Method for preparing 1-isonicotinyl-2-d-glucosyl hydrazone possessing with antituberculosis activity

FIELD: organic chemistry, chemical technology, medicine.

SUBSTANCE: invention relates to a method for preparing 1-isonicotinyl-2-D-glucosyl hydrazone. In the glucosylation reaction of isonicotinic acid hydrazide the method involves using anionite AN 31 GS as a catalyst of the enhanced effectiveness, and using 95-96.5% ethanol or 85-90% isopropanol as the reaction medium. At the final stage the method involves sorption of contaminating impurities with activated carbon followed by drying the end product in nitrogen atmosphere.

EFFECT: improved preparing method.

2 cl, 1 ex

 

The invention relates to methods of producing chemical compounds type 1-isonicotinoyl-2-glycosilation specifically 1-isonicotinoyl-2-D-glucosidase formula

where- D-glucosyl with anti-TB activity.

The prototype of the invention to provide 1-isonicotinoyl-2-exoticization (Slivkin A.I. and other proceedings of the VIII regional conference "the Problems of chemistry and chemical technology". Voronezh. Publishing house of Voronezh state University, 2000. T.1, s-86). According to the method 1-isonicotinoyl-2-D-glucosidase synthesized by boiling a mixture of 0.1 mol of D-glucose, 0.1 moles of hydrazide of isonicotinic acid (GINK), 0.5 g of anion exchange resin AB-16 HS and 0.5 g of the anion an-FN (7.2% in the calculation of the GINK) in 150 ml of absolute ethanol to dissolve the carbohydrate component (D-glucose). After separation of the anion exchange resin by filtration the resulting solution was vacuum and maintained at 0°10-20 hours, the resulting crystalline precipitate is dried in vacuum.

Get 1-isonicotinoyl-2-D-glucosidase with TPL 166° [α]D20=24°; output - 85%.

The disadvantages of the known method of producing 1-isonicotinoyl-2-D-glucosidase are reducing the purity of the target product due to the presence of coloring impurities, lack of opportunities varier is of the reaction environment in terms of absolute ethanol, the use of two-component catalyst (anion exchange - AB-16 GS and EN-FN), limiting the increase in product yield, difficult process due to the inclusion of stage degassing of the reaction mass to 50% in ethanol, accompanied by his irreparable loss. The recovery of ethanol is not provided, which reduces the possibility of process on the partially closed loop.

The objective of the proposed method is to eliminate these drawbacks. This task is solved in that in the known method, which consists in obtaining 1-isonicotinoyl-2-D-glucosidase with anti-TB activity, by reacting the hydrazide of isonicotinic acid and D-glucose in the presence of catalysts of anionite AV-16 GS and EN-FN in an environment of absolute ethanol, followed by filtration of the reaction mixture, crystallization of the desired product and drying in vacuum, according to the invention in the process of glucosylceramide the hydrazide of isonicotinic acid (GINK) as a catalyst with high efficiency is used, the anion an-31. The decrease in the concentration of the catalyst in comparison with the prototype leads to increased yield of the target compounds by 2.5%. According to the invention at the final stage, the stage of synthesis is sorbirovaniya contaminants activated carbon, and predator the distribution of the destructive processes in the mass of the target product when it is drying in vacuum is achieved by carrying out this operation in a nitrogen atmosphere. The economy of the process according to the invention is enhanced by providing the possibility of using as the reaction medium when glucosylrutin GINK 95-96,5% ethanol or 85-90% isopropanol; excludes the operation of the vacuum filtrate of the reaction mass and provides for the recovery of alcohols to their production cycle. The anion an-31 is obtained by polycondensation of ammonia, polyethylenepolyamines and epichlorohydrin, as ionic groups contains secondary and tertiary amino groups (GOST 13504-68; TU 222 7-344-00203447-99; Directory "Ion exchangers", 1975, Department Niitaka, Cherkassy, p.35-36; RU Patent No. 2253864, 2005, G 01 N 31/22; RU Patent No. 2223488, 2004, G 01 N 31/22).

EXAMPLE 1. 1-Isonicotinoyl-2-In-glucosidase

A. 0.5 mol (90 g) of D-glucose, 0.5 mol (68,5 g) GINK, 1.6 g of the anion an-31 (1% calculated on the total weight of the reactants) is boiled under stirring in 800 ml of 95% ethanol until complete dissolution of D-glucose. The mixture is cooled to 70-75°add in its composition 2.0 g of activated charcoal and continue stirring for 30 minutes. The reaction mass is passed at 70-75°through basely filter over the hot filtration with vacuum.

The filtrate is cooled to 15-17°and incubated for 10-15 hours; the mixture is cooled to 0-4°With, 5-6 hours. The resulting crystalline mass is separated by filtration and dried in vacuum at 40-50°in the atmosphere and the PTA to constant weight.

Get 138,9 g (87,5%) 1-isonicotinoyl-2-D-glucosidase with TPL 166°C, solubility in water 53% [α]D20=24° (2,3, water).

Found, %: C 48,28; N 5,62; N 14,22; C12H17N3About6.

Calculated, %: C 48,15; N 5,73; N 14,04.

B. 0.5 mol (90 g) of D-glucose, 0.5 mol (68,5 g) GINK, 1.6 g of the anion an-31 is boiled under stirring in 1300 ml of 85% isopropanol to dissolve D-glucose. The mixture is cooled to 70-75°download 1.6 g of activated charcoal and continue stirring for 30 minutes.

The reaction mass is passed through basely filter over the hot filtration at 70-75°With vacuum. The filtrate was kept at 20-25°16 hours and then cooled to 0-5°and incubated for 1-2 hours.

The precipitate is filtered off, washed with isopropanol and dried in a vacuum oven at 40-50°C, in an atmosphere of nitrogen until constant weight.

Get 139,8 g (88,0%) 1-isonicotinoyl-2-D-glucosidase with TPL 166°C, solubility in water 53%, [α]D20=24° (2,3, water).

Found, %: C 48.38 Per; 5,56 N; N 14,18;12H17N3About6.

Calculated, %: C 48,15; N 5,73; N 14,04.

A method of obtaining a 1-isonicotinoyl-2-D-glucosidase with anti-TB activity of the formula

where- glucosyl, lies the present in the interaction of the hydrazide of isonicotinic acid and D - glucose in the presence of a catalyst in an ethanol medium, filtering the reaction mixture, crystallization and drying of the target product in a vacuum, characterized in that in the process of interaction of the hydrazide of isonicotinic acid and D-glucose using the catalyst, an anion exchange resin 31 as the reaction medium used 95-96,5% ethanol or 85-90% isopropanol, at the final stage of the synthesis process of the reaction mass of activated carbon, crystallization of 1-isonicotinoyl-2-D-glucosidase spend from the filtrate of the reaction mixture, excluding its degassing and drying of the target product is carried out in a nitrogen atmosphere.



 

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