JPS59193846A - Crosslinking monomer - Google Patents

Abstract

NEW MATERIAL:A compound of formula (R is residue of monosaccharide, disaccharide or their reduction derivative; R' is alkyl, alkoxy; R'' is H, methyl; n is 2 or 3; m+n is the number of all hydroxyls in the above saccharide or its reductive derivative, 3 or more.). EXAMPLE:Tetraacetyldimethacryloyl sorbitol. USE:A starting substance of nonionic crosslinked polymers which can be made hydrophilic, when necessary. The resultant polymers are lipophilic and the partial hydrolysis, after polymerization, converts the polymer into hydrophilic one. The monomer can be used as a crosslinking agent for other monomers, without deprotection, after polymerization, too. PREPARATION:The reaction of a saccharide or its reduced derivative with a chloride of acrylic or methacrylic acid in pyridine is followed by the addition of an anhydride of carboxylic acid such as acetic acid in an excess amount. Then, the product is extracted and distilled off to give the compound of the formula.

Description

DETAILED DESCRIPTION OF THE INVENTION Technical Field The present invention relates to a crosslinkable monomer, and more particularly to a crosslinkable monomer used as a raw material for a nonionic crosslinked polymer that can be made hydrophilic if necessary.

Prior Art Crosslinked polymers are used as useful materials in a wide range of fields, especially when crosslinked monomers (
In other words, when cross-linked using a monomer having two or more polymerizable groups in the molecule, it is possible to make all kinds of hard materials, so when cross-linked polymers are polymerized, they can have various structures depending on the purpose. Crosslinking monomers are used.

Among cross-linked polymers, hydrophilic ones are used as fillers and adsorbents for aqueous chromatography and their carriers, as well as medical materials for artificial organs due to their low biological reactions, as well as separation membranes, It is also used in contact lenses, sanitary products, etc., and is an extremely important material in practical terms.

In general, the properties required of a crosslinking monomer include: high polymerizability, stability and ease of handling that allow a wide range of polymerization conditions, the ability to appropriately control the degree of crosslinking, and the ability to use other materials as a crosslinking agent. When copolymerizing with a monomer, good copolymerizability is mentioned. Especially when obtained from hydrophilic cross-linked polymers,
Even in the case of copolymerizing a small amount of crosslinking monomer with f4'jc, it is desirable that the crosslinking agent component itself is hydrophilic. In fact, when used as a packing material for aqueous chromatography, if the crosslinking agent component is hydrophobic or ionic, it tends to adsorb various substances dissolved in water, which often poses a problem.

So far, hydrophilic crosslinked polymers that have actually been developed include vinyl acetate and various crosslinking agents [for example, l,4-butanediol divinyl ether (Japanese Patent Publication No. 44-2091
7) and diethylene glycol dimethacrylate (see JP-A-52-138077)].
A product obtained by saponifying the mixture is known.

However, all of the crosslinking agents used in these polyvinyl alcohol examples had insufficient hydrophilicity and co-monomerization, which had an unfavorable effect on their main use as packing materials for liquid chromatography. .

On the other hand, as an example of obtaining a hydrophilic crosslinked polymer by homopolymerization,
A method using pen erythritol dimethac IJ rate is known (see % Japanese Patent Publication No. 160300/1983). Although this monomer is crosslinkable and has two hydroxyl groups in its molecule, it is barely distributed in the organic solvent during aqueous suspension polymerization. However, since the monomer itself is water-soluble, it must be said that the range of selection of polymerization conditions is extremely narrow.

Other prior art similar to the present invention includes crosslinking copolymerization with acrylic acid using polyallyl ether of sucrose as a crosslinking agent (US Pat. No. 4,331,572, etc.), or homopolymerization of glucose polymethacrylate (5chr.
iftenr, Dtsch・Wollforschu
ngsinst, (Tecb, Hochseb.

