JPH0372082B2 - - Google Patents

Description

[Detailed description of the invention]

This invention relates to a novel carboxyalkyl acetyl cellulose having a high degree of substitution (DS) by carboxyalkyl groups and acetyl groups, salts thereof, and a method for producing the same. There are few reports on carboxyalkyl acetyl cellulose, and those with acid-type carboxyalkyl groups have been described for use as enteric coating agents due to their solubility in organic solvents and enteric properties (Japanese Patent Publication No. 35398/1989). Public bulletin).
However, although the carboxymethyl group substitution degree of the carboxyalkyl acetyl cellulose is disclosed to be 0.3 to 1.2, the degree of substitution by the acetyl group and the production method are not disclosed at all.
Also known are methods for acetylating carboxymethyl cellulose (British Patent No. 1126244), and examples in which alkali cellulose is reacted with monochloroacetic acid and then acetylated using a large amount of acetic anhydride in the presence of a catalyst. (Soviet inventor certificate No. 612933)
No. Specification). However, these methods have drawbacks such as the elimination of the acetyl group during the reaction and the need for a large amount of acetic anhydride. Furthermore, the carboxyalkyl acetyl cellulose obtained by the former method has a significantly low degree of carboxyalkyl group substitution, and that obtained by the latter method has a significantly low degree of acetyl group substitution, and the carboxyalkyl group and acetyl group are Carboxyalkyl acetyl cellulose with a high degree of substitution of both is not known. As a result of intensive studies on the method for producing carboxyalkyl acetyl cellulose, the inventor of this invention was able to produce a novel carboxyalkyl acetyl cellulose with a high degree of substitution of the two substituents. Thus, the present invention provides carboxyalkyl acetyl cellulose and salts thereof, in which the degree of substitution (DS) of carboxyalkyl groups is 0.2 to 2.5 and the degree of substitution (DS) of acetyl groups is 0.5 to 2.8. Examples of the alkyl group of the carboxyalkyl group of the carboxyalkyl acetyl cellulose of this invention include lower alkyl groups of about C ₁ ^to ₃ .
In addition, carboxyalkyl acetyl of this invention
Salts of cellulose include sodium, potassium, calcium and ammonium salts. In particular, carboxyalkyl compounds obtained by acetylation with acetic anhydride using sulfuric acid as a catalyst.
Acetyl cellulose (acid type) is insoluble in water and water-containing lower alkyl alcohols with a high water content.
Uniformly soluble in acetone and methylene chloride/methanol. On the other hand, its sodium salt is uniformly soluble in water, aqueous lower alkyl alcohol with a high water content, and aqueous acetone with a high water content, but is insoluble in a methylene chloride/methanol mixture. Therefore, in particular, the above acid type can be used as an enteric coating agent due to its solubility in organic solvents. The alkali metal salts of the starting material carboxyalkyl cellulose used in the method of this invention include sodium salts and potassium salts, and the degree of substitution of the carboxyalkyl group is determined by the carboxyalkyl acetyl cellulose, which is the target substance of the present application. Those having a range of degrees of substitution of carboxyalkyl groups can be used. For example, commercially available carboxymethylcellulose sodium (CMC sodium)
Not only powdered ones such as, but also fibrous ones can be used. As the acid used to convert carboxyalkyl cellulose into an acid form, an aqueous solution of a mineral acid such as sulfuric acid, hydrochloric acid, or nitric acid or an organic acid such as acetic acid is used. This reaction to form the acid form is usually carried out at room temperature. In order to increase the efficiency of an acetylating agent such as acetic anhydride, it is desirable to dehydrate the acidified carboxyalkylcellulose with acetic acid or the like as much as possible.
Further, even if mineral acid remains, it is not a problem as long as it does not affect the oxidation reaction. Acetic anhydride is mainly used as the acetylating agent. Sulfuric acid, sulfoacetic acid, perchloric acid, zinc chloride, etc. can be used as a catalyst for the acetylation reaction. This acetylation reaction is carried out at a slightly elevated temperature of 40-60°C. In addition, when it is desired to obtain a salt (for example, a sodium salt or an ammonium salt), a solution of an acid form of carboxyalkyl acetyl cellulose in an organic solvent is reacted with a corresponding alkali (for example, an aqueous solution of sodium hydroxide or ammonium hydroxide). It can be easily manufactured. Next, actual embodiments will be described, but the present invention is not limited thereto. Example 1 50g of CMC sodium with a degree of substitution (DS) of 0.63 was
The sample was immersed in 1.5 kg of % sulfuric acid for 2 hours at room temperature, washed with water, and thoroughly replaced with acetic acid. After thoroughly removing the liquid, put it into a small kneader and add 250g of acetic acid, 5.6g of sulfuric acid, and 150g of acetic anhydride.
was added and reacted at 48 to 50°C for 4 hours. CMC sodium dissolved as the reaction proceeded. The reaction solution was precipitated in water, and the precipitate was thoroughly washed with water and dried in vacuum. A portion of the sample was dissolved in acetone, neutralized by dropwise addition of 0.5N sodium hydroxide solution, and dried under suction on a rotary evaporator to form the sodium salt. The degree of substitution of carboxymethyl and acetyl in the produced sodium carboxymethyl acetyl cellulose was measured by the titration method after ashing and the saponification method, and the DS was 0.63 and 2.34, respectively. Its solubility in solvents was as follows.

