Method for manufacturing core-shell porous silica particles

Abstract

The present invention provides a method for manufacturing core-shell porous silica particles, the method involving using steps a1) and a2) to produce core-shell silica particles having a core and a shell precursor, and using step b) to convert the shell precursor into a porous material. Step a1) is a first reaction initiation step for adding a silica source-containing liquid to a first aqueous suspension containing nonporous silica particles, a cationic surfactant, a basic catalyst, an electrolyte, and an alcohol, or is a second reaction initiation step for adding a silica source-containing liquid and an electrolyte to a second aqueous suspension containing nonporous silica particles, a cationic surfactant, a basic catalyst, and an alcohol. Step a2) is a first silica source continuous addition step for adding a cationic surfactant and continuously adding a silica source-containing liquid to the reaction system after the first reaction initiation step or the second reaction initiation step. Step b) is a shell porosity forming step for removing the cationic surfactant from the shell precursor.

Description

Method for producing core-shell porous silica particles

[0001] The present disclosure relates to a method for producing core-shell porous silica particles.

[0002] Porous materials such as porous silica are widely used as separation agents, adsorbents, catalyst supports, etc. due to their large specific surface area, and their applications are expected to expand by forming them into particles. In particular, micron-sized porous silica particles are used as column packing materials for liquid chromatography such as high-performance liquid chromatography (HPLC) for the separation and analysis of chemical substances.

[0003] As column packing materials for liquid chromatography, core-shell mesoporous silica particles (C-MSPs), in which the surface of a monodisperse core particle is coated with a mesoporous silica shell with a pore size of 2 to 50 nm, have attracted attention. These core-shell particles have the advantage of being superior in monodispersity and mechanical strength compared to fully porous particles without a core.

[0004] It is known that the separation performance of column packing materials depends on factors such as particle size, shell thickness, and pore size. In particular, for packing materials with the same particle size, the thicker the shell that serves as the separation field, the longer the retention time of the separated analytes. Therefore, thickening the shell is important for improving the separation performance of column packing materials, and various methods for thickening the shell have been developed.

[0005] For example, Patent Document 1 discloses a method for producing core-shell porous silica particles, which includes a shell precursor-forming step of forming a shell precursor on the surface of nonporous silica particles by continuously adding a liquid containing a silica source to an aqueous suspension containing nonporous silica particles, a cationic surfactant, a basic catalyst, and an alcohol, and a shell-forming step of forming a porous shell by removing the cationic surfactant from the shell precursor. In this method, a thick shell is achieved in the shell precursor-forming step by controlling the pH and pH change of the reaction system and controlling the relationship between the specific surface area of ​​the nonporous silica particles, the amount of nonporous silica particles used, and the amount of silica source used.

[0006] International Publication No. 2022 / 172978

[0007] In the production of core-shell particles, there is a need to develop a new method for thickening the shell in order to broaden the range of options for the method for thickening the shell. An object of the present disclosure is to provide a new method for producing core-shell porous silica particles with a large shell thickness.

[0008] In order to solve the above problems, the inventors of the present disclosure have conducted extensive research. As a result, they have found that when adding a reagent such as a silica source to a suspension containing core particles to form a shell precursor on the cores, the above problems can be solved by controlling the method and conditions for adding the reagent to the suspension. That is, the gist of the present disclosure includes the following.

[0009] [1] A method for producing core-shell porous silica particles, comprising: preparing core-shell silica particles having a core and a shell precursor by the following steps a1) and a2), and then rendering the shell precursor porous by the following step b): a1) a first reaction initiation step of adding a silica source-containing liquid containing a silica source to a first aqueous suspension containing nonporous silica particles, a cationic surfactant, a basic catalyst, an electrolyte, and an alcohol, or a second reaction initiation step of adding a silica source-containing liquid containing a silica source and an electrolyte to a second aqueous suspension containing nonporous silica particles, a cationic surfactant, a basic catalyst, and an alcohol; a2) a first silica source continuous addition step of adding a cationic surfactant to a reaction system after the first reaction initiation step or the second reaction initiation step, and continuously adding a silica source-containing liquid containing a silica source; and b) a shell porous formation step of removing the cationic surfactant from the shell precursor. [2] The method for producing core-shell porous silica particles according to [1], wherein the step a2) is carried out under conditions in which the silicate ion concentration is lower than the solubility of silica in the reaction system. [3] The method for producing core-shell porous silica particles according to [1] or [2], wherein the core-shell silica particles are produced by further carrying out the following step a3) once or a plurality of times after the step a2). a3) An nth silica source continuous addition step (n represents an integer of 2 or more) of adding a cationic surfactant and continuously adding a silica source-containing liquid containing a silica source to the reaction system after the (n-1)th silica source continuous addition step. [4] The method for producing core-shell porous silica particles according to [3], wherein the step a3) is carried out under conditions in which the silicate ion concentration is lower than the solubility of silica in the reaction system. [5] The method for producing core-shell porous silica particles according to any of [1] to [4], wherein the addition of the electrolyte to the second aqueous suspension in the second reaction initiation step is carried out within a time period from 2 minutes before to 5 minutes after the time point at which the Debye length of the reaction system reaches its minimum. [6] The method for producing core-shell porous silica particles according to any one of [1] to [4], wherein the addition of the electrolyte to the second aqueous suspension in the second reaction initiation step is carried out within a time period that satisfies the following condition I):Condition I) The Debye length of the reaction system is equal to or greater than the minimum value in the change in Debye length with time, and is equal to or less than the value obtained by multiplying the minimum value by X (X is greater than 1.00 and equal to or less than 1.10). [7] The method for producing core-shell porous silica particles according to any one of [1] to [4], wherein the addition of the electrolyte to the second aqueous suspension in the second reaction initiation step is carried out within a time period that satisfies the following condition II): Condition II) The reciprocal of the hydrolysis rate constant of the silica source under the reaction conditions is 0.1 or greater and 1.0 or less: [8] The method for producing core-shell porous silica particles according to any one of [1] to [7], wherein the basic catalyst is ammonia. [9] The method for producing core-shell porous silica particles according to any one of [1] to [8], wherein the alcohol is an alkyl alcohol.

[10] The method for producing core-shell porous silica particles according to any one of [1] to [9], wherein the silica source is an alkoxysilane.

[11] The method for producing core-shell porous silica particles according to any one of [1] to

[10] , wherein the electrolyte is either potassium chloride or cesium chloride, or both.

[12] The method for producing core-shell porous silica particles according to any one of [1] to

[11] , wherein the cationic surfactant is a tetraalkylammonium halide.

[0010] The present disclosure can provide an effect of providing a new method for producing core-shell porous silica particles having a large shell thickness. The problems and effects of the present disclosure are not limited to those specifically described above, but also include those that will become apparent to those skilled in the art from the entire specification.

[0011] 1-3 is a STEM image of particles obtained in Reference Example 1-1 (photograph substitute for drawing). 2-4 is a graph showing the change in ionic strength over time in the reaction system in Reference Example 1-1. 3-5 is a graph showing the change in Debye length over time in the reaction system in Reference Example 1-1. 4-6 is a STEM image of particles obtained in Reference Example 1-3 (photograph substitute for drawing). 5-7 is a histogram of particle size distribution of particles obtained in Reference Example 1-3. 6-8 is a STEM image of particles obtained in Reference Example 2 (photograph substitute for drawing). 7-9 are STEM images of particles obtained in Reference Examples 3-1 and 3-2 (photograph substitute for drawing). 8-10 is a graph showing the silicate ion concentration and silica solubility in the reaction system in Reference Example 4-1, and a STEM image of the obtained particles (photograph substitute for drawing). 9-11 is a graph showing the silicate ion concentration and silica solubility in the reaction system in Reference Example 4-1, and a STEM image of the obtained particles (photograph substitute for drawing). 1 is a graph showing the silicate ion concentration and silica solubility in the reaction system in Reference Example 4-1, and an STEM image (photograph substitute for drawing) of the particles obtained. 2 is a graph showing the silicate ion concentration and silica solubility in the reaction system in Reference Example 4-2, and an STEM image (photograph substitute for drawing) of the particles obtained. 3 is an STEM image (photograph substitute for drawing) of core-shell type porous silica particles obtained in Examples and Comparative Examples. 4 is a graph showing nitrogen adsorption / desorption isotherms of core-shell type porous silica particles obtained in Examples. 5 is a graph showing the pore size distribution of core-shell type porous silica particles obtained in Examples. 6 is a graph showing the relationship between the total amount of TEOS used and the shell volume of core-shell type porous silica particles in Examples and Comparative Examples. 7 is a graph showing the relationship between the shell volume and pore surface area of ​​core-shell type porous silica particles in Examples and Comparative Examples.

[0012] The present disclosure will be described below with reference to specific embodiments. However, each configuration and combination thereof in each embodiment is merely an example, and addition, omission, substitution, and other modifications of the configuration are possible as appropriate within the scope of the gist of the present disclosure. The present disclosure is not limited by the embodiments. Furthermore, each aspect disclosed in this specification can be combined with any other feature disclosed in this specification.

[0013] In the present disclosure, the range "X to Y" means "X or more and Y or less." Furthermore, when a numerical range expressed as "X to Y" or "X or more and Y or less" is described in stages (for example, in order of preference), the upper and lower limits of each numerical range can be combined in any way.

[0014] In the present disclosure, a description such as "one or more selected from the group consisting of X, Y, and Z" means any of X, Y, Z, a combination of X and Y, a combination of X and Z, a combination of Y and Z, or a combination of X, Y, and Z.

[0015] In the present disclosure, a description such as "X such as x1, x2, and x3" lists x1, x2, and x3 as examples of X, and does not mean that X is limited to x1, x2, x3, and the like.

[0016] 1. Method for Producing Core-Shell Porous Silica The method for producing core-shell porous silica particles according to the first embodiment of the present disclosure is a method based on a micelle templating method, which uses micelles, which are self-assembled structures of a cationic surfactant, as pore templates. Specifically, the method includes a shell precursor formation step of forming, on the surface of core particles, a shell precursor in which micelles of a cationic surfactant and anionic free silica (hereinafter, sometimes referred to as "silica seeds") accumulate through electrostatic interaction, and a shell formation step of removing the micelles from the formed shell precursor.

[0017] More specifically, the method for producing core-shell porous silica particles according to this embodiment comprises preparing core-shell silica particles having a core and a shell precursor by the following steps a1) and a2), and then rendering the shell precursor porous by the following step b): a1) a first reaction initiation step of adding a silica source-containing liquid containing a silica source to a first aqueous suspension containing nonporous silica particles, a cationic surfactant, a basic catalyst, an electrolyte, and an alcohol, or a second reaction initiation step of adding a silica source-containing liquid containing a silica source and an electrolyte to a second aqueous suspension containing nonporous silica particles, a cationic surfactant, a basic catalyst, and an alcohol; a2) a first continuous silica source addition step of adding a cationic surfactant to the reaction system after the first reaction initiation step or the second reaction initiation step, and continuously adding a silica source-containing liquid containing a silica source; and b) a shell porosity step of removing the cationic surfactant from the shell precursor.

