JP2000186101A - Production of hydroxypropyl cellulose - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing a hydroxypropyl cellulose having excellent solubility in alcohols such as methanol, ethanol and 2-propanol and water even in the case of using an alkali cellulose having a low degree of polymerization as a raw material so as to obtain a hydroxypropyl cellulose to supply a low-viscosity aqueous solution. SOLUTION: In etherifying an alkali cellulose, obtained by treating a cellulose with an aqueous solution of an alkali, with propylene oxide, 20-80% of the whole addition amount of propylene oxide is added in the presence of 100-700 pts.wt. of a hydrophilic organic solvent based on 100 pts.wt. of the cellulose, an etherification reaction is carried out and 20-90% of the alkali amount in the alkali cellulose is neutralized. Successively 80-20% of the whole addition amount of propylene oxide is added to perform an etherification reaction.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing hydroxypropyl cellulose. More specifically, the present invention relates to a method for producing hydroxypropylcellulose which is a semi-synthetic polymer compound which can be suitably used for various uses such as a binder for a pharmaceutical tablet and a film coating material.

[0002]

2. Description of the Related Art Conventionally, as a method for producing hydroxypropylcellulose, a so-called kneading method in which propylene oxide is allowed to act directly on alkali cellulose or in the presence of a small amount of an organic solvent, for example, 100 parts by weight of cellulose is added to alkali cellulose. A so-called slurry method or the like, in which propylene oxide is allowed to act in the presence of a large amount of 1000 to 1200 parts by weight of an organic solvent, is known.

[0003] Hydroxypropylcellulose obtained by these conventional methods has relatively good solubility in water and methanol.
-Insufficient solubility in high carbon number alcohols such as propanol.

[0004] As a method for improving the solubility in alcohols, the inventors of the present invention used a specific amount of a hydrophilic organic solvent as a reaction solvent when reacting alkali cellulose and propylene oxide in a reaction solvent. An application was made for a method for producing hydroxypropylcellulose to be used (Japanese Patent Application No. 10-175996).

[0005] However, in the above-mentioned method, when an alkali cellulose having a small degree of polymerization is used as a raw material in order to obtain a hydroxypropyl cellulose which gives a low-viscosity aqueous solution, the obtained hydroxypropyl cellulose has a solubility in alcohols. There was a drawback that it was inferior.

[0006]

SUMMARY OF THE INVENTION The present invention relates to a method for producing hydroxypropylcellulose which gives a low-viscosity aqueous solution, even when alkali cellulose having a small degree of polymerization is used as a raw material, such as alcohols such as methanol, ethanol and 2-propanol. It is an object of the present invention to provide a method for producing hydroxypropylcellulose having excellent solubility in water and water.

[0007]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies in view of the above situation, and have found that when an alkali cellulose obtained by treating cellulose with an aqueous alkali solution is etherified with propylene oxide, In the presence of a hydrophilic organic solvent as a reaction solvent, a portion of the total amount of propylene oxide added to the alkali cellulose and allowed to react, then neutralize a portion of the alkali in the alkali cellulose,
Subsequently, by adding and reacting the remainder of the total amount of propylene oxide, even when alkaline cellulose having a small degree of polymerization is used as a raw material, it is superior to alcohols such as methanol, ethanol, and 2-propanol and water. It has been found that hydroxypropylcellulose having excellent solubility can be obtained, and the present invention has been completed.

