Method for preparing 3, 5-dibromo-4-hydroxybenzaldehyde by using micro-channel photoreactor

Abstract

The invention discloses a method for preparing 3, 5-dibromo-4-hydroxybenzaldehyde as shown in a formula I in the specification by using a micro-channel photoreactor. The method comprises the following steps: pumping a mixed solution of 2, 6-dibromo-4-methylphenol and a solvent and bromine into a micro-channel reaction device provided with a light source for reaction, so as to quantitatively and rapidly synthesize 3, 5-dibromo-4-hydroxybenzaldehyde. The synthesis method disclosed by the invention is low in raw material price, low in reaction temperature, high in conversion speed, high in yield, high in product purity, short in reaction time, capable of realizing continuous production and wide in application prospect. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to the technical field of fine chemical engineering, and particularly relates to a method for preparing 3,5-dibromo-4-hydroxybenzaldehyde by using a microchannel photoreactor.

Background Art

[0002] 3,5-Dibromo-4-hydroxybenzaldehyde is an important fine chemical intermediate, which can be used in the synthesis of various drugs such as trimethoprim (TMP), tretoquinol, and 3,4,5-trimethoxycinnamoyl isopropylamine, and can also be used in the preparation of products such as fungicides and herbicides.

[0003] Currently, the developed preparation methods of 3,5-dibromo-4-hydroxybenzaldehyde include p-hydroxybenzaldehyde method, p-cresol method, etc. The price of p-hydroxybenzaldehyde used in the p-hydroxybenzaldehyde method is relatively high, and it lacks cost advantage compared with other methods. The p-cresol method needs to use o-dichlorobenzene as a solvent, which is too toxic and will produce solvent waste residues. The reaction is carried out at about 150 °C, with a long reaction time and too many side reactions. CN107954841B discloses a method for synthesizing 3,5-dibromo-4-hydroxybenzaldehyde by using p-cresol and bromine as raw materials, adopting a solvent-free continuous pipeline reaction device, through precisely controlling the material ratio, and through a two-stage control process of low temperature and high temperature, and further hydrolysis. The reaction temperature is between 160-165 °C, with large energy consumption and increased production cost. Therefore, it is of great significance to develop a method for preparing 3,5-dibromo-4-hydroxybenzaldehyde with low energy consumption, mild reaction conditions, environmental friendliness and easy continuous production.

Summary of the Invention

[0004] In order to overcome the above-mentioned drawbacks existing in the prior art, the present invention provides a method for preparing 3,5-dibromo-4-hydroxybenzaldehyde by using a microchannel photoreactor.

[0005] The present invention is realized through the following technical solutions:

[0006] A method for preparing 3,5-dibromo-4-hydroxybenzaldehyde by using a microchannel photoreactor, characterized in that a mixed solution of 2,6-dibromo-4-methylphenol and a solvent and bromine are pumped into a microchannel reaction device provided with a light source for reaction, and the compound 3,5-dibromo-4-hydroxybenzaldehyde shown in formula I is obtained:

[0007]

[0008] Among them, the light source of the illumination includes any one or a combination of at least two of visible light source, ultraviolet light source or natural light source.

[0009] Among them, the wavelength range of the light source is 180 nm - 780 nm, preferably 350 nm - 450 nm.

[0010] Among them, the temperature of the reaction is 10 - 50 °C.

[0011] Among them, the residence time of the reaction is 1 - 20 min.

[0012] Among them, the residence time of the reaction is preferably 10 min.

[0013] Among them, the solvent is one or a mixed solvent of dichloromethane, 1,2 - dichloroethane, chloroform, chlorobenzene, dichlorobenzene, nitrobenzene, and water.

[0014] Among them, the volume of the microchannel photoreactor is 30 ml

[0015] Among them, the molar ratio of 2,6 - dibromo - 4 - methylphenol to the solvent and bromine is 1:1 - 5:2 - 5.

[0016] Among them, the intensity of the light irradiation is 5 - 2000 W.

[0017] Compared with the prior art, the present invention has the following advantages:

[0018] (1) The present invention is a method for preparing 3,5 - dibromo - 4 - hydroxybenzaldehyde using a photoreactor, and 3,5 - dibromo - 4 - hydroxybenzaldehyde can be prepared only by adding a light source to the reaction system.

[0019] (2) The reaction raw materials involved in the present invention are low - cost, the reaction operation steps are simple, the reaction time is short, and continuous production can be carried out.

