JPS604204B2 - Method for modifying polymers of acyloxyalkyl methacrylates - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to the following general formula (1) [wherein, RI is (CH2)n-○(n-2-1
0) or (CH2CH2-0)n (n = 1 to 4), R2 is an alkyl group having 4 to 21 carbon atoms and having a quaternized carbon atom in the Q-position relative to the carbonyl group; It is the basis.

] A polymer or copolymer of acyloxyalkyl methacrylates having a structural unit consisting of the following, particularly a block copolymer consisting of a polymethacrylate block and a poly(acyloxyalkyl methacrylate) block produced by a polymerization reaction using an anionic polymerization initiator and a free radical polymerization initiator. The present invention relates to a method for partially or completely modifying hydrophobic acyloxyalkyl methacrylate units of a polymer into a hydrophilic hydroxyalkyl methacrylate polymer or copolymer.

Poly(glycol methacrylates) have a very wide range of uses, for example as materials for gel permeation chromatography in the medical field.

Glycol methacrylate monomers are readily polymerized by free radical methods. However, it is impossible to anionically polymerize this glycol methacrylate because the hydrogen atoms of the alcohol groups of the monomers decompose the anionic initiator due to their acidity and also inactivate the formed polymerization initiation center. be. Therefore, it has not been possible to produce stereoregular poly(hydroxyalkyl methacrylate) or block copolymers having a lipophilic block and a block having a hydrophilic hydroxyalkyl methacrylate structural unit using currently known methods. be.

It is an object of the present invention to provide such polymers or copolymers which have a very wide range of uses such as in the medical field, and in particular to provide polymers or copolymers that can be used by modification from specific polymers or copolymers. In particular, the object is to provide various stereoregular or atactic polymers or copolymers.

As mentioned above, anionic polymerization of glycol methacrylate has not been possible due to the presence of hydrogen atoms in the alcohol groups of the monomers.

Therefore, research has been conducted into methods of blocking the alcohol groups of monomers by acylation. According to our previous studies, the polymerization of acylated glycol methacrylates can be carried out using acyl residues with only one or preferably no hydrogen atoms in the Q-1 position. It is thought that this can be achieved by That is, when methyl methacrylate is polymerized with an organometallic initiator such as n-butyllithium or with a weakly basic alkali metal tertiary alkoxide (for example, lithium tertiary butoxide), Acyl residues with a hydrogen atom in the Q-position, e.g.
This is because it has been shown that when an alkyl acetate is present, the condensation reaction between these basic compounds and acetate interferes with the polymerization reaction. The product of a condensation reaction, e.g. in the form of the R-CO-C ratio -CO-RI, has a very acidic hydrogen atom due to the strong electron affinity of the carbonyl group, which terminates with the growing anion. This causes a reaction and completely prevents the polymerization reaction.

Therefore, in the synthesis of acyloxyalkyl methacrylates, a preparation method that does not have a hydrogen atom at the Q-position in the acyl residue has been sought. According to the research of the present inventors, a free radical polymerization initiator or anionic polymerization initiator is added to an acyloxyalkyl methacrylate represented by the following general formula (0) or a mixture of this acyloxyalkyl methacrylate and other polymerizable monomers. (where RI and R2 have the same meanings as described above).

) Next, by heating the obtained mixture to a temperature at or above the decomposition temperature of the free radical polymerization initiator, or a temperature required for anionic polymerization reaction, a structural unit having the following general formula (1) is prepared. and polymers or copolymers (including block copolymers) of acyloxyalkyl methacrylates having various degrees of stereoregularity.
By applying a simple modification reaction, these (hydroxyalkyl methacrylates) and their corresponding stereoregularity have a wide range of applications in various fields, including the medical field as mentioned above.

