JP2006342245A - Porous resin beads - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide porous resin beads as a carrier for synthesis, capable of efficiently carrying out chemical synthetic reaction, namely capable of increasing both of the yield and the purity of the produced synthetic substance. <P>SOLUTION: The porous resin beads are composed of styrene-hydroxystyrene-divinylbenzene-based copolymer. In the porous resin beads, the hydroxy group amount (mmole/g) and crosslinking degree (wt.%) of the porous resin beads satisfy relational expression (1): (hydroxy group amount)<SP>2</SP>×degree of crosslinking<2 and the hydroxy group amount is ≥0.01 mmole/g and the degree of crosslinking is ≥2 wt.%, wherein the degree of crosslinking represents wt.% of a divinylbenzene-based monomer to total weight of a monomer added when synthesizing the porous resin beads. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a porous resin bead made of a styrene-hydroxystyrene-divinylbenzene copolymer.

  Conventionally, as polystyrene-based porous resin beads, hydroxystyrene-polyene copolymer (see Patent Documents 1 and 2), or copolymer obtained by copolymerizing alkoxystyrenes, aromatic polyvinyls and aromatic vinyl compounds. A porous resin bead made of a coalesced resin (see Patent Document 3) is known. These porous resin beads have been mainly applied to ion exchange resins, adsorbents and the like. In such applications, it is considered to adsorb as much substance as possible. Therefore, the development guidelines for conventional porous resin beads are to add as many functional groups as possible and to increase the specific surface area as much as possible. Therefore, it has been directed to increase the adsorption capacity of the substance per unit volume of the porous resin beads. These porous resin beads are also used as a reaction field (support) for performing a chemical synthesis reaction, and in order to increase the yield of the synthetic material to be generated, as in the case of the adsorption described above, Increasing the amount of the functional group as a starting point or increasing the specific surface area is performed. However, when the yield of the synthetic material thus produced is increased, its purity tends to decrease.

JP 52-23193 A JP 58-210914 A JP-A-5-86132

  An object of the present invention is to provide a porous resin bead as a carrier for synthesis that can efficiently perform a chemical synthesis reaction, that is, can increase both the yield and purity of a synthetic substance to be produced. .

  As a result of intensive studies to solve the above problems, the present inventors have determined that the porous resin beads made of a styrene-hydroxystyrene-divinylbenzene copolymer control both the amount of hydroxyl groups and the degree of crosslinking. As a result, it has been found that it has an excellent action as a reaction field (carrier) for efficiently advancing the chemical synthesis reaction, and the present invention has been completed.

That is, the present invention is as follows.
[1] Porous resin beads made of a styrene-hydroxystyrene-divinylbenzene copolymer,
The amount of hydroxyl groups (mmole / g) and the degree of crosslinking (% by weight) of the porous resin beads are expressed by the following relational expression (1):
(Amount of hydroxyl group) ² x degree of crosslinking <2 (1)
And the amount of the hydroxyl group is 0.01 mmole / g or more and the degree of crosslinking is 2% by weight or more,
Here, the degree of crosslinking indicates the weight percentage of the divinylbenzene monomer relative to the total weight of the monomers added when synthesizing the porous resin beads.
Porous resin beads.
[2] The porous resin beads according to the above [1], wherein the specific surface area measured by the BET method is 10 to 300 m ² / g.
[3] The porous resin beads according to [1] or [2] above, wherein the average pore diameter measured by a mercury intrusion method is 1 to 200 nm.
[4] A styrene-hydroxystyrene-divinylbenzene copolymer is obtained by suspension copolymerizing a styrene monomer, an acyloxystyrene monomer, and a divinylbenzene monomer using an organic solvent and water. A styrene-acyloxystyrene-divinylbenzene copolymer is synthesized, and then obtained by hydrolyzing the styrene-acyloxystyrene-divinylbenzene copolymer. Any one of the porous resin beads.
[5] A method for producing porous resin beads comprising a styrene-hydroxystyrene-divinylbenzene copolymer,
The amount of hydroxyl groups (mmole / g) and the degree of crosslinking (% by weight) of the porous resin beads are expressed by the following relational expression (1):
(Amount of hydroxyl group) ² x degree of crosslinking <2 (1)
And the amount of the hydroxyl group is 0.01 mmole / g or more and the degree of crosslinking is 2% by weight or more,
Here, the degree of cross-linking indicates the weight percent of the divinylbenzene monomer relative to the total weight of monomers added when the porous resin beads are synthesized,
The method is
A step of suspending copolymerization of a styrene monomer, an acyloxystyrene monomer, and a divinylbenzene monomer using an organic solvent and water to synthesize a styrene-acyloxystyrene-divinylbenzene copolymer; ,
Hydrolyzing the styrene-acyloxystyrene-divinylbenzene copolymer;
A method for producing porous resin beads.