[0020] (3) There are no solid insoluble substances in the system involved in the present invention, and there is no problem of micro - reaction pore blockage.

[0021] (4) The raw material conversion rate of the present invention is 100%, and the product yield can reach 99%.

[0022] (5) The present invention does not require the use of high temperature and has low energy consumption.

Description of the Drawings

[0023] Figure 1 It is the high - performance liquid chromatography diagram of the 3,5 - dibromo - 4 - hydroxybenzaldehyde product.

Detailed Embodiments

[0024] The following further illustrates the present invention with specific embodiments, but the present invention is not limited to the following embodiments.

[0025] Example 1:

[0026] Add 20 g of 2,6-dibromo-4-methylphenol, 100 g of 1,2-dichloroethane, and 26 g of bromine into a 500 mL reaction flask. Pump the reaction solution into a microchannel reaction device, with a reaction residence time of 10 min, and heat up to 35 °C. Detect by high-performance liquid chromatography. After the reaction is completed, add sodium bisulfite to quench the unreacted bromine, extract and separate the layers, dry with anhydrous sodium sulfate, and after rotary evaporation, the mass is 20.92 g, the yield is 99.2%, and the purity is 97.67%.

[0027] Example 2:

[0028] Add 20 g of 2,6-dibromo-4-methylphenol, 100 g of 1,2-dichloroethane, and 30 g of bromine into a 500 mL reaction flask. Pump the reaction solution into a microchannel reaction device, with a reaction residence time of 15 min, and heat up to 40 °C. After the reaction is completed, detect by high-performance liquid chromatography, add sodium bisulfite to quench the unreacted bromine, extract and separate the layers, dry with anhydrous sodium sulfate, and after rotary evaporation, the mass is 21 g, the yield is 99.7%, and the purity is 98.14%.

[0029] Example 3:

[0030] Add 20 g of 2,6-dibromo-4-methylphenol, 120 g of dichloromethane, and 35 g of bromine into a 500 mL reaction flask. Pump the reaction solution into a microchannel reaction device, with a reaction residence time of 15 min, and heat up to 30 °C. After the reaction is completed, detect by high-performance liquid chromatography, add sodium bisulfite to quench the unreacted bromine, extract and separate the layers, dry with anhydrous sodium sulfate, and after rotary evaporation, the mass is 21.02 g, the yield is 99.8%, and the purity is 97.51%.

[0031] Example 4:

[0032] Add 20 g of 2,6-dibromo-4-methylphenol, 80 g of chloroform, and 26 g of bromine into a 500 mL reaction flask. Pump the reaction solution into a microchannel reaction device, with a reaction residence time of 2 min, and heat up to 50 °C. After the reaction is completed, detect by high-performance liquid chromatography, add sodium bisulfite to quench the unreacted bromine, extract and separate the layers, dry with anhydrous sodium sulfate, and after rotary evaporation, the mass is 20.95 g, the yield is 99.5%, and the purity is 97.57%.

[0033] Example 5:

[0034] Add 20 g of 2,6-dibromo-4-methylphenol, 100 g of 1,2-dichloroethane and 35 g of bromine into a 500 mL reaction flask. Pump the reaction solution into a microchannel reaction device. The reaction residence time is 8 min, and the temperature is raised to 50 °C. After the reaction is completed, detect it by high performance liquid chromatography. Add sodium bisulfite to quench the unreacted bromine, extract and separate the layers, dry with anhydrous sodium sulfate, and the mass after rotary evaporation is 20.90 g, the yield is 99.2%, and the purity is 97.82%.

[0035] Example 6:

[0036] Add 20 g of 2,6-dibromo-4-methylphenol, 130 g of chlorobenzene and 30 g of bromine into a 500 mL reaction flask. Pump the reaction solution into a microchannel reaction device. The reaction residence time is 20 min, and keep the temperature at 20 °C. After the reaction is completed, detect it by high performance liquid chromatography. Add sodium bisulfite to quench the unreacted bromine, extract and separate the layers, dry with anhydrous sodium sulfate, and the mass after rotary evaporation is 20.87 g, the yield is 99.1%, and the purity is 97.35%.

