WO2008135246A1

WO2008135246A1 - Synthetic resins based on epoxides

Info

Publication number: WO2008135246A1
Application number: PCT/EP2008/003566
Authority: WO
Inventors: Michael Weller; Caroline Peskoller; Reinhard Niessner
Original assignee: Technische Universität München
Priority date: 2007-05-02
Filing date: 2008-05-02
Publication date: 2008-11-13

Abstract

The present invention is directed to a process for manufacturing of an epoxide resin, an epoxide resin obtained by this method as well as the use of said epoxide resin.

Description

Synthetic resins based on epoxides

1. Summary

The present invention is directed to a process for manufacturing of an epoxide resin, an epoxide resin obtained by this method as well as the use of said epoxide resins.

It is one object of the present invention to provide a simple and inexpensive process for the preparation of porous and nonporous epoxide polymers. According to this invention a new polymer (II, exemplary structure) is prepared from oxiranes (I), also named as epoxides, in a polyaddition reaction.

In a specific embodiment of the invention the preparation of the new porous polymers occurs in the presence of solvents which are added to the starting material acting as porogens. Application areas of the new polymers are chromatography, water treatment technologies and other technologies.

[+ catalyst]

+ nucleophile

Figure I : Reaction scheme of the polyaddition

2. Background of the invention

The invention is directed to synthetic resins which are free from aromatic hydrocarbons, preferred in porous form, as well as the method for the manufacturing and its use.

The word "monolith" derives from the Greek language and means "single stone". It is also used in sense for objects, which consist of a single piece. Therefore, in the chromatography stationary phases of one single material are also called monoliths. Monolithic materials are used in the high-performance liquid chromatography (HPLC), preferably in affinity chromatography (AC) and gel permeation chromatography, as well as in gas chromatography (GC), capillary electrochromatography (CEC), catalysis, microfluidics and as enzyme-flow reactor'¹'.

That monolith consist of a hard and porous material. The structure of that material consists of multiple substructures and micro channels. Organic monoliths are produced by polymerization of suitable monomers and crosslinkers. In the case of adding pore forming agents, a coherent network of pores is formed during the polymerisation process by phase separation'²¹.

Nowadays multiple materials are known in separation science. They are based mainly on inorganic materials such as silica, glass, aluminium oxide, titanium dioxide, etc. or on organic materials such as polystyrene-divinylbenzene (PS-DVB), polyacrylamide and polymethacrylate.

These materials are used in a variety of separation techniques such as HPLC, affinity chromatography (AC), gas chromatography (GC), as well as in catalysis, microfluidics and as enzyme-flow reactor. Classical particulate stationary phases for chromatography separations are prepared by packing micrometer sized porous, monodisperse particles into a column. Separation of analytes takes places in the pores of particles and therefore the rate of separation is diffusion limited, meaning the rate can be increased only on the expense of lower separation quality. In addition, the relatively low porosity of such columns increases the backpressure of such columns. Thus, monolithic phases are becoming more and more important in this field.

The advantages of monolithic materials are in general^[3]:

No void volume inside the column influencing the separation.

High mechanical stability of the monoliths maintains long operation lifetime and high reproducibility.

Unique monolith morphology.

Fast mass transfer between the stationary and mobile phases.

High speed and high resolution at low backpressures. Monolithic materials based on PS-DVB (polystyrene divinyl-benzene), methacrylate and on silica are known. The silica-based monoliths Chromolith® (Merck, Darmstadt) is produced by the sol-gel process at high temperature^{[4> 5]}. The CIM®-monolith (BIA Separations d.o.o., Slovenia), is made by a radical polymerization at 65°C^[6' ^7]. Organic monoliths are generally produced by a thermally initiated radical polymerization. The preparation of such materials possible in small dimensions But the production of large monoliths is very complicated. During the polymerization process, a radial temperature gradient in the polymer often occurs, which causes strong inhomogeneities of the pore structure. For this reason, monoliths are preferably produced in small dimensions. In addition, a derivatisation of these monoliths is not possible or difficult.

The inventors have a lot of experience with the production of sol-gel glasses for the immobilization of antibodies. These glasses have to be pulverised for this application. This step is irreproducible and a great loss of material is connected with the grinding step. Furthermore the product quality does not meet the requirements.

Therefore, experiments were performed to get monolithic (porous) sol-gel glasses. These experiments were not very successful. As an increasing amount of publications about organic monoliths was observed, the further works in this field were based on methacrylate monoliths. The obtained materials were not suitable for the proposed analytical problem. The monoliths should have the following properties:

The material should be sufficiently hydrophilic for an application especially in biochromatography.

The material should be modifiable with separation ligands to adjust the separation material to the different analytical problem.

The material should be stable against hydrolysis.

The pore size of the material should be large enough.

Epoxy polymers are materials with different properties and application areas. These materials are based on the polymerization of epoxy monomers. They are characterized by a high mechanical stability, chemical resistance and no limitation in shaping. Depending on the application, the network of oligomers with epoxy groups is conducted in different ways. The common preparation method for epoxy polymers is as two-component system, whereas polymerization is achieved by polyaddition using primary or secondary amines^[8]. Epoxy polymers are used as adhesives, industrial flooring, concrete coating, corrosion protection, and as a matrix material for the production of fiber composite parts, including aerospace applications, for the motor sport and for yacht manufacturing.

The disadvantage of the known preparation processes for non-porous epoxides is the use of at least two main components, which makes efforts in large-scale manufacturing extensive¹⁹¹.

Previous works about porous epoxide polymers refer to two-component-systems (WO 2006/073173 Al, JP2001181436A2, JP2003000175193).

The German patent DE 2528022 describes the production of polyglycidylether, which is applied in the presented invention as starting material.

3. Detailed Description of the invention

3.1. Production of the non-porous epoxide polymers

It is one object of the present invention to provide a simple and inexpensive process for the preparation of polymers with high chemical and mechanical stability.

According to the present invention polymer (II) is prepared through the reaction with oxiranes (I), also named as epoxide, in a polyaddition reaction shown in figure 1.

Figure J: Reaction scheme of the polyaddition.

wherein n represents an number of 2-30, preferably 2-10, most preferred 2-4 or 3-4; R_{I i2},3 represents hydrogen (H), alkyl, O-alkyl, alkenyl, silyl, fluoroalkyl, hydroxyalkyl and/or epoxide,

X represents aliphatic or cycloaliphatic or mixed aliphatic-cycloaliphatic unsubstituted organic residue having 1 -20 C-atoms,

Catalyst represents a special catalyst like lewis- and mineral acids such as sulphuric acid (H₂SO₄), nitric acid (HNO₃), phosphoric acid (H₃PO₄), hydrochloric acid (HCl), most preferred boron trifluoride (BF₃), boron trifluoride-complexes, aluminium chloride (AlCl₃), zinc chloride (ZnCl₂), tin tetrachloride (SnCl₄), diethyl aluminium chloride ((C₂H₅)₂A1C1), titanium(IV) isopropoxide (Ti[OCH(CH₃)₂]₄, titanium tetrachloride (TiCl₄), trimethylsilyl trifluoromethanesulfonate CF₃SO₃Si(CH₃)₃ (III)) having the chemical structure according to figure 2, triphenylmethyl perchlorate

((C₆Hs)₃CClO₄),

The nucleophile represents a nucleophilic agent, such nucleophiles may be traces of water (H₂O), ammonia (NH₃), alcohol (R-OH) or primary or secondary amine (R-

NH_2, R₂-NH), or in situ catalytic opened epoxide, wherein R could be any organic residue, preferably according to the above definition of Ri, R₂, or R₃.

(III)

Figure 2 Chemical formula of one possible catalyst trimethylsilyl trifluoromethanesulfonate

(III)

Surprisingly the reaction according to Figure 1 succeeded in the production of a new material consisting of compound (II) and described in Figure 1.

According to another embodiment of the invention, epoxides with the chemical structure (IV) shown in figure 3 can be used as an alternative to compound (I) to produce the new polymer materials. The compounds having the formula (IV) are glycidyl ether derivatives of alcohols.

(IV) Figure 3: Chemical structure of chemical compound IV.

wherein n represents an number of 2-30, preferably 2-10, most preferred 2-4;

Ri_i2i3 represents hydrogen (H), alkyl, O-alkyl, alkenyl, silyl, fluoroalkyl, hydroxyalkyl and/or epoxide;

Y is selected from sugar alcohols, preferred sorbitol or hexitol; glycerol, ethylene glycol, propylene glycol, butanediol, hexanediol, pentaerythritol, polyvinyl alcohols and carbohydrates, like starch, cellulose, polyvinyl alcohol, polyvinyl glycerol, polyethylene glycol, poly propylene glycol, poly-hydroxy acrylate and poly-hydroxy- methacrylate.

An example for the reaction according to figure 1 is the polymerisation of glycerol triglycidyl ether and/or pentaerythritol tetraglycidyl ether, especially with polyglycerol-3-polyglycidyl ether (V) (see figure 4). These substances can be used according to this invention as starting material displacing chemical compound (I) in the reaction shown in figure 1, wherein m represents an number of 1 to 30, preferably in the range of 1 to 10, most preferred in the range of 1 to 3. Furthermore branched polyglycerol and (partially etherified) glycidyl ether of glycols, triols and higher polyols are applicable as starting substances.

Polyglycerol-3-polyglycidyl ether Glycerol triglycidyl ether Pentae rrythri¹tol tetraglycidyl ether

(V) (VI) (VII)

Figure 4: Example for starting materials referring to the reaction in figure 1. The polymerization shown in figure 2 is initiated according to the invention by adding a catalyst as described above, particularly preferred boron trifluoride-complexes like boron trifluoride-diethyletherate (BF₃O(CH₃CH₂)₂). The quantity of such catalyst is the range of 0.01 to 5.0 weight%, preferably 0.1-1.0 weight%, referred to the starting materials epoxides (I).

When using epoxides (I) according to figure 1 , traces of nucleophils are necessary for the initiation of the polyaddition. Examples for nucleophils are water, ammonia or alcohols and preferred in the ration of quantity < 1 mass%. These nucleophils could also be generated by an in-situ catalytic ring-opening reaction of a small amount of the epoxides. Such epoxides with already opened ring may occur as traces or contaminations in the material acting as a nucleophilic agent.

Practical reaction procedure:

First of all (reaction kickoff) the reactants according to figure 1 have to be mixed for a period of 1 to 120 seconds, preferably 15 seconds, e. g. by mixing, shaking, stirring, vibrating, panning and similar procedures, preferably with stirring for example with 200 rpm (revolutions by minute).

The polymerization shown in figure 1 is conducted according to the invention in the temperature range between 10 and 100°C, particularly preferred between 15 and 30⁰C and a pressure range between 0.1 and 10 bar, particularly preferred at 1 bar. The vessel in which the reaction occurs (shown in figure 1) and/or where the starting materials are introduced, may consist of metals, plastics, such as Plexiglas, polypropylene, polyethylene, polystyrene and polyvinyl chloride, preferred of glass. At the end of the reaction the vessel can be opened and the novel polymeric epoxide (II) can be removed. The new material can be considered as a polyoligoepoxide with a composition according to figure 1 , formula II.

The above described residues R], R₂ and R₃ in the formulas are independent from each other and may comprise the following chemical groups:

Preferably hydrogen; - Alkyl; - O-alkyl; Alkenyl;

- Alkinyl;

- Silyl;

- Haloalkyl; Hydroxyalkyl; and/or Epoxy.

The above-named substituents alkyl, alkenyl, O-alkyl, silyl, haloalkyl, hydroxyalkyl and epoxy are defined as follows:

An alkyl is a saturated hydrocarbon residue, preferred substituted, non-substituted, straight- chain, cyclic and/or branched Ci-C₂₀-alkyl, preferred Ci-Cio-alkyl, further preferred CpC₈- alkyl, Ci-C₃-alkyl and most preferred Ci-alkyl. Examples of such alkyl substitute are methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl and t-butyl.

Alkenyl is a single or a multiple unsaturated residue, i.e. an alkyl residue with one or more double bonds. The alkenyl is preferred a substituted or non-substituted, straight-chain and/or a branched Ci-C₂₀-alkenyl, preferred C₂-Ci₀-alkenyl, further preferred C₂-C₈-alkenyl and most preferred C₂-C₃-alkenyl.

Alkinyl is an unsaturated residue with one or multiple triple bonds, i.e. an alkyl residue with one or more triple bonds. The residue can also possess one or more double bonds. The alkinyl is preferred a substituted or non-substituted, straight chain, cyclic and/or branched C₂-C_2O- alkinyl, preferred C₂-Cio-alkinyl, further preferred C₂-C₈-alkinyl and C₃-C₆- alkinyl and most preferred C₂-C₃-alkinyl.

O-alkyl is a saturated hydrocarbon residue -CH-O-CH or -C-alkyl-O-C-alkyl or -CH-O-C- alkyl or O=CH₂ or O=alkyl. The O-alkyl contains one or more oxygen besides the alkyl residue. Instead of the alkyl residue the O-alkyl can also contain a single or may combine one or more alkenyl and/or alkinyl-residues. The oxygen atom(s) are/is connected via two single bonds with two neighbouring carbon atoms at any point in this molecule residue. Silyl is a residue H₃Si-, consisting of three hydrogen atoms and one silicon atom, or (Alkyl)₃- Si-. The silicon atom has one free bond. Instead of the alkyl residues the silyl could also have a single or combine one or more alkenyl and/or alkinyl residues.

Haloalkyl is a saturated hydrocarbon residue, which has additionally one or more halogen atoms in the molecule. Halogen atoms can be fluorine, chlorine, bromine, or iodine. The halogen atom(s) can have a single bond to the neighbouring carbon atoms anywhere in the molecule. Instead of the alkyl residue the molecule can also have a single or can combine one or more alkenyl and/or alkinyl-residues.

A hydroxyalkyl is a saturated hydrocarbon residue with additionally one or more additional hydroxy groups. The hydroxy is a functional group consisting of an oxygen atom and a hydrogen atom. The hydroxy-group(s) are/is bond with one or two neighbouring carbon atoms anywhere in the molecule to two single bonds. Instead of the alky residues the residues can also be single or combine one or more alkenyl and/or alkinyl-residues.

An epoxy is a saturated hydrocarbon residue with additionaly one or more epoxy groups in the molecule. The epoxy group is a functional group consisting of an oxygen atom, which is linked to two neighbouring carbon atoms with two single bonds. The epoxy group(s) are/is linked with one or two single bonds to one or two neighbouring carbon atoms anywhere in the molecule. The remaining free valences of the epoxy group are connected with one or more of the above-described functional groups or residue.

The new epoxide polymers (compound II in Figure 1) according to this invention are prepared by a very simple method with one main component - compound (I) in figure 1. This leads to much lower costs of production and production complexity in comparison to the large-scale production where multiple starting materials are required.

The present description in the following will be explained in more detailed based on the Examples and the Figures, wherein the following is shown:

Figure 1 : Reaction scheme of the polyaddition. Figure 2: Chemical formula of one possible catalyst trimethylsilyl trifluoromethanesulfonate CF₃SO₃Si(CH₃)₃) (III).

Figure 3: Chemical structure of chemical compound IV.

Figure 4: Example for starting materials referring to the reaction in figure 1.

Figure 5: Reaction scheme of the polyaddition.

Figure 6: The image on the right site shows the dried monolith. The large image is the scanning electron microscopic (SEM) image.

Figure 7: Scanning electron microscopic image of the monolith.

Figure 8: left) Pore structure of the new monolith prepared with the porogen toluene/dioxane, right) Pore structure of the monolith prepared with the porogen methyl-tert- butylether/dioxane.

Figure 9: Pore size distribution of two new monoliths with different porogens: (1) porous epoxide polymer with 80 Vol% toluenel/dioxane (4/1), (2) porous epoxide polymer with 80 Vol% MTBE/toluene (2/3). X axis: pore radius in μm (logarithmic), Y axis, left: cumulative volume in mm³/g, Y axis, right: relative pore volume in %.

Figure 10: Dependency of back pressure and applied flow rate with a monolith prepared with 80% MTBE/toluene (2/3) with the dimension 4.6 x 50 mm after this invention.

Figure 11 : Affinity chromatogram of human serum. Chromatografic conditions: 10 μL injection of diluted human serum (1 :10) in labeling buffer, enrichment with labelling buffer with 5 mL/min, elution with elution buffer with 5 mL/min. Chromatographic peaks: (1) non- interacting analyts, (2) eluted IgG. Examples:

Example 1): 1000 μL polyglycerol-3-polyglycidyl ether containing traces of nucleophilic agents like described in the detailed description of the invention were introduced in a glass tube with a size of 5 mL. At room temperature and under atmospheric pressure 10 μL (1 vol%) BF₃-solution in diethyl ether (1 : 10) were added within a few seconds. The polymerization is finished within a few minutes. By opening the glass tube, the epoxide polymer according to the invention can be removed.

Example 2): 1000 μL glycerol triglycidyl ether containing traces of nucleophilic agents like described in the details description of the invention were introduced in a glass tube with a size of 3 mL. At room temperature and under atmospheric pressure 10 μL (1 vol%) BF₃- solution in diethyl ether (1 :10) were added within a few seconds. The polymerization is finished within a few minutes. By opening the glass tube, the epoxide polymer according to the invention can be removed.

Example 3): 1000 μL pentaerythritol tetraglycidyl ether containing traces of nucleophilic agents like described in the detailed description of the invention were introduced in a glass tube with a size of 3 mL, which contains traces of nucleophiles. At room temperature and under atmospheric pressure 10 μL (1 vol%) BF₃-solution in diethyl ether (1 :10) were added within a few seconds. The polymerization is finished within a few minutes. By opening the glass tube, the epoxide polymer according to the invention can be removed.

3.2. Production of the porous epoxide polymers

One further object of the present invention is to provide a simple and inexpensive process for the preparation of porous epoxide polymers.

According to the present invention, the new porous epoxide polymer (II) is prepared through the reaction with oxiranes (I), also named as epoxides, in a polyaddition reaction shown in figure 5.

Figure 5: Reaction scheme of the polyaddition.

wherein:

- N represents a number of 2-30, preferred 2-10, most preferred 2-4;

Ri_;2,3 represent hydrogen (H), alkyl, O-alkyl, alkenyl, silyl, fluoroalkyl, hydroxyalkyl and/or epoxide,

X represents aliphatic or cycloaliphatic or mixed aliphatic-cycloaliphatic unsubstitute organic group with 1 -20 C-atoms,

Catalyst represents a special catalyst like lewis- and mineral acids such as sulphuric acid (H₂SO₄), nitric acid (HNO₃), phosphoric acid (H₃PO₄), hydrochloric acid (HCl), most preferred boron trifluoride (BF₃), boron trifluoride-complexes, aluminium chloride (AlCl₃) zinc chloride (ZnCl₂), tin tetrachloride (SnCl₄), diethyl aluminium chloride ((C₂Hs)₂AlCl), titanium(IV) isopropoxide (Ti[OCH(CH₃)₂]₄, titanium tetrachloride (TiCl₄), trimethylsilyl trifluoromethanesulfonate CF₃SO₃Si(CH₃)₃ (III)) with the chemical structure according figure 3, triphenylmethyl perchlorate

((C₆Hs)₃CClO₄),

Nucleophile represents a nucleophilic agent, such nucleophiles may be traces of water

(H₂O), ammonia (NH₃), alcohol (R-OH) or primary or secondary amine (R-NH_2, R₂-

NH), or in situ catalytic opened epoxide, of which R could be any organic residue, preferred in accordance with the above definition of Ri, R₂, or R₃. It might be not necessary to add these compounds intentionally.

Solvents may be: organic solvents like toluene, methyl-tert-butyl-ether, dioxane, tetrahydrofuran (THF), ethyl acetate, dichloromethane, or xylene, and their mixtures, or polymers.

An example for the reaction according to figure 5 is the polymerisation of glycerol triglycidyl ether and pentaerythritol tetraglycidyl ether, especially with polyglycerol-3-polyglycidyl ether (V) (see figure 4). These substances can be applied according to the invention as starting material for the reaction shown in figure 5.

The polymerization shown in figure 5 is initiated according to the invention with a catalyst as described above, particularly preferred boron trifluoride-complexes like boron trifluoride- diethyletherate (BF₃O(CH₃CH₂₎₂ ). The quantity of such catalyst is the range of 0.01 to 5.0 weight%, preferred 0.1-1.0 weight%, referred to the starting materials (I).

When using epoxides (I) respectively (II) according to figure 5, traces of nucleophils are necessary for the initiation of the polyaddition. Nucleophils are for example water, ammonia or alcohols and preferred in the ration of quantity < 1 mass%. These nucleophils could also be generated by an in-situ catalytic ring opening of a small amount of the epoxides. Such former epoxides with already opened ring could be contained as traces or contaminations in the material.

In a special embodiment of the invention the preparation of the new porous epoxide polymers occurs in the presence of solvents which are added to the starting material acting as porogens. The complex requirements to the solvent are the ability to dissolve the monomer and additionally no influence respectively no disturb to the ongoing of the chemical reaction. According to the invention the porosity of the new monoliths is specifically affected by the variation of the type of the porogenic agent and otherwise by variation of the ratio - porogenic agent to the monomer. As one result of this invention a linear dependency of the porosity the ratio - porogenic agent to the monomer- was observed. According to this invention the pore size and the morphology of the new materials can be influenced by the variation of the porogens and the porogen to monomer ratio.

At the beginning of the reaction, the reaction partners should be mixed intensively for a period of 1 to 120 seconds, preferred 15 seconds. The mixing can be made by mixing, shaking, stirring, vibrating, panning and similar procedures, preferably with stirring for example with 200 rpm (revolutions by minute).

According to the invention the polymerization shown in figure 5 is conducted in the temperature range between 10 and 100°C, particularly preferably between 15 and 30⁰C and a pressure range between 0.1 and 10 bar, particularly preferred at 1 bar. The vessel in which the reaction regarding figure 5 is conduced or in which the starting materials are introduced, may consist of metals, plastics, such as Plexiglas, polypropylene, polyethylene, polystyrene and polyvinyl chloride, preferred of glass. The diameter of the vessel is between 1 μm and 50 cm, preferred 1-10 mm.

The new polymer material consisting of a porous framework of compound (II) is built by polymerization of the mixture of the monomer and the porogenic agent within a few hours. According to the invention this new material can be washed by various solvents as described above to remove the porogens and the catalyst. Another possibility is to air-dry the new material. According to the invention, the mixture of solvent, porogenic agent and catalyst can be re-used for the reaction described in figure 5 after the end of the reaction.

According to this invention the reaction time of the polymerization can be controlled through the quantity of the catalyst. Furthermore the porosity and morphology of the new monolith can be influenced by varying the quantities of porogen-monomer-mixture and the porogen. In this way porous structures with mean pore sizes of between ca. 10 to ca. 10 μm are obtained. According to the invention the advantage of the new monoliths is the high hydrophilic surface. These monoliths posses many functional groups on the surface, which allows coupling of molecules. Thus the properties of the new materials could be varied.

Examples:

Example 1): 650 μL (65 Vol%) toluene were introduced in a glass tube with the dimensions of 5 mL. At room temperature and under atmospheric pressure 10 μL (1 Vol%) BF₃-solution in diethyl ether (1 : 10) were added in a few seconds while stirring the solution. 350 μL (35 Vol%) polyglycerol-3-polyglycidylether containing traces of nucleophils as described above, were added during the stirring process. Thereafter, the solution was mixed intensively with a Vortex-stirrer. The reaction mixture was transferred in a tube consisting of polypropylene with the dimension of 2 mL and closed. The polymerization was conducted for 3 hours. The emerged porous block was removed from the tube and washed with THF to remove the porogens. The monolith was after then dried at room temperature for 24 h. The scanning electron microscopic (SEM) image (see figure 6) shows a very homogeneous distributions of the pores with a pore size of 3 μm. The density of the monolith was 0.64 g/cm³ and the shrinkage 20%. Figure 6 The image on the right site shows the dried monolith The large image is the scanning electron microscopic (SEM) image

Example 2): 800 μL (80 Vol%) of a mixture with toluene and methyl-tert-butylether (volume ratio 3:2) were introduced in a tube of polypropylene with the dimensions of 2 mL. At room temperature and under atmospheric pressure 1.5 μL (1.5 Vol%) BF₃-solution in diethyl ether (1 : 10) were added within few second while stirring. 200 μL (35 Vol%) polyglycerol-3- polyglycidyl ether containing traces of nucleophils as described above, were added during stirring process. Thereafter the solution was mixed well with a Vortex-stirrer. The reaction mixture was transferred in a 1 mL syringe consisting of polypropylene with the dimension of 2 mL, closed and positioned in a stand at room temperature. The polymerization was conducted for 3 hours. The emerged porous block according to the invention with the dimension of 4x50 mm was removed from the syringe and washed with THF to remove the porogens. The monolith was then dried at room temperature for 24 h. The scanning electron microscopic (SEM) image (see figure 7) shows a pore size of 1 1 μm and the shrinkage by drying was 5%.

Figure 7 Scanning electron microscopic image of the monolith

Example 3): 800 μL (80 Vol%) of a mixture with toluene and dioxane (volume ration 4: 1) was introduced on a glass tube with the dimensions of 2 mL. At room temperature and under atmospheric pressure 1.5 μL (1.5 Vol%) BFβ-solution in diethyl ether (1 : 10) were added within a few seconds during stirring. 200 μL (35 Vol%) polyglycerol-3-polyglycidyl ether containing traces of nucleophils as described above, were added during the stirring process. Thereafter, the solution was mixed well with a Vortex-stirrer. The reaction mixture was transferred in a 1 mL syringe consisting of polypropylene with the dimension of 2 mL, closed and positioned in a stand at room temperature. The polymerization was conducted for 3 hours. The emerged porous block according to the invention with the dimension of 4x50 mm was removed from the syringe and washed with THF to remove the porogens. The monolith was then dried at room temperature for 24 h. The scanning electron microscopic (SEM) image (see figure 8, right side) shows a pore size of 2 μm, the shrinkage by drying was 22.3% and the porosity was 72.6%. Example 4): 800 μL (80 Vol%) of a mixture with methyl-tert-butylether and dioxane (volume ratio 3:2) was introduced in a tube of polypropylene with the dimensions of 2 mL. At room temperature and atmospheric pressure 1.5 μL (1.5 Vol%) BF₃-solution in diethyl ether (1 :10) were added within a few seconds during stirring. 200 μL (35 Vol%) polyglycerol-3- polyglycidyl ether containing traces of nucleophils as described above, was added during the stirring process. Thereafter the solution was mixed well with a Vortex-stirrer. The reaction mixture was transferred in a 1 mL syringe consisting of polypropylene with the dimension of 2 mL, closed and positioned in a stand at room temperature. The polymerization was conducted for 3 hours. The emerged porous block according to the invention with the dimension of 4x50 mm was removed from the syringe and washed with THF to remove the porogens. The monolith was then dried at room temperature for 24 h. The scanning electron microscopic (SEM) image (see figure 8, left side) shows a mean pore size of 2 μm and the shrinkage by drying was 27,9%.

Figure 8 left) Pore structure of the new monolith prepared with the porogen toluene/ dioxane, right) Pore structure of the monolith prepared with the porogen methyl-tert-butylether/dwxane

Advantages compared to the state of the art

The porosity of the new monolith could be influenced directly and selectively through the variation of the porogen-monomer-mixture. Thereby the monolith can be prepared according to the favoured applications and specifications. A linear dependency between porosity and porogen-monomer-ration exists, the porosity is between 1 -80%.

The pore size of the new porous epoxide polymer can be influenced through a variation of the porogen, as well as the porogen-monomer-ration. The porous structure has a mean pore size between 10 nm and approx. 10 μm. Figure 8 shows the pore size distribution of two monoliths determined using mercury intrusion.

Figure 9 Pore size distribution of two new monoliths with different porogens (I) porous epoxide polymer with 80 Vol% toluenel/ dioxane (4/1), (2) porous epoxide polymer with 80 Vol% MTBE/toluene (2/3) X axis pore radius in μm (logarithmic), Y axis, left cumulative volume in mmⁱ/g, Y axis, right relative pore volume in % According to the invention the porous epoxide polymers can be produced as membranes, fiber, hollow fiber, coatings and other forms.

The invented monoliths can be enclosed for an application with one or more cases of polymeric, metallic or ceramic material. The connection between case and monolith can be performed with sealing material (e.g. elastomer), or with an inorganic material.

In another embodiment for the production of monoliths, the tube used for the polymerization can be pre-treated in such way, that its inner surface consists of covalently bound polymerizable groups. Such polymerizable groups are well-known for the specialist, for example hydroxyl and epoxides groups. The polymerizable groups can be introduced by procedures known to the specialists.

An important feature of monoliths is their swelling behaviour in solvents or their shrinkage by drying procedures. Previously known monoliths often have the disadvantage, that shrinkage after the production is very strong. Therefore, the monoliths can be shelled only after the drying step. According to the invention the new epoxide polymers can be very consistent in structure and the shrinkage is very low. The shrinkage occurs in radial and in longitudinal directions. To prevent the radial shrinkage, the inner surface of the tube can be modified in a way to have polymerizable groups. These groups can also polymerize and so the monolith is covalently bound to the wall. The swelling of the monoliths in organic solvents is insignificant.

The new monoliths are prepared at room temperature in contrast to the previously known monoliths. Thus, no radial temperature gradient occurs in the polymer and so no inhomogenities in the pore structure results. For this reason, these monoliths can be produced in any size and shape without heating for structure forming.