  The porous resin beads of the present invention can be used for chemical synthesis by simultaneously controlling both the amount of hydroxyl groups and the degree of crosslinking based on the relational expression (1), that is, by adjusting the distance between adjacent hydroxyl groups. When used as a carrier, it is possible to carry out a chemical synthesis reaction that can increase both the yield and purity of the synthetic material produced.

The present invention is described in detail below.
The porous resin beads of the present invention are porous resin beads made of a styrene-hydroxystyrene-divinylbenzene copolymer. Typical examples of the styrene-hydroxystyrene-divinylbenzene copolymer include copolymers containing the following structural units (A) to (C).

  The structural units (A) to (C) are structural units contained in the styrene-hydroxystyrene-divinylbenzene copolymer in a preferred embodiment of the present invention. These structural units may be substituted as shown below.

  One or more hydrogen atoms (including a hydrogen atom of a benzene ring) in the structural unit (A) are an alkyl group having 1 to 5 carbon atoms, a halogen atom, an amino group, a carboxyl group, a sulfo group, a cyano group, It may be substituted with a methoxy group, a nitro group or the like.

  One or more hydrogen atoms (including a hydrogen atom of a benzene ring but excluding a hydrogen atom of a hydroxyl group) in the structural unit (B) are an alkyl group having 1 to 5 carbon atoms, a halogen atom, an amino group, or a carboxyl group. Group, sulfo group, cyano group, methoxy group, nitro group and the like. Further, when the obtained porous resin beads are used as a carrier for synthesis, considering the ease of inhibition of the synthesis reaction between adjacent hydroxyl groups, the bonding of the hydroxyl groups to the benzene ring is as described in (B) above. The para position with respect to the main chain is particularly preferred, but it may be in the ortho position or the meta position.

  One or more hydrogen atoms (including a hydrogen atom of a benzene ring) in the structural unit (C) are an alkyl group having 1 to 5 carbon atoms, a halogen atom, an amino group, a carboxyl group, a sulfo group, a cyano group, It may be substituted with a methoxy group, a nitro group or the like.

  The styrene-hydroxystyrene-divinylbenzene copolymer constituting the porous resin bead of the present invention may contain structural units other than the above structural units (A) to (C) and their substitution products.

The hydroxyl group amount (mmole / g) and the degree of crosslinking (% by weight) of the porous resin beads of the present invention are expressed by the following relational expression (1):
(Amount of hydroxyl group) ² x degree of crosslinking <2 (1)
And the amount of the hydroxyl group is 0.01 mmole / g or more and the degree of crosslinking is 2% by weight or more.
Preferably, the amount of hydroxyl groups (mmole / g) and the degree of crosslinking (% by weight) of the porous resin beads of the present invention are expressed by the following relational expression (2):
(Hydroxyl group amount) ² x degree of crosslinking <1.5 (2)
And the amount of the hydroxyl group is 0.01 mmole / g or more and the degree of crosslinking is 2% by weight or more.
In the present invention, the “degree of crosslinking” means the weight percent of divinylbenzene monomer relative to the total weight of monomers added when synthesizing the porous resin beads, that is,
(Weight of divinylbenzene monomer added when synthesizing porous resin beads) / (Total weight of monomer added when synthesizing porous resin beads) × 100 (% by weight)
Defined by

