JP2000169577A - Manufacture of polysuccinimide - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a polysuccinimide of high quality within a short time in high purity by thermally polymerizing aspartic acid in the presence of a hydrochloric acid aqueous solution and/or a hydrogen chloride gas. SOLUTION: This high-molecular-weight polysuccinimide is obtained by adding, to aspartic acid, a hydrochloric acid aqueous solution having a concentration of 35% and/or a hydrogen chloride gas used an acid catalyst in an amount of 0.1 to 0.95 equivalents relative to the aspartic acid, and heating for polycondensation reaction at a normal pressure or under a reduced pressure of 600 to 1 mmHg in a stream of nitrogen at 120 to 220 deg.C for 5 to 20 hours. Where the hydrochloric acid aqueous solution is used for the polycondensation reaction, aspartic acid is introduced into the hydrochloric acid aqueous solution and reacted. On the other hand, where a hydrogen chloride gas is used, aspartic acid is introduced into an organic solvent and/or water, after which a predetermined amount of a hydrogen chloride gas is absorbed therein for the reaction. Examples of the solvent employed for the absorption upon use of the hydrogen chloride gas include alcohols such as methanol and the like, aromatic hydrocarbons such as toluene and the like, aromatic halogenated hydrocarbons such as dichlorobenzene and the like, acetic esters such as ethyl acetate and the like, and the like.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to pharmaceuticals, cosmetics,
The present invention relates to a method for producing a polysuccinimide useful as an intermediate for cosmetics and the like. More specifically, the present invention relates to a method for producing polysuccinimide by heating polycondensation of aspartic acid in the presence of an aqueous hydrochloric acid solution and / or a hydrochloric acid gas. Further, the present invention relates to a method for producing a powder of polysuccinimide.

[0002]

BACKGROUND ART [Technical background] In general, polyamino acids are frequently used in the fields of medicine and biochemistry as protein model compounds. Polysuccinimides are also precursors to polyaspartic acid synthesis, which are useful as environmentally compatible water-soluble polymers. In addition, Japanese Patent Publication No. 48-20
No. 638 discloses a technique for synthesizing pharmaceutically useful poly- (aspartic acid) -hydroxyalkylamide using polysuccinimide as an intermediate.

[Solid Phase Polycondensation] As a method for obtaining polysuccinimide by solid phase polycondensation of aspartic acid, a method of heating and polycondensing aspartic acid. Numerous literatures and patents describe methods for polycondensing aspartic acid by heating in the presence of an acid catalyst.

<Non-catalyst / Heat polycondensation> Specific examples of conventional techniques for obtaining polysuccinimide by heat polycondensation without a catalyst include the following 1-2.

[0005] 1. J. Amer. Chem. So
c. 80, 3361 (1958); Ame
r. Chem. Soc. , 80, 3361 (195
8 years), using aspartic acid as a raw material at 200 ° C.
A technique of performing heat condensation for 3 hours is disclosed. However, the molecular weight of the polysuccinimide obtained by this technique is very low, about 1000.

2 JP-A-6-206937 JP-A-6-206937 discloses a technique for continuously obtaining polysuccinimide by heating aspartic acid to 110 to 300 ° C. using a rotating shelf drying apparatus. It has been disclosed.

<Heat polycondensation in the presence of an acid catalyst> Specific examples of conventional techniques for obtaining polysuccinimide by heat polycondensation in the presence of a catalyst include the following 1 to 6. . However, according to these conventional techniques, the steps are complicated and it is difficult to obtain a polysuccinimide having a high molecular weight.

[0008] Japanese Patent Publication No. 48-2038 discloses that 50 g of DL-aspartic acid is used as a raw material, and 15% of 58% phosphoric acid is used as an acid catalyst.
and then mix the mixture under vacuum on a rotary evaporator under vacuum.
A technique of heating polycondensation at 0 ° C. for 4 hours is disclosed.

2 JP-A-7-216084 JP-A-7-216084 discloses a method using an acid catalyst (oxygen acid containing phosphorus and sulfur, organic or inorganic salt containing one or more acidic hydrogens). And heat-treated.
There is disclosed a technique of pulverizing the product and subjecting it to heat polycondensation.

