protrusion 22b is semispherical. As shown in (C), the protrusion 22c has a shape like a protuberance on the skeleton surface. As shown in (D), the length of the protrusion 22d in the planar direction of the skeleton surface 21 is longer than the length of the protrusion 22d in the direction perpendicular to the skeleton surface 21. As shown in (E), the protrusion 22e has a shape that protrudes in multiple directions. The size of the protrusion is the length of the part where the width of each protrusion is the largest in the SEM image. As shown in FIG. 9, in the fifth monolith cation exchanger, multiple protrusions are formed on the skeleton surface of the organic porous body.

In the fifth monolith cation exchanger, the proportion of particles in the range of 4 to 40 μm in a dry state among all particles is, for example, 70% or more, preferably 80% or more. The proportion of the particles refers to the proportion of particles of a specific size in the total number of particles in a dry state. The surface of the skeleton phase is covered by all particles, for example, 40% or more, preferably 50% or more. The coverage of the surface of the skeleton layer by all particles refers to the area ratio on the SEM image when the surface is observed by SEM, that is, the area ratio when the surface is viewed in plan. If the size of the particles covering the wall surface or skeleton deviates from the above range, the effect of improving the contact efficiency between the fluid and the skeleton surface and inside the skeleton of the monolith cation exchanger may be easily reduced.

The fifth monolith cation exchanger in a dry state is observed at least three times under SEM, and the diameter or size of all particles in the SEM image in the dry state is calculated in the entire field of view to confirm whether particles having a diameter or size in the range of, for example, 4 to 40 μm are observed. If such particles are observed in the entire field of view, it is determined that particles having a diameter or size in the range of, for example, 4 to 40 μm in the dry state are formed on the skeleton surface of the fifth monolith cation exchanger. In addition, the diameter or size of all particles in the SEM image in the dry state is calculated for each field of view according to the above, and the proportion of particles having a diameter or size in the range of, for example, 4 to 40 μm in the dry state in the total particles is determined for each field of view. If the proportion of particles having a diameter or size in the range of, for example, 4 to 40 μm in the dry state in the total particles is 70% or more in the entire field of view, it is determined that the proportion of particles having a diameter or size in the range of, for example, 4 to 40 μm in the dry state in the total particles formed on the skeleton surface of the fifth monolith cation exchanger is 70% or more. In addition, the coverage rate of the surface of the skeleton layer by all particles, etc. in the SEM image is determined for each field of view according to the above, and if the coverage rate of the surface of the skeleton layer by all particles, etc. in the entire field of view is 40% or more, it is determined that the coverage rate of the surface of the skeleton layer of the fifth monolith cation exchanger by all particles, etc. is 40% or more.

In the fifth monolith cation exchanger, if the coverage rate of the skeletal phase surface by particulate matter or the like is less than 40%, the effect of improving the contact efficiency between the treated liquid and the inside and surface of the skeletal structure of the monolith cation exchanger may be easily reduced. An example of a method for measuring the coverage rate by the particulate matter or the like is image analysis using SEM images of the fifth monolith cation exchanger.

The total pore volume per weight of the fifth monolith cation exchanger in a dry state is, for example, in the range of 0.5 to 10 mL/g, preferably in the range of 0.8 to 8 mL/g. If the total pore volume is less than 0.5 mL/g, the amount of permeating fluid per unit cross-sectional area will be small, and the processing capacity may decrease. If the total pore volume exceeds 10 mL/g, the mechanical strength may decrease, and the ease of operation may be impaired. Furthermore, the contact efficiency between the treated liquid and the monolith cation exchanger during the reaction may decrease.

In the fifth monolith cation exchanger, the crosslink density of the polymer material constituting the skeleton may be, for example, in the range of 0.3 to 10 mol %, preferably 0.3 to 5 mol %, of crosslinked structural units relative to the total structural units constituting the polymer material. The organic polymer material constituting the skeleton of the fifth monolith cation exchanger is the same as that of the first monolith cation exchanger.

In the fifth monolithic cation exchanger, the material constituting the skeletal phase of the organic porous material and the particulate matter formed on the surface of the skeletal phase may be made of the same material with a continuous structure of the same kind, or may be made of different materials with a continuous structure of different kinds. Examples of different materials with a continuous structure of different kinds include materials in which different types of vinyl monomers are used, and materials in which the types of vinyl monomers and crosslinking agents are the same but the mixing ratios of each agent are different.

