CS209267B1 - A polymeric carrier based on a macroporous glycol methacrylate gel and a process for its preparation - Google Patents

Abstract

Polymeric carrier based on glycol methacrylate gel and method of its preparation The invention relates to a new type of polymer carrier based on a copolymer of ethyl methacrylate and ethylene glycol dimethacrylate, which is produced as Separon H or Spheron. The essence of the invention is the properties and method of production of a reactive intermediate, consisting in a two-stage reaction with a high degree of conversion. The obtained polymer material has the basic matrix of the starting polymer, which, however, contains chemically firmly bound chloromethylphenyl groups. The preparation serves as a starting substance for the preparation of anions based on Separon H with the intended use in liquid chromatography.

Description

(54) Polymeric carrier based on macroporous glycol methacrylate gel and method for its preparation

Polymeric carrier based on glycol methacrylate gel and method of preparing same

The invention relates to a new type of polymeric carrier based on a copolymer of ethyl methacrylate and ethylene glycol dimethacrylate, which is manufactured as Separon H or Spheron.

The essence of the invention is the properties and method of production of a reactive intermediate, consisting in a two-stage reaction with a high degree of conversion. The obtained polymer material has the basic matrix of the starting polymer, which, however, contains chemically firmly bound chloromethylphenyl groups.

The preparation serves as a starting material for the preparation of Separon H-based anion exchangers intended for use in liquid chromatography.

The invention relates to a polymeric carrier based on a macroporous glycol methacrylate gel and a method for its preparation. The macroporous glycol methacrylate gel is a copolymer of 2-hydroxyethyl methacrylate and ethylene glycol dimethacrylate (Separon H or also Spheron), the matrix of which contains chemically stable units of the type of 2-hydroxyethyl esters of carboxylic acids.

Polymeric carriers are widely used in various separation techniques in the field of chemical technology, isolation and purification of proteins, production of pure chemicals, in chemical and biochemical analysis of mixtures and in control of the purity of intermediates and products of chemical production. The essence of their function is the presence of suitable chemically bound groups on the molecule of the basic polymer carrier, which allow the use of various types of interactions of molecules in solution with the carrier in the solid phase. Some polymer materials can also separate mixtures of substances based on differences in their molecular weights or shape of molecules (gel filtration). One of the new widely used polymer carriers is the already mentioned Separon H, whose polymer unit has the formula II ,* •«V / ^CH 2

CH ₃ —C—COOCH^Cl^OH

CH, i 2 (Π) and which contains as reactive functional groups acid- and alkali-stable 2-hydroxyethyl esters of carboxylic acids (Czech aut. osv. no. 150 819).

The essence of the invention is a polymer carrier based on a macroporous glycol methacrylate gel, the structural unit of which has the formula I / ^CH 2 (I)

CH,— C —C00CH.CH. OCH.CHCH.O-/ ³ \ ^{2 2 2} , ² \ CH ₂ OH

This structural unit of formula I contains as a characteristic group a 1-(4-chloromethylphenyloxy)-2-hydroxy-3-propyl ether function.

The essence of the method for preparing a polymer carrier according to the invention is that a polymer whose structural unit has the formula II (II)

CH ₂

CH~C—COOCH„CH ₉ OH 3 \ ^{2 z}

CH ₂ is reacted with phenylglycidyl ether of formula III θ-Ο-ΟΗ^Ης—C« ₂ ^(,Π) in anhydrous dioxane in the presence of a complex of boron trifluoride and diethyl ether (1 : 1) at temperatures from 10 °C to 80 °C and the resulting 1-phenyloxy-2-hydroxy-3-propyl ether of the polymer with the structural unit of formula IV

is further reacted with chloromethyl methyl ether of formula V

C1CH ₂ OCH ₃ (V) in the presence of tin trichloride, without solvent or in inert organic solvents, preferably in chloroform, dichloromethane, 1,2-dichloroethane and petroleum ether at temperatures from 0 °C to 60 ^° C.

The starting materials for this process are the copolymer of 2-hydroxylethyl methacrylate and ethylene glycol dimethacrylate, hereinafter referred to as Separon H, which can be used in the entire range of pore sizes and changes that are commonly produced and which must be dried before the reaction, and the phenyl glycidyl ether of formula III, which is easily available from phenol and epichlorohydrin in the presence of aqueous alkali (D. R. Boydand and E. R. Marie: J. Chem. Soc. 83 838 (1908)). The condensation of both components is carried out at room temperature

Hv ¹ or at elevated temperature using a complex of boron trifluoride and diethyl ether (1:1) as a catalyst. Similar conditions were used for the preparation of another polymer support, the so-called PhenylSepharose CL-4B (S. Hjertén, J. Rosengren and S. Pahlman: J. Chromatogr. 101, 281 (1974)). After suctioning off the polymer support, the reaction by-products are washed successively with dioxane, methanol and ether and after drying in vacuum, 1-phenyloxy-2-hydroxy-3-propyl ether of Separon H of formula IV is obtained, which contains 1.80-2.00 milliequivalents of functional groups (determined as phenyl) per 1 g of dry weight of the support, i.e. 70-80% substitution of all 2-hydroxyethyl groups of Separon H.

This material is reacted with chloromethyl methyl ether of formula V, which is also readily available on a large scale, in the presence of tin tetrachloride, in the absence of moisture and at temperatures of 0-60 °C. Chloromethyl methyl ether can be advantageously used directly as the reaction medium and regenerated after the reaction or it can be diluted with suitable inert organic solvents, such as chloroform, dichloromethane, 1,2-dichloroethane or petroleum ether. In these cases, too, the substance V can be easily regenerated after the reaction. After removing the reaction by-products by filtering the polymer and washing it successively with dioxane, its mixture with hydrochloric acid, methanol and ether, the obtained product of formula I is dried under high vacuum. The polymer material thus prepared contains 1.80-2.0 milliequivalents of chloromethyl groups per 1 g of dry weight, so that the substitution of phenyl groups in the intermediate of formula IV is practically quantitative.

