CS207861B1 - Method of preparation of the silicagel sorbent for the liquid chromatography in the reverse phase with possibility of regulation of the quantity of the bound carbon - Google Patents

Description

(54) A method for the preparation of a reverse-phase liquid chromatography silica gel sorbent with the possibility of controlling the amount of bound carbon

BACKGROUND OF THE INVENTION The present invention relates to a process for the preparation of a reverse-phase liquid chromatography silica gel sorbent with the possibility of controlling the amount of carbon-bound.

In both preparative and analytical liquid chromatography, a polar mobile phase and a porous silica-based carrier are often used with success, the surface of which is modified by a chemically bonded non-polar organic phase, the so-called reverse phase chromatography. This is usually a modification of the aliphatic chain of one to eighteen carbon atoms, the optimum length of the attached chain and thus the percentage of carbon and hydrogen depends on the nature of the split mixture: roughly, the smaller the difference in polarity of the molecules a sorbent having a higher carbon content should be used. On the other hand, the longer the aliphatic chain bound to silica gel, the more difficult it is for spherical reasons to achieve complete conversion of the silanol groups of the original silica gel; if we want to eliminate the possibility of undesirable separation of substances by a mechanism other than reverse phase chromatography (ie sorption), we must eliminate unreacted silanol

From the group, an additional reaction with sterically low-intensity molecules (hexamethyldisilazane or trimethylchlorosilane, etc.).

As reactants for the chemical modification of the silica gel surface, alkyl halogensilanes and alkylalkoxysilanes with different alkyl sizes and optionally hexamethyldisilazane are generally used for the bonding of monocarbon residues. The alkyl halogensilane releases hydrogen halide in the reaction, and ammonia from hexamethyldisilazane, and thus silanization can be accelerated, for example, by adding dry pyridine, which binds the hydrogen halide to form pyridinium halide, and in the second, nitrogen gas is usually purged to remove ammonia gas. The disadvantage of this most commonly used process is mainly a two-step synthesis, in which in the first reaction step the bulkier alkyl is bound, in the second the hexamethyldisilazane reacts with the remaining silanol groups, with all the resulting consequences such as time, chemical costs, etc. Another disadvantage is that the surface properties of the modified sorbent and hence its separation capability in reverse phase chromatography depends on the type of alkyl reacting in the first stage of the synthesis, i.e. the relative content of bound carbon, which, when desired. to have a range of sorbents differing in carbon content, it places increased demands on the financial and raw material security of production. Also, pyridine catalysis and nitrogen purging of the apparatus is a complication and may also result in production costs when producing a larger amount of sorbent.

The disadvantages of the two-step process currently used in the preparation of the carrier for reversed phase chromatography are avoided by the production method of the present invention.

The process of the present invention is characterized in that the silica gel is silanized by treatment with a mixture of hexamethyldisilazane and an alkyl halogensilane selected from R ₁ SiX ₃ , R 1 R ₂ SiX ₂ and R 1 R ₂ SiR ₂ Si, wherein X is halogen, R is an C 8 -C 22 alkyl radical and R ₂ is an alkyl radical of 1 to 22 carbon atoms, the resulting carbon and hydrogen content of the product being controlled by the ratio of hexamethyldisilazane to alkyl halogensilane in the initial reaction mixture in the range of 5% to 98% by volume of hexamethyldisilazane.

An advantage of the process of the present invention is that it provides a sorbent that is at least equivalent to commercially available sorbents of this type and those prepared in the literature when using a spherical silica gel prepared as a starting material. according to Cs. The process for the preparation of reversed phase sorbents according to the invention allows the preparation of a sorbent with a surface completely covered by alkyl groups in a one-step reaction. Such surface quality has so far been achieved only by a two-stage reaction. Thus, the described process simplifies the preparation of the sorbent by hydrolyzing the primary alkylated silica gel, thoroughly drying the sorbent, and reacting with a methylating agent (hexamethyldisilazane, trimethylchlorosilane, etc.).

