JP5993553B2 - Method for producing filler - Google Patents

Description

  The present invention relates to a method for producing a filler, a filler, and a column.

  Conventionally, as a packing material packed in a column used in liquid chromatography, those obtained by chemically modifying silanol groups on the surface of silica gel by silylation with various silane coupling agents have been widely used. Examples of the silane coupling agent include an octadecyl chlorosilane compound, an octyl chlorosilane compound, a butyl chlorosilane compound, a cyanopropyl chlorosilane compound, a phenyl chlorosilane compound, and the like, among which the octadecyl chlorosilane compound is most widely used.

  However, such a filler has a problem that silanol groups remain on the surface of silica gel.

  Patent Document 1 discloses a method in which a silanol group remaining in chemically modified silica gel or porous glass is reacted with an end cap agent at a reaction temperature of 250 ° C. or higher in a gas phase.

  However, when such a method is used, there is a problem that the ion exchange group cannot be introduced on the surface of the silica gel or the porous glass, and the durability is low.

Japanese Patent Laid-Open No. 4-212058

  The present invention has been made in view of the above-described problems of the prior art, and is a method for producing a filler that is excellent in durability, can reduce the residual amount of hydroxyl groups, and can introduce ion exchange groups, and the production of the filler. It is an object of the present invention to provide a packing manufactured using the method and a column packed with the packing.

  The invention according to claim 1 is the method for producing a filler, wherein the inorganic particle having a hydroxyl group is a silane having an alkenyl group having 2 to 8 carbon atoms and / or an alkynyl group having 2 to 7 carbon atoms. A first step of reacting with a silane coupling agent containing a coupling agent, and inorganic particles reacted with the silane coupling agent with a hydrosilyl group and a compound having a primary amino group protected by a protecting group; It has the 3rd process of producing | generating a primary amino group by deprotecting the 2nd process made to react and the inorganic particle reacted with this compound.

  The invention according to claim 2 is the method for producing a filler according to claim 1, wherein the compound has the general formula

（式中、Ｒ^１及びＲ^２は、それぞれ独立に、水素原子、クロロ基又は炭素数が１以上４以下のアルキル基であり、Ｒ^３及びＲ^４は、それぞれ独立に、保護基であり、ｍは１以上２０以下の整数であり、ｎは１以上２０以下の整数である。）
で表されることを特徴とする。

(Wherein R ¹ and R ² are each independently a hydrogen atom, a chloro group or an alkyl group having 1 to 4 carbon atoms, and R ³ and R ⁴ are each independently a protecting group, m is an integer from 1 to 20, and n is an integer from 1 to 20.)
It is represented by.

  The invention according to claim 3 is the method for producing a filler, wherein the inorganic particles having a hydroxyl group are silane having an alkenyl group having 2 to 8 carbon atoms and / or an alkynyl group having 2 to 7 carbon atoms. A first step of reacting with a silane coupling agent including a coupling agent; and inorganic particles reacted with the silane coupling agent having a group capable of reacting with a hydrosilyl group and a primary amino group. A second step of reacting with one compound, and inorganic particles reacted with the first compound having a primary diamine, a compound having a primary amino group and a sulfonic acid group, having a primary amino group and a carboxyl group It has the 3rd process made to react with the compound or the compound which has a primary amino group and a quaternary ammonium base, It is characterized by the above-mentioned.

  The invention according to claim 4 is the method for producing a filler according to claim 3, wherein the first compound has the general formula.

（式中、Ｒ^１及びＲ^２は、それぞれ独立に、水素原子、クロロ基又は炭素数が１以上４以下のアルキル基であり、ｌは１以上６０以下の整数である。）
で表され、前記１級ジアミンは、一般式

(In the formula, R ¹ and R ² are each independently a hydrogen atom, a chloro group, or an alkyl group having 1 to 4 carbon atoms, and 1 is an integer of 1 to 60.)
The primary diamine is represented by the general formula

（式中、ｍは１以上２０以下の整数であり、ｎは１以上２０以下の整数である。）
で表され、前記１級アミノ基と４級アンモニウム塩基を有する化合物は、一般式

(In the formula, m is an integer of 1 to 20, and n is an integer of 1 to 20.)
The compound having a primary amino group and a quaternary ammonium base is represented by the general formula:

（式中、Ｒ^１は、水素原子又は炭素数が１以上５以下のアルキル基であり、Ｒ^２、Ｒ^３及びＲ^４は、それぞれ独立に、炭素数が１以上５以下のアルキル基であり、Ｘ⁻は、１価の陰イオンであり、ｌ及びｍは、それぞれ独立に、１以上２０以下の整数であり、ｎは０以上２０以下の整数である。）
で表されることを特徴とする。

(In the formula, R ¹ is a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, and R ² , R ³ and R ⁴ are each independently an alkyl group having 1 to 5 carbon atoms. , X ⁻ is a monovalent anion, l and m are each independently an integer of 1 to 20, and n is an integer of 0 to 20.
It is represented by.

  The invention according to claim 5 is the method for producing a filler, wherein the inorganic particle having a hydroxyl group is a silane having an alkenyl group having 2 to 8 carbon atoms and / or an alkynyl group having 2 to 7 carbon atoms. A first step of reacting with a silane coupling agent containing a coupling agent; and a second step of reacting inorganic particles reacted with the silane coupling agent with a compound having a hydrosilyl group and a quaternary ammonium base. It is characterized by having.

  The invention according to claim 6 is the method for producing a filler according to claim 5, wherein the compound has the general formula:

（式中、Ｒ^１及びＲ^２は、それぞれ独立に、水素原子、クロロ基又は炭素数が１以上４以下のアルキル基であり、Ｒ^３、Ｒ^４、Ｒ^５及びＲ^６は、それぞれ独立に、炭素数が１以上５以下のアルキル基であり、Ｘ⁻は、１価の陰イオンであり、ｌ及びｍは、それぞれ独立に、１以上２０以下の整数であり、ｎは１以上２０以下の整数である。）
で表されることを特徴とする。

(In the formula, R ¹ and R ² are each independently a hydrogen atom, a chloro group, or an alkyl group having 1 to 4 carbon atoms, and R ³ , R ⁴ , R ^5, and R ⁶ are each independently , An alkyl group having 1 to 5 carbon atoms, X ⁻ is a monovalent anion, l and m are each independently an integer of 1 to 20 and n is 1 to 20 Is an integer.)
It is represented by.

