JPH1073579A - Manufacture of filler for chromatography - Google Patents

Abstract

PROBLEM TO BE SOLVED: To synthesize filler, wherein remaining silanol group is made sufficiently inactive in vapor phase and liquid by chemically bonding chemical modifying agent to the silanol group of silica gel, and making two kinds of end-terminal adding agent forming a partial complex compound to act with the silica gel in the specified temperature range in inactive gas atmosphere. SOLUTION: After the chemical modifying agent is chemically bonded to the silanol group of silica gel, two kinds of end-terminal adding agents forming partial complex compound is made to react with the silica gel in the vapor phase or the liquid phase of 180-240 deg.C in a tightly sealed container under inactive gas environment atmosphere. An inactivated group is chemically bonded to the remaining silanol group of the silica gel. As the chemical modifying atent, e.g. monochloro silane compound, in details, e.g. dimethyl octadecyl chloro silane or the like is used. In the mepntime, as one end-terminal adding agent, e.g. N-(trimethyl silyl) molpholine is used, and as the other end-terminal adding agent, e.g. trimethyl bromosilane or the like is used.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a chromatographic packing material which effectively inactivates residual silanol groups of silica gel, and relates to a chromatography which can be used for quantitative analysis by reducing unreacted silanol groups. The present invention relates to a method for producing a photographic filler.

[0002]

2. Description of the Related Art Among existing packing materials for high performance liquid chromatography, a packing material in which various organic silane compounds are chemically bonded to silica gel is the most versatile, and octadecylchlorosilane compounds,
There are octylchlorosilane compounds, butylchlorosilane compounds, cyanopropylchlorosilane compounds, phenylchlorosilane compounds, and the like. Of these, octadecyl silica gel filler (ODS) is the most widely used, and while this filler has many advantages in analysis, it has many problems.

In general, the above-mentioned chemically-bonded silica gel filler has a considerable amount of unreacted silanol groups remaining on the surface of silica gel as a base material. This unreacted silanol group strongly acts on a polar substance, particularly a basic substance, and adsorbs the basic substance or causes a tailing phenomenon of a peak, so that it is difficult to obtain faithful reproducibility of the chromatogram. T

[0004]

The following means exist as methods for inactivating such residual silanol groups. The chemically bonded silica gel filler is heated to reflux with a solvent such as toluene together with a trimethylsilylating agent such as trimethylchlorosilane or hexamethyldisilazane. The above reaction is performed under high pressure and high temperature (Chromatograpy,
Vol. 17, 39, 1996). The chemically bonded silica gel filler is reacted with a single silylating agent such as hexamethyldisilazane, trimethylmethoxysilane, hexamethylcyclotrisiloxane in a gas phase at a temperature of 250 ° C. or more.

[0005] The fillers treated by these methods still have a considerable amount of unreacted silanol groups remaining. Further, in the above-mentioned method, although the deactivation is considerably improved, there is a fundamental defect that the property as a filler changes because thermal desorption of a chemically modified group already bonded occurs.

[0006] The present inventors have studied various problems in the chemically bonded silica gel filler and conducted many experiments. As a result, when at least two kinds of terminal adducts forming a complex compound are reacted with the chemically bonded silica gel, the filler in which the residual silanol groups are sufficiently inactivated, regardless of whether in the gas phase or the liquid phase, Can be synthesized.

The present invention has been proposed to improve the problem relating to the residual silanol groups in a chemically-bonded silica gel filler, and effectively removes the residual silanol groups of the silica gel in a gas phase or a liquid phase. It is an object of the present invention to provide a method for producing a packing material for chromatography which can be inactivated. It is another object of the present invention to provide a method for preparing a chromatographic packing material that can be used for quantitative analysis by sufficiently reducing unreacted silanol groups.

[0008]

In order to achieve the above object, in the method for producing a packing material for chromatography according to the present invention, first, a chemical modifier is chemically bonded to silanol groups of silica gel. Thereafter, at least two end-adding agents which form at least partly a complex compound are reacted with the silica gel in the gas or liquid phase. At this time, the condition of the gas phase is 180 ° C. in a closed vessel under an inert gas atmosphere.
The solution is heated to 180 to 240 ° C in a closed vessel under an inert gas atmosphere.

[0009]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The silica gel used in the method of the present invention is not particularly limited, but usually has a particle size of 1 to 1000.
μm, preferably 3 to 100 μm, and pore diameter of 10 to 500.
0 °, preferably 50-2000 °, specific surface area 1-10
00 m ² / g, preferably 10 to 500 m ² / g.

