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Synthesis method of N-methyl-1,2-benzenediamine dihydrochloride

A technology of methyl-o-phenylenediamine hydrochloride and methyl-o-phenylenediamine, which is applied in the field of synthesizing intermediates of the antihypertensive drug tesamitan, can solve the problems of difficult product quality assurance, low purity of o-diphenylamine, Problems such as low utilization rate, to achieve the effect of improving utilization rate, less impurities, and high preparation purity

Inactive Publication Date: 2019-09-24
武汉本杰明医药股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] Telmisartan has an outstanding effect in the treatment of hypertension than the same hypertension medicine, and as the intermediate N-methyl o-phenylenediamine hydrochloride for the preparation of the medicine, it is especially important in the preparation process. In the prior art, methyl iodide or methyl bromide or dimethyl sulfate or dimethyl carbonate are usually used as the alkylating agent. This process route is very easy to produce N, and its product quality is difficult to guarantee. At the same time, o-diphenylamine prepared by common catalysts The purity is not high and the utilization rate is low

Method used

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  • Synthesis method of N-methyl-1,2-benzenediamine dihydrochloride
  • Synthesis method of N-methyl-1,2-benzenediamine dihydrochloride
  • Synthesis method of N-methyl-1,2-benzenediamine dihydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Add 200g of o-chloronitrobenzene and 197g of monomethylamine aqueous solution into a 1L autoclave, seal it, pressurize it with nitrogen to 0.5MPa, start to raise the temperature slowly, when T=90°C, stop heating, the reaction enters a spontaneous state, exotherm , the temperature continues to rise (the highest temperature can reach 110°C, and the maximum pressure is 1.2MPa). When the temperature no longer rises, continue to raise the temperature to 120°C, and keep the temperature for 5h. After the reaction was finished, the temperature was lowered, the layers were separated, and the lower oil phase was taken to obtain 190 g of N-methyl-o-nitroaniline.

[0034] Add 120g of ethanol and 100g of N-methyl-o-nitroaniline to a 1L reaction flask in turn, start stirring, raise the temperature to 70-75°C, keep a slight reflux, slowly add hydrazine hydrate dropwise, after the addition is complete, keep it warm at 80°C Reaction 20h. After the reaction was finished, filter with suc...

Embodiment 2

[0037] Add 200g of o-chloronitrobenzene and 197g of monomethylamine aqueous solution into a 1L autoclave, seal it, pressurize it with nitrogen to 0.5MPa, start to raise the temperature slowly, when T=90°C, stop heating, the reaction enters a spontaneous state, exotherm , the temperature continues to rise (the highest temperature can reach 110°C, and the maximum pressure is 1.2MPa). When the temperature no longer rises, continue to raise the temperature to 120°C, and keep the temperature for 5h. After the reaction was finished, the temperature was lowered, the layers were separated, and the lower oil phase was taken to obtain 190 g of N-methyl-o-nitroaniline.

[0038] Add 120g of ethanol, 100g of N-methyl o-nitroaniline, 7g of FeCl to the 1L reaction flask 3 , 7g of activated carbon, start stirring, raise the temperature to 70-75°C, keep a slight reflux, slowly add hydrazine hydrate dropwise to it, after the addition is complete, keep the temperature at 80°C for 20h. After the...

Embodiment 3

[0041] Add 200g of o-chloronitrobenzene and 197g of monomethylamine aqueous solution into a 1L autoclave, seal it, pressurize it with nitrogen to 0.5MPa, start to raise the temperature slowly, when T=90°C, stop heating, the reaction enters a spontaneous state, exotherm , the temperature continues to rise (the highest temperature can reach 110°C, and the maximum pressure is 1.2MPa). When the temperature no longer rises, continue to raise the temperature to 120°C, and keep the temperature for 5h. After the reaction was finished, the temperature was lowered, the layers were separated, and the lower oil phase was taken to obtain 190 g of N-methyl-o-nitroaniline.

[0042] Add 120g of ethanol, 100g of N-methyl-o-nitroaniline, and 10g of loaded lacquer nickel finished product in sequence to a 1L reaction bottle, start stirring, raise the temperature to 70-75°C, keep a slight reflux, and slowly add hydrazine hydrate dropwise, After the dropwise addition, keep the reaction at 80°C for ...

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Abstract

The invention discloses a synthesis method of N-methyl-1,2-benzenediamine dihydrochloride. The synthesis method is characterized by comprising the following steps that 1, o-chloronitrobenzene and a monomethylamine aqueous solution are subjected to a sealing reaction, after the reaction is completed, cooling, standing and layering are conducted, and a lower-layer oil phase is collected to obtain N-methyl-2-nitroaniline; 2, a catalyst is added to a mixed solution of ethyl alcohol and the N-methyl-2-nitroaniline obtained in step 1, after mixing and heating, hydrazine hydrate is slowly dropwise added to the mixed solution, and after drop addition is completed, a heat preservation reaction is conducted; after the reaction is completed, suction filtration is conducted, and a suction filtration mother solution is reserved to obtain N-methyl-o-phenylenediamine; 3, liquid caustic soda, water and EDTA are added to the N-methyl-o-phenylenediamine obtained in step 2 for mixing, after cooling is conducted, dichloromethane is added, stirring, extraction, standing and layering are conducted, a lower-layer oil phase is collected, and through separation and purification, the target product N-methyl-1,2-benzenediamine dihydrochloride is obtained. The N-methyl-1,2-benzenediamine dihydrochloride product prepared through the method has high purity and few impurities and can be widely applied to the field of intermediate synthesis of a medicine tishamitan for reducing the blood pressure.

Description

technical field [0001] The invention relates to the field of synthesizing intermediates of the antihypertensive drug tesamitan. More specifically, the present invention relates to a kind of synthetic method of N-methyl o-phenylenediamine hydrochloride. Background technique [0002] Telmisartan has outstanding effect in the medicine of hypertension than equivalent hypertension medicine treatment, and as the intermediate N-methyl o-phenylenediamine hydrochloride of preparing this medicine, it is especially important in the preparation process, In the prior art, methyl iodide or methyl bromide or dimethyl sulfate or dimethyl carbonate are usually used as the alkylating agent. First, this process route is very easy to generate N, and its product quality is difficult to guarantee. At the same time, o-diphenylamine prepared by common catalyst The purity is not high and the utilization rate is low. Contents of the invention [0003] The purpose of this invention is to provide a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C209/10C07C209/32C07C209/74C07C211/52C07C211/51
CPCC07C209/10C07C209/325C07C209/74C07C211/52C07C211/51
Inventor 朱桂锋胡梓潼
Owner 武汉本杰明医药股份有限公司
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