Method for synthesizing N-(4-chlorphenyl)-1,2-phenylenediamine as key clofazimine intermediate

A technology of clofazimine and intermediates, which is applied in the field of the key intermediate N--1 of clofazimine, can solve problems such as large pollution, excess, and a large amount of metal residues

Inactive Publication Date: 2017-12-08
CHONGQING WERLCHEM FINE CHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The metal / Lewis acid system is used for reduction, and the metal needs to be greatly excessive. After the reaction is completed, a large amount of metal residue will be generated, causing huge pollution.
Using palladium carbon as a catalyst for catalytic hydrogenation reduction is relatively clean, but the catalyst is very expensive, resulting in high raw material costs

Method used

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  • Method for synthesizing N-(4-chlorphenyl)-1,2-phenylenediamine as key clofazimine intermediate
  • Method for synthesizing N-(4-chlorphenyl)-1,2-phenylenediamine as key clofazimine intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] In a dry and clean pressure reaction bottle, put 104 grams of o-fluoronitrobenzene and 200 grams of DMF, add 88 grams of triethylamine under stirring, then raise the temperature to 120 degrees under the protection of nitrogen, and the pressure rises less than 1 kilogram. 86 grams of p-chloroaniline was dissolved in 100 grams of DMF to prepare a solution, and then the solution was slowly added dropwise to the above reaction system. The temperature will rise during the dropwise addition, and the reaction temperature should be controlled within 125 degrees by cooling.

[0035] The reaction was continued at 120-130 degrees for 8 hours, and the progress of the reaction was monitored by HPLC. When the p-chloroaniline content was no longer declining, the reaction ended, and at this moment about 18% of p-chloroaniline remained. Then cool down to 60 degrees.

[0036] Add 300 grams of deionized water at 50-60 degrees to the reaction solution under stirring, and stir for 30 minu...

Embodiment 2

[0039] In the reaction flask, 87 grams of o-fluoronitrobenzene and 200 grams of DMAC were put into the reaction flask, and 94 grams of diisopropylethylamine were put into it under stirring, and then the temperature was raised to 120 degrees under the protection of nitrogen. 71 grams of p-chloroaniline was dissolved in 100 grams of DMAC to prepare a solution, and then the solution was slowly added dropwise to the above reaction system. The temperature will rise during the dropwise addition, and the reaction temperature should be controlled within 125 degrees by cooling.

[0040]The reaction was continued at 120-125 degrees for 8 hours, and the progress of the reaction was monitored by HPLC. When the p-chloroaniline content is no longer declining, the reaction ends, and at this moment about 11% of p-chloroaniline remains. Cool down to 60 degrees.

[0041] Afterwards, the treatment method was the same as in Example 1, and finally 100 g of the condensate intermediate N-(4-chloro...

Embodiment 3

[0043] In the reaction bottle, put 92 grams of o-fluoronitrobenzene and 200 grams of DMSO, put 117 grams of DBU under stirring, and then raise the temperature to 120 degrees under the protection of nitrogen. 75 grams of p-chloroaniline was dissolved in 100 grams of DMSO to prepare a solution, and then the solution was slowly added dropwise to the above reaction system. The temperature will rise during the dropwise addition, and the reaction temperature should be controlled within 125 degrees by cooling.

[0044] The reaction was continued at 120-125 degrees for 5 hours, and the progress of the reaction was monitored by HPLC. When the p-chloroaniline content is no longer declining, the reaction ends, and at this moment about 12% of p-chloroaniline remains. Cool down to 80 degrees.

[0045] Afterwards, the treatment method was the same as in Example 1, and finally 100 g of the condensate intermediate N-(4-chlorophenyl)-2-nitro-1-aniline was obtained, with a yield of 68% and an...

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Abstract

The invention provides a method for synthesizing N-(4-chlorphenyl)-1,2-phenylenediamine as a key clofazimine intermediate. The method specifically comprises the following steps: 1) by taking o-fluoronitrobenzene and p-chloroaniline as raw materials and utilizing organic base as a catalyst for condensation reaction, reacting in an organic solvent and performing conventional treatment after ending the reaction, thereby acquiring a condensation intermediate N-(4-chlorphenyl)-2-nitryl-1-aniline; 2) by utilizing metallic nickel as the catalyst, performing catalytic hydrogenation reaction on the acquired condensation intermediate in the organic solvent and performing conventional treatment after reducing, thereby acquiring a rough product of N-(4-chlorphenyl)-1,2-phenylenediamine; and 3) re-crystallizing the acquired rough product with the organic solvent, thereby acquiring the end product.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and more specifically relates to a method for synthesizing N-(4-chlorophenyl)-1,2-phenylenediamine, a key intermediate of chlorofazimine. Background technique [0002] Clofazimine (structural formula below), also known as clofazimine, was developed in the 1960s. The compound was originally hoped to be used as an anti-TB drug, but early studies showed it had little effect against TB. Later, the compound was used in the treatment of leprosy and achieved good results. Today, this compound is used as one of the few effective drugs for anti-leprosy, and is widely used in combined chemotherapy of MB type leprosy and type II leprosy reaction. [0003] [0004] At present, tuberculosis, especially multidrug-resistant tuberculosis, has been showing a high incidence trend, which seriously threatens human health. However, no major progress has been made in the discovery of anti-TB drugs. Some first-l...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C209/60C07C209/36C07C211/52
CPCC07C209/36C07C209/60C07C211/52
Inventor 杨冰
Owner CHONGQING WERLCHEM FINE CHEM
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