In the method of the present invention, a known organic silane compound can be used as a chemical modifier. For example, in chlorosilane or alkoxysilane, a C1-C30 alkyl group such as a triacontyl group, an eicosyl group, an octadecyl group, an octyl group, an n-butyl group, or a C6-C16 aryl such as a phenyl group is used as a chemical modifying group. Group,
Or 1 or 2 in an alkyl group having 1 to 18 carbon atoms
The above cyano group, hydroxyl group, carboxyl group, amino group,
It is an acid amide group. As the alkoxy group of the alkoxysilane, a methoxy group, an ethoxy group and the like are suitable.
Further, cyclosiloxanes and polysiloxanes having 2 to 8 chemical modifying groups can also be used.

That is, the chemical modifier is a monochlorosilane compound, a dichlorosilane compound, a trichlorosilane compound, a monoalkoxysilane compound, a dialkoxysilane compound, a trialkoxysilane compound, a cyclosiloxane compound, or a polysiloxane compound. At least one kind may be selected from the above. Specific chemical modifiers include dimethyloctadecylchlorosilane, dimethyloctadecylmethoxysilane, octadecyltrichlorosilane, octadecyltrimethoxysilane, dimethyloctylchlorosilane, octyltrichlorosilane, n
-Butyldimethylchlorosilane, di-n-butyldichlorosilane, n-butyl-trichlorosilane, dimethylphenylchlorosilane, diphenyldichlorosilane, phenyltrichlorosilane, 3-cyanopropyldimethylchlorosilane, 3-cyanopropyltrichlorosilane, hexamethylcyclotrisilane Examples include siloxane.

The reaction between the silica gel and the chemical modifying agent can be performed by a known method and under conditions, and generally, the silica gel and the chemical modifying agent are reacted in a solvent. As this solvent,
A solvent that does not react with the chemical modifier and is thermally stable at the reaction temperature, such as toluene or xylene, may be used. The reaction temperature is usually 30 to 350 ° C, and the reaction time is 30.
The reaction time is in the range of minutes to 24 hours, and the reaction environment may be an open type or a closed type under an atmosphere of an inert gas such as nitrogen.

The end-adding agent to be reacted with the chemically modified silica gel is composed of at least two kinds of reactants forming a complex compound, one of which is a silazane compound,
It is a disilazane compound, a siloxane compound or a polysiloxane compound. The other terminal addition agent comprises a halogenosilane compound, an alkylcarbonyloxysilane compound, an alkylsulfonyloxysilane compound, an alkylborane compound, an alkylzinc compound, an alkylaluminum compound, an alkyltitanium compound or an alkyltin compound. Each of the terminal additives may be used alone or in combination of up to three.

Specifically, one of the terminal additives is N-
(Trimethylsilyl) morpholine, N- (trimethylsilyl) imidazole, hexamethyldisilazane, trimethylsilylacetamide, pentamethyldisiloxane,
Hexamethyldisiloxane and the like. Further, the other terminal addition agent is trimethylbromosilane, trimethylchlorosilane, trimethyliodosilane, trimethylsilyl acetate, trimethylsilyltrifluoroacetate, trimethylsilyltrifluoromethanesulfonate, trimethylsilylmethanesulfonate, triethylborane, diethylmethoxyborane, dimethylzinc, diethyl Zinc, trimethylaluminum, triethylaluminum, diethylaluminum chloride, titanium n-butoxide or di-n-butyl-n-butoxytin.

A method for chemically bonding an inactivating group to a residual silanol group is as follows: a chemically modified silica gel and at least two types of end-adding agents are placed in a closed container, and the reaction is carried out under an inert gas atmosphere such as nitrogen or under reduced pressure. The reaction is carried out at a temperature of 240 ° C., preferably at a temperature of 200 to 230 ° C., in the gas phase for 30 minutes to 48 hours, preferably 1 hour to 24 hours. The reaction in the gas phase is preferably carried out in an atmosphere of an inert gas such as nitrogen, argon or helium. However, it is also possible to carry out the reaction in a state where the inside of the reaction system is sucked and depressurized with an aspirator or the like after replacement with the inert gas. .

This chemical bonding method may be performed in a liquid phase, that is, in a solvent, but must be performed in a closed vessel under an inert gas atmosphere. In this case, aromatic hydrocarbons such as toluene and xylene, and substituted aromatic compounds such as diphenyl ether and o-dichlorobenzene may be used as suitable solvents.

