Separation agent

Abstract

The purpose of the present invention is to provide a separation agent having both excellent molecular structure recognition capability and a hydrophobicity retention capability.　This separation agent comprises modified inorganic particles having inorganic particles and a modifying group supported by the inorganic particles, and the carbon content of the modified inorganic particles is 24 mass% or greater. The carbon content of the modified inorganic particles is preferably 60 mass% or less. Moreover, the average pore diameter of the inorganic particles is preferably 10-10,000 Å. The inorganic particles are preferably a silica gel. The average particle diameter of the modified inorganic particles is preferably 0.1-50 µm.

Description

Separating agent

[0001] This disclosure relates to a separating agent. This application claims priority to Japanese Patent Application No. 2025-015943, filed in Japan on 3 February 2025, which is incorporated herein by reference.

[0002] In techniques for separating and obtaining target substances from mixtures, such as chromatography, setting appropriate separation conditions and, in particular, selecting a separation agent suitable for the target substance, is extremely important.

[0003] Techniques for controlling the retention properties of separation agents by modifying the surface of inorganic particles with various modifying groups are known. For example, in reverse-phase chromatography, which uses a stationary phase with lower polarity than the mobile phase, columns packed with separation agents containing hydrophobic groups, such as C8 columns and C18 columns, are commonly used. In addition, Non-Patent Document 1 comprehensively reviews the separation properties of columns with various hydrophobic groups introduced on the surface of inorganic particles. Furthermore, it is known that the separation properties of columns can be evaluated by the Tanaka test, and Non-Patent Document 2 discloses a simplified evaluation method for general-purpose columns using the Tanaka test.

[0004] Zuvela,P.et al., Chem. Rev., 2019, 119, p.3674-3729McHale,C et al., Microchemical Journal, March 2021, Volume 162, 105793

[0005] However, general-purpose columns such as C8 and C18 columns sometimes have insufficient separation capabilities for compounds with similar structures, posing a challenge in terms of molecular structure recognition. Separators modified with inorganic particles such as pentafluorophenyl groups exhibit superior molecular structure recognition capabilities compared to C8 and C18 columns, but their hydrophobic retention is insufficient. Therefore, there is a need for a separation agent that combines excellent molecular structure recognition capabilities with hydrophobic retention, but this demand has not yet been met.

[0006] This disclosure has been made in view of the above circumstances, and its purpose is to provide a separation agent that possesses excellent molecular structure recognition ability and hydrophobic retention ability.

[0007] In other words, the present disclosure provides a separation agent comprising modified inorganic particles having inorganic particles and a modifying group supported on the inorganic particles, wherein the carbon content of the modified inorganic particles is 24% by mass or more.

[0008] The carbon content of the above-mentioned modified inorganic particles is preferably 60% by mass or less.

[0009] The average pore size of the inorganic particles is preferably 10 to 10,000 Å.

[0010] The inorganic particles mentioned above are preferably silica gel.

[0011] The average particle size of the above-mentioned modified inorganic particles is preferably 0.1 to 50 μm.

[0012] The above modifying group preferably includes a polymerization unit represented by the following formula (1). (In formula (1), R １ X represents hydrogen or an alkyl group having 1 to 6 carbon atoms. ２ is -O-, -NH-, or -N(CH ３ ) indicates R ２ represents an alkylene group having 1 to 30 carbon atoms, a haloalkylene group having 1 to 5 carbon atoms, or a cycloalkylene group having 3 to 10 carbon atoms. Z represents hydrogen, halogen, hydroxyl group, -N(R) ３ ) (Caution ４ ), or a hydroxyalkyl group having 1 to 6 carbon atoms. ３ , R ４ (These represent hydrogen atoms or alkyl groups having 1 to 6 carbon atoms, either identical or distinct. q represents an integer between 2 and 3000.)

[0013] The above-mentioned modified inorganic particles preferably have a structure represented by the following formula (2). (In formula (2), W' represents a single bond or an alkylene group having 1 to 10 carbon atoms. W" represents hydrogen or an alkyl group having 1 to 12 carbon atoms. X represents an amide group, an ester group, an N-alkylamide group having 1 to 3 carbon atoms, an ether group, a sulfoxide group, a sulfone group, a sulfide group, or a phosphate ester group. Y represents an alkylene group having 1 to 30 carbon atoms. V is the same or different and represents an ether group bonded to inorganic particles, an alkoxy group having 1 to 5 carbon atoms, a halogen, an alkyl mercaptyl group having 1 to 20 carbon atoms, a nitrogen-containing group, an allyl group, a 2-methyl-2-propenyl group, or an alkyl group having 1 to 3 carbon atoms. R １ represents hydrogen or an alkyl group having 1 to 6 carbon atoms. X ２ represents -O-, -NH-, or -N(CH ３ ). R ２ represents an alkylene group having 1 to 30 carbon atoms, a haloalkylene group having 1 to 5 carbon atoms, or a cycloalkylene group having 3 to 10 carbon atoms. Z represents hydrogen, a halogen, a hydroxy group, -N(R ３ )(R ４ ), or a hydroxyalkyl group having 1 to 6 carbon atoms. R ３ , R ４ are the same or different and represent hydrogen or an alkyl group having 1 to 6 carbon atoms. p represents an integer of 1 to 10, and q' represents an integer of 10 to 3000. The wavy bond in the formula binds to the surface of the inorganic particles.)

[0014] It is preferable that the above-mentioned separating agent is for liquid chromatography.

[0015] It is preferable that the above-mentioned separating agent is for reverse-phase chromatography.

[0016] According to the present disclosure, it is possible to provide a separating agent having excellent molecular structure recognition ability and hydrophobicity retention ability.

[0017] It is a chromatogram showing the separation of each sample in HPLC using the separating agent prepared in Example 1. It is a chromatogram showing the separation of each sample in HPLC using the separating agent prepared in Example 2.

[0018] The separation agent of this disclosure comprises at least modified inorganic particles. The modified inorganic particles consist of inorganic particles and a modifying group supported on the inorganic particles. In the separation agent of this disclosure, only one type of modified inorganic particle may be used, or two or more types may be used. Furthermore, in the modified inorganic particles, only one type of inorganic particle and one or more types of modifying group may be used.

[0019] The carbon content of the above-mentioned modified inorganic particles is 24% by mass or more, preferably 24.2% by mass or more, more preferably 24.4% by mass or more, and even more preferably 24.6% by mass or more, based on 100% by mass of the total amount of the above-mentioned modified inorganic particles. The carbon content of the above-mentioned modified inorganic particles is, for example, 60% by mass or less, preferably 50% by mass or less, more preferably 40% by mass or less, and even more preferably 35% by mass or less. By having the carbon content of the above-mentioned modified inorganic particles within the above range, a separation agent with excellent molecular structure recognition ability and hydrophobic retention ability can be obtained. The carbon content of the above-mentioned modified inorganic particles can be measured by elemental analysis, and specifically can be determined by the method described in the examples.

[0020] The carbon content of the above-mentioned modified inorganic particles can be adjusted by appropriately adjusting the structure of the modifying group, the type of functional group in the modifying group, the average pore size of the inorganic particles, the average particle size of the inorganic particles, and so on.

[0021] Examples of the inorganic particles mentioned above include silica (preferably silica gel), alumina, zirconia, titania, magnesia, glass, kaolin, titanium oxide, silicates, and hydroxyapatite. Among these, silica (preferably silica gel), alumina, and glass are preferred, with silica gel being more preferred. The inorganic particles may be either porous or non-porous inorganic particles. Examples of the porous inorganic particles include porous silica (preferably porous silica gel), alumina, zirconia, titania, magnesia, glass, kaolin, titanium oxide, silicates, and hydroxyapatite. Among these, porous silica (preferably porous silica gel), alumina, or glass are preferred, with porous silica gel being more preferred. Examples of the non-porous inorganic particles include non-porous silica (preferably non-porous silica gel) and non-porous titanium oxide. Among these, non-porous silica gel is preferred. In this specification, the term "silica gel" may be used to refer to a concept that includes both porous silica gel and non-porous silica gel.

[0022] The average particle size of the inorganic particles is, for example, 0.1 to 50 μm, preferably 0.1 to 30 μm, more preferably 1 to 10 μm, even more preferably 1.2 to 7.5 μm, and particularly preferably 1.5 to 6 μm. When the average particle size of the inorganic particles is within the above range, the hydrophobic retention capacity of the separation agent tends to be better.

[0023] When the inorganic particles are porous inorganic particles, the average pore size of the inorganic particles is, for example, 10 to 10,000 Å, preferably 25 to 1,000 Å, more preferably 50 to 500 Å, even more preferably 75 to 300 Å, and particularly preferably 100 to 150 Å. When the average pore size of the inorganic particles is within the above range, the hydrophobic retention capacity of the separation agent tends to be better.

[0024] The specific surface area of ​​the above inorganic particles is, for example, 5 to 1000 m² when porous inorganic particles are used. ２ The amount is / g, preferably 10 to 500m ２ It is / g. When non-porous inorganic particles are used, the above specific surface area is, for example, 0.01 m².２ / g or more, 5m ２ It is less than / g, preferably 0.01 to 4m ２ The value is / g. When using core-shell type particles, as described later, as the inorganic particles, their specific surface area corresponds to the specific surface area of ​​the shell.

[0025] The average particle size of the modified inorganic particles can be considered to be the same as the average particle size of the inorganic particles used. Generally, when the modifying group is supported on the inorganic particles, there is no change in the average particle size beyond the error before and after support. Therefore, the average particle size of the modified inorganic particles is, for example, 0.1 to 50 μm, preferably 0.1 to 30 μm, more preferably 1 to 10 μm, even more preferably 1.2 to 7.5 μm, and particularly preferably 1.5 to 6 μm. The average particle size of the inorganic particles and the modified inorganic particles refers to the diameter if they are spherical, and in the case of amorphous particles, it is expressed as the diameter of the sphere that is equal to the volume of the amorphous particle. The average particle size of the inorganic particles and the modified inorganic particles can be measured using a device that measures using a microscope image, for example, a Mastersizer 2000E (manufactured by Malvern Panalogical).