3 JP-A-8-231710 JP-A-8-231710 discloses that the amount of an acid catalyst (phosphoric acid, phosphorus pentoxide or polyphosphoric acid) is reduced to 40 mol% or less based on aspartic acid. A technique for preventing foaming and coagulation at the time of heating polycondensation is disclosed.

4 JP-A-8-239468 JP-A-8-239468 discloses that the amount of acid catalyst (phosphoric acid) used is 0.01 to 0.3 with respect to 1 equivalent of aspartic acid.
There is disclosed a technique of manufacturing with a reduced equivalent amount.

5 JP-A-9-31197 JP-A-9-31197 discloses that a continuous extrusion kneader is used to reduce the amount of acid catalysts (mineral acids, phosphoric acids, and organic acids) to reduce the heating weight. A technique for preventing solidification during condensation is disclosed.

6 JP-A-7-196796 JP-A-7-196796 discloses that a polymer is formed into a bulk state by heat polycondensation in the presence of an acid catalyst / amino acid at a molar ratio of at least 0.001. A technology for preventing the reaction medium from being produced and producing the reaction medium in a form that is easily crushed is disclosed.

In these conventional techniques for obtaining polysuccinimide by heat polycondensation in the presence of an acid catalyst, phosphoric acids are mainly used as the acid catalyst.

For example, JP-A-7-216084, JP-A-8-239468 and JP-A-9-31197 also disclose:
Hydrochloric acid is specified as a mineral acid. However, there is no description in Examples or the like, but it is described that phosphoric acid is preferred in that a high yield and a high molecular weight polymer can be obtained.

On the other hand, JP-A-7-196796 describes an example using aspartic acid hydrochloride. Specifically, 1. A method of heating L-aspartic acid hydrochloride to 240 ° C. in a rotary evaporator flask under a nitrogen atmosphere. 2. After mixing L-aspartic acid and the hydrochloride salt of aspartic acid at a ratio of 1: 1, the mixture was heated at 200 ° C. in a decalin solvent.
How to heat.

The advantage of using hydrochloride instead of condensed phosphoric acid or the like as a catalyst is that hydrochloric acid dissociates during the reaction and is removed out of the system as hydrochloric acid gas, so that the acid content in the polymer is small. This is an advantageous method.

However, 1. The low molecular weight of the polysuccinimide obtained by the above method is considered to be due to the protection of the amino group of aspartic acid with an equimolar hydrochloric acid. That is, the dissociation of hydrochloric acid tends to be slow in the solid-state polycondensation reaction after the hydrochloride of aspartic acid has gone through the hydrochloride of aspartic anhydride. The cause is
It is considered that heat is not sufficiently transmitted to the inside of the polymer in the powder state, and unreacted aspartic anhydride hydrochloride tends to remain.

2. According to the findings of the present inventors, the molecular weight of polysuccinimide is also low in the above method, although decalin is used as an organic solvent in the reaction system, since decalin is not a solvent for dissolving the polymer, it is 1 and It is considered that similar results were obtained. In addition, since it is necessary to once treat aspartic acid as a raw material with hydrochloric acid or the like to form a salt, the process tends to be complicated.

[0020]

The problem to be solved by the present invention is to obtain a high-quality polysuccinimide in a short time, with high purity and by using a suitable amount of hydrochloric acid as a catalyst. It is an object of the present invention to provide a method for producing the polysuccinimide with high productivity, and to obtain a polymer which is easy to powder polysuccinimide.

[0021]

DISCLOSURE OF THE INVENTION In view of the above-mentioned problems in the prior art, the present inventors have studied to efficiently obtain high-quality polysuccinimide, and as a result, have found that aspartic acid can be used in the presence of an acid catalyst. By heating polycondensation below,
They have found that a highly pure polysuccinimide can be obtained in a short time, and have completed the present invention.

That is, the present invention is a manufacturing method described below. A process for producing polysuccinimide, comprising subjecting aspartic acid to heat polycondensation in the presence of a specific amount of hydrochloric acid.

The process of the present invention is a process for producing a polysuccinimide in which the polymerization is carried out in the absence of a solvent.

The present invention is also a method for producing a polysuccinimide powder comprising a step of collecting the polysuccinimide obtained by the above method in a granular state (recovery step).

