Porous silica particle

Abstract

To provide an improved porous silica material having a desirable combination of a large median pore diameter or mean pore diameter, a pore volume, and a narrow pore size distribution that contributes to improving separation efficiency while maintaining high performance efficiency and high mechanical strength.SOLUTION: This invention relates to a porous silica having a median pore diameter of 210Å-500Å and a pore volume of 0.80 cm3 g-1-1.2 cm3 g-1. This invention also relates to a method for producing porous silica by gelating liquid-phase dispersed nanoparticulate silica in the presence of (i) a Bronsted acid and an amine compound having two or more primary or secondary amine groups, or (ii) an amino acid. This invention further relates to the use of a porous silica as a stationary phase for separation and to a separation column or a container containing the porous silica.SELECTED DRAWING: Figure 2

Description

[Technical Field]

[0001] The present invention relates to materials comprising porous silica particles and methods for producing them. can be used in many applications either as is or after surface modification, especially in It can be used as a stationary phase in chromatography separation techniques. [Background technology]

[0002] Silica-based materials are used in many applications, e.g., as stationary phases in chromatography. They are commonly used as catalysts or catalyst supports, or as ion exchange materials. Applications include, for example, particle purity, alkali metal content, pore characteristics, and mechanical strength. There are different requirements.

[0003] The advantage of silica is that it can be modified, for example, by changing the pore characteristics or by chemically modifying the surface. The advantage of this is that its properties can be adjusted greatly by modifying it. For example, this versatility allows for many different types of separations. This can be very useful in separation applications.

[0004] A common route to prepare porous silica materials suitable for separation techniques is via, for example, sol-gel synthesis. Silica precursors, such as nanoparticulate or colloidal silica, are used in the synthesis of silica. The gel is formed under controlled conditions. Such a technique is described in EP 0298062. This is typically a porous silica having an average pore diameter of up to 100 Å. Such silica has relatively small molecular weights, for example, 10,000 or less. However, it can be used to separate molecules with a fairly large molecular weight. For the separation of larger molecules such as proteins, larger pores, typically 200 Pores greater than Å, often on the order of 300 Å, are preferred.

[0005] Such large pore materials are typically silica precursor materials (e.g., pores on the order of 100 Å). It can be made by Ostwald ripening of granular materials (those with pore sizes), which sometimes such processes, e.g. as a separation medium for small molecules or as a catalyst support In addition, silica, which has value in itself, is often consumed as a To achieve the final large pore product, silica starting materials must be prepared. It may take a lot of effort and time.

[0006] Another technique for producing large pore silica is described in U.S. Pat. No. 3,855,172. and U.S. Pat. No. 4,874,518. However, the prior art A further problem with these materials is that the large pore sizes often result in a relatively wide pore size distribution. The fabric is attached and can have a negative effect on the mechanical strength. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] European Patent No. 0298062

[0008] [Patent Document 2] U.S. Patent No. 3,855,172 [Patent Document 3] U.S. Patent No. 4,874,518 Summary of the Invention [Problem to be solved by the invention]

[0009] The present invention provides a large median range within which high performance efficiency and also high mechanical strength are ensured. It helps to further improve the pore diameter or average pore diameter, pore volume, and also separation efficiency. The present invention provides improved porous silica materials having a desirable combination of high molecular weight and narrow pore size distribution. The present invention also provides a method for preparing such a material as a stationary phase for separation. The present invention is further directed to methods for making such materials. . [Means for solving the problem]

[0010] In one embodiment, the present invention provides a porous membrane having a median pore diameter of 210 Å to 500 Å and a median pore size of 0.80 cm 3 g -1 ~1.2cm 3 g -1 The present invention relates to a porous silica having a pore volume of

[0011] In another aspect, the present invention provides a method for preparing a Brønsted acid-containing polymer comprising: (i) a Brønsted acid and two or more primary or secondary in the presence of either (i) an amine compound having a primary amine group, or (ii) an amino acid, in a liquid phase. The present invention relates to a method for producing porous silica by gelling dispersed nanoparticulate silica.

[0012] In a further aspect, the present invention relates to the use of porous silica as a stationary phase for separations. do.

[0013] In yet another aspect, the present invention relates to a separation column or vessel containing porous silica. do. [Brief explanation of the drawings]

[0014] [Figure 1]1 is an exemplary plot of cumulative pore volume versus pore diameter for a porous material, highlighting how to interpret the D10, D50, and D90 values. [Figure 2] 1 is a BJH desorption dV / dD pore volume plot of an inventive material and a comparative material. Both curves are normalized to 1. DETAILED DESCRIPTION OF THE INVENTION

[0015] [Porous silica] The porous silica typically contains up to 10% by weight of other oxide components. %, up to 5 wt. % of other oxide constituents are present. The other oxide constituents may be other refractory oxides, e.g. For example, aluminum, titanium, iron, chromium, zinc, zirconium, magnesium, calcium The oxides may be oxides of cerium and cerium.

[0016] The alkali and alkaline earth contents are also typically low, e.g., less than 1% by weight combined. and in a further embodiment less than 0.1 wt %, for example less than 100 ppm.

[0017] In an embodiment, silica is present in an amount of 0.1% by weight or less, for example 100 ppm or less, of any other Contains oxides or alkali / alkaline earth metal impurities.

[0018] The exception to the above levels of other oxides is the surface of the porous silica or the porous silica itself. The surface of the nanoparticulate silica used to prepare it is intentionally modified or doped. This is described in more detail below, but in embodiments, up to 10 wt. % aluminium oxide, for example up to 5% by weight aluminium oxide may be present.

[0019] Porous silica is 0.80 to 1.2 cm 3 g -1The pore volume is in the range of In this state, the pore volume is 0.81 to 1.2 cm 3 g -1 Within the range of 0.81~1.0cm 3 g -1 For example, within the range.

[0020] In an embodiment, the average pore diameter of the porous silica is in the range of 100 to 500 Å, for example 2 00 to 450 Å, 220 to 400 or 220 to 350 Å, etc.

[0021] Porous silica is 50 to 500 m 2 g -1 , for example, 80 to 300 m 2 g -1 Within the range of In embodiments, the specific surface area is between 90 and 200 m 2 g -1 ,Ma or 95-150m 2 g -1 , for example 95-135m 2 g -1 is within the range.

[0022] Porous silica has a median pore diameter of 210 to 500 Å or 250 to 450 Å. In embodiments, the silica has a mean / median pore diameter in the range of 300 to 400 Å. It has.

[0023] The median pore diameter may optionally be referred to as the "D50" pore diameter. Pores with diameters less than or equal to the D50) pore diameter contain 50% of the total pore volume of the material. Similarly, the "D10" or "D90" pore diameters are those that are 10% or 9% of the pore volume, respectively. Therefore, the diameter of the fine particles with a diameter of less than the D10 or D90 diameter is The pores contain 10% or 90% of the total pore volume, respectively. The D90 and D90 scores are shown in Figure 1.

[0024] Pore ​​size distribution is a measure of the spread of pore sizes in a material. It is expressed as D90 / This can be conveniently expressed by the D10 ratio, where a smaller number indicates a narrower range of pore sizes. This suggests a problem.

[0025] In an embodiment, the D90 / D10 ratio is 2.30 or less. The D90 / D10 ratio is in the range of 0.01 to 2.30. The / D10 ratio is in the range of 0.10 to 2.30 or 1.00 to 2.30. In another embodiment, the D90 / D10 ratio is in the range of 1.50 to 2.30. In this form, the upper limit for the D90 / D10 value is 2.25.

