CN112142579A

CN112142579A - Preparation process of 2-hydroxy-4-methoxybenzophenone

Info

Publication number: CN112142579A
Application number: CN201910564282.0A
Authority: CN
Inventors: 李斌栋; 李斌鸿; 王冉
Original assignee: Jiangsu Ziqi Chemical Technology Co ltd
Current assignee: Jiangsu Ziqi Chemical Technology Co ltd
Priority date: 2019-06-27
Filing date: 2019-06-27
Publication date: 2020-12-29

Abstract

The invention discloses a preparation process of 2-hydroxy-4-methoxybenzophenone, which takes 2, 4-dihydroxy benzophenone and methyl halide as initial raw materials and generates the 2-hydroxy-4-methoxybenzophenone under the action of alkali liquor and a phase transfer catalyst. The invention uses cheap and easily obtained 2, 4-dihydroxy benzophenone and halogenated methane as starting materials, and the preparation method has the advantages of simple process, environmental protection, relatively high product yield and purity and wide industrial application prospect.

Description

Preparation process of 2-hydroxy-4-methoxybenzophenone

Technical Field

The invention relates to a preparation process of 2-hydroxy-4-methoxybenzophenone, and belongs to the field of organic synthetic chemistry.

Background

The trade name of 2-Hydroxy-4-methoxybenzophenone is UV-9, the English name is 2-Hydroxy-4-methoxybenzophenone, and the structural formula:

the 2-hydroxy-4-methoxybenzophenone is light yellow crystal powder, and is named as an ultraviolet absorbent UV-9 because the 2-hydroxy-4-methoxybenzophenone can effectively absorb ultraviolet light with the wavelength of 290-400 nm and then emits fluorescence to recover. Because of the excellent characteristics of 2-hydroxy-4-methoxybenzophenone, the 2-hydroxy-4-methoxybenzophenone has been widely applied in the fields of aerospace, medicine and polymer, the market demand of 2-hydroxy-4-methoxybenzophenone is far greater than the supply in recent years, and the new method for synthesizing 2-hydroxy-4-methoxybenzophenone has been the heat of chemist's researchAnd (4) point. The prior production process of 2-hydroxy-4-methoxybenzophenone comprises the following steps:

the method comprises the following steps:

2-hydroxy-4-methoxybenzophenone (JP 2017137276A; Benzophenone derivatives as cysteine protease inhibitors and biological activity assay of Leishmania (L.)) is obtained by methylation reaction using 2, 4-dihydroxybenzophenone and dimethyl sulfate as initial raw materials

The method uses highly toxic dimethyl sulfate as initial raw material, has low safety factor, more byproducts and environmental pollution, and is not beneficial to industrial production.

The method 2 comprises the following steps:

resorcinol, benzoyl chloride and dimethyl sulfate are used as initial raw materials, and 2-hydroxy-4-methoxybenzophenone (CN 104163756A) is prepared through methylation, Friedel-Crafts acylation and hydrolysis.

Although the method reduces the reaction steps compared with the traditional method and has higher yield, the method still has more reaction steps and complicated operation, and also uses highly toxic substances of dimethyl sulfate, thereby being not beneficial to industrial production.

The method 3 comprises the following steps:

2, 4-dimethoxy benzophenone is taken as an initial raw material and is mixed with a Lewis acid catalyst to obtain the 2-hydroxy-4-methoxy benzophenone (CN 103467267A).

The catalyst used in the method is Lewis acid, and the Lewis acid has corrosiveness, so that the service life of equipment is shortened, the corrosion resistance of the equipment is required to be improved, the production cost is increased, and the raw material is not easy to obtain and is not suitable for industrial production.

Disclosure of Invention

The technical problem to be solved by the present invention is to provide a process for preparing 2-hydroxy-4-methoxybenzophenone, which is directed to the shortcomings of the prior art.

The technical scheme for realizing the purpose of the invention is as follows:

the production process of the invention comprises the following steps:

the method comprises the following specific steps:

and sequentially adding 2, 4-dihydroxy benzophenone, alkali liquor, a phase transfer catalyst, a solvent and methyl halide into the high-pressure kettle. Heating to 60-140 ℃, maintaining the pressure in the kettle at 0.3-0.5 MPa, reacting for 1-4 hours, cooling to room temperature, extracting the reaction liquid with n-hexane, separating liquid, and concentrating to obtain the 2-hydroxy-4-methoxybenzophenone.

According to the production process, the alkali liquor is potassium hydroxide solution, sodium hydroxide solution, potassium carbonate solution or sodium carbonate solution.

According to the production process, the mass fraction of the alkali liquor is 20-50 wt%.

According to the production process, the phase transfer catalyst is tetrabutylammonium chloride, tetrabutylammonium bromide, PEG-200 or PEG-400.

According to the production process, the solvent is toluene, xylene, chlorobenzene or butyl acetate.

According to the production process, the methyl halide is methyl chloride, methyl bromide or methyl iodide.

According to the production process, the molar ratio of the 2, 4-dihydroxy benzophenone to the halogenated methane is 1: 1-2.

According to the production process, the molar ratio of the 2, 4-dihydroxy benzophenone to the alkali liquor is 1: 1-1.5.

According to the production process, the molar weight of the phase transfer catalyst is 0.5-5% of that of the 2, 4-dihydroxy benzophenone.