The fifth monolith cation exchanger has a thickness of, for example, 1 mm or more, and is distinguished from a membrane-like porous body. The thickness of the fifth monolith cation exchanger is preferably in the range of 3 to 1000 mm.

The cation exchange capacity per weight in a dry state is as described above. In addition, the fact that "cation exchange groups are distributed in the organic porous cation exchanger" is as described above.

(Fifth method for producing monolithic cation exchanger)
The fifth monolithic cation exchanger can be produced, for example, by the following method.

The fifth monolith can be obtained, for example, by preparing a water-in-oil emulsion and then carrying out the following steps I to III. In step I, for example, the water-in-oil emulsion can be polymerized to obtain a monolithic organic porous intermediate (hereinafter, monolith intermediate (5)) having a continuous macropore structure with a total pore volume in the range of, for example, 5 to 30 mL/g. In step II, for example, a mixture containing a vinyl monomer, a crosslinking agent having at least two vinyl groups in one molecule, an organic solvent that dissolves the vinyl monomer and the crosslinking agent but not the polymer produced by polymerization of the vinyl monomer, and a polymerization initiator is prepared. In step III, for example, the mixture obtained in step II is left to stand and polymerized in the presence of the monolith intermediate (5) obtained in step I to obtain the fifth monolith.

Step I in the fifth monolith manufacturing method is the same as step I in the third monolith manufacturing method.

In step I, when forming the water-in-oil emulsion, a polymerization initiator may be used as necessary. The polymerization initiator is preferably a compound that generates radicals when exposed to heat or light. The polymerization initiator may be water-soluble or oil-soluble, and examples thereof include 2,2'-azobis(isobutyronitrile), 2,2'-azobis(2,4-dimethylvaleronitrile), 2,2'-azobis(2-methylbutyronitrile), 2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile), 2,2'-azobisdimethylisobutyrate, 4,4'-azobis(4-cyanovaleric acid), 1,1'-azobis(cyclohexane-1-carbonitrile), benzoyl peroxide, lauroyl peroxide, potassium persulfate, ammonium persulfate, hydrogen peroxide-ferrous chloride, sodium persulfate-acidic sodium sulfite, etc.

The monolith intermediate (5) obtained in step I has a continuous macropore structure. When this is allowed to coexist in a polymerization system, particulate matter, etc. is formed on the surface of the skeletal phase of the continuous macropore structure using the structure of the monolith intermediate (5) as a template, or particulate matter is formed on the surface of the skeletal phase of the cocontinuous structure. The monolith intermediate (5) is also an organic polymer material having a crosslinked structure. The crosslink density of the polymer material contains crosslinked structural units in the range of, for example, 0.3 to 10 mol %, preferably 0.3 to 5 mol %, of the total structural units constituting the polymer material.

The type of polymer material of the monolith intermediate (5) is the same as the type of polymer material of the monolith intermediate (3) in the third monolith manufacturing method.

The total pore volume per weight of the monolith intermediate (5) obtained in step I in a dry state is, for example, in the range of 5 to 30 mL/g, preferably in the range of 6 to 28 mL/g. To bring the total pore volume of the monolith intermediate (5) into the above numerical range, the ratio (by weight) of monomer to water may be, for example, approximately 1:5 to 1:35.

In step I, if the ratio of monomer to water is approximately 1:5 to 1:20, the monolith intermediate (5) will have a continuous macropore structure with a total pore volume of, for example, 5 to 16 mL/g, and the monolith obtained through step III will be a monolith No. 5-1. On the other hand, if the ratio of monomer to water is approximately 1:20 to 1:35, the monolith intermediate (5) will have a continuous macropore structure with a total pore volume of, for example, more than 16 mL/g and 30 mL/g or less, and the monolith obtained through step III will be a monolith No. 5-2.

The monolith intermediate (5) obtained in step I of the fifth monolith manufacturing method has an average diameter in a dry state of the openings (mesopores), which are the overlapping portions of the macropores, of, for example, 20 to 200 μm.