That is, the gist of the present invention is that (1) when alkali cellulose obtained by treating cellulose with an alkaline aqueous solution is etherified with propylene oxide, 100 to 700 parts by weight of hydrophilic cellulose is added to 100 parts by weight of cellulose. 20-80% of the total amount of propylene oxide is added in the presence of a neutral organic solvent to carry out the etherification reaction, and then 20-90% of the alkali amount in the alkali cellulose is neutralized. (2) A method for producing hydroxypropylcellulose, comprising adding 80 to 20% of propylene oxide to an etherification reaction and adding (2) a total amount of propylene oxide of 300 to 900 with respect to 100 parts by weight of cellulose. The production method according to (1), which is parts by weight,
(3) an aliphatic ketone having 3 to 5 carbon atoms as a hydrophilic organic solvent,
A lower alcohol having 3 to 5 carbon atoms and a formula (1): R ¹ O (CH ₂ CH ₂ O) _n R ² (1) (in the formula, R ¹ and R ² each independently represent a C ^{1 to} C 1
(4) The method according to (1), wherein at least one selected from the group consisting of (poly) ethylene glycol dialkyl ethers represented by (3), wherein n represents an integer of 1 to 3), (3) The method according to (3), wherein the aliphatic ketone having 3 to 5 carbon atoms is acetone, 2-butanone or 3-pentanone, and (5) the lower alcohol having 3 to 5 carbon atoms is 2
And (6) the (poly) ethylene glycol dialkyl ether represented by the formula (1) is ethylene glycol dimethyl ether, diethylene glycol dimethyl ether or triethylene glycol. The production method according to (3), which is dimethyl ether.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION In the production method of the present invention, after treating cellulose with an aqueous alkali solution and etherifying the obtained alkali cellulose with propylene oxide, 100 to 700 parts by weight based on 100 parts by weight of cellulose. Of the total amount of propylene oxide added in the presence of the hydrophilic organic solvent
After adding 0 to 80% and performing the etherification reaction in the former stage, 20 to 90% of the alkali amount in the alkali cellulose
, Followed by adding 80 to 20% of the total amount of propylene oxide to carry out a subsequent etherification reaction.

In the present invention, first, cellulose is treated with an aqueous alkali solution.

Representative examples of the cellulose include, for example, wood pulp in sheet form and powder form, cotton linter, and the like, but the present invention is not limited to these examples.

The alkaline aqueous solution is not particularly restricted but includes, for example, sodium hydroxide, potassium hydroxide,
And aqueous solutions of alkali metal hydroxides such as lithium hydroxide. Among these alkali aqueous solutions, an aqueous solution of sodium hydroxide is preferably used. The concentration of the alkali metal hydroxide in the alkaline aqueous solution is not particularly limited, but is preferably about 5 to 40% by weight.

The amount of the aqueous alkali solution used is such that the time required for the reaction between the alkali cellulose and propylene oxide can be shortened based on 100 parts by weight of the alkali metal hydroxide contained in the aqueous alkali solution. Therefore, it is desirable that the content be 20 parts by weight or more, preferably 50 parts by weight or more. Further, from the viewpoint of easily removing the neutralized salt of the alkali metal hydroxide remaining after the reaction between the alkali cellulose and propylene oxide, the amount is 500 parts by weight or less, preferably 400 parts by weight or less. It is desirable to adjust as follows.

As a method of mixing the above-mentioned cellulose with an aqueous alkali solution, for example, cellulose is immersed in an aqueous alkali solution, and is usually placed in a vessel equipped with stirring blades at 15 to 35 ° C.
And then squeezing and grinding after mixing for about 30 minutes to 2 hours.

Further, as a method for obtaining an alkali cellulose having a small degree of polymerization, for example, the alkali cellulose obtained above is usually placed in a vessel equipped with a stirring blade in an amount of 40 to 7%.
A method of leaving or stirring in air at 0 ° C. for about 15 to 25 hours is exemplified. Note that the present invention is not limited to only such a method.

Next, the obtained alkali cellulose is etherified with propylene oxide.

At this time, in the presence of 100 to 700 parts by weight of the hydrophilic organic solvent with respect to 100 parts by weight of the cellulose,
After adding 20 to 80% of the total amount of propylene oxide to carry out the etherification reaction in the former stage, then, 20 to 90% of the alkali amount in the alkali cellulose is neutralized, and subsequently, the total amount of 80 to 80% is added. The subsequent etherification reaction is performed by adding を 20% of propylene oxide.

In the present invention, when the alkali cellulose is etherified, a part of the total amount of propylene oxide is added to the alkali cellulose and reacted in the presence of a hydrophilic organic solvent as a reaction solvent. It is characterized in that a part of the alkali in the alkali cellulose is neutralized, and then the reaction is carried out by adding the remaining propylene oxide of the total amount.

In the present invention, by doing so,
Even when alkali cellulose having a low degree of polymerization is used as a raw material, hydroxypropyl cellulose having excellent solubility in water such as alcohols such as methanol, ethanol and 2-propanol and water can be obtained.