[0025]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Preferred embodiments of the present invention will be described below. In the present invention, aspartic acid is used as a raw material. This aspartic acid has L-form, D-form, D-form
Any of L-forms may be used.

In the present invention, an aqueous hydrochloric acid solution (usually 35% hydrochloric acid solution) or a hydrochloric acid gas is used as the acid catalyst. It is preferable that the used amount is in the range of 0.1 equivalent to 0.95 equivalent as hydrochloric acid with respect to aspartic acid. More preferably, it is used in the range of 0.2 equivalent to 0.4 equivalent. If the amount is less than 0.1 equivalent, aspartic acid as a raw material remains, so that a high molecular weight polysuccinimide cannot be obtained. On the other hand, if it exceeds 0.90 equivalents, the dissociation of hydrochloric acid becomes slow, and the hydrochloride of aspartic anhydride remains, leading to a decrease in molecular weight.

The polysuccinimide obtained by using the hydrochloric acid in the above range has a characteristic that it has a high molecular weight and can be easily powdered.

In the present invention, the starting material aspartic acid is used by supporting a hydrochloric acid catalyst. The supporting method may be a dispersion or a homogeneous system, and is usually carried out by inserting aspartic acid into an aqueous hydrochloric acid solution. When hydrochloric acid gas is used, a predetermined amount of hydrochloric acid gas may be absorbed after aspartic acid is inserted into water or an organic solvent, or aspartic acid may be absorbed after absorbing hydrochloric acid gas in water or an organic solvent. May be inserted, and when a water-containing organic solvent mixed with water is used, the same operation can be performed.

In the present invention, the organic solvent absorbed when using hydrochloric acid gas includes alcohols such as methanol, ethanol, isopropyl alcohol, isobutyl alcohol and pentyl alcohol; mesitylene, naphthalene,
Aromatic hydrocarbons such as diethylbenzene and toluene; aromatic halogenated hydrocarbons such as dichlorobenzene and trichlorobenzene; aromatic ethers such as phenetole and diphenylether; and acetates such as ethyl acetate, isopropyl acetate and isobutyl acetate are preferred. used. This amount is 0.5 parts by weight to 8 parts by weight of aspartic acid.
It is preferred to use in the range of parts by weight. When the amount is 8 parts by weight or less, it is preferable in recovering the organic solvent, and at the same time, it is economically advantageous.

The heating polycondensation reaction temperature in the present invention is usually in the range of 120 to 220 ° C., preferably 140 to 20 ° C.
A high molecular weight polymer can be obtained by performing the reaction at a temperature of 0 ° C. and a reaction time of 5 to 20 hours.

If the reaction temperature is lower than 120 ° C., the reaction hardly proceeds, leaving aspartic acid as a raw material. Also, 22
When the temperature exceeds 0 ° C., the polymer is partially decomposed and colored, which may lead to deterioration of the quality of the polymer.

The reaction of the present invention can be carried out under normal pressure or reduced pressure. When the reaction is carried out under normal pressure, after heating to a predetermined temperature under a nitrogen stream, the heating polycondensation can be carried out under a nitrogen stream. On the other hand, when the operation is performed under reduced pressure, the degree of reduced pressure is 60.
A pressure range of 0 to 1 mmHg is preferred.

When the melt polycondensation is carried out stepwise in at least two steps in a pressure range of 600 to 1 mmHg, the first step is 300 to 60
0 mmHg pressure range, the second stage is 5-15
The pressure range is preferably mmHg.

By reducing the pressure, the molten paste foams and becomes Hartz-like, whereby a polymer having a high molecular weight is easily produced, and the polymer is easily isolated later as a powder.

As the reaction equipment that can be used for the polycondensation of the present invention, an ordinary stirrer or kneader can be used, but an apparatus that mixes so as to scrape off the reaction wall surface is preferable.
Specific examples include a paddle dryer, a table type kneader, and a blender.

As a reaction device that can be used for the heat polycondensation of the present invention, a usual stirrer or kneader can be used. Specifically, a desk-type kneader and a blender are mentioned.

In the method of the present invention, polymerization is carried out through a molten state and / or a molten paste state. The term “molten paste” refers to a turbid state in a molten state.