  According to a seventh aspect of the present invention, in the method for producing a filler according to any one of the first to sixth aspects, the first step includes the step of treating the inorganic particles having the hydroxyl group with the carbon number of 2. The step of reacting with an alkenyl group having 8 or less and / or a silane coupling agent having an alkynyl group having 2 to 7 carbon atoms, and the inorganic particles reacted with the silane coupling agent, It includes a step of reacting with a silane coupling agent which does not have.

  According to an eighth aspect of the present invention, in the method for producing a filler, the inorganic particles having a hydroxyl group react with a silane coupling agent including a silane coupling agent having a group capable of reacting with a primary amino group. A first step of reacting the inorganic particles reacted with the silane coupling agent with a primary diamine, a compound having a primary amino group and a sulfonic acid group, a compound having a primary amino group and a carboxyl group, or a primary amino It has the 2nd process made to react with the compound which has group and a quaternary ammonium base, It is characterized by the above-mentioned.

  The invention according to claim 9 is the method for producing a filler according to claim 8, wherein the primary diamine is represented by the general formula:

（式中、ｍは１以上２０以下の整数であり、ｎは１以上２０以下の整数である。）
で表され、前記１級アミノ基と４級アンモニウム塩基を有する化合物は、一般式

(In the formula, m is an integer of 1 to 20, and n is an integer of 1 to 20.)
The compound having a primary amino group and a quaternary ammonium base is represented by the general formula:

（式中、Ｒ^１は、水素原子又は炭素数が１以上５以下のアルキル基であり、Ｒ^２、Ｒ^３及びＲ^４は、それぞれ独立に、炭素数が１以上５以下のアルキル基であり、Ｘ⁻は、１価の陰イオンであり、ｌ及びｍは、それぞれ独立に、１以上２０以下の整数であり、ｎは０以上２０以下の整数である。）
で表されることを特徴とする。

(In the formula, R ¹ is a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, and R ² , R ³ and R ⁴ are each independently an alkyl group having 1 to 5 carbon atoms. , X ⁻ is a monovalent anion, l and m are each independently an integer of 1 to 20, and n is an integer of 0 to 20.
It is represented by.

  According to a tenth aspect of the present invention, in the method for producing a filler according to the eighth or ninth aspect, the first step may react the inorganic particles having the hydroxyl group with the primary amino group. Reacting with a silane coupling agent having a group capable of reacting, and reacting the inorganic particles reacted with the silane coupling agent with a silane coupling agent not having a group capable of reacting with a primary amino group A step of causing

  According to the present invention, the filler is manufactured using the method for manufacturing a filler, which is excellent in durability, reduces the residual amount of hydroxyl groups, and can introduce ion-exchange groups, and the method for manufacturing the filler. A packing and a column packed with the packing can be provided.

It is a figure which shows the analysis result of the analysis example 1. FIG. It is a figure which shows the analysis result of the analysis example 2. FIG. It is a figure which shows the analysis result of the analysis example 3.

  Next, the form for implementing this invention is demonstrated with drawing.

  In the first embodiment of the method for producing a filler of the present invention, the inorganic particles having a hydroxyl group are converted into silane couplings having an alkenyl group having 2 to 8 carbon atoms and / or an alkynyl group having 2 to 7 carbon atoms. A first step of reacting with a silane coupling agent containing an agent (hereinafter referred to as a first silane coupling agent), and the inorganic particles reacted with the silane coupling agent are protected by a hydrosilyl group and a protective group. Deprotecting the inorganic particles reacted with the second step of reacting with the compound having a primary amino group, the hydrosilyl group, and the compound having a primary amino group protected by a protecting group. A third step of generating groups. Thus, before introducing a group derived from a compound having a hydrosilyl group and a primary amino group protected by a protecting group onto the surface of the inorganic particle, the hydroxyl group present in the vicinity of the surface of the inorganic particle, and the silane Since the coupling agent is reacted, the residual amount of hydroxyl groups in the vicinity of the surface of the inorganic particles can be reduced and primary amino groups can be introduced.

The protective group is not particularly limited, but a trimethylsilyl group, t-butoxycarbonyl group, benzyloxycarbonyl group, 9-fluorenylmethyloxycarbonyl group, 2,2,2-trichloroethoxycarbonyl group, allyloxycarbonyl group, A trifluoroacetyl group, p-toluenesulfonyl group, 2-nitrobenzenesulfonyl group and the like can be mentioned. Further, R ³ and R ⁴ bonded to the same nitrogen atom may form a ring, and such a protecting group is not particularly limited, and examples thereof include a phthaloyl group.

  Although it does not specifically limit as a compound which has a hydrosilyl group and the primary amino group protected by the protective group, The compound represented by General formula (1) is preferable.

  Although it does not specifically limit as a compound represented by General formula (1), 3- [N, N-bis (trimethylsilyl) amino] propyl dimethylsilane etc. are mentioned, You may use 2 or more types together.

In the compound represented by the general formula (1), when n is 2 to 20, a plurality of R ³ and m may be the same or different.

  In addition, it is derived from the silane coupling agent remaining in the inorganic particles using a known method before deprotecting the inorganic particles reacted with the hydrosilyl group and the compound having a primary amino group protected by a protecting group. The silanol group may be blocked.

