JPS60143763A - Amphipathic gel - Google Patents

Abstract

PURPOSE:To produce a gel usable as both hydrophilic and lipophilic solvents from a copolymer obtained by polymerization of (poly)oxyalkylene mono(meth) acrylate as main component and (poly)oxyalkylene polyol poly (meth)acrylate as crosslinking agent. CONSTITUTION:40-99wt% of (poly)oxyalkylene mono(meth)acrylate of formula I and 1-60wt% of (poly)oxyalkylene polyol poly(meth)acrylate of formula II are polymerized to make a gel, wherein R<1> and R<3> are each H or CH3, R<2> and R<4> are each H or a 1-28C hydrocarbon group, m and n are each 2-4, a, b and c are average addition molar numbers the oxyalkylene group, 1-200 for a and 0- 200 for b and c, A is 2-6 polyhydric alcohol residues, x is 2-6, y is 0.1-4 and x+y is 2-6. The gel of this copolymer is excellent as amphipathic gel for liquid chromatography.

Description

DETAILED DESCRIPTION OF THE INVENTION (Technical Field of the Invention) This invention relates to amphiphilic gels, particularly amphiphilic gels useful as packing materials for liquid chromatography.

[Prior art]

Conventionally used as a packing material for liquid chromatography.

Hydrophilic gels such as dextran gel, cellulose gel, polyacrylamide gel, polyvinyl alcohol gel,
Also known are lipophilic gels such as polystyrene gel and polymethacrylate gel. However, all of these gels have the problem that they can only be used in either hydrophilic or lipophilic solvent systems.

[Object of the invention] This invention is intended to solve the problems of the conventional products as described above.
The aim is to provide an amphiphilic gel that can be used in both hydrophilic and lipophilic solvent systems by forming a gel from a copolymer of meth)acrylate and (poly)oxyalkylene polyol poly(meth)acrylate. There is.

[Structure of the invention]

This invention relates to compounds 40 to 99 represented by the following formula (13)
It is an amphipathic gel consisting of a copolymer of 1 to 60% by weight of the compound represented by formula (II).

1 (Here, R1 and R3 are each a hydrogen atom or a methyl group, R2 and R4 are each a hydrogen atom or a hydrocarbon group having 1 to 28 carbon atoms, and m and n are each 2 to 4
an integer, a, b and C are each the average number of added moles of an oxyalkylene group having 2 to 4 carbon atoms, a is 1 to 200,
b and C are θ ~ 200, A is a residue of a divalent to hexavalent polyhydric alcohol or polyhydric phenol, X is an integer of 2 to 6, y
is 0 or an integer from 1 to 4, and x+y is an integer from 2 to 6. ) In formulas (1) and (II), R2 and R4 each represent hydrogen or a hydrocarbon group having 1 to 28 carbon atoms, and hydrogen or a hydrocarbon group having 1 to 6 carbon atoms is particularly preferred. Examples of the above hydrocarbon group include methyl group, ethyl group, propyl group, and butyl group.

Examples include pentyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group, undecyl group, dodecyl group, tridecyl group, tetradecyl group, pentadecyl group, hexadecyl group, heptadecyl group, octadecyl group, nonadecyl group, eicosyl group. , may be linear or branched.

In formulas (1) and (II), the oxyalkylene groups represented by CmH2mO and CnH2no include oxyethylene group, oxypropylene group, oxybutylene group, oxytetramethylene group, etc., and these include ethylene oxide, propylene oxide, Indicates that it is an adduct of alkylene oxide having 2 to 4 carbon atoms such as butylene oxide and tetrahydrofuran. a, b, c
represents the average number of moles added, a is preferably 1 to 50, and b and C are preferably 0 to 50.

In formula (II), examples of the polyhydric alcohol or polyhydric phenol having A as a residue include ethylene gelicol, propylene glycol, butylene glycol, hexylene glycol, styrene glycol, and carbon atoms of 8 to
Neopentyl glycol, a glycol derived from 18 olefins.

Examples include glycerin, diglycerin, trimethylolethane, trimethylolpropane, 1,3.5-pentanetriol, erythritol, pentaerythritol, sorbitol, catechol, resorcinol, hydroquinone, formalin condensate of phenol or alkylphenol, and bisphenol compounds.