[0026] Preferred Methods for Measuring Pore Size Distribution, and D10, D50, and D90 Pore Diameters The Barrett-Joyner-H method, based on nitrogen adsorption / desorption, is particularly useful from desorption isotherms. The surface area, pore volume, and (surface area and The preferred method for measuring average pore diameter (from pore volume) is also based on nitrogen adsorption / desorption. This is based on the Brunauer-Emmett-Teller (BET) method, and the surface area is typically calculated from the linear part of the isotherm. An example of such a method is 277:2010 (for BET), and ISO 15901-2:2006 (for gas (for adsorption / desorption)

[0027] The combination of pore volume, pore diameter, and narrow pore size distribution allows porous silica to This means that it is highly effective as a stationary phase in the separation of large molecules (e.g., proteins). This is because the pore size is large enough to allow such large molecules to enter and exit the pores. This is because good mass transfer is possible and efficient absorption is possible. A sufficiently large pore volume combined with a large surface area and narrow pore size distribution allows for highly This results in a defined pore structure, which also helps ensure high separation efficiency. Ensuring that the volume is not too large ensures the mechanical strength and integrity of the porous silica. maintains its integrity and thus avoids damage to the material, for example when packing separation columns In addition, high separation efficiency can be ensured.

[0028] The porous silica may be provided in solid form, for example as a dry powder. In embodiments, the porous silica can be packed into a separation column, such as an HPLC column. In dry powder form, the particle size (diameter) is in the range of 0.5 to 100 μm, e.g. It can be in the range of 0.7 to 50 μm, 0.8 to 30 μm, or 1 to 25 μm. In this case, these are sieved to give a narrower, more specific range of particle sizes. It is possible.

[0029] [Organosilane-modified silica] In embodiments, the porous silica comprises one or more organic groups, e.g., one or more C1~C 30 an aliphatic group or one or more C 5~10 Aromatic group, or C 5~1 In embodiments, the aryl group may be modified by a heteroaromatic group (hereinafter, "A" group). The aromatic or heteroaromatic group is C 5~6 It is an aromatic or heteroaromatic group.

[0030] In A, the aliphatic organic group is, for example, —OR, —C(O)O - , -C(O)OR, - C(O)NR2, -OC(O)R, -NRC(O)R, -NR-C(O)-NR2, -N R2, -[NR3] + , halide, epoxy, oxo, C 5~6 Aromatic group, C 5~6 Haitai aromatic group, C 5~6 Heterocyclic aliphatic groups, and groups of the general formula -[O-(CR a 2) n ] m - OR b and optionally substituted with one or more groups selected from the glycol ether groups may be replaced.

[0031] In A, the aromatic organic group is, for example, —OR, —C(O)O - , -C(O)OR, - C(O)NR2, -OC(O)R, -NRC(O)R, -NR-C(O)-NR2, -N R2, -[NR3] + , halide, epoxy, oxo, C 1~30 aliphatic group, C 5~6 F Heterocyclic aliphatic groups, and groups of the general formula -[O-(CR a 2) n ] m -OR b Glycol A The alkyl group may be optionally substituted with one or more groups selected from aryl groups.

[0032] Each R group is independently hydrogen, C 1~30 aliphatic group, C 5~6 Aromatic group, C 5~6 Hetero Aromatic groups, and C 5~6heterocyclic aliphatic groups, and each R a is hydrogen and C1 ~4 alkyl groups, and each R b The group is hydrogen or C 1~10 is an alkyl group, and n is an integer of 2 to 3, and m is an integer of 2 to 20.

[0033] Any aliphatic or alkyl group described herein (alkoxy, amide, amine, and functional groups such as ester groups) may be linear, branched, or cyclic. They may be saturated or unsaturated. Typically, they are saturated. In embodiments, straight chain and branched chain groups are used, and in further embodiments, straight chain groups are used.

[0034] R groups (other than hydrogen) are hydroxyl, epoxy, C 1~4 Alkoxy, carboxyl, one or more selected from halide (e.g., fluorine or chlorine), and —NH may be optionally substituted by a substituent of

[0035] R a and R b Groups (other than hydrogen) include hydroxyl, C 1~4 Alkoxy and Halal and optionally one or more substituents selected from In embodiments, R a The group is not halide substituted. is R a and / or R b The group does not include any optional substituents.

[0036] Any heteroaromatic or heterocyclic aliphatic group described herein may contain, within the ring, O, and one or more heteroatoms selected from S and N, typically O or N In embodiments, there may be no more than three heteroatoms in the ring, for example no more than two, and further embodiments may include: In embodiments, there is only one heteroatom.

[0037] An unsaturated aliphatic group has one or more double bonds and / or one or more It may contain triple bonds. In embodiments, there are no triple bonds.

[0038] Charged groups, e.g. -C(O)O - or -[NR3] + For compounds containing the group, Each of these may also contain a counter cation or counter anion. A cation is a group of atoms that are bonded to a proton ( H + ), alkali metals, alkaline earth metals, formula [NR4] + ammonium ion or The cation may be selected from organoammonium ions, where R is as defined above. The anion is a halide (e.g., F - , Cl - , Br - , and I - ), hydroxide salts, nitric acid Salts, sulfates, chlorates, bromates, iodates, phosphates, tetrafluoroborates, fluorophosphate, formula R c SO3 - and sulfonates of formula R c R2PO3 - of phosphonates, wherein each R is as defined above and each R c is C1 ~30 aliphatic group, C 5~6 Aromatic groups, and C 5~6 heteroaromatic groups, which may be optionally substituted as described above for the R group.

[0039] The modification of silica can be achieved by mixing the silica with a suitable organic compound, e.g., an organosiloxane containing the required group. This can be achieved by reacting with silanes, which can be achieved by known procedures, e.g. , using the procedure described in International Publication No. WO2007 / 070001. , can be achieved. Organosilanes have the formula Si[Z] 4-y [A] y Represented by Each Z is typically selected from halide, hydroxyl, and lower alkoxy groups. , e.g., C 1~6 Alkoxy group, or C 1~4 alkoxy groups. In some embodiments, Z is selected from hydroxyl and lower alkoxy groups.

[0040] Each A is optionally substituted C as defined above. 1~30 aliphatic group, C 5~10 aromatic group, or C 5~10 It is a heteroaromatic group. y is an integer ranging from 1 to 3. If y is greater than 1, each A may be the same or different. If y is less than 3, each Z may be the same or different, but in embodiments, all Z groups are the same. Compounds such as these can be purchased commercially or prepared by known techniques, e.g., Ullmann's s Encyclopadie der Technischen Chemie in the section "Silicium-Verbindungen, Org anische", and the Kirk-Othmer Encyclopedia of Chemical Technology, in the sect They can be prepared by the techniques described in the book "Silicon Compounds (Silanes)." Cut.

[0041] When organosilanes are used to modify silica, one or more surface silanols may be added. The reaction with the alkyl group forms one or more Si-O-Si linkages with the silica surface. For convenience, this linkage is referred to as [SiO2]-Si-[A] y It may be expressed by:

[0042] In other embodiments, they are halohydrins based on the formula HO-CR(CR2X)A. The compound can be modified with an amine compound, wherein R and A are each as defined above. and X is a halogen, typically chlorine or bromine, preferably chlorine. They have used known techniques, for example, those described in International Publication No. WO2014 / 206893. The R is H or methyl. Halohydrin compounds can be purchased commercially and For example, see International Publication No. WO2013 / 092778, Ullmann's Encyclopedia adie der Technischen Chemie, in the section on "Epoxidverbindungen", and also t he Kirk-Othmer Encyclopedia of Chemical Technology, in the section on "Chlorohyd" These can be prepared using known procedures, as described in "rins".

[0043] When reacted with the silica surface (e.g., by stirring the compound with silica at high temperature), Thus, the hydroxyl groups react with the surface silanol groups of the silica. It is sometimes expressed as [SiO2]-O-CR(CR2X)A.

[0044] When silica is modified with two or more different organic groups, this is done by using different modifying reactants. (For example, two different Si[Z] 4-y [A] y reactants, or two different HO- This can be achieved by using either C(CR2X)A reactants) wherein each reactant has a different A group. In other embodiments, Si[Z] 4-y [A ] y Reactants can be used where y is at least 2 and two or more different containing the A group].