  In a second embodiment of the method for producing a filler of the present invention, a first step of reacting inorganic particles having a hydroxyl group with a silane coupling agent containing a first silane coupling agent, and a silane coupling agent A second step of reacting the inorganic particles reacted with the first compound having a group capable of reacting with a hydrosilyl group and a primary amino group; and the inorganic particles reacted with the first compound. It has a third step of reacting a primary diamine, a compound having a primary amino group and a sulfonic acid group, a compound having a primary amino group and a carboxyl group, or a compound having a primary amino group and a quaternary ammonium base. Thus, the surface of the inorganic particle is derived from a primary diamine, a compound having a primary amino group and a sulfonic acid group, a compound having a primary amino group and a carboxyl group, or a compound having a primary amino group and a quaternary ammonium base. In order to react the hydroxyl group existing near the surface of the inorganic particle with the silane coupling agent before introducing the group of, the residual amount of the hydroxyl group near the surface of the inorganic particle is reduced and the primary amino group, Sulfonic acid groups, carboxyl groups or quaternary ammonium bases can be introduced.

  The group capable of reacting with the primary amino group is not particularly limited, and examples thereof include an epoxy group, a halogen group, a chlorocarbonyl group, a carboxyl group, and an isocyanate group.

  Although it does not specifically limit as a 1st compound which has a hydrosilyl group and a group which can react with a primary amino group, The compound represented by General formula (2) is preferable.

  Although it does not specifically limit as a compound represented by General formula (2), 5, 6- epoxy hexyl dimethylsilane etc. are mentioned, You may use 2 or more types together.

  Although it does not specifically limit as primary diamine, The compound represented by General formula (3) is preferable.

  In the compound represented by the general formula (3), when n is 2 to 20, a plurality of m may be the same or different.

  Although it does not specifically limit as a compound represented by General formula (3), Pentaethylenehexamine etc. are mentioned, You may use together 2 or more types.

  Although it does not specifically limit as a compound which has a primary amino group and a sulfonic acid group, Sulfanilic acid etc. are mentioned.

  Although it does not specifically limit as a compound which has a primary amino group and a carboxyl group, 4-aminobutyric acid etc. are mentioned.

  Although it does not specifically limit as a compound which has a primary amino group and a quaternary ammonium base, The compound represented by General formula (4) is preferable.

  The counter ion of the quaternary ammonium base is not particularly limited as long as it is a monovalent anion, and examples thereof include a chloride ion.

In the compound represented by the general formula (4), when n is 2 to 20, a plurality of R ¹ and m may be the same or different.

  Although it does not specifically limit as a compound represented by General formula (4), 3-aminopropyl trimethyl ammonium chloride etc. are mentioned, You may use together 2 or more types.

  The inorganic particles reacted with the silane coupling agent are converted into primary diamine, compound having primary amino group and sulfonic acid group, compound having primary amino group and carboxyl group, or primary amino group and quaternary ammonium base. Before making it react with the compound which has, you may block the silanol group derived from the silane coupling agent which remained in the inorganic particle using a well-known method.

  The third embodiment of the method for producing a filler according to the present invention includes a first step of reacting inorganic particles having a hydroxyl group with a silane coupling agent containing a first silane coupling agent, and a silane coupling agent. And a second step of reacting the inorganic particles reacted with a compound having a hydrosilyl group and a quaternary ammonium base. In this way, before introducing a hydrosilyl group and a group derived from a compound having a quaternary ammonium base on the surface of the inorganic particle, the hydroxyl group present in the vicinity of the surface of the inorganic particle and the silane coupling agent are reacted. The residual amount of hydroxyl groups in the vicinity of the surface of the inorganic particles can be reduced, and a quaternary ammonium base can be introduced.

  Although it does not specifically limit as a compound which has a hydrosilyl group and a quaternary ammonium base, The compound represented by General formula (5) is preferable.

In the compound represented by the general formula (5), when n is 2 to 20, a plurality of R ³ and m may be the same or different.

  Although it does not specifically limit as a compound represented by General formula (5), You may use 2 or more types together.

  In addition, before reacting when the inorganic particle reacted with the silane coupling agent reacts with the compound having a hydrosilyl group and a quaternary ammonium base, it is derived from the silane coupling agent remaining on the inorganic particle using a known method. The silanol group may be blocked.

  When the inorganic particles having a hydroxyl group are reacted with the silane coupling agent in the first step of the first, second and third embodiments of the method for producing the filler of the present invention, a known method is used. For example, the reaction is performed at 0 to 400 ° C. for 30 minutes to 72 hours in the presence of a solvent such as toluene.

  When reacting the inorganic particles reacted with the silane coupling agent with the compound having a hydrosilyl group in the second step of the first, second and third embodiments of the method for producing a filler of the present invention. A known method can be used. For example, the reaction is performed at 50 to 300 ° C. for 2 hours or more in the presence of a solvent such as toluene. As the catalyst, a ruthenium, rhodium, palladium, osmium, iridium or platinum compound can be used, but a palladium compound or a platinum compound is preferred. The palladium compound is not particularly limited, and examples thereof include palladium chloride (II), ammonium tetraamminepalladium chloride (II), palladium oxide (II), palladium hydroxide (II) and the like. The platinum compound is not particularly limited, but platinum (II) chloride, tetrachloroplatinic acid (II), platinum (IV) chloride, hexachloroplatinic acid (IV), ammonium hexachloroplatinate (IV), platinum (II) oxide Platinum hydroxide (II), platinum dioxide (IV), platinum oxide (IV), platinum disulfide (IV), platinum sulfide (IV), potassium hexachloroplatinum (IV), and the like.

  In the third step of the second embodiment of the method for producing a filler of the present invention, inorganic particles reacted with a first compound having a group capable of reacting with a hydrosilyl group and a primary amino group When reacting with a primary diamine, a compound having a primary amino group and a sulfonic acid group, a compound having a primary amino group and a carboxyl group, or a compound having a primary amino group and a quaternary ammonium base, a known method is used. Can be used. For example, the inorganic particles reacted with the compound represented by the general formula (2) are put in water or a mixed solvent of water and methanol in which the compound represented by the general formula (3) or (4) is dissolved. The method of heating is mentioned.