The condensate obtained by the method of the present invention has a feature that even if it is a polymer having bubbles therein, it is extremely easy to turn into a powder. For example, the powder polymer is extremely easily formed by a pulverizer, a mixer, or the like, so that the obtained powder polymer is extremely easy to handle, and for example, the acid is easily removed by washing.

Further, the condensate or an intermediate thereof can be spray-dried and dehydrated in a heated apparatus to form a powder, and if necessary, further dehydrated to obtain a polymer. In this case, for example, a fluidized bed reactor can be used. Further, a reactor capable of directly pulverizing simultaneously with the reaction, for example, a paddle dryer or the like may be used.

[0040]

EXAMPLES The present invention will be described below in detail with reference to examples, but the present invention is not limited to the following examples.

Example 1 A reaction vessel equipped with a stirrer was charged with 52.0 g (0.5 mol) of 35% hydrochloric acid, and then 133.1 g of aspartic acid (L-Asp) (1.
0 mol) was charged, and hydrochloric acid was supported on aspartic acid.
The temperature of the support was raised to 150 ° C. under a reduced pressure of 160 mmHg, and the mixture was stirred at 150 to 155 ° C. for 2 hours, then heated to 190 ° C. and reacted at 190 to 195 ° C. for 2 hours. After the reaction, the pressure was adjusted to a normal pressure at 25 to 30 ° C., and the light yellow polymer was powdered in a mortar, and the powder was discharged into 266.2 g of water.
Filtration and the filter cake were washed with 66.6 g of deionized water and dried. The yield was 97.0 g, the yield was 99.9%, and the weight average molecular weight (MW) was 30,000. In addition, Mw was measured by GPC using polystyrene as a standard.

The results of elemental analysis of the isolated polysuccinimide were as follows: Elemental analysis (%) (calculated as C ₄ H ₃ NO ₂ ) Calculated CH N 49.49 3. 12 14.43 Analytical value 49.46 3.11 14.42.

Example 2 A reactor equipped with a stirrer was charged with 133.1 g of isopropyl alcohol (IPA) and 166.4 g of ionized water. After absorbing hydrochloric acid gas (18.2 g, 0.5 mol) into the mixed solution at 25 to 30 ° C., 133.1 g of L-Asp (1.0 mol) was stirred at the same temperature.
Mol), and the mixture was heated to 90 ° C., and water-containing IPA was distilled off. Thereafter, the degree of decompression was adjusted to 20 to 30 mmHg,
After the temperature was raised to 180 ° C, the reaction was carried out at 180 to 185 ° C for 6 hours.

After the reaction, the reaction product was pulverized with a mixer, and the obtained pale yellow polymer powder was treated with methanol 26
The mixture was discharged to 6.2 g, sludged at 25 to 30 ° C. for 1 hour, filtered, and the filter cake was washed with 133.1 g of methanol and dried. Yield 97.0 g Crude yield 99.9% Weight average molecular weight (MW) 34,000 [Example 3] 109.4 g (0.3 mol) of a 10% hydrochloric acid solution was placed in a reaction vessel equipped with a stirrer. After charging, 133.1 g (1.0 mol) of L-Asp was inserted at 25-30 ° C. with stirring. The temperature was raised to 150 ° C under a reduced pressure of 300 mmHg, and the reaction was performed at 150 to 155 ° C for 2 hours. After adjusting the degree of decompression to 15 mmHg, the temperature was raised to 180 ° C.
The reaction was performed at 0 to 185 ° C for 5 hours. The reaction product was powdered in a mortar, and the obtained polymer powder was mixed with 97.1 g of ionized water.
And after sludge at 25-30 ° C for 1 hour,
Filtration and the filter cake were washed with 133.1 g of ionized water to pH 6 to 7, and then dried. Yield 96.1 g Crude yield 98.9% Weight average molecular weight (MW) 27,000.