[0045] In embodiments, the silica may be modified with one or more A groups, the A groups being C respectively. 1~30 alkyl groups, each optionally as described above. In embodiments, the silica may be substituted, but in embodiments, the alkyl groups are unsubstituted. 10~20 Alkyl groups and C 1~4 and alkyl groups, respectively. Although optionally substituted as described above, in embodiments, both alkyl groups are unsubstituted. be.

[0046] Silica can be prepared using known techniques, for example by dissolving one of the above-defined silicas in an aqueous solution at basic pH. Alternatively, silica can be modified by stirring it with multiple organosilane compounds. Such a technique is described, for example, in International Publication No. WO2007 / 070001. FRET and the pamphlet of International Publication No. WO2014 / 206893 do.

[0047] In another embodiment, the starting material is organically modified to produce silica according to the present invention. For example, organosilane compounds can be hydrolyzed to produce organosilane-modified silicas. In other embodiments, for example, WO 2004 / 020944, 4 / 035473 brochure and International Publication No. WO2004 / 035474 Before gelling the colloidal silica starting material, using the procedure described in Fret It can be modified with organosilanes to form silica according to the present invention.

[0048] [Nanoparticulate silica] In producing the large pore silica of the present invention, a source of nanoparticulate silica is used. may be in the form of colloidal silica, as further described below. In this paper, the nanoparticulate silica source is a solid form of silica dispersed or suspended in a liquid phase. In embodiments, the silica nanoparticles (before dispersion or suspension) may be fumed. These types of silica are in the form of silica dioxide, precipitated silica, or silica fume. In this case, the primary particle size is preferably 200 nm or less, for example, in the range of 4 to 200 nm. The primary particles tend to aggregate or agglomerate into larger particles, ranging from 300 nm to 1 The diameter (or effective diameter) may be in the range of 00 μm.

[0049] Crystalline forms of silica, such as quartz, can also be used. However, the crystalline form is not healthy. These are preferably avoided as they can be harmful to the

[0050] [Colloidal silica] In a preferred embodiment of the present invention, the nanoparticulate silica source is 2 to 200 nm A colloid in which primary colloidal silica particles having a diameter within the range are suspended in an aqueous medium. Typically, the level of aggregation of primary particles is low and the silica colloids can be stored for several months. highly stable for a period of time, typically 4 months or more, in embodiments 6 months or more (i.e., it does not gel or coagulate automatically). Colloidal silica is called silica sol. and in this disclosure, the two terms are used interchangeably.

[0051] The degree of gelation or aggregation of colloidal silica can be described by the so-called "S value". In an embodiment, for unmodified colloidal silica, the S value is 10 to 95%, e.g. For example, it is in the range of 20 to 90% or 30 to 90%. The S value is calculated by Iler & Dalton. As described by Iler & Dalton (J. Phys. Chem., 60 (1956), 955-957), A high S value indicates a high degree of dispersion of silica particles with a low level of aggregation. Conversely, a lower S value indicates a higher level of microaggregation.

[0052] When colloidal silicas are used, they generally contain no or little organic solvents. When an organic solvent is present, the aqueous medium is usually 10% by weight or less. % by weight or less of an organic solvent, for example, 5% by weight or less of an organic solvent. The solvent is preferably water-miscible, e.g., C 1~6 Alkyl alcohol, C 1~6 a Rudehyde, C 3~6 Ketone, C 1~6 Carboxylic acids and their C 1~6 Alkyl ester Typically, when an organic solvent is present, it is selected from one or more of the following: is C 1~6 Alcohols are selected from the group consisting of:

[0053] The aqueous colloidal silica has a pH in the range of 8.0 to 12.0, e.g., 8.5 to 11.0. Other components of such a sol may be basic, having an alkali metal Presence of, typically one or more of, lithium, sodium, and potassium; or ammonium or organoammonium ions [NR p 4] + Examples include: In the formula, each R p are independently hydrogen, C 1~30 aliphatic group, C 5~6 Aromatic groups, and C 5~ 6 heteroaromatic groups, which are selected from one or more -OH or C 1~4 Al optionally substituted with a koxy group].

[0054] Suitable aqueous silicates or glass that can be used to prepare aqueous silica sols Examples of silicates include ammonium silicate, lithium silicate, sodium silicate, and silicate. Examples include potassium phosphate.

[0055] Colloidal silica with a neutral or acidic pH can also be used, for example at pH values ​​of 2 to 7. In such embodiments, the silica particles may be, for example, those described in International Publication No. WO00 / 04999. No. 1 / 98227, U.S. Pat. No. 5,368,833, and Iler et al. As described in The Chemistry of Silica, John Wiley and Sons (1979), The surface may be modified with cations such as aluminum ions.

[0056] In embodiments, the colloidal silica may be a soluble silicate (e.g., water glass), or a poly It is made from a silicic acid solution, which is obtained by ion exchange or treatment with acid. The salt is converted to polysilicic acid (typically having a pH in the range of 1 to 3) and treated with an alkali metal or [NR p 4] + Use basic salts such as hydroxides or silicates to maintain a pH of 7 or higher. This can be achieved by increasing the pH to typically 8-12, e.g., 8.5-11. can.

[0057] [NR] in the starting silica sol p 4] + Or the alkali metal content is [NR p 4] and or alkali metal oxides, typically in the range of 0.01 to 5.0 wt.%. In an embodiment, the content is 0.07 to 3.0% by weight.

[0058] The silica concentration in colloidal silica is expressed as SiO2 and is typically between 1 and 60 wt. The amount of colloidal silica is, for example, in the range of 2 to 50% by weight or 3 to 35% by weight. Particles are typically between 50 and 500 m 2 g -1 Within the range of, for example, 75 to 300 m 2 g -1 Within the range of 100-150m 2 g -1 The colloidal silica in the sol has a surface area of The surface area of ​​silica particles was determined by the Sears method (Sears; Anal. Chem., 1956, 28(12), 1981-1983). It can be calculated from NaOH titration according to

[0059] The colloidal silica particles may be sized to 2 to 150 nm, for example, 2 to 100 nm, or 3 to 75 nm. In a further embodiment, the particle diameter may be in the range of 4 to 5 nm. 0 nm.

[0060] The average particle diameter is given in "The Chemistry of Silica" by Iler, K. Ralph, page 465, John Wiley & Sons, 1989. It can be calculated from the titration surface area using the method described by Y & Sons (1979) Silica particles are 2.2gcm -3 has a density of 1000, and all particles are the same size , assuming a spherical shape with smooth planar areas, the mean particle diameter (PD) can be calculated from Equation 1.

[0061]

number

[0062] Another method for measuring the mean particle diameter is ES-DMA (electrospray differential spectroscopy). mobility analysis), CLS (liquid phase centrifugation analysis), SEM (scanning electron microscope), and TEM ( transmission electron microscope).

[0063] The density of a silica sol depends, at least in part, on the silica content, but is typically 1.01~1.30gcm -3 In one embodiment, the range is 1.2 gcm -3 Less than do.

[0064] The viscosity of the colloidal silica is typically less than 40 cP, for example less than 30 cP, especially less than 20 In embodiments, the viscosity is less than 10 cP. These viscosities are The viscosity of silica sols, including those described herein, is measured at 100°C. It can be measured using a rotational viscometer. The method that can be used is ASTM D4 The number is 016-14.

[0065] In aqueous systems, colloidal silica particles are often soluble in alkali metals (e.g., K + , Na + , L i + ), and the formula [NR4] + ammonium ion or amino ion In the presence of a stabilizing cation capable of dispersing the compound, R is as defined above. Typically, these are alkali metal and ammonium (NH4 + ) alkali metal ions are preferred, for example, for high purity chromatographic separation applications. Since this is often undesirable, the preferred embodiment uses ammonium ions.

