CN103183588A

CN103183588A - Preparation method of veratrole

Info

Publication number: CN103183588A
Application number: CN2013100826229A
Authority: CN
Inventors: 张梅; 彭学东; 赵金召; 弓旻
Original assignee: ZHANGJIAGANG WEISHENG BIOLOGICAL PHARMACEUTICAL CO Ltd
Current assignee: ZHANGJIAGANG WEISHENG BIOLOGICAL PHARMACEUTICAL CO Ltd
Priority date: 2013-03-15
Filing date: 2013-03-15
Publication date: 2013-07-03

Abstract

The invention relates to a synthetic method of veratrole which is an important medicinal chemical midbody. Pyrocatechol is taken as raw material, and high-purity veratrole oil can be obtained through methylation. The process has the advantages of mild condition, convenience in operation, high yield, good quality, low energy consumption, environmental protection, safety and the like, and is suitable for industrial production.

Description

A kind of preparation method of veratrole

Technical field

The present invention relates to the preparation of chemical intermediate, a kind of preparation method of veratrole is to be the method for raw material chemosynthesis veratrole with the pyrocatechol specifically.

Background technology

Veratrole (Veratrole) has another name called adjacent dme, and CAS NO.91-16-7, its chemical name are 1,2-dimethoxy benzene, and molecular formula is C ₈H ₁₀O ₂, molecular weight is 138.16.Colourless liquid or crystallization are dissolved in ethanol, ether and fatty oil, are slightly soluble in water, and fusing point is 15 ℃.Veratrole has industrial use widely as a kind of pharmaceutical chemistry synthesis material, is a kind of important fine chemical material, equally also is one of important source material of a kind of compound essence and field of medicaments.Be mainly used in synthetic veratraldehyde, tetrahydropalmatine, isoptin, lactic acid, mensuration glycerine etc. in the calibrating blood.At present, relevant veratrole preparation technology reports less.Most is raw material with pyrocatechol or methyl catechol.Wherein, utilizing pyrocatechol and methyl-sulfate to carry out methylation reaction is industrial the most frequently used method.Because methyl-sulfate belongs to hypertoxic chemical, careless slightly meeting causes significant damage to human body and environment in the use.Simultaneously, generate sulfuric acid in the reaction, severe corrosion equipment, and mass consumption alkali lye also can increase the difficulty of separating and purifying.Another method is to use pyrocatechol to generate sodium salt with the sodium hydroxide effect earlier, gets finished product with the methyl chloride reaction then under certain pressure.Comparatively harsh and yield is not high for reaction conditions control.How solving the feasibility of industrialized production and the problem of ease-to-operate, reduce environmental pollution, reduce production costs, is present main research direction.

Summary of the invention

The object of the present invention is to provide a kind of is starting raw material with the pyrocatechol, many shortcomings such as the environmental safety harm that overcomes prior art is big, production cost is higher, reaction conditions is not easy to control, equipment corrosion is serious, schedule of operation is loaded down with trivial details, provide a kind of mild condition, easy to operate, yield is high, quality good, energy consumption is low, the optimization synthetic method of the veratrole of the suitable suitability for industrialized production of Environmental Safety.

The present invention adopts following technical scheme:

Be raw material with the pyrocatechol, add the inorganic strong alkali aqueous solution, under the phase-transfer catalyst effect, carry out methylation reaction with methylating reagent, purified processing, products therefrom is high purity black false hellebore ether oil.

The mol ratio of described pyrocatechol, inorganic strong alkali, phase-transfer catalyst, methylating reagent is 1.0: 1.5-3.0: 0.01-0.05: 1.0-2.0.The optimum mol ratio is 1.0: 2.0: 0.02: 1.5.

Described methylating reagent is methylcarbonate.

The concentration of the described inorganic strong alkali aqueous solution is 35%-50%.Optimum concentration is 40%.

Described preparation method's temperature of reaction is 80-110 ℃.Optimal temperature is 95 ℃.

The described reaction times is 4-10 hour.The optimum time is 8 hours.

Also comprise with soda lye wash gained mixture, obtain thick oil.70-90 ℃ following underpressure distillation 30-50 minute, get finished product.

Advantage of the present invention is:

1, adopts novel environment friendly material carbon dimethyl phthalate as methylating reagent, reduce environmental toxicity, operational safety, and the alkali consumption problem of avoiding using sulfated dimethyl ester to cause.

2, technological process is easy, easy handling, and the reaction times is short, and energy consumption is low.

3, entire reaction is raw materials used cheap and easy to get, and yield is good, and total recovery reaches as high as 98%, and purity reaches more than 99.5%.