[0018] In the present disclosure, "continuous addition" means addition that is carried out continuously over a predetermined time. Here, the predetermined time is a time longer than the shortest addition time when performing discontinuous addition (lump addition), and may be, for example, 30 seconds or more, 1 minute or more, or 5 minutes or more. In the present disclosure, addition that is carried out continuously over a predetermined time is referred to as "continuous addition" to distinguish it from discontinuous addition, but even when simply referring to "addition," "continuous addition" is not excluded unless otherwise specified.

[0019] According to the method for producing core-shell porous silica particles of this embodiment, it is possible to provide core-shell porous silica particles having a thick shell, and therefore the core-shell porous silica particles obtained by the method for producing core-shell porous silica particles of this embodiment are expected to exhibit high separation performance when used as a column packing material for liquid chromatography.

[0020] 1-1. Reaction Initiation Step The reaction initiation step may be a first reaction initiation step in which a silica source-containing liquid containing a silica source is added to a first aqueous suspension containing nonporous silica particles, a cationic surfactant, a basic catalyst, an electrolyte, and an alcohol, or a second reaction initiation step in which a silica source-containing liquid containing a silica source and an electrolyte are added to a second aqueous suspension containing nonporous silica particles, a cationic surfactant, a basic catalyst, and an alcohol (hereinafter, the first aqueous suspension and the second aqueous suspension may be collectively referred to as "aqueous suspensions"; further, the first reaction initiation step and the second reaction initiation step may be collectively referred to as "reaction initiation steps"). In the reaction initiation step, a hydrolysis and condensation reaction of the silica source begins, and silica species are produced.

[0021] 1-1-1. Aqueous Suspensions The first aqueous suspension contains nonporous silica particles, a cationic surfactant, a basic catalyst, an electrolyte, and an alcohol. The second aqueous suspension contains nonporous silica particles, a cationic surfactant, a basic catalyst, and an alcohol. The second aqueous suspension is similar to the first aqueous suspension except that the electrolyte is not an essential component. The second aqueous suspension may contain an electrolyte, but preferably does not contain an electrolyte. The nonporous silica particles are preferably dispersed in the aqueous suspension.

[0022] The method for preparing the aqueous suspension is not particularly limited, and is usually prepared by mixing the respective components in any order. For example, as shown in the examples described later, the second aqueous suspension can be prepared by ultrasonically treating a mixed liquid containing nonporous silica particles, alcohol, and water to disperse the nonporous silica particles in a dispersion medium, adding a basic catalyst to the obtained dispersion and subjecting it to ultrasonic treatment, and further adding a cationic surfactant and subjecting it to ultrasonic treatment.

[0023] (Non-porous silica particles) The non-porous silica particles contained in the aqueous suspension are used as core particles of core-shell porous silica particles, and are substantially non-porous particles. In the present disclosure, the term "substantially non-porous" refers to the specific surface area (S ｍ ) is 50m ２ / g or less. ｍ ) for 50m２ By setting the specific surface area (S ｍ ) is preferably 30 m ２ / g or less, more preferably 20m ２ / g or less, more preferably 15m ２ / g or less. ｍ ) is 0.5m ２ / g or more.

[0024] In the present disclosure, the specific surface area (S ｍ ) refers to the specific surface area calculated by the following formula (1): In formula (1), ρ represents the density of the non-porous silica particles measured by the pycnometer method, d ｖ indicates the volume average particle size of the non-porous silica particles. ｍ = 6 / (ρd ｖ ) (1)

[0025] The volume average particle diameter (d ｖ From the viewpoint of ensuring a reaction field for growing the shell precursor, the volume average particle diameter (d ｖ In order to achieve high separation performance, particularly high separation performance at high flow rates, when the core-shell porous silica particles are used as a column packing material for liquid column chromatography, the volume average particle diameter (d ｖ Preferred ranges of the thickness of the nanoparticles are, for example, 300 nm or more and 2,400 nm or less, 400 nm or more and 2,000 nm or less, 450 nm or more and 1,500 nm or less, and 500 nm or more and 1,000 nm or less.

[0026] The volume average particle diameter (dｖ ) is calculated based on the following formula (2) by randomly selecting about 200 particles from a particle image taken with a scanning transmission electron microscope (STEM) (for example, "HD-2700" manufactured by Hitachi High-Technologies Corporation), measuring their particle sizes using image analysis software (for example, "Image J" manufactured by Wayne Rasband). ｉ represents the particle size, and n ｉ represents the number of particles.

[0027]

[0028] The shape of the non-porous silica particles is preferably spherical. In the present disclosure, spherical does not only mean a true sphere, but also includes shapes with a circular, nearly circular, elliptical, or nearly elliptical cross-sectional shape, such as a prolate spheroid or an oblate spheroid. Furthermore, spherical particles preferably mean particles with a shape that does not have rod-like protrusions on the particle surface.

[0029] The volume fraction of the nonporous silica particles in the aqueous suspension is not particularly limited, but is preferably 0.01 vol% or more, more preferably 0.10 vol% or more, even more preferably 0.40 vol% or more, even more preferably 0.60 vol% or more, and is preferably 20.00 vol% or less, more preferably 10.00 vol% or less, even more preferably 5.00 vol% or less, and even more preferably 2.00 vol% or less. That is, preferred ranges for the volume fraction of the nonporous silica particles in the aqueous suspension include, for example, 0.01 vol% or more and 20.00 vol% or less, 0.10 vol% or more and 10.00 vol% or less, 0.40 vol% or more and 5.00 vol% or less, and 0.60 vol% or more and 2.00 vol% or less.

[0030] By setting the volume fraction of nonporous silica particles in the aqueous suspension to the above lower limit or more, the proportion of the silica source consumed in forming the shell precursor increases, and the by-production of silica particles (hereinafter referred to as "secondary silica particles") resulting from the aggregation of silica species can be suppressed.By setting the volume fraction of nonporous silica particles in the aqueous suspension to the above upper limit or less, the frequency of collisions between nonporous silica particles can be reduced, and the shell precursor can be formed uniformly on the nonporous silica particles.

[0031] The nonporous silica particles may be commercially available or may be produced by any method such as a known method or a method similar thereto. Examples of known methods include the production method described in "Preparation Example 1 of Core Particles (Nonporous Silica Particles)" in the Examples of WO 2017 / 141821.

[0032] (Cationic surfactant) The cationic surfactant contained in the aqueous suspension self-assembles to form micelles, which act as templates for forming pores in the shell. The type and concentration of the cationic surfactant have a significant effect on the shape of the pores in the shell. The cationic surfactant may be used alone or in any combination and ratio of two or more kinds, but it is preferable to use one kind alone in order to form a shell with uniform pores.

[0033] The cationic surfactant is not particularly limited, and suitable examples include tetraalkylammonium halides and alkylamines.

[0034] The alkyl group of the tetraalkylammonium halide is preferably an alkyl group having 1 to 30 carbon atoms. Specific examples of the tetraalkylammonium halide include tetradecyltrimethylammonium halide, hexadecyltrimethylammonium halide, octadecyltrimethylammonium halide, eicosyltrimethylammonium halide, and docosyltrimethylammonium halide, and are preferably one or more selected from the group consisting of hexadecyltrimethylammonium halide and octadecyltrimethylammonium halide, and more preferably one or more selected from the group consisting of hexadecyltrimethylammonium bromide (cetyltrimethylammonium bromide (CTAB)) and octadecyltrimethylammonium bromide (stearyltrimethylammonium bromide (STAB)).

[0035] The alkylamine may be a straight-chain alkylamine having 8 to 20 carbon atoms, and dodecylamine is particularly preferred because it easily forms uniform pores.

[0036] The concentration of the cationic surfactant in the aqueous suspension is not particularly limited, but is preferably equal to or greater than the critical micelle concentration, more preferably equal to or greater than 5 times the critical micelle concentration, and even more preferably equal to or greater than 10 times the critical micelle concentration, in order to fully exert the cationic surfactant's template function. Furthermore, the concentration of the cationic surfactant in the aqueous suspension is preferably equal to or less than 100 times the critical micelle concentration, more preferably equal to or less than 80 times the critical micelle concentration, and even more preferably equal to or less than 40 times the critical micelle concentration, in order to form uniform pores. That is, preferred ranges of the concentration of the cationic surfactant in the aqueous suspension include, for example, the ranges of equal to or greater than the critical micelle concentration and equal to or less than 100 times the critical micelle concentration, 5 to 80 times the critical micelle concentration, and 10 to 40 times the critical micelle concentration.

[0037] The critical micelle concentration of a cationic surfactant is the concentration at which the cationic surfactant begins to form micelles in water. In the present disclosure, the concentration of the cationic surfactant in an aqueous solution of the cationic surfactant is plotted on the horizontal axis against the electrical conductivity of the aqueous solution of the cationic surfactant at 25°C on the vertical axis, and the Krafft point is taken as the critical micelle concentration. Alternatively, if the critical micelle concentration of a cationic surfactant is known from literature, the literature value can be used as the critical micelle concentration of the cationic surfactant. For example, the critical micelle concentration of CTAB can be found in Journal of Molecular Liquids, Volume 399, 2024, Article 124387.

[0038] (Basic catalyst) The basic catalyst contained in the aqueous suspension is not particularly limited, and can be appropriately selected from organic basic substances and inorganic basic substances that can promote the reaction of converting the silica source into silica. The basic catalyst may be used alone or in any combination and ratio of two or more.

[0039] Preferred examples of the basic catalyst include nitrogen-based basic catalysts such as ammonium and amine-based basic catalysts. Among these, the basic catalyst is more preferably ammonia, which has high reactivity. When ammonia is used as the basic catalyst, it is preferable to use aqueous ammonia from the viewpoint of safety.

[0040] The concentration of the basic catalyst in the aqueous suspension is not particularly limited, but is preferably 1 mM or more, more preferably 5 mM or more, and even more preferably 10 mM or more, in order to promote the production of silica species. Furthermore, the concentration of the basic catalyst in the aqueous suspension is preferably 3,000 mM or less, more preferably 1,000 mM or less, and even more preferably 500 mM or less, in order to facilitate reaction control. Preferred ranges for the concentration of the basic catalyst in the aqueous suspension include, for example, 1 mM or more and 3,000 mM or less, 5 mM or more and 1,000 mM or less, and 10 mM or more and 500 mM or less.

[0041] (Electrolyte) The electrolyte contained in the aqueous suspension is not particularly limited, and examples thereof include chlorine-based electrolytes, bromine-based electrolytes, iodine-based electrolytes, etc. The electrolyte may be used alone or in any combination and ratio of two or more kinds.

[0042] Examples of chlorine-based electrolytes include alkali metal chlorides such as lithium chloride, sodium chloride, and potassium chloride; alkaline earth metal chlorides such as calcium chloride, strontium chloride, and barium chloride; and tetraalkylammonium chlorides having an alkyl group having 1 to 4 carbon atoms, such as tetramethylammonium chloride.

[0043] Examples of bromine-based electrolytes include alkali metal bromides such as lithium bromide, sodium bromide, and potassium bromide; alkaline earth metal bromides such as calcium bromide, strontium bromide, and barium bromide; and tetraalkylammonium bromides having an alkyl group having 1 to 4 carbon atoms, such as tetramethylammonium bromide.

[0044] Examples of iodine-based electrolytes include alkali metal iodides such as lithium iodide, sodium iodide, and potassium iodide; alkaline earth metal iodides such as calcium iodide, strontium iodide, and barium iodide; and tetraalkylammonium iodides having an alkyl group having from 1 to 4 carbon atoms, such as tetramethylammonium iodide.