  When the amount of hydroxyl groups and the degree of crosslinking of the porous resin beads do not satisfy the above relational expression, for example, when the amount of hydroxyl groups is too high, the yield of the synthetic substance obtained (when used as a carrier for chemical synthesis) is The purity is low because the density of hydroxyl groups is too high. The upper limit of the amount of hydroxyl groups is preferably 1 mmole / g or less, more preferably 0.8 mmole / g or less, and still more preferably 0.4 mmole / g or less. On the other hand, when the degree of cross-linking is too high, the synthetic material cannot be obtained in high yield, and in some cases, its purity is low. The upper limit of the degree of crosslinking is preferably 10% by weight or less, more preferably 8% by weight or less. In addition, when the amount of hydroxyl group is too low, the yield of the resultant synthetic material is reduced, so the lower limit of the amount of hydroxyl group is 0.01 mmole / g or more, preferably 0.05 mmole / g or more, more preferably 0.1 mmole / g. g or more. On the other hand, if the degree of crosslinking is too low, it is difficult to obtain a porous structure, and the solvent resistance is lowered, which is disadvantageous for use as a carrier for chemical synthesis. It is 2% by weight or more, preferably 3% by weight or more, more preferably 5% by weight or more.

The amount of the hydroxyl group mainly depends on the amount of the hydroxystyrene-based structural unit (for example, the above-described structural unit (B) or a substituted product thereof) in the copolymer.
The hydroxyl group content of the porous resin beads of the present invention can be measured by titration shown below according to JIS K0070. That is, the hydroxyl group of the porous resin beads to be measured is acetylated with a known amount of acetylating reagent (acetic anhydride), and the amount of acetylating reagent (acetic anhydride) that has not been consumed for acetylation is determined by titration with potassium hydroxide. Thus, the amount of hydroxyl group of the measurement object is calculated. The specific procedure for this measurement is as follows.

Pyrimidine is added to 25 g of acetic anhydride until the total amount is 100 ml to obtain an acetylating reagent. Weigh 0.5-2 g of a measurement sample (dried porous resin beads) into a flask, and accurately add 0.5 ml of the acetylating reagent and 4.5 ml of pyridine. The mixture in the flask is maintained at 95-100 ° C. for 2 hours, then cooled to room temperature and 1 ml of distilled water is added. Acetic anhydride that has not been consumed for acetylation is decomposed by heating for 10 minutes. The contents of the flask are all transferred to a beaker, diluted with distilled water to a total volume of 150 ml, cooled, and titrated with a 0.5 mol / l aqueous potassium hydroxide solution. Separately, blank measurement is performed by the same operation as described above without inserting a measurement sample. The amount of hydroxyl groups in the measurement sample is calculated by the following formula (3). However, A (micromol / g) is the amount of hydroxyl groups of a measurement sample, B (ml) is the titration amount of the potassium hydroxide aqueous solution in a blank measurement, and C (ml) is the potassium hydroxide aqueous solution in the measurement of a measurement sample. It is a titration amount, f is a factor of an aqueous potassium hydroxide solution, and M (g) is the weight of the measured sample weighed.
A = (BC) × 0.5 (mol / l) × f × 1000 ÷ M (3)

  The porous resin beads of the present invention have a network structure in which styrene-hydroxystyrene polymer chains are crosslinked by a structural unit based on a divinylbenzene monomer (in the preferred embodiment, the structural unit (C) or a substituted product thereof). Consists of. Therefore, the degree of crosslinking of the porous resin beads depends on the divinylbenzene monomer added when the porous resin beads are synthesized. The higher the amount of divinylbenzene monomer added, the higher the degree of crosslinking. The network structure becomes denser, and conversely, the smaller the amount of divinylbenzene monomer added, the lower the degree of crosslinking and the rougher the network structure.

The surface / internal shape of the porous resin beads of the present invention is not particularly limited, and the specific surface area measured by the BET method is preferably 10 to 300 m ² / g, more preferably 30 to 200 m ² / g. . When porous resin beads having a specific surface area that is too small are used as a carrier for synthesis, there is a concern that the yield of the synthetic substance obtained by reducing the reaction field of the chemical synthesis reaction may be reduced. On the contrary, the fact that the specific surface area of the porous resin beads is large may be that a large number of fine pores are generated or a case where the porosity is large. When there are too many pores, there is a concern that the synthesis reaction is difficult to proceed when the beads are used as a carrier for synthesis. When the porosity is too large, the physical strength of the porous resin beads becomes low, and there is a concern that the beads may be broken during the synthesis operation.