The amount of propylene oxide added in the first-stage etherification reaction is 20 to 80%, preferably 40 to 80%, of the total amount of propylene oxide added. If the amount of propylene oxide added in the first-stage etherification reaction is less than 20% of the total amount added, the amount of alkali in the alkali cellulose is reduced by the subsequent neutralization, so that the second-stage etherification reaction proceeds. It becomes difficult. Further, when the amount of propylene oxide added in the etherification reaction in the former stage exceeds 80% of the total amount, the effect is not obtained even if the neutralization is continuously performed, and methanol, ethanol,
The solubility in alcohols such as 2-propanol and water is deteriorated.

After the etherification reaction in the first stage, a part of the alkali in the alkali cellulose is neutralized. The ratio of the alkali to be neutralized is in the range of 20 to 90%, preferably 50 to 85% of the total alkali amount in the alkali cellulose. If the proportion of the alkali to be neutralized is less than 20%, the solubility in alcohols such as methanol, ethanol, and 2-propanol and in water is deteriorated.
On the other hand, if the ratio of the alkali to be neutralized exceeds 90%, propylene oxide is unlikely to react in the subsequent etherification reaction.

Examples of the acid used for the neutralization include inorganic weak acids such as phosphoric acid and organic weak acids such as formic acid, acetic acid, citric acid, malic acid and tartaric acid. The concentration of these acids is not particularly limited, but those having usually 10 to 100% are preferably used.

In the latter-stage etherification reaction, the amount of propylene oxide to be added is determined by subtracting the amount of propylene oxide added in the first-stage etherification reaction from the total addition amount, that is, 80 to 20 of the total addition amount. %, Preferably 60 to 20%.

The total amount of propylene oxide used in the first and second stage etherification reactions cannot be determined unconditionally depending on the desired number of moles of propylene oxide to be added, but is preferably 100 parts by weight of cellulose. 300 to 900 parts by weight, more preferably 4
It is in the range of 00 to 700 parts by weight. If the total amount of propylene oxide is less than 300 parts by weight, the amount of propylene oxide added is small, and the desired properties of hydroxypropyl cellulose are not exhibited.
Even if it is more than part by weight, the addition of propylene oxide in an amount commensurate with the added amount does not occur, so that it is not economical.

The hydrophilic organic solvent used in the etherification reaction includes, for example, an aliphatic ketone having 3 to 5 carbon atoms, a lower alcohol having 3 to 5 carbon atoms and a compound represented by the formula (1) in view of a relatively low boiling point. R ¹ O (CH ₂ CH ₂ O) _n R ² (1) (wherein, R ¹ and R ² each independently have 1 to 1 carbon atoms)
3 represents a hydrocarbon group, and n represents an integer of 1 to 3. )), And the like. These may be used alone or in combination of two or more.

Examples of the ketone having 3 to 5 carbon atoms include acetone, 2-butanone, 2-pentanone, and 3-pentanone. However, acetone, 2-butanone, and 3-pentanone are preferred because of their high solubility in water. Pentanone is preferably used.

The lower alcohol having 3 to 5 carbon atoms includes
Secondary or tertiary alcohols are preferably used because they do not easily react with propylene oxide. Specific examples thereof include 2-propanol, 2-methyl-2-propanol, 2-butanol, 2-methyl-2-butanol, 3-methyl-2-butanol, 2-pentanol,
Examples thereof include 3-pentanol, and 2-propanol and 2-methyl-2-propanol are preferably used because of their high solubility in water.

The (poly) ethylene glycol dialkyl ethers represented by the above formula (1) include ethylene glycol dimethyl ether, ethylene glycol diethyl ether, ethylene glycol dipropyl ether, ethylene glycol methyl ethyl ether, ethylene glycol methyl propyl ether. Ether, ethylene glycol ethyl propyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, diethylene glycol dipropyl ether, diethylene glycol methyl ethyl ether, diethylene glycol methyl propyl ether, diethylene glycol ethyl propyl ether, triethylene glycol dimethyl ether, triethylene glycol diethyl ether, triethylene Glycol dipropyl ether, triethylene glycol methyl ethyl ether, triethylene glycol methyl propyl ether, triethylene glycol ethyl propyl ether.
Among them, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, and triethylene glycol dimethyl ether are preferably used. These solvents may be used alone or in combination of two or more.