Example 4 A reaction vessel equipped with a stirrer was charged with 72.9 g (0.7 mol) of 35% hydrochloric acid, and then 133.1 g (1.0 mol) of L-Asp. . After stirring at 25 to 30 ° C. for 1 hour, 160 mmHg
After the temperature was raised to 150 ° C under reduced pressure and stirred at 150 to 155 ° C for 2 hours, the temperature was raised to 190 ° C and reacted at 190 to 195 ° C for 2 hours. After the reaction, the pressure was returned to normal pressure at 25 to 30 ° C., the reaction product was powdered in a mortar, and the obtained pale yellow polymer powder was discharged into 97.1 g of water. After washing with 6 g, it was dried. Yield 97.0
g, the yield is 99.9%, and the weight average molecular weight (MW) is 3.
It was 10,000.

Example 5 A reaction vessel equipped with a stirrer was charged with 39.9 g (0.3 mol) of L-Asp, and 4 g (0.038 mol) of 35% hydrochloric acid was inserted with stirring. . Stirred at 25-30 ° C for 1 hour. After the stirring was stopped, the temperature was raised to 200 ° C under a nitrogen stream, and the mixture was heated and polycondensed at 205 to 210 for 3 hours. , 2
Heat polycondensation was performed at 20 to 225 ° C for 2 hours. After the reaction, 25
After the pressure was returned to normal pressure at ３０30 ° C., the light yellow polymer powder was discharged into 290 g of water, and then filtered and the cake was 79.86 g of ionic water.
And then dried. Yield 29.0 g, yield 9
9.6%, the weight average molecular weight (MW) was 25,000.

Comparative Example 1 L-aspartic acid was placed in a reaction vessel equipped with a stirrer.
After charging 3 g (0.1 mol), 195
The reaction was carried out at -200 ° C for 5 hours to obtain a brown powder. Yield 12.8g Crude yield 121.5% Mainly aspartic acid as raw material.

Comparative Example 2 Hydrochloride of aspartic acid 1 was placed in a reaction vessel equipped with a stirrer.
After charging 7.0 g (1.0 mol), 1 g was added under a nitrogen stream.
The temperature was raised to 90 ° C, and the reaction was carried out at 190 to 195 ° C for 8 hours to obtain a yellow powder. Yield 9.8 g Crude yield 100.9% Weight average molecular weight (MW) 1,000,000 Comparative Example 3 L-Asp 133.1 g and 85% in a 1 L eggplant type flask
13.3 g of phosphoric acid (0.10 volume / L-Asp) and IP
After charging 120 g of A, it was attached to a rotary evaporator (rotary evaporator). 40mmHg under reduced pressure, 6
The temperature was raised to 0 ° C., and 121 g of water-containing IPA was recovered at the same temperature. After heating for 2 hours to 180 ° C. while rotating, the reaction was further performed at 180 to 190 ° C. for 2 hours. After the reaction, a part of the polymer was taken and subjected to GPC analysis. As a result, it was found to be polysuccinimide having a weight average molecular weight (MW) of 20,000.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Yoshihiro Iruri 1190 Kasama-cho, Sakae-ku, Yokohama-shi, Kanagawa Prefecture Inside Mitsui Chemicals Co., Ltd. (72) Inventor Hiroaki Tamaya 1190 Kasama-cho, Sakae-ku, Yokohama-shi, Kanagawa Mitsui Chemicals Corporation F term (reference) 4J043 PA02 QB06 RA34 SA05 SB01 TA12 TB01 XA03 XA08 XB13 XB27 XB34 YA25 ZB60

Claims (6)

[Claims] 1. A process for producing polysuccinimide, comprising subjecting aspartic acid to heat polycondensation in the presence of an aqueous hydrochloric acid solution and / or a hydrochloric acid gas. 2. The amount of hydrochloric acid used is in the range of 0.1 to 0.90 equivalent to 1 equivalent of aspartic acid.
The method for producing the polysuccinimide according to the above. 3. The process for producing a polysuccinimide according to claim 1, wherein the heating polycondensation temperature is in the range of 120 to 220 ° C. 4. The method for producing a polysuccinimide according to claim 3, wherein the heating polycondensation temperature is 140 to 200 ° C. 5. The method according to claim 1, wherein the polymerization is carried out in the absence of a solvent.
5. The method for producing a polysuccinimide according to 4. 6. A step of recovering the polysuccinimide obtained by the method according to claim 1 in a granular state (recovery step).
A method for producing a polysuccinimide powder comprising: