Porous Silica Particles

Abstract

To provide an improved porous silica material that has a desirable combination of a large median pore diameter or an average pore diameter, pore volumes, and a narrow pore size distribution that further helps to improve separation efficiency in a range that ensures high performance efficiency and high mechanical strength.SOLUTION: The present invention relates to a porous silica having a median pore diameter of 210 Å to 500 Å and a pore volume of 0.80 cm3 g-1 to 1.2 cm3 g-1. The present invention also relates to a method for producing the porous silica including gelling a liquid phase-dispersed nanoparticulate silica in the presence of either (i) a Bronsted acid and an amine compound having two or more primary or secondary amine groups or (ii) an amino acid. The present invention further relates to a use of a porous silica as a stationary phase for separation, and also relates to a separation column or vessel 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. The particles, either as such or after surface modification, can be used in many applications, in particular as stationary phases in chromatographic separation techniques. [Background technology]

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

[0003] An advantage of silica is that its properties can be highly tuned, for example, by changing the pore characteristics or by chemically modifying the surface, which can be very useful in separation applications, for example, because such versatility allows it to be used for many different types of separations.

[0004] A common route to producing porous silica materials suitable for separation techniques is via sol-gel chemistry, in which a silica precursor, such as nanoparticulate or colloidal silica, is gelled under controlled conditions. Such a technique is described in EP 0298062. This typically produces porous silica with an average pore diameter of up to 100 Å. Such silica can be used to separate relatively small molecules, e.g., molecules with molecular weights of 10,000 or less. However, for the separation of larger molecules, such as proteins, which have significantly larger molecular weights, larger pores, typically greater than 200 Å and often on the order of 300 Å, are preferred.

[0005] While such large pore materials can be made by Ostwald ripening of silica precursor materials (e.g., those with pore sizes on the order of 100 Å), this is a time-consuming process that often consumes silica that has value in its own right, for example, as a separation medium for small molecules or as a catalyst support. Additionally, it can be laborious and time-consuming to prepare the silica starting material to arrive at the final large pore product with the desired characteristics.

[0006] Other techniques for making large pore silica are described in U.S. Patent Nos. 3,855,172 and 4,874,518. However, a further problem with prior art materials is that the large pore size is often accompanied by a relatively broad pore size distribution, which can negatively affect 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 aims to provide improved porous silica materials that have a desirable combination of large median or average pore diameter, pore volume, and narrow pore size distribution, which helps to further improve separation efficiency, while ensuring high performance efficiency and also high mechanical strength. The present invention also aims to use such materials as stationary phases for separations. The present invention further aims to provide 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 relates to a method for producing porous silica, comprising gelling liquid-phase dispersed nanoparticulate silica in the presence of either (i) a Bronsted acid and an amine compound having two or more primary or secondary amine groups, or (ii) an amino acid.

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

[0013] In yet another aspect, the present invention relates to a separation column or vessel containing porous silica. [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. In embodiments, up to 5% by weight of other oxide components are present. The other oxide components may be other refractory oxides, such as oxides of aluminum, titanium, iron, chromium, zinc, zirconium, magnesium, calcium, and cerium.

[0016] The alkali and alkaline earth content is also typically low, for example less than 1 wt. % total, and in a further embodiment less than 0.1 wt. %, for example less than 100 ppm.

[0017] In an embodiment, the silica contains no more than 0.1% by weight, such as no more than 100 ppm, of any other oxide or alkali / alkaline earth metal impurities.

[0018] An exception to the above levels of other oxides are embodiments in which the surface of the porous silica, or the surface of the nanoparticulate silica used to make the porous silica, has been intentionally modified or doped, as described in more detail below, in which embodiments up to 10% by weight aluminum oxide may be present, for example up to 5% by weight aluminum oxide.

[0019] Porous silica is 0.80 to 1.2 cm 3 g -1 In an embodiment, the pore volume is in the range of 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, such as in the range of 200 to 450 Å, such as 220 to 400 or 220 to 350 Å.

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

[0022] The porous silica may have a median pore diameter of 210 to 500 Å, or 250 to 450 Å. In embodiments, the silica has an average / median pore diameter in the range of 300 to 400 Å.

[0023] The median pore diameter is optionally referred to as the "D50" pore diameter. Pores having a diameter equal to or less than the median (D50) pore diameter contain 50% of the total pore volume of the material. Similarly, a "D10" or "D90" pore diameter is the diameter within which 10% or 90% of the pore volume is contained, respectively. Thus, pores having a diameter equal to or less than the D10 or D90 diameter contain 10% or 90% of the total pore volume, respectively. The D10, D50, and D90 points are shown in Figure 1.

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

[0025] In an embodiment, the D90 / D10 ratio is 2.30 or less. In a further embodiment, the D90 / D10 ratio is within the range of 0.01 to 2.30. In a further embodiment, the D90 / D10 ratio is within the range of 0.10 to 2.30 or 1.00 to 2.30. In yet a further embodiment, the D90 / D10 ratio is within the range of 1.50 to 2.30. In another embodiment, the upper limit for the D90 / D10 value is 2.25.

[0026] The preferred method for measuring pore size distribution and D10, D50 and D90 pore diameters is by the Barrett-Joyner-Halenda (BJH) method, which is based on nitrogen adsorption / desorption, especially from desorption isotherm.The preferred method for measuring surface area, pore volume and average pore diameter (from surface area and pore volume) is also by the Brunauer-Emmett-Teller (BET) method, which is based on nitrogen adsorption / desorption, and surface area is typically calculated from the linear part of the isotherm.Examples of such methods are given in ISO 9277:2010 (for BET) and ISO 15901-2:2006 (for gas adsorption / desorption).

[0027] The combination of pore volume, pore diameter, and narrow pore size distribution means that porous silica is highly effective as a stationary phase for the separation of large molecules (e.g., proteins). This is because the pore size is large enough to allow good mass transfer of such large molecules into and out of the pores, allowing for efficient absorption. In addition, a sufficiently large pore volume combined with a large surface area and narrow pore size distribution results in a highly defined pore structure, which also helps ensure high separation efficiency. Furthermore, ensuring that the pore volume is not too large can maintain the mechanical strength and integrity of the porous silica, thus avoiding damage to the material, for example, during packing of a separation column, and again ensuring high separation efficiency.