The amount of the hydrophilic organic solvent used is in the range of 100 to 700 parts by weight, preferably 100 to 500 parts by weight, based on 100 parts by weight of cellulose. If the amount of the hydrophilic organic solvent is more than 700 parts by weight, the volumetric efficiency is undesirably reduced.

The reaction temperature in the first and second stage etherification reactions is usually 40 to 80 ° C., preferably 50 to 80 ° C.
It is in the range of 70 ° C. If the reaction temperature is lower than 40 ° C., the reaction rate is slow and the reaction requires a long time. If the reaction temperature is higher than 80 ° C., the pressure during the reaction increases, and the structure of the reaction vessel is limited.

The reaction time for the etherification is usually 2 to 8 hours, preferably 3 to 6 hours, respectively, in the first and second stages.
If the reaction time is less than 2 hours, propylene oxide remains unreacted, so that the desired hydroxypropylcellulose cannot be obtained. Even if the reaction time exceeds 8 hours, the effect corresponding thereto cannot be obtained, but it is not economical. .

After the end of the above-mentioned etherification reaction,
In accordance with a conventional method, an acid is added to the obtained reaction solution to neutralize the remaining alkali, and is formed by neutralizing unreacted propylene oxide, by-produced propylene glycol, and alkali by washing with hot water. After removing the salt and the like, dried and pulverized, powdery hydroxypropylcellulose is obtained.

The quality of the hydroxypropylcellulose thus obtained is evaluated based on the gelation temperature, viscosity, solubility in water or alcohols, etc. of the aqueous solution of hydroxypropylcellulose. The gelation temperature and viscosity of the aqueous solution of hydroxypropylcellulose obtained according to the present invention and the solubility in water or alcohols are improved as compared with those obtained by the conventional method.

[0034]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Preparation Examples, Examples and Comparative Examples, but the present invention is not limited to only these Examples.

Preparation Example As a raw material cellulose, 32 g of sheet pulp was 19%
It was immersed in 960 g of an aqueous sodium hydroxide solution, and stirred and mixed at 30 ° C. for 1 hour in a 2 liter flask to allow alkali to act. Thereafter, the mixture was filtered under pressure to remove the aqueous sodium hydroxide solution by squeezing, and left in the air at 50 to 60 ° C. for 20 hours to obtain 86.4 g of alkali cellulose. The amount of alkali in the obtained alkali cellulose was 0.36 mol.

Example 1 A 1-liter kneader was charged with 86.4 g of the alkali cellulose obtained in the preparation example, 64 g of acetone and 80 g of propylene oxide, and reacted by stirring and mixing at 65 ° C. for 3 hours. After the reaction, 85.8 g of a 20% acetic acid aqueous solution was added to neutralize 80% of the alkali amount in the alkali cellulose. Subsequently, 80 g of propylene oxide was charged, and 65 g of propylene oxide was added.
The mixture was reacted by stirring and mixing at a temperature of 3 ° C. for 3 hours.

The obtained reaction mixture was neutralized with 8.8 g of acetic acid according to a conventional method to neutralize the alkali, washed with hot water, purified, dried and pulverized to obtain 62.8 g of powdery hydroxypropylcellulose. Was.

The obtained hydroxypropylcellulose was dissolved in water, methanol, ethanol and 2-propanol at room temperature, and the following physical properties were evaluated using the obtained 2% hydroxypropylcellulose solutions. Table 1 shows the results.

(A) Gelation temperature About 80 ml of 2% aqueous solution of hydroxypropylcellulose
Was placed in a 100 ml glass container, and then the glass container was immersed in a 90 ° C. water bath with shaking to measure the temperature at which white insolubles appeared in the liquid. (B) Aqueous solution of hydroxypropylcellulose of 2% viscosity about 300 m
was placed in a 500 ml beaker, kept at 20 ° C., and measured with a BM viscometer. (C) Solubility in each solvent About 30 ml of each 2% hydroxypropylcellulose solution
Was placed in a 50 ml glass container, and whether hydroxypropyl cellulose was dissolved in a transparent state was visually observed.