Compared with the prior art, the invention has the following advantages:

1. the invention uses the methyl halide to replace the dimethyl sulfate as the initial raw material in the traditional process, thereby solving the potential safety hazard in the production from the source;

2. the synthesis method only relates to methylation reaction, reduces the reaction steps of Friedel-Crafts acylation and the like compared with the traditional process, and greatly improves the production efficiency;

3. the byproducts in the reaction process are only salt and water, so that the method is pollution-free and environment-friendly;

4. no complex post-treatment operation procedure, simple separation, energy saving and consumption reduction, higher yield and purity of the product, low cost and wide application prospect.

Detailed Description

The present invention will be described in detail below with reference to specific examples.

Example 1

21.4g of 2, 4-dihydroxybenzophenone, 53g of sodium carbonate aqueous solution (20 wt%), 0.28g of tetrabutylammonium chloride, 100ml of chlorobenzene and 100ml of chloromethane (1.0M in MTBE) were sequentially added into an autoclave, the temperature was raised to 100 ℃, the pressure in the autoclave was maintained at 0.3MPa, after 2 hours of reaction, cooling was performed to room temperature, and the reaction solution was washed with n-hexane, separated and concentrated to obtain 2-hydroxy-4-methoxybenzophenone, with a yield of 91% and a purity of 99%.

Example 2

21.4g of 2, 4-dihydroxybenzophenone, 53g of sodium carbonate aqueous solution (20 wt%), 0.28g of tetrabutylammonium chloride, 100ml of toluene and 100ml of chloromethane (1.0M in MTBE) were sequentially added into an autoclave, the temperature was raised to 100 ℃, the pressure in the autoclave was maintained at 0.3MPa, after 2 hours of reaction, cooling was performed to room temperature, and the reaction solution was washed with n-hexane, separated and concentrated to obtain 2-hydroxy-4-methoxybenzophenone, with a yield of 90% and a purity of 99%.

Example 3

21.4g of 2, 4-dihydroxybenzophenone, 53g of sodium carbonate aqueous solution (20 wt%), 0.28g of tetrabutylammonium chloride, 100ml of chlorobenzene and 100ml of chloromethane (1.0M in MTBE) were sequentially added into an autoclave, the temperature was raised to 120 ℃, the pressure in the autoclave was maintained at 0.3MPa, after 2 hours of reaction, cooling was performed to room temperature, and the reaction solution was washed with n-hexane, separated and concentrated to obtain 2-hydroxy-4-methoxybenzophenone, with a yield of 88% and a purity of 98%.

Example 4

21.4g of 2, 4-dihydroxybenzophenone, 53g of sodium carbonate aqueous solution (20 wt%), 0.28g of tetrabutylammonium chloride, 100ml of chlorobenzene and 100ml of chloromethane (1.0M in MTBE) were sequentially added into an autoclave, the temperature was raised to 120 ℃, the pressure in the autoclave was maintained at 0.4MPa, after 2 hours of reaction, cooling was performed to room temperature, and the reaction solution was washed with n-hexane, separated and concentrated to obtain 2-hydroxy-4-methoxybenzophenone, the yield was 89%, and the purity was 99%.

Example 5

21.4g of 2, 4-dihydroxybenzophenone, 20g of aqueous sodium hydroxide solution (20 wt%), 0.28g of tetrabutylammonium chloride, 100ml of chlorobenzene and 100ml of chloromethane (1.0M in MTBE) were sequentially added to an autoclave, the temperature was raised to 100 ℃, the pressure in the autoclave was maintained at 0.3MPa, after 2 hours of reaction, cooling was performed to room temperature, and the reaction solution was washed with n-hexane, separated and concentrated to obtain 2-hydroxy-4-methoxybenzophenone, the yield was 90%, and the purity was 98%.

Claims

1. A preparation process of 2-hydroxy-4-methoxybenzophenone is characterized in that 2, 4-dihydroxybenzophenone, alkali liquor, a phase transfer catalyst, a solvent and methyl halide are sequentially added into a high-pressure kettle; heating to 60-140 ℃, maintaining the pressure in the kettle at 0.3-0.5 MPa, reacting for 1-4 hours, cooling to room temperature, extracting, separating and concentrating the reaction liquid by using n-hexane to obtain 2-hydroxy-4-methoxybenzophenone, wherein the process route is as follows:

2. the process of claim 1, wherein the alkali solution is potassium hydroxide solution, sodium hydroxide solution, potassium carbonate solution or sodium carbonate solution.

3. The preparation process according to claim 1 or 2, wherein the mass fraction of the alkali liquor is 20-50 wt%.

4. The process of claim 1, wherein the phase transfer catalyst is tetrabutylammonium chloride, tetrabutylammonium bromide, PEG-200, or PEG-400.

5. The process according to claim 1, wherein the solvent is toluene, xylene, chlorobenzene or butyl acetate.

6. The process according to claim 1, wherein the methyl halide is methyl chloride, methyl bromide or methyl iodide.

7. The preparation process according to claim 1, wherein the molar ratio of the 2, 4-dihydroxybenzophenone to the halogenated methane is 1: 1-2.

8. The preparation process of claim 1, wherein the molar ratio of the 2, 4-dihydroxybenzophenone to the alkali solution is 1:1 to 1.5.

9. The process of claim 1, wherein the molar amount of the phase transfer catalyst is 0.5 to 5% of 2, 4-dihydroxybenzophenone.