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

[0029] [Organosilane-modified silica] In embodiments, the porous silica may comprise one or more organic groups, such as one or more C1-C 30 an aliphatic group or one or more C 5~10 Aromatic group, or C 5~10 It can be modified by a heteroaromatic group (hereinafter, "A" group). In embodiments, 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, -NR2, -[NR3] + , halide, epoxy, oxo, C 5~6 Aromatic group, C 5~6 Heteroaromatic groups, C 5~6 Heterocyclic aliphatic groups, and groups of the general formula -[O-(CR a 2) n ] m -OR b The glycol ether groups may be optionally substituted with one or more groups selected from the following:

[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, -NR2, -[NR3] + , halide, epoxy, oxo, C 1~30 aliphatic group, C 5~6 Heterocyclic aliphatic groups, and groups of the general formula -[O-(CR a 2) n ] m -OR b The glycol ether groups may be optionally substituted with one or more groups selected from the following:

[0032] Each R group is independently hydrogen, C 1~30 aliphatic group, C 5~6 Aromatic group, C 5~6 Heteroaromatic groups, and C 5~6heterocyclic aliphatic groups, and each R a is hydrogen and C 1~4 alkyl groups, and each R b The group is hydrogen or C 1~10 It is an alkyl group, 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 (including those in functional groups such as alkoxy, amide, amine, and ester groups) can be linear, branched, or cyclic, and can be saturated or unsaturated. Typically, they are saturated. In embodiments, linear and branched groups are used, and in further embodiments, linear groups are used.

[0034] R groups (other than hydrogen) are hydroxyl, epoxy, C 1~4 It may be optionally substituted with one or more substituents selected from alkoxy, carboxyl, halide (eg, fluorine or chlorine), and -NH2.

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

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

[0037] Unsaturated aliphatic groups can contain one or more double bonds and / or one or more triple bonds, in embodiments, there are no triple bonds.

[0038] Charged groups, e.g. -C(O)O - or -[NR3] + For compounds containing groups, these may also contain a countercation or counteranion, respectively. A cation is a group that is formed by the reaction of a proton (H + ), alkali metals, alkaline earth metals, formula [NR4] + where R is as defined above. The anion may be selected from ammonium or organoammonium ions of the formula: - , Cl - , Br - , and I - ), hydroxides, nitrates, sulfates, chlorates, bromates, iodates, phosphates, tetrafluoroborates, hexafluorophosphates, formula R c SO3 - and sulfonates of formula R c R2PO3 - wherein each R is as defined above and each R c is C 1~30 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] Modification of silica can be achieved by reacting it with a suitable organic compound, for example, an organosilane containing the required group. This can be achieved using known procedures, for example, the procedure described in WO 2007 / 070001. The organosilane has the formula Si[Z] 4-y [A] y Each Z is typically a halide, hydroxyl, and lower alkoxy group, e.g., C 1~6 Alkoxy group, or C 1~4In 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 A is a heteroaromatic group. y is an integer ranging from 1 to 3. When y is greater than 1, each A may be the same or different. When y is less than 3, each Z may be the same or different, although in embodiments, all Z groups are the same. Such compounds can be purchased commercially or prepared by known techniques, such as those described in Ullmann's Encyclopadie der Technischen Chemie in the section "Silicium-Verbindungen, Organische" and the Kirk-Othmer Encyclopedia of Chemical Technology, in the section "Silicon Compounds (Silanes)."

[0041] When an organosilane is used to modify silica, it forms one or more Si-O-Si linkages with the silica surface by reaction with one or more surface silanol groups. For convenience, this linkage is referred to as [SiO2]-Si-[A]. y It may be expressed by:

[0042] In other embodiments, they can be modified with halohydrin compounds based on the formula HO-CR(CRX)A, where R and A are each as defined above, and X is a halogen, typically chlorine or bromine, preferably chlorine. These can be reacted with the silica surface using known techniques, such as those described in International Publication No. WO 2014 / 206893. In embodiments, each R is H or methyl. Halohydrin compounds can be purchased commercially or produced using known procedures, for example, as described in International Publication No. WO 2013 / 092778, Ullmann's Encyclopadie der Technischen Chemie, in the section on "Epoxidverbindungen," and also in the Kirk-Othmer Encyclopedia of Chemical Technology, in the section on "Chlorohydrins."

[0043] When reacted with a silica surface (e.g., by stirring the compound with silica at elevated temperatures), the hydroxyl groups react with the surface silanol groups of the silica, which for convenience may be represented by [SiO2]-O-CR(CR2X)A.

[0044] When silica is modified with two or more different organic groups, this can be achieved by using different modifying reactants (e.g., two different Si[Z] 4-y [A] y This can be achieved by using either one reactant, or two different HO-C(CR2X)A reactants, where 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 contains two or more different A groups.

[0045] In embodiments, the silica may be modified with one or more A groups, each of which may be selected from the group consisting of C1~30 In embodiments, the silica is selected from the group consisting of C alkyl groups, each of which is optionally substituted as described above, although in embodiments the alkyl groups are unsubstituted. 10~20 Alkyl groups and C 1~4 and alkyl groups, each optionally substituted as described above, although in embodiments both alkyl groups are unsubstituted.

[0046] Silica can be modified using known techniques, for example, by stirring the silica with one or more organosilane compounds as defined above in an aqueous solution at basic pH. Such techniques are described, for example, in International Publication Nos. WO2007 / 070001 and WO2014 / 206893.

[0047] In other embodiments, the starting material can be organically modified to produce silica according to the present invention. For example, organosilane compounds can be hydrolyzed to form organosilane-modified silica particles, or in other embodiments, colloidal silica starting materials can be modified with organosilanes before gelation to form silica according to the present invention, for example, using procedures described in WO 2004 / 035473 and WO 2004 / 035474.

[0048] [Nanoparticulate silica] In producing the large pore silica of the present invention, a source of nanoparticulate silica is used, which may be in the form of colloidal silica, as further described below. In other embodiments, the source of nanoparticulate silica may be a solid form of silica dispersed or suspended in a liquid phase. In embodiments, the silica nanoparticles (prior to dispersion or suspension) are in the form of fumed silica, precipitated silica, or silica fume. In these types of silica, 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, which may have diameters (or effective diameters) ranging from 300 nm to 100 μm.

[0049] Crystalline forms of silica, such as quartz, may also be used, however these are preferably avoided as crystalline forms may be harmful to health.