  In the third step of the first embodiment of the method for producing a filler of the present invention, when deprotecting inorganic particles reacted with a compound having a primary amino group protected by a protecting group, it is known. This method can be used. For example, the method of heating the inorganic particle made to react with the compound represented by General formula (1) in methanol is mentioned.

  When the first silane coupling agent has an alkenyl group having 9 or more carbon atoms and / or an alkynyl group having 8 or more carbon atoms, due to steric hindrance, inorganic particles having a hydroxyl group and silane The reaction of the coupling agent is difficult to proceed.

In the compound represented by the general formula (1), (2) or (5), when R ¹ or R ² is an alkyl group having 5 or more carbon atoms, the number of carbon atoms is 2 to 8 due to steric hindrance. Reaction of the compound represented by the general formula (1), (2) or (5) with the inorganic particles into which the alkenyl group and / or the alkynyl group having 2 to 7 carbon atoms is introduced.

  In the first step of the first, second and third embodiments of the filler production method of the present invention, the inorganic particles having a hydroxyl group may be reacted with only the first silane coupling agent. Since the introduction amount of the alkenyl group can be controlled, it is preferable to react with the first silane coupling agent and the silane coupling agent having no alkenyl group or alkynyl group (hereinafter referred to as the second silane coupling agent). . At this time, it is more preferable to react the inorganic particles having a hydroxyl group with a predetermined amount of the first silane coupling agent and then to react with an excessive amount of the second silane coupling agent. Thereby, while the amount of alkenyl groups and / or alkynyl groups introduced on the surface of the inorganic particles can be controlled, the residual amount of hydroxyl groups can be reduced.

  In addition, in 2nd embodiment of the manufacturing method of the filler of this invention, the inorganic particle which has a hydroxyl group is made to react with a 2nd silane coupling agent between a 2nd process and a 3rd process. Also good.

  Moreover, you may make the inorganic particle which has a hydroxyl group react with a 1st silane coupling agent and / or a 2nd silane coupling agent in multiple times.

  The inorganic particles having a hydroxyl group are not particularly limited, and examples thereof include silica, titanium oxide, zinc oxide, zirconium oxide, aluminum oxide, and zeolite. Among these, porous particles having a hydroxyl group such as silica gel, porous glass, and monolithic silica are preferable.

The inorganic particles having a hydroxyl group preferably have an average particle size of 1 to 200 μm, more preferably 3 to 50 μm. The porous particles having a hydroxyl group preferably have a pore size of 1 to 100 nm, more preferably 4 to 50 nm. Furthermore, porous particles having a hydroxyl group preferably a specific surface area of 50 to 800 m ² / g, more preferably 100~600m ² / g.

  In the specification and claims of the present application, an inorganic particle having a hydroxyl group is an organic-inorganic hybrid having a hydroxyl group such as a particle obtained by reacting an inorganic particle having a hydroxyl group with a silane coupling agent having a hydroxyl group. Contains particles.

  The first silane coupling agent is not particularly limited, but the general formula

（式中、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４の少なくとも一つは、炭素数が２〜８のアルケニル基又は炭素数が２〜７のアルキニル基であり、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４の少なくとも一つは、水素原子、ハロゲン基、ヒドロキシル基又は炭素数が１〜４のアルコキシル基であり、上記以外のＲ^１、Ｒ^２、Ｒ^３及びＲ^４は、それぞれ独立に、炭素数が１〜８の置換若しくは無置換のアルキル基、炭素数が２〜８の置換アルケニル基、炭素数が２〜７の置換アルキニル基又は炭素数が６〜１２の置換若しくは無置換のアリール基である。）
で表される化合物、一般式

(In the formula, at least one of R ¹ , R ² , R ^3, and R ⁴ is an alkenyl group having 2 to 8 carbon atoms or an alkynyl group having 2 to 7 carbon atoms, and R ¹ , R ² , R ^At least one of ³ and R ⁴ is a hydrogen atom, a halogen group, a hydroxyl group or an alkoxyl group having 1 to 4 carbon atoms, and R ¹ , R ² , R ³ and R ⁴ other than the above are independently A substituted or unsubstituted alkyl group having 1 to 8 carbon atoms, a substituted alkenyl group having 2 to 8 carbon atoms, a substituted alkynyl group having 2 to 7 carbon atoms, or a substituted or unsubstituted group having 6 to 12 carbon atoms An aryl group.)
A compound represented by the general formula

（式中、ｎは、１〜１００であり、Ｒ^１、Ｒ^２、Ｒ^３及びＲ^４の少なくとも一つは、炭素数が２〜８のアルケニル基又は炭素数が２〜７のアルキニル基であり、上記以外のＲ^１、Ｒ^２、Ｒ^３及びＲ^４は、それぞれ独立に、水素原子、ハロゲン基、ヒドロキシル基、ビニルジメチルシロキシ基、炭素数が１〜４のアルコキシル基、炭素数が１〜８の置換若しくは無置換のアルキル基、炭素数が２〜８の置換アルケニル基、炭素数が２〜７の置換アルキニル基又は炭素数が６〜１２の置換若しくは無置換のアリール基であり、複数のＲ^１及びＲ^３並びに複数存在する場合のＲ^３は、同一であってもよいし、異なっていてもよい。）
で表される化合物、一般式

(In the formula, n is 1 to 100, and at least one of R ¹ , R ² , R ³ and R ⁴ is an alkenyl group having 2 to 8 carbon atoms or an alkynyl group having 2 to 7 carbon atoms. And R ¹ , R ² , R ³ and R ⁴ other than the above are each independently a hydrogen atom, a halogen group, a hydroxyl group, a vinyldimethylsiloxy group, an alkoxyl group having 1 to 4 carbon atoms, or a carbon number of 1 A substituted or unsubstituted alkyl group having 8 to 8 carbon atoms, a substituted alkenyl group having 2 to 8 carbon atoms, a substituted alkynyl group having 2 to 7 carbon atoms, or a substituted or unsubstituted aryl group having 6 to 12 carbon atoms, A plurality of R ¹ and R ³ and a plurality of R ³ when present may be the same or different.)
A compound represented by the general formula