[0045] As will be shown in the examples described later, from the viewpoint of producing core-shell porous silica particles having a large shell thickness by efficiently precipitating silica seeds on core particles while suppressing the by-production of secondary silica particles, more preferred electrolytes include monovalent-monovalent electrolytes, such as potassium chloride and cesium chloride.

[0046] Furthermore, as will be shown in the Examples below, since the remaining particles not coated with a shell (hereinafter, core particles not coated with a shell or a shell precursor are referred to as "uncoated core particles") can be suppressed, core-shell porous silica particles with high monodispersity can be produced. More preferred electrolytes include those that have little steric hindrance and the ability to moderately disrupt the hydration structure. Specific examples of such electrolytes include potassium chloride and cesium chloride.

[0047] The electrolyte concentration in the first aqueous suspension is not particularly limited, but from the viewpoint of suppressing the remaining of uncoated core particles, suppressing the by-production of silica secondary particles, and thickening the shell, the electrolyte concentration in the reaction system in the reaction initiation step is preferably 2.0 mM or more, more preferably 3.0 mM or more, and even more preferably 4.0 mM or more. Furthermore, from the viewpoint of suppressing aggregation of the core particles, the electrolyte concentration in the first aqueous suspension is preferably 8.0 mM or less, more preferably 6.0 mM or less, and even more preferably 5.0 mM or less. That is, preferred ranges of the electrolyte concentration in the first aqueous suspension include, for example, amounts such that the electrolyte concentration in the reaction system is 2.0 mM or more and 8.0 mM or less, 3.0 mM or more and 6.0 mM or less, and 4.0 mM or more and 5.0 mM or less.

[0048] (Alcohol) The alcohol contained in the aqueous suspension is not particularly limited and can be appropriately selected from alcohols having any number of carbon atoms and any number of hydroxyl groups. The alcohol may be used alone or in any combination and ratio of two or more kinds.

[0049] The alcohol is preferably an alkyl alcohol. The alkyl group of the alkyl alcohol may be linear, branched, or cyclic, preferably linear or branched, more preferably linear. The number of carbon atoms in the alkyl group is usually 1 or more, preferably 2 or more, and preferably 12 or less, more preferably 8 or less, and even more preferably 6 or less.

[0050] Specific examples of the alcohol include methanol, ethanol, isopropanol, n-propanol, n-butanol, ethylene glycol, and glycerin. Among these, from the viewpoint of the solubility of the silica source, the alcohol is preferably methanol or ethanol, and more preferably ethanol.

[0051] The concentration of the alcohol in the aqueous suspension is not particularly limited, but is preferably 100 mM or more, more preferably 500 mM or more, even more preferably 1,000 mM or more, and is preferably 20,000 mM or less, more preferably 15,000 mM or less, even more preferably 10,000 mM or less. That is, preferred ranges of the alcohol concentration in the aqueous suspension include, for example, 100 mM or more and 20,000 mM or less, 500 mM or more and 15,000 mM or less, and 1,000 mM or more and 10,000 mM or less.

[0052] When an alkoxysilane is used as the silica source, the concentration of the alcohol in the aqueous suspension is set to the above lower limit or more to improve the hydrolysis rate of the alkoxysilane and to form a uniform shell precursor on the surface of the core particles.The concentration of the alcohol in the aqueous suspension is set to the above upper limit or less to efficiently consume the silica source in the formation of the shell precursor.

[0053] (Hydrophobe-Containing Additive) The aqueous suspension may contain a hydrophobe-containing additive. The hydrophobe-containing additive is a swelling agent that increases the volume of micelles formed by the cationic surfactant and has a hydrophobic organic group. The presence of the hydrophobe-containing additive in the reaction system allows the hydrophobe-containing additive to dissolve in the hydrophobic environment formed by the cationic surfactant, expanding the size of the hydrophobic field and forming a porous shell with a large pore size. The hydrophobe-containing additive may be used alone or in any combination and ratio of two or more.

[0054] The type of hydrophobic moiety-containing additive is not particularly limited, and examples include those having low solubility in water, such as benzene, toluene, cyclohexane (CyH), cyclohexanol, dodecanol, decane, chlorododecane, 1,3,5-trimethylbenzene (TMB), and 1,3,5-triisopropylbenzene. Among these, the hydrophobic moiety-containing additive is preferably one or more selected from the group consisting of cyclohexane (CyH), 1,3,5-trimethylbenzene (TMB), and 1,3,5-triisopropylbenzene, in view of its high non-polarity, and more preferably one or more selected from the group consisting of cyclohexane (CyH) and 1,3,5-trimethylbenzene (TMB).

[0055] When the aqueous suspension contains a hydrophobic-containing additive, the concentration of the hydrophobic-containing additive in the aqueous suspension is preferably 1.0 mM or more, more preferably 5.0 mM or more, from the viewpoint of exhibiting the pore size expansion effect, while the concentration of the hydrophobic-containing additive in the aqueous suspension is preferably 1,000 mM or less, preferably 500 mM or less, from the viewpoint of maintaining the micelle structure formed by the cationic surfactant.

[0056] When the aqueous suspension contains a hydrophobic-moiety-containing additive, the mass ratio of the hydrophobic-moiety-containing additive to the cationic surfactant is preferably 0.1 or more, more preferably 0.5 or more, even more preferably 1.0 or more, still more preferably 3.0 or more, and particularly preferably 5.0 or more, from the viewpoint of expanding the hydrophobic environment space formed by the cationic surfactant. On the other hand, the mass ratio of the hydrophobic-moiety-containing additive to the cationic surfactant is preferably 15.0 or less, more preferably 12.0 or less, and even more preferably 10.0 or less, from the viewpoint of avoiding shell collapse in the shell formation step.

[0057] 1-1-2. Electrolyte In the second reaction initiation step, the electrolyte added to the second aqueous suspension is the same as the electrolyte contained in the first aqueous suspension. In the second reaction initiation step, only the electrolyte may be added to the second aqueous suspension, or an electrolyte solution in which the electrolyte is dissolved in a solvent may be added to the second aqueous suspension. When an electrolyte solution is added to the second aqueous suspension, the solvent of the electrolyte solution is not particularly limited as long as it can dissolve the electrolyte. The solvent may be used alone, or two or more solvents may be used in any combination and ratio.

[0058] Suitable solvents for the electrolyte solution include water and alcohols, including those listed in the description of the alcohol contained in the aqueous suspension.

[0059] The electrolyte concentration in the electrolyte solution is not particularly limited and may be appropriately selected so that the electrolyte concentration in the reaction system is in a desired range. The electrolyte concentration of the electrolyte solution may be, for example, 5 mM or more and 1,000 mM or less, or 10 mM or more and 500 mM or less.

[0060] The amount of electrolyte added to the second aqueous suspension is not particularly limited, but from the viewpoint of suppressing the remaining of uncoated core particles, suppressing the by-production of silica secondary particles, and thickening the shell, the amount is such that the electrolyte concentration in the reaction system in the reaction initiation step is preferably 2.0 mM or more, more preferably 3.0 mM or more, and even more preferably 4.0 mM or more. Furthermore, from the viewpoint of suppressing aggregation of the core particles, the amount of electrolyte added to the second aqueous suspension is such that the electrolyte concentration in the reaction system is preferably 8.0 mM or less, more preferably 6.0 mM or less, and even more preferably 5.0 mM or less. That is, preferred ranges of the amount of electrolyte added to the second aqueous suspension include, for example, amounts such that the electrolyte concentration in the reaction system is 2.0 mM or more and 8.0 mM or less, 3.0 mM or more and 6.0 mM or less, and 4.0 mM or more and 5.0 mM or less.

[0061] In the second reaction initiation step, the target to which the electrolyte is added is the second aqueous suspension for convenience, but this second aqueous suspension may be one to which a part or all of the silica source-containing liquid has been added. That is, in the second reaction initiation step, the timing of adding the silica source-containing liquid and the electrolyte to the second aqueous suspension is not particularly limited, and for example, the silica source-containing liquid and the electrolyte may be added to the second aqueous suspension simultaneously, or the electrolyte may be added at the timing when a part or all of the silica source-containing liquid has been added to the second aqueous suspension.

[0062] In this embodiment, the addition of the electrolyte to the second aqueous suspension is preferably performed at any timing after the addition of the silica source-containing liquid to the second aqueous suspension is completed (or, in the case of continuous addition, the addition is started), and more preferably when the Debye length of the reaction system becomes small. As shown in the examples described below, adding an electrolyte to the reaction system when the Debye length of the reaction system becomes small can suppress the electrostatic repulsion between the silica species and the core particles (hereinafter, nonporous silica particles and nonporous silica particles having a shell precursor deposited on their surfaces may be collectively referred to as "core particles"), which is thought to promote the precipitation of the silica species onto the core particles. If the silica species can be efficiently precipitated onto the core particles, the shell thickness can be increased, and highly monodisperse core-shell porous silica particles can be produced by suppressing the by-production of secondary silica particles. Note that, in the present disclosure, the "Debye length of the reaction system" strictly refers to the Debye length of the solution portion of the reaction system excluding insoluble matter.

[0063] The timing at which the Debye length of the reaction system becomes small can be derived by calculating the change in the Debye length of the reaction solution over time using the method described in the Examples below. In other words, the time at which the Debye length of the reaction system becomes its minimum value is determined from the change in the Debye length of the reaction system over time, and the time around this time is determined to be the time at which the Debye length of the reaction system becomes small.

[0064] The vicinity of the time when the Debye length of the reaction system is minimum refers to, for example, a time period from 2 minutes before to 5 minutes after this time, preferably a time period from 1 minute before to 3 minutes after this time, and more preferably a time period from this time to 1 minute after this time.

[0065] The vicinity of the time when the Debye length of the reaction system is minimum may be within a time period that satisfies the following condition I): Condition I) The Debye length of the reaction system is equal to or greater than the minimum value in the change in Debye length over time and equal to or less than the value obtained by multiplying the minimum value by X. In condition I), X is greater than 1.00 and equal to or less than 1.10, preferably greater than 1.00 and equal to or less than 1.05.

[0066] Alternatively, the vicinity of the time when the Debye length of the reaction system is minimized may be within a time period that satisfies the following condition II): Condition II) The reciprocal of the hydrolysis rate constant of the silica source under the reaction conditions is 0.1 or more and 1.0 or less.

[0067] 1-1-3. Silica Source-Containing Liquid The silica source-containing liquid added to the aqueous suspension in the reaction initiation step is not particularly limited as long as it contains a silica source, and may consist of only the silica source, or may be a silica source solution obtained by diluting the silica source with a solvent. The concentration of the silica source solution is not particularly limited and may be appropriately selected depending on the solubility and reactivity of the silica source, etc. The method for preparing the silica source solution is not particularly limited, and the silica source solution is usually prepared by mixing the components in any order.

[0068] The addition of the silica source-containing liquid to the aqueous suspension does not need to be continuous addition, and may be either a lump-sum addition or a continuous addition, but is preferably a lump-sum addition.

[0069] (Silica Source) The silica source is not particularly limited as long as it can form silicon oxide by reaction. The silica source may be used alone or in any combination and ratio of two or more kinds.