Description of drawings

Fig. 1 is the building-up reactions formula of veratrole

Embodiment

Following case study on implementation is used for explanation the present invention, but is not used for limiting the scope of the invention.

Embodiment 1:

Add the 140mL methylcarbonate in 500mL glass there-necked flask, open and stir, add the 110g pyrocatechol, add catalyzer Tetrabutyl amonium bromide 6g, drip 40% sodium hydroxide solution 200mL, be warming up to backflow after adding, reflux temperature is about 95 ℃.Backflow 8h.Reflux after the end, leave standstill 1h, tell lower aqueous layer.The upper strata oil reservoir adds liquid caustic soda, and washing once.Obtain thick oily 143kg.Then thick oil is carried out underpressure distillation and obtain finished product 133g, yield 98%, purity 99.5% (GC).

Embodiment 2:

Add the 120mL methylcarbonate in 500mL glass there-necked flask, open and stir, add the 110g pyrocatechol, add catalyzer Tetrabutyl amonium bromide 6g, drip 40% sodium hydroxide solution 200mL, be warming up to backflow after adding, reflux temperature is about 95 ℃.Backflow 8h.Reflux after the end, leave standstill 1h, tell lower aqueous layer.The upper strata oil reservoir adds liquid caustic soda, and washing once.Obtain thick oily 132kg.Then thick oil is carried out underpressure distillation and obtain finished product 122g, yield 90%, purity 99.6% (GC).

Embodiment 3:

In 500mL glass there-necked flask, add the 140mL methylcarbonate, open and stir, add the 110g pyrocatechol, add catalyzer cetyl trimethylammonium bromide 6g, drip 40% sodium hydroxide solution 200mL, be warming up to backflow after adding, reflux temperature is about 95 ℃.Backflow 8h.Reflux after the end, leave standstill 1h, tell lower aqueous layer.The upper strata oil reservoir adds liquid caustic soda, and washing once.Obtain thick oily 137kg.Then thick oil is carried out underpressure distillation and obtain finished product 126g, yield 93%, purity 99.6% (GC).

Embodiment 4:

In 500mL glass there-necked flask, add the 140mL methylcarbonate, open and stir, add the 110g pyrocatechol, add catalyzer Tetrabutyl amonium bromide 6g, drip 40% sodium hydroxide solution 200mL, add the back and heat up about 85 ℃.Reaction 10h.Leave standstill 1h, tell lower aqueous layer.The upper strata oil reservoir adds liquid caustic soda, and washing once.Obtain thick oily 129kg.Then thick oil is carried out underpressure distillation and obtain finished product 118g, yield 87%, purity 99.0% (GC).

Embodiment 5:

Add the 140mL methylcarbonate in 500mL glass there-necked flask, open and stir, add the 110g pyrocatechol, add catalyzer Tetrabutyl amonium bromide 6g, Dropwise 35 % sodium hydroxide solution 200mL adds the back and heats up about 85 ℃.Reaction 10h.Leave standstill 1h, tell lower aqueous layer.The upper strata oil reservoir adds liquid caustic soda, and washing once.Obtain thick oily 131kg.Then thick oil is carried out underpressure distillation and obtain finished product 121g, yield 89%, purity 99.2% (GC).

Claims

1. a veratrole preparation method is characterized in that with the pyrocatechol being raw material, adds the inorganic strong alkali aqueous solution, carries out methylation reaction with methylating reagent under the phase-transfer catalyst effect, and treated, products therefrom is high purity black false hellebore ether oil.

2. the synthetic method of veratrole according to claim 1, the mol ratio that it is characterized in that described pyrocatechol, inorganic strong alkali, phase-transfer catalyst, methylating reagent is 1.0: 1.5-3.0: 0.01-0.05: 1.0-2.0.

3. be methylcarbonate according to claim 1,2 described methylating reagents.

4. claim 1,2 described inorganic strong alkalis are sodium hydroxide, potassium hydroxide.

5. claim 1,2,4 described inorganic strong alkali concentration of aqueous solution are 35%-50%.

6. claim 1,2 described phase-transfer catalysts are Tetrabutyl amonium bromide, cetyl trimethylammonium bromide, dodecyl benzyl dimethyl ammonium chloride, two octadecyl dimethyl brometo de amonio, octadecyl dimethyl hydroxyethyl ammonium nitrate.

7. the synthetic method of veratrole according to claim 1, the temperature of reaction that it is characterized in that described pyrocatechol and methylating reagent is 80-110 ℃.

8. the synthetic method of veratrole according to claim 1, the reaction times that it is characterized in that described pyrocatechol and methylating reagent is 4-10 hour.