[0050] [Colloidal silica] In a preferred embodiment of the present invention, the nanoparticulate silica source is colloidal silica in which primary colloidal silica particles having diameters in the range of 2-200 nm are suspended in an aqueous medium. Typically, the level of aggregation of the primary particles is low, and the silica colloid is highly stable (i.e., does not spontaneously gel or coagulate) for periods of several months, typically 4 months or more, and in embodiments 6 months or more. Colloidal silica is also often referred to as silica sol, and these two terms are used interchangeably in this disclosure.

[0051] The degree of gelation or aggregation of colloidal silica can be described by the so-called "S value." In embodiments, for unmodified colloidal silica, the S value is in the range of 10-95%, for example, 20-90%, or 30-90%. The S value is measured and calculated as described by Iler & Dalton (Iler & Dalton; J. Phys. Chem., 60 (1956), 955-957). A high S value indicates a low level of aggregation and highly dispersed silica particles. Conversely, a lower S value indicates a higher level of microaggregation.

[0052] When colloidal silica is used, it is generally an aqueous sol containing no or a small amount of organic solvent. When an organic solvent is present, the aqueous medium usually contains 10% by weight or less of organic solvent, for example 5% by weight or less of organic solvent. When an organic solvent is present, the organic solvent is preferably water-miscible, for example, C 1~6 Alkyl alcohol, C 1~6 Aldehyde, C 3~6 Ketone, C 1~6 Carboxylic acids and their C 1~6 Typically, when an organic solvent is present, it is selected from one or more of a C alkyl ester. 1~6 Alcohols are selected from the group consisting of:

[0053] The aqueous colloidal silica may be basic, having a pH in the range of 8.0 to 12.0, for example 8.5 to 11.0. Other components of such sols include the presence of alkali metals, typically one or more of lithium, sodium, and potassium, or ammonium or organoammonium ions [NR p 4] + [wherein 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 optionally substituted with alkoxy groups].

[0054] Examples of suitable aqueous silicates or water glasses that can be used to make the aqueous silica sol include ammonium silicate, lithium silicate, sodium silicate, and potassium silicate.

[0055] Colloidal silica having 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 surface-modified with cations such as aluminum ions, as described, for example, in WO 01 / 98227, U.S. Pat. No. 5,368,833, and by Iler in *The Chemistry of Silica*, John Wiley and Sons (1979).

[0056] In embodiments, colloidal silica is prepared from a soluble silicate (e.g., water glass) or polysilicic acid solution by ion exchange or treatment with an acid to convert the soluble silicate to a polysilicic acid (typically having a pH in the range of 1-3) and then adding an alkali metal or [NR p 4] + This can be achieved by raising the pH to above 7, typically 8-12, for example 8.5-11, using a basic salt such as a hydroxide or silicate of

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

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

[0059] The colloidal silica particles can have an average primary particle diameter in the range of 2 to 150 nm, for example, 2 to 100 nm, or 3 to 75 nm. In a further embodiment, the particle diameter is in the range of 4 to 50 nm.

[0060] The average particle diameter can be calculated from the titration surface area using the method described by Iler, K. Ralph in "The Chemistry of Silica," page 465, John Wiley & Sons (1979). For silica particles with a mass of 2.2 g cm -3 and based on the assumption that all particles are the same size, have smooth planar areas, and are spherical, the mean particle diameter (PD) can be calculated from Equation 1:

[0061]

number

[0062] Other methods for measuring average particle diameter include ES-DMA (electrospray differential mobility spectroscopy), CLS (liquid phase centrifuge spectroscopy), SEM (scanning electron microscopy), and TEM (transmission electron microscopy).

[0063] The density of silica sol depends, at least in part, on the silica content, but is typically between 1.01 and 1.30 g cm -3 In one embodiment, the range is 1.2 gcm -3 is less than.

[0064] The viscosity of colloidal silica is typically less than 40 cP, for example less than 30 cP, particularly less than 20 cP. In an embodiment, the viscosity is less than 10 cP. These viscosities are measured at 20.0°C. The viscosity of silica sol can be measured using a conventional rotational viscometer, including the one described herein. A method that can be used is ASTM D4016-14.

[0065] In aqueous systems, colloidal silica particles are often soluble in alkali metals (e.g., K + , Na + , Li + ), and the formula [NR4] + The dispersion can be carried out in the presence of a stabilizing cation which can be selected from the ammonium or amino ions of the formula: where R is as defined above. Typically, these are alkali metal and ammonium (NH + ) wherein alkali metal ions are often undesirable for, for example, high purity chromatographic separation applications, and in a preferred embodiment, ammonium ions are used.

[0066] Examples of sols that can be used as the starting aqueous silica sol include silica sols sold by Nouryon under the names Levasil™ or Bindzil™, in particular alkali metal-free grades such as those in

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

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

[0069] [ka] ·Rd 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 C optionally substituted with one or two groups each selected from 1~6 alkyl groups, T, independently in each occurrence, represents one or more C 1~3 C optionally substituted with alkyl groups 1~3 Alkylene units (e.g., C 2~3 alkylene units), 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 those in which all occurrences of T are C2 ethylene groups, such as ethylenediamine (EDA), diethylenetriamine (DETA), triethylenetetramine (TETA), tetraethylenepentamine (TEPA), pentaethylenehexamine (PEHA), piperazine (PIP), aminoethylpiperazine (AEP), hydroxyethylethylenediamine (HE-EDA), hydroxyethyldiethylenetriamine (HE-DETA), hydroxyethyltriethylenetetramine (HE-TETA), hydroxyethylpiperazine (HEP), methylethylenediamine (MeEDA, i.e., Me-NH-CH2-CH2-NH2), and tetramethylethylenediamine (TMEDA, i.e., Me2N-CH2CH2-NMe2).

[0072] Further examples include those in which at least one, and optionally all, occurrences of T are C3 propylene groups, such as propylene diamine (PDA), dipropylene triamine (DPTA), tripropylene tetramine (TPTA), 1,5-diazocane (DAZ), aminopropyl-1,5-diazocane (AP-DAZ), hydroxypropyl propylene diamine (HP-PDA), hydroxypropyl dipropylene triamine (HPDPTA), hydroxypropyl propylene diamine (HP-PDA), hydroxypropyl dipropylene triamine (HP-DPTA), hydroxypropyl tripropylene tetramine (HP-TPTA), and hydroxypropyl-1,5-diazocane (HP-DAZ).