Aachen) 84.186 (1981)), but the former crosslinking monomer is structurally polymerizable 75
The latter monomer is not easy to handle because it is water-soluble. Also known are dimethacrylates of sugars and sugar alcohols in which other hydroxyl groups are protected with methylene acecool, benzylidene acetal, or intramolecular ether (dehydrated derivatives) (J.

chem, soc, 488 (1946)). Although these compounds have sufficient polymerizability and are relatively easy to handle, the acetal forms of the former two are extremely unstable under acidic conditions, and cannot necessarily be said to be stable in the presence of water even near neutrality. On the other hand, if we try to convert the latter dehydrated derivatives into hydrophilic ones after polymerization, it is extremely difficult to hydrolyze the dimensional ether bonds that maintain crosslinks and ends, and in reality, hydrophilic polymers are I can't get it.

Like this, a hydrophilic crosslinked column? To date, a crosslinkable monomer with a preferred structure for use in remer synthesis has not been obtained.

OBJECTS AND STRUCTURE OF THE INVENTION Accordingly, the present inventors studied to develop a crosslinking monomer with a more preferable structure, and found that di- or tri(meth)acrylates of monosaccharides or trisaccharides or reduced derivatives thereof with other hydroxyl groups The present inventors have discovered that a monomer protected with an ester group has excellent vinyl polymerizability, is stable and lipophilic, and is therefore an excellent crosslinking monomer that can be used under a wide range of polymerization conditions, leading to the present invention. After polymerization, this material can be very easily converted to hydrophilic properties by partial hydrolysis.

That is, the crosslinking monomer according to the invention has the general formula % (%) (where R is the residue of a monosaccharide or trisaccharide or a reduced derivative thereof, R' is an alkyl group or an alkoxy group, R'
is a hydrogen atom or a methyl group, n is 2 or 3, and m + n is the number of all hydroxyl groups possessed by the sugar or its reduced derivative, which is 3 or more.

Outline of the invention and explanation of its effects The present invention will be explained in detail below.

First, the sugars or reduced derivatives thereof that form the skeleton of the monomer of the present invention include glycose, fructose, mannose, galactose, and hyxylose.
i[[j, trisaccharides such as sucrose, maldose and lactose, or reduced derivatives of sugars, i.e. sugar alcohols such as sorbitol, mannitol, xylitol and arabitol, or deoxysaccharides such as rhamnose, 7cose and quinovose, etc. used. Since these have a low molecular weight, they have a good balance between the degree of crosslinking and the quantity of hydroxyl groups, and therefore appropriate strength and hydrophilicity can be obtained at the same time. However, for this purpose, it is necessary that the number of all hydroxyl groups in the A-tsuno 1 hardened or reduced derivative thereof used is 3 or more, preferably 4 or more. Due to the hemiacetal structure and glycosidic bond of the monomer to be degraded, reduced derivatives of saccharides are preferable, and alcohols are particularly preferable, especially sorbitol, mannitol, etc. Hexitol is most preferred.

If 21 or more polymerizable functional groups are introduced into this, a crosslinkable monomer, that is, a monomer that can give a three-dimensional polymer by performing a polymerization reaction, is obtained. By forming an acid ester structure, a monomer with high vinyl polymerizability can be obtained. Moreover, this monomer is extremely excellent in its copolymerizability with many acrylic ester and methacrylic ester monomers. In addition, the number of (meth)acryloyl groups per molecule is necessarily required to be 2 or more in order to have crosslinking properties, but 3
Those that exceed the individual are too polymerized and unstable, and many parts of the (meta) acryloyl group cannot substantially contribute to the polymerization reaction. Therefore, it is desirable that the number of (meth)acryloyl groups in the crosslinkable monomer of the present invention is two or three.

υ) The hydroxyl group to which the acryloyl group is not bonded is used to make the crosslinking monomer lipophilic and easier to use in polymerization.
Protect with appropriate protective groups.