When performing the entire above procedure, the basic polymer /^2 is not macroscopically disturbed.

C—C00CH„CH,0CH,CHCH,0 \ 2 2 2 | 2 ^X CH ₀ OH

I ²

CH.

^ch ₂ r Separon H matrix: intermediate of formula IV and final product of formula I retain the spherical shape of the particles and the basic parameters crucial for use even in high-performance liquid chromatography (HPLC), i.e. e.g. flow rate and low compressibility at high operating pressures. The above procedure is feasible both in the laboratory and on a large scale, since it does not require special equipment or difficult-to-access raw materials.

The polymer obtained according to the invention (formula I) is characterized by the presence of an ether-linked group with an aromatic nucleus containing a chloromethyl group. The latter function is sufficiently stable in the absence of strong nucleophilic reagents, so that the product can be stored under suitable conditions without loss of reactivity. Furthermore, it is sufficiently reactive for the preparation of new moderately and strongly basic anion complexes based on Separon H with the structural unit of formula VI (VI) where R is an amino, alkylamino, dialkylamino or trialkylammonium functional group.

In the following, the subject matter of the invention is illustrated by examples of embodiments, without being limited thereto in any way.

Example 1.

A suspension of 20 g of the substance of formula II (Separon H 40.10—15 μ) dried for 24 hours at 13 Pa over phosphorus pentoxide in 200 ml of dioxane is stirred at 60 °C in a reflux condenser with a calcium chloride stopper and a dropping funnel. 10 ml of boron trifluoride and diethyl ether complex (1: 1) (redistilled) are added to the mixture and a solution of 15 g of phenylglycidyl ether in 50 ml of dioxane is added dropwise over 1 hour. The mixture is stirred first for 8 hours at 60 °C and then for 16 hours at room temperature _, then filtered off with suction, the polymer material is washed successively (2 x 100 ml) with dioxane, boiling dioxane, boiling methanol and ether. The product obtained is dried at 13 Pa over phosphorus pentoxide. 20 g of the substance of formula IV and containing 1.93 meq. are obtained.

of phenoxyl groups per 1 g of dry weight.

Example 2.

g of the substance of formula II (SéparonH-1000,25-63 μ) is reacted and processed as described in Example I (with half the amount of reagents). 9.9 g of the substance of formula IV with a content of 1.97 meq. of phenyloxy group per 1 g of dry weight is obtained.

Example 3.

A suspension of 20 g of the substance of formula IV prepared according to Example 1 in 120 ml of chloromethylmethyl ether is stirred under reflux with a calcium chloride stopper at 60 °C for 1 hour and then 4 ml of tin tetrachloride are added over 5 min. The mixture is stirred at 60 °C for 5 hours and then for 16 hours at room temperature. The polymer product is filtered off with suction, washed successively (3 x 100 ml) with dioxane, a mixture of dioxane with 3N hydrochloric acid (3:1), a mixture of dioxane with water (3:1), dioxane, methanol and ether. After drying at 13 Pa over phosphorus pentoxide, 20 g of the product of formula I with a content of 1.90 meq. chloromethyl groups per 1 g of dry weight are obtained.

Example 4.

g of the substance of formula IV prepared according to Example 2 is reacted and processed as described in Example 3 (on a half scale). 9.9 g of the substance of formula I containing 1.96 meq. chloromethyl group per 1 g of dry weight is obtained.

Example 5.

A suspension of 10 g of the substance of formula IV, prepared according to Example 1, in a mixture of 80 ml of chloroform and 60 ml of chloromethyl methyl ether is stirred under a reflux condenser and a calcium chloride stopper at 60 °C and, after adding 4 ml of tin tetrachloride, it is stirred at this temperature for 10 hours. It is treated as in Example 3. 10 g of the substance of formula I is obtained with a content of 1.90 meq. chloromethyl groups per 1 g of dry weight.

CORRECTION of the description of the invention to the copyright certificate No. 209 267

International Cl? C C8F 20/18 C 08 P 20/pO 3 01 J 41/14

The description of the invention for copyright certificate No. 209,267 was not printed.

Claims (2)

Object of the invention. 1. A polymeric support based on a macroporous glycol methacrylate gel whose structural unit has the formula σΗ ^ -0ςα000Η ₂ 0Η ₂ 00Η ₂ 0Η0Η ₂ 0 - </ Α0Η ₂ 01 (I) ./ OH 2. A process for the preparation of a polymeric carrier according to claim 1, wherein the polymer having a structural unit of formula II I ch ₂ GH-- C00CH ₂ C-CH ₂ 0H (II) \ h ~ ¹² reacts with the phenylglycidyl ether of formula III O-CH ₉ CH-CH _o V / (III) in an anhydrous dioxane environment in the presence of a 1: 1 boron trifluoride-diethyl ether complex at temperatures of from 10 ° to 80 ° and the resulting 1-phenyloxy-2-hydroxy-3-propyl ether polymer having the formula IV. CH.z -C C0CCH _{of about} 0CH CH CH CH _N OP ^ \ 2 2 2 | 2 CH 2 OH (IV) is further reacted with chloromethyl methyl ether of formula V (V) in the presence of tin tetrachloride, either in solvent or in internal organic solvents, preferably in chloroform, chloroform, 1,2-dichloroethane and petroleum at temperatures from 0 ° C to 60 ° C. UKAL FOR INVENTIONS AND DISCOVERIES