The mild reaction conditions lead to a good biocompatibility, respectively to antibodies. So an application of the monoliths is possible in new application areas, for example as surface of plastic biochips. A further advantage of the new monoliths is the short reaction time during the preparation process. This lasts compared to the synthesis of common organic monoliths, the new monoliths only take a few hours to procedure.

The materials according to the invention have a very good chemical resistance, high rigidity, very low abrasion and high structural consistency.

The new porous epoxide polymers have a low back pressure for a high applied flow. Thereby the material can be operated with high flow rates and a high sample throughput. Figure 10 shows the dependency of the back pressure of the flow rate with a monolith with the dimensions of 4.6 x 50 mm.

The invented epoxide polymers can be used in native form, i.e. without further derivatisation steps. They can also be derivatised by one or more steps to introduce others or additional functionalities. In particular, separation effectors can be introduced. Separation effectors can covalently bind directly on the polymer with their contained functional groups, hydroxyl and epoxide groups, or via a linker or distance operator.

Separation effectors for chromatographic purposes are known to the specialist. Separation effectors are substituents, which are either introduced to the synthesis of the monolith or added later on. Examples are halogens, Cig-phases, C_n-phases, phenyl-, metal chelates, chiral residues or biomolecules, such as proteins (i. g. antibodies), peptides, amino acids, biotin, nucleic acids, etc.

With this procedure the surface properties of the carrier material can be influenced. In particular, through a selective derivatisation of the carrier materials with separation effectors chromatographic material with specific properties can be obtained. Thus, monolithic materials with enhanced properties are accessible.

The new porous epoxide polymers according to the invention are economical, time-saving in production and easy to obtain. Applications

The new monolithic material can be applied according to the invention in various fields.

The main application is affinity chromatography. At the time of the invention an application of the monoliths was performed in the high-performance affinity chromatography (HPAC). The new monolith was used as a protein- A-affϊnity-column for the enrichment and separation of immunoglobulin G (IgG) from the human serum. Affinity chromatography is a chromatographic method to separate accompanying substances, based on highly specific biological interactions between analyte and affinity ligand, such as antibodies, enzymes or substrates. The target molecule is bound reversibly to the affinity ligand, while accompanying substances are not bound and therefore can easily be eluted. By using the reversible bond, the analyte can be eluted for example through pH changes, changes in ionic strength or by the addition of competing affinity ligands. Details of these procedures and process variants are known to the expert.

In this application porous rods of the monolith were used with the dimensions 10x4 mm. The monolith was tightly shelled by a teflon shrinking tube and connected to peak capillaries on both ends. For a stabilization the monolithic column was embedded in polyester cast resin. The affinity ligand was immobilized on the available hydroxyl and epoxide groups of the porous epoxide polymer using the standard CDI method. Figure 12 shows an example of the separation of IgG from human serum.

Figure 11 Affinity chromatogram of human serum Chromatografic conditions 10 μL injection of diluted human serum (1 10) in labeling buffer, enrichment with labelling buffer with 5 mL/min, elution with elution buffer with 5 mL/min Chromatographic peaks (1) non-interacting analyts, (2) eluted IgG

The functionalized porous epoxide polymers after this invention can be used as stationary phase for chromatographic separation processes. The techniques are for example adsorption chromatography, gas- and liquid chromatography, capillary electrophoreses, size exclusion chromatography, ion exchange chromatography, chiral chromatography, capillary electrochromatography etc.

The porous epoxy polymers can be prepared in several shapes and geometries and used for further applications: Filter for corrosive liquids, bacteria or analytical, clinical purposes; Surfaces in microarray technology; Flow cartridges for biosensors; Enrichment cartridges (Solid Phase Extraction (SPE)); Food filtration, e.g. separation of bacteria;

Medical applications (biocompatible material for prosthesis, filter materials, etc.); Gel electrophoreses (e.g similar to Sodiumdodecylsulfat (SDS)-Page); Production of porous particles (e.g. for flow cytometry, immunoassay); Bioreactors (e.g. immobilized enzymes);

Solid phase synthesis (e.g. Merrifield synthesis, instead of polystyrene- Divinylbenzene tentacle polymers or gels); UV-permeable materials (no aromatics);

Ion exchange for technical purposes, including catalysis;

References

[1] Svec, F., Tennikova, T., Deyl, Z.: Monolithic Materials, Preparation, Properties and Applications. Journal of Chromatography, Library 2003, Volume 67, Elsevier.

[2] Svec, F., Huber, CG. : Monolithic Materials: Promises, Challenges, Achievements. Anal. Chem. 2006, 78, 2102-2107.

[3] Xie, S., Allington, R. W., Frechet, J. M., Svec, F.: Porous Polymer Monoliths: An Alternative to Classical Beads. Adv. Biochem. Eng. Biotechnol. 2002, 76, 87-125.

[4] Gao, W.H., Yang, G.L., Yang, J., Liu, F.F., Yin, Y., Cgen, Y.: Preparation of Monolithic Silica Column. Coll. Chem. Environ. Sci., 2004, 25, 2250-2252.