[0070] As the silica source, from the viewpoints of reaction efficiency and handling, one or more selected from the group consisting of alkoxysilanes and silicates are preferred, and alkoxysilanes are more preferred.

[0071] In terms of versatility, examples of alkoxysilanes include trialkylalkoxysilanes such as trimethylmethoxysilane and trimethylethoxysilane, and tetraalkoxysilanes such as tetraethoxysilane (tetraethylorthosilicate (TEOS)) and tetramethoxysilane, with TEOS being particularly preferred. Examples of silicates include sodium silicate and potassium silicate.

[0072] The amount of silica source added to the reaction system in the reaction initiation step depends on the type of silica source and the volume average particle diameter (d ｖ), etc., it is preferable that the ratio of the amount of substance of the cationic surfactant to the amount of substance of silicon in the reaction system (hereinafter sometimes referred to as the "cationic surfactant / silicon amount ratio") be in a specific range. More specifically, from the viewpoint of efficiently forming the shell precursor, the amount of substance ratio of the cationic surfactant / silicon in the reaction system is preferably 0.01 or more, more preferably 0.05 or more, and even more preferably 0.10 or more. Furthermore, from the viewpoint of suppressing the by-production of silica secondary particles, the amount of substance ratio of the cationic surfactant / silicon in the reaction system is preferably 10 or less, more preferably 5 or less, and even more preferably 1 or less. That is, preferred ranges of the amount of silica source added to the reaction system in the reaction initiation step include amounts such that the amount of substance ratio of the cationic surfactant / silicon in the reaction system is, for example, 0.01 or more and 10 or less, 0.05 or more and 5 or less, and 0.10 or more and 1 or less.

[0073] (Solvent) The solvent for the silica source solution is not particularly limited as long as it does not inhibit the formation of the shell precursor. The solvent may be used alone or in any combination and ratio of two or more. Suitable solvents include water and alcohol. As the alcohol, the alcohols listed in the description of the alcohol contained in the aqueous suspension can be used.

[0074] 1-1-4. Reaction Conditions The temperature of the reaction system in the reaction initiation step is preferably 5°C or higher, more preferably 10°C or higher, and even more preferably 15°C or higher, from the viewpoint of reaction rate. On the other hand, the temperature of the reaction system is preferably 80°C or lower, more preferably 70°C or lower, and even more preferably 60°C or lower, from the viewpoint of reaction controllability and the boiling point of the solvent. That is, preferred ranges of the temperature of the reaction system in the reaction initiation step include, for example, ranges of 5°C or higher and 80°C or lower, 10°C or higher and 70°C or lower, and 15°C or higher and 60°C or lower.

[0075] 1-2. First Silica Source Continuous Addition Step The first silica source continuous addition step is a step of adding a cationic surfactant and continuously adding a silica source-containing liquid containing a silica source to the reaction system after the reaction initiation step.

[0076] 1-2-1. Cationic Surfactant The cationic surfactant added to the reaction system in the first silica source continuous addition step can be the same as the cationic surfactant contained in the aqueous suspension in the reaction initiation step. The cationic surfactant added to the reaction system in the first silica source continuous addition step may be the same as or different from the cationic surfactant contained in the aqueous suspension in the reaction initiation step, but from the viewpoint of improving the uniformity of the pore shape and pore size of the shell, it is preferable that the cationic surfactant be the same. Furthermore, it is preferable that the cationic surfactant be added to the reaction system so that the concentration of the cationic surfactant in the reaction system is in the same range as the concentration of the cationic surfactant in the aqueous suspension described above.

[0077] 1-2-2. Silica Source-Containing Liquid The silica source-containing liquid continuously added to the reaction system in the first silica source continuous addition step can be the same as the silica source-containing liquid added to the reaction system in the reaction initiation step. The silica source-containing liquid continuously added to the reaction system in the first silica source continuous addition step may be the same as or different from the silica source-containing liquid added to the reaction system in the reaction initiation step, but is preferably the same.

[0078] The continuous addition of the silica source-containing liquid to the reaction system in the first silica source continuous addition step is carried out under conditions such that the molar ratio of cationic surfactant to silicon in the reaction system is preferably 0.01 or more, more preferably 0.05 or more, and even more preferably 0.10 or more, from the viewpoint of efficiently forming a shell precursor. Furthermore, the continuous addition of the silica source-containing liquid to the reaction system in the first silica source continuous addition step is carried out under conditions such that the molar ratio of cationic surfactant to silicon in the reaction system is preferably 10 or less, more preferably 5 or less, and even more preferably 1 or less, from the viewpoint of suppressing the by-production of secondary silica particles. That is, preferred conditions for the continuous addition of the silica source-containing liquid to the reaction system in the first silica source continuous addition step include, for example, conditions such that the molar ratio of cationic surfactant to silicon in the reaction system is 0.01 or more and 10 or less, 0.05 or more and 5 or less, and 0.10 or more and 1 or less.

[0079] 1-2-3. Timing for Starting Continuous Addition of Silica Source-Containing Liquid to Reaction System As will be shown in the Examples described later, in order to produce core-shell porous silica particles having a large shell thickness, it is considered desirable to continuously add the silica source-containing liquid slowly so as to maintain the silicate ion concentration in the reaction system lower than the solubility of silica after the silicate ion concentration, which increases as a result of adding the silica source-containing liquid to the reaction system in the reaction initiation step, has sufficiently decreased.

[0080] The silicate ion concentration increases when the silica source-containing liquid is added to the reaction system, and then decreases as the silicate ions are consumed for shell formation. The state in which the silicate ion concentration has been sufficiently decreased means that the silicate ion concentration, which has been decreased by consumption for shell formation, has decreased to 5.0 times or less, preferably 3.0 times or less, more preferably 1.0 times or less, and even more preferably less than 1.0 times the amount of silica that can be dissolved in the reaction system (i.e., the solubility of silica).

[0081] 1-2-4. Rate of Addition of Silica Source-Containing Liquid to Reaction System As long as the reaction is carried out under conditions where the silicate ion concentration is lower than the solubility of silica in the reaction system, the rate (flow rate) at which the silica source-containing liquid is continuously added to the reaction system does not necessarily have to be constant, but it is preferable to continuously add the silica source-containing liquid to the reaction system at a constant or approximately constant rate.

[0082] As described above, the rate at which the silica source-containing liquid is continuously added to the reaction system is preferably a rate at which the silicate ion concentration in the reaction system can be maintained lower than the solubility of silica. However, as shown in the examples described below, if the continuous addition rate of the silica source-containing liquid is too slow, the monodispersity of the resulting core-shell porous silica particles tends to decrease. Therefore, the silicate ion concentration is preferably 50% or more of the solubility of silica, more preferably 60% or more, and even more preferably 70% or more, and preferably less than 100%, more preferably 95% or less, and even more preferably 90% or less. That is, preferred ranges of the silicate ion concentration include, for example, 50% or more but less than 100%, 60% or more but 95%, and 70% or more but 90% of the solubility of silica.

[0083] The solubility of silica can be determined from literature values ​​or predicted data obtained by applying an approximation curve to the literature values. For example, the solubility of silica in a water / ethanol mixed solvent can be determined from the values ​​described in R.K. Iler, "The Chemistry of Silica," Wiley-Interscience (1982) or a value predicted from these values.

[0084] Since the concentration of each ion in a liquid correlates with the electrical conductivity, the silicate ion concentration in a reaction system can be estimated by measuring the electrical conductivity of the reaction system. More specifically, the silicate ion concentration in a reaction system can be estimated by comparing the electrical conductivity of the reaction system with the time-dependent change in electrical conductivity and the estimated ion concentration described in Journal of Chemical Engineering of Japan, Vol. 33, No. 3, pp. 468-473, 2000.

[0085] 1-2-5. Reaction Conditions The temperature of the reaction system in the first silica source continuous addition step is preferably 5°C or higher, more preferably 10°C or higher, and even more preferably 15°C or higher, from the viewpoint of reaction rate. On the other hand, the temperature of the reaction system is preferably 80°C or lower, more preferably 70°C or lower, and even more preferably 60°C or lower, from the viewpoint of reaction controllability and the boiling point of the solvent. That is, preferred ranges of the temperature of the reaction system in the first silica source continuous addition step include, for example, ranges of 5°C or higher and 80°C or lower, 10°C or higher and 70°C or lower, and 15°C or higher and 60°C or lower.

[0086] 1-3. n-th Silica Source Continuous Addition Step In the method for producing core-shell type porous silica particles according to this embodiment, the core-shell type silica particles may be produced by further performing an n-th silica source continuous addition step after the first silica source continuous addition step. The n-th silica source continuous addition step is a step of adding a cationic surfactant to the reaction system after the (n-1)th silica source continuous addition step, and continuously adding a silica source-containing liquid containing a silica source. In other words, the method for producing core-shell type porous silica particles according to this embodiment may include one or more (n-1) n-th silica source continuous addition steps, i.e., after the reaction is initiated by adding a silica source-containing liquid to an aqueous suspension, the silica source may be additionally supplied to the reaction system two or more times.

[0087] In the n-th silica source continuous addition step, n is a value obtained by subtracting 1 from the number of additional supplies of silica source carried out after the reaction initiation step, and is an integer of 2 or greater. From the viewpoint of increasing the shell thickness, n is preferably 3 or greater, more preferably 4 or greater. The upper limit of n is not particularly limited, but is preferably 10 or less, more preferably 8 or less, and even more preferably 6 or less. That is, preferred ranges of n include, for example, 2 or more and 10 or less, 3 or more and 8 or less, and 4 or more and 6 or less, and n is particularly preferably 2, 3, or 4.

[0088] 1-3-1. Cationic Surfactant The cationic surfactant added to the reaction system in the nth silica source continuous addition step can be the same as the cationic surfactant added to the reaction system in the first silica source continuous addition step. The cationic surfactant added to the reaction system in the nth silica source continuous addition step may be the same as or different from the cationic surfactant added to the reaction system in the first silica source continuous addition step, but from the viewpoint of improving the uniformity of the pore shape and pore size of the shell, it is preferable that the cationic surfactant be the same. Furthermore, it is preferable that the cationic surfactant be added to the reaction system so that the concentration of the cationic surfactant in the reaction system is in the same range as the concentration of the cationic surfactant in the aqueous suspension described above.

[0089] 1-3-2. Silica Source-Containing Liquid The silica source-containing liquid continuously added to the reaction system in the n-th silica source continuous addition step can be the same as the silica source-containing liquid continuously added to the reaction system in the first silica source continuous addition step. The silica source-containing liquid continuously added to the reaction system in the n-th silica source continuous addition step may be the same as or different from the silica source-containing liquid continuously added to the reaction system in the first silica source continuous addition step, but is preferably the same.

[0090] The continuous addition of the silica source-containing liquid to the reaction system in the n-th silica source continuous addition step is carried out under conditions such that the molar ratio of cationic surfactant to silicon in the reaction system is preferably 0.01 or more, more preferably 0.05 or more, and even more preferably 0.10 or more, from the viewpoint of efficiently forming a shell precursor. Furthermore, the continuous addition of the silica source-containing liquid to the reaction system in the n-th silica source continuous addition step is carried out under conditions such that the molar ratio of cationic surfactant to silicon in the reaction system is preferably 10 or less, more preferably 5 or less, and even more preferably 1 or less, from the viewpoint of suppressing the by-production of secondary silica particles. That is, preferred conditions for the continuous addition of the silica source-containing liquid to the reaction system in the n-th silica source continuous addition step include, for example, conditions such that the molar ratio of cationic surfactant to silicon in the reaction system is 0.01 or more and 10 or less, 0.05 or more and 5 or less, and 0.10 or more and 1 or less.