[0066] Examples of sols that can be used as the starting aqueous silica sol include those from Nouryon Silica gels sold under the names Levasil (trademark) or Bindzil (trademark) Examples of suitable grades include alkali metal-free grades such as those in

[0067] [Amine compounds having two or more amine groups] The nanoparticulate silica has two or more primary or secondary amine groups (i.e., It gels in the presence of an amine compound (having at least one N-H bond). It occurs in the presence of a Rönsted acid.

[0068] In embodiments, the amine compound has a molecular formula according to any one of Formulas 1-3 below: do.

[0069] [ka] ·R d is independently in each occurrence H, as well as halogens (e.g., F, Cl, Br) , -OR e , -COOR e , and -N[R e ]2[In the formula, each R e are independently H and C 1~6 and one or two groups selected from the group consisting of alkyl, Optionally substituted C 1~6 alkyl groups, T, independently in each occurrence, represents one or more C 1~3 Arbitrarily selected by alkyl group C replaced by 1~3 Alkylene units (e.g., C 2~3 alkylene units) R, X, independently in each occurrence, is -O-, -NR d - and

[0070] [ka] is selected from q is independently selected in each occurrence from a non-negative integer in the range of 0 to 7.

[0071] Examples of amine compounds in formulas 1 and 2 that contain two or more amine groups include all The occurrence of T in the formula (I) is a C2 ethylene group, for example, ethylenediamine (EDA ), diethylenetriamine (DETA), triethylenetetramine (TETA), tetra Ethylenepentamine (TEPA), Pentaethylenehexamine (PEHA), Pipera azine (PIP), aminoethylpiperazine (AEP), hydroxyethylethylenediamine Hydroxyethyldiethylenetriamine (HE-EDA), Hydroxyethyldiethylenetriamine (HE-DETA), Hydroxyethyldiethylenetriamine (HE-DETA), Hydroxyethyltriethylenetetramine (HE-TETA), Hydroxyethylpiperazine (HEP), methylethylenediamine (MeEDA, i.e., Me-NH-CH2-C H2-NH2), and tetramethylethylenediamine (TMEDA, i.e., Me2 N-CH2CH2-NMe2).

[0072] As a further example, at least one, and optionally all, occurrences of T may be C3 propyl Examples of the amines include propylenediamine (PDA), dipropylenetriamine ( DPTA), tripropylenetetramine (TPTA), 1,5-diazocane (DAZ), Aminopropyl-1,5-diazocane (AP-DAZ), hydroxypropyl propylene Diamine (HP-PDA), Hydroxypropyldipropylenetriamine (HPDPTA ), hydroxypropyl propylene diamine (HP-PDA), hydroxypropyl dip Hydroxypropyltripropylenetetramine (HP-DPTA), Hydroxypropyltripropylenetetramine (HP-TPTA), and hydroxypropyl-1,5-diazocane (HP-DAZ) And so on.

[0073] As a still further example, at least one, and optionally all, occurrences of T are methylated. Examples of the alkylene group include isopropyldiamine (iPDA) ), and diisoprylamine triamine (DiPTA).

[0074] Yet further examples include groups where the T group is C2 alkylene, methyl-substituted C2 alkylene, and C3 alkylene, for example, aminopropylethylenediamine. Diaminopropyl ethylenediamine (AP-EDA), diaminopropyl ethylenediamine (DAP-EDA), diamino Isopropylethylenediamine (DAiP-EDA), and aminopropylpiperazine (AP-PIP).

[0075] Thus, in embodiments, T is C2 alkylene, monomethyl-substituted C2 alkylene, and and C3 alkylene units. In a further embodiment, p is in the range of 0 to 4. is a non-negative integer, and R d is H, and OH and / or N[R e ]2[wherein, R e is H or C 1~3 C optionally substituted by alkyl 1~3 Alkyl is selected from.

[0076] For compounds where p is 2 or greater, different isomers may exist. TETA, TEPA and PEHA, for example, can exist in linear and different branched forms. L-TETA (linear isomer) H2N-C2H4-NH-C2H4-NH-C2H4-NH2 I-TETA (branched isomer, also known as tris(aminoethyl)amine)

[0077] [ka] L-TEPA (linear isomer) H2N-C2H4-NH-C2H4-NH-C2H4-NH-C2H4-NH2 I-TEPA (branched isomer)

[0078] [ka] L-PEHA (linear isomer) H2N-C2H4-NH-C2H4-NH-C2H4-NH-C2H4-NH-C2H4 -NH2 I1-PEHA (branched isomer)

[0079] [ka] I2-PEHA (branched isomer)

[0080] [ka] I3-PEHA (double branched isomer)

[0081] [ka]

[0082] All such isomers are included in the above definition.

[0083] Examples of compounds according to formula 3 include those in which one or more A groups are optionally methyl-substituted C2 It is also an alkylene group, where q in each instance can be 0, 1, or 2.

[0084] In embodiments, in any of Formulas 1, 2, or 3, R d is H or unsubstituted C1 ~6 Alkyl, e.g., H or C 1~2 In embodiments, T may be non-alkyl. substitution C 2~3 alkylene. X is O and NR d wherein R d teeth, H or unsubstituted C 1~6 Alkyl, e.g., H or C 1~2 alkyl].

[0085] In embodiments, the amine compound is of formula 1 or 2. In further embodiments, The amine compound is of formula 1, for example EDA.

[0086] One or more amine compounds can be used.

[0087] [Bronsted acid] The Bronsted acid may be an organic acid or an inorganic acid.

[0088] Suitable inorganic Bronsted acids include hydrohalic acids (e.g., hydrochloric acid, hydrobromic acid, hydrochloric acid, or hydroiodic acid), halogen acids (e.g., chloric acid, bromic acid, or iodic acid) , HIO3), perhalogen acids (e.g., perchloric acid, perbromic acid, periodic acid), nitric acid, nitrous acid Acids include sulfuric acid, sulfurous acid, phosphoric acid, and phosphorous acid.

[0089] Suitable organic Bronsted acids include carboxylic acids, such as one or more COO The organic acid may be an organic compound of formula A containing one or more C H groups. OOH groups, e.g., C containing 1, 2, or 3 COOH groups 1~8 It is an organic acid. In the form, the carboxylic acid may be, for example, a corresponding acyl halide (e.g., acyl chloride, acyl iodide or acyl iodide) or anhydrides (e.g., through reaction with water) ) by creating conditions under which they are hydrolyzed to form carboxylic acids, in s The organic acid can be formed by two or more carboxylic acid groups, e.g. may contain three carboxylic acid groups. Examples include optionally one or more hydroxy groups. C 1~8 Carboxylic acids, dicarboxylic acids, and tricarboxylic acids are included. Carbonic acid is also included. Specific examples of carboxylic acids include acetic acid, citric acid, and oxalic acid. Examples include:

[0090] The organic acid may be a sulfonic acid or a phosphonic acid. An example of this is the formula R c SO3H and R c R2PO3H [wherein R and Yobi R c is as defined above].

[0091] Salts of organic acids can also be used. When salts are used, they are typically alkali metal salts. a metal or alkaline earth metal salt, or a compound of the formula [NR p 4] + Nokachi The ammonium salt or organoammonium salt has an ion.

[0092] In embodiments, the Bronsted acid is an organic acid or a salt thereof. The organic acid is carboxylic acid, carbonic acid, or oxalic acid. The organic acid is used to prepare porous silica. After high temperature calcination, a process step that can be used to prepare silica, residues (e.g. This has the advantage that no residual organic compounds (e.g., in the form of non-volatile nitrate or phosphate moieties) remain. For similar reasons, when salts of organic acids are used, these are preferably salts of the organic acids as defined above. [NR p 4] + Organic salts such as salt.

[0093] [amino acid] In embodiments, amino acids may be used in the preparation of porous silica. In this state, the amino acid has the formula NR a 2-CR a R f Has -COOH.

