SU1298211A1 - Method for isolating 2-methyl-3-nitro-4-methoxymethyl-5-cyano-6-chlorpyridine - Google Patents

Abstract

The invention relates to measured pyridines, in particular the isolation of 2-methyl-3-nitro-4-methoxymethyl-5-cyano-6-chloropyridine (CP), which is used as an intermediate in the synthesis of vitamin Bj. The purity and uniformity of CP is achieved by certain conditions and ratios of the starting materials. CP is separated from the reaction mixture obtained by the reaction of 2-methyl-3-nitro-4-m-toxymethyl-5-diano-6-oxypyridone (OP) with thionyl chloride in the presence of dimethylformamide in CHCI j. The latter is distilled off, the residue is diluted with isopropanol, purified with activated carbon and crystallized at a temperature of from 75 to (-2) - (- 5) C and a ratio of CP, CHCI ". And isopropanol I: (0,7-S): :(, 2). Next, the crystals are washed with water at a temperature of from 10 to (-2) - (-5) C to the ratio in the system of crystalline and dissolved CP, CHCl3 j isopropanol and water 1: (0.7-1) :( 3.0 - 3.2 ) :( 2.75-3.15). The method provides a yield of 83% with the content of the main substance of 99.4%, so pl. 73 ,, in the absence of sulfur in the TLC control of CP homogeneity in dispersion, table 2. t (ljo with 00

Description

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The invention relates to an improved process for the isolation of 2-methyl-3-nitro-4-methoxymethyl-5-cyano-chloropyridine (nitrochloropyridine), which is an intermediate product of pyridoxine pyridoxine hydrochloride (viamine B).

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The aim of the invention is to increase the purity of the target product and homogeneity.

The goal is achieved by conducting the crystallization of a product from a solution with the ratio of the components of nitrochloropyridine: chloroform:: isopropyl alcohol 1: (O, 7-1.0):: (3.0-3.2), followed by treatment with water at a temperature of from 10 to (-2) - (-5) with up to the ratio of components in the system of crystalline and dissolved nitrochloropirrzdine: chloroform: isopoopyl alcohol: water 1: (O, 7-1.0):: (3.0-3.2): (2.75-3.15).

Example 1. A solution of nitrochloropyridine is obtained by reacting 135.93 g of 97% (131.85 g of 100%) 2-methyl-3-nitro-4-methoxymethyl-5-cyano-6-oxypyridone with 93.35 ml of 98% (149.54 g of 100%) thionyl chloride in 1000 ml of chloroform in the presence of 7.04 ml of 98.9% (6.59 g of 100%) dimethylformamide at 59- 62 ° C for 10 hours. After alkaline (solution of 15.08 g of 98% sodium hydroxide in YuOO), and acidic (solution of 2.0 ml of 35.6% hydrochloric acid in 750 ml of water), remove from the solution Nitrochloropyridine distills chloroform at the boiling point of the solution (temperature in pairs 57-6.) under normal conditions. Obtain 219.7 g of a solution containing 124.72 g of nitrochloropyridine and 87.3 g of chloroform. The solution was diluted with 470 ml (374.16 g) of 85% isopropyl alcohol heated to 70 ° C and 12 g of activated carbon was added. The solution is filtered, the clarified solution of nitrochloropyridine (the ratio of the components in the system of nitrochloropyridine: chloroform: isopropyl JQ alcohol 1: 0.7: 3.0) is crystallized with stirring and cooling to.

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At the same time, when cooling from 10 to -5 ° C, 350 ml of water in doses of 50 ml are introduced into the crystallizing system (the ratio of the components in the nitrochloropyridine: chloroform: isopropyl alcohol: water 1: 0.7: 3.0: 2.75) system. Cooling time from the initial temperature

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solution (-68 ° C) to -5t 4.5 hours. After holding at the final temperature for 1.5 hours, the suspension is filtered, the crystals of nitrochloropyridine are washed with 120 ml of 85% isopropyl alcohol, cooled to 650 ml of water and 450 ml of solution hydrochloric acid (1.2 ml of 35.6% hydrochloric acid in 450 ml of water). The precipitate is dried under vacuum at 40-45 s.

118.48 g of nitrochloropyridine crystals are obtained, the content of the basic substance is 99.4%, the yield is 83% of theory, considering 2-methyl-3-nitro-4-methoxy 5 methyl-5-cyano-6-oxypyridone, m.p.

73 ,, there is no sulfur in the TLC-control of nitrochloropyridine, there is no monoamine in 2-methyl-3-amino-4-methoxymethyl-5-aminomethylpyridine psi dichlorohydrate psi experimental nitrochloropyridine hydrogenation by TLC control, pro-; a dispersed composition with the absence of nitrochloropyridine with a fuzzyly pronounced crystalline structure.

Examples 2-6. Prepared according to Example 1 by varying the amount of chloroform distilled from the reaction solution and the amount of isopropyl alcohol and water added.

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Characteristics of the solutions and modes of experiments are given in table.1. The results of the experiments are given in

Table 2.

In examples 2, 3 and 5 get a homogeneous dispersion of kris

tallic nitrochloropyridine with the absence of a product with a poorly pronounced crystalline structure, in examples 4 and 6 - heterogeneous with the presence of a product with a poorly pronounced crystalline structure.

The predicted release of nitrochloropyridine improves; the purity of the target product and avoid recrystallization (examples 1-3). In this case, the uniformity of the crystals increases. When the parameters change beyond the specified intervals (examples 4-6), the purity or yield of crystalline nitrochloropyridine decreases, the product is heterogeneous in dispersion with the presence of nitrochloropyridine with a poorly defined crystalline structure (examples 4 and 6).

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Claims (1)

Claims 2-methyl-3-nitro-4-methoxymethyl-5-cyano-6-chloropyridine (nitrochloropyridine) obtained by the reaction of 2-methyl-3-nitro-4-β-methoxymethyl-5-cyano-6 -oxypyridone with thionyl chloride in chloroform in the presence of dimethylfornamide, including distilling off chloroform at the boiling point of the solution, diluting with isopropyl alcohol, cleaning the solution with activated carbon, crystallizing by cooling at a temperature of 75 to (-2) - (- 5) C, section 1: 0, 7: 3,0219,7 21: 1.0: 3.2252.8 31: 0.85: 3.1237.5 "1: 0.6: 3.4201.89 51: 1,1: 2, G267,7 61: 0.7: 3.0218.1 crystallization and washing, characterized in that, in order to increase the purity of the target product and its homogeneity, crystallization is carried out from a solution with a ratio of components in the nitrochloropyridine: chloroform: isopropyl alcohol 1: (0.7-1.0) system: (3.0-3.2) followed by treatment with water at a temperature from 10 to (-2) - (- 5) C to the ratio of components in the system of crystalline and dissolved nitrochloropyridine: chloroform: isopropyl alcohol: water:: (0.7 g1 , 0): (3.0-3.2): (2.75-3.15). Table I The cottage input ode, CP 1: 0.7: 3.0: 2.75 1: 1,0: 3,2: 3,15 1: 0.35: 3.1: 3.0 1: 0.6: 3.4: 3.2 1: 1,1: 2,8: 2,6 1: 0.7: 3.0: 2.75 table 2 Note. According to a known method, 40% of batches of nitrochloropyridine, according to one or several purity indicators, are outside the established limits: the content of the main substance is 96-97.5%, the presence of sulfur compounds by TLC control, the melting point is 70-72 s, the presence of monoamine in dihydrochloride 2- Mets-1-3-amino-4-meth-hydroxymethyl-5-aminomethylpyridine, which necessitates additional recrystallization of the target product.