The specific surface area of the porous resin beads of the present invention is measured by the BET method.
Nitrogen gas is used as an adsorption gas in the BET method, and a specific surface area measurement device NOVA1200 (manufactured by Quanta Chrome Co.) is used as a measurement device. A measurement sample (porous resin beads) is put into this apparatus, deaerated at room temperature under vacuum for 120 minutes, and then the specific surface area of the measurement sample is determined by the BET multipoint method.

  The size and number of pores of the porous resin beads of the present invention are not particularly limited. The pore size can be quantified by the average pore size. The average pore diameter measured by the mercury intrusion method of the porous resin beads of the present invention is preferably 1 to 200 nm, more preferably 5 to 100 nm. When the average pore diameter of the porous resin beads is too small, there is a concern that the yield and purity of the synthetic substance obtained by the chemical synthesis reaction when used as a carrier for chemical synthesis is lowered. On the contrary, when the average pore diameter of the porous resin beads is too large, there is a concern that the hydroxyl group on the bead surface, which is a reaction field, is less likely to come into contact with a substance involved in the reaction, which is disadvantageous as a carrier for chemical synthesis.

  The average pore diameter of the porous resin beads of the present invention is measured by a mercury intrusion method. Specifically, about 0.2 g of a measurement sample (porous resin beads) was put into a mercury porosimeter, PorMaster 60-GT (manufactured by QuantaChrome Co.), and mercury under conditions of a mercury contact angle of 140 ° and a mercury surface tension of 480 dyn / cm. The average pore diameter of the measurement sample is determined from the injection pressure.

  The “bead” in the porous resin bead of the present invention does not mean a strict spherical shape, but is a fixed shape (for example, an approximately spherical shape such as an elliptical sphere, a polyhedral shape, a cylindrical shape, an irregular shape such as a slab shape) It is necessary to have a shape or the like. When the porous resin beads are used as a carrier for synthesis, the packing efficiency into the synthesis reaction vessel can be increased, and the reaction vessel is not easily damaged, and is preferably substantially spherical. Further, the size (volume) of one bead is not particularly limited, but preferably the size (volume) is such that the average particle size is 1-1000 μm, more preferably 5-500 μm, and even more preferably 10-200 μm. is there. In the present invention, the average particle diameter of the porous resin beads is measured by a measuring device using a laser diffraction / light scattering method, for example, a laser diffraction / scattering particle size distribution measuring device (LA-920, manufactured by Horiba, Ltd.). be able to.

  The method for producing the porous resin beads of the present invention is not particularly limited. Hereinafter, as an example, a production method by subjecting a copolymer obtained by suspension copolymerization of monomers to hydrolysis will be described. In the production method, first, styrene-acyloxystyrene-divinyl is obtained by suspension copolymerization of a styrene monomer, an acyloxystyrene monomer, and a divinylbenzene monomer using an organic solvent and water. A benzene copolymer is obtained.

  The styrene monomer is styrene or a substituted product thereof, and is preferably styrene. As a substituted styrene, one or more hydrogen atoms of styrene are substituted with an alkyl group having 1 to 5 carbon atoms, a halogen atom, an amino group, a carboxyl group, a sulfo group, a cyano group, a methoxy group, a nitro group, or the like. Compounds.

  The acyloxystyrene monomer is acyloxystyrene or a substituted product thereof, preferably unsubstituted p-acetoxystyrene. As the substituted acyloxystyrene, one or more hydrogen atoms other than hydrogen of the acyloxy group are alkyl groups having 1 to 5 carbon atoms, halogen atoms, amino groups, carboxyl groups, sulfo groups, cyano groups, methoxy groups, nitro groups. And a compound substituted with a group or the like. As an acyloxy group, a C1-C5 thing is preferable, More preferably, it is an acetoxy group. The acyloxy group is particularly preferably para to the vinyl group, but may be ortho or meta.

  The divinylbenzene monomer is divinylbenzene or a substituted product thereof, preferably divinylbenzene. As a substitute of divinylbenzene, one or more hydrogen atoms of divinylbenzene are alkyl groups having 1 to 5 carbon atoms, halogen atoms, amino groups, carboxyl groups, sulfo groups, cyano groups, methoxy groups, nitro groups, etc. Examples include substituted compounds.