（式中、ｎは、３〜５０であり、複数のＲ^１及びＲ^２の少なくとも一つは、炭素数が２〜８のアルケニル基又は炭素数が２〜７のアルキニル基であり、上記以外のＲ^１及びＲ^２は、それぞれ独立に、水素原子、ハロゲン基、ヒドロキシル基、炭素数が１〜４のアルコキシル基、炭素数が１〜８の置換若しくは無置換のアルキル基、炭素数が２〜８の置換アルケニル基、炭素数が２〜７の置換アルキニル基又は炭素数が６〜１２の置換若しくは無置換のアリール基であり、Ｘは、オキシ基又はイミノ基である。）
で表される化合物、一般式

(In the formula, n is 3 to 50, and at least one of the plurality of R ¹ and R ² is an alkenyl group having 2 to 8 carbon atoms or an alkynyl group having 2 to 7 carbon atoms, other than the above) R ¹ and R ² each independently represent a hydrogen atom, a halogen group, a hydroxyl group, an alkoxyl group having 1 to 4 carbon atoms, a substituted or unsubstituted alkyl group having 1 to 8 carbon atoms, or 2 carbon atoms. A substituted alkenyl group having 8 to 8 carbon atoms, a substituted alkynyl group having 2 to 7 carbon atoms, or a substituted or unsubstituted aryl group having 6 to 12 carbon atoms, and X is an oxy group or an imino group.
A compound represented by the general formula

（式中、複数のＲ^１、Ｒ^２及びＲ^３の少なくとも一つは、炭素数が２〜８のアルケニル基又は炭素数が２〜７のアルキニル基であり、上記以外のＲ^１、Ｒ^２及びＲ^３は、それぞれ独立に、水素原子、ハロゲン基、ヒドロキシル基、炭素数が１〜４のアルコキシル基、炭素数が１〜８の置換若しくは無置換のアルキル基、炭素数が２〜８の置換アルケニル基、炭素数が２〜７の置換アルキニル基又は炭素数が６〜１２の置換若しくは無置換のアリール基であり、Ｘは、単結合、イミノ基又は一般式

(In the formula, at least one of the plurality of R ¹ , R ² and R ³ is an alkenyl group having 2 to 8 carbon atoms or an alkynyl group having 2 to 7 carbon atoms, and R ¹ and R ² other than those described above) And R ³ each independently represents a hydrogen atom, a halogen group, a hydroxyl group, an alkoxyl group having 1 to 4 carbon atoms, a substituted or unsubstituted alkyl group having 1 to 8 carbon atoms, or 2 to 8 carbon atoms. A substituted alkenyl group, a substituted alkynyl group having 2 to 7 carbon atoms, or a substituted or unsubstituted aryl group having 6 to 12 carbon atoms, and X is a single bond, an imino group or a general formula

（式中、Ｒ^４及びＲ^５は、それぞれ独立に、水素原子又はトリメチルシリル基であり、ｎは、１〜８の整数である。）
で表される基である。）
で表される化合物、１，１−ビス（トリメトキシシリルメチル）エチレン等が挙げられ、二種以上併用してもよい。

(In the formula, R ⁴ and R ⁵ are each independently a hydrogen atom or a trimethylsilyl group, and n is an integer of 1 to 8.)
It is group represented by these. )
And compounds such as 1,1-bis (trimethoxysilylmethyl) ethylene may be used, and two or more of them may be used in combination.

  In the general formulas (6) to (9), as the alkenyl group having 2 to 8 carbon atoms or the alkynyl group having 2 to 7 carbon atoms, a hydrosilylation reaction with a compound having a hydrosilyl group is possible. Although not particularly limited, a vinyl group, ethynyl and the like can be mentioned. The halogen group is not particularly limited as long as it can undergo a condensation reaction with the hydroxyl group of the inorganic particles, and examples thereof include a chloro group, a bromo group, and an iodo group. Furthermore, the substituent in the alkyl group, alkenyl group, alkynyl group, and aryl group is not particularly limited as long as it does not inhibit the reaction, but is not limited to cyano group, hydroxyl group, carboxyl group, amide group, imide group, sulfo group. Group, amino group, glyceroyl group and the like.

  Examples of the compound represented by the general formula (6) include vinyltrichlorosilane, vinyltrimethoxysilane, vinyltriethoxysilane, vinyltriisopropoxysilane, vinyltriphenoxysilane, vinylphenylmethylsilane, vinylphenylmethylchlorosilane, and vinylphenyl. Diethoxysilane, vinylphenyldichlorosilane, vinyldiphenylchlorosilane, vinyldiphenylethoxysilane, vinyloctyldichlorosilane, vinyldimethylsilane, vinyldimethylchlorosilane, divinyldichlorosilane, trivinylchlorosilane, trivinylmethoxysilane, trivinylethoxysilane, tri Vinyl silane etc. are mentioned.

  Examples of the compound represented by the general formula (7) include 1,5-divinyl-3,3-diphenyl-1,1,5,5-tetramethyltrisiloxane.

  Examples of the compound represented by the general formula (8) include 1,3,5-trivinyl-1,3,5-trimethylcyclotrisiloxane, 1,3,5-trivinyl-1,3,5-trimethylcyclotrisilazane. Etc.

  Examples of the compound represented by the general formula (9) include 1,3-divinyltetramethyldisiloxane and 1,3-divinyltetramethyldisilazane.