[0091] 1-3-3. Timing for Starting Continuous Addition of Silica Source-Containing Liquid to Reaction System In the nth silica source continuous addition step, as in the first silica source continuous addition step, in order to produce core-shell porous silica particles with a large shell thickness, it is considered desirable to continuously add the silica source-containing liquid slowly after the silicate ion concentration has been sufficiently reduced after the (n-1)th silica source continuous addition step, so that the silicate ion concentration in the reaction system can be maintained at a level lower than the solubility of silica. The "state in which the silicate ion concentration has been sufficiently reduced" referred to here is as described above in the section "1-2-3. Timing for Starting Continuous Addition of Silica Source-Containing Liquid to Reaction System."

[0092] 1-3-4. Rate of Addition of Silica Source-Containing Liquid to Reaction System The rate (flow rate) at which the silica source-containing liquid is continuously added to the reaction system in the n-th silica source continuous addition step is the same as the rate at which the silica source-containing liquid is continuously added to the reaction system in the first silica source continuous addition step, and therefore the explanation in the above section "1-2-4. Rate of Addition of Silica Source-Containing Liquid to Reaction System" is incorporated herein by reference. Note that the rate at which the silica source-containing liquid is added to the reaction system in the silica source continuous addition step does not need to be the same for each addition.

[0093] 1-3-5. Reaction conditions The temperature of the reaction system in the nth silica source continuous addition step is the same as that explained as the reaction temperature in the first silica source continuous addition step, and therefore the explanation in the above section "1-2-5. Reaction conditions" is incorporated herein by reference (with the proviso that "first time" should be read as "nth time").

[0094] 1-4. Shell Porosity Forming Step The shell porosity forming step is a step of converting the shell precursor into a porous shell by removing the cationic surfactant from the shell precursor of the core-shell silica particle. The cationic surfactant to be removed is the cationic surfactant used as a pore template, and includes the cationic surfactant contained in the aqueous suspension in a1) and the cationic surfactant added to the reaction system in a2) and a3). When an aqueous suspension containing a hydrophobic-containing additive is used in the reaction initiation step, the hydrophobic-containing additive is also removed from the shell precursor in the shell porosity forming step in addition to the cationic surfactant. From the viewpoint of reducing production costs and simplifying operations, it is preferable to remove the hydrophobic-containing additive together with the cationic surfactant in the treatment for removing the cationic surfactant.

[0095] As a method for removing the cationic surfactant from the shell precursor, there can be mentioned an elution method in which the core-shell silica particles having a core and a shell precursor are put into a solvent in which the cationic surfactant is dissolved, and the cationic surfactant is eluted into the solvent; and a calcination method in which the core-shell silica particles having a core and a shell precursor are calcined, and the cationic surfactant contained in the shell precursor is burned off; etc. As a method for removing the cationic surfactant from the shell precursor, either the elution method or the calcination method is preferable, and it is also preferable to carry out both of these two methods from the viewpoint that the cationic surfactant can be completely removed.

[0096] The calcination temperature in the calcination method is preferably 300°C or higher, more preferably 400°C or higher, and even more preferably 500°C or higher, from the viewpoint of sufficiently removing the cationic surfactant. On the other hand, the calcination temperature is preferably 1,000°C or lower, more preferably 900°C or lower, and even more preferably 800°C or lower, from the viewpoint of maintaining the porous structure. That is, preferred ranges of the calcination temperature include, for example, 300°C or higher and 1,000°C or lower, 400°C or higher and 900°C or lower, and 500°C or higher and 800°C or lower.

[0097] From the viewpoint of sufficiently removing the cationic surfactant, the baking time is preferably 30 minutes or more, more preferably 1 hour or more, and even more preferably 2 hours or more. On the other hand, the baking time is preferably 24 hours or less, more preferably 12 hours or less, and even more preferably 6 hours or less. That is, preferred ranges of the baking time include, for example, 30 minutes to 24 hours, 1 hour to 12 hours, and 2 hours to 6 hours.

[0098] The shell porous formation step may include any steps such as a washing step of separating the core-shell silica particles formed in the n-th silica source continuous addition step from the reaction system and washing them; and a drying step of drying the core-shell silica particles.

[0099] In the washing step, the shell precursor can be precipitated by, for example, centrifugation, and then the solution can be exchanged for washing. The solution used for washing is preferably water, particularly deionized water (ultrapure water). Washing may be performed once or multiple times (for example, two or three times).

[0100] The drying step can be carried out, for example, by separating the core-shell silica particles from the reaction system and then leaving them to stand overnight under vacuum at room temperature or under heated conditions. In the present disclosure, "room temperature" refers to a temperature range of 15°C or higher and 35°C or lower. The heating conditions are not particularly limited, and are preferably 40°C or higher and 100°C or lower.

[0101] 2. Core-shell porous silica particles Preferred physical properties of the core-shell porous silica particles obtained by the method for producing core-shell porous silica particles according to this embodiment will be described below.

[0102] The volume average particle diameter (d ｖ ) is preferably 800 nm or more, more preferably 1,000 nm or more, even more preferably 1,100 nm or more, and is preferably 2,500 nm or less, more preferably 2,000 nm or less, even more preferably 1,800 nm or less, from the viewpoint of separation performance when used as a column packing material for liquid chromatography.

[0103] The volume average particle diameter (d ｖ ) is the volume average particle size (d ｖ ) is measured by the same method.

[0104] The volume average particle diameter (d ｖ ) is the volume average particle diameter (d ｖ ) is measured by the same method as that for measuring the same.

[0105] The volume average particle diameter (d ｖ ) is determined as follows. When the shell thickness is about 300 nm or less, about 200 core-shell porous silica particles are randomly selected from a particle image taken with an STEM, the particle size of the core particle portion in the particle image is measured, and the particle size is calculated based on the above formula (2). When the shell thickness is thicker than about 300 nm, it is difficult to identify the boundary between the core particle and the shell, so the measurement is performed by utilizing the difference in refractive index between the core particle and the shell as described below. That is, the core-shell porous silica particles are immersed in a medium having a refractive index similar to that of the shell, and about 200 core-shell porous silica particles are randomly selected from the particle image obtained by photographing the particle with an optical microscope, the particle size of the core particle portion in the particle image is measured, and the particle size is calculated based on the above formula (2).

[0106] The average shell thickness of the core-shell porous silica particles (T ｓFrom the viewpoint of high porosity, the average shell thickness (T ｓ ) is preferably 500 nm or less, more preferably 480 nm or less, even more preferably 450 nm or less, and particularly preferably 400 nm or less, from the viewpoint of the mechanical strength of the particles.

[0107] The average shell thickness of the core-shell porous silica particles (T ｓ ) is the volume average particle diameter (d ｖ ) to calculate the volume average particle diameter (d ｖ ) and divide the result by 2.

[0108] The average shell thickness (T ｓ ) is preferably 0.500 or more, more preferably 0.580 or more, and even more preferably 0.600 or more, and from the viewpoint of the mechanical strength of the particles, is preferably 1.000 or less, more preferably 0.800 or less, and even more preferably 0.700 or less.

[0109] The peak pore diameter (D ｐ ) is preferably 1.0 nm or more, more preferably 2.0 nm or more, even more preferably 2.1 nm or more, still more preferably 2.2 nm or more, because the shell functions as an adsorption layer when used as a column packing material for liquid chromatography. Also, it is usually preferably 10.0 nm or less, more preferably 6.0 nm or less, even more preferably 3.0 nm or less, and even more preferably 2.4 nm or less.

[0110] The peak pore diameter (D ｐThe nitrogen adsorption / desorption isotherm is determined by BJH analysis of the nitrogen adsorption / desorption isotherm using analytical software (for example, "BEL Master" manufactured by Microtrac-BEL Co., Ltd.). The nitrogen adsorption / desorption isotherm is created by nitrogen adsorption / desorption measurement using an automatic specific surface area / pore distribution measuring device (for example, "BELSORP-mini II" manufactured by Microtrac-BEL Co., Ltd.).

[0111] The pore volume (V ｐ ) is preferably 0.100 cm in order to ensure sufficient permeability of the substances to be separated when used as a column packing material for liquid chromatography. ３ / g or more, more preferably 0.200 cm ３ / g or more, and more preferably 0.300 or more. On the other hand, the pore volume (V ｐ ) is preferably 5.000 cm in terms of improving the elution time of the substance to be separated and the ease of operation when used as a column packing material for liquid chromatography. ３ / g or less, more preferably 2.000 cm ３ / g or less, more preferably 1.000 cm ３ / g or less, and even more preferably 0.500 cm ３ / g or less.

[0112] The pore volume (V ｐ ) is the ratio of vapor pressure to saturated vapor pressure (p / p ０ The nitrogen adsorption amount is determined by the nitrogen adsorption / desorption measurement described above.

[0113] The BET specific surface area (S ＢＥＴ ) is preferably 150 m in order to ensure sufficient permeability of the substances to be separated when used as a column packing material for liquid chromatography. ２ / g or more, more preferably 300m ２ / g or more, more preferably 400m ２ / g or more, and even more preferably 500m ２On the other hand, the BET specific surface area (S ＢＥＴ ) is preferably 3,000 m in terms of improving the elution time of the substances to be separated and the ease of operation when used as a column packing material for liquid chromatography. ２ / g or less, more preferably 2,000m ２ / g or less, more preferably 1,000m ２ / g or less, and even more preferably 800m ２ / g or less.

[0114] The BET specific surface area (S ＢＥＴ The nitrogen adsorption / desorption isotherm is determined by BET analysis of the nitrogen adsorption / desorption isotherm using analysis software (for example, "BEL Master" manufactured by Microtrac BEL Co., Ltd.). The nitrogen adsorption / desorption isotherm is created by the nitrogen adsorption / desorption measurement described above.

[0115] When core-shell porous silica particles are used as a column packing material for liquid column chromatography, it is believed that the smaller the particle size of the column packing material, the higher the separation performance, particularly at high flow rates. Therefore, in consideration of use as a column packing material, it is desirable that the particle size of the core-shell porous silica particles be smaller than the particle size (2.6 to 5.0 μm) of conventional core-shell particles for column packing materials.

[0116] To improve the separation performance of a column packing material, it is necessary to shorten the diffusion distance of the substance to be separated into and out of the pores and ensure a sufficient retention time. To achieve this, it is important to increase the shell thickness so that the substance to be separated is retained for a longer period of time. Since the improvement of the separation performance of a column packing material also depends on the porosity of the shell, the peak pore diameter (D ｐ ) and BET specific surface area, etc. are also preferably within the above ranges.

[0117] Hereinafter, the present disclosure will be described in more detail with reference to examples, but the present disclosure is not limited to the examples as long as it does not deviate from the gist of the disclosure.