[0073] Still further examples include those in which at least one, and optionally all, occurrences of T are C2 alkylene groups with methyl substituents, such as isopropyldiamine (iPDA) and diisoprylaminetriamine (DiPTA).

[0074] Still further examples include those in which the T group is selected from C2 alkylene, methyl-substituted C2 alkylene, and C3 alkylene, such as aminopropylethylenediamine (AP-EDA), diaminopropylethylenediamine (DAP-EDA), diaminoisopropylethylenediamine (DAiP-EDA), and aminopropylpiperazine (AP-PIP).

[0075] Thus, in embodiments, T is selected from C2 alkylene, monomethyl-substituted C2 alkylene, and C3 alkylene units. In further embodiments, p is a non-negative integer in the range of 0 to 4, 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.

[0076] For compounds where p is 2 or greater, different isomers can exist. For example, TETA, TEPA, and PEHA 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 are also those in which one or more A groups are optionally methyl-substituted C2 alkylene groups, and 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 C 1~6 Alkyl, e.g., H or C 1~2 In embodiments, T is an unsubstituted C 2~3 alkylene. X is O and NR d wherein R d is 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, hydrobromic, or hydroiodic acid), halogen acids (e.g., chloric, bromic, or iodic acid, HIO), perhalogen acids (e.g., perchloric, perbromic, periodic), nitric acid, nitrous acid, sulfuric acid, sulfurous acid, phosphoric acid, and phosphorous acid.

[0089] Suitable organic Bronsted acids include carboxylic acids, e.g., organic compounds of formula A, containing one or more COOH groups. Typically, the organic acid is a C carboxylic acid containing one or more COOH groups, e.g., 1, 2, or 3 COOH groups. 1~8In embodiments, the carboxylic acid can be formed in situ, for example, by using the corresponding acyl halide (e.g., acyl chloride, bromide, or iodide) or anhydride and providing conditions under which it is hydrolyzed (e.g., through reaction with water) to produce the carboxylic acid. The organic acid can contain two or more carboxylic acid groups, for example, two or three carboxylic acid groups. Examples include C 1~8 Examples of carboxylic acids include carboxylic acids, dicarboxylic acids, and tricarboxylic acids. Carbonic acids are also included. Specific examples of carboxylic acids include acetic acid, citric acid, and oxalic acid.

[0090] The organic acid may be a sulfonic acid or a phosphonic acid. Examples of sulfonic and phosphonic acids include those of formula R c SO3H and R c R2PO3H, wherein R and R c is as defined above].

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

[0092] In an embodiment, the Bronsted acid is an organic acid or a salt thereof. In a further embodiment, the organic acid is a carboxylic acid, a carbonic acid, or an oxalic acid. Organic acids have the advantage that they do not leave residues (e.g., in the form of non-volatile nitric acid or phosphoric acid moieties) on the silica surface after high-temperature calcination, a process step that may be used in preparing porous silica. For the same reason, when salts of organic acids are used, they are preferably [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 embodiments, the amino acids may be of 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 C optionally substituted with one or more groups selected from -OH 5~10 Aromatic groups; and R a and C optionally substituted with one or more groups selected from -OH 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 and heterocyclic aliphatic groups, each of which may be R a and —OH.

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

[0098] To aid in the stabilization of the water-in-oil emulsion, one or more emulsifiers can be used, which can be selected from organic emulsifiers, which are typically anionic, cationic, amphoteric, zwitterionic, or nonionic surfactants, and are commonly known and commercially available.

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

[0100] Further examples of emulsifiers include sorbitan esters (such as those sold under the Span™ trade name), such as sorbitan monolaurate (e.g., Span™ 20), and sorbitan monooleate (e.g., Span™ 80). Further examples include polyethoxylated sorbitan esters (such as those sold under the Tween™ trade name), such as PEG-20 sorbitan monolaurate (Tween™ 20), PEG-20 sorbitan monooleate (Tween™ 80), and polyoxyethylene sorbitan trioleate (Tween™ 85). Other examples include C6-C8 sorbitan monolaurates (e.g., Span™ 20), PEG-20 sorbitan monooleate (Tween™ 80), and polyoxyethylene sorbitan trioleate (Tween™ 85). 22 Alkyl sulfates, such as sodium dodecyl sulfate; n H 2n+1 (OC m H 2m ) p -OSO3 - wherein n is 6 to 22, m is 2 to 3, and p is 2 to 4, 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 1~4glucamides of alkyl groups, such as caprylmethyl glucamide, laurylmethyl glucamide, and dodecyl glucamide; C 2~16 Carboxylate-substituted amino acids and their salts, such as sodium or disodium cocoyl glutamate, and sodium lauroyl sarcosinate; C 6~22 Fatty acids and their salts, such as sodium oleate and potassium oleate; polyethylene glycol-substituted phenols having 5 to 25 glycol units, such as polyethylene glycol p-(1,1,3,3-tetramethylbutyl)-phenyl ether (available as Triton™ X-100); 6~22 Alkylamine oxides, such as lauramine oxide and C 6~22 Alkyl alcohols, such as cetyl alcohol and stearyl alcohol, are included. Further examples include polymeric emulsifiers, such as (meth)acrylate polymers and (meth)acrylic acid polymers (e.g., polymethyl methacrylate), and at least one C 3~10 an alkenyl group and at least one C 1~4 Examples of the polymer include organoammonium salts having alkyl groups, such as polydiallyldimethylammonium chloride (polyDADMAC).

[0101] Often in combination with an emulsifier, one or more protective colloids can be used, examples of which include polyvinyl alcohol or polyvinylpyrrolidone.

[0102] The polyvinyl alcohol can be optionally partially or fully saponified. In embodiments, the polyvinyl alcohol has a degree of hydrolysis in the range of 70-100 mol%, e.g., 80-100 mol%, or 80-98 mol%. The Hoppler viscosity in a 4% aqueous solution can be in the range of 1-70 mPas, or in other embodiments, 3-40 mPas (measured at 20°C according to DIN 53015).

[0103] One or more thickening agents may be used, for example selected from water-soluble polysaccharide or protein-based thickeners, cellulose derivatives and starches.