The compound of formula (1) is the main structural unit of the copolymer, and is obtained by adding an alkylene oxide such as ethylene oxide, propylene oxide, butylene oxide, or tetrahydrofuran to an alcohol or phenol containing R2 as a residue. It can be produced by subjecting a monoether type (poly)oxyalkylene glycol to an esterification reaction with acrylic acid or methacrylic acid, or by subjecting a hydroxyalkyl acrylate or methacrylate to an addition reaction with the alkylene oxide.

The compound of formula (If) serves as a crosslinking agent, and is added to 1 mole of (poly)oxyalkylene polyol obtained by adding the above-mentioned alkylene oxide to a polyhydric alcohol or polyhydric phenol having A as a residue, if necessary. On the other hand, 2~
A monohalogenated hydrocarbon having R4 as a residue is produced by esterifying 6 moles of acrylic acid or methacrylic acid, or by converting the terminal hydroxyl group of a (poly)oxyalkylene polyol into an alcoholade with metallic sodium or the like. It can be produced by reacting to etherify and then reacting with acrylic acid or methacrylic acid.

(Representative examples of Formula 11 compounds include the following.

■, octaoxyethylene glycol monomethacrylate (HE(8)MA) ■, hydroxyethyl monomethacrylate (HE(1)
) MA) ■, Tetraoxyethylene glycol monomethacrylate (HE(4)MA) ■, Methoxyhebutacosaoxyethylene monomethacrylate (ME(27)MA) ■, Heptaoxypropylene glycol monomethacrylate (HP(7) ) MA) ■, Methoxydecaoxypropylene pentaoxyethylene acrylate (MP(10)E(5)A) CH2=C
HC00(C2H40)5 (C3He O)+oCH
In addition, the following are representative examples of the compound of formula (II).

■, Tetraoxyethylene glycol dimethacrylate (EG (4) DM) ■, Ethylene glycol dimethacrylate (EG (1)
) DM) ■, tetradeoxyethylene glycol dimegacrylate [EG (14) DM) X, pentaoxypropylene glycol dimethacrylate (PG (5) DM) E
G (2) PG (2) DA ]CH2=C
HC00(C2H40)2 (Ca Hs O) 20
CHC=CH2XI1. Beptaoxyethylene glycerol triacrylate (EGI (7) TA) 99 Formula (II) compound 1-60% by weight, preferably 2-40%
These compounds may be copolymerized with other polymerizable monomers in an amount of 30 or less times by weight.

Examples of other monomers that can be polymerized include methyl (meth)
Acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, butyl (meth)acrylate,
Amyl (meth)acrylate, hexyl (meth)acrylate, octyl (meth)acrylate, nonyl (meth)acrylate, decyl (meth)acrylate, dodecyl (meth)acrylate, tetradecyl (meth)acrylate, hexadecyl (meth)acrylate.

Octadecyl (meth)acrylate, oleyl (meth)
Acrylate, cyclohexyl (meth)acrylate,
Vinyl acetate, styrene, α-methylstyrene, acrylonitrile, vinyl chloride, acrylic acid, methacrylic acid, maleic acid, fumaric acid, maleic acid monoalkyl esters, maleic acid dialkyl esters, fumaric acid monoalkyl ester, fumaric acid dialkyl ester (However, the number of carbon atoms in the alkyl is 1 to 18).

The reason why the ratio of formula (1) and formula (II) compounds in the copolymer is limited is that if the formula (II) compound is less than 1% by weight, the strength of the gel produced is low, making it difficult to use as a gel for liquid chromatography. This is not preferable, and if it exceeds 60% by weight, copolymerization becomes difficult and a uniform gel cannot be obtained.