[0118] [Reference Example 1: Examination of the timing of adding electrolyte to the reaction system] [Reference Example 1-1: Observation of the change over time in the average thickness of the shell precursor] The volume average particle size (d ｖ ) 460 nm spherical non-porous silica particles (manufactured by Sakai Chemical Industry Co., Ltd., C ｖ =5.0%, ρ=1.9g / cm ３ , S ｍ ≦50m ２ 0.390 g of PEG-100 (16.2 mL / g), 16.2 mL of ethanol, and 32.4 mL of water were mixed and ultrasonicated for 30 minutes to disperse nonporous silica particles in the solvent. 0.364 g of CTAB was added to the resulting dispersion and ultrasonicated for 30 minutes, followed by addition of 0.375 mL of 25% by mass ammonia water and ultrasonication for 30 minutes to prepare an aqueous suspension containing 0.40 vol% nonporous silica particles. 1.12 mL (5 mmol) of TEOS was added to this aqueous suspension and allowed to react.

[0119] The particles formed at 1 minute, 3 minutes, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 45 minutes, 90 minutes, and 18 hours after the addition of TEOS were observed by STEM. The STEM images are shown in Figure 1 (A) to (K), respectively. The average shell thickness (T ｓ The measurement method for the average thickness of the shell precursor was also shown in Table 1.

[0120]

[0121] As shown in FIG. 1, after 1 minute had passed since the addition of TEOS, no shell precursors were observed to be formed on the core particles. On the other hand, after 3 minutes had passed since the addition of TEOS, the formation of a shell precursor with a thickness of approximately 42 nm was confirmed, and after 5 minutes, the thickness of the shell precursor was confirmed to have further increased. After 10 minutes since the addition of TEOS, irregularities were observed on the surface of the generated particles, indicating that a shell precursor with a low coating density had been formed. After 15 minutes since the addition of TEOS, the surface of the generated particles was smooth, and the coating density had also increased. After 20 and 25 minutes since the addition of TEOS, it was confirmed that shell precursors of similar thickness had been formed on the core particles. This suggests that the densification of the shell precursor was progressing at this stage. After 30 minutes since the addition of TEOS, the shell precursor was observed to grow slowly. The thickness of the shell precursor was approximately 194 nm 90 minutes after the addition of TEOS and approximately 261 nm 18 hours after the addition, which suggests that the shell precursor gradually grew between 90 minutes and 18 hours after the start of the reaction.

[0122] From the STEM images taken 3 minutes and 18 hours after the addition of TEOS, approximately 20% of the particles observed at each time point were uncoated core particles. This suggests that the formation of shell precursors on core particles occurs only in the early stage of the reaction. If uncoated core particles remain, the particle size uniformity of the resulting core-shell porous silica particles decreases. Therefore, in order to obtain highly monodisperse core-shell porous silica particles, it is considered important to promote the formation of shell precursors on core particles in the early stage of the reaction.

[0123] Reference Example 1-2: Observation of change in Debye length over time In Reference Example 1-1, the change in pH (35° C.) in the reaction system over time was measured, and the NH ４ ＋ , H ＋ , and OH － The ionic strength of the sample was calculated.

[0124]

[0125] Kｗ = [H ＋ ][OH － ] (II) [NH ３ ] Ｔ = [NH ３ ]+[NH ４ ＋ ] (III)

[0126] In the formula, [NH ３ ] Ｔ represents the concentration of added ammonia, and a portion of the added ammonia is protonated to form NH ４ ＋ However, since the reaction solvent was a mixed solvent of water and ethanol, the measured pH value was corrected using the following formula (IV) (see R.G. Bates, M. Paabo, R.A. Robinson, J. Phys. Chem., 67, 1833-1838, (1963) and G. Douheret, Bull. Soc. Chim. Fr., 1412-1419 (1967)).

[0127] pH ｃｏｒｒｅｃｔｅｄ = pH ｍｅａｓｕｒｅｄ -δ (IV) where pH ｃｏｒｒｅｃｔｅｄ represents the corrected pH, and pH ｍｅａｓｕｒｅｄ represents the measured pH value, and δ represents the corrected value. δ is a value determined depending on the solvent composition, and the value obtained by linear approximation of the literature value was used. The pH corrected values ​​and dissociation constants in a water / ethanol mixed solvent are shown in Table 2.

[0128]

[0129] Here, the time-dependent changes in the concentration of each ion species were calculated by making the following assumptions: CTAB is completely ionized, and Br － does not participate in the reaction and its concentration remains constant before and after the reaction. CTAB in excess of the critical micelle concentration is entirely consumed in shell formation. The ratio of excess CTAB to Si derived from the added TEOS (CTA ＋ / Si) and SiO ２ From the amount formed, [CTA] at each reaction time was calculated. ＋ ] is estimated.

[0130] The change in ionic strength over time in the reaction system was calculated from the pH measurement results and the above assumptions. The results are shown in Figure 2. Figure 2 confirms that the silicate ion concentration rises sharply due to the hydrolysis of TEOS immediately after the start of the reaction, resulting in a large change in ionic strength.

[0131] The change in the Debye length of particles in the reaction system over time calculated based on Figure 2 is shown in Figure 3. －１ ) means the thickness of the layer when ion species near the particle surface are distributed in a cloud-like manner due to Coulomb force and thermal motion, and is calculated by the following formula (V).

[0132]

[0133] where κ represents the Debye-Hückel parameter and ε ｒ represents the relative permittivity (ε ｒ = 58.9; see Chemical Society of Japan, Basic Chemistry Handbook, Revised 5th Edition, 2004), ε ０ represents the dielectric constant in a vacuum, and k Ｂ represents the Boltzmann constant, T represents the reaction temperature, and N Ａ represents Avogadro's constant, e represents the elementary charge, and I represents the ionic strength.

[0134] It was confirmed from Figure 3 that the Debye length reached its minimum approximately 150 seconds after the start of the reaction. It is presumed that if the electrostatic repulsion between the silica species and the particles can be suppressed at the stage when the Debye length becomes shorter, the precipitation of the silica species onto the core particles will be promoted.

[0135] Reference Example 1-3: Examination of the timing of adding electrolyte to the reaction system Volume average particle size (d ｖ ) 460 nm spherical non-porous silica particles (manufactured by Sakai Chemical Industry Co., Ltd., C ｖ =5.0%, ρ=1.9g / cm ３ , S ｍ ≦50m ２0.390 g of HCl (16.2 mL / g), 16.2 mL of ethanol, and 31.4 mL of water were mixed and ultrasonicated for 30 minutes to disperse nonporous silica particles in the solvent. 0.364 g of CTAB was added to the resulting dispersion and ultrasonicated for 30 minutes, followed by 0.375 mL of 25% by mass aqueous ammonia and ultrasonicated for 30 minutes to prepare an aqueous suspension of 0.40 vol% nonporous silica particles. 1.12 mL (5 mmol) of TEOS was added to this aqueous suspension, and an aqueous potassium chloride solution was added simultaneously with the addition of TEOS, 3 minutes after the addition of TEOS, or 10 minutes after the addition of TEOS. The reaction was allowed to proceed for 18 hours from the addition of TEOS to obtain particles. The aqueous potassium chloride solution was prepared by mixing 0.20 mmol (0.0149 g) of potassium chloride with 1 mL of water to achieve a potassium chloride concentration of approximately 4.0 mM in the reaction system.

[0136] The particles obtained by adding a potassium chloride aqueous solution simultaneously with the addition of TEOS, 3 minutes after the addition of TEOS, or 10 minutes after the addition of TEOS were observed by STEM. The STEM images are shown in Figures 4(A) to 4(C), respectively. The average shell thickness (T ｓ The average thickness of the shell precursor was measured by the same method as in Example 1.

[0137]

[0138] 4, it was confirmed that when the electrolyte was added simultaneously with the addition of TEOS or 3 minutes after the addition of TEOS, the number of remaining uncoated core particles was extremely small. It was also confirmed that when the electrolyte was added 3 minutes after the addition of TEOS, the thickness of the shell precursor was maximized. On the other hand, when the electrolyte was added 10 minutes after the addition of TEOS, it was confirmed that many uncoated core particles remained and the thickness of the shell precursor was small.

[0139] The potassium chloride solution was added simultaneously with the addition of TEOS, 3 minutes after the addition of TEOS, or 10 minutes after the addition of TEOS, and the particles obtained by the reaction were observed under an electron microscope. Histograms of the particle size distribution measured from the obtained electron microscope images are shown in Figures 5(A) to 5(C), respectively.

[0140] Figure 5 confirms that the number of remaining uncoated core particles was lowest when the electrolyte was added 3 minutes after the addition of TEOS. Furthermore, in comparison with Figure 3, it can be seen that there is a correlation between the Debye length and the number of uncoated core particles. In other words, it is presumed that adding an electrolyte when the Debye length is short can reduce the amount of electrolyte used, thereby promoting the precipitation of silica species onto the core particles.

[0141] [Reference Example 2: Study of electrolyte type] Volume average particle size (d ｖ ) 460 nm spherical non-porous silica particles (manufactured by Sakai Chemical Industry Co., Ltd., C ｖ =5.0%, ρ=1.9g / cm ３ , S ｍ ≦50m ２ 0.390 g of HCl (0.390 g / g), 16.2 mL of ethanol, and 31.4 mL of water were mixed and ultrasonicated for 30 minutes to disperse nonporous silica particles in the solvent. 0.364 g of CTAB was added to the resulting dispersion and ultrasonicated for 30 minutes. 0.375 mL of 25% by mass aqueous ammonia was then added and ultrasonicated for 30 minutes to prepare an aqueous suspension containing 0.40 vol% nonporous silica particles. 1.12 mL (5.0 mmol) of TEOS was added to this aqueous suspension, and an aqueous electrolyte solution was added 3 minutes after the addition of TEOS. The reaction was allowed to proceed for 18 hours from the addition of TEOS to obtain particles. The aqueous electrolyte solution was prepared by mixing 0.20 mmol of electrolyte with 1 mL of water to achieve an electrolyte concentration of approximately 4.0 mM in the reaction system. The electrolytes used are listed in Table 4. The resulting particles were also observed using STEM. The STEM images are shown in Figures 6(A) to 6(F).

[0142]

[0143] 6, it was confirmed that when potassium bromide was used as the electrolyte, many uncoated core particles remained and core-shell silica particles having an extremely thin shell precursor were produced. In addition, when potassium bromide was used as the electrolyte, the particle size dispersity (C ｖ) was 21%, and polydisperse particles were produced. From this, it is thought that when potassium bromide is used as the electrolyte, the silica aggregation rate is high, and silica species aggregate with each other before diffusing to the core particle surface, making it easier to produce secondary silica particles as a by-product.

[0144] 6, it was confirmed that when sodium chloride was used as the electrolyte, many uncoated core particles remained and the thickness of the shell precursor was smaller than when potassium chloride was used as the electrolyte. On the other hand, when cesium chloride was used as the electrolyte, it was confirmed that few uncoated core particles remained and the shell thickness was similar to that of potassium chloride.