Step II in the fifth monolith manufacturing method is the same as step II in the third monolith manufacturing method. In step III in the fifth monolith manufacturing method, for example, the mixture obtained in step II is left to stand and polymerized in the presence of the monolith intermediate (5) obtained in step I to obtain the fifth monolith.

As disclosed in JP-A-7-501140 and other publications, when a vinyl monomer and a crosslinking agent are subjected to static polymerization in a specific organic solvent in the absence of the monolith intermediate (5), a particle-aggregated monolithic organic porous body can be obtained. In contrast, when the monolith intermediate (5) having a continuous macropore structure is present in the above polymerization system, the structure of the composite monolith after polymerization changes dramatically, and a fifth monolith having the above-mentioned specific skeletal structure can be obtained, rather than a particle-aggregated structure.

In step III of the fifth monolith manufacturing method, the internal volume of the reaction vessel is not particularly limited as long as it is large enough to allow the monolith intermediate (5) to exist in the reaction vessel. When the monolith intermediate (5) is placed in the reaction vessel, either a gap is formed around the monolith in a plan view, or the monolith intermediate (5) fits almost without gaps in the reaction vessel. Of these, the fifth monolith after polymerization is hardly subjected to pressure from the inner wall of the vessel and fits almost without gaps in the reaction vessel, which is efficient with almost no distortion of the fifth monolith and almost no waste of reaction raw materials. Note that even if the internal volume of the reaction vessel is large and gaps exist around the fifth monolith after polymerization, the vinyl monomer and crosslinking agent are adsorbed and distributed to the monolith intermediate (5), so that particle aggregate structures are hardly generated in the gaps in the reaction vessel.

In this step III, for example, the monolith intermediate (5) is placed in a reaction vessel in a state of being impregnated with the mixture (solution). As described above, the mixture obtained in step II and the monolith intermediate (5) may be mixed in such a ratio that the amount of vinyl monomer added is, for example, in the range of 3 to 50 times, preferably in the range of 4 to 40 times, by weight, relative to the monolith intermediate (5). This makes it possible to obtain a fifth monolith, which is a composite monolith having a specific skeleton while having an appropriate opening diameter. In the reaction vessel, the vinyl monomer and crosslinking agent in the mixture are adsorbed and distributed to the skeleton of the stationary monolith intermediate (5), and polymerization proceeds within the skeleton of the monolith intermediate (5).

In step III of the fifth monolith manufacturing method, the polymerization conditions are almost the same as those in step III of the third monolith manufacturing method.

When producing the fifth monolith described above, if step II or step III is carried out under conditions that satisfy at least one of the following conditions (1) to (5), a monolith having particles and the like formed on the skeleton surface can be produced.
(1) The polymerization temperature in step III is at least 5° C. lower than the 10-hour half-life temperature of the polymerization initiator.
(2) The mole percentage of the crosslinking agent used in step II is at least twice the mole percentage of the crosslinking agent used in step I.
(3) The vinyl monomer used in step II has a structure different from that of the oil-soluble monomer used in step I.
(4) The organic solvent used in step II is a polyether having a molecular weight of 200 or more.
(5) The concentration of the vinyl monomer used in step II is 30% by weight or less in the mixture in step II.

Preferred structures of the fifth monolith thus obtained include a continuous macropore structure ("Fifth-1 monolith") in which bubble-like macropores overlap each other, and the overlapping portions form openings with an average diameter of, for example, 10 to 120 μm in the dry state, and a co-continuous structure ("Fifth-2 monolith") consisting of a three-dimensionally continuous skeleton with a thickness of, for example, 0.8 to 40 μm in the dry state, and three-dimensionally continuous pores between the skeletons with a diameter of, for example, 8 to 80 μm in the dry state. The method for introducing cation exchange groups into the fifth monolith is the same as the method for introducing cation exchange groups into the first monolith.

[Conditions for producing carboxylic acid thioester]
In the method for producing a carboxylic acid thioester according to the present embodiment, the reaction temperature is not particularly limited as long as the carboxylic acid and the thiol react in the presence of a strongly acidic cation exchange resin, but is, for example, in the range of 100 to 180° C., and preferably in the range of 120 to 160° C. If the reaction temperature is less than 100° C., the production efficiency may decrease, and if it exceeds 180° C., there is a concern that the strongly acidic cation exchange resin in the catalyst may be decomposed or a side reaction may proceed.

