RU2185387C2 - Carboxymethylchitosan production method - Google Patents

Abstract

FIELD: production of chitosan and its derivatives. SUBSTANCE: dispersing of chitosan in organic solvent is followed by mercerization in alkaline medium, carboxymethylation of chitosan for 3-4 h at 60 C, ageing at 25 C for 12 to 20 h, and addition of ice acetic acid in water-free ethanol to neutralize product (pH 7). EFFECT: avoided heating and use of poisoning reagents. 2 ex

Description

 The invention relates to the field of polymer-analogous transformations of natural macromolecular compounds, namely carboxymethylation of chitosan-poly-β-D-glucosamine, and can be used in the chemical, textile, paper, food industry and medicine.

 A known method of producing carboxymethylchitosan (N, O-carboxymethyl-poly-β-D-glucosamine), which consists in the deacetylation of chitin dispersed in an organic solvent, followed by mercerization of the resulting chitosan in a cooled aqueous solution of concentrated alkali; after processing the reaction mixture with monochloroacetic acid and neutralization with glacial acetic acid, water-soluble carboxymethylchitosan precipitates with the addition of methanol (AS USSR 1666459, 08 08 37/08).

 A disadvantage of the known method is the use of chitin as a raw material, requiring preliminary deacetylation, which is carried out in an organic solvent using a concentrated sodium hydroxide solution, which makes this process additionally heterogeneous and little controlled, and the resulting carboxymethylchitosan is predominantly O-substituted derivative with a low yield.

A known method of producing chitosan, in which chitosan obtained from krill and dispersed in isopropyl alcohol is used as a feedstock; carboxymethylation is carried out with monochloroacetic acid for 0.5-1 hours, and then 30-45 wt.% aqueous sodium hydroxide solution is introduced and the mixture is kept for 1.5-2 hours at a temperature of 70-80 ^o С, in order to increase the degree of substitution, the reaction is carried out in two steps then neutralize the mixture with glacial acetic acid to pH 7; the isolated carboxymethylchitosan is washed with methanol and dried (AS USSR 1520067, C 08 V 37/08).

 The disadvantage of this method is its multi-stage process, taking into account two-fold processing and the use of large quantities of reagents, which results in a poorly soluble product in water, due to its low degree of substitution.

The closest to the achieved positive result is a method for producing carboxymethylchitosan, which consists in the following sequence of operations:
- dispersion of chitosan in an organic solvent for 0.5-1 hours;
- mercerization in an alkaline medium, by adding to the suspension of chitosan a 30 wt.% aqueous solution of alkali (3-8 mol of sodium hydroxide per 1 mol of glucosamine unit) for 1-3 hours;
- carboxymethylation of chitosan with monochloracetic acid (1 mol of acid per 2 mol of alkali) when heated for 2-12 hours at a temperature of 40-70 ^o C;
- the introduction of water in an amount necessary to control the pH;
- neutralization of the reaction mixture with glacial acetic acid to pH 7;
- the selection of solid carboxymethylchitosan, washing with methanol, drying (US patent 4619995, 08 08 37/08, 1987).

 The known method allows to obtain carboxymethylchitosan with a total degree of substitution of 0.6-1.1 and a yield of the final product of 70-80%, soluble in water by 75-85%. However, a significant drawback of the method is the introduction of water into the heated reaction mixture, which causes the hydrolysis of monochloracetic acid, while the amount of alkylating agent per basic reaction is reduced and, as a result, the low degree of substitution of carboxymethylchitosan and the low yield of the final product. The disadvantage of this method is the use of toxic and inaccessible methanol.

 A positive result of the proposed method is the simplification of the method, which allows under heterogeneous conditions to provide a high yield of carboxymethylchitosan with a high degree of substitution and solubility in water of at least 80%.

 A positive result is achieved by the fact that carboxymethylation is also carried out in the absence of heating, and a solution of glacial acetic acid in anhydrous ethonol is used to neutralize it.