[0026] The above-mentioned modified inorganic particles are preferably spherical particles with an aspect ratio of 2 or less, more preferably 1.5 or less. The closer the modified inorganic particles are to a perfect sphere, the better, and the lower limit of the aspect ratio is, for example, 1. The aspect ratio can be measured, for example, by the following method: The sample is randomly scattered on an observation table and observed from directly above with an electron microscope or optical microscope. In any screen where 10 or more primary particles that are not in contact with or overlapping with any other particles are observed, the major axis and minor axis (the length of the longest part perpendicular to the major axis) are determined for each individual primary particle in the screen, and the ratio of the two is taken as the aspect ratio of the individual particle. The aspect ratio used herein is the arithmetic mean of the aspect ratios for all independent primary particles in the screen. A primary particle is a particle in which the interface between particles can be clearly observed. Normally, observations are performed by appropriately dispersing primary particles on the sample stage to avoid overlapping; however, accidental overlapping is unavoidable, and there are also bulk particles formed by the aggregation of multiple primary particles, but these are excluded from observation.

[0027] As the inorganic particles mentioned above, core-shell type particles having a non-porous core and a porous shell on its outer surface may be used. In this specification, the core-shell type particles are classified as porous inorganic particles. Here, non-porous refers to the specific surface area (m²) of the core particle's surface as measured by the BET method. ２ Let A be the amount of particles per gram ( / g), and the surface area (calculated from the particle radius r, 4πr) obtained from the particle size of the core particles. ２ The surface area per unit weight (m²) can be calculated from the above. ２ When B is the amount of energy per gram (A-B), then (A-B) / B × 100 is less than 20. On the other hand, porosity refers to a material whose specific surface area, as measured by the BET method, is 10 mm². ２ This refers to items that are 1 / g or more in weight.

[0028] The ratio of the core thickness to the shell thickness of the above-mentioned core-shell type particle is usually 1:9 to 9:1, and is preferably 4:1 to 2:1 from the viewpoint of ensuring good separation characteristics of the target substance. Here, the core thickness refers to the diameter of the core, and the shell thickness refers to the value obtained by subtracting the core diameter from the diameter of the core-shell type particle and dividing that value by 2. The above ratio can be adjusted by adjusting the shell thickness of the core-shell particle using the method described later.

[0029] The average particle size of the core-shell type particles is, for example, 0.1 to 10 μm, preferably 1 to 5 μm. In this specification, the average particle size of the core-shell type particles refers to the average particle size measured by the centrifugal sedimentation method.

[0030] Examples of materials for the core constituting the above-mentioned core-shell type particles include inorganic substances, specifically glass, metals such as titanium and zirconium or their oxides, and clay minerals such as bentonite and mica.

[0031] As the material for the shell constituting the above-mentioned core-shell type particles, from the viewpoint of easily producing the core-shell type particles, it is preferable that the material is a compound obtained by further hydrolysis of a polyalkoxysiloxane obtained by partial hydrolysis of an alkoxysilane. The above-mentioned alkoxysilane is preferably a tetraalkoxysilane, and among these, it is preferable to use tetramethoxylane, tetraethoxysilane, tetrapropoxysilane, and tetrabutoxysilane, and more preferably tetraethoxysilane.

[0032] A method for producing the above-mentioned core-shell type particles can be found in Japanese Patent Publication No. 49-36396. Specifically, first, partial hydrolysis of alkoxysilane is performed to produce polyalkoxysiloxane. Then, the obtained polyalkoxysiloxane is dissolved in a solvent such as ether, acetone, or dichloromethane to prepare a solution of polyalkoxysiloxane. This solution is applied to the core particles or the core particles are immersed in this solution, and then the solvent is removed to deposit the polyalkoxysiloxane as a shell on the surface of the core particles. Subsequently, the deposited polyalkoxysiloxane is subjected to polycondensation (hydrolysis) in the presence of water. This yields core-shell type particles.

[0033] The thickness of the shell constituting the above-mentioned core-shell type particle can be appropriately adjusted within the range of 0.1 to 100 μm, and one method for doing so is to adjust the viscosity of the alkoxysilane that forms the shell. For example, to increase the thickness of the shell, the viscosity of the alkoxysilane can be lowered.

[0034] One method for adjusting the specific surface area and pore diameter of a shell is to adjust the pH of the aqueous solution used when stacking the shells and carrying out polycondensation. For example, to increase the specific surface area and pore diameter, one can consider increasing the pH.

[0035] The average pore diameter of the shell of the above-mentioned core-shell type particles may be, for example, 9 nm or more, or 30 nm or more. The average pore diameter is usually 300 nm or less. When the average pore diameter is within the above range, it is expected that the ligand substance will penetrate into the interior of the shell of the above-mentioned core-shell type particles, contributing to good separation of the target substance. The average pore diameter can be measured by the gas adsorption method. The gas adsorption method is a method in which a gas is adsorbed onto a porous sample by changing the pressure, the amount of adsorption is measured, and the specific surface area, pore volume, pore distribution, etc. are calculated from the adsorption-desorption isotherm obtained by plotting the relative pressure (= ratio of the pressure at the adsorption equilibrium state to the saturated vapor pressure) and the amount of adsorption. JIS Z8831-2 (mesopores and macropores) or JIS Z8831-3 (micropores), which specify the pore size distribution and pore characteristics of powders (solids), can be applied mutatis mutandis.

[0036] As the core-shell particles mentioned above, commercially available core-shell silica gel may be used. In addition, commercially available core-shell silica gel may be used in which the core is made of glass and the shell is made of silica gel (hydrolyzed polyalkoxysiloxane).

[0037] In the separation agent of this disclosure, the modifying group is a group supported on the surface of the inorganic particles, and modifies the surface of the inorganic particles. That is, the inorganic particles support a compound as a modifying group. The compound supported by the inorganic particles may be a polymer or a low molecular weight compound.

[0038] In particular, the modifying group is preferably a group containing a polymerization unit represented by the following formula (1). That is, it is preferable that the modified inorganic particles have a polymer containing a polymerization unit represented by the following formula (1) supported on them. Hereafter in this specification, the polymer containing a polymerization unit represented by the following formula (1) may be referred to as a "hydrophobic polymer".

[0039] In formula (1), R １ X represents hydrogen or an alkyl group having 1 to 6 carbon atoms. ２ is -O-, -NH-, or -N(CH３ ) indicates R ２ represents an alkylene group having 1 to 30 carbon atoms, a haloalkylene group having 1 to 5 carbon atoms, or a cycloalkylene group having 3 to 10 carbon atoms. Z represents hydrogen, halogen, hydroxyl group, -N(R) ３ ) (Caution ４ ), or a hydroxyalkyl group having 1 to 6 carbon atoms. ３ , R ４ represents hydrogen or an alkyl group having 1 to 6 carbon atoms, either identical or different. q represents an integer between 2 and 3000.

[0040] The above R １ R represents hydrogen or an alkyl group having 1 to 6 carbon atoms. １ Examples of C1-C6 alkyl groups in include linear or branched alkyl groups such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, pentyl, and hexyl groups. １ Hydrogen, methyl groups, and ethyl groups are preferred as the elements.

[0041] The above X ２ is -O-, -NH-, or -N(CH ３ ) indicates.

[0042] The above R ２ This represents an alkylene group having 1 to 30 carbon atoms, a haloalkylene group having 1 to 5 carbon atoms, or a cycloalkylene group having 3 to 10 carbon atoms. In particular, the above R ２ Preferably, it is an alkylene group having 1 to 30 carbon atoms.

[0043] The above R ２Examples of alkylene groups having 1 to 30 carbon atoms include methylene group, dimethylethylene group, 1-methylethylene group, 1,1-dimethylmethylene group, trimethylene group, 2-methyltrimethylene group, tetramethylene group, pentamethylene group, 2-methylpentamethylene group, 2-ethylpentamethylene group, 3-methylpentamethylene group, 3-ethylpentamethylene group, hexamethylene group, and 2-methyl Examples of linear or branched alkylene groups include hexamethylene group, 2-ethylhexamethylene group, 3-methylhexamethylene group, 3-ethylhexamethylene group, octamethylene group, nonamethylene group, decamethylene group, undecamethylene group, dodecamethylene group, tridecamethylene group, tetradecamethylene group, pentadecamethylene group, hexadecamethylene group, and octadecamethylene group. Among these, linear or branched alkylene groups having 3 to 30 carbon atoms are preferred, more preferably linear or branched alkylene groups having 8 to 20 carbon atoms, even more preferably linear or branched alkylene groups having 10 to 20 carbon atoms, and particularly preferably linear or branched alkylene groups having 12 to 18 carbon atoms.

[0044] The above R ２ Examples of C1-C5 haloalkylene groups in this context include fluoromethylene group, perfluoromethylene group, fluorodimethylene group, 1,1-difluorodimethylene group, 1,2-difluorodimethylene group, perfluorodimethylene group, 1,1-difluorotrimethylene group, 1,2-difluorotrimethylene group, 1,3-difluorotrimethylene group, 1,1,2,2-tetrafluorotrimethylene group, and perfluorotrimethylene group. Examples include fluoroalkylene groups such as 1,1-difluorotetramethylene group, 1,1,2,2-tetrafluorotetramethylene group, 1,1-difluoropentamethylene group, and 1,1,2,2-tetrafluoropentamethylene group; chloroalkylene groups such as chloromethylene group and chlorodimethylene group; bromoalkylene groups such as bromomethylene group and bromodimethylene group; and iodidealkylene groups such as iodide methylene group and iodide dimethylene group. Among these, fluoroalkylene groups having 1 to 5 carbon atoms are preferred, and fluoroalkylene groups having 1 to 3 carbon atoms are more preferred.

[0045] The above R２ Examples of cycloalkylene groups having 3 to 10 carbon atoms include cyclopropylene, cyclobutylene, 1,2-cyclopentylene, 1,3-cyclopentylene, cyclopentylidene, 1,2-cyclohexylene, 1,3-cyclohexylene, 1,4-cyclohexylene, and cyclohexylidene. Among these, cycloalkylene groups having 3 to 6 carbon atoms are preferred, and 1,2-cyclohexylene, 1,3-cyclohexylene, and 1,4-cyclohexylene are more preferred.