[0094] Each R a is as defined above, and in embodiments, all R a is H.

[0095] R f is C1~C 30 aliphatic groups, these groups being -OR a , -SR a , -C (O)O - , C(O)OR a , -C(O)-NR a 2;R a and —OH C optionally substituted with one or more groups 5~10 Aromatic groups; and R a oh C optionally substituted with one or more groups selected from - 5~10 It is optionally substituted with one or more groups selected from heteroaromatic groups.

[0096] In addition, in the embodiment, CR a R f The group is C 5~6 Cycloaliphatic group or C 5~6 Heterocycle aliphatic groups of the formula R a and one selected from -OH Or it may be optionally substituted with multiple groups.

[0097] [Other ingredients] Other ingredients may be present in the mixture.

[0098] Use of one or more emulsifiers to help stabilize the water-in-oil emulsion The emulsifier can be selected from organic emulsifiers, which are typically Anionic, cationic, amphoteric, zwitterionic, or nonionic surfactants, generally are well known and commercially available.

[0099] Examples include fatty acids, fatty amines, and polyhydric alcohols (e.g., mono-, di-, or Fatty acid esters or partial fatty acid esters of fatty acids (e.g., triglycerides), or The corresponding anhydrides are also included. 6~22 may be selected from aliphatic groups .

[0100] Further examples of emulsifiers include sorbitan esters (sold under the trade name Span™) sorbitan monolaurate (e.g., Span™) 20), and sorbitan monooleate (e.g., Span™ 80). Further examples include polyethoxylated sorbitan esters (e.g., Tween (Trademark), such as PEG-20 monolaurate sol Tween™ 20, PEG-20 sorbitan monooleate (Twe en™ 80), and polyoxyethylene sorbitan trioleate (Twee n (trademark) 85). Other examples include C6-C 22 Alkyl sulfates, e.g. Sodium dodecyl sulfate; Formula C n H 2n+1 (OC m H 2m ) p -OSO3 - [where n is 6-22, m is 2-3, and p is 2-4], e.g., sulfates For example, sodium lauryl ether sulfate, and C 12~14 Pareth-3 sodium sulfate; C 6~22 Alkyl glycosides, such as lauryl glucoside; n H 2n+1 C(O) N(X)CH(CH[OH])CHOH, where n is 6 to 22 and X is H or C 1~4 glucamides of the formula [wherein the alkyl is methyl], for example caprylmethyl glucamide, Lauryl methyl glucamide, and dodecyl glucamide; C 2~16 carboxylate group substituted amino acids and their salts, for example, sodium cocoyl glutamate or or disodium cocoyl glutamate, and sodium lauroyl sarcosinate; C6 ~22 Fatty acids and their salts, such as sodium oleate and potassium oleate; Polyethylene glycol-substituted phenols having 5 to 25 glycol units, e.g., poly Ethylene glycol p-(1,1,3,3-tetramethylbutyl)-phenyl ether ( available as Triton™ X-100); C 6~22 Alkylamineoxy Desirable amines include lauramine oxide and C 6~22 Alkyl alcohols, e.g., cetyl Further examples include polymeric alcohols and stearyl alcohol. Emulsifiers, such as (meth)acrylate polymers and (meth)acrylic acid polymers (e.g. For example, polymethyl methacrylate), and at least one C 3~10 Alkenyl group and at least one C 1~4 Organoammonium salt polymer with alkyl groups - for example, polydiallyldimethylammonium chloride (polyDADMAC) .

[0101] One or more protective colloids can be used, often in combination with an emulsifier. Examples include polyvinyl alcohol, or polyvinylpyrrolidone.

[0102] The polyvinyl alcohol can optionally be partially or fully saponified In an embodiment, the polyvinyl alcohol is in the range of 70 to 100 mol %, for example, 8 The degree of hydrolysis ranges from 0 to 100 mol%, or from 80 to 98 mol%. 4% water The Hoppler viscosity in solution is 1 to 70 mPas, or in other embodiments, 3 to 40 mPas. s (measured at 20° C. according to DIN 53015).

[0103] One or more thickening agents may be used, for example, water-soluble polysaccharides or proteins. The thickeners are selected from the group consisting of clay-based thickeners, cellulose derivatives and starches.

[0104] Examples of cellulose derivatives include alkyl cellulose ethers and hydroxyalkyl celluloses. cellulose ether, carboxyalkyl cellulose ether, hydroxyalkyl polyoxy Alkyl cellulose ethers, as well as alkyl, hydroxyalkyl, and carboxyalkyl at least one selected from alkyl and / or hydroxyalkyl polyoxyalkyl; The alkyl group may be a mixed ether having two different substituents. 10 a Cellulose derivatives may also, or alternatively, be used as emulsifiers. can.

[0105] The cellulose ether has a degree of substitution (D) in the range of 1.2 to 2.9, for example, 1.6 to 2.2. S), but can reach up to 3, which means complete etherification of the cellulose. The substituents may be alkoxy groups, such as methoxy, ethoxy, and / or propoxy groups. C etc. 1~4 In embodiments, the at least one thickening agent may be a methyl group. ethyl cellulose, ethyl cellulose, propyl cellulose, hydroxymethyl cellulose , hydroxyethyl cellulose, hydroxypropyl cellulose, methylhydroxymethyl cellulose, methylhydroxyethyl cellulose, methylhydroxypropyl cellulose cellulose, ethyl hydroxymethyl cellulose, ethyl hydroxyethyl cellulose, ethyl hydroxymethyl cellulose Hydroxypropyl cellulose, propyl hydroxymethyl cellulose, propyl hydroxy The cellulose acetate solution is selected from propyl hydroxypropyl cellulose, ... and propyl hydroxypropyl cellulose.

[0106] Other polysaccharides that can be used include chemically modified and unmodified polysaccharides. , e.g., guar, dextran, chitin, chitosan, mannan, galactan, xylan , starch, xanthan gum, welan gum, gellan gum, alginate, arabinoxy These include orchids, glucans, and pectins.

[0107] Gelatin can also be used as a thickening agent.

[0108] One or more gelation promoters may also be used. Examples include -OH and halides. optionally with one or more groups selected from the group consisting of fluoride and chloride; Quaternary ammonium compounds containing optionally substituted C1-4 alkyl groups, such as chlorides [ Another example of an accelerator is ammonium nitrate. Hexamethylenetetramine (also known as methenamine).

[0109] [Water-in-oil emulsion or dispersion] The process typically involves the formation of a water-in-oil dispersion or emulsion.

[0110] The aqueous phase typically suspends, for example, nanoparticulate silica in solid form in an aqueous medium. or by using aqueous colloidal silica as a source of nanoparticulate silica. and thereby containing nanoparticulate silica.

[0111] The continuous "oil" phase is typically at least one oil that is insoluble in water or partially soluble in water. Contains one organic compound and measures the solubility of the organic compound in water and / or water in organic solvents. The solubility is 10% by weight or less, for example 5% by weight or less, for example 1% to 10% by weight, or It is in the range of 1% to 5% by weight.

[0112] In embodiments, the organic compounds (or at least some of the organic compounds) that form the "oil" phase 1) is higher than the boiling point of water, i.e., above 100°C, for example, 110°C or higher, 150°C In an embodiment, the boiling point is 400° C. or less.

[0113] One or more organic compounds may be used in the continuous "oil" phase of the dispersion. can be mixed with an aqueous phase to form an emulsion or dispersion. To improve stability, emulsifiers, thickeners, and / or protective colloids may be used. Cut.

[0114] Organic compounds are typically stored at room temperature (atmospheric pressure, i.e., 25°C at 1.013 bara). ) in the liquid phase, and the molecules have polar groups, e.g., esters, amides, aldehydes, ketones, and one or more selected from chol (including glycol), ether, and sulfoxide; In an embodiment, the organic molecule may be selected from those containing 3 to 12 groups. The esters, ketones, and ethers may, in embodiments, have a cyclic structure. It could be a part of it.