Example 2 A 1-liter kneader was charged with 86.4 g of the alkali cellulose obtained in the preparation example, 64 g of 2-propanol and 134.4 g of propylene oxide, and was heated at 65 ° C. to 4.5.
The mixture was stirred and reacted for a period of time. After the reaction, 63.7 g of a 20% acetic acid aqueous solution was added to neutralize 60% of the alkali amount in the alkali cellulose. Subsequently, propylene oxide 5
7.6 g was charged and reacted by stirring and mixing at 65 ° C. for 3 hours.

The obtained reaction mixture was neutralized with 10.1 g of acetic acid to neutralize the alkali and washed with hot water to purify the reaction mixture, thereby obtaining 61.3 g of hydroxypropylcellulose.

The obtained hydroxypropylcellulose was dissolved at room temperature in water, methanol, ethanol and 2-propanol, and each physical property was determined in the same manner as in Example 1 using each of the resulting 2% hydroxypropylcellulose solutions. Was evaluated. Table 1 shows the results.

Example 3 A 1-liter kneader was charged with 86.4 g of the alkali cellulose obtained in the preparation example, 96 g of 2-methyl-2-propanol and 38.4 g of propylene oxide.
The mixture was reacted by stirring and mixing at a temperature of 3 ° C. for 3 hours. After the reaction, 42.9 g of a 40% acetic acid aqueous solution was added to neutralize 80% of the alkali amount in the alkali cellulose. Subsequently, 89.6 g of propylene oxide was charged and reacted by stirring and mixing at 65 ° C. for 4 hours.

The obtained reaction mixture was neutralized with 9.1 g of acetic acid to neutralize the alkali and washed with hot water to purify the reaction mixture, thereby obtaining 64.3 g of hydroxypropylcellulose.

The obtained hydroxypropylcellulose was dissolved in water, methanol, ethanol and 2-propanol at room temperature, and each physical property was obtained in the same manner as in Example 1 using each of the obtained 2% hydroxypropylcellulose solutions. Was evaluated. Table 1 shows the results.

Example 4 A 1-liter kneader was charged with 86.4 g of the alkali cellulose obtained in the Preparation Example, 48 g of diethylene glycol dimethyl ether and 76.8 g of propylene oxide, and reacted by stirring and mixing at 65 ° C. for 3 hours. After the reaction,
14.2 g of a 60% acetic acid aqueous solution was added to neutralize 40% of the alkali amount in the alkali cellulose. Subsequently, 51.2 g of propylene oxide was charged and reacted by stirring and mixing at 65 ° C. for 3 hours.

The obtained reaction mixture was neutralized with 12.9 g of acetic acid to neutralize the alkali and washed with hot water to purify, thereby obtaining 64.4 g of hydroxypropyl cellulose.

The obtained hydroxypropylcellulose was dissolved at room temperature in water, methanol, ethanol and 2-propanol, and each physical property was obtained in the same manner as in Example 1 using each of the obtained 2% hydroxypropylcellulose solutions. Was evaluated. Table 1 shows the results.

Example 5 A hydroxypropyl cellulose 61 was prepared in the same manner as in Example 2 except that the alkali cellulose prepared in Example 2 without standing in air at 50-60 ° C. for 2 hours was used. 0.3 g were obtained.

The obtained hydroxypropylcellulose was dissolved in water, methanol, ethanol and 2-propanol at room temperature, and each physical property was obtained in the same manner as in Example 1 using each of the obtained 2% hydroxypropylcellulose solutions. Was evaluated. Table 1 shows the results.

Comparative Example 1 86.4 g of the alkali cellulose obtained in the Preparation Example, 64 g of acetone and 80 g of propylene oxide were charged into a 1-liter kneader, and the mixture was stirred and reacted at 65 ° C. for 5 hours. Subsequently, 80 g of propylene oxide was charged,
The reaction was carried out by stirring and mixing at 65 ° C. for 5 hours.

The obtained reaction mixture was neutralized with 12 g of acetic acid to neutralize the alkali according to a conventional method, purified by washing with hot water, dried and pulverized to obtain 61.6 g of powdery hydroxypropylcellulose.