  The amount of acyloxystyrene monomer in the total amount of styrene monomer, acyloxystyrene monomer, and divinylbenzene monomer during suspension copolymerization is preferably 0.2-20. % By weight, more preferably 1-15% by weight, still more preferably 2-8% by weight.

  In the production method, the acyloxystyrene structural unit is finally converted into a hydroxystyrene structural unit (for example, the above-mentioned structural unit (B) or a substituted product thereof) by hydrolysis (described later). The blending ratio of the monomer determines the amount of hydroxyl groups in the porous resin beads finally obtained. However, as will be described later, the degree of hydrolysis in the hydrolysis treatment is not necessarily 100%, so the amount of hydroxyl groups in the finally obtained porous resin beads is not uniquely determined by the amount of acyloxystyrene monomer. .

  The amount of divinylbenzene monomer in the total amount of styrene monomer, acyloxystyrene monomer and divinylbenzene monomer during suspension copolymerization is obtained as described above. It defines the “crosslinking degree” of the porous resin beads, and may be appropriately adjusted so that the crosslinking degree satisfies the relational expression (1) (and is 2% by weight or more). It is 10% by weight, more preferably 3 to 8% by weight, and further preferably 5 to 8% by weight.

  In the porous resin beads of the present invention, the amount of hydroxyl groups and the degree of crosslinking satisfy the above relational expression (1) (and the amount of hydroxyl groups is 0.01 mmole / g or more and the degree of crosslinking is 2% by weight or more). It is necessary to set as follows. Therefore, in this production method, the amount of acyloxystyrene monomer and divinylbenzene monomer during suspension copolymerization and the degree of hydrolysis during hydrolysis treatment are comprehensively adjusted.

  Suspension copolymerization is performed by stirring each monomer and the organic solvent described above in water. In the present specification, the “organic solvent” means a solvent other than water in the suspension copolymerization system. In the production method, liquid hydrocarbons and alcohols are preferably used as the organic solvent. Liquid hydrocarbons include aliphatic saturated or unsaturated hydrocarbons, or aromatic hydrocarbons. Preferred are aromatic hydrocarbons such as benzene, toluene and xylene, and aliphatic hydrocarbons having 5 to 12 carbon atoms, and more preferred are n-hexane, n-heptane, n-octane, isooctane, undecane, dodecane, etc. It is. Moreover, as alcohol, an aliphatic alcohol is mentioned, for example, Carbon number of the alkyl group becomes like this. Preferably it is 5-12. More preferable alcohols include 2-ethylhexyl alcohol, t-amyl alcohol, nonyl alcohol, 2-octanol, decanol, lauryl alcohol, cyclohexanol and the like.

  The above organic solvents may be used alone or in combination of two or more, but are preferably used by mixing liquid hydrocarbon and alcohol.

  In the suspension copolymerization, the amount of the organic solvent relative to the total amount of monomers is weight ratio (organic solvent / monomer) from the viewpoint of easily obtaining porous resin beads having a specific surface area within the above-mentioned range. ), Preferably 0.5 to 2.0, more preferably 0.8 to 1.8. Further, the weight ratio in the case of using a mixture of liquid hydrocarbon and alcohol as the organic solvent may be appropriately determined according to the specific combination of liquid hydrocarbon and alcohol. For example, when isooctane and 2-ethylhexyl alcohol are used, the weight ratio (to isooctane / 2-ethyl) is selected from the viewpoint that the obtained porous resin beads have a specific surface area within the above-described range. (Xyl alcohol) is preferably 1/9 to 6/4.