Generally, alkyl ethers, acetals, silyl ethers, and carboxylic acid esters are used to protect hydroxyl groups.

Carbonic esters, orthoesters, etc. are used, and these are actually often used to protect the hydroxyl groups of sugars. However, in order to carry out aqueous 1' turbidity polymerization, as in the case of synthesizing spherical chromatography packing materials, it is strongly desired to be stable in water at least near neutrality; Among the groups, acetals, silyl ethers and orthoesters are extremely unstable in the presence of water, particularly under acidic conditions, and are therefore undesirable. On the other hand, alkyl ethers such as methyl ether are too stable and unsuitable under conditions that do not change the poly(meth)acrylic acid ester moiety when disassociating after polymerization. Therefore, carboxylic acid esters and carbonate esters are stable even under weakly alkaline to near neutral conditions and under slightly acidic conditions, and can be easily released under alkaline conditions after polymerization.
Suitable as one unit. If the general formula % is a ru group or an alkoxy group, νj is n? It is rapidly deprotected even under mild conditions where the (meth)acrylic acid ester is not hydrolyzed. R' is specifically CH3,
C2H5, C4H2, C6H13, CACH2゜CH3
Alkyl groups such as 0CH2 (λ including substituted alkyl groups or alkoxy groups such as CH30, C2H3O, C4H2O, etc.), among which alkyl groups and alkoxy groups having 6 or less carbon atoms are preferred because they have less steric hindrance. Particularly stable From the viewpoint of properties and ease of deprotection, an alkyl group with a small number of carbon atoms is preferable, and one in which 1.R' is CH6 is most preferable.

The crosslinkable monomer of the present invention can be synthesized, for example, by the method shown below. That is, first, an appropriate amount of (meth)acrylic acid chloride or anhydride is added to a pyridine solution or suspension of a raw material, saccharide or its reduced derivative. An appropriate amount is an amount slightly in excess (1.1 to 2 times) of the theoretical amount depending on the number of (meth)acryloyl groups to be introduced.

After sufficient reaction, acetic acid, propionic acid,
An excess amount of a chloride or anhydride of a carboxylic acid such as chloroacetic acid, or a chloroformate ester such as methyl chloroformate is added and reacted. By extracting the reaction product with a suitable organic solvent and distilling off the solvent, a mixture containing the crosslinkable monomer of the present invention as a main component can be obtained. The obtained mixture can be used for polymerization as it is, or if necessary, recycled by a precipitation method or the like.

The structure of the monomer was determined by elemental analysis, nuclear magnetic resonance spectroscopy,
This can be confirmed by infrared absorption spectrum, etc.

In order to obtain the crosslinkable monomer of the present invention, the order of adding the 2m acylating agent may of course be reversed, and as long as it has the monomer structure shown in the above general formula, the essential physical properties may be determined by other synthesis methods. It doesn't change what you get from it.

The monomer ~ synthesized by the above method is lipophilic,
Does not dissolve in water. Therefore, in the presence of water, it is of course stable under neutral and acidic conditions, and even under alkaline conditions it can exist stably as long as a phase transfer solvent or a water-soluble organic solvent is not present.

Since the monomer of the present invention is a (meth)acrylic ester, it is particularly excellent in terms of polymerizability. For example, if aqueous suspension polymerization is carried out using a commonly used radical initiator such as benzoyl peroxide or 2,27-azobisisobutyronitrile, a spherical insoluble polymer can be easily obtained and has high mechanical strength. This indicates that a crosslinked polymer was produced. This polymer is made by alkaline hydrolysis under mild conditions, whereby only the protecting groups, i.e., the carboxylic ester groups or carbonate ester groups other than the poly(meth)acrylic ester moiety, are selectively converted into hydroxyl groups, making it hydrophilic. gives a polymer of

In addition to the suspension polymerization described above, polymers in the form of pellets, films, or fine powders can also be obtained by methods such as bulk polymerization or solution polymerization, depending on the shape of the polymer required. Furthermore, it is also possible to convert only the interface of the obtained polymer into hydrophilic by controlling the hydrolysis conditions as necessary.