In the copolymerization method, an inorganic salt such as sodium sulfate, potassium sulfate, sodium chloride, potassium chloride, sodium phosphate, potassium phosphate, etc. is added to a reaction vessel, and the formula (1) and (I
Prepare an aqueous solution at a concentration such that the monomers such as the compound of formula I) do not dissolve together, for example, 20 to 40% by weight, and add 0.1 to 2 parts of carboxymethyl cellulose sodium salt or the like as a dispersion stabilizer to 100 parts by weight of this inorganic salt aqueous solution. Add parts by weight and dissolve. To this, 0.5 to 30 parts by weight, preferably 2 to 10 parts by weight, of monomers such as compounds of formulas (1) and (11) in a predetermined ratio, and an organic peroxide such as benzoyl peroxide or cumyl peroxide as a polymerization initiator. or azo compounds such as azobisisobutyronitrile 0.0
2 to 0.5 parts by weight is added, and the reaction temperature is 60 to 9.
Suspension polymerization is performed at 0° C. for 5 to 10 hours to synthesize a gel.

In this case, aliphatic alcohols such as 1-butanol, 1-pentanol, 1-hexanol, 1-heptatool, 1-octanol, ■nonanol, 1-decanol, and isopropanol are used as diluents during suspension polymerization. , isobutanol, aromatic hydrocarbons such as benzene, 1-helene, xylene, or ketones such as 3-pentanone, 2-pentanone, 2-hexanone, and 2-heptanone may be added.

During polymerization, compound (II) acts as a crosslinking agent to produce a granular gel, and the particle size of the gel can be adjusted by changing the stirring speed during polymerization. After unreacted or by-products are extracted from the resulting gel particles using acetone or the like, they are washed with warm water and used as a product.

The gel thus obtained is an amphiphilic gel and can be used as a filler for Liquid Chroma 1 to Graphie.
In this case, it can be used not only with hydrophilic solvent systems such as water, methanol, acetone, and tetrahydrofuran, but also with lipophilic solvent systems such as benzene and ethyl ether. is also excellent.

In addition, this gel has small changes in the bed volume of gel particles due to changes in inorganic salts and pH, and has excellent properties as a gel for liquid chromatography. It is extremely effective in separating

Although the amphiphilic gel of the present invention is excellent as a packing material for liquid chromatography, it can also be used for other purposes by taking advantage of its properties.

〔Effect of the invention〕

According to this invention, since a gel consisting of a copolymer of compounds of formulas (1) and (II) is used, it can be used in both hydrophilic and lipophilic solvent systems, and is excellent as a packing material for liquid chromatography. Amphiphilic gels with specific properties can be obtained.

[Embodiments of the invention]

Examples of the present invention will be described below. Compounds I to II of formula (I) and compounds II to XIII of formula (II) used in the Examples are those exemplified above.

Example (1) Production of amphiphilic gel Into a three-necked flask equipped with a reflux condenser, 500 mQ of a 25% by weight aqueous sodium sulfate solution and 3 g of carboxymethyl cellulose sodium salt as a dispersion stabilizer were added, and the formula (1) was added. Taking 12 g of octaoxyethylene glycol monomethacrylate as a compound, 0.9 g of tetraoxyethylene glycol dimethacrylate as a compound of formula (II), 12 g of isobutyl alcohol as a diluent, and 0.6 g of benzoyl peroxide as a polymerization initiator, Gel particles were synthesized by suspension polymerization at 80°C for 7 hours while controlling the size by stirring speed. The obtained gel particles were extracted with acetone using a Soxhlet extractor for 6 hours, thoroughly washed with warm water at about 50°C, and then sieved to obtain particles of 74 to 179 μm.
12.5 g of gel having a uniform size of m was obtained. For details, please refer to Table 1.
61.

In addition, 12 g of the compound of formula (1) shown in Table 1 was subjected to layer temperature polymerization under the above conditions except that the compound of formula (n) and the diluent were used in a predetermined ratio, and an amphiphilic gel (Table 1 No. 2 to No. 17) were synthesized.

Amphipathic gels No. 1 to No. 1 of Examples in Table 1.

Regarding No. 12, all had strength in the water-swollen state and a uniform gel was obtained, but - Comparative Example No. 13, No.
Regarding 15, the gel strength is weak (, No. 14, No.
Regarding No. 16, No. 17, even though the diluent was increased, the suspension polymerization was non-uniform and a spherical gel could not be obtained, and all of them were unsuitable as gels for liquid chromatography.

