JPH06172404A - Production of hydroxypropylchitosan - Google Patents

Abstract

PURPOSE:To readily carry out the industrial mass production at a low temperature in a short time without causing the reduction in viscosity of the resultant product by reacting chitosan with propylene oxide in the presence of a quaternary ammonium hydroxide. CONSTITUTION:Chitosan composed of deacetylated chitin is etherified with propylene oxide in the presence of a quaternary ammonium hydroxide expressed by the formula R1R2R3R4NOH (R1 to R4 are 1-4C alkyl or aromatic-substituted alkyl). The quaternary ammonium hydroxide is used at 0.05-1.0 weight ratio to the chitosan. Furthermore, the chitosan is etherified with the propylene oxide in the presence of a quaternary ammonium salt expressed by the formula R1R2R3 R4NX (X is Cl, Br, I, etc.) and an alkaline hydroxide. Sodium or potassium hydroxide is used as the alkaline hydroxide.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a method for producing hydroxypropyl chitosan.

[0002]

2. Description of the Related Art Chitosan can be obtained inexpensively and in large quantities by deacetylating chitin, which is a natural unused resource. Due to its unique chemical structure and properties, it is expected to be used in a wide range of fields such as medicines, agricultural chemicals, polymer materials, and ion exchange resins. Furthermore, in order to increase the utilization of such chitosan, an attempt to obtain a water-soluble derivative (hydroxypropyl chitosan) has hitherto been made in Japanese Patent Publication No.
5601 or JP-A-3-234702.

[0003]

However, according to the production methods described in these publications, suitable conditions for proceeding the reaction are 80 to 120 ° C. in the presence of alkali.
Then, the reaction was carried out for 5 to 10 hours, or if an alkali was not present, a reaction time of 100 hours was required. For this reason, the conventional manufacturing method has poor production efficiency and is not suitable for industrially mass-producing the target derivative. Further, these methods have a problem that since the treatment is performed under severe conditions, depolymerization of chitosan molecules is often involved and the viscosity of the product is lowered.

Therefore, an object of the present invention is to provide a method for producing hydroxypropyl chitosan which facilitates industrial mass production of hydroxypropyl chitosan and does not cause a decrease in viscosity of the product.

[0005]

Means for Solving the Problems In the hydroxypropylation of chitosan, the present inventors have made earnest studies to promote the reaction under mild conditions, and as a result, in the presence of quaternary ammonium hydroxide. It was found that the reaction of chitosan with propylene oxide causes etherification of free hydroxyl groups and hydroxypropylation of free amino groups of chitosan at low temperature and in a short time, and conceived the present invention.

To achieve the above object, the invention of claim 1 is
Chitosan composed of deacetylated chitin can be prepared by using the following general formula (I), R ₁ R ₂ R ₃ R ₄ NOH (I) (wherein R ₁ , R ₂ , R ₃ and R ₄ have 1 to 1 carbon atoms). 4 represents an alkyl group of 4 or an aromatic substituted alkyl group, R ₁ ,
R ₂ , R ₃ and R ₄ may be the same) and are etherified with propylene oxide in the presence of a quaternary ammonium hydroxide.

To achieve the above object, the invention of claim 2 is
In the method for producing hydroxypropyl chitosan according to claim 1, the weight ratio of the quaternary ammonium hydroxide to chitosan is 0.05 to 1.0.

In order to achieve the above object, the invention of claim 3 is
Chitosan composed of deacetylated chitin can be prepared by using the following general formula (II), R ₁ R ₂ R ₃ R ₄ NX (II) (wherein R ₁ , R ₂ , R ₃ , and R ₄ have 1 to 1 carbon atoms). 4 represents an alkyl group of 4 or an aromatic substituted alkyl group, R ₁ ,
R ₂ , R ₃ and R ₄ may include the same thing, and X
Is any one of Cl, Br, I, HSO ₄ , NO ₃ , and IO ₄ ) and is etherified with propylene oxide in the presence of a quaternary ammonium salt and an alkali hydroxide. To do.

To achieve the above object, the invention of claim 4 is
In the method for producing hydroxypropyl chitosan according to claim 3, the weight ratio of the quaternary ammonium salt to chitosan is 0.05 to 1.0.