[0104] The cellulose derivatives include alkyl cellulose ethers, hydroxyalkyl cellulose ethers, carboxyalkyl cellulose ethers, hydroxyalkyl polyoxyalkyl cellulose ethers, and mixed ethers having at least two different substituents selected from alkyl, hydroxyalkyl, carboxyalkyl, and / or hydroxyalkyl polyoxyalkyl. The alkyl groups are C1 to C6. 10 The alkyl group may be an alkyl group. Cellulose derivatives may also or alternatively be used as emulsifiers.

[0105] The cellulose ethers may have a degree of substitution (DS) ranging from 1.2 to 2.9, e.g., from 1.6 to 2.2, but may also reach a maximum of 3, which means complete etherification of the cellulose. The substituents may be C alkoxy groups, e.g., methoxy, ethoxy, and / or propoxy groups. 1~4 In embodiments, the at least one thickening agent is selected from methyl cellulose, ethyl cellulose, propyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, methyl hydroxymethyl cellulose, methyl hydroxyethyl cellulose, methyl hydroxypropyl cellulose, ethyl hydroxymethyl cellulose, ethyl hydroxyethyl cellulose, ethyl hydroxypropyl cellulose, propyl hydroxymethyl cellulose, propyl hydroxyethyl cellulose, and propyl hydroxypropyl cellulose.

[0106] Other polysaccharides that can be used include chemically modified or unmodified polysaccharides such as guar, dextran, chitin, chitosan, mannan, galactan, xylan, starch, xanthan gum, welan gum, gellan gum, alginates, arabinoxylan, glucan, and pectin.

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

[0108] One or more gelation accelerators can also be used. Examples include quaternary ammonium compounds containing a C1-4 alkyl group, optionally substituted with one or more groups selected from —OH and halide (e.g., fluoride or chloride), such as [3-chloro-2-propyl]trimethylammonium chloride. Another example of an accelerator is 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 contains nanoparticulate silica, for example, by suspending nanoparticulate silica in solid form in an aqueous medium or by using aqueous colloidal silica as a source of nanoparticulate silica.

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

[0112] In embodiments, the organic compound (or at least one of the organic compounds) forming the "oil" phase has a boiling point higher than that of water, i.e., greater than 100°C, e.g., 110°C or higher, 150°C or higher, etc. In embodiments, the boiling point is 400°C or lower.

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

[0114] The organic compounds are typically in the liquid phase at room temperature (atmospheric pressure, i.e., 25°C at 1.013 bara) and can be selected from those whose molecules contain polar groups, such as one or more groups selected from esters, amides, aldehydes, ketones, alcohols (including glycols), ethers, and sulfoxides. In embodiments, the organic molecules have 3 to 12 carbon atoms. The esters, ketones, and ethers can, in embodiments, be part of a cyclic structure.

[0115] In embodiments, the organic compound may additionally or alternatively be non-polar, e.g., selected from an alkane or aromatic compound optionally substituted with one or more halides (e.g., F, Cl, Br, or I). Examples include C 1~20 Paraffin, C 1~20 Haloparaffin, C 6~20 Aromatic compounds, and C 6~20 The aromatic compound or haloaromatic compound may be one or more C 1~10 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, isopropyl formate, n-propyl acetate, isopropyl acetate, isobutyl acetate, n-butyl acetate, n-pentyl formate, isopentyl formate, n-pentyl acetate, isopentyl acetate, ethyl propionate, isobutyl isobutyrate, n-butyl propionate, ethyl 3-ethoxypropionate, 2-ethylhexyl acetate, diethyl ketone, methyl isobutyl ketone, methyl isoamyl ketone, methyl n-amyl ketone, mesityl oxide, acetophenone, cyclohexanone, diethyl phthalate, benzyl acetate, methylcyclohexanone, benzaldehyde, benzyl alcohol, diisopropyl ether, anisole, and phenetole. 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., basic aqueous colloidal silica as described above) is mixed with an organic medium to form a water-in-oil dispersion or emulsion. Emulsions are preferred because they avoid the need for active procedures, such as vigorous stirring, to maintain dispersion of the aqueous droplets containing the nanoparticulate silica over time. The organic medium comprises at least one or more water-insoluble or partially water-soluble organic solvents, as described above.

[0120] The nanoparticulate silica is present in the aqueous phase. The amine compound and acid or amino acid in the system may also be water-miscible, such that they are completely or predominantly mixed in the aqueous phase, i.e., they are water-soluble or at least partially water-soluble, for example, at least 1% by weight, e.g., at least 10% by weight, or at least 20% by weight (i.e., at least 10 g / m ) under ambient conditions (i.e., atmospheric pressure, 25°C). -3 , e.g., at least 100gdm -3 , or at least 200gdm -3 In embodiments where the water solubility is only partial, the amounts used are such that they are within the water solubility limits.

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

[0122] The silica content (based on the dry weight of SiO2) in the total synthesis mixture can be in the range of 0.01 to 50 wt%, for example, 0.1 to 30 wt%, 0.5 to 15 wt%, or 1 to 10 wt%.

[0123] The weight ratio of Bronsted acid or amino acid to silica (based on the dry weight of SiO 2 ) can be in the range of 0.005:1 to 1:1, such as 0.01:1 to 0.6:1, or 0.01:1 to 0.3:1.

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

[0125] In the above ratios, when more than one amino acid, amino compound, or Bronsted acid is present, 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 is achieved by removing water from the system, typically by using heat and / or reduced pressure. Other conditions may also be controlled to aid gelation.

[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 aqueous phase of the dispersion / emulsion, may be in the range of 5 to 9. To control the pH, an acid or base may be added. For example, a Bronsted acid, an amino compound, or an amino acid, as defined above, may be used. Other basic compounds that may be used include alkali metal hydroxides, alkaline earth metal hydroxides, ammonia or ammonium hydroxide, or [NR p 4] + The hydroxides of ions, typically ammonium ions, are used. In embodiments, a basic pH is used. In embodiments, alkali metal hydroxides and alkaline earth metal hydroxides are avoided so that no metal residues remain in the porous silica after gelation, washing, and calcination.

[0129] Typical gelation conditions include temperatures of 0 to 100° C. To increase the rate of gelation, higher temperatures can be used, for example, in the range of 50 to 100° C., or 55 to 95° C. Higher temperatures tend to increase the rate of water evaporation.

[0130] Pressures in the range of 0.01 to 1.10 bara (bar absolute) may be used, and in embodiments, reduced pressures are used to assist water evaporation, for example, pressures in the range of 0.01 to 0.50 bara, for example, 0.03 to 0.25 bara.