(2) Measurement of bed volume change of gel particles in response to changes in salt aqueous solution concentration and pH
After filling with mQ and first stabilizing the bed by flowing 50 ml of ion-exchanged water, the bed volume was measured.

Next, the bed volume was measured by flowing sodium sulfate aqueous solutions with different concentrations until there was no change in bed volume, and the ratio of ion-exchanged water to the bed volume was taken as the original area ratio of gel particles to the salt aqueous solution concentration. The change in bed volume of gel particles due to pH change was also measured by the same procedure, and the dry gel weight (
The bed volume (moQ) for g) was calculated. Note that pl+ was adjusted using C1ark-Lobs and Menzel buffer solutions. The respective results are shown in Tables 2 and 3.

Table 2: Change in bed volume of gel particles with respect to salt aqueous solution concentration Table 3: Change in bed volume of gel particles with respect to p) l change From the results of Tables 2 and 3, it can be seen that the amphiphilic gel of the present invention does not react with inorganic salts or pH in an aqueous solvent. It can be seen that the change in the original area of the gel particles due to the change is small, making it suitable as a gel for liquid chromatography.

(3) Measurement of the degree of swelling of gel particles by solvents To measure the degree of swelling of gel particles by various solvents, 1 g of gel was placed in a petri dish, dried at 40°C, approximately 30 mm, and 11 g for 24 hours, and then immersed in a solvent to swell. Original evaluation of gel particles (mf
l) and calculated the value relative to the dry gel weight (g). The results are shown in Table 4.

From the results in Table 4, it can be seen that the product of the present invention does not change much in swelling degree even when various solvents are used compared to the comparative gel, and can be used in both hydrophilic and lipophilic solvent systems.

(4) Measurement of separation ability of amino acids by liquid chromatography The prepared gel was packed into a column with an inner diameter of 0.5 cm and a length of 30 cm + n, and 25 μl of a 2% aqueous solution of amino acids was injected, and ion-exchanged water and 0.9% by weight were added. Using an aqueous sodium chloride solution as the elution solvent, the flow rate was 10 to 30 mQ/hour.
It was eluted by the ascending method and the partition coefficient was determined. As a sample,
For comparison, commercially available polyvinyl gels using diethylene glycol (DEG) and various amino acids,
Cellulose-based gels and dextran-based gels were also measured. The results are shown in Table 5.

From the results in Table 5, it can be seen that the amphiphilic gel of the present invention has excellent separation ability, and the separation ability is not easily affected by inorganic salts.

(5) Measurement of separation ability of polyethylene glycol (PEG) by liquid chromatography The above No. 1 gel was packed into a column with an inner diameter of 0.5 c+s and a length of 30 cm, and PEG with different molecular weights (number average molecular weight 62 to 28,500
Inject 25μQ each of 2% aqueous solution of
At Q1, it was eluted using the ascending method. Further, elution was carried out in the same manner by changing the elution solvent to methanol and tetrahydrofuran. The results are shown in the graphs in the drawing. In the figure, Ve is the elution volume of PEG having a molecular weight of Mn, and Vt is the column volume. Ve/Vt is plotted on the horizontal axis and log Mn (Mn: number average molecular weight) is plotted on the vertical axis.

As is clear from the drawing, no matter which solvent is used, P
It can be seen that EG is eluted in descending order of molecular weight, indicating excellent separation ability.

[Brief explanation of the drawing]