The reaction time is not particularly limited as long as it is a time during which the reaction between the carboxylic acid and the thiol proceeds, but is, for example, in the range of 3 to 120 hours. If the reaction time is less than 3 hours, the reaction may not proceed sufficiently, and even if the reaction time exceeds 120 hours, improvement in production efficiency may not be expected.

In the method for producing a carboxylic acid thioester according to the present embodiment, the reaction between the carboxylic acid and the thiol can be carried out in a solvent. The type of solvent is not particularly limited as long as it does not inhibit the reaction between the carboxylic acid and the thiol. Examples of the solvent include hydrocarbon solvents such as octane and decane, aromatic solvents such as toluene and xylene, halogen solvents such as chlorobenzene, ether solvents such as 1,2-dimethoxymethane and diglyme, amide solvents such as N,N-dimethylformamide, sulfoxide solvents such as dimethyl sulfoxide, and sulfone solvents such as sulfolane. A single type of solvent may be used, or a mixture of two or more types may be used.

The reaction may be carried out under an inert gas atmosphere such as argon or nitrogen. By carrying out the reaction under an inert gas atmosphere, discoloration of the reaction solution can be suppressed.

The carboxylic acid thioester obtained by this production method may be purified by a purification step as necessary. The purification method is not particularly limited as long as it can improve the purity of the obtained carboxylic acid thioester, and examples of the purification method include silica gel flash column chromatography and recrystallization.

The reaction of carboxylic acid and thiol in the presence of a strong acid cation exchange resin may be carried out, for example, by introducing a raw material liquid (liquid to be treated) containing carboxylic acid and thiol into a filling container filled with a strong acid cation exchange resin as a solid acid catalyst through an inlet path of the filling container, passing the raw material liquid through and contacting the strong acid cation exchange resin, and discharging the reaction liquid through a discharge path of the filling container. The filling container may be heated to a predetermined temperature by a heating device. Alternatively, the raw material liquid containing carboxylic acid, thiol, and strong acid cation exchange resin may be reacted in a reaction container, for example, under an inert gas atmosphere, at a predetermined temperature for a predetermined time, while stirring as necessary.

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

[Preparation of monolithic cation exchanger]
(Production of Monolith Intermediate (Process I))
9.28 g of styrene as a monomer, 0.19 g of divinylbenzene, 0.50 g of sorbitan monooleate (hereinafter abbreviated as SMO) as a surfactant, and 0.25 g of 2,2'-azobis(isobutyronitrile) as a polymerization initiator were mixed and dissolved uniformly. Next, this styrene/divinylbenzene/SMO/2,2'-azobis(isobutyronitrile) mixture was added to 180 g of pure water and stirred under reduced pressure using a vacuum stirring and degassing mixer (manufactured by EME Co., Ltd.), which is a planetary stirring device, to obtain a water-in-oil type emulsion. This emulsion was quickly transferred to a reaction vessel, sealed, and polymerized at 60°C for 24 hours under static conditions. After the polymerization was completed, the contents were removed, extracted with methanol, and then dried under reduced pressure to produce a monolith intermediate having a continuous macropore structure. The internal structure of the monolith intermediate (dried body) obtained in this manner was observed by SEM. An SEM image is shown in Figure 10. Although the wall separating two adjacent macropores is extremely thin and rod-like, it has a continuous macropore structure. The average diameter of the openings (mesopores) where the macropores overlap, as measured by mercury intrusion porosimetry, was 40 μm, and the total pore volume was 18.2 mL/g.

(Production of Monolith (Step II))
Next, 216.6 g of styrene as a monomer, 4.4 g of divinylbenzene as a crosslinking agent, 220 g of 1-decanol as an organic solvent, and 0.8 g of 2,2'-azobis(2,4-dimethylvaleronitrile) as a polymerization initiator were mixed and dissolved uniformly (step II).

(Production of Monolith (Step III))
Next, the monolith intermediate was placed in a reaction vessel, immersed in the styrene/divinylbenzene/1-decanol/2,2'-azobis(2,4-dimethylvaleronitrile) mixture, and degassed in a vacuum chamber, after which the reaction vessel was sealed and left to polymerize for 24 hours at 50° C. After polymerization was completed, the contents were taken out, subjected to Soxhlet extraction with acetone, and then dried under reduced pressure (III step).