[Table] FIG. 1 shows the infrared absorption spectrum of the acid type carboxymethyl acetyl cellulose obtained in this example. Comparative Example 1 50 g of CMC sodium with a degree of substitution (DS) of 0.63 was immersed in 1 kg of acetic acid at room temperature for 2 hours, the liquid was thoroughly removed, and then placed in a small kneader, and 250 g of acetic acid, 15.3 g of sulfuric acid, and 15 g of acetic anhydride were added and heated at 48 to 50°C. The reaction took place for 4 hours. CMC sodium did not dissolve in acetic acid over time. After a period of time, it was filtered, thoroughly washed with water, and then vacuum dried. The infrared spectrum of this sample is acid type.
It is the same as CMC, and the degree of acetylation substitution was determined by the saponification method after converting it into a sodium salt, and it was less than 0.1. Example 2 50 g of CMC sodium with a degree of substitution (DS) of 0.65 was
% sulfuric acid for 2 hours at room temperature. After washing with water, replacing well with acetic acid and removing liquid, put into a small kneader, add 84 g of acetic acid, 316 g of methylene chloride, and acetic anhydride.
210 g and 1.5 g of sulfuric acid were added, and the mixture was reacted at 48 to 50°C for 6 hours. CMC sodium dissolved as the reaction proceeded. The reaction solution was precipitated in water, and the precipitate was thoroughly washed with water and then dried in vacuum. A portion of the sample was dissolved in acetone, neutralized with 0.1N sodium hydroxide solution, and then dried under reduced pressure on a rotary evaporator to obtain the sodium salt. The degree of substitution of the generated carboxymethyl acetyl cellulose sodium is carboxymethyl
DS was 0.5g and acetyl DS was 2.19. The solubility in solvents is as follows.