[0046] The above Z is hydrogen, halogen (preferably fluorine), hydroxyl group, -N(R) ３ ) (Caution ４ ) or a hydroxyalkyl group having 1 to 6 carbon atoms. ３ , R ４ R represents hydrogen or an alkyl group having 1 to 6 carbon atoms, either identical or different. ３ and R ４ Examples of C1-C6 alkyl groups in include linear or branched alkyl groups such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, pentyl, and hexyl groups. ３ and R ４ The preferred group is hydrogen, a methyl group, an ethyl group, a propyl group, or an isopropyl group, with a methyl group or an ethyl group being more preferred. The above Z is hydrogen, a halogen, or -N(R ３ ) (Caution ４ ) is preferred, and hydrogen or halogen is more preferred.

[0047] The above q represents an integer between 2 and 3000. In one embodiment, the above q is preferably an integer between 10 and 3000, more preferably an integer between 15 and 2500, and even more preferably an integer between 20 and 2000. In another embodiment, the above q is preferably an integer between 2 and 300.

[0048] In the above formula (1), R ２ When R is an alkylene group having 1 to 30 carbon atoms, １ X is hydrogen or an alkyl group having 1 to 6 carbon atoms.２ is -O-, -NH-, or -N(CH ３ )- and Z is hydrogen, hydroxyl group, -N(R ３ ) (Caution ４ ), or preferably a hydroxyalkyl group having 1 to 6 carbon atoms. In this case, Z is more preferably hydrogen or -N(R ３ ) (Caution ４ ) and more preferably hydrogen.

[0049] In the above formula (1), R ２ When R is a haloalkylene group having 1 to 5 carbon atoms, １ X is hydrogen or an alkyl group having 1 to 6 carbon atoms. ２ is -O-, -NH-, or -N(CH ３ )- and Z is preferably hydrogen or a halogen.

[0050] In the above formula (1), R ２ When R is a cycloalkylene group having 3 to 10 carbon atoms, １ X is hydrogen or an alkyl group having 1 to 6 carbon atoms. ２ is -O-, -NH-, or -N(CH ３ )- and Z is hydrogen, -N(R ３ ) (Caution ４ ), or preferably a hydroxyalkyl group having 1 to 6 carbon atoms. In this case, Z is more preferably hydrogen or -N(R ３ ) (Caution ４ ) and more preferably hydrogen.

[0051] The weight-average molecular weight of the hydrophobic polymer described above is preferably between 1,000 and 5,000,000, from the viewpoint of the polymer's solubility in the solvent, preventing aggregation of inorganic particles when the polymer is supported on inorganic particles, suppressing dissolution in the mobile phase solvent, and maintaining the amount of bonding when chemically bonding to inorganic particles, but the optimal point varies depending on the type of polymer. In this specification, the weight-average molecular weight of the polymer is, for example, when the modified inorganic particles described above have a structure represented by formula (2) or (4) described later, the repeating unit of the main chain is -(CH ２ -CAB) ｋThis refers to the part marked with -. The above weight-average molecular weight can be measured by gel permeation chromatography (GPC) using polystyrene, poly(methyl methacrylate), and poly(ethylene glycol) as standard substances. In the method for producing the separation agent described later, if the method includes steps (i), (iv), or (v), the polymerization of the monomer having a hydrophobic group and bonding with inorganic particles occur simultaneously, so the weight-average molecular weight is estimated from the supernatant of the polymerization solution. In addition, in the method for producing the separation agent described later, if the method includes steps (ii) or (iii), the weight-average molecular weight of the polymer having a hydrophobic group in the repeating unit of the main chain is measured before bonding the polymer to the inorganic particles.

[0052] The loading rate (%) of the hydrophobic polymer in the above-mentioned separation agent is preferably 1 to 50% by mass, more preferably 10 to 40% by mass, and even more preferably 20 to 30% by mass. The above loading rate indicates the proportion of the hydrophobic polymer carried by the modified supported particles in the above-mentioned separation agent. By having the above loading rate within the above range, it is possible to appropriately exhibit hydrophobic retention while avoiding unnecessarily strong retention or broad peaks. The above loading rate can be measured by elemental analysis and can be calculated based on the measurement results of the carbon content of the inorganic particles before the hydrophobic polymer is bound and the carbon content of the obtained modified supported particles, assuming that all carbon other than the carbon contained in the inorganic particles before the hydrophobic polymer is bound originates from the hydrophobic polymer.

[0053] The above-mentioned modified inorganic particles may have a structure represented by, for example, the following formula (2) or (4).

[0054]

[0055] In formula (2), W' represents a single bond or an alkylene group having 1 to 10 carbon atoms. W'' represents hydrogen or an alkyl group having 1 to 12 carbon atoms. X represents an amide group, an ester group, an N-alkylamide group having 1 to 3 carbon atoms, an ether group, a sulfoxide group, a sulfone group, a sulfide group, or a phosphate ester group. Y represents an alkylene group having 1 to 30 carbon atoms. V represents the same or different ether group bonded to an inorganic particle, an alkoxy group having 1 to 5 carbon atoms, a halogen, an alkyl mercaptyl group having 1 to 20 carbon atoms, a nitrogen-containing group, an allyl group, a 2-methyl-2-propenyl group, or an alkyl group having 1 to 3 carbon atoms. １ X represents hydrogen or an alkyl group having 1 to 6 carbon atoms. ２ is -O-, -NH-, or -N(CH ３ ) indicates R ２ represents an alkylene group having 1 to 30 carbon atoms, a haloalkylene group having 1 to 5 carbon atoms, or a cycloalkylene group having 3 to 10 carbon atoms. Z represents hydrogen, halogen, hydroxyl group, -N(R) ３ ) (Caution ４ ), or a hydroxyalkyl group having 1 to 6 carbon atoms. ３ , R ４ ' represents hydrogen or an alkyl group having 1 to 6 carbon atoms, either identical or different. p is an integer from 1 to 10, and q' is an integer from 10 to 3000. Bonds indicated by wavy lines in the formula are bonded to the surface of inorganic particles.

[0056] In formula (2) above, the bonding method of the polymerization units represented by formula (1) and the polymerization units with p attached may be random, alternating, or block.

[0057] The above W' represents a single bond or an alkylene group having 1 to 10 carbon atoms. Examples of linear or branched alkylene groups in the above W' include methylene group, dimethylethylene group, 1-methylethylene group, 1,1-dimethylmethylene group, trimethylene group, 2-methyltrimethylene group, tetramethylene group, pentamethylene group, hexamethylene group, octamethylene group, nonamethylene group, decamethylene group, etc. Among these, linear or branched alkylene groups having 1 to 5 carbon atoms are preferred as the alkylene group having 1 to 10 carbon atoms in the above W', and linear alkylene groups having 1 to 3 carbon atoms are more preferred. The above W' is preferably a single bond, methylene group, dimethylethylene group, or trimethylene group.

[0058] The above W'' represents hydrogen or an alkyl group having 1 to 12 carbon atoms. Examples of C1 to C12 alkyl groups in the above W'' include linear or branched alkyl groups such as methyl group, ethyl group, propyl group, isopropyl group, n-butyl group, isobutyl group, s-butyl group, t-butyl group, pentyl group, hexyl group, 2-ethylhexyl group, nonyl group, and decanyl group. Hydrogen, methyl group, and ethyl group are preferred as the above W''.

[0059] The above X represents an amide group, an ester group, an N-alkylamide group having 1 to 3 carbon atoms, an ether group, a sulfoxide group, a sulfone group, a sulfide group, or a phosphate ester group. Among these, the above X is preferably an amide group, an ester group, or an N-alkylamide group having 1 to 3 carbon atoms.

[0060] The above Y represents an alkylene group having 1 to 30 carbon atoms. Examples of alkylene groups having 1 to 30 carbon atoms in Y include methylene group, dimethylethylene group, 1,1-methylethylene group, trimethylene group, 2-methyltrimethylene group, tetramethylene group, pentamethylene group, 2-methylpentamethylene group, 2-ethylpentamethylene group, 3-methylpentamethylene group, 3-ethylpentamethylene group, hexamethylene group, 2-methylpentamethylene group. Examples of linear or branched alkylene groups include ethylhexamethylene, 2-ethylhexamethylene, 3-methylhexamethylene, 3-ethylhexamethylene, octamethylene, nonamethylene, decamethylene, undecamethylene, dodecamethylene, tridecamethylene, tetradecamethylene, pentamethylene, hexadecamethylene, and octamethylene. Among these, linear or branched alkylene groups having 1 to 10 carbon atoms are preferred, linear or branched alkylene groups having 1 to 5 carbon atoms are more preferred, and methylene, dimethylene, or trimethylene groups are particularly preferred.

[0061] The above V may be the same or different ether group bonded to inorganic particles, a C1-C5 alkoxy group, a halogen, a C1-C20 alkyl mercaptyl group, a nitrogen-containing group, an allyl group, a 2-methyl-2-propenyl group, or a C1-C3 alkyl group. Among these, the above V is preferably an ether group bonded to inorganic particles or a C1-C5 alkoxy group. Examples of the C1-C5 alkoxy group in the above V include a methoxy group or an ethoxy group. Examples of the nitrogen-containing group in the above V include a dimethylamino group, a diethylamino group, a pyrrolidino group, and an imidazolyl group.

[0062] R in equation (2) above １ , X ２ , R ２ As for Z, R in equation (1) above １ , X ２ , R ２ Similar examples can be given to Z, and the preferred embodiments are also similar.

[0063] The above value of p represents an integer between 1 and 10.

[0064] The above q' represents an integer from 10 to 3000, preferably an integer from 15 to 2500, more preferably an integer from 20 to 2000.

[0065] In the above formula (2), R ２ When it is an alkylene group having 1 to 30 carbon atoms, the preferred combinations of R １ , X ２ , and Z are the same as those in the above formula (1). At this time, W' is a single bond or an alkylene group having 1 to 10 carbon atoms, W" is hydrogen or an alkyl group having 1 to 12 carbon atoms, X is an amide group, an ester group, an N-alkylamide group having 1 to 3 carbon atoms, an ether group, a sulfoxide group, a sulfone group, a sulfide group, or a phosphate ester group, and V is, identically or differently, an ether group bonded to inorganic particles, an alkoxy group having 1 to 5 carbon atoms, a halogen, an alkyl mercaptyl group having 1 to 20 carbon atoms, a nitrogen-containing group, an allyl group, a 2-methyl-2-propenyl group, or an alkyl group having 1 to 3 carbon atoms. At this time, W' is more preferably a single bond, X is more preferably an amide group, an ester group, or an N-alkylamide group having 1 to 3 carbon atoms, still more preferably an amide group or an N-alkylamide group having 1 to 3 carbon atoms, and V is more preferably an ether group bonded to inorganic particles or an alkoxy group having 1 to 5 carbon atoms.

[0066] In the above formula (2), R ２ When it is a haloalkylene group having 1 to 5 carbon atoms, R １ , X ２0. The preferred combination of Z is the same as in the above formula (1). At this time, W' is a single bond or an alkylene group having 1 to 10 carbon atoms, W" is hydrogen or an alkyl group having 1 to 12 carbon atoms, X is an amide group, an ester group, an N-alkylamide group having 1 to 3 carbon atoms, an ether group, a sulfoxide group, a sulfone group, a sulfide group, or a phosphate ester group, and V is the same or different and is preferably an ether group bonded to inorganic particles, an alkoxy group having 1 to 5 carbon atoms, a halogen, an alkyl mercaptyl group having 1 to 20 carbon atoms, a nitrogen-containing group, an allyl group, a 2-methyl-2-propenyl group, or an alkyl group having 1 to 3 carbon atoms. At this time, W' is more preferably a single bond, X is more preferably an amide group, an ester group, or an N-alkylamide group having 1 to 3 carbon atoms, still more preferably an amide group or an N-alkylamide group having 1 to 3 carbon atoms, and Z is more preferably an ether group bonded to inorganic particles or an alkoxy group having 1 to 5 carbon atoms.

[0067] 3. In the above formula (2), R ２ When is a cycloalkylene group having 3 to 10 carbon atoms, R １ , X ２ 0. The preferred combination of, Z is the same as in the above formula (1). At this time, W' is a single bond or an alkylene group having 1 to 10 carbon atoms, W" is hydrogen or an alkyl group having 1 to 12 carbon atoms, X is an amide group, an ester group, an N-alkylamide group having 1 to 3 carbon atoms, an ether group, a sulfoxide group, a sulfone group, a sulfide group, or a phosphate ester group, and V is the same or different and is preferably an ether group bonded to inorganic particles, an alkoxy group having 1 to 5 carbon atoms, a halogen, an alkyl mercaptyl group having 1 to 20 carbon atoms, a nitrogen-containing group, an allyl group, a 2-methyl-2-propenyl group, or an alkyl group having 1 to 3 carbon atoms. At this time, W' is more preferably a single bond, X is more preferably an amide group, an ester group, or an N-alkylamide group having 1 to 3 carbon atoms, still more preferably an amide group or an N-alkylamide group having 1 to 3 carbon atoms, and Z is more preferably an ether group bonded to inorganic particles or an alkoxy group having 1 to 5 carbon atoms.

[0068] In formula (4), V' represents an ether group, a C1-C5 alkoxy group, a halogen, a C1-C20 alkyl mercaptyl group, a nitrogen-containing group, an allyl group, a 2-methyl-2-propenyl group, or a C1-C3 alkyl group, either identical or different, bonded to an inorganic particle. Y' represents a single bond or a C1-C30 alkylene group. T' is derived from T, described later, and is a group produced by a chain transfer reaction. R １ X represents hydrogen or an alkyl group having 1 to 6 carbon atoms. ２ is -O-, -NH-, or -N(CH ３ ) indicates R ２ represents an alkylene group having 1 to 30 carbon atoms, a haloalkylene group having 1 to 5 carbon atoms, or a cycloalkylene group having 3 to 10 carbon atoms. Z represents hydrogen, halogen, hydroxyl group, -N(R) ３ ) (Caution ４ ), or a hydroxyalkyl group having 1 to 6 carbon atoms. ３ , R ４ '' represents hydrogen or an alkyl group having 1 to 6 carbon atoms, either identical or different. q'' represents an integer between 2 and 300. The underlined bonds in the formula are bonded to the surface of inorganic particles.

[0069] The above V' represents, either the same or different, an ether group bonded to inorganic particles, a C1-C5 alkoxy group, a halogen, a C1-C20 alkyl mercaptyl group, a nitrogen-containing group, an allyl group, a 2-methyl-2-propenyl group, or a C1-C3 alkyl group. Among these, the above V' is preferably an ether group bonded to inorganic particles or a C1-C5 alkoxy group. Examples of the C1-C5 alkoxy group in the above V' include a methoxy group or an ethoxy group. Examples of the nitrogen-containing group in the above V' include a dimethylamino group, a diethylamino group, a pyrrolidino group, and an imidazolyl group.

[0070] The above Y' represents a single bond or an alkylene group having 1 to 30 carbon atoms. In particular, a single bond or an alkylene group having 1 to 10 carbon atoms is preferred for Y'.

[0071] The above T' is derived from T, which will be described later, and is a group produced by a chain transfer reaction. When T is a C1-C12 haloalkyl group, T' is a halogen-substituted C1-C12 alkylene residue, and when T is a C1-C12 alkyl group having a thiol at its terminus or a C1-C12 alkyl group having a disulfide group within the group, T' is a thioether.

[0072] R in equation (4) above １ , X ２ , R ２ As for Z, R in equation (1) above １ , X ２ , R ２ Similar examples can be given to Z, and the preferred embodiments are also similar.

[0073] The above q'' represents an integer between 2 and 300.

[0074] In the above formula (4), R ２ When R is an alkylene group having 1 to 30 carbon atoms, １ , X ２ Preferably, the combination of Z is the same as in formula (1) above. In this case, V' is the same or different ether group bonded to inorganic particles, a carbon-1 to carbon-5 alkoxy group, a halogen, a carbon-1 to carbon-20 alkyl mercaptyl group, a nitrogen-containing group, an allyl group, a 2-methyl-2-propenyl group, or a carbon-1 to carbon-3 alkyl group, Y' is a single bond or a carbon-1 to carbon-30 alkylene group, and T' is a group derived from T and produced by a chain transfer reaction. In this case, V' is more preferably an ether group bonded to inorganic particles or a carbon-1 to carbon-5 alkoxy group.

[0075] In the above formula (4), R ２ When R is a haloalkylene group having 1 to 5 carbon atoms, １ , X ２Preferably, the combination of Z is the same as in formula (1) above. In this case, V' is the same or different ether group bonded to inorganic particles, a carbon-1 to carbon-5 alkoxy group, a halogen, a carbon-1 to carbon-20 alkyl mercaptyl group, a nitrogen-containing group, an allyl group, a 2-methyl-2-propenyl group, or a carbon-1 to carbon-3 alkyl group, Y' is a single bond or a carbon-1 to carbon-30 alkylene group, and T' is a group derived from T and produced by a chain transfer reaction. In this case, V' is more preferably an ether group bonded to inorganic particles or a carbon-1 to carbon-5 alkoxy group.

[0076] In the above formula (4), R ２ When R is a cycloalkylene group having 3 to 10 carbon atoms, １ , X ２ Preferably, the combination of Z is the same as in formula (1) above. In this case, V' is the same or different ether group bonded to inorganic particles, a carbon-1 to carbon-5 alkoxy group, a halogen, a carbon-1 to carbon-20 alkyl mercaptyl group, a nitrogen-containing group, an allyl group, a 2-methyl-2-propenyl group, or a carbon-1 to carbon-3 alkyl group, Y' is a single bond or a carbon-1 to carbon-30 alkylene group, and T' is a group derived from T and produced by a chain transfer reaction. In this case, V' is more preferably an ether group bonded to inorganic particles or a carbon-1 to carbon-5 alkoxy group.

[0077] The separation agent of this disclosure can separate various chemical substances by contacting them with the substance to be separated. Therefore, the separation agent of this disclosure can be used, for example, as a stationary phase in chromatography, a separation agent in batch processing, etc. Chromatography using the above separation agent may be for analytical purposes or for separation and acquisition purposes.

[0078] Examples of the above-mentioned chromatography include gas chromatography, liquid chromatography, and supercritical fluid chromatography. Examples of the above-mentioned liquid chromatography include column chromatography, high-performance liquid chromatography (HPLC), and thin-layer chromatography (TLC). The above-mentioned liquid chromatography may be normal-phase chromatography or reverse-phase chromatography. In particular, the above-mentioned separation agent is preferably used in liquid chromatography, and more preferably in reverse-phase chromatography.

[0079] When the separation agent of this disclosure is used as a packing material in chromatography, for example, the separation agent can be packed inside a column or capillary to form a stationary phase, and the substance to be separated can be separated by distributing it between the stationary phase and a fluid (mobile phase) that is moving in contact with the stationary phase. Since the separation agent contains modified inorganic particles on which the modifying group is supported, even if a solvent that can dissolve the compound contained in the modifying group, or a mixed solvent containing such a solvent, is used as the developing solvent (mobile phase), the compound will not dissolve, and the function of the stationary phase will not be impaired.

[0080] When the separation agent of this disclosure is used as a stationary phase in liquid chromatography, for example, the target substance can be obtained (separated and acquired) by separating the mobile phase after it has passed through a column packed with the separation agent of this disclosure using a fraction collector, depending on the target substance to be separated.

[0081] The column can be of a known size depending on the volume of the sample. The flow rate in the liquid chromatography is not particularly limited, but is, for example, 0.1 to 8 mL / min, preferably 0.1 to 4 mL / min. The column temperature in the liquid chromatography is, for example, about 0 to 50°C, preferably about 20 to 45°C.

[0082] The mobile phase is preferably a polar solvent, and may contain additives soluble in the polar solvent. Examples of polar solvents include water, alcohols such as methanol and ethanol, acetonitrile, and mixed solvents thereof. Examples of additives include acids, bases, salts, polyethylene glycol, and the like.

[0083] The separation agent of this disclosure can be manufactured by the method described later.

[0084] (Method for producing the separating agent) The method for producing the separating agent of this disclosure includes any of the following steps (i) to (v). (i) A step of radical copolymerizing a hydrophobic (meth)acrylic monomer and / or a hydrophobic (meth)acrylamide monomer with surface-modified inorganic particles to which polymerizable functional groups are bonded. (ii) A step of obtaining a polymer by radical polymerization of a hydrophobic (meth)acrylic monomer and / or a hydrophobic (meth)acrylamide monomer in the presence of a chain transfer agent having a crosslinkable silyl group at its terminus, and a step of silane coupling of the obtained polymer on the surface of the inorganic particles. (iii) A step of obtaining a polymer by radical copolymerizing a hydrophobic (meth)acrylic monomer and / or a hydrophobic (meth)acrylamide monomer with a polymerizable double bond with a silane coupling agent having a polymerizable double bond, and a step of silane coupling of the obtained polymer on the surface of the inorganic particles. (iv) A step of radical copolymerizing a hydrophobic (meth)acrylic monomer and / or a hydrophobic (meth)acrylamide monomer with a polymerizable double bond with a silane coupling agent having a polymerizable double bond in the presence of inorganic particles. (v) A step of introducing chain-mobile functional groups onto the surface of inorganic particles and radically polymerizing a hydrophobic (meth)acrylic monomer and / or a hydrophobic (meth)acrylamide monomer.

[0085] The (meth)acrylic monomer and / or (meth)acrylamide monomer having the hydrophobic group in steps (i) to (v) (hereinafter sometimes simply referred to as "monomer") have the structure represented by the following formula (I).

[0086] In formula (I), R １ X represents hydrogen or an alkyl group having 1 to 6 carbon atoms. ２ is -O-, -NH-, or -N(CH ３ ) indicates R ２ represents an alkylene group having 1 to 30 carbon atoms, a haloalkylene group having 1 to 5 carbon atoms, or a cycloalkylene group having 3 to 10 carbon atoms. Z represents hydrogen, halogen, hydroxyl group, -N(R) ３ ) (Caution ４ ), or a hydroxyalkyl group having 1 to 6 carbon atoms. ３ , R ４ These represent hydrogen or an alkyl group having 1 to 6 carbon atoms, either identical or distinct.

[0087] In the above formula (I), R １ , X ２ , R ２ As Z, the R in equation (1) above is １ , X ２ , R ２ Similar examples can be given to Z, and the preferred embodiments are also similar.

[0088] In the above formula (I), R ２ When R is an alkylene group having 1 to 30 carbon atoms, １ , X ２ The preferred combinations of Z are the same as in equation (1) above.

[0089] In the above formula (I), R ２ When R is a haloalkylene group having 1 to 5 carbon atoms, １ , X ２ The preferred combinations of Z are the same as in equation (1) above.

[0090] In the above formula (I), R ２ When R is a cycloalkylene group having 3 to 10 carbon atoms, １ , X ２ The preferred combinations of Z are the same as in equation (1) above.

[0091] A manufacturing method including step (i) is described below. In step (i), a hydrophobic (meth)acrylic monomer and / or hydrophobic (meth)acrylamide monomer are radically copolymerized with surface-modified inorganic particles to which polymerizable functional groups are attached.

[0092] In the manufacturing method including step (i), examples of polymerizable functional groups bonded to the surface-modified inorganic particles include radical polymerizable functional groups, such as vinyl groups, allyl groups, isopropenyl groups, or C4-C12 alkenyl groups having a double bond at the ω position.

[0093] Surface-modified inorganic particles to which the above polymerizable functional groups are attached can be obtained, for example, by silane coupling of the inorganic particles with a compound represented by the following formula (II). Examples of inorganic particles used in silane coupling with the compound represented by the following formula (II) are the same as those used in the inorganic particles in the separation agent of this disclosure.

[0094] W-X-Y-Si(R ａ ) ３－ｎ (Z ２ ) ｎ (II) In formula (II), W represents a vinyl group, an allyl group, an isopropenyl group, or a C4-C12 alkenyl group having a double bond at the ω position. X represents an amide group, an ester group, a C1-C3 N-alkylamide group, an ether group, a sulfoxide group, a sulfone group, a sulfide group, or a phosphate ester group. Y represents an alkylene group having C1-C30. R ａ Each of these independently represents an alkyl group having 1 to 3 carbon atoms. ２ n is a leaving group that can form a bond between the silicon atom and the inorganic particle in formula (II). n is an integer from 1 to 3.

[0095] The above W represents a vinyl group, an allyl group, an isopropenyl group, or an alkenyl group having 4 to 12 carbon atoms and a double bond at the ω position. Among these, the above W is preferably a vinyl group, an allyl group, or an isopropenyl group.

[0096] The above X represents an amide group, an ester group, an N-alkylamide group having 1 to 3 carbon atoms, an ether group, a sulfoxide group, a sulfone group, a sulfide group, or a phosphate ester group. Among these, the above X is preferably an amide group, an ester group, or an N-alkylamide group having 1 to 3 carbon atoms.

[0097] The above Y represents an alkylene group having 1 to 30 carbon atoms. Examples of alkylene groups having 1 to 30 carbon atoms in Y include methylene group, dimethylethylene group, 1,1-methylethylene group, trimethylene group, 2-methyltrimethylene group, tetramethylene group, pentamethylene group, 2-methylpentamethylene group, 2-ethylpentamethylene group, 3-methylpentamethylene group, 3-ethylpentamethylene group, hexamethylene group, 2-methylpentamethylene group. Examples of linear or branched alkylene groups include ethylhexamethylene, 2-ethylhexamethylene, 3-methylhexamethylene, 3-ethylhexamethylene, octamethylene, nonamethylene, decamethylene, undecamethylene, dodecamethylene, tridecamethylene, tetradecamethylene, pentamethylene, hexadecamethylene, and octamethylene. Among these, linear or branched alkylene groups having 1 to 10 carbon atoms are preferred, linear or branched alkylene groups having 1 to 5 carbon atoms are more preferred, and methylene, dimethylene, or trimethylene groups are particularly preferred.

[0098] The above R ａ Each of these independently represents an alkyl group having 1 to 3 carbon atoms. Among them, the above R ａ A methyl group or an ethyl group is preferred.

[0099] The above Z ２Z is a leaving group that can form a bond between the silicon atom in formula (II) and the inorganic particle. For example, if the inorganic particle is silica gel, it can form a bond between the oxygen atom present on the silica gel surface and the silicon atom in formula (II). Commonly used leaving groups that offer a balance between ease of handling and reactivity include alkoxy groups with 1 to 5 carbon atoms, halogens (chlorine, bromine, or iodine), alkyl mercaptyl groups with 1 to 20 carbon atoms, nitrogen-containing groups (e.g., dimethylamino group, diethylamino group, pyrrolidino group, imidazolyl group), allyl group, or 2-methyl-2-propenyl group. ２ Preferably, the leaving group is an alkoxy group having 1 to 5 carbon atoms, and more preferably a methoxy group or an ethoxy group. The reaction conditions (including catalyst addition) can be adjusted depending on the type of leaving group.

[0100] The compound represented by formula (II) above comprises a compound having the structure represented by W in formula (II) above, and Y-SiR in formula (II) above. ３－ｎ Z ｎ It can be obtained by reacting a compound having the structure represented by the above formula (II) with the compound, and the reaction of these compounds produces "-X-" in formula (II) above.

[0101] Compounds having the structure represented by W in the above formula (II) include acrylic acid in which the hydrogen atoms of the vinyl group may be substituted with an alkyl group having 1 to 12 carbon atoms, and halogenated acrylic acid in which the hydrogen atoms of the vinyl group may be substituted with an alkyl group having 1 to 12 carbon atoms.

[0102] In the above formula (II), Y - SiR ３－ｎ Z ｎ Compounds having the structure represented by the above include silane coupling agents that have a group that is a precursor of X as described above and have an alkoxy group with 1 to 5 carbon atoms as a leaving group.

[0103] A separation agent according to one embodiment of the present disclosure, when produced by a manufacturing method including step (i) described above, is obtained by radical copolymerization of a hydrophobic (meth)acrylic monomer and / or a hydrophobic (meth)acrylamide monomer with surface-modified inorganic particles to which the polymerizable functional group is bonded. The copolymerization method involves radical copolymerization of both the (meth)acryloyl group of the monomer and the polymerizable functional group bonded to the inorganic particle, and known reaction conditions can be used.

[0104] The radical polymerization in step (i) can be carried out, for example, by using a small amount of radical generator as a catalyst. As the radical generator, known ones used in radical polymerization reactions can be used, for example, azo compounds and peroxides. The separation agent of this disclosure obtained by the manufacturing method including step (i) is presumed to contain modified inorganic particles having the structure represented by formula (2) above.

[0105] Next, a manufacturing method including step (ii) will be described. This manufacturing method includes the steps of obtaining a polymer by radical polymerization of a hydrophobic (meth)acrylic monomer and / or a hydrophobic (meth)acrylamide monomer in the presence of a chain transfer agent having a crosslinkable silyl group at its terminal, and silane coupling of the obtained polymer on the surface of inorganic particles.

[0106] In step (ii), first, a hydrophobic (meth)acrylic monomer and / or a hydrophobic (meth)acrylamide monomer are radically polymerized in the presence of a chain transfer agent having a crosslinkable silyl group at the terminal to obtain a polymer.

[0107] Examples of chain transfer agents having a crosslinkable silyl group at the terminal in step (ii) include compounds represented by the following formula (III). (R ｂ ) ３－ｎ (Z ２ ) ｎ Si-Y'-T (III) In formula (III), R ｂ Each of these independently represents an alkyl group having 1 to 5 carbon atoms.２ represents a leaving group that can form a bond between the silicon atom and the inorganic particle in formula (III). Y' represents a single bond or an alkylene group having 1 to 30 carbon atoms. T represents a chain-transfer functional group. n represents an integer from 1 to 3.

[0108] The above R ｂ Each of these independently represents an alkyl group having 1 to 5 carbon atoms. The above R ｂ Examples of C1-C5 alkyl groups in include linear or branched alkyl groups such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, and pentyl groups. ｂ The preferred group is a methyl group, an ethyl group, or a propyl group.

[0109] The above Z ２ Z in equation (II) above is ２ Similar examples can be given.

[0110] The above Y' represents a single bond or an alkylene group having 1 to 30 carbon atoms. Examples of alkylene groups having 1 to 30 carbon atoms in the above Y' include methylene group, dimethylethylene group, 1-methylethylene group, 1,1-dimethylmethylene group, trimethylene group, 2-methyltrimethylene group, tetramethylene group, pentamethylene group, 2-methylpentamethylene group, 2-ethylpentamethylene group, 3-methylpentamethylene group, 3-ethylpentamethylene group, hexamethylene group, 2-methylpentamethylene group. Examples of linear or branched alkylene groups include ethylhexamethylene, 2-ethylhexamethylene, 3-methylhexamethylene, 3-ethylhexamethylene, octamethylene, nonamethylene, decamethylene, undecamethylene, dodecamethylene, tridecamethylene, tetradecamethylene, pentamethylene, hexadecamethylene, and octamethylene. Among these, Y' is preferably a single bond or an alkylene group having 1 to 10 carbon atoms.

