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Simple preparation method of 2, 5-dichloropyridine

A technology of dichloropyridine and chlorinated reagents, applied in the field of medicinal chemistry, can solve the problems of a large amount of ethanol solvent, unfavorable safety and environmental protection, and inconvenient operation, and achieve the effect of simple post-processing, low cost, and easy operation

Active Publication Date: 2019-05-07
XINFA PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0013] The raw material 2,3,6-trichloropyridine used in the above synthetic route 3 method is expensive, and benzene and toluene are used as highly toxic solvents, and zinc powder is added in batches, which is inconvenient to operate. The crude product needs to be recrystallized and refined, and a large amount of ethanol solvent is required. And produce a large amount of solid waste, which is not conducive to safety and environmental protection

Method used

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  • Simple preparation method of 2, 5-dichloropyridine
  • Simple preparation method of 2, 5-dichloropyridine
  • Simple preparation method of 2, 5-dichloropyridine

Examples

Experimental program
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Effect test

Embodiment 1

[0048] Embodiment 1: Preparation of 2,5-dihydroxypyridine

[0049] In the 500 milliliter four-necked flask that is connected with stirring, thermometer, reflux condenser, add 30.5 grams (0.5 moles) Nitromethane, 72.0 grams (0.5 moles) dimethyl maleate, 1.8 grams DBU, 60- Stir the reaction at 65°C for 5 hours, then cool to 20-25°C. The resulting reaction liquid is transferred to a 1-liter autoclave, 400 grams of methanol is added, and 1.0 grams of palladium mass content is 5% palladium-carbon (50 wt %) catalyst. After nitrogen replacement three times, feed hydrogen to keep the hydrogen pressure at 0.1 -0.2MPa, react at 50-55°C for 4 hours. After nitrogen replacement three times, the catalyst was removed by filtration, the filtrate was concentrated and evaporated to dryness, and 100 g of methyl tert-butyl ether was added for recrystallization to obtain 51.7 g of light yellow solid 2,5-dihydroxypyridine (Ⅲ), with a liquid phase purity of 99.7%. The rate is 93.1%.

Embodiment 2

[0050] Embodiment 2: Preparation of 2,5-dihydroxypyridine

[0051]In the 500 milliliter four-necked flask that is connected with stirring, thermometer, reflux condenser, add 30.5 grams (0.5 mol) nitromethane, 86.1 gram (0.5 mol) diethyl maleate, 1.8 gram DBN, 65- Stir the reaction at 70°C for 5 hours, then cool to 20-25°C. The resulting reaction liquid is transferred to a 1-liter autoclave, and 400 grams of ethanol is added, and 1.2 grams of palladium mass content is 5% palladium-carbon (water-containing 50wt%) catalyst. After nitrogen replacement three times, feed hydrogen to keep the hydrogen pressure at 0.1 -0.2MPa, react at 50-55°C for 4 hours. After nitrogen replacement three times, the catalyst was removed by filtration, the filtrate was concentrated and evaporated to dryness, and 100 g of methyl tert-butyl ether was added for recrystallization to obtain 52.2 g of light yellow solid 2,5-dihydroxypyridine (Ⅲ), with a liquid phase purity of 99.8%. The rate is 94.0%.

Embodiment 3

[0052] Embodiment 3: Preparation of 2,5-dihydroxypyridine

[0053] In the 500 milliliter four-neck flask that is connected with stirring, thermometer, reflux condenser, add 30.5 grams (0.5 mol) nitromethane, 100.1 gram (0.5 mol) diisopropyl maleate, 1.8 gram DBU, 65 Stir the reaction at -70°C for 5 hours, then cool to 20-25°C. The resulting reaction liquid is transferred to a 1-liter autoclave, 400 grams of isopropanol is added, and 8.0 grams of nickel mass content is a 50% Raney nickel (50 wt %) catalyst. After nitrogen replacement for three times, hydrogen is introduced to maintain the hydrogen pressure. 0.1-0.2MPa, 60-65°C for 4 hours. After nitrogen replacement three times, the catalyst was removed by filtration, the filtrate was concentrated and evaporated to dryness, and 100 g of methyl tert-butyl ether was added for recrystallization to obtain 52.0 g of light yellow solid 2,5-dihydroxypyridine (Ⅲ), with a liquid phase purity of 99.6%. The rate is 93.6%.

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Abstract

The invention provides a green, safe, simple and convenient preparation method of 2, 5-dihydroxybenzene. The method comprises the following steps: by taking maleic acid diester as an initial raw material, carrying out condensation with nitromethane, hydrogenation cyclization and chlorination to prepare 2, 5-dibromobenzene. The preparation method is simple, easy to operate, high in reaction selectivity and high in product yield and purity; The method disclosed by the invention is low in wastewater yield, environment-friendly and high in reaction safety; the used raw materials are cheap and easily available, and the cost is low.

Description

technical field [0001] The invention relates to a convenient preparation method of 2,5-dichloropyridine, which belongs to the technical field of medicinal chemistry. Background technique [0002] 2,5-Dichloropyridine is an important pesticide and pharmaceutical intermediate, which can be used to synthesize drug intermediates such as anti-AIDS and anti-peptic ulcer drugs, and can also be used as an intermediate for pyridine insecticides. Pesticides and other fields have a wide range of applications. [0003] 2,5-Dichloropyridine mainly has the following three synthesis methods, which are respectively prepared from 2-chloropyridine, 2-aminopyridine and 2,3,6-trichloropyridine as starting materials. [0004] 1. Using 2-chloropyridine as raw material, react with n-butanol to obtain 2-butoxypyridine, then pass chlorine to obtain 85wt% 2-butoxy-5-chloropyridine and 15wt% 2-butoxypyridine -3-chloropyridine mixture, and then use phosphorus oxychloride chlorination to prepare 2,5-d...

Claims

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Application Information

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IPC IPC(8): C07D213/61
Inventor 戚聿新吕强三李艳平鞠立柱
Owner XINFA PHARMA