WO2000073262A1

WO2000073262A1 - Polymerizable, olefinically unsaturated monomers

Info

Publication number: WO2000073262A1
Application number: PCT/EP2000/004419
Authority: WO
Inventors: Wolfgang Podszun; Rainer Neumann; Joachim Krüger
Original assignee: Bayer Aktiengesellschaft
Priority date: 1999-05-29
Filing date: 2000-05-16
Publication date: 2000-12-07
Also published as: AU5394400A; DE19924790A1

Abstract

The invention relates to novel polymerizable, olefinically unsaturated monomers with alkaline groups of general formula (I), wherein R1 is H or methyl, L¿1?, L2 independently represent alkylene with 1 to 6 carbon atoms, A is oxygen or N-R?3, R3¿ is H or C¿1?-C4 alkyl, n represents an integer from 0 to 10 and R?2¿ is NH¿2? or a secondary or tertiary amine group or a 5- or 6-membered ring with at least one N atom. The invention further relates to a method of producing said monomers and to the polymers produced therefrom.

Description

Polymerizable, olefinically unsaturated monomers

The invention relates to new polymerizable, olefinically unsaturated monomers with basic groups of the general formula (I)

in which

R ^{1 represents} H or methyl,

L _j , L- ₂ independently of one another represent alkylene with 1 to 6 C atoms,

A represents oxygen or NR ³ ,

R ^{3 represents} H or C, -C ₄ alkyl,

n stands for an integer from 0 to 10 and

R ^{2 represents} NH ₂ or a secondary or tertiary amino group or a 5- or 6-membered ring with at least one N atom,

and polymers made from them.

Polymers with basic groups find diverse applications, for example as

Anion exchangers, as chromatography resins or as aids in medical diagnostics for the separation of nucleic acids. Such polymers can be obtained, for example, from non-basic polymers by polymer-analogous reaction. be fathered. However, it is also possible to produce basic polymers directly by polymerizing basic monomers.

For example, US Pat. No. 5,434,270 describes the monomer of the formula

This monomer can be converted into water-soluble polymers by homo- or copolymerization. The monomer is used to synthesize crosslinked spherical basic polymers, especially those with a high specific surface area

US-A 5 434 270, however, is less suitable.

New monomers have now been found which are suitable in a variety of ways for the production of basic polymers.

The invention relates to monomers of the general formula (I)

characterized in that

R ^{1 represents} H or methyl,

L _j , 1_ ₂ independently of one another represent alkylene with 1 to 6 C atoms,

A represents oxygen or NR ³ , R ^{3 represents} H or C, -C ₄ alkyl,

n stands for an integer from 0 to 10 and

R ^{2 represents} NH2 or a secondary or tertiary amino group or a 5- or 6-membered ring with at least one N atom.

The monomers according to the invention with basic groups according to the general formula (I) are particularly suitable for the preparation of anion exchangers which, in turn, can be used as chromatography resins or as aids in medical diagnostics for separating nucleic acids.

The invention therefore also relates to ion exchangers, in particular anion exchangers, which are prepared from the monomers of the general formula (I), and to their use as chromatography resins or as auxiliaries in medical diagnostics, in particular for separating nucleic acids. Finally, the present invention relates to a method for separating nucleic acids, characterized in that anion exchangers constructed from monomers according to claim 1 are used.

Preferred monomers for the purposes of the present invention are monomers of the general formula (Ia)

characterized in that

L- _{2 represents} alkylene with 1 to 6 carbon atoms,

A represents oxygen or NR ³ , R ³ for H or C _! -C ₄ - alkyl,

n stands for a 5 whole number from 0 to 10 and

R ^{2 represents} NH ₂ or a secondary or tertiary amino group or a 5- or 6-membered ring with at least one N atom.

Both Li in formula (I) and L ₂ , independently of one another, preferably represent divalent straight-chain or branched alkylene radicals having 1 to 6 carbon atoms.

In formula (I), Li and L ₂ are particularly preferably, independently of one another, a radical of the series methylene, dimethylmethylene, ethylene, propylene- (1,2), propylene- (1,3) (= trimethylene), 2,2-dimethylpropylene - (1,3) and butylene- (1,4) (= tetramethylene).

The radical A is preferably oxygen, NH, or with a C1-C ₄ - alkyl group substituted nitrogen. A particularly preferably represents NH or oxygen.

n is an integer from 0 to 10, preferably from 0 to 6, particularly preferably from 0 to 4.