It was discovered that it could be modified into a Tsuku copolymer and was published. That is, the present invention provides for removing the ester protecting group from a polymer or copolymer of acyloxyalkyl methacrylates having the structural unit of general formula (1) by selective chemical reaction, for example, at a temperature of 0 to 10,000°C. or selective catalytic alcoholysis using 5% sodium methoxide in anhydrous methanol, or selective aminolysis, especially if desired with an anionic polymerization initiator and the corresponding alcohol. A polymer or copolymer of acyloxyalkyl methacrylates having the structural unit of general formula 1, characterized in that the alkoxide is partially or completely removed by using the alkoxide in this selective catalytic alcoholysis. It is a modification method that can be used to prepare cohesive, stereoregular or atactic polymers or copolymers.

The method of the present invention will be explained in detail below, but first, the details of the method for producing a polymer or copolymer of acyloxyalkyl methacrylates, which is a precursor of the method of the present invention, will be explained in detail.

Anionic initiators used in the homopolymerization of methacrylate-based monomers have the advantage of producing polymers that differ substantially in microscopic structure, indicated by stereoregularity.

For example, lithium-based initiators form isotactic polymers in hydrocarbon media and in polar media, e.g.
In tetrahydrofuran, it forms atactic to syndiotactic polymers. In connection with the diversity of stereoregularity, these polymers also differ in their mechanical properties, such as, for example, the glass transition temperature. The technology of active polymers (living polymers) obtained by anionic polymerization is the most advantageous technology and at the same time is virtually the only method that allows the production of block copolymers.

Polymerization is carried out using an anionic initiator to obtain 100% of the first monomer.
The second monomer added as the second monomer is connected to the end of the polymer chain while maintaining the reactivity of the growing end of the polymer chain. Homopolymerization of acyloxyalkyl methacrylates by a radical mechanism is carried out using a free radical polymerization initiator, for example, dibenzoyl peroxide or isopropyl peroxocarbonate in a benzene solution or as such (bulk polymerization).

For example, it is also possible to produce acyloxyalkyl methacrylate homopolymers in the presence of a crosslinking agent such as glycol dimethacrylate. Network-structured polymers are also insoluble in organic solvents when polymerizing acyloxyalkyl methacrylates in the presence of a crosslinking agent such as glycol dimethacrylate, and depending on the amount of crosslinking agent such as glycol dimethacrylate. , it can also be formed so that it swells to some extent. Homopolymerization of acyloxyalkyl methacrylates by an anionic mechanism is carried out using alkali metal trivalent alkoxides, such as sodium t-butoxide, lithium organometallic compounds, such as n-butyllithium, as initiators.

The polymerization reaction using an alkali metal alkoxide is carried out at room temperature. Polymerization of acyloxyalkyl methacrylate with n-butyllithium is carried out in situ (bulk polymerization) or in solution at a low temperature of -30 to -170 qo. It was also confirmed that anionic polymerization of acyloxyalkyl methacrylate is possible in the presence of glycol dimethacrylate. Polymers with network cross-structures are formed by polymerization in the presence of cross-linking agents, such as glycol dimethacrylate, which are insoluble in organic solvents and only swell to some extent depending on the amount of cross-linking agent (glycol dimethacrylate). It became a thing with a sexual nature. If a small amount, for example, 1 to 2% of a crosslinking agent (glycol dimethacrylate) is added to the acyloxyalkyl methacrylate and the concentrations of the monomer and initiator are appropriately selected,
Polymers soluble in organic solvents such as benzene, toluene, chloroform, etc. can be obtained.

In this case, if the ratio of the monomer concentration to the growth center concentration is adjusted to a range of 50:1 to 200:1 with respect to the crosslinking agent concentration,
A soluble block copolymer is obtained. Block copolymers of methacrylates and acyloxyalkyl methacrylates were prepared by anionic living polymer technology.

The polymerization of the first monomer (methacrylate) is initiated by n-butyllithium in toluene solution at a temperature of -70°C, but the center of growth of the polymer chain undergoes a Grignard-type reaction with the ester group. The conditions are such that no side reactions occur.This reaction is carried out to a certain extent at a temperature of 120°C, resulting in the termination of the polymer chain such that the monomer molecules are no longer bonded.The first monomer After the monomer methacrylate is consumed, the second monomer acyloxyalkyl methacrylate is added and the polymerization reaction is carried out until the entire amount is reacted.