[0145] Here, Na ＋ , K. ＋ , and Cs ＋ When arranged in the Hofmeister series (a permutation of ions in order of their ability to structure water), Na ＋ >K ＋ >Cs ＋ In other words, the ability to structurize water increases in the order of sodium chloride > potassium chloride > cesium chloride. Therefore, sodium chloride has a low effect of destroying the hydration structure on the particle surface, and it is thought that silica species are difficult to precipitate on the core particles, which is why many uncoated core particles remain. － and Br － When arranged in the Hofmeister series, Cl － >Br － Therefore, it is thought that if an electrolyte with a low ability to disrupt the hydration structure (e.g., sodium chloride) is used, a large number of uncoated core particles will likely remain, while if an electrolyte with a high ability to disrupt the hydration structure (e.g., potassium bromide) is used, secondary silica particles will likely be produced as a by-product. From the above, it is presumed that by selecting potassium chloride and cesium chloride as the electrolyte, it is possible to disrupt the hydration structure on the particle surface and promote the aggregation of silica species onto the core particles, while suppressing the by-production of secondary silica particles due to the aggregation of only the silica species, i.e., it is possible to suppress the remaining uncoated core particles and suppress the by-production of secondary silica particles.

[0146] As shown in Figure 6, when calcium chloride was used as the electrolyte, a large number of secondary silica particles were observed. This is presumably because the divalent cation electrolyte increases the ionic strength in the system, causing aggregation of silica species before they precipitate on the core particles, resulting in the by-production of secondary silica particles. Therefore, it is presumed that selecting a monovalent-monovalent electrolyte is preferable in order to suppress the by-production of secondary silica particles.

[0147] 6, it was confirmed that when tetramethylammonium chloride was used as the electrolyte, many uncoated core particles remained. Furthermore, when potassium bromide was used as the electrolyte, the particle size dispersity (C ｖ ) was 30%, and polydisperse particles were produced. This is thought to be because the steric hindrance of the electrolyte species had a greater effect of inhibiting the deposition of silica species onto the core particles than the reduction in electrostatic repulsion due to the short Debye length. Therefore, in order to suppress the remaining uncoated core particles and obtain highly monodisperse core-shell porous silica particles, it is presumed that it is preferable to select an electrolyte with small steric hindrance, such as a metal halide.

[0148] [Reference Examples 3-1 and 3-2: Study of Electrolyte Concentration] ｖ ) 460 nm spherical non-porous silica particles (manufactured by Sakai Chemical Industry Co., Ltd., C ｖ =5.0%, ρ=1.9g / cm ３ , S ｍ ≦50m ２ 0.390 g of PEG-100 (1 / g), 16.2 mL of ethanol, and 31.4 mL of water were mixed and ultrasonicated for 30 minutes to disperse nonporous silica particles in the solvent. 0.364 g of CTAB was added to the resulting dispersion and ultrasonicated for 30 minutes, followed by 0.375 mL of 25% by mass aqueous ammonia and ultrasonicated for 30 minutes to prepare an aqueous suspension of 0.40 vol% nonporous silica particles. 1.12 mL (5 mmol) of TEOS was added to this aqueous suspension, and simultaneously with the addition of TEOS, an aqueous potassium chloride solution was added 3 minutes after the addition of TEOS, and the reaction was continued for 18 hours from the addition of TEOS to obtain particles.

[0149] In Reference Example 3-1, the potassium chloride aqueous solution was prepared by mixing 0.20 mmol (0.0149 g) of potassium chloride with 1 mL of water so that the potassium chloride concentration in the reaction system was about 4.0 mM. In Reference Example 3-2, the potassium chloride aqueous solution was prepared by mixing 0.30 mmol (0.0224 g) of potassium chloride with 1 mL of water so that the potassium chloride concentration in the reaction system was about 6.0 mM.

[0150] The obtained particles were observed by STEM. The STEM images are shown in Figures 7(A) and 7(B). The average shell thickness (T ｓ The average thickness of the shell precursor was measured by the same method as in Example 1.

[0151]

[0152] As can be seen from Figure 7, when the electrolyte concentration in the reaction system was about 6.0 mM (Reference Example 3-2), not only were uncoated core particles and silica secondary particles observed in greater numbers than when the electrolyte concentration was about 4.0 mM, but also aggregates of core particles. From these results, it can be seen that an electrolyte concentration of about 4.0 mM is preferable from the viewpoint of increasing the ionic strength of the reaction system to a level that does not promote the by-production of silica secondary particles and suppressing the aggregation of core particles. On the other hand, Figure 7 and Table 5 show that a thick shell can be achieved even when the electrolyte concentration is about 6.0 mM.

[0153] Reference Example 4: Study on the conditions for continuous addition of silica source-containing liquid The start timing and rate of continuous addition of TEOS to a reaction system have a significant effect on the increase or decrease in the silicate ion concentration in the reaction system. Therefore, after the start of the reaction by adding TEOS, TEOS was continuously added to the reaction system during the time period when the silicate ion concentration reached its maximum (150 seconds after the addition of TEOS) at a flow rate of 0.53 mL / min at which the silicate ion concentration maintained its maximum value, twice that flow rate of 1.06 mL / min, and half that flow rate of 0.27 mL / min, to study the effect of the addition rate of TEOS to the reaction system on the formation of a shell precursor (Reference Example 3-1).

[0154] Separately, after the start of the reaction, when the silicate ion concentration had sufficiently decreased (20 minutes after the start of the reaction), TEOS was continuously added to the reaction system at a flow rate of 0.080 mL / min to examine the effect of the start timing of the continuous TEOS addition on the formation of the shell precursor (Reference Example 4-2).

[0155] Reference Example 4-1: Study on the rate of addition of silica source-containing liquid to reaction system ｖ ) 460 nm spherical non-porous silica particles (manufactured by Sakai Chemical Industry Co., Ltd., C ｖ =5.0%, ρ=1.9g / cm ３ , S ｍ ≦50m ２ 0.390 g of HCl (16.2 mL / g), 16.2 mL of ethanol, and 31.4 mL of water were mixed and ultrasonicated for 30 minutes to disperse the nonporous silica particles in the solvent. 0.364 g of CTAB was added to the resulting dispersion and ultrasonicated for 30 minutes, followed by 0.375 mL of 25% by mass aqueous ammonia and ultrasonicated for 30 minutes to prepare an aqueous suspension of 0.40 vol% nonporous silica particles. 1.12 mL (5.0 mmol) of TEOS was added to this aqueous suspension, and 150 seconds later, an aqueous potassium chloride solution was added to the reaction system and the reaction was carried out. The aqueous potassium chloride solution was prepared by mixing 0.20 mmol (0.0149 g) of potassium chloride with 1 mL of water so that the potassium chloride concentration in the reaction system was approximately 4.0 mM.

[0156] Thirty minutes after the addition of TEOS, 0.56 mL (2.5 mmol) of TEOS was continuously added to the reaction system. The flow rate during the continuous addition of TEOS was 1.06 mL / min, 0.53 mL / min, or 0.27 mL / min. The reaction was then terminated 18 hours after the addition of TEOS.

[0157] Graphs showing the TEOS concentration, silicate ion concentration, and silica solubility in the reaction system, and STEM images of the generated particles are shown in Figures 8 to 10. In this disclosure, the silica solubility was determined based on the value described in R.K.I.ler, The Chemistry of Silica, Wiley-Interscience (1982) and a value based on predicted data obtained by drawing an approximation curve thereto.

[0158] As shown in Figure 8, when the flow rate during continuous TEOS addition was 1.06 mL / min, core-shell silica particles with small shell thickness were produced, and it was confirmed that many uncoated core particles remained. This is thought to be due to the increase in silicate ion concentration prior to the formation of the shell precursor, which resulted in secondary silica particles being produced as a by-product, and the produced silica species not being able to precipitate sufficiently on the core particles. Furthermore, as shown in Figures 9 and 10, when the flow rate during continuous TEOS addition was slowed, the monodispersity of the produced core-shell silica particles tended to decrease.

[0159] From the above, it is considered that conditions under which the silicate ion concentration in the reaction system is higher than the solubility of silica are not appropriate for producing core-shell porous silica particles with a large shell thickness. In other words, it is presumed that, in order to produce core-shell porous silica particles with a large shell thickness, it is desirable to maintain the silicate ion concentration in the reaction system lower than the solubility of silica.

[0160] Reference Example 4-2: Consideration of the start timing of continuous addition of silica source-containing liquid to the reaction system Particles were obtained in the same manner as in Reference Example 4-1, except that the continuous addition of TEOS to the reaction system was started 20 minutes after the addition of TEOS, and the flow rate during continuous addition of TEOS to the reaction system was changed to 0.080 mL / min.

[0161] FIG. 11 shows a graph showing the TEOS concentration, silicate ion concentration and silica solubility in the reaction system, and an STEM image of the produced particles.

[0162] From FIG. 11 , it was confirmed that when TEOS is continuously added to the reaction system as described above, the silicate ion concentration in the reaction system is maintained at a state slightly lower than the solubility of silica, particles with a thick shell precursor are produced, particles with high monodispersity are produced, and the production of secondary silica particles is suppressed.

[0163] From the above investigations, the following 1) to 3) have been derived as preferable conditions for producing core-shell porous silica particles with a large shell thickness: 1) An electrolyte is added to the reaction system near the point at which the Debye length of the particles in the reaction system is minimized. 2) A monovalent-monovalent electrolyte (more preferably an alkali metal chloride, even more preferably KCl and / or CsCl) capable of moderately disrupting the hydration structure is used as the electrolyte. 3) After the silicate ion concentration, which rises sharply immediately after the start of the reaction, has sufficiently decreased, a silica source-containing liquid is slowly and continuously added, thereby maintaining the silicate ion concentration in the reaction system lower than the solubility of silica.

[0164] Hereinafter, core-shell porous silica particles were produced under the above conditions.

[0165] [Example 1] (Reaction initiation step) Volume average particle size (d ｖ ) 460 nm spherical non-porous silica particles (manufactured by Sakai Chemical Industry Co., Ltd., C ｖ =5.0%, ρ=1.9g / cm ３ , S ｍ ≦50m ２ 0.390 g of HCl (16.2 mL / g), 16.2 mL of ethanol, and 31.4 mL of water were mixed and ultrasonicated for 30 minutes to disperse the nonporous silica particles in the solvent. 0.364 g of CTAB was added to the resulting dispersion and ultrasonicated for 30 minutes, followed by 0.375 mL of 25% by mass aqueous ammonia and ultrasonicated for 30 minutes to prepare an aqueous suspension of 0.40 vol% nonporous silica particles. 1.12 mL (5 mmol) of TEOS was added to this aqueous suspension, and after 3 minutes, an aqueous potassium chloride solution was added to the reaction system and the reaction was carried out. The aqueous potassium chloride solution was prepared by mixing 0.20 mmol (0.0149 g) of potassium chloride with 1 mL of water so that the potassium chloride concentration in the reaction system was approximately 4.0 mM.

[0166] (First Silica Source Continuous Addition Step) 0.364 g of CTAB, 1.67 mL of ethanol, and 3.33 mL of water were mixed to prepare a CTAB solution. 30 minutes after the addition of TEOS, the CTAB solution was added to the reaction system, and 0.56 mL (2.5 mmol) of TEOS was continuously added at a flow rate of 0.080 mL / min to carry out the reaction.

[0167] (Second Silica Source Continuous Addition Step) Thirty minutes after the start of the previous CTAB addition and the continuous addition of TEOS, the CTAB solution prepared in the first silica source continuous addition step was added to the reaction system, and a reaction was carried out while continuously adding 0.56 mL (2.5 mmol) of TEOS at a flow rate of 0.080 mL / min.