[Table] Example 3 16.7g of CMC sodium with a degree of substitution (DS) of 0.64
It was immersed in 500 g of 20% sulfuric acid for 2 hours at room temperature. After removing liquid and washing with water, replace the liquid thoroughly with acetic acid, remove liquid, and then remove toluene.
350 g. Meanwhile, add 60g of acetic anhydride to sulfuric acid.
After adding 1.27 g and heating at 70°C for 15 minutes to convert sulfuric acid into sulfoacetic acid, the mixture was mixed with the above mixture of CMC and toluene and reacted at 50°C for 6.5 hours. After removing the liquid from the reactant, it was thoroughly replaced with methanol.
Washed with water and dried. When the degree of substitution was measured in the same manner as in Example 1, carboxymethyl DS was 0.64, acetyl DS was 1.73,
The acid form did not dissolve in acetone. Example 4 17 g of CMC sodium with a degree of substitution (DS) of 0.65 was added to 20
% sulfuric acid for 2 hours at room temperature. After removing liquid and washing with water, thoroughly replacing with acetic acid and removing liquid, 250g of acetic acid,
39 g of acetic anhydride and 14 g of subsalt chloride were added, and the mixture was reacted at 60° C. for 7 hours. It was precipitated in 1000 g of 5% saline, washed with water, and dried. The degree of substitution was measured in the same manner as in Example 1. Carboxymethyl DS0.63 Acetyl DS2.23
The acid type did not dissolve uniformly in acetone. In addition, the degree of carboxymethyl substitution (DS) and the degree of acetyl substitution (DS) of carboxymethyl acetyl cellulose in the above examples were measured by the following method. (1) Degree of substitution of acid type carboxymethyl acetyl cellulose Accurately weigh approximately 1 g of acid type carboxymethyl acetyl cellulose (purity m ₁ g), add it to 70 ml of acetone and 30 ml of water, and add phenol to 70 ml of acetone and 30 ml of water. Quickly titrate with phthalene as indicator. 1/10N
The amount of NaOH used is V ₁ ml, its factor is ₁ ,
Let the degree of carboxymethyl substitution DS be x and the degree of acetyl substitution DS be y. V _{1 1} /10000m ₁ = x / 162 + 58x + 42y = A Also, accurately weigh about 1 g of acid type carboxymethyl acetyl cellulose (purity m ₂ g) and weigh 1/10N.
Dissolve in 150 ml of NaOH, leave to stand overnight at room temperature, and titrate excess NaOH with 1/10N H ₂ SO ₄ using phenolphthalene as an indicator. 1/10N H ₂ SO ₄
Assume that the amount used is V ₂ ml and its factor is ₂ . 150 ₁ −V _{2 2} /10000m ₂ =x+y/162+58x+42y=
B Calculate x and y from the following formula derived from this simultaneous equation. x=162A/1-16A-42B, y=162(B-A)/1-1
6A−42B (2) Degree of substitution of sodium salt type carboxymethyl acetyl cellulose Sodium salt type carboxymethyl acetyl cellulose
Approximately 1 g of cellulose was accurately weighed (purity m ₁ g), placed in a magnetic crucible, and incinerated at 600°C. The sodium oxide produced by the ashing was neutralized with 100 ml of 1/10N H ₂ SO ₄ . , add excess H ₂ SO ₄ to 1/10N NaOH
Titration was carried out using phenolphthalene as an indicator.
The appropriate amount is V ₁ ml, the factor of 1/10N NaOH is ₁ , and the factor of 1/10N H ₂ SO ₄ is ₂ . Let the degree of carboxymethyl substitution DS be x' and the degree of acetyl substitution DS be y'. 100 ₂ − ₁ V ₁ /10000m ₁ =x′/162+80x′+42y′=
A: Also, accurately weigh approximately 1 g of sodium salt type carboxymethyl acetyl cellulose (purity m ₂ g),
Dissolve in 150ml of 1/10N NaOH and leave overnight.
Excess NaOH is titrated with 1/10N H ₂ SO ₄ using phenolphthalene as indicator. 1/10N
The amount of H ₂ SO ₄ used is V ₂ ml. 150 ₁ −V _{2 2} /10000m ₂ =y′/162+80x′+42y′=
B Calculate x' and y' from the following formula derived from this simultaneous equation. x'=162A/1-80A-42B, y'=162B/1-80A-42B

[Brief explanation of drawings]

FIG. 1 is an infrared absorption spectrum of acid type carboxymethyl acetyl cellulose obtained in Example 1.

Claims (1)

[Scope of Claims] 1. An alkali metal salt of carboxyalkyl cellulose in which the degree of substitution of the carboxyalkyl group is 0.2 to 2.5 is treated in an aqueous acid solution to form an acid form, and then anhydrous in the presence of a catalyst. By reacting with acetic acid and acetylating, the degree of substitution of the carboxyalkyl group is increased.
A carboxyalkyl acetyl cellulose having a substitution degree of 0.2 to 2.5 and acetyl group substitution of 0.5 to 2.8.
Method of manufacturing cellulose. 2. The production method according to claim 1, wherein an aqueous solution of a mineral acid such as sulfuric acid, hydrochloric acid, or nitric acid or an organic acid such as acetic acid is used to convert the alkali metal salt of carboxyalkyl cellulose into an acid form. 3. The production method according to claim 1, wherein the catalyst is sulfuric acid, sulfoacetic acid, perchloric acid, or zinc chloride.