In the method of the present invention, at least two types of terminal addition agents are mixed, and a part of the mixture forms a complex compound, whereby trimethylsilylation of an unreacted silanol group is more enhanced than each of the single terminal addition agents. Effectively promotes and chemically bonds deactivating groups to the remaining silanol groups of the silica gel. This complex compound can be formed in a gas phase or a liquid phase, and the silanol groups remaining on the silica gel can be sufficiently inactivated at a relatively low temperature in a closed container.

In the method of the present invention, the reaction temperature is from 180 to 24.
Deactivation can be sufficiently achieved even at a temperature as low as 0 ° C., and due to such a low-temperature reaction, thermal elimination of a chemically modified group already chemically bonded hardly occurs. Therefore, the residual silanol groups of the silica gel can be more inactivated than when a single terminal additive is added, and there is no defect that the properties as a filler change.

As a preceding step of the method of the present invention, a production example of introducing a chemical modifying group into silica gel will be disclosed.

Production Example 1 50 g of porous silica gel having a particle size of 5 μm and a pore diameter of 120 °
Is heated and refluxed in a dilute hydrochloric acid aqueous solution and then filtered off with suction, and the solid collected by filtration is sequentially washed with water and methanol with suction and washed. After removing the solvent by suction and reduced pressure, the silica gel particles are dried at 110 ° C. for 5 hours. 50 g of the dried silica gel particles were placed in a 1-liter flask, and 500 ml of dry toluene, 46.9 g (150 mmol) of dimethyloctadecylchlorosilane, and pyridine 15
Add ml. The mixture is heated under reflux for 6 hours with stirring, then cooled to room temperature, and the solid substance is filtered off with suction. This solid is washed by suction filtration with toluene, 50% methanol and methanol in that order, and then dried under reduced pressure at 60 ° C. for 10 hours to obtain 53 g of dimethyloctadecylsilylated silica gel. The carbon content of this silica gel is
It was 16.3% from elemental analysis.

Production Example 2 50 g of silica gel particles treated with dilute hydrochloric acid in the same manner as in Production Example 1
Into a 1 liter glass autoclave and dry o-
Dichlorobenzene 350 ml, dimethyloctadecylchlorosilane 46.9 g (150 mmol), pyridine 15
Then, the inside of the autoclave is replaced with nitrogen and sealed. The mixture is heated at 180 ° C. for 8 hours with stirring, then cooled to room temperature and the solid is filtered off with suction. This solid is washed and dried under reduced pressure in the same manner as in Production Example 1 to obtain 52 g of dimethyloctadecylsilylated silica gel.
The carbon content of the silica gel was 16.5 from elemental analysis.
%Met.

Production Examples 3 to 12 The same operation as in Production Example 1 was carried out using 150 mmol of the chemical modifier shown in Table 1 below in place of dimethyloctadecylchlorosilane in Production Example 1. A modified silica gel is obtained.

[0023]

[Table 1]

[0024]

EXAMPLES The present invention will be described based on examples, but the present invention is not limited to the following examples. Each embodiment discloses a step of chemically bonding an inactivating group to the remaining silanol group of the chemically modified silica gel.

Example 1 10 g of the dimethyloctadecylsilylated silica gel obtained in Production Example 1 and 1.62 g of hexamethyldisiloxane
(10 mmol) and 2.0 g of trimethyliodosilane
(10 mmol) is placed in a glass sealed container (50 cc), the inside of the container is replaced with nitrogen, and the container is sealed under reduced pressure. The container is heated in a constant temperature bath at 220 ° C. for 8 hours, and then left to cool. The content is suspended in 200 ml of toluene and filtered by suction. Further, by successively washing and filtering with toluene, methanol-water (1: 1) and methanol, suction-drying, and further drying under reduced pressure at 60 ° C. for 10 hours,
9.8 g of filler (I) into which an inactivating group has been introduced are obtained.

Example 2 A glass-enclosed mixture of 50 g of the dimethyloctadecylsilylated silica gel obtained in Production Example 2, 7.0 g (50 mmol) of N- (trimethylsilyl) imidazole, and 5.4 g (50 mmol) of trimethylchlorosilane. Container (300
cc), and the inside of the container is purged with nitrogen, and then closed under reduced pressure. The container is heated in a thermostat at 230 ° C. for 8 hours, and then left to cool. The content is suspended in 500 ml of toluene and filtered by suction. Further, the mixture was washed and filtered with toluene, methanol-water (1: 1) and methanol, suction-dried, and further dried under reduced pressure at 60 ° C. for 10 hours to obtain a filler (II) into which an inactivating group was introduced. 5 g are obtained.