  The second silane coupling agent is not particularly limited, but the general formula

（式中、Ｒ^１、Ｒ^２及びＲ^３は、それぞれ独立に、炭素数が１〜９のアルキル基であり、Ｘは、単結合又はイミノ基である。）
で表される化合物、一般式

(In the formula, R ¹ , R ² and R ³ are each independently an alkyl group having 1 to 9 carbon atoms, and X is a single bond or an imino group.)
A compound represented by the general formula

（式中、ｎは、０〜５０であり、複数のＲ^１、Ｒ^２及びＲ^３のうち、１〜３個は、水素原子又は炭素数が１〜４のアルコキシル基であり、上記以外のＲ^１、Ｒ^２及びＲ^３は、それぞれ独立に、炭素数が１〜９のアルキル基である。）
で表される化合物、一般式

(In the formula, n is 0 to 50, and among the plurality of R ¹ , R ² and R ³ , 1 to 3 are a hydrogen atom or an alkoxyl group having 1 to 4 carbon atoms. R ¹ , R ² and R ³ are each independently an alkyl group having 1 to 9 carbon atoms.)
A compound represented by the general formula

（式中、ｎは、１〜５０であり、Ｒ^１、Ｒ^２及びＲ^３は、それぞれ独立に、炭素数が１〜９のアルキル基である。）
で表される化合物、一般式

(In the formula, n is 1 to 50, and R ¹ , R ² and R ³ are each independently an alkyl group having 1 to 9 carbon atoms.)
A compound represented by the general formula

（式中、ｎは、３〜１０であり、Ｒ^１及びＲ^２は、それぞれ独立に、炭素数が１〜９のアルキル基であり、Ｘは、オキシ基又はイミノ基である。）
で表される化合物等が挙げられ、二種以上併用してもよい。

(In the formula, n is 3 to 10, R ¹ and R ² are each independently an alkyl group having 1 to 9 carbon atoms, and X is an oxy group or an imino group.)
Or a combination of two or more of them may be used.

  Examples of the compound represented by the general formula (10) include hexamethyldisilane and hexamethyldisilazane.

  Examples of the compound represented by the general formula (11) include dimethyldimethoxysilane, diethylmethylsilane, triethylsilane, trimethylmethoxysilane, 1,1,3,3-tetramethyldisiloxane, 1,1,3,3,5. , 5-hexamethyltrisiloxane, 1,3-dimethoxytetramethyldisiloxane, and the like.

  Examples of the compound represented by the general formula (12) include hexamethyldisiloxane and tetradecamethylhexasiloxane.

  Examples of the compound represented by the general formula (13) include hexamethylcyclotrisiloxane, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane, hexamethylcyclotrisilazane, and the like.

  In the fourth embodiment of the method for producing a filler of the present invention, a silane coupling agent having a group capable of reacting an inorganic particle having a hydroxyl group with a primary amino group (hereinafter referred to as a third silane cup). A first step of reacting with a silane coupling agent containing a primary diamine, a compound having a primary amino group and a sulfonic acid group, and a primary amino. And a second step of reacting with a compound having a group and a carboxyl group or a compound having a primary amino group and a quaternary ammonium base. Thus, the surface of the inorganic particle is derived from a primary diamine, a compound having a primary amino group and a sulfonic acid group, a compound having a primary amino group and a carboxyl group, or a compound having a primary amino group and a quaternary ammonium base. In order to react the hydroxyl group existing near the surface of the inorganic particle with the silane coupling agent before introducing the group of, the residual amount of the hydroxyl group near the surface of the inorganic particle is reduced and the primary amino group, Sulfonic acid groups, carboxyl groups or quaternary ammonium bases can be introduced.

  The group capable of reacting with the primary amino group is not particularly limited, and examples thereof include an epoxy group, a halogen group, a chlorocarbonyl group, a carboxyl group, and an isocyanate group.

  Although it does not specifically limit as primary diamine, The compound represented by General formula (3) is preferable.

  In the compound represented by the general formula (3), when n is 2 to 20, a plurality of m may be the same or different.

  Although it does not specifically limit as a compound represented by General formula (3), Pentaethylenehexamine etc. are mentioned, You may use together 2 or more types.

  Although it does not specifically limit as a compound which has a primary amino group and a sulfonic acid group, Sulfanilic acid etc. are mentioned.

  Although it does not specifically limit as a compound which has a primary amino group and a carboxyl group, 4-aminobutyric acid etc. are mentioned.

  Although it does not specifically limit as a compound which has a primary amino group and a quaternary ammonium base, The compound represented by General formula (4) is preferable.

  The counter ion of the quaternary ammonium base is not particularly limited as long as it is a monovalent anion, and examples thereof include a chloride ion.

In the compound represented by the general formula (4), when n is 2 to 20, a plurality of R ¹ and m may be the same or different.

  Although it does not specifically limit as a compound represented by General formula (4), 3-aminopropyl trimethyl ammonium chloride etc. are mentioned, You may use together 2 or more types.

  The inorganic particles reacted with the silane coupling agent are converted into primary diamine, compound having primary amino group and sulfonic acid group, compound having primary amino group and carboxyl group, or primary amino group and quaternary ammonium base. Before making it react with the compound which has, you may block the silanol group derived from the silane coupling agent which remained in the inorganic particle using a well-known method.

  In the first step of the fourth embodiment of the method for producing a filler of the present invention, when the inorganic particles having a hydroxyl group are reacted with a silane coupling agent, a known method can be used. The reaction is carried out in the presence of a solvent such as toluene at 0 to 400 ° C. for 30 minutes to 72 hours.

  In the second step of the fourth embodiment of the method for producing a filler of the present invention, inorganic particles reacted with a silane coupling agent are converted into a compound having a primary diamine, a primary amino group and a sulfonic acid group, 1 When reacting with a compound having a primary amino group and a carboxyl group or a compound having a primary amino group and a quaternary ammonium base, a known method can be used. For example, a method in which inorganic particles reacted with a silane coupling agent are placed in water in which a compound represented by the general formula (3) or (4) is dissolved or a mixed solvent of water and methanol and heated. .

  In the first step of the fourth embodiment of the method for producing a filler of the present invention, the inorganic particles having a hydroxyl group may be reacted only with the third silane coupling agent. Since the introduction amount of the group capable of reacting can be controlled, the third silane coupling agent and the silane coupling agent having no group capable of reacting with the primary amino group (hereinafter referred to as fourth silane). It is preferable to react with a coupling agent). At this time, it is more preferable to react the inorganic particles having a hydroxyl group with a predetermined amount of the third silane coupling agent and then to react with an excessive amount of the fourth silane coupling agent. Thereby, the introduction amount of the group capable of reacting with the primary amino group on the surface of the inorganic particle can be controlled, and the residual amount of the hydroxyl group can be reduced.