Furthermore, the monomer of the present invention has excellent copolymerizability, and can be copolymerized not only with various (meth)acrylic esters such as methyl methacrylate and 2-hydroxyethyl methacrylate, but also with styrene, acrylonitrile, and methyl. Copolymerization with various monomers such as vinyl ketones is also possible in a wide range. Therefore, by using this crosslinking monomer, it is possible to obtain hydrophilic properties. It is not only possible to obtain a remer, but it can also be used simply as a crosslinking agent in crosslinking copolymerization with other monomers without deprotection after polymerization, making it extremely useful industrially.

EXAMPLES Hereinafter, the present invention will be explained in detail with reference to Examples, but it goes without saying that the scope of the present invention is not limited to these Examples.

Example 1 Sorbitol 55I in a 1 ton flask! and pyridine 3
001n/14-, and after stirring, 60 ml of methacryloyl chloride was added dropwise. After heating and stirring at 60°C for 2 hours, 170 ml of anhydrous vinegar H was added dropwise, and heating and stirring was continued while maintaining the temperature at 60°C. After 20 hours, the mixture was poured into ice water and extracted with isopropyl ether. The extract is diluted with acid 5
It was washed with sodium bicarbonate solution and fertilizer saline, and the solvent was distilled off under reduced pressure to obtain tetraacetyl dimecacryloyl sorbitol as an oil (80%, P, crude yield 57t, content 63t, in addition to pentaacetyl methacryloyl. sorbitol and triacetyl trimethacryloyl norbitol were produced as by-products). The structure was determined using a nuclear magnetic resonance spectrum (measuring device: JEOL PMX) after being separated by preparative thin layer chromatography.
-60, measurement solvent: chloroform-ds) and infrared absorption spectrum (measurement device: JASCO A-1, measurement solvent: chloroform). Figure 1 shows the data for each sitter.

It is shown in FIG. 2 and Table 1.

Although stirring was continued in the sodium hydroxide aqueous solution of the monomer i1M, no reaction occurred. Moreover, it did not react at all even in neutral and acidic aqueous solutions and was stable.

80g of monomer and azobisisobutyronitrile2.
The solution was dissolved in 64 m of butyl acetate, suspended in 450 TL of water containing 1 g of polyvinyl alcohol, and heated and stirred first at 60°C for 18 hours and then at 75°C for 5 hours. After the reaction was completed, the polymer was taken off, washed with water and acetone, and dried to obtain spherical particles 689 (yield: 85 cm). When the infrared absorption spectrum of this polymer was measured, it was found that 1
1] at 750 crn showed absorption of acid ester. Note that this polymer was not soluble at all in water or organic solvents.

50.9 of this polymer was added to 700 ml of a methanol solution containing 17 g of sodium hydroxide, and a hydrolysis reaction was carried out at 15° C. for 20 hours. After the reaction was completed, it was filtered, thoroughly washed with methanol and water, and then dried to obtain polymer particles.

This polymer has a water affinity, and when its infrared absorption spectrum was measured, it showed strong absorption of hydroxyl groups at 3500 t'm-1 and absorption of polymethacrylic acid ester at 1720 crn.

Example 2 182 g of sorbitol and 1 liter of pyridine in a 3 ton flask
Add 30% of methacryloyl chloride while stirring.
0 rnlf was dropped. After heating and stirring at 60°C for 2 hours, 420 ml of acetic anhydride was added dropwise, and the mixture was heated and stirred at 60°C for 20 hours. Thereafter, an extraction operation was carried out in the same manner as in Example 1 to obtain a mixture of triacetyl trimethacryloyl sorbitol and tetraacetyl dimethacryloyl sorbitol as an oil (175F, crude yield 35%, contents 46 and 41q6, respectively). The structure of the former was confirmed by preparative thin layer chromatography and nuclear magnetic resonance spectroscopy and infrared absorption spectrum. The respective spectral data are shown in Table 1.