Example 3 Dimethyl octadecyl methoxysilane was used instead of dimethyl octadecyl chlorosilane in Production Example 1,
By the same operation as in Production Example 1, dimethyloctadecylsilylated silica gel is obtained. 50 g of this silica gel
6.6 g (50 mmol) of trimethylsilylacetamide and 4.9 g (50 mmol) of triethylborane were added to 250 ml of diphenyl ether, and this was placed in a glass sealed container (500 cc). I do. While stirring the inside of the container, the container is heated at 210 ° C. for 8 hours and then allowed to cool, and the contents are suction-filtered. Further, toluene and methanol-water (1:
1) Washing and filtering with methanol, followed by suction drying, and further drying under reduced pressure at 60 ° C. for 10 hours to obtain 48.5 g of a filler (III) into which an inactivating group has been introduced.

Examples 4 to 10 10 g of the dimethyloctadecylsilylated silica gel obtained in Production Example 1 and 10 mmol each of a mixture of terminal adducts shown in Table 2 below were placed in a closed glass container (50 cc). After the inside of the vessel is replaced with nitrogen, the vessel is closed under reduced pressure. The container was heated in a thermostat at the temperature and time shown in Table 2 and then allowed to cool. The content was suspended in 200 ml of toluene and suction-filtered. Further, the mixture is washed with toluene, methanol-water (1: 1), and methanol, filtered, suction-dried, and further dried under reduced pressure at 60 ° C. for 10 hours, whereby a filler (IV to X) into which an inactivating group is introduced. Get.

[0029]

[Table 2]

Examples 11 to 17 10 g of the dimethyloctadecylsilylated silica gel obtained in Production Example 1 and 10 mmol each of a mixture of terminal additives shown in Table 3 below were placed in a closed glass container (50 cc). After the inside of the container is replaced with nitrogen, the container is closed. After heating the container in a thermostat at the temperature and time shown in Table 3, the container is allowed to cool, and the content is suspended in 200 ml of toluene, followed by suction filtration. Further, by successively washing and filtering with toluene, methanol-water (1: 1) and methanol, suction-drying, and further drying under reduced pressure at 60 ° C. for 10 hours,
A filler (XI to XVII) into which an inactivating group is introduced is obtained.

[0031]

[Table 3]

Examples 18 to 24 A sealed glass container was prepared by mixing 10 g of the dimethyloctadecylsilylated silica gel obtained in Production Example 1, 10 mmol each of a mixture of a terminal additive shown in Table 4 below, and a solvent shown in Table 4. (50 cc), the inside of the container is replaced with nitrogen, and then sealed. While stirring the inside of this container, the container was heated at the temperature and for the time shown in Table 4, then allowed to cool, and the contents were filtered by suction. Further, toluene and methanol-water (1:
1) Washing and filtering with methanol, suction drying, and further drying under reduced pressure at 60 ° C. for 10 hours to obtain fillers (XVIII to XXIV) into which an inactivating group has been introduced.

[0033]

[Table 4]

Test Example Increase and decrease of carbon content and pyridine-
Enol analysis In Examples 1 to 24, elemental analysis of the filler into which the inactivating group was introduced is performed. In order to obtain a chromatogram for pyridine-phenol analysis using these packing materials, each packing material was packed in a stainless steel column having an inner diameter of 4.6 mm and a length of 150 mm, and acetonitrile / water (30 / volume ratio) was used as a mobile phase. 70), flow rate 1 ml / min, temperature 37 ° C,
Mixed sample of pyridine and phenol at a detection wavelength of 254 nm (each content is 0.07 μl / ml, 0.8 mg / ml) 7
Inject μl.

The obtained chromatogram is illustrated in FIGS. 1 to 3. 1 is the filler obtained in Example 1, and FIG. 2 is Example 7
FIG. 3 is a chromatogram of the filler obtained in Example 16 and the filler obtained in Example 16;
From the obtained chromatogram, the degree of separation Rs of pyridine and phenol and the tailing factor of pyridine were calculated, and the results are summarized in Table 5 below.

Here, the value of the degree of separation Rs and the value of the tailing factor are defined as in Equations 1 and 2 below.

[0037]

(Equation 1) In the formula, t _R indicates the retention time (minute) of each compound, and W _{h / 2} indicates the peak width at half the peak height from the peak baseline of each compound.

[0038]

(Equation 2) Wherein, W h _{/ 20} peak width at a height of 1/20 of the peak height from the peak baseline, a is perpendicular and W _{h / 20} fulcrum and the rise of the peak of the peak apex in W _{h / 20} Indicates the distance to a point.

