CN106431903A

CN106431903A - Synthesis method for 1,2,4-triacetoxybenzene serving as Catalin medical intermediate

Info

Publication number: CN106431903A
Application number: CN201610826444.XA
Authority: CN
Inventors: 彭响亮
Original assignee: Xiamen Laiensi Special Mdt Infotech Ltd
Current assignee: Xiamen Laiensi Special Mdt Infotech Ltd
Priority date: 2015-12-23
Filing date: 2016-09-18
Publication date: 2017-02-22
Also published as: CN105503585A

Abstract

The invention discloses a synthesis method for 1,2,4-triacetoxybenzene serving as a Catalin medical intermediate. The synthesis method comprises the following steps: adding 2.9 to 3.1 mol of 4'-methyl acetoacetanilide and 200 ml of phosphoric acid solution with a certain concentration into a reaction container which is provided with a stirrer and a thermometer, wherein the stirring speed is controlled to be 200 to 260 rpm; adding 0.9 mol of p-benzoquinone in a plurality of times, wherein the temperature of a solution is controlled to be 60 to 65 DEG C, and the temperature of the reaction solution reduces naturally during a stirring process; separating out a solid after the solution is cooled, reducing the temperature of the solution to be 15 to 19 DEG C, adding 2L of potassium chloride solution with a certain concentration to separate out white crystals, reducing the temperature of the solution to be 11 to 13 DEG C, filtering, re-crystallizing a product by using an acetone solution with the mass fraction of 90 percent, and performing vacuum drying to obtain a white granular crystal product, namely, the 1,2,4-triacetoxybenzene.

Description

A kind of synthetic method of Catalin pharmaceutical intermediate 1,2,4- triacetoxyl group benzene

Technical field

The present invention relates to a kind of synthetic method of Catalin pharmaceutical intermediate 1,2,4- triacetoxyl group benzene.

Background technology

Catalin, as cataract medication, can suppress quinoness, prevent cataractous develop, and have antagonism kidney The Detoxication of upper parathyrine.The quinones substance that ArAA abnormal metabolism can be suppressed to generate, prevents insoluble protein in crystal The formation of matter, suppresses cataractous development.Its chemical constitution and insecticide ommochrome fairly similar, have the water solublity preventing crystalline lenss Albuminous degeneration, stops cataract disease progression effectiveness.Crystalline lenses degeneration can be prevented, stop the development of the cataract state of an illness.1,2,4- As Catalin pharmaceutical intermediate, its synthetic method quality, for improving pharmaceutical synthesis product quality, reduces triacetoxyl group benzene By-products content has Important Economic meaning.

Content of the invention

It is an object of the invention to provide a kind of synthetic method of Catalin pharmaceutical intermediate 1,2,4- triacetoxyl group benzene, Comprise the steps：

I (), equipped with agitator, the reaction vessel of thermometer, adds 4'- methyl vinyl acetanilide 2.9 3.1mol, certain density phosphoric acid solution 200ml, control mixing speed in 200 260rpm, add 1,4-benzoquinone several times 0.9mol, controls solution temperature at 60--65 DEG C, in whipping process, reaction solution temperature declines naturally, has solid to analyse after cooling Go out, reduce solution temperature to 15--19 DEG C, add the certain density Klorvess Liquid of 2L, separate out white crystal, reduce solution temperature Spend to 11--13 DEG C, filter, product mass fraction is 90% acetone soln recrystallization, vacuum drying, obtain white particulate knot Brilliant product 1,2,4- triacetoxyl group benzene.

Wherein, the phosphoric acid solution mass fraction described in step (i) is 80 95%.

The mass fraction of the Klorvess Liquid described in step (i) is 60--75%.

Whole course of reaction can use following reaction equation to represent：

The invention has the advantages that：Decrease the intermediate link of reaction, reduce reaction temperature and response time, improve anti- Answer yield.

Specific embodiment

With reference to being embodied as example, the invention will be further described：

Example 1：

Equipped with agitator, the reaction vessel of thermometer, add 4'- methyl vinyl acetanilide 2.9mol, quality is divided The phosphoric acid solution 200ml for 80% for the number, controls mixing speed in 200rpm, adds 1,4-benzoquinone 0.9mol several times, control solution At 60 DEG C, in whipping process, reaction solution temperature declines temperature naturally, has solid to separate out after cooling, reduction solution temperature to 15 DEG C, add the Klorvess Liquid that 2L mass fraction is 60%, separate out white crystal, reduce solution temperature to 11 DEG C, filter, product The acetone soln recrystallization being 90% with mass fraction, vacuum drying, obtain white particulate crystallized product 1,2,4- triacetoxyl group Benzene 192.78g, yield 85%.

Example 2：

Equipped with agitator, the reaction vessel of thermometer, add 4'- methyl vinyl acetanilide 3.0mol, quality is divided The phosphoric acid solution 200ml for 85% for the number, controls mixing speed in 230rpm, adds 1,4-benzoquinone 0.9mol several times, control solution At 62 DEG C, in whipping process, reaction solution temperature declines temperature naturally, has solid to separate out after cooling, reduction solution temperature to 17 DEG C, add the Klorvess Liquid that 2L mass fraction is 70%, separate out white crystal, reduce solution temperature to 12 DEG C, filter, product The acetone soln recrystallization being 90% with mass fraction, vacuum drying, obtain white particulate crystallized product 1,2,4- triacetoxyl group Benzene 197.32g, yield 87%.

Example 3：

Equipped with agitator, the reaction vessel of thermometer, add 4'- methyl vinyl acetanilide 3.1mol, quality is divided The phosphoric acid solution 200ml for 95% for the number, controls mixing speed in 260rpm, adds 1,4-benzoquinone 0.9mol several times, control solution At 65 DEG C, in whipping process, reaction solution temperature declines temperature naturally, has solid to separate out after cooling, reduction solution temperature to 19 DEG C, add the Klorvess Liquid that 2L mass fraction is 75%, separate out white crystal, reduce solution temperature to 13 DEG C, filter, product The acetone soln recrystallization being 90% with mass fraction, vacuum drying, obtain white particulate crystallized product 1,2,4- triacetoxyl group Benzene 206.39g, yield 91%.

Claims

1. a kind of synthetic method of Catalin pharmaceutical intermediate 1,2,4- triacetoxyl group benzene is it is characterised in that include following walking Suddenly：

I () equipped with agitator, the reaction vessel of thermometer, is adding 4'- methyl vinyl acetanilide 2.9 3.1mol, and one Determine the phosphoric acid solution 200ml of concentration, control mixing speed in 200 260rpm, add 1,4-benzoquinone 0.9mol several times, control molten At 60--65 DEG C, in whipping process, reaction solution temperature declines liquid temp naturally, has solid to separate out, reduce solution temperature after cooling To 15--19 DEG C, add the certain density Klorvess Liquid of 2L, separate out white crystal, reduce solution temperature to 11--13 DEG C, mistake Filter, product mass fraction is 90% acetone soln recrystallization, vacuum drying, obtains white particulate crystallized product 1,2,4- tri- second Acyloxy benzene.

2. a kind of synthetic method of Catalin pharmaceutical intermediate 1,2,4- triacetoxyl group benzene according to claim 1, it is special Levy and be, the phosphoric acid solution mass fraction described in step (i) is 80 95%.

3. a kind of synthetic method of Catalin pharmaceutical intermediate 1,2,4- triacetoxyl group benzene according to claim 1, it is special Levy and be, the mass fraction of the Klorvess Liquid described in step (i) is 60--75%.