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

[0132] Previously used methods that do not use the combination of acid and amine compounds or amino acids defined above have not been able to achieve silica with the required combination of large pore size and large pore volume characteristics. Typically, large pore sizes can be achieved, but the pore volumes are much smaller, resulting in significantly reduced separation efficiency when used as a stationary phase.

[0133] Without being bound by theory, it is believed that the amine compound and the Bronsted acid act as salts, shielding the charge of the silica nanoparticles and reducing electrostatic repulsion. This facilitates interparticle Si-O-Si bonding, helping the silica nanoparticles present in the aqueous droplets to bond with each other at a faster rate than would otherwise be achieved by simply reducing the water content of the dispersion (e.g., through evaporation). This increased gelation rate results in larger pore volume and surface area. An additional benefit is a narrower pore size distribution, which is a desirable property for helping to achieve even greater improvements in chromatographic separation efficiency. [Example]

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

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

[0136] With constant stirring, 91.6 g of 14 wt. % aqueous colloidal silica (prepared by dilution of 40 wt. % Levasil® CS40-614P silica sol, which yielded 130 ml by titration according to Sear's method) was added. 2 g -1 Silica particles (having a surface area of ​​0.01g) were added. Stirring was continued for 30 minutes to ensure a stable water-in-oil emulsion.

[0137] 0.16 g of glacial acetic acid, 0.22 g of tetrabutylammonium hydroxide, 0.34 g of ethylenediamine, 0.22 g of butylamine, and 0.27 g of water were added. The resulting emulsion was heated to 75°C using a heating jacket and distilled under reduced pressure (200 mbar absolute pressure). After 117 ml of emulsion liquid was distilled, the reactor was cooled to room temperature. The remaining benzyl alcohol and silica-containing suspension were centrifuged, the benzyl alcohol 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. It was then 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 To a round-bottom flask, 50 g of benzyl alcohol was added. 4.5 g of emulsifier solution was also added. The emulsifier solution was prepared from a mixture of 4.2 g of water, 0.23 g of hexamethylenetetramine, and 38 mg of cellulose ether (Bermocoll E230X). The benzyl alcohol / emulsifier mixture was stirred until homogeneous, and then 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 and rotated at room temperature for 30 minutes until a stable water-in-oil emulsion was formed. 23 mg of a 76% (wt / wt) aqueous solution of acetic acid and 91 mg of an 87% (wt / wt) aqueous solution of ethylenediamine were added to the emulsion. The emulsion was then heated to a temperature of 70°C using a heating bath attached to the rotary evaporator under a vacuum of 160 mbar. After distilling off approximately 10 mL of the liquid phase, the flask was cooled to room temperature. The remaining contents were filtered to remove the porous silica, which was then washed with 40 g of ethanol. The silica was resuspended in 40 g of ethanol, refiltered, and washed with another 40 g of ethanol. The silica was then 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 132 m 2 g -1 The average pore size was 262 Å, and the D90 / D10 value was 2.24.

[0140] [Example 3] 1500cm equipped with an overhead stirrer 3To the reactor, 900 g of benzyl alcohol was added, followed by 82 g of emulsifier solution. The emulsifier solution was made from 77.1 g of water, 4.2 g of hexamethylenetetramine, and 0.7 g of cellulose ether (Bermocoll E230X). The mixture was stirred until homogeneous, and then, with constant stirring, 92.2 g of 20% (wt / wt) silica sol, made by diluting the same 40 wt% silica sol as in Example 1, was added. Stirring was continued for 30 minutes to produce a stable water-in-oil emulsion. After 30 minutes, 0.92 g of a 76% (wt / wt) aqueous solution of acetic acid and 1.83 g of an 87% (wt / wt) aqueous solution of ethylenediamine were added to the emulsion. The emulsion was then heated (water bath temperature 75°C) under a reduced pressure of 200 mbar. After approximately 120 mL of emulsion liquid was distilled, 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 benzyl alcohol 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 another wash with 120 g of ethanol. The silica was resuspended, refiltered, and rewashed in the same manner once more. The resulting 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 The average pore size was 273 Å, and the D90 / D10 value was 1.81.

[0141] [Example 4] 1500cm equipped with an overhead stirrer 3800 g of benzyl alcohol was added to the reactor along with 73 g of emulsifier solution. The emulsifier solution was made from 68.6 g of water, 3.7 g of hexamethylenetetramine, and 0.6 g of cellulose ether (Bermocoll E230X). 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. The mixture was stirred for an additional 30 minutes to achieve a stable water-in-oil emulsion, after which 0.92 g of a 76% (wt / wt) aqueous solution of acetic acid and 1.83 g of an 87% (wt / wt) aqueous solution of ethylenediamine were added. The emulsion was then heated under 200 mbar pressure (water bath temperature 75°C). When approximately 120 mL of liquid had distilled, 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 benzyl alcohol was decanted, and the silica was filtered and washed with 120 g of ethanol. The silica was resuspended in 120 g of ethanol, filtered again, and washed with another 120 g of ethanol. The silica was resuspended, refiltered, and rewashed in the same manner once more. The resulting silica was then 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, the average 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 silica with relatively small pore sizes, with an average pore diameter of 100 Å, 319 m 2 g -1 of surface area, and 0.84 cm 3 g -1 The pore volume was 1000 .mu.m.

[0145] The resulting material was then subjected to Ostwald ripening to grow the particles and increase the average pore diameter. 3 A steel autoclave was charged with 31 g of silica along with 619 g of water and 73 g of 25% aqueous ammonia solution. The autoclave was sealed and heated to 120°C for 116 hours. After cooling to 30°C, 105 g of 63 wt% nitric acid was added. The silica was then filtered and washed with 300 g of water followed by 158 g of acetone. The silica was then dried in an oven at 90°C for 16 hours. This process was repeated six times. The resulting silica had the properties set forth in Table 2.

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

[0147] This narrow pore size distribution is evident from FIG. 2, which compares the distributions for Example 2 and Comparative Example 5.

[0148] [Table 2]

[0149] [Comparative Examples 11 to 15] Five commercially available butyl-modified silicas with pore sizes of approximately 300 Å and particle sizes of 10 or 15 μm were calcined in air at 650°C for 5 hours to remove the organic modification. This calcination process does not significantly affect the porous characteristics of the silica (see Examples 16-17 below). The properties of the resulting silicas are shown in Table 3.

