CN105503585A - Synthesis method of 1,2,4-triacetoxybenzene serving as catalin drug intermediate - Google Patents
Synthesis method of 1,2,4-triacetoxybenzene serving as catalin drug intermediate Download PDFInfo
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- CN105503585A CN105503585A CN201510982723.0A CN201510982723A CN105503585A CN 105503585 A CN105503585 A CN 105503585A CN 201510982723 A CN201510982723 A CN 201510982723A CN 105503585 A CN105503585 A CN 105503585A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
- C07C67/52—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Abstract
A synthesis method of 1,2,4-triacetoxybenzene serving as a catalin drug intermediate comprises steps as follows: 2.9-3.1 mol of 4'-methyl-acetoacetanilide and 200 ml of a phosphoric acid solution with certain concentration are added to a reaction container provided with a stirrer and a thermometer, the stirring speed is controlled in the range from 200 rpm to 260 rpm, 0.9 mol of p-benzoquinone is added several times, the temperature of the solution is controlled in the range of 60-65 DEG C, the temperature of the reaction solution is naturally reduced in the stirring process, solids are separated out after the solution is cooled, the temperature of the solution is reduced to 15-19 DEG C, 2L of a potassium chloride solution with certain concentration is added, white crystals are separated out, the temperature of the solution is reduced to 11-13 DEG C, filtration is performed, a product is recrystallized with an acetone solution with the mass percentage being 90% and dried in the vacuum, and the white granular crystal product 1,2,4-triacetoxybenzene is obtained.
Description
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 quinones, prevents cataractous development, and has the adrenergic detoxification of antagonism.The quinones substance that aromatic amino acid abnormal metabolism can be suppressed to generate, prevents the formation of insoluble protein in crystal, suppresses cataractous development.Its chemical structure and insect ommochrome fairly similar, have the water-soluble protein sex change preventing crystalline, stops cataract disease progression effectiveness.Lens sex change can be prevented, stop the development of the cataract state of an illness.1,2,4-triacetoxyl group benzene is as Catalin pharmaceutical intermediate, and its synthetic method is good and bad for raising pharmaceutical synthesis quality product, reduces by-products content and has Important Economic meaning.
Summary of the invention
The object of the present invention is to provide a kind of synthetic method of Catalin pharmaceutical intermediate 1,2,4-triacetoxyl group benzene, comprise the steps:
I () is being equipped with agitator, in the reaction vessel of thermometer, add 4'-methyl vinyl Acetanilide 2.9-3.1mol, certain density phosphoric acid solution 200ml, control stirring velocity at 200-260rpm, add para benzoquinone 0.9mol several times, control solution temperature at 60--65 DEG C, in whipping process, reaction soln temperature declines naturally, solid is had to separate out after cooling, reduce solution temperature 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, filter, product massfraction is the acetone soln recrystallization of 90%, vacuum-drying, obtain white particulate crystallized product 1, 2, 4-triacetoxyl group benzene.
Wherein, the phosphoric acid solution massfraction described in step (i) is 80-95%.
The massfraction of the Klorvess Liquid described in step (i) is 60--75%.
Whole reaction process can represent with following reaction formula:
The invention has the advantages that: the middle-chain decreasing reaction, reduce temperature of reaction and reaction times, improve reaction yield.
Embodiment
Below in conjunction with concrete embodiment, the invention will be further described:
A kind of synthetic method of Catalin pharmaceutical intermediate 1,2,4-triacetoxyl group benzene
Example 1:
Be equipped with agitator, in the reaction vessel of thermometer, add 4'-methyl vinyl Acetanilide 2.9mol, massfraction is the phosphoric acid solution 200ml of 80%, control stirring velocity at 200rpm, add para benzoquinone 0.9mol several times, control solution temperature at 60 DEG C, in whipping process, reaction soln temperature declines naturally, solid is had to separate out after cooling, reduce solution temperature to 15 DEG C, add the Klorvess Liquid that 2L massfraction is 60%, separate out white crystal, reduce solution temperature to 11 DEG C, filter, product massfraction is the acetone soln recrystallization of 90%, vacuum-drying, obtain white particulate crystallized product 1, 2, 4-triacetoxyl group benzene 192.78g, yield 85%.