  In addition, you may make the inorganic particle which has a hydroxyl group react with a 3rd silane coupling agent and / or a 4th silane coupling agent in multiple times.

  The inorganic particles having a hydroxyl group are not particularly limited, and examples thereof include silica, titanium oxide, zinc oxide, zirconium oxide, aluminum oxide, and zeolite. Among these, porous particles having a hydroxyl group such as silica gel, porous glass, and monolithic silica are preferable.

The inorganic particles having a hydroxyl group preferably have an average particle size of 1 to 200 μm, more preferably 3 to 50 μm. The porous particles having a hydroxyl group preferably have a pore size of 1 to 100 nm, more preferably 4 to 50 nm. Furthermore, porous particles having a hydroxyl group preferably a specific surface area of 50 to 800 m ² / g, more preferably 100~600m ² / g.

  In the specification and claims of the present application, an inorganic particle having a hydroxyl group is an organic-inorganic hybrid having a hydroxyl group such as a particle obtained by reacting an inorganic particle having a hydroxyl group with a silane coupling agent having a hydroxyl group. Contains particles.

  Although it does not specifically limit as a 3rd silane coupling agent, 3-glycidyl oxypropyl trimethoxysilane etc. are mentioned, You may use together 2 or more types.

  Although it does not specifically limit as a 4th silane coupling agent, The compound similar to a 2nd silane coupling agent can be used.

  The column of the present invention is packed with a filler produced using the method for producing a filler of the present invention, and is applied to liquid chromatography to analyze or fractionate a sample of sugar or nucleotide sugar. Can do.

  Hereinafter, examples of the present invention will be described in more detail. In addition, this invention is not limited by this.

[Example 1]
15 g of silica gel having an average particle diameter of 5 μm and a specific surface area of 450 m ² / g was dispersed in 60 mL of dehydrated toluene. Next, 5.79 mL of pyridine and 3.12 mL of vinyltrichlorosilane were added, and the mixture was heated to reflux for 3 hours, then cooled and filtered. The obtained residue was washed with 100 mL of toluene, 100 mL of acetonitrile, and 100 mL of a 60% by mass acetonitrile aqueous solution. Furthermore, it was dispersed in 100 mL of a 60% by mass acetonitrile aqueous solution, stirred at room temperature for 1.5 hours, and filtered. The obtained residue was washed with 100 mL of a 60% by mass acetonitrile aqueous solution and 100 mL of methanol, and then dried under reduced pressure at 120 ° C. for 10 hours. The obtained particles had a carbon content of 4.00% by mass.

  2 g of the obtained particles were put into an ampule and dried under reduced pressure at 120 ° C. for 10 hours. After the ampoule was cooled, 0.416 mL of dimethyldimethoxysilane was added and sealed in a nitrogen atmosphere, and the mixture was reacted at 350 ° C. for 6 hours. Further, the product was taken out, washed with 20 mL of chloroform and 20 mL of methanol, and then dried under reduced pressure at 120 ° C. for 10 hours.

  After 0.7 g of the obtained particles were dispersed in 3 mL of dehydrated toluene, 3.0 mL of 3- [N, N-bis (trimethylsilyl) amino] propyldimethylsilane was added and stirred. Next, 8.0 μL of a 3% by mass toluene solution of chloroplatinic acid was added and reacted at 70 ° C. for 8 hours, and then cooled and filtered. The obtained residue was washed with 10 mL of chloroform and 10 mL of methanol, and then dried under reduced pressure at 120 ° C. for 10 hours.

  After 0.5 g of the obtained particles were dispersed in 2 mL of methanol, 0.1 mL of concentrated hydrochloric acid was added, and the mixture was stirred overnight at room temperature and filtered. The obtained residue was washed with 10 mL of methanol, 10 mL of milli-Q water and 10 mL of methanol, and then dried under reduced pressure at 80 ° C. for 10 hours to obtain a filler.

[Analysis Example 1]
The packing material of Example 1 was packed in a column having an inner diameter of 2.0 mm and a length of 150 mm. A column packed with packing material is installed in a high-performance liquid chromatograph, an 80% by mass acetonitrile aqueous solution is used as a mobile phase, a flow rate is set to 0.2 mL / min, a temperature is set to 40 ° C., and a mixture of fructose, glucose and lactose. Were analyzed by injecting 7 μL of sample diluted in mobile phase. FIG. 1 shows the analysis results. An RI detector was used as the detector.

[Analysis Example 2]
The packing material of Example 1 was packed in a column having an inner diameter of 2.0 mm and a length of 150 mm. A column packed with packing material was installed in a high-performance liquid chromatograph, 50 mmol / L diammonium hydrogen phosphate aqueous solution (pH = 3) was used as the mobile phase, the flow rate was set to 1.0 mL / min, and the temperature was set to 40 ° C. Then, 7 μL of a sample obtained by diluting a mixture of CMP, AMP, UMP and GMP with a mobile phase was injected and analyzed. FIG. 2 shows the analysis results. As a detector, a UV detector (wavelength 254 nm) was used.

[Example 2]
15 g of silica gel having an average particle diameter of 5 μm and a specific surface area of 450 m ² / g was dispersed in 60 mL of dehydrated toluene. Next, 6.9 mL of 3-glycidyloxypropyltrimethoxysilane was added and heated under reflux for 5 hours, then cooled and filtered. The obtained residue was washed with 100 mL of toluene and methanol, and then dried under reduced pressure at 120 ° C. for 10 hours. The obtained particles had a carbon content of 4.17% by mass.

  2 g of the obtained particles were put into an ampule and dried under reduced pressure at 120 ° C. for 10 hours. After the ampoule was cooled, 0.416 mL of dimethyldimethoxysilane was added and sealed in a nitrogen atmosphere, and the mixture was reacted at 350 ° C. for 6 hours. Further, the product was taken out, washed with 20 mL of chloroform and 20 mL of methanol, and then dried under reduced pressure at 120 ° C. for 10 hours.