  A conventionally known method may be used as the suspension copolymerization method itself. For example, the dispersion stabilizer used in the suspension copolymerization includes one or more hydrophilic colloid components such as polyhydric alcohol, polyacrylic acid, carboxymethylcellulose, gelatin, or poorly soluble powder such as calcium carbonate. , Calcium phosphate, calcium sulfate, barium sulfate, bentonite and the like. A specific example of a preferred dispersion stabilizer is polyvinyl alcohol. What is necessary is just to select the usage-amount of a dispersion stabilizer suitably according to the kind etc. of a dispersion stabilizer, for example, it is 0.01-20 weight% of the weight of the water to be used. Examples of the polymerization initiator used in suspension copolymerization include peroxides and azo compounds as radical polymerization initiators. Specific examples of the polymerization initiator include benzoyl peroxide, dilauroyl peroxide, 1,1-di (t-butylperoxy) -2-methylcyclohexane, di-t-butyl peroxide, distearoyl peroxide, di- t-hexyl peroxide, t-butylcumyl peroxide, 1,1-di (t-hexylperoxy) -3,3,5-trimethylcyclohexane, 1,1-di (t-butylperoxy) cyclohexane, 1,1 , 3,3-tetramethylbutylperoxy-2-ethylhexanoate, t-hexylperoxy-2-ethylhexanoate, 2,2'-azobisisobutyronitrile, 2,2'-azobis-2- Examples include methylbutyronitrile and 2,2′-azobis-2,4-dimethylvaleronitrile. The reaction conditions for suspension copolymerization can be appropriately set, and examples include stirring at 60 to 90 ° C. for 30 minutes to 24 hours.

  By the suspension copolymerization, a styrene-acyloxystyrene-divinylbenzene copolymer can be obtained. Next, the obtained copolymer is appropriately washed, classified, etc., and then subjected to a hydrolysis treatment described below.

  By subjecting the styrene-acyloxystyrene-divinylbenzene copolymer obtained by the suspension copolymerization to a hydrolysis treatment, the acyloxy group is converted to a hydroxyl group to obtain a styrene-hydroxystyrene-divinylbenzene copolymer. be able to. Such hydrolysis treatment can be performed by known means and conditions. For example, an acid catalyst (hydrochloric acid in dioxane, hydrochloric acid in acetone, hydrobromic acid, etc.) may be used, and an alkaline catalyst ( Hydrazine monohydrate, an aqueous solution of sodium hydroxide containing an organic solvent, tetramethylammonium hydroxide, aqueous ammonia, etc.) may be used. Examples of the solvent include tetrahydrofuran, ethanol, dioxane and the like. The reaction conditions for the hydrolysis treatment can be set as appropriate. For example, when hydrolyzing using an aqueous sodium hydroxide solution containing ethanol, the amount of sodium hydroxide used is 1 to 10 times equivalent to that of acyloxystyrene. The amount of ethanol used is 1 to 10 times the weight of water used, and the reaction is carried out at 50 to 80 ° C. for 1 to 48 hours. In this hydrolysis treatment, it is not always necessary to convert all acyloxy groups to hydroxyl groups (that is, the degree of hydrolysis is 100%), and the amount of hydroxyl groups in the obtained porous resin beads is the above relational expression (1). The degree of hydrolysis may be appropriately adjusted so as to satisfy the above (and 0.01 mmole / g or more). The degree of hydrolysis can be adjusted to a desired percentage by the temperature, time, amount of catalyst, etc. of the hydrolysis reaction.

  After the hydrolysis treatment, treatments such as washing and classification may be performed as appropriate. Through the treatment as described above, the porous resin beads of the present invention can be obtained.

  The porous resin beads of the present invention can be used as a carrier for chemical synthesis. In particular, it can be preferably used in the synthesis of nucleotides such as oligonucleotides or derivatives thereof. In this case, the porous resin beads of the present invention can be used as a solid support in the synthesis by the solid phase phosphoramidite method or the like, which has been conventionally performed using glass beads or the like as a support. An apparatus for automatically performing such synthesis is also commercially available, and porous resin beads in which a linker is bonded to a hydroxyl group in advance can be applied to such an automatic synthesis apparatus.

  As described above, when the nucleotide or derivative thereof is synthesized in an organic solvent using the porous resin beads of the present invention as a solid phase carrier, the distance between adjacent hydroxyl groups is determined by an appropriate swelling action by the organic solvent, and the adjacent synthesis reaction. Are presumed to be retained to a degree sufficient to prevent mutual inhibition, and as a result, the target product can be obtained with high purity and high yield.

  EXAMPLES Hereinafter, although an Example demonstrates this invention concretely, this invention is not limited to these Examples.