Example 3 Glucose 5411 and Pyridine 60 in a 1 ton flask
0 ml was added, and methacryloyl chloride 9Q+aj was added dropwise while stirring. After stirring at room temperature for 2 hours, 120-acetic anhydride was added dropwise, and stirring was continued for 20 hours. Thereafter, an extraction operation was carried out in the same manner as in Example 1 to obtain triacetyl dimethacryloylglucose as an oil (75 g, crude yield 60 g, content 40 g; approximately the same amount of tetraacetyl methacryloyl glucose was produced as a by-product). The structure was confirmed by nuclear magnetic resonance spectrum and infrared absorption spectrum after fractionation by preparative thin layer chromatography. The respective spectral data are shown in Table 1.

Examples 4 to 9 The same procedure was carried out using the sugars or reduced derivatives thereof shown in Table 2 in place of glucose in Example 3, and the acylating agents shown in Table 2 in place of acetic anhydride. The corresponding monomers were obtained by performing the following operations.

Each 41ζ structure was separated by preparative thin layer chromatography and confirmed by nuclear magnetic resonance spectroscopy and infrared absorption spectroscopy. These spectral data are the first
Shown in the table.

Second coating Example 10 6.8 g of sucrose octaacetate, 8 g of methacrylic acid
-5 ml A mixture of 0.5 # of 1zf radruene sulfonic acid and 20 # of 1,2-dichloroethane was heated at 60°C.
Stirred for 0 hours. After cooling to room temperature, the mixture was washed with an aqueous sodium bicarbonate solution and then with water, and the solvent was distilled off to obtain a mixture containing pentaacetyltrimethacryloyl sucrose. The spectral data of the products are shown in Table 1.

Example 11 Acryloyl chloride 3. Oml and acetyl chloride3. Om
Sorbitol 1.82F-! is dissolved in 30ml of chloroform. i: The suspension was suspended, and a solution of triethylamine 1Qm7i30TIL1 dissolved in chloroform was added dropwise at room temperature. After stirring for 1 hour, water was added, extracted with isopropyl ether, and the solvent was distilled off to obtain acetylacryloyl sorbitol isomer mixture 4.1.
I got g. This was separated by preparative thin layer chromatography to obtain tetraacetyl diacryloyl sorbitol, whose structure was confirmed by nuclear magnetic resonance spectroscopy and infrared absorption spectroscopy. The respective spectral data are shown in Table 1.

Example 12 The same operation as in Example 11 was carried out using fructose in place of sorbitol (9) to obtain triacetyl diacryloylfructose. The structure was confirmed by nuclear magnetic co-gl) spectrum and infrared absorption spectrum, and the data are shown in Table 1.

Margin below

[Brief explanation of the drawing]

FIG. 1 shows the nuclear magnetic resonance spectrum of tetraacetyl dimethacryloyl sorbitol obtained in Example 1, and FIG. 2 shows the infrared absorption spectrum of the compound. Patent applicant Asahi Kasei Kogyo Co., Ltd. Patent agent Akira Aoki Patent attorney Kazuyuki Nishidate Patent attorney Ishi 1) Honorable patent attorney Akira Yamaguchi

Claims (1)

[Claims] 1. General formula %) (wherein, R represents the remainder of a monosaccharide, disaccharide, or a reduced derivative thereof; H/ represents an alkyl group or an alkoxy group; R'' represents a hydrogen atom or Methyl foundation, n is 2 or 3i
and m 10n is the number of all hydroxyl groups possessed by the saccharide or its reduced derivative, and is a number of 3 or more. 2. The crosslinkable monomer 0 according to claim 1, wherein R in the general formula is a residue of a sugar alcohol.