Example 2:
Be equipped with agitator, in the reaction vessel of thermometer, add 4'-methyl vinyl Acetanilide 3.0mol, massfraction is the phosphoric acid solution 200ml of 85%, control stirring velocity at 230rpm, add para benzoquinone 0.9mol several times, control solution temperature at 62 DEG C, in whipping process, reaction soln temperature declines naturally, solid is had to separate out after cooling, reduce solution temperature to 17 DEG C, add the Klorvess Liquid that 2L massfraction is 70%, separate out white crystal, reduce solution temperature to 12 DEG C, filter, product massfraction is the acetone soln recrystallization of 90%, vacuum-drying, obtain white particulate crystallized product 1, 2, 4-triacetoxyl group benzene 197.32g, yield 87%.
Example 3:
Be equipped with agitator, in the reaction vessel of thermometer, add 4'-methyl vinyl Acetanilide 3.1mol, massfraction is the phosphoric acid solution 200ml of 95%, control stirring velocity at 260rpm, add para benzoquinone 0.9mol several times, control solution temperature at 65 DEG C, in whipping process, reaction soln temperature declines naturally, solid is had to separate out after cooling, reduce solution temperature to 19 DEG C, add the Klorvess Liquid that 2L massfraction is 75%, separate out white crystal, reduce solution temperature to 13 DEG C, filter, product massfraction is the acetone soln recrystallization of 90%, vacuum-drying, obtain white particulate crystallized product 1, 2, 4-triacetoxyl group benzene 206.39g, yield 91%.
Claims (3)
1. the synthetic method of Catalin pharmaceutical intermediate 1,2, a 4-triacetoxyl group benzene, is characterized in that, comprise the steps:
I () is being equipped with agitator, in the reaction vessel of thermometer, add 4'-methyl vinyl Acetanilide 2.9-3.1mol, certain density phosphoric acid solution 200ml, control stirring velocity at 200-260rpm, add para benzoquinone 0.9mol several times, control solution temperature at 60--65 DEG C, in whipping process, reaction soln temperature declines naturally, solid is had to separate out after cooling, reduce solution temperature 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, filter, product massfraction is the acetone soln recrystallization of 90%, vacuum-drying, obtain white particulate crystallized product 1, 2, 4-triacetoxyl group benzene.
2. the synthetic method of a kind of Catalin pharmaceutical intermediate 1,2,4-triacetoxyl group benzene according to claim 1, it is characterized in that, the phosphoric acid solution massfraction described in step (i) is 80-95%.
3. the synthetic method of a kind of Catalin pharmaceutical intermediate 1,2,4-triacetoxyl group benzene according to claim 1, it is characterized in that, the massfraction of the Klorvess Liquid described in step (i) is 60--75%.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510982723.0A CN105503585A (en) | 2015-12-23 | 2015-12-23 | Synthesis method of 1,2,4-triacetoxybenzene serving as catalin drug intermediate |
| CN201610826444.XA CN106431903A (en) | 2015-12-23 | 2016-09-18 | Synthesis method for 1,2,4-triacetoxybenzene serving as Catalin medical intermediate |
| AU2016102230A AU2016102230A4 (en) | 2015-12-23 | 2016-12-23 | Catalin drug intermediates 1,2,4-trihydroxybenzene triacetate synthesis method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510982723.0A CN105503585A (en) | 2015-12-23 | 2015-12-23 | Synthesis method of 1,2,4-triacetoxybenzene serving as catalin drug intermediate |
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| Publication Number | Publication Date |
|---|---|
| CN105503585A true CN105503585A (en) | 2016-04-20 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201510982723.0A Pending CN105503585A (en) | 2015-12-23 | 2015-12-23 | Synthesis method of 1,2,4-triacetoxybenzene serving as catalin drug intermediate |
| CN201610826444.XA Pending CN106431903A (en) | 2015-12-23 | 2016-09-18 | Synthesis method for 1,2,4-triacetoxybenzene serving as Catalin medical intermediate |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201610826444.XA Pending CN106431903A (en) | 2015-12-23 | 2016-09-18 | Synthesis method for 1,2,4-triacetoxybenzene serving as Catalin medical intermediate |
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| CN (2) | CN105503585A (en) |
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2015
- 2015-12-23 CN CN201510982723.0A patent/CN105503585A/en active Pending
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2016
- 2016-09-18 CN CN201610826444.XA patent/CN106431903A/en active Pending
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Application publication date: 20160420 |