Figure 11 shows the results of SEM observation of the internal structure of the monolith (dried body) thus obtained, which contains 1.2 mol% of a crosslinking component made of a styrene/divinylbenzene copolymer. As is clear from Figure 11, the skeleton and pores of this monolith are each three-dimensionally continuous and consist of a continuous skeleton phase and a continuous pore phase, respectively, and the two phases are intertwined to form a co-continuous structure. The thickness of the continuous skeleton measured from the SEM image was 20 μm. The average diameter of the three-dimensionally continuous pores of this monolith, measured by mercury intrusion porosimetry, was 70 μm, and the total pore volume was 4.4 mL/g. The average diameter of the pores was determined from the maximum value of the pore distribution curve obtained by mercury intrusion porosimetry.

(Preparation of monolithic cation exchanger)
The monolith produced by the above method was placed in a column reactor, and a solution containing 500 g of chlorosulfonic acid and 4 L of dichloromethane was passed through it to react at 20° C. for 3 hours. After the reaction was completed, methanol was added to the system to deactivate unreacted chlorosulfonic acid, and the product was extracted by washing with methanol. Finally, it was washed with pure water to obtain a monolith cation exchanger.

The cation exchange capacity of the obtained monolith cation exchanger was 4.7 mg equivalent/g in a dry state, and it was confirmed that sulfonic acid groups were quantitatively introduced. As is clear from FIG. 11, this monolith cation exchanger had a co-continuous structure in which the skeleton and pores were three-dimensionally continuous and the two phases were entangled. The average thickness of the skeleton in a dry state measured from SEM images was 20 μm, and the average diameter of the three-dimensionally continuous pores of this monolith cation exchanger in a dry state determined from measurements using mercury intrusion porosimetry was 70 μm, and the total pore volume in a dry state was 4.4 mL/g.

Next, to confirm the distribution of sulfur in the monolith cation exchanger, the distribution of sulfur was observed using an electron probe microanalyzer (EPMA). The distribution of sulfur on the surface of the monolith cation exchanger is shown in Figure 12, and the distribution of sulfur in the cross section of the skeleton is shown in Figure 13. It was confirmed that sulfur was distributed almost uniformly not only on the skeleton surface of the monolith cation exchanger, but also inside the skeleton, and that sulfur groups were introduced almost uniformly into the monolith cation exchanger.

The monolithic cation exchanger produced in this manner is hereinafter also referred to as "monolith-SO ₃ H" or "monolith-SO ₃ H catalyst".

<Example 1-1>
75.1 mg (0.5 mmol) of 3-phenylpropionic acid (hereinafter also referred to as "PPA") as a substrate, 75.1 mg (100 mass%) of monolith-SO ₃ H catalyst cut into 1-2 mm squares with a knife, 238.1 μL (2 equivalents relative to the substrate) of 1-dodecanethiol (hereinafter also referred to as "DDT"), and 1 mL of toluene were placed in a dried test tube. After that, an argon balloon was attached and the atmosphere was replaced with argon, and the reaction temperature was set to 120° C. and stirred for 72 hours to react.

Thereafter, ethyl acetate was added to the reaction solution obtained, and the mixture was filtered using a cotton plug to obtain a reaction filtrate from which the monolith-SO ₃ H catalyst had been removed. Toluene and ethyl acetate were distilled off under reduced pressure, and the reaction residue obtained was dissolved in deuterated chloroform, and 1,1,2,2-tetrachloroethane (0.5 mmol) was added as an internal standard substance. Measurement was performed using ¹ HNMR (manufactured by JEOL Ltd., ECS-400 model) to calculate the yields of the raw material substrate that remained unreacted and the target product S-dodecyl 3-phenylpropanethioester (hereinafter also referred to as "DPT"), which were 12% and 88% (corresponding to 147.2 mg), respectively. The results are shown in Table 1. When the reaction was carried out in the same manner at reaction temperatures of 60° C. and 80° C., almost no target product was obtained.