[0150] The pore size distribution (D90 / D10) of the commercial samples is significantly larger than that of the silica prepared by the method described herein. It is noteworthy that Example 15, which has the smallest pore size distribution among the comparative examples, has a significantly larger pore volume than the inventive examples. This is an indication of a decrease in the mechanical strength of the silica.

[0151] [Table 3]

[0152] The following examples show that calcining organo-modified silica does not have a significant effect on the properties of the resulting silica.

[0153] [Example 16] The silica sample was post-treated in a manner equivalent to that described in Example 1(4) of EP 0298062, and after post-treatment, 0.94 mL g -1 Pore ​​volume of 122m 2 g -1 and an average pore size of 307 Å. The pore size distribution D90 / D10 was 2.07 and the D50 was 389 Å.

[0154] 7 g of this "rehydroxylated" silica was added to 250 cm 3 Disperse the mixture in 139 g of toluene in a three-necked glass flask, and evaporate to a volume of approximately 40 cm 3 The mixture was heated to the boiling point until 2.1 g of liquid was removed. The temperature was then reduced to 90°C, and 2.1 g of pyridine and 2 g of butyldimethylchlorosilane were added. The silica dispersion was heated to reflux overnight. After 16 hours, the temperature was reduced to room temperature, and 32 g of ethanol was added to deactivate the remaining silane. The silica 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. Elemental analysis gave a carbon content of 2.6 wt%, which corresponds to 3.1 μmol m -2 corresponds to a ligand coverage of

[0155] [Example 17] To burn off the silane, 3 g of the organo-modified silica of Example 16 was calcined in air at 650° C. for 5 hours. The pore volume after post-treatment was 0.89 mL g. -1 and its surface area is 120m 2 g -1The average pore size was 299 Å, the pore size distribution D90 / D10 was 2.07, and the D50 was 371 Å. The present invention includes the following aspects. Section 1. An average pore diameter of at least 210 Å and at least 0.80 cm 3 g -1 Porous silica having a pore volume of Section 2. The pore diameter is up to 500 Å and / or the pore volume is up to 1.2 cm 3 g -1 Item 2. The porous silica according to Item 1, Section 3. The following conditions (i) the pore volume is at least 0.84 cm 3 g -1 is (ii) the pore volume is at most 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) Specific surface area is 50 to 500 m 2 g -1 and / or between 80 and 300 m 2 g -1 is within the range (vi) The surface is modified with one or more organic groups. (vii) the pore size distribution, D90 / D10, is within the range of 0.10 to 2.30, or 1.00 to 2.30; (viii) The porous silica is in solid form. Item 1 or 2. The porous silica according to item 1 or 2, wherein one or more of the following applies: Section 4. Item 1. A process for producing porous silica according to Item 1, comprising gelling liquid-phase dispersed nanoparticulate silica in the presence of (i) a Bronsted acid and an amine compound having two or more amine groups selected from a primary amine group and a secondary amine group, or (ii) an amino acid. Section 5. Item 5. The process according to Item 4, wherein the primary particles of the nanoparticulate silica have an average diameter in the range of 2 to 200 nm, and / or the liquid phase dispersion of the nanoparticulate silica is a water-in-oil emulsion or dispersion, wherein the aqueous phase comprises the nanoparticulate silica and any Bronsted acid, amine compound, and amino acid, and the oil phase comprises at least one organic compound that is insoluble in water or partially soluble in water, and the solubility of the organic compound in water and / or the solubility of water in the organic compound is 10% by weight or less. Section 6. 6. The process of claim 4 or 5, wherein the nanoparticulate silica is in the form of colloidal silica. Section 7. The following conditions (i) the colloidal silica is aqueous, made from a soluble silicate or polysilicic acid solution, and has a pH in the range of 8 to 12; (ii) the colloidal silica has an S value in the range of 10 to 95%; (iii) The colloidal silica particles are 50 to 1000 m 2 g -1 having a surface area in the range Item 7. The process of item 6, wherein one or more of the following applies: Section 8. the amine compound has a formula according to any one of Formulas 1-3, [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 C optionally substituted with one or two groups each selected from 1~6 alkyl groups, A, independently in each occurrence, optionally represents one or more C1~3 C substituted by alkyl groups 1~3 Alkylene units (e.g., C 2~3 alkylene units), X, independently in each occurrence, is -O-, -NR d - and [ka] 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 of any one of paragraphs 4 to 7. Section 9. 9. The process of any one of paragraphs 4 to 8, wherein the acid is an organic acid optionally selected from oxalic acid, carbonic acid, carboxylic acid, sulfonic acid, and phosphonic acid. Section 10. The carboxylic, sulfonic, and phosphonic acids are represented by the formula RC(O)OH, R c -SO3H, and R c R2PO3H, wherein Each R is independently H, optionally substituted C 1~30 Aliphatic groups, optionally substituted C 5~10 Aryl groups, and optionally substituted C 5~10 heteroaryl groups; ·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, The process according to paragraph 9. Section 11. ·Above C 1~30 The aliphatic group may be saturated or unsaturated, linear, branched, or cyclic; C 1~30 Each of the aliphatic organic groups is -OR, -C(O)OH, -C(O)OR, -C(O)NR2, -OC(O)R, -NRC(O)R, -NR-C(O)-NR2, -NR2, -[NR3]+ , halide, epoxy, oxo, C 5~6 Aromatic group, C 5~6 Heteroaromatic 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 glycol ether groups of the formula: ·Above C 5~10 Aryl groups and C 5~10 Each heteroaryl group is selected from the group consisting of -OR, -C(O)OH, -C(O)OR, -C(O)NR2, -OC(O)R, -NRC(O)R, -NR-C(O)-NR2, -NR2, and -[NR3] + , halide, epoxy, oxo, C 1~30 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 glycol ether groups of the formula: During the ceremony, Each R is hydrogen, C 1~30 aliphatic group, C 5~6 Aromatic groups, and C 5~6 heteroaromatic groups; ·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 between 2 and 3, m is an integer between 2 and 20, and in the formula: In the optional substituents, any aromatic, heteroaromatic, aliphatic, alkyl, or alkoxy group may be hydroxyl, C 1~4 which may itself be optionally substituted by one or more substituents selected from alkoxy, carboxyl, halide, and —NH; The process of paragraph 10, wherein any heteroaromatic or cycloaliphatic group can have one or more heteroatoms in the ring selected from O, S, and N, typically O or N. Section 12. The following conditions (i) The weight ratio of the amine compound and / or the amino acid to silica (based on the dry weight of SiO2) is within the range of 0.005 to 1. (ii) The silica content (based on the dry weight of SiO2) of the total synthetic mixture is in the range of 0.001 to 50 wt.%. (iii) the weight ratio of the organic acid and / or amino acid to silica (based on the dry weight of SiO2) is within 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 compounds of formula (1) and formula (2) described in item 8. 12. The process of any one of paragraphs 4 to 11, wherein one or more of the following applies: Section 13. 13. The process of any one of paragraphs 4 to 12, wherein the porous silica is separated from the liquid phase and optionally modified with one or more organic groups. Section 14. 4. Use of the porous silica according to any one of paragraphs 1 to 3 as a stationary phase in chromatography. Section 15. A separation column or container comprising the porous silica according to any one of items 1 to 3.