[0039]

[Table 5]

Examination of the results of the elemental analysis in Table 5 shows that only the fillers VI, X, XV, and XVI showed a decrease in the carbon content, and the other fillers did not decrease the carbon content. As a result, it was confirmed that the thermal elimination of the chemical modifying group (dimethyloctadecyl group in this test) was small, and it was found that the method of the present invention was particularly excellent as a method for inactivating a terminal group.

From the results of the pyridine-phenol analysis, the pyridine / phenol separation Rs value was 15.3.
１７17.3, Rs value 8 of the same type of commercially available column
As compared with Nos. To 14, it can be determined that the silanol groups of the fillers in Table 5 were almost completely inactivated. The reason for this is that the smaller the residual silanol group, the shorter the retention time of the basic substance pyridine, and the greater the degree of separation Rs from phenol. Further, this reason can be confirmed by the value of the tailing factor of pyridine. In the packing material in Table 5, the tailing factor value of pyridine is 0.93 to 1.32, and in the case of a commercially available column of the same type, 1.5 or more is more inactivated than usual. I understand.

Examples 25 to 34 Each of the chemically modified silica gels obtained in Production Examples 3 to 12 was 10
g and 10 mmol each of a mixture of the terminal additive shown in Table 6 below are placed in a hermetically sealed glass container, the inside of the container is replaced with nitrogen, and the container is then sealed under reduced pressure. After heating the container in a thermostat at the temperature and time shown in Table 6, the container is allowed to cool, and the content is suspended in 200 ml of toluene, followed by suction filtration. Further, it was washed and filtered with toluene, methanol-water and methanol in that order, suction-dried, and further dried under reduced pressure at 60 ° C. for 10 hours to obtain a filler (XX) into which an inactivating group was introduced.
V ~ XXXIV).

[0043]

[Table 6]

[0044]

According to the method of the present invention, at least two types of terminal adducts are mixed, and a part of the mixture forms a complex compound to further promote the inactivation of unreacted silanol groups. In the method of the present invention, the reaction temperature is from 180 to 24.
By achieving effective inactivation even at temperatures as low as 0 ° C., thermal elimination of already chemically bonded chemical modifying groups does not occur. Therefore, when the present invention is used, when the residual silanol group is inactivated, the defect that the property as a filler changes as in the prior art does not occur, and the residual silanol group remains regardless of whether it is in the gas phase or the liquid phase. A filler in which silanol groups are sufficiently inactivated can be synthesized.

In the silica gel filler produced by the method of the present invention, the unreacted silanol groups on the surface of the silica gel as the base material are almost disappeared, and the unreacted silanol groups may cause adsorption of a basic substance and tailing of peaks. To eliminate. This silica gel packing retains the analytical advantages of the conventional chemically-bonded packing, and also enables the fidelity of chromatograms to be obtained.

[Brief description of the drawings]

FIG. 1 is a chromatogram of pyridine-phenol analysis using the filler obtained in Example 1.

FIG. 2 is a chromatogram of pyridine-phenol analysis using the filler obtained in Example 7.

FIG. 3 is a chromatogram of pyridine-phenol analysis using the filler obtained in Example 16.

Claims (4)

[Claims] At least two kinds of compounds which form a complex compound at least partially in a gas phase at 180 to 240 ° C. in a closed vessel under an inert gas atmosphere after a chemical modifier is chemically bonded to silanol groups of silica gel. A method for producing a packing material for chromatography, comprising reacting an end-adding agent with a silica gel and chemically bonding an inactivating group to a residual silanol group of the silica gel. 2. A method for chemically bonding a silanol group of silica gel with a chemical modifier, and forming at least a part of a complex compound in a liquid phase at 180 to 240 ° C. in a closed vessel under an inert gas atmosphere. A method for producing a packing material for chromatography, comprising reacting an end-adding agent with a silica gel and chemically bonding an inactivating group to a residual silanol group of the silica gel. 3. One of the terminal addition agents is a silazane compound,
3. The method according to claim 1, wherein at least one selected from a disilazane compound, a siloxane compound, and a polysiloxane compound. 4. The other terminal addition agent is at least one selected from a halogenosilane compound, an alkylcarbonyloxysilane compound, an alkylsulfonyloxysilane compound, an alkylborane compound, an alkylzinc compound, an alkylaluminum compound, an alkyltitanium compound, and an alkyltin compound. 3. The method according to claim 1 or 2, wherein said method is selected.