The obtained hydroxypropylcellulose was dissolved at room temperature in water, methanol, ethanol and 2-propanol, and each of the physical properties were obtained in the same manner as in Example 1 using each of the obtained 2% hydroxypropylcellulose solutions. Was evaluated. Table 1 shows the results.

Comparative Example 2 86.4 g of the alkali cellulose obtained in the Preparation Example, 64 g of 2-propanol and 28.8 g of propylene oxide were charged into a 1-liter kneader, and the mixture was stirred and mixed at 65 ° C. for 4.5 hours to conduct a reaction. I let it. After the reaction, 63.7 g of a 20% acetic acid aqueous solution was added to neutralize 60% of the alkali amount in the alkali cellulose. Subsequently, propylene oxide 16
3.2 g was charged and reacted by stirring and mixing at 65 ° C. for 3 hours.

The obtained reaction mixture was neutralized with 10.1 g of acetic acid to neutralize the alkali and washed with hot water to purify, thereby obtaining 61.3 g of hydroxypropylcellulose.

The obtained hydroxypropylcellulose was dissolved at room temperature in water, methanol, ethanol and 2-propanol, and each physical property was obtained in the same manner as in Example 1 by using each of the obtained 2% hydroxypropylcellulose solutions. Was evaluated. Table 1 shows the results.

[0057]

[Table 1]

From the results shown in Table 1, the hydroxypropylcellulose obtained in Examples 1 to 4 was
It can be seen that a low-viscosity aqueous solution is provided and, similarly to the hydroxypropylcellulose obtained in Example 5, exhibits extremely excellent solubility in water and alcohols.

On the other hand, the hydroxypropyl celluloses obtained in Comparative Examples 1 and 2 were all ethanol,
It turns out that it does not show good solubility with respect to alcohols such as 2-propanol.

[0060]

According to the production method of the present invention, in order to obtain hydroxypropylcellulose giving a low-viscosity aqueous solution, methanol, ethanol, 2-propanol, etc. are used even when alkali cellulose having a small degree of polymerization is used as a raw material. And a method for producing hydroxypropylcellulose having excellent solubility in alcohols and water.

Continued on the front page (72) Inventor Sadaki Yano 1st Irifune-cho, Shimarima-ku, Himeji-shi, Hyogo Sumitomo Seika Chemicals Co., Ltd. F-term (reference) in 2nd Laboratory Co., Ltd. 4C090 AA05 BA28 CA07 CA32 CA36 CA37 CA47 DA10 DA22

Claims (6)

[Claims] 1. An alkali cellulose obtained by treating cellulose with an aqueous alkali solution is etherified with propylene oxide.
In the presence of 0 to 700 parts by weight of a hydrophilic organic solvent, 20 to 80% of the total amount of propylene oxide is added to cause an etherification reaction, and then 20 to 90% of the alkali amount in the alkali cellulose is added. And then add 80 to 2 of the total amount
A method for producing hydroxypropylcellulose, which comprises adding 0% propylene oxide to carry out an etherification reaction. 2. The process according to claim 1, wherein the total amount of propylene oxide is 300 to 900 parts by weight based on 100 parts by weight of cellulose. 3. The hydrophilic organic solvent is an aliphatic ketone having 3 to 5 carbon atoms, a lower alcohol having 3 to 5 carbon atoms and a compound represented by formula (1): R ¹ O (CH ₂ CH ₂ O) _n R ² (1) (Wherein, R ¹ and R ² each independently represent a carbon number of 1 to
3. The method according to claim 1, wherein the hydrocarbon group is 3 and n is an integer of 1 to 3). 4. The aliphatic ketone having 3 to 5 carbon atoms is acetone, 2-butanone or 3-pentanone.
Production method as described. 5. The method according to claim 3, wherein the lower alcohol having 3 to 5 carbon atoms is 2-propanol or 2-methyl-2-propanol. 6. The method according to claim 3, wherein the (poly) ethylene glycol dialkyl ether represented by the formula (1) is ethylene glycol dimethyl ether, diethylene glycol dimethyl ether or triethylene glycol dimethyl ether.