R ² preferably denotes NH ₂ or a secondary or tertiary amino group or a 5- or 6-membered ring with at least one N atom. R ² particularly preferably represents a radical from the series NH ₂ , methylamino, dimethylamino, ethylamino,

Diethylamino. Hydroxyethylamino, bis (hydroxyethyl) amino, propylamino, dipropylamino, bis (hydroxypropyl) amino, n-butylamino or tert-butylamino, N-imidazolyl, methylimidazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyridazinyl, Pyrimidyl, pyrazolyl, N-piperidyl, oxazolyl, isoxazolyl, triazolyl. Also preferred for the purposes of the present invention are monomers of the general formula (Ib)

characterized in that

represents an integer from 0 to 10 and

R ^{4 represents} a radical of the series H, methyl, ethyl or 2-hydroxyethyl.

Further preferred in the sense of the invention are monomers of the more general! i formula

characterized in that

n stands for an integer from 0 to 6.

Also preferred for the purposes of the invention are monomers of the general formula (Id)

characterized in that

R ³ for H or C _! -C ₄ - alkyl and R ^{4 represents} a radical of the series H, methyl, ethyl or 2-hydroxyethyl.

The following compounds are particularly preferred monomers according to the invention for the purposes of the present invention:

Table 1

connection

Connection 2

Connection 3

Connection 4

Connection 5

Connection 6

Connection 7

Connection 8

Connection 9

Connection 10

Connection 11

The present invention further relates to a process for the preparation of the monomers of the general formulas (I), (Ia), (Ib), (Ic) or (Id) according to the invention by stoichiometric conversion of hydroxyl or amine compounds according to the general formula (II)

in which

A, n, L and R ^{2 have} the meanings given above,

with isocyanates of the general formula (III)

in which

R ⁱ and L _{j have} the meanings given above.

Hydroxyl compounds of the general formula (II), with n = 1 to 10, can be obtained in a known manner by ethoxylation. It has been shown that the use of ^" strongly acidic ion exchangers is very suitable for the isolation and purification of the ethoxylation products.

Said reaction of the hydroxyl or amine compounds according to the general formula (II) with isocyanates of the general formula (III) is preferably carried out in an inert solvent in the presence of a catalyst at temperatures of, for example, from -20 ° C. to 60 ° C. Examples of inert solvents which may be mentioned are acetone, 2-butanone, tetrahydrofuran, methylene chloride, chloroform, toluene and acetonitrile. Examples of catalysts which can be used in the process according to the invention are metal salts higher fatty acids, such as dibutyltin laurate, triaryl compounds such as triphenylstibine or triphenylphosphate, or tertiary amines such as triethylamine. The catalysts are usually used in amounts of 50 to 5000 ppm, based on the starting materials.

To prevent premature undesired polymerization, it is expedient to add small amounts of a polymerization inhibitor to the monomers according to the invention during the synthesis. Suitable polymerization inhibitors are, for example, hydroquinone, hydroquinone monomethyl ether, 2,6-di-tert-butylphenol, 2,6-di-tert-butyl-4-methylphenol or 2,6-di-octadecyl-4-methylphenol.

The amount of inhibitor used is 5 to 1000 ppm, preferably 10 to 500 ppm, based on the monomer.

The monomers according to the invention can be converted into copolymers by polymerization in homopolymers or in a mixture with comonomers. to

Production of crosslinked polymers from the monomers according to the invention are polymerized in a mixture with multifunctional, olefinically unsaturated monomers as crosslinkers. A very suitable crosslinker is, for example, divinylbenzene.

The polymerization is preferably carried out by initiation with radical formers. Suitable radical formers are, for example, peroxy compounds such as dibenzoyl peroxide, dilauryl peroxide, bis (p-chlorobenzoyl peroxide), dicyclohexyl peroxidicarbonate, tert.-butyl peroctoate, 2,5-bis (2-ethylhexanoyl peroxy) -2,5-dimethylhexane or tert.-amylperox 2-ethylhexane, further azo compounds such as 2,2'-azobis (isobutyronitrile), 2,2'-azobis (2,4-dimethylvaleronitrile) or 2,2'-azobis (2-methylisobutyronitrile). The radical formers are generally used in amounts of 0.05 to 2.5% by weight, preferably 0.2 to 1.5% by weight, based on the monomer or on the monomer mixture. The monomers according to the invention are particularly suitable for the preparation of bead polymers, in particular for the preparation of macroporous bead polymers by the suspension polymerization procedure.