[0111] The above T represents a chain-transfer functional group. A chain-transfer functional group is a functional group that actively causes a chain-transfer reaction in polymerization, involving the movement of growth-active species and a restart reaction. The presence of the above chain-transfer functional group makes it possible to control the molecular weight and terminal structure of the polymer to some extent. Examples of the above chain-transfer functional group include C1-C12 haloalkyl groups, C1-C12 alkyl groups having a thiol at the terminal, or C1-C12 alkyl groups having a disulfide group within the group.

[0112] The above n represents an integer between 1 and 3.

[0113] Radical polymerization in step (ii) can be carried out, for example, by using a small amount of radical generator as a catalyst in the presence of the above-mentioned chain transfer agent. In this case, the molecular weight of the polymer can be controlled to some extent by the molar ratio of the chain transfer agent to the monomer. As the above-mentioned radical generator, known ones used in radical polymerization reactions can be used, and examples similar to those of the radical generator in step (i) can be given. By radical polymerization in step (ii), a polymer having the structure represented by the following formula (3) can be obtained.

[0114] In formula (3), R ｂ Z ２ Y' is the same as in formula (III) above. T' is derived from T in formula (III) and is a group produced by the chain transfer reaction. R １ , X ２ , R ２ Z is the same as in equation (1) above. n is an integer from 1 to 3, and q'' is an integer from 2 to 300.

[0115] The above T' is derived from T in formula (III) and is a group produced by a chain transfer reaction. When T is a C1-C12 haloalkyl group, T' is a halogen-substituted C1-C12 alkylene residue, and when T is a C1-C12 alkyl group having a thiol at its terminus or a C1-C12 alkyl group having a disulfide group within the group, T' is a thioether.

[0116] The above R ｂ Z ２As for Y', R in equation (III) above ｂ Z ２ Similar examples can be given to Y'.

[0117] The above R １ , X ２ , R ２ As for Z, R in equation (1) above １ , X ２ , R ２ Similar examples can be given to Z.

[0118] The above n represents an integer from 1 to 3, and the above q'' represents an integer from 2 to 300.

[0119] In the above formula (3), R ２ When R is an alkylene group having 1 to 30 carbon atoms, １ , X ２ The preferred combinations of Z are the same as in equation (1) above, and the preferred combinations of Y' and T' are the same as in equation (4) above. In this case, R ｂ Each of these is an alkyl group having 1 to 5 carbon atoms, and Z ２ It is preferable that Z is an alkoxy group having 1 to 5 carbon atoms, a halogen (chlorine, bromine, or iodine), an alkyl mercaptyl group having 1 to 20 carbon atoms, a nitrogen-containing group, an allyl group, or a 2-methyl-2-propenyl group. ２ The more preferably, it is an alkoxy group having 1 to 5 carbon atoms.

[0120] In the above formula (3), R ２ When R is a haloalkylene group having 1 to 5 carbon atoms, １ , X ２ The preferred combinations of Z are the same as in equation (1) above, and the preferred combinations of Y' and T' are the same as in equation (4) above. In this case, R ｂ Each of these is an alkyl group having 1 to 5 carbon atoms, and Z ２ It is preferable that Z is an alkoxy group having 1 to 5 carbon atoms, a halogen (chlorine, bromine, or iodine), an alkyl mercaptyl group having 1 to 20 carbon atoms, a nitrogen-containing group, an allyl group, or a 2-methyl-2-propenyl group. ２ The more preferably, it is an alkoxy group having 1 to 5 carbon atoms.

[0121] In the above formula (3), R ２ When R is a cycloalkylene group having 3 to 10 carbon atoms, １ , X ２ The preferred combinations of Z are the same as in equation (1) above, and the preferred combinations of Y' and T' are the same as in equation (4) above. In this case, R ｂ Each of these is an alkyl group having 1 to 5 carbon atoms, and Z ２ It is preferable that Z is an alkoxy group having 1 to 5 carbon atoms, a halogen (chlorine, bromine, or iodine), an alkyl mercaptyl group having 1 to 20 carbon atoms, a nitrogen-containing group, an allyl group, or a 2-methyl-2-propenyl group. ２ The more preferably, it is an alkoxy group having 1 to 5 carbon atoms.

[0122] In step (ii), the polymer is obtained by radical polymerization of the monomer, and then the obtained polymer is subjected to silane coupling on the surface of inorganic particles.

[0123] Examples of inorganic particles in step (ii) are similar to those of inorganic particles in the separation agent of this disclosure.

[0124] A known silane coupling method can be used to bond the above polymer and the above inorganic particles by silane coupling. The separation agent of this disclosure obtained by the manufacturing method including step (ii) above is presumed to contain modified inorganic particles having the structure represented by formula (4) above.

[0125] Next, a manufacturing method including step (iii) will be described. This manufacturing method includes the steps of obtaining a polymer by radical copolymerizing a (meth)acrylic monomer having a hydrophobic group and / or a (meth)acrylamide monomer having a hydrophobic group with a silane coupling agent having a polymerizable double bond, and silane coupling the obtained polymer on the surface of inorganic particles.

[0126] In step (iii), a polymer is first obtained by radical copolymerizing a hydrophobic (meth)acrylic monomer and / or a hydrophobic (meth)acrylamide monomer with a silane coupling agent having a polymerizable double bond.

[0127] Examples of the silane coupling agent having the polymerizable double bond in step (iii) include the compound represented by formula (II).

[0128] Radical polymerization in step (iii) can be generated, for example, by using a small amount of radical generator as a catalyst. At this time, the molecular weight can be controlled by using a suitable chain transfer agent or a known living radical polymerization method. As the radical generator, any known radical generator used in radical polymerization reactions can be used, and examples similar to those of the radical generator in step (i) can be given.

[0129] In step (iii), a polymer is obtained by radical polymerization of the monomer and the silane coupling agent, and then the obtained polymer is subjected to silane coupling on the surface of inorganic particles.

[0130] Examples of inorganic particles in step (iii) are similar to those in the separation agent of this disclosure.

[0131] A known silane coupling method can be used to bond the above polymer and the above inorganic particles by silane coupling. The separation agent of this disclosure obtained by the manufacturing method including step (iii) above is presumed to contain modified inorganic particles having the structure represented by formula (2) above.

[0132] Next, a manufacturing method including step (iv) will be described. This manufacturing method includes a step of radical copolymerizing a (meth)acrylic monomer having a hydrophobic group and / or a (meth)acrylamide monomer having a hydrophobic group with a silane coupling agent having a polymerizable double bond in the presence of inorganic particles.

[0133] Examples of the silane coupling agent having the polymerizable double bond in step (iv) include the compound represented by formula (II).

[0134] Examples of inorganic particles in step (iv) are similar to those in the inorganic particles in the separation agent of this disclosure.

[0135] Radical polymerization in step (iv) can be brought about, for example, by using a small amount of radical generator as a catalyst. Known radical generators used in radical polymerization reactions can be used as the radical generator, and examples similar to those of the radical generator in step (i) can be given. The separation agent according to one embodiment of the present disclosure obtained by the manufacturing method including step (iv) is presumed to contain modified inorganic particles having the structure represented by formula (2) above.

[0136] Next, a manufacturing method including step (v) will be described. This manufacturing method includes the step of introducing a chain-mobile functional group onto the surface of inorganic particles and radical polymerization of a hydrophobic (meth)acrylic monomer and / or a hydrophobic (meth)acrylamide monomer.

[0137] In step (v), a method for introducing chain-mobile functional groups to the surface of inorganic particles is obtained by silane coupling a compound having the structure represented by formula (III) above with inorganic particles using a known method.

[0138] Examples of inorganic particles in step (v) are similar to those in the separation agent of this disclosure.

[0139] Examples of chain-transfer functional groups in step (v) are similar to those in formula (III) above.

[0140] In step (v), radical polymerization can be carried out by using a small amount of radical generator as a catalyst in the presence of inorganic particles on which chain-transfer functional groups have been introduced (chemically bonded) to the surface, thereby obtaining modified inorganic particles. As the radical generator, known ones used in radical polymerization reactions can be used, and examples similar to those of the radical generator in step (i) can be given. The separation agent according to one embodiment of the present disclosure obtained by the manufacturing method including step (v) is presumed to contain modified inorganic particles having the structure represented by formula (4) above.

[0141] An embodiment of the present disclosure will be described in more detail below based on examples, but each embodiment can be combined with any other features disclosed herein. Each configuration and combination thereof in each embodiment is an example, and additions, omissions, substitutions, and other modifications are possible as appropriate without departing from the spirit of the present disclosure. Furthermore, the inventions relating to the present disclosure are not limited by the embodiments or the following examples.

[0142] Preparation Example 1 <Preparation of silica gel with acrylamide groups> 100.0 g of silica gel (average particle size 5 μm, average pore size 120 Å) was added to a flask, 450 mL of toluene was added to form a slurry, and then 10.0 g of water was added. 38.6 g of N-methyl-N-[3-(trimethoxysilyl)propyl]2-propenamide and 50 mL of toluene were weighed into a beaker and mixed with the silica gel in the flask. The flask was then heated in an oil bath and heated under reflux for 6 hours. After the reaction, the solution was cooled and solid-liquid separation was performed. The obtained powder was washed seven times with 500 mL of methanol and vacuum-dried at 80°C for 8 hours to obtain silica gel with acrylamide groups (hereinafter referred to as acrylamide-treated silica gel).

[0143] The acrylamide-treated silica gel obtained in Preparation Example 1 was subjected to CHN elemental analysis using the "Flash Smart CHNS" instrument (Thermo Fisher Scientific) (N=2). The carbon content of the acrylamide-treated silica gel was 7.31% by mass, and the nitrogen content was 1.06% by mass.

