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Method for coproducing key intermediates of quinolone medicines by using o-dichlorobenzene as raw material

A technology of o-dichlorobenzene and quinolones, which is applied in the field of preparation of pharmaceutical intermediates, can solve the problems of diazonium and fluorine decomposition hazards, unfriendly environment, high price, etc., to reduce pollution, solve high production costs, and clean the environment Effect

Active Publication Date: 2011-11-23
内蒙古永太化学有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the price of raw materials such as 2,6-dichloroaniline and 2,6-difluorobromoaniline is relatively high, and the risk of diazofluorine decomposition is not friendly to the environment.

Method used

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  • Method for coproducing key intermediates of quinolone medicines by using o-dichlorobenzene as raw material
  • Method for coproducing key intermediates of quinolone medicines by using o-dichlorobenzene as raw material
  • Method for coproducing key intermediates of quinolone medicines by using o-dichlorobenzene as raw material

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Put 210g of o-dichlorobenzene into a 500ml four-necked flask, raise the temperature to 90°C, add dropwise 340g of mixed acid (100g of 69% nitric acid and 240g of 98% sulfuric acid), control the reaction at 95-100°C, keep warm for 2 hours after the addition, and divide the mixture after cooling. layer, reclaim sulfuric acid, wash the organic phase with water, neutralize, and obtain 210g3, 4-dichloronitrobenzene (content ≥ 99.5%), 53g 2, 3-dichloronitrobenzene (content ≥ 99.6%), the total yield was 95.8%.

[0036] 2. Step (2)

[0037] 1. 2,3-dichloronitrobenzene is fluorinated to obtain 2-fluoro-3-chloronitrobenzene, then chlorinated to obtain 2,6-dichlorofluorobenzene, and nitrated to obtain 2,4-dichloro-3 - fluoronitrobenzene, finally fluorinated to give 2,3,4-trifluoronitrobenzene,

[0038] 1.1. Fluorination reaction

Embodiment 2

[0040] Put 400g (2.08mol) of 2,3-dichloronitrobenzene into a 500ml four-neck flask, raise the temperature to 140°C and put in 112g (1.93mol) of KF, carry out dehydration under reduced pressure, keep warm at 140-150°C for 3 hours, after dehydration Raise the temperature to 140°C, add 6.6g (0.06mol) tetramethylammonium chloride into the reaction kettle between 150°C and 160°C, keep it at 165±5°C for 8 hours after adding, stop the reaction, cool, wash with water, and separate After the layer, the organic phase was first distilled and then rectified, and 100 g of 2,3-dichloronitrobenzene was recovered to generate 240 g of 2-fluoro-3-chloronitrobenzene, with a content of 99.6% and a yield of 87.6%.

Embodiment 3

[0042] According to embodiment 2, phase transfer catalyst tetramethylammonium chloride is reduced to 3.3g (0.03mol) direct reaction, reclaims 2,3-dichloronitrobenzene 230g, generates 2-fluoro-3-chloronitrobenzene 108g, Content 97.8%, yield 69.5%.

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Abstract

The invention relates to the field of methods for preparing medicinal intermediates, in particular to the field of methods for preparing key intermediates of quinolone medicines, and develops a method for coproducing the key intermediates of the quinolone medicines by using o-dichlorobenzene as a raw material. The method comprises the following steps of: nitrifying the o-dichlorobenzene serving as the raw material, and performing distillation, purification and stepwise crystallization to obtain 2,3-dichloronitrobenzene and 3,4-dichloronitrobenzene; performing fluoridation on the 2,3-dichloronitrobenzene to obtain 3-chloro-2-fluoronitrobenzene, performing chlorination to obtain 2,6-dichlorofluorobenzene, performing nitration to obtain 1,3-dichloro-2-fluoro-4-nitrobenzene, and finally performing fluoridation to obtain 2,3,4-trifluoronitrobenzene; and performing fluoridation on the 2,3,4-trifluoronitrobenzene to obtain 3-chloro-4-fluoronitrobenzene, performing chlorination to obtain 1,3-dichloro-4-fluorobenzene, and finally performing acylation reaction on the 1,3-dichloro-4-fluorobenzene and acetylchloride to obtain 2,4-dichloro-5-fluoroacetophenone.

Description

technical field [0001] The invention relates to the field of preparation methods of pharmaceutical intermediates, in particular to the field of preparation methods of key intermediates of quinolones, and develops a method for co-producing key intermediates of quinolones with o-dichlorobenzene as raw materials. Background technique [0002] 2-fluoro-3-chloronitrobenzene, 4-fluoro-3-chloronitrobenzene, 2,6-dichlorofluorobenzene, 2,4-dichlorofluorobenzene, 2,3,4-trifluoronitrobenzene Benzene and 2,4-dichloro-5-fluoroacetophenone are key intermediates for the preparation of quinolones such as ciprofloxacin, norfloxacin hydrochloride, ofloxacin and pesticides. [0003] Chinese patent 92107812.9 reports that o-dichlorobenzene is used as a raw material, nitrated by a mixed acid of concentrated nitric acid and concentrated sulfuric acid, and the dried organic layer is fluorinated under the action of dimethyl sulfoxide and potassium fluoride, separated and purified. 4-Fluoro-3-chlor...

Claims

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Application Information

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IPC IPC(8): C07C49/807C07C45/46
Inventor 何人宝邵鸿鸣
Owner 内蒙古永太化学有限公司
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