The term suspension polymerization is understood to mean a process in which a monomer or a monomer-containing mixture which contains an initiator soluble in the monomer (s) in a phase which is essentially immiscible with the monomer (s), preferably in an aqueous phase, the one Contains dispersant, is divided into droplets and is cured by increasing the temperature with stirring. Further details of suspension polymerization are described, for example, in H. Green's "Polymerization Processes", in: Ullmanns Encyclopedia of Industrial Chemistry, Vol. A21, 5th ed. (B. Elvers, S. Hawkins, G. Schulz, ed.), VCH, Weinheim 1992, pp. 363-373.

So-called porogens are used for the production of macroporous bead polymers. Porogens are liquid, water-immiscible compounds that dissolve the monomers used and precipitate the polymer that is formed. Examples include aliphatic hydrocarbons such as hexane, heptane, octane, isooctane, isododecane and alcohols such as octanol. The porogen is used in amounts of 10 to 150% by weight, preferably 20 to 100% by weight, based on the sum of the monomers and crosslinking agents used.

example 1

Preparation of Compound 1 from Table 1

13.35 g of dimethylaminoethanol, 0.05 g of 2,6-di-tert-butylcresol (polymerization inhibitor) and 0.05 g of di-butyltin dilaurate (catalyst) were dissolved in 160 ml of chloroform with exclusion of moisture and at -10 ° C. chilled. Thereafter, 30.19 g of 3-isopropenyl, α-dimethylbenzyl isocyanate, dissolved in 40 ml of chloroform, were metered in over the course of 30 minutes. The temperature was then raised to 60 ° C. and stirring continued (about 10 h) until no NCO band was detectable in the IR spectrum. After evaporation of the solvent, 43.4 g of monomer 1 from Table 1 remained.

Example 2

Reaction of dimethylaminoethanol with ethylene oxide

887 g of dimethylaminoethanol (DMAE) were weighed out into a 5 1 VA pressure reactor under nitrogen and heated to 120.degree. A total of 1535 g of ethylene oxide (EO) were pressed in portions within 6 hours. After cooling and relaxing, 2031 g of a colored viscous mixture of ethylene oxide-extended dimethylaminoethanol were obtained. The mixture was then purified by distillation over a 1.5 m long silver-jacketed column with a column top in a high vacuum at a bath temperature of 70 to 240 ° C. 3 fractions with constant boiling points were obtained.

Fraction 1: 387 g, boiling point at 0.15 mbar 45 ° C,

DMAE x 1 EO (identification by elemental analysis and NMR spectrum) Fraction 2: 319 g, boiling point at 0.15 mbar 70 ° C,

DMAE x 2 EO (identification by elemental analysis and NMR spectrum)

Fraction 3: 128 g, boiling point at 0.15 mbar 110 ° C,

DMAE x 3 EO (identification by elemental analysis and NMR spectrum)

For further purification of fractions 1, 2 and 3, 15 g of product were placed in a column, which was filled with 200 ml of water and 500 ml of Lewatit cation exchanger

SP 112 WS (H-Form) ® was filled. After the products had been applied, they were rinsed with 2 l of deionized water. The column was then eluted with 1.5 1 6.5% ammonia solution. The eluate running off was collected and then concentrated on a rotary evaporator at 55 ° C. and 15 mbar. About 12 g of purified fractions 1 to 3 were obtained.

Example 3

Preparation of compound 2 from Table 1

12 g of purified fraction 1 from Example 2, 0.05 g of 2,6-di-tert-butylcresol (polymerization inhibitor) and 0.05 g of dibutyltin dilaurate (catalyst) were dissolved in 160 ml of chloroform with exclusion of moisture and cooled to -10 ° C. . Then 18.14 g of 3-isopropenyl-α, α-dimethylbenzyl isocyanate, dissolved in 40 ml of chloroform, were metered in over the course of 30 minutes. The temperature was then raised to 60 ° C. and stirring continued (approx. 10 h) until no NCO band was detectable in the IR spectrum. After evaporation of the solvent, 29.4 g of monomer 2 from Table 1 remained. Example 4

Preparation of compound 3 from Table 1

Example 3 was repeated using 12 g of purified fraction 2 from Example 2 and 13.63 g of 3-isopropenyl-α, α-dimethylbenzyl isocyanate. 24.2 g of monomer 3 from Table 1 were obtained.

Example 5

Preparation of compound 4 from Table 1

Example 3 was repeated, using 12 g of purified fraction 3 from Example 2 and 10.91 g of 3-isopropenyl-α, α-dimethylbenzyl isocyanate. 21.6 g of monomer 4 from Table 1 were obtained.