The resulting block copolymer is precipitated in methanol, reprecipitated and dried at 4500 vacuo to dryness. The process of the invention can also be used for the production of stereoregular homopolymers of acyloxyalkyl methacrylates and block copolymers of these compounds with other methacrylates (methyl methacrylate, butyl methacrylate, etc.). Polymers having various degrees of stereoregularity (isotactic,
Syndiotactic and atactic polymers) can then be prepared according to the present invention by applying a simple modification reaction to poly(hydroxyalkyl methacrylates) and the like, which have a wide range of applications in various fields including the medical field as mentioned above. These block copolymers can be produced with a stereoregularity of.

This modification method will be explained below. Until now, a method for producing a block copolymer having a hydrophobic block and a block of hydrophilic structural units had not been achieved. This is because the polymerization reaction was hindered by the reaction.

According to the research of the present inventors, as mentioned above, when using a monomer with its hydrophilic group protected in the form of an appropriate ester, in addition to radical polymerization, anionic polymerization or copolymerization reaction or block copolymerization reaction A polymerization reaction is possible, and the protecting groups in the obtained polymer are partially or completely removed by the following reaction process to become a hydrophilic hydroxyalkyl methacrylate structural unit: CH2=
C(CH3)-CO-○-(C France) n-○-CO-R where R is a group that does not have an acidic hydrogen at the ○-position (for example, tert-butyl, phenyl, substituted phenyl, etc.)
, P indicates the degree of polymerization, and n is an integer nZ2.

A feature of this reaction process is the utilization of different dissociation rates of various ester bonds in one structural unit.

For example, in the above case, the essential stability of the ester bond to the polymethacrylic skeleton and the relatively easy dissociation of the protecting group from the ester bond are utilized. Regarding anionic polymerization or copolymerization reaction conditions, suitable protecting groups include acyl groups that do not have an acidic hydrogen atom at the Q-position of the carbonyl group (in the sense of Perkin synthesis), such as pivaloyl group and benzoyl group. and so on. Removal of some or all of the protecting groups can be carried out by many methods, such as hydrolysis, alcoholysis, aminolysis, etc. In this case, the reactivity of the ester linkage towards the protecting group should be high and the ester linkage to the polymer backbone should be The reactivity difference must be maintained such that the reactivity of the bond is substantially low.

A suitable method includes alcoholysis using the alkoxide used in the polymerization reaction or an alkoxide obtained by reacting an added alcohol with an anionic catalyst. This reaction is carried out using soluble or crosslinked (co)polymers, homopolymers and block copolymers.

The crosslinked copolymer can be produced in the form of a film, a block or a suspension (
It is also transformed into the shape of a granular product. Monomers with one or more vinyl groups are advantageously used as crosslinking agents.

That is, ethylene glycol dimethacrylate or diacrylate, diethyresoglycol dimethacrylate, glycol divinyl ether, divinyl adibate, divinyltoluene, trivinylbenzene, divinylbenzene, divinylnaphthalene, triallyl cyanurate, and the like. The modified polymer thus obtained is a polymer. Differences in the affinity of the hydrophilic moieties for polar molecules (e.g., water, biochemical fluids, etc.) and hydrophobic interactions of the non-sacrificial residues of the macromolecules, e.g. at the phase interface, can cause block copolymers, e.g. (Hydroxyethyl methacrylate-b-methyl methacrylate) or the like can be used in applications where it plays a role in the permeation of trough or non-polar molecules through membranes or semipermeable membranes.

The modified polymer according to the present invention can be advantageously used, for example, in the following applications. Wind Synthetic leather with hygienic properties (this property can vary depending on the degree of modification after hydrolysis).

) [B} For chromatographic materials in a form in which the protecting group is not hydrolyzed or partially or completely hydrolyzed} Utilizing the strength of the (co)polymer that is the base material before modification, it is possible to apply a suitable material to the surface. Medical applications such as forming a hydrophilic film by performing a modification reaction (for example, hydrolysis) The present invention will be explained in more detail with reference to Examples below. Of course, there is no limitation.