The figure is a graph showing the separation ability of polyethylene glycol when No. 1 gel of the present invention is used in liquid chromatography. Agent Patent attorney Yanagi Hara Written amendment January 7, 1980 Director of the Patent Office Kazuo Wakasugi (1, not listed in the case) -, I,, ys- Patent application filed on December 30, 1988 2. Name of the invention Amphiphilic Gel 3. Relationship with the case of the person making the amendment Patent applicant representative Teruji Ogawa 4, agent Address: 105 Phone: 436-4700
Address: 3-15-8-5 Nishi-Shinbashi, Minato-ku, Tokyo, Date of amendment order: Voluntary amendment: 6, Number of inventions increased by amendment: 07, Scope of claims and detailed description of the invention in the specification subject to amendment 8. Contents of amendment (1) The scope of claims is amended as shown in the attached sheet. (2) Formula (1) on page 4, line 15 of the specification is corrected as follows. “R1 1...(Il CH2=CC00(C:m HzmO)aR2J2, Claims (1) 40 to 99% by weight of a compound represented by the following formula (1)
and [11) An amphiphilic gel consisting of a copolymer of 1 to 60% by weight of the compound represented by the formula. 1 (Here, R1 and R3 are each a hydrogen atom or a methyl group, R2 and R4 are each a hydrogen atom or a hydrocarbon group having 1 to 28 carbon atoms, and m and n are each 2 to 4
an integer, a, b and C are each the average number of added moles of an oxyalkylene group having 2 to 4 carbon atoms, a is 1 to 200,
b and C are 0-200, A is a residue of a di- to hexavalent polyhydric alcohol or polyhydric phenol, X is an integer of 2-6, y
is 0 or an integer from 1 to 4, and x + y is an integer from 2 to 6. ) (2) The hydrocarbon group represented by R'' or R4 is a methyl group, ethyl group, propyl group, butyl group, pentyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group, undecyl group, dodecyl group The amphiphilic gel according to claim 1, wherein A is a tridecyl group, a tetradecyl group, a pentadecyl group, a hexadecyl group, a heptadecyl group, an octadecyl group, a nonadecyl group, or an eicosyl group. (3) A is ethylene glycol, propylene glycol , butylene glycol, hexylene glycol, styrene glycol, glycol derived from olefins having 8 to 18 carbon atoms, neopentyl glycol, glycerin, diglycerin, trimethylolethane, trimethylolpropane, l. 3.5-pentanetriol, Erythritol. The amphiphilic gel according to claim 1 or 2, which is a residue of pentaerythritol, sorbitol, catechol, resorcinol, hydroquinone, a formalin condensate of phenol or alkylphenol, or a bisphenol compound. (4) CmH2110 The amphiphilic gel according to any one of claims 1 to 3, wherein C, dan, and no are oxyethylene, oxypropylene, oxybutylene, or oxytetramethylene groups.

Claims (4)

[Claims] (1) 40 to 99% by weight of a compound represented by the following formula (1)
and an amphiphilic gel consisting of a copolymer of 1 to 60% by weight of a compound represented by the formula Cl11. 1 (Here, R1 and R3 are each a hydrogen atom or a methyl group, R2 and R4 are each a hydrogen atom or a hydrocarbon group having 1 to 28 carbon atoms, and m and n are each 2 to 4
an integer, a, b and C are each the average number of added moles of an oxyalkylene group having 2 to 4 carbon atoms, a is 1 to 200,
b and C are 0-200, A is a residue of a di- to hexavalent polyhydric alcohol or polyhydric phenol, X is an integer of 2-6, y
is 0 or an integer from 1 to 4, and x+y is an integer from 2 to 6. ) (2) The hydrocarbon group represented by R'' or R4 is a methyl group, ethyl group, propyl group, butyl group, pentyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group, undecyl group, dodecyl group, The amphipathic gel according to claim 1, which is a tridecyl group, a tetradecyl group, a pentadecyl group, a hexadecyl group, a heptadecyl group, an octadecyl group, a nonadecyl group, or an eicosyl group. (3) A is ethylene glycol, propylene glycol, butylene glycol, hexylene glycol, styrene glycol, glycol derived from an olefin having 8 to 18 carbon atoms, neopentyl glycol, glycerin, diglycerin, trimethylolethane, trimethylolpropane , 1°3.5-pentanetriol, erythritol, pentaerythritol, sorbitol, catechol, resorcinol, hydroquinone, phenol or a formalin condensate of alkylphenol, or a residue of a bisphenol compound according to claim 1 or 2. amphiphilic gel. (4) The amphiphilic gel according to any one of claims 1 to 3, wherein Cm I (zm O or C6C2oO is an oxyethylene group, oxypropylene group, oxybutylene group, or oxytetramethylene group) .