[0144] Preparation Example 2: 188.9 g of silica gel (average particle size 3 μm, average pore size 300 Å) was added to a flask, and after degassing, nitrogen purging was performed. 800 mL of toluene was added to form a slurry, and then 18.9 g of water was added. 25.5 g of N-methyl-N-[3-(trimethoxysilyl)propyl]2-propenamide and 139 mL of toluene were weighed into a beaker and mixed with the silica gel in the flask. The flask was then heated in an oil bath and heated under reflux for 6 hours. After the reaction, the solution was cooled and solid-liquid separation was performed. The obtained powder was washed seven times with 950 mL of methanol and vacuum-dried at 80°C for 8 hours to obtain acrylamide-treated silica gel.

[0145] The acrylamide-treated silica gel obtained in Preparation Example 2 was subjected to CHN elemental analysis using the "Flash Smart CHNS" instrument (Thermo Fisher Scientific) (N=2). The carbon content of the acrylamide-treated silica gel was 3.28% by mass.

[0146] <Preparation of Separating Agent> Example 1 In a beaker, 18.2 g of stearyl acrylate, 23.4 g of propylene glycol 1-monomethyl ether 2-acetate, 0.26 g of toluene, 0.35 g of 2,2'-azobis(2,4-dimethylvaleronitrile), and 10.0 g of acrylamide-treated silica gel (average particle size 5 μm, average pore size 120 Å) obtained in Preparation Example 1 were added to form a slurry. This slurry was placed in a 100 mL three-necked flask. Then, the slurry remaining in the beaker was added to the three-necked flask with 8.7 g of propylene glycol 1-monomethyl ether 2-acetate. After purging with nitrogen, the flask was kept heated in an oil bath at 65°C for 6 hours to allow the copolymerization reaction to proceed. After the copolymerization reaction was complete, the obtained powder was collected by filtration and washed five times with 50 mL of toluene and three times with acetone. The obtained modified inorganic particles were vacuum-dried at 60°C for 6 hours to be used as a separation agent.

[0147] The separation agent obtained in Example 1 was subjected to CHN elemental analysis using the "Flash Smart CHNS" instrument (Thermo Fisher Scientific) (N=2). The carbon content of the obtained separation agent was 28.19% by mass, the nitrogen content was 0.82% by mass, and the hydrogen content was 4.80% by mass. Since the carbon content of the acrylamide-treated silica gel used as a raw material was 7.31% by mass, the loading rate of the hydrophobic polymer was estimated to be approximately 29.65% by mass.

[0148] It can be inferred that the separating agent obtained in Example 1 has a structure represented by the following formula.

[0149] Example 2 In a beaker, 13.50 g of dodecyl acrylate, 29.3 g of propylene glycol 1-monomethyl ether 2-acetate, 0.25 g of toluene, 0.35 g of 2,2'-azobis(2,4-dimethylvaleronitrile), and 10.0 g of acrylamide-treated silica gel (average particle size 5 μm, average pore size 120 Å) obtained in Preparation Example 1 were added to form a slurry. This slurry was placed in a 100 mL three-necked flask. Then, the slurry remaining in the beaker was added to the three-necked flask with 8.74 g of propylene glycol 1-monomethyl ether 2-acetate. After purging with nitrogen, the flask was kept heated in an oil bath at 65°C for 6 hours to allow the copolymerization reaction to proceed. After the copolymerization reaction was complete, the obtained powder was collected by filtration and washed five times with 50 mL of toluene and three times with acetone. The obtained modified inorganic particles were vacuum-dried at 60°C for 6 hours to be used as a separation agent.

[0150] The separation agent obtained in Example 2 was subjected to CHN elemental analysis using the "Flash Smart CHNS" instrument (Thermo Fisher Scientific) (N=2). The carbon content of the obtained separation agent was 24.62% by mass, the nitrogen content was 0.87% by mass, and the hydrogen content was 4.16% by mass. Since the carbon content of the acrylamide-treated silica gel used as a raw material was 7.31% by mass, the loading rate of the hydrophobic polymer was estimated to be approximately 25.6% by mass.

[0151] It can be inferred that the separating agent obtained in Example 2 has a structure represented by the following formula.

[0152] Comparative Example 1: 15.0 g of acrylamide-treated silica gel (average particle size 3 μm, average diameter 300 Å) obtained in Preparation Example 2 was placed in a flask, degassed, and purged with nitrogen. 23.6 mL of toluene, 0.3 mL of dimethyl sulfoxide, 27.6 g of stearyl acrylate, and 0.52 g of 2,2'-azobis(2,4-dimethylvaleronitrile) were added under a nitrogen atmosphere. The flask was heated in an oil bath to 65°C for 6 hours to allow the copolymerization reaction to proceed. After copolymerization was complete, the obtained powder was collected by filtration using a glass filter and washed five times with 75 mL of toluene, twice with acetone, and once with methanol. The obtained modified inorganic particles were vacuum-dried at 60°C for 6 hours and used as a separation agent.

[0153] The separation agent obtained in Comparative Example 1 was subjected to CHN elemental analysis using the "Flash Smart CHNS" instrument (Thermo Fisher Scientific) (N=2). The carbon content of the obtained separation agent was 19.42% by mass. Since the carbon content of the acrylamide-treated silica gel used as a raw material was 3.28% by mass, the loading rate of the hydrophobic polymer was estimated to be approximately 21.7% by mass.

[0154] It can be inferred that the separation agent obtained in Comparative Example 1 has a structure represented by the following formula.

[0155] (Evaluation of Separation Characteristics: Tanaka Test) The separation characteristics of the separation agent can be evaluated by the Tanaka test (K. Kimata, et al., J. Chromatogr. Sci., Vol. 27, 1989, pp. 721-728). Reverse-phase high-performance liquid chromatography (reverse-phase HPLC) was performed under the following conditions using a 0.46φ × 15 cm column packed with slurry of the separation agents obtained in Examples 1 and 2, a 0.21φ × 15 cm column packed with slurry of the separation agent obtained in Comparative Example 1, and commercially available chromatography columns as Comparative Examples 2 to 14, and the separation characteristics of the separation agents were evaluated by the Tanaka test. Note that in the Tanaka test performed in this disclosure, the retention coefficient k' of each compound was used to determine the retention of uracil. ０ The following calculation was performed using the retention time t of each compound: (k' = (t - t) ０ ) / t ０ ). And for each column, the hydrogen bond recognition ability (k'(Caffeine) / k' （Ｐｈｅｎｏｌ） Four statuses were calculated: hydrophobicity retention (k'(Amylbenzene)), hydrophobicity difference recognition ability (k'(Amylbenzene) / k'(Butylbenzene)), and molecular structure recognition ability (k'(Triphenylene) / k'(o-Terphenyl)). The results are shown in Table 1.

[0156] The analytical conditions for the Tanaka test conducted in this disclosure are as follows: <Analytical Conditions> Apparatus: Nexera X2, manufactured by Shimadzu Corporation Mobile phase: methanol / water = 80 / 20 Linear velocity: 1.0 mm / s Detection: UV 254 nm Temperature: 40°C Samples: uracil, caffeine, phenol, butylbenzene, amylbenzene, o-terphenyl, triphenylene

[0157] The commercially available chromatography columns used in Comparative Examples 2 to 14 are as follows: Comparative Example 2: Product name "L-column3 C18", 0.21φ × 15 cm, manufactured by the Chemicals Evaluation and Research Institute Comparative Example 3: Product name "L-column2 ODS (C18)", 0.21φ × 15 cm, manufactured by the Chemicals Evaluation and Research Institute Comparative Example 4: Product name "InertSustain® AQ-C18 HP", 0.21φ × 15 cm, manufactured by GL Sciences Co., Ltd. Comparative Example 5: Product name "InertSustainSwift® C18 HP", 0.21φ × 15 cm, manufactured by GL Sciences Co., Ltd. Comparative Example 6: Product name "InertSustain® C18", 0.46φ × 15 cm, manufactured by GL Sciences Co., Ltd. Comparative Example 7: Product name "Inertsil® WP300 Comparative Example 8: Product name "Inertsil (registered trademark) ODS-HL HP", 0.21φ x 15cm, manufactured by GL Sciences Co., Ltd. Comparative Example 9: Product name "ACQUITY (registered trademark) UPLC BEH C18 Column", 0.21φ x 15cm, manufactured by Waters Corporation Comparative Example 10: Product name "TSKgel (registered trademark) ODS-100V", 0.20φ x 15cm, manufactured by Tosoh Corporation Comparative Example 11: Product name "TSKgel (registered trademark) ODS-120H", 0.20φ x 15cm, manufactured by Tosoh Corporation Comparative Example 12: Product name "SunBridge Comparative Example 13: Product name "SP-120-5-ODS-RPS", 0.46φ x 15cm, manufactured by Chromanic Technologies Co., Ltd. Comparative Example 14: Product name "InertSustain (registered trademark) AX-C18", 0.46φ x 15cm, manufactured by GL Sciences Co., Ltd.

[0158]

[0159] In evaluating the separation characteristics, a value of 6.0 or higher for hydrophobic retention [k'(Amylbenzene)] and 2.5 or higher for molecular structure recognition ability [k'(Triphenylene) / k'(o-Terphenyl)] calculated by the Tanaka test was considered excellent in terms of hydrophobic retention and molecular structure recognition ability, respectively. As shown in Table 1, when a separation agent with a carbon content of 24% by mass or more in the modified inorganic particles was used (Examples 1 and 2), the hydrophobic retention was 11.01, 7.94, and 6.0 or higher, respectively, and the molecular structure recognition ability was 2.94, 2.70, and 2.5 or higher, indicating excellent performance in both hydrophobic retention and molecular structure recognition ability. On the other hand, when a separation agent with a carbon content of less than 24% by mass in the modified inorganic particles was used (Comparative Examples 1 to 14), one or both of the hydrophobic retention and molecular structure recognition ability did not meet the above criteria. These results demonstrate that the separation agent of this disclosure possesses both excellent molecular structure recognition ability and hydrophobic retention capabilities.