Example 1
(Suspension copolymerization)
A 2 L separable flask equipped with a cooler, a stirrer and a nitrogen introduction tube was placed in a constant temperature water bath, and 48 g of polyvinyl alcohol (manufactured by Wako Pure Chemical Industries, average polymerization degree: about 500) and 1600 g of distilled water were added at 400 rpm. Stir. While flowing cooling water and nitrogen gas, the temperature of the constant temperature bath was set to 55 ° C. and stirring was continued to dissolve polyvinyl alcohol. Separately, 80 g of styrene (manufactured by Wako Pure Chemical Industries), 5 g of p-acetoxystyrene (manufactured by Aldrich), 15 g of divinylbenzene having a purity of 55% (manufactured by Wako Pure Chemical Industries), 50 g of 2-ethylhexanol (manufactured by Wako Pure Chemical Industries) Then, 50 g of isooctane (manufactured by Wako Pure Chemical Industries, Ltd.) and 1.8 g of benzoyl peroxide (manufactured by Nippon Oil & Fats, 25% water content) were mixed and dissolved, and the resulting solution was added to the above separable flask. The mixture was stirred at room temperature under a nitrogen stream at a peripheral speed of 2.0 m / s, then heated to 80 ° C. and subjected to suspension copolymerization for 24 hours.

(Washing)
The copolymerized product obtained above was filtered and washed with distilled water and acetone (manufactured by Wako Pure Chemical Industries, Ltd.), and then dispersed in acetone so that the total amount was about 2 L. The dispersed copolymer product was further uniformly dispersed by an ultrasonic homogenizer. Next, the dispersed copolymer product was filtered and washed again with distilled water and acetone, and then dispersed again in acetone so that the total amount was about 1 L.

(Classification)
The dispersion obtained above was allowed to stand to precipitate a bead-shaped copolymer. After the dispersion was tilted, it was left to the extent that the precipitate was not disturbed, and then the supernatant acetone was discarded. Acetone was added again to the remaining precipitate to make a total volume of about 1 L, and the mixture was allowed to stand as described above, and then the supernatant acetone was discarded. Classification was performed by repeating this operation procedure 12 times. Finally, the remaining precipitate was collected by filtration and dried under reduced pressure to obtain 88 g of a powdery styrene-acetoxystyrene-divinylbenzene copolymer.

(Hydrolysis)
A 1 L separable flask equipped with a cooler, a stirrer and a nitrogen introduction tube was placed in a constant temperature water bath, and 70 g of the styrene-acetoxystyrene-divinylbenzene copolymer obtained above and 467 g of tetrahydrofuran (manufactured by Wako Pure Chemical Industries, Ltd.) were used. The mixture was added and stirred at 200 rpm. While flowing cooling water and nitrogen gas, the temperature of the constant temperature bath was set to 50 ° C. and stirring was continued to disperse the copolymer. To this dispersion, 105 g of hydrazine monohydrate (manufactured by Wako Pure Chemical Industries, Ltd.) was added and subjected to a hydrolysis reaction for 15 hours. The reaction mixture was neutralized with hydrochloric acid, and then filtered and washed with distilled water and acetone. The remaining precipitate was collected by filtration and dried under reduced pressure to obtain 83 g of porous resin beads composed of a powdery styrene-hydroxystyrene-divinylbenzene copolymer.

(Measurement)
It was 0.35 mmole / g when the amount of hydroxyl groups of the porous resin bead obtained above was measured by the above-mentioned method. The degree of crosslinking of the porous resin beads was (15 × 0.55) ÷ (80 + 5 + 15) × 100 = 8.25.
Therefore, (hydroxyl amount) ² × crosslinking degree is 0.35 ² × 8.25 = 1.01, which satisfies the relational expression (1) of the present invention.

Furthermore, when the specific surface area and average pore diameter of the porous resin beads were measured by the above-described methods, they were 55 m ² / g and 22 nm, respectively.