To achieve the above object, the invention of claim 5 is
In the method for producing hydroxypropyl chitosan according to claim 3 or 4, the alkali hydroxide is sodium hydroxide or potassium hydroxide.

The raw material chitosan used in the present invention is a deacetylated product of chitin, which is contained in the shells or mushrooms of crabs, shrimps, insects, etc. and is a natural polymer, and D-glucosamine. It is a basic polysaccharide having a structural unit of. Such deacetylated chitin is industrially produced by itself, and various grades are commercially available, but any of them can be used in the present invention. Particularly preferred are those having a degree of deacetylation of about 50-100%. Of course, it can be produced by a conventionally known method (method described in Japanese Patent Publication No. 64-5601).

In the present invention, the quaternary ammonium hydroxide acts as a catalyst for the etherification reaction. The quaternary ammonium hydroxide which can be used in the present invention is represented by the following general formula (I), R ₁ R ₂ R ₃ R ₄ NOH (I) (wherein R ₁ , R ₂ , R ₃ and R ₄ are carbon atoms). Represents an alkyl group of formula 1 to 4 or an aromatic substituted alkyl group, R ₁ ,
R ₂ , R ₃ and R ₄ may include the same one).

Specifically, tetramethylammonium hydroxide, tetraethylammonium hydroxide,
Examples thereof include tetrapropylammonium hydroxide, tetrabutylammonium hydroxide, benzyltrimethylammonium hydroxide and benzyltriethylammonium hydroxide.

In the present invention, the quaternary ammonium hydroxide may be produced in the reaction system. That is, a combination of a quaternary ammonium salt and an alkali hydroxide can be used.

As the quaternary ammonium salt, the following general formula (II), R ₁ R ₂ R ₃ R ₄ NX (II) (wherein R ₁ , R ₂ , R ₃ and R ₄ have 1 carbon atoms) ~ 4 alkyl group or aromatic substituted alkyl group, R ₁ ,
R ₂ , R ₃ and R ₄ may include the same thing, and X
Is any one of Cl, Br, I, HSO ₄ , NO ₃ , and IO ₄ ).

Specifically, tetramethylammonium,
Examples thereof include salts of chlorides, bromides, iodides, hydrogen sulfides, nitric oxides and periodate such as tetraethylammonium, tetrapropylammonium, tetrabutylammonium, trimethylbenzylammonium and triethylbenzylammonium.

Examples of the alkali hydroxide to be combined with the quaternary ammonium salt include sodium hydroxide and potassium hydroxide.

Hydroxypropylation of the above chitosan is
Although it can be carried out in a dispersion system, as the reaction medium, one solvent alone selected from the group of poorly water-soluble organic solvents or one solvent selected from the group of water-miscible organic solvents, A mixed reaction medium with water can be used. Also,
It is also possible to use a mixed reaction medium of water and a mixed solvent of one solvent selected from the group of poorly water-soluble organic solvents and one solvent selected from the group of water-compatible organic solvents.

The group of the poorly water-soluble organic solvent includes aliphatic hydrocarbons such as hexane and heptane, aromatic hydrocarbons such as benzene, toluene and xylene, and ketones.

The group of water-soluble organic solvents includes isopropanol, t-butanol and other aliphatic alcohols having 3 to 4 carbon atoms, dioxane, tetrohydrofuran, dimethyl sulfoxide and the like.

It is preferable to use toluene alone as the poorly water-soluble organic solvent or t-butanol alone as the water-miscible organic solvent, and a mixture of water or a mixed solvent of hexane and isopropanol and water. Here, to use a mixture with water, specifically, for example, in a mixed solvent of hexane and isopropanol, the starting chitosan is charged and stirred, to disperse the chitosan in the mixed solvent, then, The addition of quaternary ammonium hydroxide and water to the chitosan slurry.

Since the quaternary ammonium hydroxide is used as a catalyst, it can be separated and recovered by washing after the reaction. That is, the reaction product is washed with a solvent in which hydroxypropyl chitosan is insoluble but quaternary ammonium hydroxide is dissolved. This makes it possible to obtain high-purity hydroxypropyl chitosan and to reuse the quaternary ammonium hydroxide.