[0037] Example 7:

[0038] Add 20 g of 2,6-dibromo-4-methylphenol, 100 g of 1,2-dichloroethane and 26 g of bromine into a 500 mL reaction flask. Pump the reaction solution into a microchannel reaction device. The reaction residence time is 15 min, and keep the temperature at 10 °C. After the reaction is completed, detect it by high performance liquid chromatography. Add sodium bisulfite to quench the unreacted bromine, extract and separate the layers, dry with anhydrous sodium sulfate, and the mass after rotary evaporation is 20.97 g, the yield is 99.6%, and the purity is 97.24%.

[0039] Example 8:

[0040] Add 20 g of 2,6-dibromo-4-methylphenol, 100 g of nitrobenzene and 26 g of bromine into a 500 mL reaction flask. Pump the reaction solution into a microchannel reaction device. The reaction residence time is 5 min, and the temperature is raised to 50 °C. After the reaction is completed, detect it by high performance liquid chromatography. Add sodium bisulfite to quench the unreacted bromine, extract and separate the layers, dry with anhydrous sodium sulfate, and the mass after rotary evaporation is 20.85 g, the yield is 99.0%, and the purity is 97.19%.

[0041] Comparative Example 1:

[0042] Add 20 g of 2,6-dibromo-4-methylphenol, 100 g of 1,2-dichloroethane and 10% azobisisobutyronitrile as an initiator into a 500 ml reaction flask. Heat up to 80 °C, dropwise add 26 g of bromine, react for 7 hours, add sodium bisulfite to quench the unreacted bromine, extract and separate the layers, dry with anhydrous sodium sulfate, and the mass after rotary evaporation is 11.5 g, the yield is 54.6%, and the purity is 48.72%.

[0043] Comparative Example 2:

[0044] Add 20 g of 2,6-dibromo-4-methylphenol, 100 g of 1,2-dichloroethane and 10% benzoyl peroxide as an initiator into a 500 ml reaction flask, heat up to 80 °C, dropwise add 26 g of bromine, react for 7 hours, add sodium bisulfite to quench the unreacted bromine, extract and separate the liquid, dry with anhydrous sodium sulfate, and the mass after rotary evaporation is 10.2 g, the yield is 48.4%, and the purity is 40.68%.

[0045] The test results of the above examples and comparative examples are shown in Table 1.

[0046] Table 1

[0047]

[0048]

[0049] As can be seen from Table 1

[0050] Compared with the preparation of 3,5-dibromo-4-hydroxybenzaldehyde using an initiator, the preparation of 3,5-dibromo-4-hydroxybenzaldehyde using a microchannel photoreactor in the present invention has the advantages of high conversion rate and high product purity. At the same time, the reaction conditions are milder, the reaction time is short, it is prepared by microchannel continuous flow, the production capacity scale is large, and it is suitable for industrial production.

[0051] The above are only the preferred embodiments of the present invention. For the present invention, it is merely illustrative and not restrictive; those of ordinary skill in the art understand that within the scope defined by the claims of the present invention, many changes, modifications, and even equivalent changes can be made to it, but they will all fall within the protection scope of the present invention.

Claims

1. A method for preparing 3,5-dibromo-4-hydroxybenzaldehyde using a microchannel photoreactor, characterized in that: A mixed solution of 2,6-dibromo-4-methylphenol, a solvent and bromine is pumped into a microchannel reaction device equipped with a light source for reaction to obtain 3,5-dibromo-4-hydroxybenzaldehyde.

2. The method according to claim 1, characterized in that The microchannel reaction device provided with a light source comprises a feed pump, a microchannel reactor, a light source and a receiver, wherein the feed pump, the microchannel reactor and the receiver are connected in series in sequence through pipelines, and the microchannel reactor is placed under the irradiation of the light source.

3. The method according to claim 1, characterized in that The light source of the illumination includes any one of a visible light source, an ultraviolet light source or a natural light source, or a combination of at least two of them.

4. The method according to claim 1, characterized in that: The wavelength range of the light source is 180nm-780nm, preferably 350nm-450nm.

5. The method according to claim 1, characterized in that The reaction temperature is 10-50°C.

6. The method according to claim 1, characterized in that The residence time of the reaction is 1-20 min.

7. The method according to claim 1, characterized in that The solvent is selected from one of dichloromethane, 1,2-dichloroethane, chloroform, chlorobenzene, dichlorobenzene, water, nitrobenzene or a mixed solvent.

8. The method according to claim 1, characterized in that The molar ratio of 2,6-dibromo-4-methylphenol to the solvent and bromine is 1:1-5:2-5.

9. The method according to claim 1, characterized in that: The intensity of the illumination is 5-2000W.

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