A kind of preparation method of 4-amino-2-chloro-3-nitropyridine

A technology of nitropyridine and trichloronitroethylene, applied in the direction of organic chemistry, can solve the problems of flammability and explosion of recrystallization solvents, restrictions on industrial production, large amount of waste acid and wastewater, etc., and achieve appropriate reactivity and low cost , good yield effect

Active Publication Date: 2020-08-04
XINFA PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

It also has a large amount of waste acid waste water, flammable and explosive recrystallization solvents, high safety operation, and poor environmental protection, which limits industrial production.

Method used

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  • A kind of preparation method of 4-amino-2-chloro-3-nitropyridine

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Embodiment 1: Preparation of 4-amino-2-chloro-3-nitropyridine

[0029] In the reactor with stirring, thermometer and reflux system, add 60 kg of tetrahydrofuran, 7.5 kg (107 moles) of 3-aminopropionitrile, 17.5 kg (100 moles) of trichloronitroethylene, 0.1 kg of DBU, 50- Stir and react at 55°C for 4 hours, then cool to 30-40°C, add 30.5 kg (220 moles) of potassium carbonate, stir and react at 55-60°C for 3 hours, then cool to 20-25°C, filter, filter cake with 20 kg of tetrahydrofuran Wash, combine the filtrates, distill and recover the solvent, add 45 kg of isopropanol and 0.5 kg of activated carbon to the residue, decolorize at 55-60 ° C for 1 hour, filter while hot, recrystallize, filter, and dry to obtain 16.2 kg of light yellow solid 4 -Amino-2-chloro-3-nitropyridine, yield 93.4%, gas phase purity 99.8%.

[0030] The NMR data of the product are as follows:

[0031] 1 HNMR (CDCl 3 , δ, ppm): 8.25 (d, 1H), 7.29 (d, 1H), 4.71 (b, 2H).

Embodiment 2

[0032] Embodiment 2: Preparation of 4-amino-2-chloro-3-nitropyridine

[0033] In the reactor connected with stirring, thermometer and reflux system, add 70 kg of methanol, 7.5 kg (107 moles) of 3-aminopropionitrile, 17.5 kg (100 moles) of trichloronitroethylene, 0.1 kg of 4-dimethylamino Piperidine, stirred and reacted at 35-40°C for 5 hours, then added 10 kg (250 moles) of sodium hydroxide, stirred and reacted at 30-35°C for 2 hours, filtered, the filter cake was washed with 20 kg of methanol, the filtrates were combined, and the solvent was recovered by distillation. Add 45 kg of isopropanol and 0.5 kg of activated carbon to the residue, decolorize at 55-60 ° C for 1 hour, filter while hot, recrystallize, filter, and dry to obtain 15.7 kg of light yellow solid 4-amino-2-chloro-3- Nitropyridine, yield 90.5%, gas phase purity 99.7%.

Embodiment 3

[0034] Embodiment 3: Preparation of 4-amino-2-chloro-3-nitropyridine

[0035]In the reactor connected with stirring, thermometer and reflux condenser, add 60 grams of acetonitrile, 7.5 grams (0.107 moles) of 3-aminopropionitrile, 17.5 grams (0.1 moles) of trichloronitroethylene, 0.1 grams of DBU, 55- Stir and react at 60°C for 4 hours, then cool to 30-40°C, add 12.7 grams (0.12 moles) of sodium carbonate, stir and react at 40-45°C for 4 hours, then cool to 20-25°C, filter, filter cake with 20 grams of acetonitrile Wash, combine the filtrates, distill and recover the solvent, add 45 g of isopropanol and 0.5 g of activated carbon to the residue, decolorize at 55-60 ° C for 1 hour, filter while hot, recrystallize, filter, and dry to obtain 16.0 g of light yellow solid 4 -Amino-2-chloro-3-nitropyridine, yield 92.2%, gas phase purity 99.6%.

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Abstract

The invention relates to an environmental protection preparation method of 4-amino-2-chloro-3-nitropyridine. The method uses 3-amino propionitrile and trichloronitroethylene for 1,4-Addition and cyclization reaction to obtain 4-amino--2, 2, 3-trichloro-3-nitro-1, 2, 3, 6-tetrahydropyridine, and eliminates hydrogen chloride with an acid binding agent to prepare the 4-amino-2-chloro-3-nitropyridine.The method has the advantages of good reaction selectivity, good target product yield, high purity, short process flow, safe and simple operation, mild conditions, no waste acid and wastewater, environmental protection and low cost, and is carried out by a one-pot method.

Description

technical field [0001] The invention relates to a preparation method of 4-amino-2-chloro-3-nitropyridine, belonging to the technical field of chemistry and chemical engineering. Background technique [0002] 4-Amino-2-chloro-3-nitropyridine is an important pyridine derivative, which can be used in the preparation of antiviral hydrolase inhibitors, nucleoside derivatives (E1 active enzyme inhibitors) and other pharmaceutical and pesticide active compounds. [0003] The existing preparation techniques of 4-amino-2-chloro-3-nitropyridine all adopt the method of nitrating 4-amino-2-chloropyridine. For example, the world patent WO200684281 uses 90% fuming nitric acid and concentrated sulfuric acid as a mixed acid for nitration reaction to obtain 4-amino-2-chloro-3-nitropyridine and 4-amino-2-chloro-5-nitropyridine, and then 4-amino-2-chloro-3-nitropyridine was separated by column chromatography with a yield of 44%. The world patent WO2007047793 uses 70% fuming nitric acid and c...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D213/73
CPCC07D213/73
Inventor 鞠立柱戚聿新胡金山王涛
Owner XINFA PHARMA
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