[0115] In embodiments, the organic compound may additionally or alternatively be non-polar, e.g. , optionally with one or more halides (e.g., F, Cl, Br, or I) substituted, alkane or aromatic compounds. Examples include C 1~20 Para Finn, C. 1~20 Haloparaffin, C 6~20 Aromatic compounds, and C 6~20 Hello Yoshi The aromatic or haloaromatic compound may be one or more C1 ~10 Alkyl group, or C 1~10 It may contain haloalkyl groups.

[0116] Examples of organic compounds that can be used include ethyl acetate, ethyl formate, n-propyl formate, Pyrrole, Isopropyl Formate, n-Propyl Acetate, Isopropyl Acetate, Isobutyl Acetate, Acetic Acid n-Butyl, n-pentyl formate, isopentyl formate, n-pentyl acetate, isopentyl acetate ethyl propionate, isobutyl isobutyrate, n-butyl propionate, 3-ethoxy Ethyl propionate, 2-ethylhexyl acetate, diethyl ketone, methyl isobutyl ketone Methyl isoamyl ketone, methyl n-amyl ketone, mesityl oxide, acetophenone Non, cyclohexanone, diethyl phthalate, benzyl acetate, methylcyclohexanone, benzaldehyde, benzyl alcohol, diisopropyl ether, and anisole, Other examples of solvents include toluene, xylene, methyl chloride, Chloroform, carbon tetrachloride, methyl bromide, methyl iodide, trichloroethylene, and tetrachloroethylene. The organic solvent may be a mixture of two or more solvents. .

[0117] [Process conditions] In the process according to the invention, nanoparticulate silica is gelled to produce porous silica. .

[0118] Gelation is carried out in a two-phase system, which includes an aqueous phase dispersed or emulsified in a continuous "oil" phase.

[0119] In this method, a basic nanoparticulate dispersion (e.g., a basic aqueous colloid as described above) is prepared. The silica (silica) is mixed with an organic medium to form a water-in-oil dispersion or emulsion. Vigorous stirring is required to maintain dispersion of the aqueous droplets containing nanoparticulate silica for an extended period of time. Emulsions are preferred as they avoid the need for active steps such as stirring. As described above, at least one or more water-insoluble or partially water-soluble active ingredients Contains organic solvent.

[0120] The nanoparticulate silica is present in the aqueous phase. The acids may also be water-miscible such that they are completely or predominantly mixed into the aqueous phase; That is, they are water soluble or at least partially water soluble, e.g., under ambient conditions. (i.e., atmospheric pressure, 25°C) at least 1 wt%, for example at least 10 wt% , or at least 20% by weight (i.e., at least 10 gdm-3 , for example, less Tomo 100gdm -3 , or at least 200gdm -3 ) in water. In embodiments where they are only partially soluble, the amounts used will be within their water solubility limits. Do so.

[0121] The weight ratio of the amine compound or amino acid to silica (based on the dry weight of SiO2) is: In an embodiment, it is in the range of 0.005 to 1, for example, in the range of 0.01 to 0.6.

[0122] The silica content (based on the dry weight of SiO2) in the total synthetic mixture is 0.01-50 % by weight, for example, 0.1 to 30% by weight, 0.5 to 15% by weight, or 1 to 10% by weight The amount of the hydroxybenzoate may be in the range of % by volume.

[0123] Weight ratio of Bronsted acid or amino acid to silica (based on dry weight of SiO2) is in the range of 0.005:1 to 1:1, for example, 0.01:1 to 0.6:1, or 0. It can be in the range of 0.1:1 to 0.3:1.

[0124] In an embodiment, the weight ratio of the organic acid to the amine compound is 0.02:1 to 1:1, for example, It is in the range of 0.05:1 to 0.8:1.

[0125] In the above ratio, two or more amino acids, amino compounds, or Bronsted acids are present. When calculating the total amount of amino acids, total amino compounds, and total Bronsted acids, the calculation is based on the total amount of amino acids, total amino compounds, and total Bronsted acids. Amino acids are counted as both amino compounds and Bronsted acids.

[0126] The gelation of nanoparticulate silica into larger particles of porous silica removes water from the system. This is typically done by using heat and / or reduced pressure. Other conditions may also be controlled to aid in this.

[0127] For example, a gelling agent may be added, as described above.

[0128] In embodiments, the pH of the dispersion / emulsion, or at least the pH of the dispersion / emulsion, The pH of the aqueous phase can be in the range of 5 to 9. To control the pH, an acid or base can be added. For example, a Bronsted acid, an amino compound, or Amino acids can be used. Other basic compounds that can be used include those defined above. As defined above, alkali metal hydroxides, alkaline earth metal hydroxides, ammonia or hydroxide Ammonium chloride, or [NR p 4] + hydroxides of ions, typically ammonium ions In embodiments, a basic pH is used. In embodiments, gelation, washing, After calcination, alkali metal hydroxide and and alkaline earth metal hydroxides are avoided.

[0129] Typical gelation conditions include temperatures between 0 and 100°C. For example, a high temperature in the range of 50 to 100°C or 55 to 95°C is used to High temperatures tend to increase the rate at which water evaporates.

[0130] Pressures in the range of 0.01 to 1.10 bara (bar absolute pressure) can be used. In an embodiment, a reduced pressure, for example, between 0.01 and 0.50 bara, is applied to assist in the evaporation of water. A pressure in the range, for example, 0.03 to 0.25 bara, is used.

[0131] To recover the large pore porous silica of the present invention, for example, centrifugation, decantation, The remainder of the liquid (typically mostly the organic phase) is removed by filtration or by filtration. The solid porous silica product is washed and / or dried if necessary and optionally calcined. The firing conditions are in the range of 400°C to 900°C, for example, 550°C to 700°C. and in the range of 0.5 to 5.0 bara, for example, in the range of 0.9 to 2.5 bara Heating in air or oxygen-containing gas containing 5 to 100% by volume of oxygen at a pressure of Examples include:

[0132] This does not use a combination of acid and amine compounds or amino acids as defined above. The methods used to date have not been able to achieve the desired combination of large pore size and large pore volume characteristics. Typically, silica with large pore sizes cannot be achieved. Although it can be achieved, the pore volume is much smaller and when used as a stationary phase, This results in lower separation efficiency.

[0133] Without being bound by theory, it is believed that the amine compound and the Bronsted acid form a salt. It is believed that the charge of the silica nanoparticles can be shielded by using the ion beam, reducing the electrostatic repulsion. This makes it easier for the Si-O-Si bonds to form between particles, and the water content of the dispersion (e.g. the rate that would otherwise be achieved by simply slowing it down (for example, through evaporation) This helps the silica nanoparticles present within the aqueous droplets to bond with each other at a faster rate. This increased gelation rate results in greater pore volume and surface area. The advantage is a narrower pore size distribution, which leads to a higher chromatographic separation efficiency. These are desirable characteristics to help achieve further improvements. [Example]

[0134] [Example 1] Average pore size of 286Å, 128m 2 g -1 of surface area, and 0.91 cm 3 g -1 A silica having a pore volume of

[0135] Silica was heated in a 1500 cm 3 Prepared using a reactor 500g of benzyl alcohol was added to the reactor, followed by 42.6g of water and 2.3g of of hexamethylenetetramine and 0.4 g of cellulose ether (Bermocoll E230X-ethylhydroxyethylcellulose) solution was added until homogeneous. The mixture was stirred.

[0136] With constant stirring, add 91.6 g of 14 wt. % aqueous colloidal silica (40 wt. % L It was prepared by dilution of evasil™ CS40-614P silica sol and According to the titration method, 130m 2 g -1 The silica particles (having a surface area of ​​10 ... Stirring was continued for 30 minutes to ensure a water-in-water emulsion.