Claims

1. Average pore diameter of at least 210 Å and at most 350 Å, at least 0.80 cm ３ g －１ and a maximum of 1.0 cm ３ g －１ and a pore size distribution (D90 / D10) of 1.50 to 2.

30.

2. The pore volume is at least 0.84 cm ３ g －１ 2. The porous silica according to claim 1, wherein

3. 3. The porous silica of claim 1, wherein the average pore diameter is at least 250 Å.

4. Specific surface area: 80 to 300 m ２ g －１ 4. The porous silica according to claim 1, wherein the molecular weight of the porous silica is in the range of:

5. 5. A porous silica according to any one of claims 1 to 4, the surface of which is modified with one or more organic groups.

6. 6. The porous silica of claim 1, wherein the porous silica is in solid form.

7. A liquid-phase dispersed nanoparticulate silica having an average pore diameter of at least 210 Å and a pore size of at least 0.80 cm is gelled in the presence of (i) an amine compound having two or more amine groups selected from a primary amine group and a secondary amine group, or (ii) an amino acid. ３ g －１ 1. A process for producing porous silica having a pore volume of

8. 8. The process of claim 7, wherein the primary particles of the liquid-phase-dispersed nanoparticulate silica have an average diameter in the range of 2 to 200 nm, and / or the liquid-phase dispersion of the liquid-phase-dispersed nanoparticulate silica is a water-in-oil emulsion or dispersion, wherein the aqueous phase comprises the liquid-phase-dispersed nanoparticulate silica and, optionally, a Bronsted acid, an amine compound, and an amino acid, and the oil phase comprises at least one organic compound that is insoluble in water or partially soluble in water, and wherein the solubility of the organic compound in water and / or the solubility of water in the organic compound is 10% by weight or less.

9. 9. The process of claim 7 or 8, wherein the liquid phase dispersed nanoparticulate silica is in the form of colloidal silica.

10. 10. The process of claim 9, wherein the colloidal silica is aqueous, made from a soluble silicate or polysilicic acid solution, and has a pH in the range of 8 to 12.

11. 11. The process of claim 9 or 10, wherein the colloidal silica has an S value in the range of 10 to 95%.

12. The colloidal silica is 75 to 300 m ２ g －１ 12. The process according to claim 9, wherein the specific surface area is in the range of

13. 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 C optionally substituted with one or two groups each selected from １～６ alkyl groups, A, independently in each occurrence, optionally comprises one or more C １～３ C substituted by alkyl group １～３ Alkylene units (e.g., C ２～３ alkylene units), 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; 13. The process according to any one of claims 7 to 12.

14. 14. The process of any one of claims 7 to 13, wherein the Bronsted acid is an organic acid optionally selected from oxalic acid, carbonic acid, carboxylic acid, sulfonic acid, and phosphonic acid.

15. 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 C ５～１０ aryl groups, and optionally substituted C ５～１０ heteroaryl groups; ・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, 15. The process of claim 14.

16. ・C above １～３０ The aliphatic group may be saturated or unsaturated, linear, branched, or cyclic; ・C above １～３０ Each of the aliphatic groups 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, oxo, C ５～６ aromatic group, C ５～６ Heteroaromatic 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 glycol ether groups of the formula: ・C above ５～１０ Aryl group and the C ５～１０ Each heteroaryl group is selected from the group consisting of —OR, —C(O)OH, —C(O)OR, and —C(O)NR ２ , -OC(O)R, -NRC(O)R, -NR-C(O)-NR ２ , -NR ２ , -[NR ３ ] ＋ , halide, epoxy, oxo, C １～３０ 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 glycol ether groups of the formula: During the ceremony, Each R is hydrogen, C １～３０ aliphatic group, C ５～６ Aromatic groups, and C ５～６ heteroaromatic groups, ・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, heteroaromatic, aliphatic, alkyl, or alkoxy group may be selected from the group consisting of hydroxyl, C １～４ Alkoxy, carboxyl, halide, and —NH ２ which may themselves be optionally substituted by one or more substituents selected from 16. The process of claim 15, wherein any heteroaromatic or cycloaliphatic group may have one or more heteroatoms in the ring selected from O, S, and N, typically O or N.

17. The weight ratio of the amine compound and / or the amino acid to silica (SiO ２ 17. The process of any one of claims 7 to 16, wherein the % saturation energy (based on the dry weight of the product) is in the range of 0.005 to 1.

18. Silica content (SiO ２ 18. The process according to any one of claims 7 to 17, wherein the amount of the cellulose acetate derivative (based on the dry weight of the cellulose acetate derivative) is in the range of 0.001 to 50 wt.%.

19. The weight ratio of the Bronsted acid and / or the amino acid to silica (SiO ２ 19. The process of any one of claims 7 to 18, wherein the ratio of the hydroxybenzoates to the total hydroxybenzoates (based on the dry weight of the hydroxybenzoates) is in the range of 0.005:1 to 1:

1.

20. 20. The process of any one of claims 7 to 19, wherein the weight ratio of the Bronsted acid to the amine compound is in the range of 0.02:1 to 1:

1.

21. 21. The process of any one of claims 7 to 20, wherein the amine compound is selected from those of formula 1 and formula 2 of claim 13.

22. 22. The process of any one of claims 7 to 21, wherein the porous silica is separated from the liquid phase and optionally modified with one or more organic groups.

23. 7. Use of the porous silica according to any one of claims 1 to 6 as a stationary phase in chromatography.

24. A separation column or vessel comprising the porous silica of any one of claims 1 to 6.

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