<Examples 1-2 to 1-4, Reference Examples 1-5 to 1-7 , Comparative Examples 1-1 and 1-2>
The reaction was carried out under the same conditions as in Example 1-1, except that the thiol equivalent, reaction temperature, reaction time, and catalyst in Example 1-1 were changed to those shown in Table 1, to obtain a mixed product, and the internal standard yield was calculated using ¹ HNMR (manufactured by JEOL Ltd., ECS-400 model or ECA-500 model). The results are shown in Table 1. "Amberlyst (trademark) 16WET" (cation exchange capacity: 4.8 mg equivalent/g), "Amberlyst (trademark) 15DRY" (cation exchange capacity: 4.7 mg equivalent/g), "Amberlyst (trademark) 45" (cation exchange capacity: 2.95 mg equivalent/g), and "Amberlite (trademark) XH2071H" (cation exchange capacity: 2.7 mg equivalent/g) shown in Table 1 are strongly acidic cation exchange resins manufactured by Organo Corporation.

As can be seen from Table 1 , under conditions in which a strongly acidic cation exchange resin (Amberlyst (trademark) 45) was used (Comparative Example 1) and under conditions in which no catalyst was used (Comparative Example 2), the target thioester could not be produced, and therefore, in the production of thioesters, the coexistence of a non-particulate organic porous strongly acidic cation exchanger of 1 mg equivalent/g or more is important.

In particular, it is seen from Example 1-1 that when monolith-SO ₃ H is used as the strongly acidic cation exchanger, thioesterification proceeds and the target compound can be produced in high yield.

<Example 2-1>
75.1 mg (0.5 mmol) of 3-phenylpropionic acid (PPA) as a substrate, 75.1 mg (100 mass%) of monolith-SO ₃ H catalyst cut into 1-2 mm cubes with a knife, 124.2 mg (2 equivalents relative to the substrate) of p-toluenethiol (hereinafter also referred to as "PTT"), and 1 mL of toluene were placed in a dried test tube. After that, an argon balloon was attached and the atmosphere was replaced with argon, and the reaction temperature was set to 120°C and stirred for 72 hours to react.

Thereafter, ethyl acetate was added to the reaction solution obtained, and the mixture was filtered using a cotton plug to obtain a reaction filtrate from which the monolith-SO ₃ H catalyst had been removed. Toluene and ethyl acetate were distilled off under reduced pressure, and the reaction residue obtained was dissolved in deuterated chloroform, to which 1,1,2,2-tetrachloroethane (0.5 mmol) was added as an internal standard substance. By measuring ¹ H NMR, the yields of the raw material substrate remaining unreacted and the target product S-(p-tolyl)-3-phenylpropanethioester (hereinafter also referred to as "TPT") were calculated to be 79% and 15% (corresponding to 19.2 mg), respectively. In addition, the mixed product was purified using a column, and isolated with an isolation yield of 14% (17.9 mg). The results are shown in Table 2.

<Example 2-2>
The reaction was carried out under the same conditions as in Example 2-1, except that the thiol in Example 2-1 was changed to 157.5 μL (2 equivalents relative to the substrate) of 1-heptanethiol (hereinafter also referred to as "HT"), to obtain a mixed product containing S-heptyl-3-phenylpropanethioester (hereinafter also referred to as "HPT"). The yields of the raw material substrate that remained unreacted and the target product HPT were calculated to be 0% and 96% (corresponding to 126.9 mg), respectively. In addition, the mixed product was purified by column and isolated with an isolation yield of 92% (121.7 mg). The results are shown in Table 2.

<Example 2-3>
The reaction was carried out under the same conditions as in Example 2-1, except that the thiol in Example 2-1 was changed to 174.2 μL (2 equivalents relative to the substrate) of 1-octanethiol (hereinafter also referred to as "OT"), to obtain a mixed product containing S-octyl-3-phenylpropanethioester (hereinafter also referred to as "OPT"). The yields of the raw material substrate that remained unreacted and the target product OPT were calculated to be 0% and 98% (corresponding to 136.4 mg), respectively. In addition, the mixed product was purified using a column and isolated with an isolation yield of 90% (125.3 mg). The results are shown in Table 2.

<Example 2-4>
The reaction was carried out under the same conditions as in Example 2-1, except that the raw material substrate in Example 2-1 was changed to 61.1 mg (0.5 mmol) of benzoic acid (hereinafter also referred to as "BA"), to obtain a mixed product containing S-(p-tolyl)-benzothioester (hereinafter also referred to as "TBT"). The yields of the raw material substrate remaining unreacted and the target product TBT were calculated to be 50% and 44% (corresponding to 50.2 mg), respectively. In addition, the mixed product was purified by column and isolated with an isolation yield of 44% (49.8 mg). The results are shown in Table 2.

