CS271855B1 - Preparing method of sorbent on a base cyclo-dextrine - Google Patents

Abstract

The solution concerns the production method of sorbent based on cyclodextrin, during which cyclodextrin is bound firmly to the carrier without the coupling chain. It starts from the carrier containing the final hydroxyl group, which is activated by a halogen chemical agent and exposed to the reaction with cyclodextrin, or its derivates, at a temperature of 70 to 140 degrees C in the presence of the weak base in the ambient medium of the aprotic solvent with boiling point over 80 degrees C. This sorbent can be used for example as stationary phase in liquid chromatography, thin-layer chromatography, etc.

Description

The invention relates to a process for preparing a cyclodextrin-based eorbent.

In high performance liquid chromatography, ee has recently abandoned the use of universal sorbents, such as silica gel or octadecyleilane-modified C-18 silica or other types of alkyl-modified silica, and has shifted to the use of sorbents with properties modified to enhance their selectivity for separation of some type of substances. These include, for example, aminopropyl or cyanopropyl modified silica gels. Many large groups consist of sorbents for the separation of enantiomers, various polymeric sorbents, sorbents for ion exchange chromatography and, last but not least, sorbents for bioaffinity chromatography. One of the types of selective sorbents recently used is unbound cyclodextrinine silica, which has selectivity to a variety of structural isomers, including a variety of optical isomers of barbiturates and amino acid derivatives.

Currently, three methods are used to prepare sorbents with cyclodextrin-bound:

1. non-binding of cyclodextrin to silica gel through the C3-C20 linker, which does not contain a hydrolytically unstable bond. The process of this preparation is patent protected (D.W. Armstrong, US 4,539,399) and utilizes glycidopropylsilane modified silica gel and cyclodextrin sodium. This adsorbent is currently commercially available under the name Cyclobond (Advanced Separation Technologies Ltd.). Although the resulting product is hydrolytically stable, the absence of heteroatoms in the attachment chain when used in liquid chromatography, however, in some cases makes separation impossible.

2. binding of the cyclodextrin to an euccinyl-terminated chain-modified gel which is the reaction center for subsequent cyclodextrin binding. Cyclodextrin is bound as a 6-mono-ethylenediamine derivative. (M. Tanaka et al., O. Chrom. 370, 283, 1986).

3. coupling of cyclodextrin in the form of a monoilate to silica gel modified with 3-aminopropylsilane, which may be further modified with ethylenediamine or diethylenetriamine (K.Fujimura et.al.O.Chrom. 350, 371, 1985).

In these two processes, the products are hydrolytically less stable than in the first process, which results in a gradual deterioration in the properties of the sorbents during use. Binding of the cyclodextrin through the linker also allows for spatial mobility and a difficult position of the molecule.

Other methods of binding cyclodextrin to silica gel have also been used and the cyclodextrin has also been polymerized or bound to a polymeric carrier. In these cases, the main disadvantage of the prepared sorbet is the low bond strength, which is unpleasant in the use of such a substance in liquid chromatography.

In the novel sorbents prepared by the process of the invention, the cyclodextrin is not bound to the support via any linker, thereby firmly anchoring the cyclodsxtrin molecule to the support and providing its definable position. The process according to the invention also reduces the preparation effort in terms of both the number of steps and the degree of demand for an anhydrous inert atmosphere than in the above processes.

The present invention provides a process for the preparation of cyclodextrin-based sorbents starting from a hydroxyl-containing carrier, e.g. silica gel, HEMMA. These terminal hydroxyl groups of the support are activated with an agent selected from the group of halogenating agents, then the activated support is reacted with a cyclodextrin selected from the group consisting of, (3, or 4) cyclodextrins or derivatives thereof with alkylated, aryl or acylated hydroxyl groups. at a temperature of 70 to 104 [deg.] C. with a weak base in an aprotic solvent medium boiling above 80 [deg.] C., preferably dimethylforCS 271 855 B1 amide and pyridine.

The sorbent prepared by the process according to the invention can be used in various ways, for example as a stationary phase in liquid chromatography, thin layer chromatography, after preliminary addition of samples by so-called solid-phaae extractlon. The advantage of this sorbent over other types is that it can be used for resolving optical isomers.

In the following, the invention is illustrated in more detail by way of examples, which, however, are not intended to limit the scope of the invention in any way.

Example 1

Silica gel with particles of irregular size 10 µm is well formed. Drying is carried out under vacuum over phosphorus pentoxide at 110 ° C. The dry silica gel is then refluxed at normal pressure with β thionyl chloride in dry benzene to exclude air humidity. The reaction time is 24 hours. The solid reaction products were separated, washed with dry benzene and dried under vacuum over phosphorus pentoxide in the same manner as the original silica gel.

The cyclodextrin was reacted under phosphorus pentoxide for 24 hours at 105 ° C under vacuum.

The actual binding of cyclodaxtrin to ailica gel and is carried out in pyridine. For reaction ae 2 cyclodextrin weight parts and 3 parts of the first reaction product are used, Cylodaxtrin ee is dissolved in the solvent and the first reaction product is added. The reaction mixture was heated to reflux at 95 ° C for 10 hours. In the reaction Air humidity must be eliminated. The solid products of the reaction were separated and thoroughly washed with the solvent in which the reaction was carried out, methanol, water and finally methanol and dried under vacuum at 50 ° C.

Example 2

As in Example 1, but using ae silica gel and a spherical particle size of 8 µm. The reaction is carried out at 80 ° C in benzene, in the presence of an equimolar amount of tristhylamine.

Example 3

Separone-HEMA was used for the reaction instead of silica gel and the procedure was as in Example 1. The reaction was carried out in toluene at 104 ° C in the presence of an equimolar amount of tristhylamine.

Example 4

The reaction is carried out as in Example 1, the reaction temperature for the preparation of activated silica gel being 70 ° C and dimethylformamide as solvent.

Example 5

Activated silica gel was prepared as in Example 1, but the reaction temperature was 95 ° C for cyclodextrin coupling.

Example 6

The same procedure as in Example 1 was followed to prepare the reaction with silica 8 with thionyl bromide.

Example 7

The preparation procedure is the same as in Example 1, but the β-cyclodextrin is replaced by β-cyclodextrin instead.

CS 271 855 Bl

Example 8

The preparation procedure is the same as in Example 1, but uses α-cyclodextrin for reaction ea.

Example 9

The preparation of aa is carried out as in Example 1, except that acylated 4-cyclodaxtrin is used for the reaction of aa.

Example 10

As in Example 1, aa used aa silica gel and a spherical particle size of 8 µm and 2.3 dl methyl 4 - / or CC, respectively cyclodaxtrin. The reaction is carried out at 80 ° C in benazan, in the presence of an equimolar amount of triethylamine.

Example 11

The reaction is carried out as in Example 1 and the reaction temperature in the preparation of the activated algel is 70 ° C and dimethylsulphoxide is used as the solvent.

Claims (2)

of the invention CLAIMS 1. A process for preparing a cyclodextrin-based aorbant starting from a hydroxyl-containing bioreactor, characterized in that the terminal hydroxyl groups of the carrier aa are activated with a reagent selected from a group of halogenating agents. its derivatives at a temperature of 70 to 104 ° C, in the presence of a weak base in an aprotic solvent environment and boiling above 80 ° C, preferably pyridine, dimethylformamide. 2. A method according to claim 1, wherein the cyclodaxtrin is selected from the group consisting of C, S, or C cyclodaxtrins, respectively. derivatives thereof and alkylated, aryl or acylated hydroxyl groups;