Hydroxypropyl chitosan is insoluble, but as a solvent for dissolving quaternary ammonium hydroxide, for example, isopropyl alcohol, t-
There are aliphatic alcohols having 3 to 4 carbon atoms such as butanol.

Next, the procedure of the method for producing hydroxypropyl chitosan according to the present invention will be described. First, the raw material chitosan is put into an organic solvent having a weight ratio of 1 to 10 to the raw material chitosan and stirred to disperse the chitosan in the organic solvent. The chitosan slurry is then added to the chitosan in a weight ratio of 0.05 to 1.0, preferably 0.08 to 0.8 of quaternary ammoium hydroxide and a weight ratio of 0.1 to 1.5 in chitosan, Preferably 0.3 to 1.0 of water is added. At this time, as described above, instead of the quaternary ammonium hydroxide, a quaternary ammonium salt and an alkali hydroxide corresponding to the same molar number may be used. Further, propylene oxide was added to this slurry in an amount corresponding to a desired average addition mole number (addition mole number of propylene oxide per glucosamine residue), and etherification was performed at a temperature of 20 to 100 ° C. for 1 to 10 hours. Allow the reaction to take place. This produces the desired hydroxypropyl chitosan with the desired average number of moles added.

The conditions such as reaction temperature and reaction time vary slightly depending on the degree of ether group substitution, the type and amount of solvent used, etc., but in order to ensure good viscosity physical properties of the product, it is preferably 40-70. The etherification reaction is carried out at a temperature of ° C for 2 to 6 hours. The average number of moles of hydroxypropyl groups added, which is necessary for hydroxypropyl chitosan to exhibit uniform water solubility, is 1.2 or more, and preferably 1.5 or more. This is certainly achieved in the present invention.

The hydroxypropyl chitosan produced is
Wash with the water-miscible organic solvent, preferably isopropyl alcohol. By this, most of the by-products are removed, and hydroxypropyl chitosan having a low impurity content can be obtained. Furthermore, by purifying with hot water, a higher purity product can be obtained.

[0027]

EXAMPLES Examples and comparative examples of the present invention will be given below, but the present invention is not limited to these examples and the like.

Example 1 100 parts by weight of commercially available powdered chitosan (deacetylation degree 80%) was dispersed in 500 parts by weight of isopropanol, 10 parts by weight of tetramethylammonium hydroxide and 5 parts of water.
Nitrogen substitution was performed by adding 0 part by weight, and 250 parts by weight of propylene oxide was added while stirring at 25 ° C. The reactor was gradually heated to 60 ° C. and kept at that temperature for 3 hours. After completion of the reaction, the mixture was cooled to room temperature, the suspension was filtered, and then washed thoroughly with isopropanol. 60 ° C
It was dried below and pulverized to obtain a pale yellowish white powder of hydroxypropyl chitosan. When the substitution degree of the hydroxypropyl group was analyzed by the Zei-sel-GC method, the average number of added moles was 2.2. The 1% aqueous solution viscosity of this hydroxypropyl chitosan is shown in Table 1 together with the raw material chitosan and the hydroxypropylated chitosans obtained in Examples 2 to 4 and Comparative Examples described later. Was not seen.

Example 2 100 parts by weight of commercially available powdered chitosan (deacetylation degree 80%) was dispersed in 500 parts by weight of isopropanol, and 12 parts by weight of tetramethylammonium chloride and 4.4 parts by weight of sodium hydroxide were added to 50 parts of water. What was melt | dissolved in the weight part was added, nitrogen substitution was performed, and it stirred at 25 degreeC,
250 parts by weight of propylene oxide were added. The reactor was gradually heated to 60 ° C. and kept at that temperature for 3 hours. After completion of the reaction, cooled to room temperature, filtered the suspension,
Then, it was thoroughly washed with isopropanol. By drying at 60 ° C. and pulverizing, hydroxypropyl chitosan having an average addition mole number of 2.3 as a pale yellowish white powder was obtained.

Example 3 100 parts by weight of commercially available powdered chitosan (deacetylation degree 80%) was dispersed in 550 parts by weight of toluene, and a solution prepared by dissolving 20 parts by weight of tetrabutylammonium hydroxide and 50 parts by weight of water was added. The atmosphere was replaced with nitrogen, and 150 parts by weight of propylene oxide was added with stirring at 25 ° C. The reactor was gradually heated to 60 ° C. and kept at that temperature for 2 hours. After the reaction was completed, it was cooled to room temperature and the suspension was filtered. It was then washed with isopropanol. 6
By drying at 0 ° C. and pulverizing, hydroxypropyl chitosan having an average addition mole number of 1.6 as a white powder was obtained.