<Example 2-5>
The reaction was carried out under the same conditions as in Example 2-1, except that the raw material substrate in Example 2-2 was changed to 61.1 mg (0.5 mmol) of benzoic acid (BA), to obtain a mixed product containing S-heptyl benzothioester (hereinafter also referred to as "HBT"). The yields of the raw material substrate remaining unreacted and the target product HBT were calculated to be 0% and 97% (corresponding to 114.6 mg), respectively. In addition, the mixed product was purified by column purification and isolated with an isolation yield of 94% (111.1 mg). The results are shown in Table 2.

<Example 2-6>
The reaction was carried out under the same conditions as in Example 2-1, except that the raw substrate in Example 2-3 was changed to 61.1 mg (0.5 mmol) of benzoic acid (BA), to obtain a mixed product containing S-octylbenzothioester (hereinafter also referred to as "OBT"). The yields of the raw substrate remaining unreacted and the target product OBT were calculated to be 0% and 100% (corresponding to 124.2 mg), respectively. In addition, the mixed product was purified by column purification and isolated with an isolation yield of 100% (125.0 mg). The results are shown in Table 2.

<Example 2-7>
53.1 mg (0.5 mmol) of benzaldehyde (hereinafter also referred to as "BDA") as a substrate, 53.1 mg (100 mass%) of monolith-SO ₃ H catalyst, 100.2 μL (2 equivalents relative to the substrate) of 1,3-propanedithiol (hereinafter also referred to as "PDT"), and 1 mL of toluene were placed in a dried test tube. After that, an argon balloon was attached and the atmosphere was replaced with argon, and the reaction temperature was set to 120°C and the reaction was carried out with stirring for 72 hours.

Thereafter, ethyl acetate was added to the reaction solution obtained, and the mixture was filtered using a cotton plug to obtain a reaction filtrate from which the monolith-SO ₃ H catalyst had been removed. Toluene and ethyl acetate were distilled off under reduced pressure, and the reaction residue obtained was dissolved in deuterated chloroform, to which 1,1,2,2-tetrachloroethane (0.5 mmol) was added as an internal standard substance. By measuring ¹ H NMR, the yields of the raw material substrate remaining unreacted and the target product 2-phenyl-1,3-dithiane (hereinafter also referred to as "PDT") were calculated to be 0% and 91% (corresponding to 89.3 mg), respectively. In addition, the mixed product was purified using a column, and isolated with an isolation yield of 89% (87.2 mg). The results are shown in Table 2.

As such, the method of the embodiment is a method that is easy to manufacture, reduces waste, and is sustainable.

1 Skeleton phase, 2 Pore phase, 10 Bicontinuous structure, 11 Rectangular image area, 12 Skeleton, 13 Macropores, 21 Skeleton surface, 22a, 22b, 22c, 22d, 22e Protrusions.

Claims (3)

A method for producing a carboxylic acid thioester, comprising reacting a carboxylic acid with a thiol in the presence of a solid acid catalyst to produce a carboxylic acid thioester, the method comprising the steps of:
The method for producing a carboxylic acid thioester, wherein the solid acid catalyst is a non-particulate organic porous strongly acidic cation exchanger . A method for producing the carboxylic acid thioester according to claim 1, comprising the steps of:
The method for producing a carboxylic acid thioester, wherein the non-particulate organic porous strongly acidic cation exchanger has a cation exchange capacity of more than 1 mg equivalent/g. A method for producing a carboxylic acid thioester according to claim 1 or 2 , comprising the steps of:
The non-particulate organic porous strongly acidic cation exchanger comprises a continuous skeleton phase and a continuous pore phase, the thickness of the continuous skeleton being in the range of 1 to 100 μm, the average diameter of the continuous pores being in the range of 1 to 1000 μm, the total pore volume being in the range of 0.5 to 50 mL/g, and the cation exchange capacity per weight in a dry state being in the range of 1 to 5 mg equivalent/g, and the cation exchange groups being distributed throughout the non-particulate organic porous strongly acidic cation exchanger.