[0160] The following describes variations of the invention relating to this disclosure. [Note 1] A separation agent comprising modified inorganic particles having inorganic particles and a modifying group supported on the inorganic particles, wherein the carbon content of the modified inorganic particles is 24% by mass or more (preferably 24.2% by mass or more, more preferably 24.4% by mass or more, and even more preferably 24.6% by mass or more). [Note 2] The separation agent according to Note 1, wherein the carbon content of the modified inorganic particles is 60% by mass or less (preferably 50% by mass or less, more preferably 40% by mass or less, and even more preferably 35% by mass or less). [Note 3] The separation agent according to Note 1 or 2, wherein the average pore size of the inorganic particles is 10 to 10000 Å (preferably 25 to 1000 Å, more preferably 50 to 500 Å, even more preferably 75 to 300 Å, and particularly preferably 100 to 150 Å). [Note 4] The separation agent according to any one of Notes 1 to 3, wherein the inorganic particles are silica gel. [Note 5] The separation agent according to any one of Notes 1 to 4, wherein the average particle size of the modified inorganic particles is 0.1 to 50 μm (preferably 0.1 to 30 μm, more preferably 1 to 10 μm, even more preferably 1.2 to 7.5 μm, and particularly preferably 1.5 to 6 μm). [Note 6] The separation agent according to any one of Notes 1 to 5, wherein the average particle size of the inorganic particles is 0.1 to 50 μm (preferably 0.1 to 30 μm, more preferably 1 to 10 μm, even more preferably 1.2 to 7.5 μm, and particularly preferably 1.5 to 6 μm). [Note 7] The inorganic particles are porous inorganic particles, and the specific surface area of ​​the inorganic particles is 5 to 1000 m². ２ / g (preferably 10 to 500m) ２ A separating agent according to any one of the appendices 1 to 6, wherein the amount is ( / g). [Appendix 8] The inorganic particles are non-porous inorganic particles, and the specific surface area of ​​the inorganic particles is 0.01 m². ２ / g or more, 5m ２ Less than / g (preferably 0.01 to 4m) ２A separation agent according to any one of Appendix 1 to 6, wherein the amount is ( / g). [Appendix 9] A separation agent according to any one of Appendix 1 to 8, wherein the aspect ratio of the modified inorganic particles is 2 or less (preferably 1.5 or less). [Appendix 10] A separation agent according to any one of Appendix 1 to 9, wherein the modifying group contains a polymer. [Appendix 11] A separation agent according to any one of Appendix 1 to 10, wherein the modifying group contains a polymerization unit represented by the following formula (1). (In formula (1), R １ X represents hydrogen or an alkyl group having 1 to 6 carbon atoms. ２ is -O-, -NH-, or -N(CH ３ ) indicates R ２ represents an alkylene group having 1 to 30 carbon atoms, a haloalkylene group having 1 to 5 carbon atoms, or a cycloalkylene group having 3 to 10 carbon atoms. Z represents hydrogen, halogen, hydroxyl group, -N(R) ３ ) (Caution ４ ), or a hydroxyalkyl group having 1 to 6 carbon atoms. ３ , R ４ (wherein q represents the same or different hydrogen or an alkyl group having 1 to 6 carbon atoms. q represents an integer from 2 to 3000.) [Note 12] The separation agent according to any one of Notes 1 to 11, wherein the loading rate of the polymer containing the polymerization unit represented by formula (1) in the separation agent is 1 to 50% by mass (preferably 10 to 40% by mass, more preferably 20 to 30% by mass). [Note 13] The separation agent according to any one of Notes 1 to 12, wherein the modified inorganic particles have a structure represented by the following formula (2). (In formula (2), W' represents a single bond or an alkylene group having 1 to 10 carbon atoms. W'' represents hydrogen or an alkyl group having 1 to 12 carbon atoms. X represents an amide group, an ester group, an N-alkylamide group having 1 to 3 carbon atoms, an ether group, a sulfoxide group, a sulfone group, a sulfide group, or a phosphate ester group. Y represents an alkylene group having 1 to 30 carbon atoms. V represents the same or different ether group bonded to an inorganic particle, an alkoxy group having 1 to 5 carbon atoms, a halogen, an alkyl mercaptyl group having 1 to 20 carbon atoms, a nitrogen-containing group, an allyl group, a 2-methyl-2-propenyl group, or an alkyl group having 1 to 3 carbon atoms. R １ X represents hydrogen or an alkyl group having 1 to 6 carbon atoms.２ is -O-, -NH-, or -N(CH ３ ) indicates R ２ represents an alkylene group having 1 to 30 carbon atoms, a haloalkylene group having 1 to 5 carbon atoms, or a cycloalkylene group having 3 to 10 carbon atoms. Z represents hydrogen, halogen, hydroxyl group, -N(R) ３ ) (Caution ４ ), or a hydroxyalkyl group having 1 to 6 carbon atoms. ３ , R ４ R represents hydrogen or an alkyl group having 1 to 6 carbon atoms, either identical or different. p is an integer from 1 to 10, and q' is an integer from 10 to 3000. The bonds indicated by the wavy lines in the formula are bonded to the surface of inorganic particles.) [Note 14] In formula (1) above, R ２ R is an alkylene group having 1 to 30 carbon atoms (preferably a linear or branched alkylene group having 3 to 30 carbon atoms, more preferably a linear or branched alkylene group having 8 to 20 carbon atoms, even more preferably a linear or branched alkylene group having 10 to 20 carbon atoms, and particularly preferably a linear or branched alkylene group having 12 to 18 carbon atoms), １ is hydrogen or an alkyl group having 1 to 6 carbon atoms (preferably hydrogen, a methyl group, or an ethyl group), X ２ is -O-, -NH-, or -N(CH ３ )- and Z is hydrogen, hydroxyl group, -N(R ３ ) (Caution ４ ), or a hydroxyalkyl group having 1 to 6 carbon atoms (preferably hydrogen or -N(R) ３ ) (Caution ４ A separating agent according to any one of the appendices 11 to 13, wherein R is more preferably hydrogen. [Appendix 15] In formula (1), R ２ is a haloalkylene group having 1 to 5 carbon atoms (preferably a fluoroalkylene group having 1 to 5 carbon atoms, more preferably a fluoroalkylene group having 1 to 3 carbon atoms), and R １ is hydrogen or an alkyl group having 1 to 6 carbon atoms (preferably hydrogen, a methyl group, or an ethyl group), X ２ is -O-, -NH-, or -N(CH ３) - and Z is hydrogen or halogen, as described in any one of the appendices 11 to 13. [Appendix 16] In formula (1) above, R ２ R is a cycloalkylene group having 3 to 10 carbon atoms (preferably a cycloalkylene group having 3 to 6 carbon atoms, more preferably a 1,2-cyclohexylene group, a 1,3-cyclohexylene group, or a 1,4-cyclohexylene group), １ is hydrogen or an alkyl group having 1 to 6 carbon atoms (preferably hydrogen, a methyl group, or an ethyl group), X ２ is -O-, -NH-, or -N(CH ３ )- and Z is hydrogen, -N(R ３ ) (Caution ４ ), or a hydroxyalkyl group having 1 to 6 carbon atoms (preferably hydrogen or -N(R) ３ ) (Caution ４ A separation agent according to any one of appendices 11 to 13, wherein the separation agent is (more preferably hydrogen). [Appendix 17] A separation agent according to any one of appendices 1 to 16, for use in liquid chromatography. [Appendix 18] A separation agent according to any one of appendices 1 to 17, for use in reverse-phase chromatography.

Claims

1. A separation agent comprising modified inorganic particles having inorganic particles and a modifying group supported on the inorganic particles, wherein the carbon content of the modified inorganic particles is 24% by mass or more.

2. The separation agent according to claim 1, wherein the carbon content of the modified inorganic particles is 60% by mass or less.

3. The separation agent according to claim 1 or 2, wherein the average pore size of the inorganic particles is 10 to 10,000 Å.

4. The separation agent according to claim 1 or 2, wherein the inorganic particles are silica gel.

5. The separation agent according to claim 1 or 2, wherein the average particle size of the modified inorganic particles is 0.1 to 50 μm.

6. The separation agent according to claim 1 or 2, wherein the modifying group comprises a polymerization unit represented by the following formula (1). (In formula (1), R １ X represents hydrogen or an alkyl group having 1 to 6 carbon atoms. ２ is -O-, -NH-, or -N(CH ３ ) indicates R ２ represents an alkylene group having 1 to 30 carbon atoms, a haloalkylene group having 1 to 5 carbon atoms, or a cycloalkylene group having 3 to 10 carbon atoms. Z represents hydrogen, halogen, hydroxyl group, -N(R) ３ ) (Caution ４ ), or a hydroxyalkyl group having 1 to 6 carbon atoms. ３ , R ４ (These represent hydrogen atoms or alkyl groups having 1 to 6 carbon atoms, either identical or distinct. q represents an integer between 2 and 3000.) 7. The separating agent according to claim 1 or 2, wherein the modified inorganic particles have a structure represented by the following formula (2). (In formula (2), W' represents a single bond or an alkylene group having 1 to 10 carbon atoms. W'' represents hydrogen or an alkyl group having 1 to 12 carbon atoms. X represents an amide group, an ester group, an N-alkylamide group having 1 to 3 carbon atoms, an ether group, a sulfoxide group, a sulfone group, a sulfide group, or a phosphate ester group. Y represents an alkylene group having 1 to 30 carbon atoms. V is the same or different and represents an ether group bonded to the inorganic particles, an alkoxy group having 1 to 5 carbon atoms, a halogen, an alkyl mercaptyl group having 1 to 20 carbon atoms, a nitrogen-containing group, an allyl group, a 2-methyl-2-propenyl group, or an alkyl group having 1 to 3 carbon atoms. R １ represents hydrogen or an alkyl group having 1 to 6 carbon atoms. X ２ represents -O-, -NH-, or -N(CH ３ ). R ２ represents an alkylene group having 1 to 30 carbon atoms, a haloalkylene group having 1 to 5 carbon atoms, or a cycloalkylene group having 3 to 10 carbon atoms. Z represents hydrogen, a halogen, a hydroxy group, -N(R ３ )(R ４ ), or a hydroxyalkyl group having 1 to 6 carbon atoms. R ３ , R ４ are the same or different and represent hydrogen or an alkyl group having 1 to 6 carbon atoms. p represents an integer of 1 to 10, and q' represents an integer of 10 to 3000. The wavy bond in the formula is bonded to the surface of the inorganic particles.) 8. The separation agent according to claim 1 or 2, for use in liquid chromatography.

9. The separation agent according to claim 1 or 2, for use in reverse-phase chromatography.

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