  After 0.7 g of the obtained particles were dispersed in 3 mL of dehydrated methanol, 0.3 mL of ethylenediamine was added and stirred, reacted at 25 ° C. for 16 hours, and filtered. The obtained residue was washed with 10 mL of milli-Q water and 10 mL of methanol, and then dried under reduced pressure at 120 ° C. for 10 hours.

[Analysis Example 3]
The packing material of Example 2 was packed in a column having an inner diameter of 2.0 mm and a length of 150 mm. A column packed with packing material is installed in a high-performance liquid chromatograph, an 80% by mass acetonitrile aqueous solution is used as a mobile phase, a flow rate is set to 0.2 mL / min, a temperature is set to 40 ° C., fructose, glucose, sucrose, and lactose. The maltose mixture was analyzed by injecting 4 μL of a sample diluted in mobile phase. FIG. 3 shows the analysis results. A CAD detector was used as the detector.

Claims (10)

A first step of reacting inorganic particles having a hydroxyl group with a silane coupling agent containing a silane coupling agent having an alkenyl group having 2 to 8 carbon atoms and / or an alkynyl group having 2 to 7 carbon atoms. When,
A second step of reacting the inorganic particles reacted with the silane coupling agent with a hydrosilyl group and a compound having a primary amino group protected by a protective group;
A method for producing a filler, comprising a third step of generating a primary amino group by deprotecting inorganic particles reacted with the compound. The compound has the general formula

(Wherein R ¹ and R ² are each independently a hydrogen atom, a chloro group or an alkyl group having 1 to 4 carbon atoms, and R ³ and R ⁴ are each independently a protecting group, m is an integer from 1 to 20, and n is an integer from 1 to 20.)
It is represented by these, The manufacturing method of the filler of Claim 1 characterized by the above-mentioned. A first step of reacting inorganic particles having a hydroxyl group with a silane coupling agent containing a silane coupling agent having an alkenyl group having 2 to 8 carbon atoms and / or an alkynyl group having 2 to 7 carbon atoms. When,
A second step of reacting the inorganic particles reacted with the silane coupling agent with a first compound having a group capable of reacting with a hydrosilyl group and a primary amino group;
The inorganic particles reacted with the first compound are converted into a primary diamine, a compound having a primary amino group and a sulfonic acid group, a compound having a primary amino group and a carboxyl group, or a primary amino group and a quaternary ammonium base. A method for producing a filler, comprising a third step of reacting with a compound having the third step. The first compound has the general formula

(In the formula, R ¹ and R ² are each independently a hydrogen atom, a chloro group, or an alkyl group having 1 to 4 carbon atoms, and 1 is an integer of 1 to 60.)
Represented by
The primary diamine has the general formula

(In the formula, m is an integer of 1 to 20, and n is an integer of 1 to 20.)
Represented by
The compound having a primary amino group and a quaternary ammonium base has the general formula

(In the formula, R ¹ is a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, and R ² , R ³ and R ⁴ are each independently an alkyl group having 1 to 5 carbon atoms. , X ⁻ is a monovalent anion, l and m are each independently an integer of 1 to 20, and n is an integer of 0 to 20.
It is represented by these. The manufacturing method of the filler of Claim 3 characterized by the above-mentioned. A first step of reacting inorganic particles having a hydroxyl group with a silane coupling agent containing a silane coupling agent having an alkenyl group having 2 to 8 carbon atoms and / or an alkynyl group having 2 to 7 carbon atoms. When,
A method for producing a filler, comprising a second step of reacting the inorganic particles reacted with the silane coupling agent with a compound having a hydrosilyl group and a quaternary ammonium base. The compound has the general formula

(In the formula, R ¹ and R ² are each independently a hydrogen atom, a chloro group, or an alkyl group having 1 to 4 carbon atoms, and R ³ , R ⁴ , R ^5, and R ⁶ are each independently , An alkyl group having 1 to 5 carbon atoms, X ⁻ is a monovalent anion, l and m are each independently an integer of 1 to 20 and n is 1 to 20 Is an integer.)
It is represented by these, The manufacturing method of the filler of Claim 5 characterized by the above-mentioned.   The first step is a step of reacting the inorganic particles having a hydroxyl group with a silane coupling agent having an alkenyl group having 2 to 8 carbon atoms and / or an alkynyl group having 2 to 7 carbon atoms. And reacting the inorganic particles reacted with the silane coupling agent with a silane coupling agent not having an alkenyl group or an alkynyl group. The manufacturing method of the filler as described. A first step of reacting inorganic particles having a hydroxyl group with a silane coupling agent including a silane coupling agent having a group capable of reacting with a primary amino group;
The inorganic particles reacted with the silane coupling agent are mixed with a primary diamine, a compound having a primary amino group and a sulfonic acid group, a compound having a primary amino group and a carboxyl group, or a primary amino group and a quaternary ammonium base. The manufacturing method of the filler characterized by having the 2nd process made to react with the compound which has. The primary diamine has the general formula

(In the formula, m is an integer of 1 to 20, and n is an integer of 1 to 20.)
Represented by
The compound having a primary amino group and a quaternary ammonium base has the general formula

(In the formula, R ¹ is a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, and R ² , R ³ and R ⁴ are each independently an alkyl group having 1 to 5 carbon atoms. , X ⁻ is a monovalent anion, l and m are each independently an integer of 1 to 20, and n is an integer of 0 to 20.
It is represented by these, The manufacturing method of the filler of Claim 8 characterized by the above-mentioned.   In the first step, the inorganic particles having the hydroxyl group are reacted with a silane coupling agent having a group capable of reacting with the primary amino group, and the silane coupling agent is reacted. The method for producing a filler according to claim 8 or 9, comprising a step of reacting inorganic particles with a silane coupling agent having no group capable of reacting with a primary amino group.

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