In addition, pivaloyloxyethyl methacrylate used in the following synthesis examples has the following formula (m) (CH3)3C-COC
It was obtained by the following reaction of pivaloyl chloride of 1(m) and 2-hydroxyethyl methacrylate in pyridine medium.

1. To explain the method of producing pivaloyloxyethyl methacrylate, for example, it was produced as follows: In a 250-volume flask equipped with an electromagnetic flywheel, on
．． 07 mol) of 2-hydroxyethyl methacrylate,
0.5 g of hydroquinone and 60 g of anhydrous pyridine were added.

To this mixture was slowly added 9.3 moles (0.77 moles) of pivaloyl chloride in 25 moles of pyridine.
It was added every 1 second while keeping the temperature between 0 and 35°C.
The mixture was then heated to 40:00 for 2 hours. The reaction product was then poured into 600 ml of water and acidified with hydrochloric acid.
The extraction was repeated 5 times with 200' portions of ether.
The ether extract was then shaken twice in a 5% aqueous sodium carbonate solution, shaken twice in 25 batches of water, and shaken three times in 25 batches of water.
It was dried over magnesium sulfate and the ether was distilled off. A crab fraction boiling at 79-80°C/1.5 side Hg was obtained: the yield was 10.91 min (72.74%).

Synthesis Example 1 In a vessel pre-flushed with argon or nitrogen for vacuum tubes, add 8.8' of toluene, 0.8' of toluene, and 0.8' of toluene.
The free radical initiators, isopropyl peroxocarbonate and pivaloyloxyethyl methacrylate, were charged.

After the initiator has dissolved, the temperature of the polymerization reaction mixture is gradually increased to 3
The temperature was raised from 000 to 7000 over 5 hours. The polymer was obtained in almost 100% yield. Synthesis Example 2 The polymerization reaction shown in Synthesis Example 1 was carried out without a solvent.

Synthesis Example 3 Into a pre-evacuated and flame-heated container flushed with inert gas (nitrogen for vacuum tubes, argon), 2.
3 parts of pivaloyloxyethyl methacrylate (previously dried with CaH2) and 0.039 parts of sodium talibutoxide were added to 2 parts of toluene in a syringe in countercurrent with an inert gas. Introduced.

A polymer was obtained in a yield of 45% in a 24 hour polymerization reaction at 20 qo.

Synthesis Example 4 A polymerization reaction was carried out in the same manner as in Synthesis Example 3, except that solid tributoxide was used as an initiator and the solvent was evaporated at a low temperature.

Synthesis Example 5 A polymerization reaction was carried out in the same manner as in Synthesis Example 3.

However, 7.6 parts of toluene is added to 1.8 parts of pivaloyloxyethyl methacrylate, the mixture is cooled to -78°C, and 0.44 parts of toluene is added to 1.8 parts of pivaloyloxyethyl methacrylate. A state-of-the-art n-butyllithium solution was used. After 2 hours the polymer was obtained with a yield of 85%.

Synthesis example 6 A polymerization reaction was carried out in the same manner as in Synthesis Example 5.

However, penzoyloxyethyl methacrylate was used instead of pivaloyloxyethyl methacrylate. 2
The polymer yield after a short time was 35%.

Synthesis Example 7 A polymerization reaction was carried out in the same manner as in Synthesis Example 5. However, pivaloyloxyethyloxyethyl methacrylate was used instead of pivaloyloxyethyl methacrylate. Synthesis Example 8 A polymerization reaction was carried out in the same manner as in Synthesis Example 3 as follows.

Add 0.5 ml of methyl methacrylate to 24 ml of toluene and cool the polymerization reaction mixture to -78 oo.
1' of 0. Added n-butyllithium from Su.

Polymerization of methyl methacrylate was completed in 1 to 5 hours.