The described process reduces the consumption of silanizing agents, which need not be added in excess of the two-step reactions. This appears to be a considerable advantage, especially in the case of longer alkyl chain silanes, the cost of which is high. In addition, the described process allows the reaction to be carried out with a good result even in the cold, which reduces the apparatus costs, the labor intensity and the safety of the work with respect to the toxicity of the substances used in the reaction.

Thus, it is essentially a one-step synthesis in which silica gel reacts simultaneously with a mixture of alkyl halogensilane, preferably octadecyltrichlorosilane having 18 carbon atoms in the chain and hexamethyldisilazane (monocyclic chain), the resulting amount of bound carbon being determined by the ratio of the two silanizing agents. hydrogen chloride and ammonia to form ammonium chloride which is insoluble in the reaction mixture.

The reaction according to the invention is preferably carried out in a temperature range of 25 to 125 ° C. The content of hexamethyldisilazane in the silanization mixture is preferably in the range of 70 to 95 vol%.

The practice of carrying out the reaction is relatively simple. Purified silica gel (e.g., by repeated boiling in dilute HCl and distilled H ₂ O) is freed from free molecular bound water by drying, then dispersed in a solvent that does not react with the silanizing agents used such as toluene, hexane, benzene and the like. sieve, sodium, solid caustic, and the like. In order to ensure the homogeneity of the reaction mixture by stirring, at least the same volume of solvent as the bulk volume of silica gel should be used. A calculated and measured amount of alkyl halogensilane, preferably octadecyltrichlorosilane and hexamethyldisilazane, is then added to the slurry in a preselected ratio, either simultaneously or first with halogensilane, followed by silazane; when the two components are added immediately at a temperature of 20 ± 5 ° C, elemental analysis in both cases gives practically identical results for the final bound organic phase content. It will be appreciated that the molar ratio of the two silanizing agents in the original mixture is not identical to the molar ratio of the bound molecules due to their different reactivity. In calculating the total amount of the silanizing agent, it is possible either to take over the data from the original literature or to approximate 6 millimoles of reagent per 1 g of silica gel with a specific surface area of 600 m ² / g. Finally, care should be taken to ensure that the total volume concentration of the silanizing agents in the organic solvent is not less than 5% by volume, as otherwise the reaction is running too slowly and greater than 40% by volume. ). The silanization proceeds already at room temperature (20 ± 5 ° C), when free silanol groups react almost completely in 5 days; it is convenient to mix the suspension at least once every day. At the boiling point of toluene, the reaction is complete in 6 hours; it is not necessary to flush the apparatus with nitrogen during the reaction;

Product processing is conventional and is described in the literature. Essentially, it involves washing with a non-reactive solvent such as dry toluene to remove unreacted reagents, such as acetone, hydrolysis by washing with methanol-water and drying the product. No sorbent prepared according to the process described in this invention showed a positive reaction in the test for the presence of free silanol groups by methyl red. In view of the production of a larger amount of sorbent, it is necessary to emphasize the advantage of the above-mentioned process in which the reaction takes place at room temperature, because of its cheapness and technological simplicity.

In the following, the invention is illustrated by the following examples.

Example 1.

g of spherical silica gel prepared according to CS. of certificate 179184 was boiled twice in dilute HCl p. a. (1:

: 10), then twice in distilled H ₂ O for 20 min. A fraction with an average particle size of 0.010 mm and a specific surface area of 451 m ² / g was used. The silica gel was dried in an oven at 150 ° C for 12 hours, then immediately transferred to a reaction flask equipped with a stirrer and reflux condenser along with 62 ml of freshly activated molecular sieve dried toluene. 5.6 ml of hexamethyldisilazane (HMDS) and 0.6 ml of octadecyltrichlorosilane (ODTS) were simultaneously added to the suspension, stirring and heating were started, and the flask was sealed with a reflux condenser fitted with a molecular sieve tube. After 6 hours at reflux, the product was transferred to a frit and washed successively with dry toluene, acetone, methanol, methanol: water (2: 1) and again with acetone. The washed sorbent was air dried (5 hours, 25 ° C) and in an oven (12 hours, 120 ° C); elemental analysis found 9.3% C, 2.2% H.