 The method is as follows.

Chitosan, crushed in a ball mill, is placed in a three-necked flask equipped with a propeller stirrer, reflux condenser and thermometer. The flask is fixed in the foot of a tripod, isopropyl alcohol (C ₃ H ₇ OH) is added, observing a mass ratio of chitosan-isopropyl alcohol of 1:50. Dispersion of the mixture is carried out at a temperature of 25 ^o C for 0.5-1 hours. After a time, 28.5 wt.% Aqueous solution of sodium hydroxide (NaOH) is poured into the flask, based on 3.5 mol of sodium hydroxide per 1 mol of D-glucosamine unit, the mercerization is carried out at a temperature of 25 ^o C for 1 hour at a constant stirring. After mercerization, monochloracetic acid (0.5 mol of acid (ClCH ₂ COOH) per 1 mol of alkali) is added to the reaction mixture, the flask is placed on a preheated sand bath, the reaction is carried out with constant stirring for 3-4 hours, after which time the reaction is left the mixture at a temperature of 25 ^o With another 12-20 hours continuously mixing. Ethanol, acidified with glacial acetic acid, is added to the son-in-law until the carboxymethylchitosan is completely precipitated, the process is carried out under pH control to pH 7. At the end, the reaction mixture is poured onto a filter, and the precipitated carboxymethylchitosan is washed with dried ethanol.

 The yield of carboxymethylchitosan is 90-95% of theoretical, the total degree of substitution reaches 1.2-1.4, and the solubility in water is 85-92%. The intrinsic viscosity of aqueous solutions of carboxymethylchitosan obtained in this way is 1.9-2.0 dl / g.

 Example 1

4.5 g of Gammarus crustacean chitosan is ground in a ball mill, placed in a three-necked flask and 250 ml of isopropyl alcohol are added, and stirred for 30 minutes. Then poured 28.5 wt.% An aqueous solution of sodium hydroxide and stirred for another 1 hour. After mercerization, 4.8 g of monochloroacetic acid is added to the reaction mixture and heated in a sand bath with constant stirring for 3 hours and a temperature of 60 ^° C. After some time, heating is turned off and the reaction mixture is left for 12 hours, then ethanol is added to the reaction mixture acidified with glacial acetic acid, until completely neutralized (pH 7). The reaction mixture was poured onto a filter and the precipitated carboxymethylchitosan was washed with dried ethanol. The yield of chitosan is 9 g, which is 91.5% of the theoretical. The solubility of carboxymethylchitosan in water obtained in Example 1 was 91.7%, and the degree of substitution was 1.4.

 Example 2

The preparation is carried out according to example 1, but dispersion in an organic solvent is carried out for 1 hour, and carboxymethylation for 4 hours at the same temperature, after which the reaction mixture is left for 20 hours at a temperature of 25 ^o C. The yield of carboxymethylchitosan is 95%, degree of substitution 1, 2, solubility in water 88%.

 The main advantage of the present invention is that the production of carboxymethylchitosan under conditions of prolonged alkaline catalysis in a heterogeneous mixture in the absence of heating makes it possible to obtain carboxymethylchitosan with a high content of carboxymethyl groups, along with this the product yield reaches 95%, and a solution of glacial acetic acid in anhydrous ethanol is used to neutralize Thus, the limited use of aqueous media increases the yield of the product, its degree of substitution and solubility.

Claims (1)

The method of producing carboxymethylchitosan, including dispersing chitosan in an organic solvent, mercerization in an alkaline medium, carboxymethylation of chitosan with monochloracetic acid, characterized in that the carboxymethylation of chitosan is carried out under heating at a temperature of 60 ^{° C.} for 3-4 hours, then the reaction mixture is left at a temperature of 25 ^o C for 12-20 hours, followed by the addition of a solution of glacial acetic acid in anhydrous ethanol until neutralization (pH-7).