Example 4 100 parts by weight of commercially available powdered chitosan (deacetylation degree 80%) was dispersed in a mixed solvent of 250 parts by weight of toluene and 250 parts by weight of isopropanol, and 20 parts by weight of benzyltrimethylammonium bromide and hydroxylation were added. A solution prepared by dissolving 3.5 parts by weight of sodium in 50 parts by weight of water was added to perform nitrogen substitution, and 200 parts by weight of propylene oxide was added with stirring at 25 ° C. The reactor was gradually heated to 60 ° C. and kept at that temperature for 3 hours. After the reaction was completed, it was cooled to room temperature and the suspension was filtered. Then, it was washed with isopropanol and purified with hot water.
By drying at 60 ° C. and pulverizing, hydroxypropyl chitosan having an average added mole number of 1.9 as a white powder was obtained.

Comparative Example 1 Treatment was carried out under the same conditions as in Example 1 except that 10 parts by weight of sodium hydroxide was used in place of 10 parts by weight of tetramethylammonium hydroxide, and the white powdery average added mole number of 0. 6 hydroxypropyl chitosan was obtained.

Comparative Example 2 100 parts by weight of commercially available powdered chitosan (deacetylation degree of 80%), 500 parts by weight of toluene, 20 parts by weight of sodium hydroxide and 50 parts by weight of water were charged into a reactor, and nitrogen substitution was carried out. The mixture was stirred at a temperature of ° C for 3 hours. Then, 250 parts by weight of propylene oxide was added, the temperature was raised to 80 ° C., and the temperature was maintained for 5 hours. After the reaction was completed, the product was neutralized with acetic acid, and then gel washing was performed with hot water. Average number of moles of white powder added by drying at 60 ° C. and crushing 2.
3 of hydroxypropyl chitosan was obtained.

[0034]

[Table 1]

[0035]

As is clear from the above, according to the present invention, hydroxypropyl chitosan can be produced under mild reaction conditions of low temperature and short time, and its mass production is advantageous in terms of cost. Will be able to run. Moreover, since hydroxypropyl chitosan according to the present invention develops high viscosity in an aqueous solution,
It is excellent in many ways, including the problem of viscosity reduction.

Claims (5)

[Claims] 1. A chitosan comprising deacetylated chitin is prepared by using the following general formula (I), R ₁ R ₂ R ₃ R ₄ NOH (I) (wherein R ₁ , R ₂ , R ₃ and R ₄ are Represents an alkyl group having 1 to 4 carbon atoms or an aromatic substituted alkyl group, R ₁ ,
R ₂ , R ₃ and R ₄ may include the same one), and a method for producing hydroxypropyl chitosan, which comprises etherifying with propylene oxide in the presence of a quaternary ammonium hydroxide represented by . 2. The method for producing hydroxypropyl chitosan according to claim 1, wherein the weight ratio of the quaternary ammonium hydroxide to chitosan is 0.05 to 1.0. 3. Chitosan composed of deacetylated chitin can be prepared by using the following general formula (II), R ₁ R ₂ R ₃ R ₄ NX (II) (wherein R ₁ , R ₂ , R ₃ and R ₄ are Represents an alkyl group having 1 to 4 carbon atoms or an aromatic substituted alkyl group, R ₁ ,
R ₂ , R ₃ and R ₄ may include the same thing, and X
Is any one of Cl, Br, I, HSO ₄ , NO ₃ , and IO ₄ ) and is etherified with propylene oxide in the presence of a quaternary ammonium salt and an alkali hydroxide. A method for producing hydroxypropyl chitosan. 4. The method for producing hydroxypropyl chitosan according to claim 3, wherein the weight ratio of the quaternary ammonium salt to chitosan is 0.05 to 1.0. 5. The alkali hydroxide is sodium hydroxide or potassium hydroxide.
Alternatively, the method for producing hydroxypropyl chitosan according to claim 4.