To the thus obtained poly(methyl methacrylate) polymer, 178 qo of pivaloyloxyethyl methacrylate (0.5 qo) was added. It was precipitated inside.

A floc copolymer was obtained in 0.8 hours, or a yield of 82%. It was simply swollen by the organic solvent (more than 19 times the volume). Synthesis Example 9 A polymerization reaction was carried out in the same manner as in Synthesis Example 8.

However, double the amount of initiator, i.e. 2.3' of 0. State n-butyllithium was used. The polymer is soluble in organic solvents such as chloroform, benzene, etc., and was isolated in 80% yield by precipitation. Example 1 1.89% ethylene dimethacrylate (0.1252
Poly(2-pivaloyloxyethyl methacrylate-b-methyl methacrylate) crosslinked with
'swelled in toluene.

After 4.5 hours, 10' methanol and 0.51867
A 0.63779 mL aqueous solution containing milliequivalents of sodium hydroxide was added.

The mixture was heated to 50 qo in a short time and left to stand for 12 hours at room temperature with occasional shaking. Then, it was evaporated to dryness in a rotary evaporator, and the remaining soluble components were removed by decantation with water twice (2 x 50 [)], and filtered through a bonded sintered glass filter. The furnace liquor was concentrated by evaporation in a rotary evaporator and, after addition of hydrochloric acid (2.501% of 0.10107N hydrochloric acid), 0.104% of the indicator mixture (phenol red + bromothymol flu) was added.
Basicity reduction was determined by back titration with sodium hydroxide in 8 states. The waterfall quantification ([) of 0.292 corresponded to the total amount of pivaloyl group removed. According to the results confirmed by NMR spectrum, it was confirmed that all the pivaloyl groups had undergone hydrolysis and that the modified block copolymer had an isotactic structure. Example 2 Soluble copolymer poly(2-pivaloyloxyethyl methacrylate-b-methyl methacrylate) (0.11
864 mm) was swollen in 2.5 mm of toluene, then 10 mm of methanol and 0.59894 mm of aqueous sodium hydroxide (containing 0.48708 meq. NaOH) were added.

The subsequent operations were carried out in the same manner as in the previous example, and the conversion of pivaloyl groups reached 83.64% after one hour. Synthesis Example 10 24'
of toluene and 1.5' of methyl methacrylate were charged in a syringe in countercurrent with the inert gas.

This polymerization mixture was cooled to -7800 and 23 min.
．． 3N Butyllithium was added. Polymerization reaction is 1-5
It was completed after hours. Poly(methyl methacrylate) was mixed with 0.5' of 2-pivaloyloxyethyl methacrylate at 7,800 °C. After 2 hours, the polymerization mixture contained methyl methacrylate and 2
- A block copolymer of pivaloyloxyethyl methacrylate was included.

Example 3 The copolymer obtained in Synthesis Example 10 above was previously dried with barium oxide and sodium metal and treated with 5M methanol, and the mixture was heated to the boiling point and refluxed for 2 hours.

Claims (1)

[Claims] 1 The following general formula I ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [However, in the formula, R^1 is (CH_2)n-O(n=
2-10) or (CH_2CH_2-O)n (n=1
~4), and R_2 is an alkyl group having 4 to 21 carbon atoms, and has a quaternized carbon atom at the α-position relative to the carbonyl group. ] From the polymer or copolymer of acyloxyalkyl methacrylates having the structural unit of the ester protecting group ▲ mathematical formula, chemical formula, table, etc. ▼, selective chemical reaction, for example, at a temperature of 0 to 100℃ selective hydrolysis reaction in , and selective catalytic alcoholysis using 5% sodium methoxide in anhydrous methanol,
or selective aminolysis, in particular, if desired, by using an alkoxide formed by an anionic polymerization initiator and the corresponding alcohol in this selective catalytic alcoholysis to partially or completely remove the alkoxide. A method for modifying a polymer or copolymer of acyloxyalkyl methacrylates having the structural unit of general formula I, characterized in that it can be used to prepare a stereoregular or atactic polymer or copolymer.