[0168] (Shell Porosity Forming Step) 18 hours after the addition of TEOS in the reaction initiation step, the produced particles were centrifuged. The separated particles were washed three times with ultrapure water, vacuum dried overnight at 60°C, and then calcined in air at 550°C for 4 hours to obtain core-shell porous silica particles. The obtained core-shell porous silica particles were subjected to various evaluations. The results are shown in Table 6.

[0169] [Example 2] Core-shell type porous silica particles were obtained in the same manner as in Example 1, except that after the second silica source continuous addition step, the third silica source continuous addition step was carried out in the same manner as in the second silica source continuous addition step. The obtained core-shell type porous silica particles were subjected to various evaluations. The results are shown in Table 6.

[0170] [Example 3] Core-shell porous silica particles were obtained in the same manner as in Example 1, except that after the second silica source continuous addition step, the third and fourth silica source continuous addition steps were carried out in the same manner as the second silica source continuous addition step. The obtained core-shell porous silica particles were subjected to various evaluations. The results are shown in Table 6.

[0171] Example 4 Volume average particle size (d ｖ Instead of spherical non-porous silica particles with a volume average particle diameter (d ｖ ) was spherical non-porous silica particles (manufactured by Sakai Chemical Industry Co., Ltd., Cｖ =6.7%, ρ=1.9g / cm ３ , S ｍ ≦50m ２ Core-shell porous silica particles were obtained in the same manner as in Example 1, except that a 100% aqueous solution of 100% cellulose acetate (C100 / g) was used and the volume fraction of the non-porous silica particles in the aqueous suspension was changed to 0.60 vol %. The obtained core-shell porous silica particles were subjected to various evaluations. The results are shown in Table 6.

[0172] Comparative Example 1 Core-shell type porous silica particles were obtained in the same manner as in Example 1, except that the first and second silica source continuous addition steps were not performed. The obtained core-shell type porous silica particles were subjected to various evaluations. The results are shown in Table 6.

[0173] [Comparative Example 2] Core-shell type porous silica particles were obtained in the same manner as in Example 1, except that CTAB was not added in the first and second silica source continuous addition steps. The obtained core-shell type porous silica particles were subjected to various evaluations. The results are shown in Table 6.

[0174] [Comparative Example 3] Volume average particle size (d ｖ Instead of spherical non-porous silica particles with a volume average particle diameter (d ｖ ) was a 1200 nm spherical non-porous silica particle (manufactured by Sakai Chemical Industry Co., Ltd., C ｖ =3.6%, ρ=1.9g / cm ３ , S ｍ ≦50m ２ Core-shell porous silica particles were obtained in the same manner as in Comparative Example 1, except that a 100% aqueous suspension of 1.03 vol% non-porous silica particles was used and the volume fraction of the non-porous silica particles in the aqueous suspension was changed to 1.03 vol%. The obtained core-shell porous silica particles were subjected to various evaluations. The results are shown in Table 6.

[0175] [Evaluation Method] STEM Image of Particles The morphology of the generated particles was observed using a scanning transmission electron microscope ("HD-2700" manufactured by Hitachi High-Technologies Corporation). A suspension of the particles before firing was dropped onto a Cu grid with a support film ("Cu200-A Mesh" manufactured by JEOL Ltd.), and the grid was allowed to air dry to prepare a sample for STEM observation.

[0176] Volume average particle size (d ｖ ), standard deviation (σ), and particle size dispersity (C ｖ The particle size was measured from the STEM image of the generated particles using image analysis software ("Image J" manufactured by Wayne Rasband). The volume average particle size (d ｖ The particle size of about 200 particles per sample was measured, and the volume average particle size (d ｖ ), the standard deviation (σ) from equation (3), and the particle size dispersity (C ｖ ) was calculated. ｉ represents the particle size, and d Ｎ represents the number average particle size, and n ｉ represents the number of particles.

[0177]

[0178]

[0179]

[0180] Average shell thickness (T ｓ ) The average shell thickness (T ｓ ) was calculated.

[0181]

[0182] In the formula, d ｖ，Ｃ－ＭＳＰｓ represents the volume average particle size of the particles produced, and d ｖ，ｃｏｒｅ represents the volume average particle diameter of the core particles.

[0183] Nitrogen adsorption / desorption isotherm, BET specific surface area, peak pore diameter (D ｐ ), pore size distribution, and pore volume (V ｐ) Nitrogen adsorption / desorption measurements of the generated particles were performed using an automatic specific surface area / pore distribution measurement device ("BELSORP-mini II" manufactured by Microtrac-Bell Corporation) to obtain nitrogen adsorption / desorption isotherms. At this time, a standard Pyrex test tube was used as the test tube, and the measurements were performed after pretreatment at 300°C for 3 hours under reduced pressure. The BET specific surface area was determined by BET analysis of the nitrogen adsorption / desorption isotherm using analysis software ("BEL Master" manufactured by Microtrac-Bell Corporation). In addition, the peak pore diameter (D ｐ ) and pore size distribution were determined. ｐ ) is the ratio of vapor pressure to saturated vapor pressure (p / p ０ The nitrogen adsorption amount was calculated by converting the amount of nitrogen adsorbed when the σ was 0.99.

[0184] In measuring the nitrogen adsorption / desorption isotherm, a Pyrex standard sample tube was used as the sample tube, and BELPREP-vac II was used for pretreatment. The measurement sample was particles calcined at 550°C, and the measurement was started after pretreatment at 300°C for 3 hours under vacuum.

[0185] Shell Volume The shell volume of the produced particles is calculated by assuming the produced particles to be spherical and subtracting the geometrically determined volume of the non-porous silica particles from the geometrically determined volume of the produced particles.

[0186]

[0187] As shown in Table 6, the core-shell porous silica particles obtained in Example 4 had a particle size dispersity (C ｖ ) is the particle size dispersity of the core particles (C ｖ ) This shows that highly monodisperse particles can be obtained by this production method.

[0188] Table 6 confirms that in Comparative Example 2, in which CTAB was not added during the continuous addition of TEOS, the shell volume per core-shell porous silica particle was smaller than those in Examples 1 to 3. This suggests that CTAB added together with TEOS was used as a template for pores.

[0189] 13, the nitrogen adsorption / desorption isotherms of the core-shell porous silica particles obtained in Examples 1 to 3 exhibited type IV without hysteresis, indicating that cylindrical mesopores were formed in the shell. Furthermore, Table 6 indicates that the pore volume of the core-shell porous silica particles tends to decrease as the shell thickness increases.

[0190] FIG. 15 is a graph plotting the shell volume per core-shell porous silica particle versus the total amount of TEOS used in Examples 1 to 3 and Comparative Examples 1 and 2.

[0191] 15, it can be seen that the shell volume per core-shell porous silica particle is proportional to the total amount of TEOS used in Examples 1 to 3, in which the ratio of the total amount of CTAB used to the total amount of TEOS used was constant. From this, it can be considered that the proportions of uncoated cores and secondary silica particles present are roughly constant in Examples 1 to 3.

[0192] 15 and Table 6, it was confirmed that the shell did not become thick in Comparative Example 1, in which TEOS was not continuously added to the reaction system. Furthermore, when Example 3, in which TEOS was continuously added to the reaction system and CTAB was added, was compared with Comparative Example 2, in which CTAB was not added, it was confirmed that core-shell porous silica particles with a thicker shell were obtained in Example 3, even though the total amount of TEOS used was the same. This shows that the shell thickness can be increased by continuously adding TEOS to the reaction system while replenishing CTAB consumed as a template, and by maintaining a constant amount of CTAB added relative to the amount of TEOS added.

[0193] Fig. 16 is a graph plotting the pore surface area per particle against the shell volume per particle for the core-shell porous silica particles obtained in Examples 1 to 4 and Comparative Examples 1 and 3. The pore surface area per particle was calculated from the BET specific surface area of ​​the particle.

[0194] 16, the pore surface area shows a strong positive correlation, which suggests that the pores are connected without being blocked. In other words, it can be seen from Fig. 16 that the shell thickness can be increased without reducing the porosity according to this production method.

Claims

1. A method for producing core-shell porous silica particles, comprising: preparing core-shell silica particles having a core and a shell precursor by the following steps a1) and a2), and rendering the shell precursor porous by the following step b). a1) a first reaction initiation step of adding a silica source-containing liquid containing a silica source to a first aqueous suspension containing nonporous silica particles, a cationic surfactant, a basic catalyst, an electrolyte, and an alcohol, or a second reaction initiation step of adding a silica source-containing liquid containing a silica source and an electrolyte to a second aqueous suspension containing nonporous silica particles, a cationic surfactant, a basic catalyst, and an alcohol. a2) a first silica source continuous addition step of adding a cationic surfactant and continuously adding a silica source-containing liquid containing a silica source to the reaction system after the first reaction initiation step or the second reaction initiation step, and b) a shell porosity formation step of removing the cationic surfactant from the shell precursor.

2. The method for producing core-shell porous silica particles according to claim 1, wherein step a2) is carried out under conditions in which the silicate ion concentration is lower than the solubility of silica in the reaction system.

3. The method for producing core-shell porous silica particles according to claim 1, wherein the core-shell silica particles are produced by further performing the following a3) once or a plurality of times after the a2): a3) an n-th silica source continuous addition step (n represents an integer of 2 or more) of adding a cationic surfactant and continuously adding a silica source-containing liquid containing a silica source to the reaction system after the (n-1)-th silica source continuous addition step:

4. The method for producing core-shell porous silica particles according to claim 3, wherein step a3) is carried out under conditions in which the silicate ion concentration is lower than the solubility of silica in the reaction system.

5. The method for producing core-shell porous silica particles described in claim 1, wherein the addition of the electrolyte to the second aqueous suspension in the second reaction initiation step is carried out within a period from 2 minutes before to 5 minutes after the point at which the Debye length of the reaction system reaches its minimum value.

6. The method for producing core-shell porous silica particles according to claim 1, wherein the addition of the electrolyte to the second aqueous suspension in the second reaction initiation step is carried out within a time period that satisfies the following condition I): Condition I) the Debye length of the reaction system is equal to or greater than the minimum value in the change in Debye length over time, and is equal to or less than the value obtained by multiplying the minimum value by X (X is greater than 1.00 and equal to or less than 1.10).

7. The method for producing core-shell porous silica particles according to claim 1, wherein the addition of the electrolyte to the second aqueous suspension in the second reaction initiation step is carried out within a time period that satisfies the following condition II): Condition II) the reciprocal of the hydrolysis rate constant of the silica source under the reaction conditions is 0.1 or more and 1.0 or less.

8. The method for producing core-shell porous silica particles according to claim 1, wherein the basic catalyst is ammonia.

9. The method for producing core-shell porous silica particles according to claim 1, wherein the alcohol is an alkyl alcohol.

10. The method for producing core-shell porous silica particles according to claim 1, wherein the silica source is an alkoxysilane.

11. The method for producing core-shell porous silica particles according to claim 1, wherein the electrolyte is one or both of potassium chloride and cesium chloride.

12. The method for producing core-shell porous silica particles according to claim 1, wherein the cationic surfactant is a tetraalkylammonium halide.

Images