Example 2.

A similar reaction to that of Example 1 was carried out. However, 74 ml of toluene and a mixture of 5 ml of hexamethyldisilazane (HMDS) and 2.4 ml of octadecyltrichlorosilane (ODTS) were used on 5 g of silica gel. The time, reaction, temperature and work-up of the product were the same as in Example 1; elemental analysis revealed 15.2% C and 3.1% H.

Example 3.

The silica gel used, the reaction medium, the temperature and the silanization time were the same as in Example 1. A mixture of 1.2 ml of octadecyltrichlorosilane (ODTS) and 5 ml of silica gel was used.

5.5 ml hexamethyldisilazane (HMDS) in 67 ml toluene. The treatment of the product was the same as in Example 1; elemental analysis determined 13.3% C and 2.7% H, respectively.

Example 4.

g of silica gel according to Cs. No. 179184 with a specific surface area of 460 m ² / g was silanized with a mixture of 4 ml octadecyltrichlorosilane (ODTS) and 4 ml hexamethyldisilazane (HMDS) in 80 ml toluene. The reaction and work-up conditions were the same as in Example 1; elemental analysis revealed 19.7% C and 3.9% H.

Example 5.

4 g of silica gel with a specific surface area of 451 m ² / g was stirred at 25 ° C with 4 ml of octadecyltrichlorosilane (ODTS) and 4 ml of hexamethyldisilazane (HMDS) in 40 ml of toluene. The reaction flask was sealed with a molecular sieve tube and the suspension was allowed to stand at room temperature for 120 hours (5 days). Each day the flask was shaken once. The treatment of the silica gel before the reaction and the product after silanization was the same as in Example 1. Elemental analysis showed 18.7% C and

3.6% H. In reverse phase chromatography (mobile phase methanol: water (7: 3)), capacitance factors for benzene k < = 4.92 were found. By way of comparison, when the silica gel was modified with octadecyltrichlorosilane alone, the product contained 22.3% C, 4.3% H, and under comparable conditions the capacitance factors for benzene k ’= 1.281, for diphenyl k = = 6.27. Conversely, when modified with pure HMDS, 5.6% C, 1.5% H were found, and for benzene, k k = 0.24 for diphenyl k ‘= 0.62.

Example 6.

g of silica gel with a specific surface area of 480 m ² / g was formed and dried as in the example

1. The dry silica gel was then suspended in a mixture of 4.75 ml octadecyltrichlorosilane (ODTS) and 3.75 ml hexamethyldisilazane (HMDS) in 40 ml toluene. The reaction was carried out analogously to Example 5 at 25 ° C for 144 hours (6 days). The mixing and processing of the sorbent was the same as in Example 5; elemental analysis determined 21.1% C and 4.1% H, respectively.

Claims (4)

Subject 1. A method of preparing a silica gel sorbent for liquid chromatography in inverted phase with adjustable quantity of fixed carbon, characterized in that the silica is silanized by treatment with a mixture of hexamethyldisilazane and alkylhalosilane selected from RiSiX ₃ RIR ₂ SiX ₂ and R ₁ (R _{2) 2} SiX wherein X is halogen, R is an alkyl radical having 8-22 carbon atoms and R ₂ is an alkyl radical having 1 to 22 carbon atoms, wherein the resulting carbon and hydrogen content in the product is governed by the ratio of hexamethyldisilazane and alkylhalogenvynálezu silane in the initial reaction mixture in the range of 5% to 98% by volume of hexamethyldisilazane. 2. The process of claim 1 wherein the silica gel is silanized by treatment with a mixture of hexamethyldisilazane and octadecyltrichlorosilane. 3. The process according to claim 1, wherein the mixed silane of the silica gel is carried out in a temperature range of 25 to 125 [deg.] C. 4. The process of claim 1 wherein the silanization mixture comprises from about 70% to about 95% hexamethyldisilazane.