(Comparative Example 1)
A 2 L separable flask equipped with a cooler, a stirrer and a nitrogen introduction tube was placed in a constant temperature water bath, and 48 g of polyvinyl alcohol (manufactured by Wako Pure Chemical Industries, average polymerization degree: about 500) and 1600 g of distilled water were added at 400 rpm. Stir. While flowing cooling water and nitrogen gas, the temperature of the constant temperature bath was set to 55 ° C. and stirring was continued to dissolve polyvinyl alcohol. Separately, 60 g of styrene (manufactured by Wako Pure Chemical Industries), 10 g of p-acetoxystyrene (manufactured by Aldrich), 30 g of divinylbenzene (manufactured by Wako Pure Chemical Industries) 30 g, 50 g of 2-ethylhexanol (manufactured by Wako Pure Chemical Industries) Then, 50 g of isooctane (manufactured by Wako Pure Chemical Industries, Ltd.) and 1.8 g of benzoyl peroxide (manufactured by Nippon Oil & Fats, 25% water content) were mixed and dissolved, and the resulting solution was added to the above separable flask. The mixture was stirred at room temperature under a nitrogen stream at a peripheral speed of 2.0 m / s, then heated to 80 ° C. and subjected to suspension copolymerization for 24 hours.

  The copolymerized product obtained above was washed, classified and hydrolyzed in the same manner as in Example 1 to obtain 87 g of porous resin beads consisting of a powdery styrene-hydroxystyrene-divinylbenzene copolymer. .

It was 0.54 mmole / g when the amount of hydroxyl groups of the porous resin bead obtained above was measured by the above-mentioned method. The degree of crosslinking of the porous resin beads was (30 × 0.55) ÷ (60 + 10 + 30) × 100 = 16.5.
Therefore, (hydroxyl amount) ² × crosslinking degree is 0.54 ² × 16.5 = 4.81, which does not satisfy the relational expression (1) of the present invention.

Furthermore, when the specific surface area and average pore diameter of the porous resin beads were measured by the above-described methods, they were 80 m ² / g and 27 nm, respectively.

  The porous resin beads of the present invention are useful as a carrier for chemical synthesis, and can perform a chemical synthesis reaction that can increase both the yield and purity of the synthetic substance to be produced.

Claims (5)

A porous resin bead comprising a styrene-hydroxystyrene-divinylbenzene copolymer,
The amount of hydroxyl groups (mmole / g) and the degree of crosslinking (% by weight) of the porous resin beads are expressed by the following relational expression (1):
(Amount of hydroxyl group) ² x degree of crosslinking <2 (1)
And the amount of the hydroxyl group is 0.01 mmole / g or more and the degree of crosslinking is 2% by weight or more,
Here, the degree of crosslinking indicates the weight percentage of the divinylbenzene monomer relative to the total weight of the monomers added when synthesizing the porous resin beads.
Porous resin beads. The porous resin bead according to claim 1 whose specific surface area measured by BET method is 10-300 m < ² > / g.   The porous resin beads according to claim 1 or 2, wherein an average pore diameter measured by a mercury intrusion method is 1 to 200 nm.   A styrene-hydroxystyrene-divinylbenzene copolymer is obtained by suspension copolymerization of a styrene monomer, an acyloxystyrene monomer, and a divinylbenzene monomer using an organic solvent and water. The porous material according to any one of claims 1 to 3, which is obtained by synthesizing a styrene-divinylbenzene copolymer and then hydrolyzing the styrene-acyloxystyrene-divinylbenzene copolymer. Resin beads. A method for producing a porous resin bead comprising a styrene-hydroxystyrene-divinylbenzene copolymer,
The amount of hydroxyl groups (mmole / g) and the degree of crosslinking (% by weight) of the porous resin beads are expressed by the following relational expression (1):
(Amount of hydroxyl group) ² x degree of crosslinking <2 (1)
And the amount of the hydroxyl group is 0.01 mmole / g or more and the degree of crosslinking is 2% by weight or more,
Here, the degree of cross-linking indicates the weight percent of the divinylbenzene monomer relative to the total weight of monomers added when the porous resin beads are synthesized,
The method is
A step of suspending copolymerization of a styrene monomer, an acyloxystyrene monomer, and a divinylbenzene monomer using an organic solvent and water to synthesize a styrene-acyloxystyrene-divinylbenzene copolymer; ,
Hydrolyzing the styrene-acyloxystyrene-divinylbenzene copolymer;
A method for producing porous resin beads.