[5] Hench, L.L., Orcel, G.F.: Ultraporous Gel Monoliths having Predetermined Pore Sizes and their Production. United States Patent 18.07.1989, US 4,849,378.

[6] Xioe, S., Svec, F., Frechet, J. M.: Porous Polymer Monoliths: Preparation of Sorbent Materials with High-Surface Areas and Controlled Surface Chemistry for High- Throughput, Online Solid-Phase Extraction of Polar Organic Compounds. Chem. Mater. 1998, 10, 4072-4078.

[7] Benes, M.J., Horak, D., Svec, F.: Methacrylate-Based Chromatographic Media. J. Sep. Sci. 2005, 28, 1855-1875.

[8] Parker, R. E., Isaacs, N. S.: Mechanisms of Epoxide Reactions. Chem. Rev. 1959, 737, 737-799.

[9] Green, M. M., Wittcoff, H. A.: Organic Chemistry Principles and Industrial Practice. Wiley- VCH, 2003, 80-81.

Claims

P24582CLAIMS

1. A process for manufacturing an epoxide resin comprising the following steps:

- providing an epoxide or mixtures thereof according to formula I

and/or formula

(IV) therein

- n represents a number of 2-30;

- Ri, R₂, and R₃ are, independently from each other, selected from hydrogen, alkyl, O-alkyl, alkenyl, silyl, fluoroalkyl, hydroxyalkyl and/or an epoxide;

- X is an aliphatic, cycloaliphatic or mixed aliphatic-cycloaliphatic, unsubstituted organic residue of 1-20 C-atoms;

- Y is, independently from each other, selected from sugar alcohols, preferred sorbitol or hexitol; glycerol, ethylene glycol, propylene glycol, butanediol, hexanediol, pentaerythritol, polyvinyl alcohols and carbohydrates, like starch, cellulose, polyvinyl alcohol, polyvinyl glycerol, polyethylene glycol, poly propylene glycol, poly-hydroxy acrylate and poly- hydroxy-methacrylate.

- adding a catalyst and

- performing a polyaddition reaction in order to obtain a polymer resin (II).

2. The process for manufacturing a polymer resin according to claim 1, wherein one or more solvents are added to the reaction components and a porous epoxide resin is obtained.

3. The process according to claim 1 or 2, wherein between the steps of adding a catalyst and performing the polyaddition reaction, a nucleophilic agent is added.

4. The process according to one or more of the preceding claims, wherein the step of performing a polyaddition reaction is done by intensive mixing under environmental conditions, more preferably in the temperature range between 10 and 100⁰C, particularly preferred between 15 and 30⁰C.

5. The process according to to one or more of the preceding claims, characterized in that the epoxide (I) is selected from a polyglycidylether according to formula V, VII or VIII.

Polyglycerol-3-polyglycidyl ether Glycerol triglycidyl ether Pentaerythritol tetraglycidyl ether

(V) (VI) (VII)

wherein m represents a number of 1-30.

6. The process according to one or more of the preceding claims, characterized in that the nucleophilic agent is selected from water, ammonia, an alcohol and/or primary or secondary amine.

7. The process according to one or more of the preceding claims, characterized in that the catalyst is a lewis-acid and/or a mineral acid, preferably selected from sulphuric acid, nitric acid, phosphoric acid, hydrochloric acid, boron trifluoride, boron trifluoride-complexes, preferably boron trifluoride-diethyltrietherate, aluminium chloride, zinc chloride, tin tetrachloride, diethyl aluminium chloride, titanium isopropoxide, titanium tetrachloride, trimethylsilyl triflate and triphenylmethyl perchlorate.

8. The process according to one or more of the preceding claims, characterized in that the catalyst is selected from boron trifluoride, boron trifluoride-complexes, preferably boron trifluoride-diethyltrietherate, aluminium chloride, zinc chloride, tin tetrachloride, diethyl aluminium chloride, titanium isopropoxide, titanium tetrachloride, trimethylsilyl triflate and triphenylmethyl perchlorate.

9. The process according to one or more of the preceding claims, characterized in that the catalyst is added in a ratio of 0.01 to 5.0 mass-%, preferably 0.1 to 1.0 mass-%, referred to the amount of epoxide.

10. The process according to one or more of the preceding claims, characterized in that nucleophile and/or catalyst is added in a solvent.

1 1. The process according to one or more of the preceding claims, characterized in that the epoxide is solved in a solvent in order to produce a porous epoxide resin.

12. The process according to claim 1 1 , characterized in that the solvent is selected from toluene, methyl-tert-butyl-ether, dioxane, tetrahydrofuran, ethyl acetate, dichloromethane and xylene or mixtures thereof.

13. Non-porous epoxide resin according to formula (II)

obtained by a process according to one or more of the preceding claims.

14. Porous epoxide resin comprising of a polymer material according to formula (II)

obtained by a process according to one or more of the preceding claims.

15. Use of the porous epoxide resin, obtained according to one or more of the preceding claims, in chromatography columns.

16. Use of the porous epoxide resin, obtained according to one or more of the preceding claims, in the separation of soluted particles, preferred ions, or undissolved particles, preferred bacteria and viruses from water.