Example 6

Preparation of compounds 5, 6, 7, 8, 9, 10 and 11 from Table 1

The experiments were carried out as described in Example 1, with the change that instead of 13.35 g of dimethylaminoethanol, the amines listed below were used in the stated amounts.

Example 7

Production of a macroporous bead polymer

A solution of 42.5 g of polyvinyl alcohol (Moviol 40-88®) and 12.75 g of disodium hydrogen sulfate in 1240 g of deionized water was placed in a 2 liter reaction vessel with a blade stirrer, reflux condenser, thermometer, gas inlet and gas outlet tube. An organic solution of 23.71 g of monomer from Example 1, 13.04 g of styrene, 10.67 g of divinylbenzene, 0.71 g of 2,2'- was added to this aqueous solution at 20 ° C. while stirring at 280 revolutions per minute. Azobis (2,4-dimethylvaleronitrile) and 35 g of hexane were added within 30 minutes. It was flushed lightly with nitrogen and the temperature was raised to 66 ° C. and kept at this temperature for 20 hours. After cooling, the bead polymer formed was separated from the reaction liquor by decanting and dried in vacuo at 50.degree. 42.8 g of bead polymer were obtained with an average particle size of 18 μm and a specific surface area of 87.4 m ² / g.

Claims

claims

Monomers of the general formula (I)

characterized in that

R ^{1 represents} H or methyl,

Li, L independently of one another represent alkylene with 1 to 6 C atoms,

A represents oxygen or NR ³ ,

R ^{3 represents} H or C _r C ₄ alkyl,

n stands for an integer from 0 to 10 and

2. Monomers of the general formula (Ia)

characterized in that A represents oxygen or NR ³ ,

R ^{3 represents} H or C _r C ₄ alkyl,

represents an integer from 0 to 10,

L _{2 represents} alkylene with 1 to 6 carbon atoms and

R ^{2 represents} NH ₂ ^{0 (} it represents a secondary or tertiary amino group or a 5- or 6-membered ring with at least one N atom.

3. Monomers of the general formula (Ib)

characterized in that

represents an integer from 0 to 10 and

R ^{4 represents} a radical of the series H, methyl, ethyl or 2-hydroxyethyl.

4. Monomers of the general formula (Ic)

characterized in that

n stands for an integer from 0 to 6. Monomers of the general formula (Id)

characterized in that

R ^{3 represents} H or C, -C ₄ alkyl and

R ^{4 represents} a radical of the series H, methyl, ethyl or 2-hydroxyethyl.

Process for the preparation of monomers of the general formula (I)

in which

R ¹ , L _j , L ₂ , A, R ³ , n and R ^{2 have} the meanings given in Claim 1,

characterized in that one

Hydroxyl or amine compounds of the general formula (II)

O A-

HA '(II),

woπn A, n, L ₂ and R ^{2 have} the meanings given above,

with isocyanates of the general formula (III)

wonn

R ¹ and L _{j have} the meanings given above,

implemented stoichiometrically.

7. The method according to claim 6, characterized in that the reaction is carried out in an inert solvent.

8. The method according to claim 6, characterized in that this is carried out in the presence of a catalyst.

9. Use of the monomers according to claims 1 to 5 for the production of crosslinked polymers, homopolymers, copolymers or macroporous bead polymers.

10. A process for the preparation of homopolymers or in a mixture with comonomers to give copolymers, characterized in that monomers according to claim 1 with multifunctional, olefinically unsaturated

Monomers polymerized as crosslinkers according to the suspension polymerization procedure.

11. A process for the preparation of homopolymers or in a mixture with comonomers to give copolymers according to claim 10, characterized in that monomers according to claim 1 are polymerized with divinylbenzene.

12. A process for the preparation of macroporous bead polymers, characterized in that the monomers according to claim 1 are dissolved in porogens and polymerized according to the suspension polymerization procedure.

13. Homopolymers, copolymers or macroporous bead polymers obtainable by the process according to claims 10 to 12.

14. Anion exchanger, characterized in that they are prepared from monomers with basic groups of the general formula (I) according to claim 1.

15. Use of the anion exchanger according to claim 14 as chromatography resins or as an aid in medical diagnostics.

16. Use of the anion exchanger according to claim 14 for the separation of nucleic acids.

17. A method for separating nucleic acids, characterized in that anion exchangers composed of monomers according to claim 1 are used.