[0137] 0.16g of glacial acetic acid, 0.22g of tetrabutylammonium hydroxide, 0.34g of ethanol ethylenediamine, 0.22 g of butylamine, and 0.27 g of water were added. The emulsion was heated at 75°C by means of a heating jacket and cooled under reduced pressure (200 mbar absolute). After distilling 117 ml of emulsion liquid, the reactor was cooled to room temperature. The remaining suspension containing benzyl alcohol and silica was centrifuged to remove the benzyl alcohol. The liquid phase was decanted and the recovered silica was resuspended in ethanol and filtered. The filtered solid was washed with 790 g of ethanol and dried in an oven at 90°C for 16 hours. Then, it was calcined in air at 650°C for 5 hours.

[0138] The pore volume of the calcined material is 0.91 cm 3 g -1 and the specific surface area is 128m 2 g -1 The average pore size was 286 Å and the D90 / D10 value was 2.05.

[0139] [Example 2] 250cm 3 In a round-bottom flask, add 50 g of benzyl alcohol. The emulsifier solution was also added. The emulsifier solution consisted of 4.2 g of water and 0.23 g of hexamethylenetetramine. A mixture of 38 mg of cellulose ether (Bermocoll E230X) and 100 mg of cellulose ether (Bermocoll E230X) was used. The benzyl alcohol / emulsifier mixture was stirred until homogeneous, then added to 9. 2 g of the same 14% (wt / wt) silica sol as in Example 1 was added to the mixture with constant stirring. The round-bottom flask was then attached to a rotary evaporator to obtain a stable water-in-oil emulsion. Rotate at room temperature for 30 minutes until a nucleus forms. 76% of 23 mg (wt / wt) An aqueous solution of acetic acid and 91 mg of an 87% (wt / wt) aqueous solution of ethylenediamine were added to the emulsion. The mixture was then added to a rotary evaporator under a reduced pressure of 160 mbar. Using a heating bath, the emulsion was heated to a temperature of 70° C. Approximately 10 mL of the liquid phase was distilled off. After that, the flask was cooled to room temperature. The remaining contents were filtered to remove the porous silica. This was washed with 40 g of ethanol. The silica was resuspended in 40 g of ethanol. The mixture was filtered again and washed with 40 g of ethanol. The silica was dried for 20 hours and calcined in air at 650°C for 6 hours. The pore volume after calcination was 0 0.87mL / g and the surface area is 132m 2 g -1 The average pore size is 262 Å. The D90 / D10 value was 2.24.

[0140] [Example 3] 1500cm equipped with an overhead stirrer 3 Into the reactor, 900 g of benzyl alcohol Alcohol was added, followed by 82 g of an emulsifier solution, which consisted of 77.1 g of water and , 4.2 g of hexamethylenetetramine, and 0.7 g of cellulose ether (Bermo The mixture was stirred until homogeneous, then stirred at constant This was prepared by diluting the same 40% by weight silica sol as in Example 1 while stirring. 92.2 g of 20% (wt / wt) silica sol was added to form a stable water-in-oil emulsion. Stirring was continued for 30 minutes to yield 0.92 g of 76% (w / w) An aqueous solution of acetic acid and 1.83 g of an 87% (wt / wt) aqueous solution of ethylenediamine were added to the The emulsion was then heated (75°C) under a vacuum of 200 mbar. After distilling off about 120 mL of emulsion liquid, the reactor was cooled to room temperature. The remaining contents were poured into a plastic bottle and the silica was allowed to settle overnight. The mixture was decanted and the silica was filtered and washed with 120 g of ethanol. The silica was resuspended in 120 g of ethanol and refiltered, followed by a further 120 g of ethanol. The silica was resuspended, refiltered, and rewashed in the same manner one more time. The silica was dried in an oven at 90°C for 20 hours and calcined in air at 650°C for 6 hours. After calcination, the pore volume was 0.88 mL / g and the surface area was 128 m 2 g -1 and The average pore size was 273 Å, and the D90 / D10 value was 1.81.

[0141] [Example 4] 1500cm equipped with an overhead stirrer 3 A reactor was charged with 73 g of emulsifier solution and Both were mixed with 800g of benzyl alcohol. The emulsifier solution consisted of 68.6g of water and 3. 7 g of hexamethylenetetramine and 0.6 g of cellulose ether (Bermocol The mixture was stirred until homogeneous, and then 92.2 g of The same 20% (wt / wt) silica sol as in Example 3 was added with constant stirring. was stirred for an additional 30 minutes to achieve a stable water-in-oil emulsion, after which 0.92 g of 76% (wt / wt) acetic acid in water, and 1.83 g of 87% (wt / wt) ethylene The aqueous diamine solution was then added. The emulsion was then heated under a pressure of 200 mbar ( Water bath temperature 75°C. When approximately 120 mL of liquid had distilled, the reactor was cooled to room temperature. The contents were poured into a plastic bottle and the silica was allowed to settle overnight. The mixture was decanted, the silica filtered and washed with 120 g of ethanol. Resuspend the silica in ethanol, filter again, and wash with a further 120 g of ethanol. The silica was resuspended, refiltered, and rewashed once more in the same manner. The silica was dried in an oven at 90°C for 20 hours and calcined in air at 650°C for 6 hours. After calcination, the pore volume was 0.87 mL / g and the surface area was 129 m 2 / g, average The pore size was 269 Å and the D90 / D10 value was 1.97.

[0142] The properties of these four examples are shown in Table 1.

[0143] [Table 1]

[0144] [Comparative Examples 5 to 10] The process described in EP 0298062 produces relatively small pores. The silica was prepared with an average pore diameter of 100 Å and a pore size of 319 m. 2 g -1 Surface area of , and 0.84 cm 3 g -1 The pore volume was 1000 .mu.m.

[0145] The resulting material is then subjected to Ostwald ripening to grow the particles and increase the average pore diameter. The process was carried out in 1 dm 3 In a steel autoclave, add 619 g of water and 73 This involved adding 31 g of silica along with 1 g of 25% aqueous ammonia solution. The vessel was sealed and heated to 120°C for 116 hours. After cooling to 30°C, 105g of 63 weight percent was obtained. % nitric acid was added. The silica was then filtered and added to 300 g of water, followed by 158 g of acetone. The silica was then dried in an oven at 90°C for 16 hours. The silica obtained had the properties listed in Table 2.

[0146] As can be clearly seen, the new inventive method is faster than the traditional Ostwald ripening process. It is simple and also achieves a significantly narrower pore size distribution.

[0147] This narrow pore size distribution can be seen from Figure 2, which compares the distributions for Example 2 and Comparative Example 5. It's obvious.

[0148] [Table 2]

[0149] [Comparative Examples 11 to 15] Five types of silica gel with pore sizes of approximately 300 Å and particle sizes of 10 or 15 μm. The commercially available butyl-modified silica was calcined in air at 650°C for 5 hours to remove the organic modification. The calcination process does not significantly affect the porous characteristics of the silica (see Examples 16-1 below). 7) The properties of the obtained silica are shown in Table 3.

[0150] The pore size distribution (D90 / D10) of the commercial samples was determined by the method described herein. The pore size distribution of the silica prepared by the comparative example is significantly larger than that of the silica prepared by the comparative example. For Example 15, which has a size distribution, the pore volume is significantly larger than that of the examples of the present invention. , which is a sign of a decrease in the mechanical strength of the silica.

[0151] [Table 3]

[0152] The following examples demonstrate that calcining organo-modified silica has a significant effect on the properties of the resulting silica. Indicates no effect.

[0153] [Example 16] The silica sample was prepared according to the method described in Example 1(4) of EP 0298062. After post-treatment, the volume was 0.94 mL. -1 pore volume, 122 m 2 g -1 The pore size distribution D The 90 / D10 was 2.07 and the D50 was 389 Å.

