Method of producing 2,3-dihydroxypropyl chitosan

FIELD: chemistry.

SUBSTANCE: invention relates to production of hydroxyalkyl derivatives of polysaccharides. The method of producing 2,3-dihydroxypropyl chitosan involves reacting chitosan with glycidol in the presence of hydrochloric acid with ratio glycidol:chitosan:hydrochloric acid = (2-6):1:1, at room temperature until a gel forms. The mixture is then heated at 55-65°C for 12-14 hours and the reaction mass is treated with water. The mixture is then deposited, subjected to hot extraction with water-soluble alcohols or ketones and dried.

EFFECT: invention simplifies the method of production and output of the end product and improves sorption properties of the compound.

1 tbl, 3 ex


The invention relates to the synthesis of hydroxyalkyl derivatives of polysaccharides, namely, to a method for producing 2,3-dihydroxypropane (GPC). This compound finds application as a component of antibiotics (Chemistry Letters. 2010. V.39. No. 9 P.935-937) and as a sorbent for the extraction of boron from aqueous solutions (Analytica Chimica Acta. 1998. V.371. No. 8. P.187-193).

A method of obtaining GPC through the interaction of a 2% dispersion of chitosan in a mixture of methanol-dioxane with 3-chloro-1,2-propane diol in the presence of NaOH at a temperature of 60-70°C and stirring for 24 hours. The resulting product has a degree of substitution of 0.64 and shows the extraction of boron ions is 0.1 mmol/g at pH=4 (Analytica Chimica Acta. 1998. V.371. No. 8. P.187-193).

The disadvantages of this method of obtaining a civil act is the need to use the base NaOH that in subsequent operations requires additional purification of the product, process temperature up to 70°C, the time up to 24 hours, the need to use organic solvents (methanol, dioxane) in large volumes and mixing of the reaction mass, the low degree of substitution, not more of 0.64. The product yield per unit download size is 4.3%.

A method of obtaining civil act by reacting 2,4% aqueous dispersion of chitosan with glycidol at 60°C and stirring for 15 hours. Received the product today is the degree of substitution 2,85. The product yield per unit download size is 3.6% (Eur. Polym. J. 1989. V.25. No. 4. P.379-384) prototype.

The disadvantages of the method are the use of highly diluted dispersion of chitosan, which leads to an increase in the size of the used reactors and other equipment, and to a large consumption of solvents for the reaction and to precipitate the product, and to a minor product yield per unit of download size.

General shortcomings of the above-mentioned methods are the use of 6-fold molar amount dihydroxypropyl reagents relative to the chitosan and the reaction takes place in highly diluted chitosan dispersions and solutions of reagents (area of concentration of chitosan dispersions 2-2,4%). These circumstances may cause inefficient use of the reagents and solvent, as well as technological inconvenience, because large amounts of the substances inefficiently operated equipment. The use of dispersions of chitosan leads to heterogeneous reactions, which does not ensure the completeness of the modifying polymer of 2,3-dihydroxypropyl groups.

Because sorption properties of GPC relative to the boron-containing ions, and hence antimicrobial properties of complexes GPC and boron depend on the number entered is s 2,3-dihydroxypropyl groups, the most valuable should be considered as target product - GPC with a greater degree of substitution.

The problem solved by the invention is a simplified method of obtaining a civil act, the increase of yield per unit of download size and improving its quality as sorbent by increasing the degree of substitution of hydrogen atoms in the amino group by 2,3-dihydroxypropyl radical.

The problem is solved by the interaction of chitosan with an aqueous solution of glycidol in the presence of hydrochloric acid at the ratio glycidol:chitosan:hydrochloric acid=(2-6):1:1 at room temperature to gel formation, followed by heating at 55-65°C for 12-14 hours and processing the cooled reaction mixture with water, planting and hot extraction of water-soluble alcohols or ketones.

The use of a concentrated solution of chitosan gel helps to obtain a product with the degree of substitution is from 1.21 to 3.00. The method allows the use of chitosan with high molecular weight, since the formed gel does not require mixing. The use of concentrated solutions reduces the loaded volume, which increases the product yield per unit of download size and thus allows more efficient use of equipment.

Below 55°C degree of substitution is greatly reduced, and when the temperature is over 65°C - significantly reduced molecular weight, due to processes of degradation of the polymer chain. Carrying out modification less than 12 hours is not effective, because the degree of substitution is low, and more than 14 hours does not lead to a noticeable increase in the degree of adherence. This single-stage method, proceeds at a lower temperature for a relatively short period of time, can significantly reduce the use of organic solvents in the process of modification, and in the process of selection of the product.

The process is carried out by heating in the reactor, then the product is extracted with hot water-soluble alcohols or ketones and air-dried. The composition of the obtained GPC characterize the elemental analysis data, the presence of introduced 2,3-dihydroxypropyl groups NMR1H spectroscopy of the solution.

The proposed solution is illustrated by the following synthetic examples.

Example 1

A mixture of 3.3 g (0.02 mol) of chitosan, 1.8 ml (0.02 mol) of 37% hydrochloric acid in 10 ml of water stand 10 min before the formation of gel-like mass. Then add to 5.3 ml (0.08 mol) of glycidol, the mixture is heated at 60°C for 13 h and cooled. To the resulting mixture add 5 ml of distilled water, after homogenization, the product is precipitated with acetone, subjected to hot extraction with ethanol for 24 hours, the Product is dried at 50°C until constant in the sa. Obtain 6.7 g GPC.

Found, %: C 44,82; H 7,71; N to 5.21; for formula (C8H13NO5)0,16(C6H11O4N)0,84(C3H7O2)1,21(HCl)of 0.2calculated, %: C 44,92; H EUR 7.57; N 5,26.

An NMR spectrum1H (D2O/DCl), δ ppm: 2.07 (CH3), 3.40-4.29 (HOCH2CH(OH)CH2CH2OH, H-2,3,4,5,6), 4.67 (H-1 GlcNHAc), 4.94 (H-1 GlcNH2), 5.08 (H-1 GlcNHCH2CH(OH)CH2OH), 5.21 (H-1 of GlcN{CH2CH(OH)CH2OH)}2). The degree of substitution according to NMR1H-2.85.

Examples 2 and 3

The method further experiments corresponds to example 1. Reaction conditions and characteristics of the products obtained are presented in the table.

Table 1
Conditions for obtaining and characteristics of civil
# exampleChitosan, gGlycidol, mlH2O mlThe molar ratio of glycidol:chitosanTemperature, °CTime, hOutput, gThe output of product per unit of the loaded volume %The degree of substitution
The placeholder 0,51201:660150,923,62,85

The way to obtain 2,3-dihydroxypropane interaction of chitosan with glycidol in water by heating, characterized in that the interaction is carried out in the presence of salt is islote when the ratio glycidol:chitosan:hydrochloric acid=(2-6):1:1 at room temperature to gel formation, subsequent heating at 55-65°C for 12-14 hours, treating the reaction mass with water, planting, hot extraction of water-soluble alcohols or ketones and drying.


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