[0154] 7 g of this "rehydroxylated" silica was added to 250 cm 3 1 medium 3-neck glass flask Disperse in 39 g of toluene and evaporate to about 40 cm 3 until the liquid is removed The temperature was then lowered to 90°C, and 2.1 g of pyridine and butyldimethyl 2 g of dichlorosilane was added. The silica dispersion was heated to reflux overnight. After 16 hours, The temperature was lowered to room temperature, and 32 g of ethanol was added to deactivate the remaining silane. The slurry was poured into a glass filter funnel and filtered. The filter cake was washed with 356 g of ethanol. The material was dried in an oven at 90°C for 17 hours. This gave a carbon content of 3.1 μmol m -2 corresponds to a ligand coverage of do.

[0155] [Example 17] To burn the silane, 3 g of the organo-modified silica of Example 16 was heated in air at 650°C. The calcination was carried out for 5 hours. The pore volume after the post-treatment was 0.89 mL g -1and its surface area is 120m 2 g -1 The average pore size is 299 Å, and the pore size distribution D90 / D10 is 2 07 and the D50 was 371 Å.

Claims

1. An average pore diameter of at least 210 Å and at least 0.80 cm ３ g －１ Pore ​​volume of Porous silica having a product.

2. The pore diameter is up to 500 Å and / or the pore volume is up to 1.2 cm ３ g －１ 2. The porous silica according to claim 1, wherein

3. The following conditions (i) the pore volume is at least 0.84 cm ３ g －１ is (ii) the pore volume is up to 1.0 cm ３ g －１ is (iii) the average pore diameter is at least 250 Å (iv) the average pore diameter is at most 450 Å and / or at most 350 Å (v) A specific surface area of ​​50 to 500 m ２ g －１ and / or between 80 and 30 0m ２ g －１ is within the range (vi) the surface is modified with one or more organic groups; (vii) pore size distribution, D90 / D10, of 0.10 to 2.30, or 1.00 to Within the range of 2.30 (viii) the porous silica is in solid form 3. The porous silica according to claim 1 or 2, wherein one or more of the following applies:

4. (i) a Brønsted acid and two groups selected from a primary amine group and a secondary amine group; In the presence of an amine compound having the above amine group, or (ii) an amino acid, a liquid phase dispersion nanoparticle is prepared.

2. The process for producing porous silica according to claim 1, wherein particulate silica is gelled. vinegar.

5. the primary particles of the nanoparticulate silica have an average diameter in the range of 2 to 200 nm; and and / or the liquid phase dispersion of nanoparticulate silica is a water-in-oil emulsion or dispersion. and the aqueous phase contains the nanoparticulate silica, an optional Bronsted acid, an amine compound, and and an amino acid, wherein the oil phase comprises at least one water-insoluble or partially water-soluble component. the solubility of said organic compounds in water and / or the 5. The process of claim 4, wherein the solubility of water in the aqueous solution is 10% by weight or less.

6. 6. The method of claim 4, wherein the nanoparticulate silica is in the form of colloidal silica. process.

7. The following conditions (i) the colloidal silica is aqueous and prepared from a soluble silicate or polysilicic acid solution; and has a pH in the range of 8-12 (ii) the colloidal silica has an S value in the range of 10 to 95%; (iii) The colloidal silica particles have a particle size of 50 to 1000 m ２ g －１ The surface area within the range have 7. The process of claim 6, wherein one or more of the following applies:

8. the amine compound has a formula according to any one of Formulas 1-3; 【Chemistry 1】 ・R ｄ is independently in each occurrence H, as well as halogen (e.g., F, Cl, Br) , -OR ｅ , -COOR ｅ , and -N[R ｅ ] ２ [In the formula, each R ｅ are independently H and C １～６ and alkyl, Optionally substituted C １～６ alkyl groups, A, independently in each occurrence, optionally comprises one or more C １～３ Alkyl groups C substituted with １～３ Alkylene units (e.g., C ２～３ alkylene units) R, X is independently in each occurrence -O-, -NR ｄ - and 【Chemistry 2】 is selected from q is independently selected in each occurrence from a non-negative integer in the range of 0 to 7; 8. The process according to any one of claims 4 to 7.

9. The acid is optionally selected from oxalic acid, carbonic acid, carboxylic acid, sulfonic acid, and phosphonic acid.

9. The process of claim 4, wherein the organic acid is selected from the group consisting of:

10. The carboxylic, sulfonic, and phosphonic acids are of the formula R—C(O)OH, R ｃ -SO ３ H, and R ｃ R ２ P.O. ３ H, wherein Each R is independently H, optionally substituted C １～３０ Aliphatic groups, optionally substituted TaC ５～１０ aryl groups, and optionally substituted C ５～１０ From heteroaryl groups Selected, ・R ｃ is an optionally substituted C １～３０ Aliphatic groups, optionally substituted C ５～１０ aryl groups, and optionally substituted C ５～１０ heteroaryl groups, 10. The process of claim 9.

11. ・C above １～３０ The aliphatic group may be saturated or unsaturated, and may be linear, branched, or may be cyclic, ・C １～３０ Each of the aliphatic organic groups is -OR, -C(O)OH, -C(O)OR, - C(O)NR ２ 、-OC(O)R、-NRC(O)R、-NR-C(O)-NR ２ 、-N R ２ , -[NR ３ ] ＋ , halide, epoxy, oxo, C ５～６ aromatic group, C ５～６ Haitai Aromatic groups, and groups represented by the general formula -[O-(CR ａ ２ ) ｎ ] ｍ -OR ｂ Glycol ether group and optionally substituted with one or more groups selected from ・C above ５～１０ Aryl groups and C ５～１０ Each heteroaryl group is —OR, -C(O)OH、-C(O)OR、-C(O)NR ２ 、-OC(O)R、-NRC(O) R, -NR-C(O)-NR ２ , -NR ２ , -[NR ３ ] ＋ , halide, epoxy, oxy So, C １～３０ Aliphatic groups, and groups of the general formula -[O-(CR ａ ２ ) ｎ ] ｍ -OR ｂ Glico optionally substituted with one or more groups selected from aryl ether groups; During the ceremony, Each R is hydrogen, C １～３０ aliphatic group, C ５～６ Aromatic groups, and C ５～６ Heteroaromatic is selected from the group ・Each R ａ is hydrogen and C １～４ alkyl groups, ・Each R ｂ is hydrogen or C １～１０ is an alkyl group, n is an integer from 2 to 3, m is an integer from 2 to 20, and in the formula: In the optional substituents, any aromatic group, heteroaromatic group, aliphatic group, alkyl group , or the alkoxy group is hydroxyl, C １～４ Alkoxy, carboxyl, halide , and —NH ２ which may itself optionally be substituted by one or more substituents selected from may be substituted with Any heteroaromatic or cycloaliphatic group may contain O, S, and N in the ring, typically 11. The compound according to claim 10, which may have one or more heteroatoms selected from O or N. process.

12. The following conditions (i) The weight ratio of the amine compound and / or the amino acid to silica (SiO ２ Dry based on dry weight) is in the range of 0.005 to 1 (ii) Silica content (SiO ２ (based on dry weight) is 0.001 in the range of up to 50% by weight (iii) the weight ratio of the organic acid and / or amino acid to silica (SiO ２ Dry weight of (based on the ratio of 1:1 to 0.005:1) is in the range of 0.005:1 to 1:

1. (iv) The weight ratio of the organic acid to the amine compound is within the range of 0.02:1 to 1:

1. (v) The amine compound is selected from the formula (1) and formula (2) according to claim 8. can 12. The process according to claim 4, wherein one or more of the following applies: vinegar.

13. The porous silica is separated from the liquid phase and optionally modified with one or more organic groups.

13. The process of any one of claims 4 to 12.

14. 4. The method of claim 1, wherein the chromatographic stationary phase is a chromatographic stationary phase. Use of porous silica.

15. A separation column or vessel comprising the porous silica of any one of claims 1 to 3.

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