A method for continuous flow synthesis of alpha-tetralone

Abstract

The invention relates to a method for synthesizing α-tetralone by continuous flow, and belongs to the field of chemical synthesis. The method for synthesizing α-tetralone by continuous flow adopts an autocatalytic method, has a single reaction, fewer impurities, and simpler purification; simplifies the reaction process, shortens the reaction time; adopts a continuous flow reaction device to replace a traditional reactor, and has higher safety; significantly improves the yield of the reaction product, realizes safe, environmentally friendly, healthy, and efficient green chemical production, and has broad application prospects.

Description

Technical Field

[0001] The invention belongs to the field of chemical synthesis, and in particular relates to a method for synthesizing alpha-tetralone in a continuous flow through product autocatalysis. Background Art

[0002] α-Tetralone is an important intermediate in the production of pharmaceuticals and agricultural chemicals, and is also an important raw material for organic synthesis in the chemical production process. It is currently mainly used in the pharmaceutical, pesticide, dye and fuel industries. In the pharmaceutical industry, α-tetralone is used as a pharmaceutical intermediate to synthesize antidepressant sertraline, anti-inflammatory, anti-rheumatic, anti-diabetic, anti-hypertensive drugs and other drugs; in the pesticide industry, α-tetralone can be used to synthesize the insecticide naphthylamine; in the fuel industry, α-tetralone is used as an antioxidant and additive to mitigate the stability of hydrogen donor tetralin and improve the cetane number of diesel fuel. In addition, α-tetralone can also be used in the synthesis and preparation of a variety of chiral food additives, nutritional additives, and the synthesis of plastic softeners.

[0003] At present, the main methods used in industry to produce α-tetralone are Friedel-Crafts reaction and oxidation reaction. The Friedel-Crafts method for synthesizing α-tetralone mainly uses benzene and γ-butyrolactone as raw materials, uses AlC13 as a catalyst, and is prepared under liquid-solid phase reaction. This method has high raw material cost, large catalyst dosage, and a large amount of acidic wastewater will be produced during the catalyst post-treatment process, which will cause problems such as equipment corrosion and environmental pollution. Tetralin is cheap and easy to obtain, and oxygen is a clean resource. Therefore, using air or oxygen as the oxygen source, direct catalytic oxidation of tetralin to prepare α-tetralone is a low-cost and environmentally friendly synthesis method. However, the oxidation catalysts currently used are mostly chromium-containing compounds, and the loss of chromium during the reaction process will cause serious environmental pollution.

[0004] In order to overcome the above problems, a Chinese patent application with publication number CN101177386A provides a method for preparing α-tetralone by catalytic oxidation of tetralin, wherein N-hydroxyphthalimide is a fixed component, another organic compound (quinone or diphenol organic matter capable of generating quinone compounds under oxygen conditions) is used as a second component to form a non-metallic composite catalytic system, and air or oxygen is used as an oxygen source to catalytically oxidize tetralin. Although the method avoids the use of metal catalysts and solves the problem of environmental pollution, on the one hand, the method is a traditional autoclave reaction, which has the problems of high cost, high safety risk, complex operation, long reaction time, limited production capacity, and difficulty in industrial production; on the other hand, the yield of the product prepared by the method is low and needs to be further improved. Summary of the invention

[0005] In order to solve the above problems existing in the prior art, the object of the present invention is to provide a method for synthesizing α-tetralone in a continuous flow.

[0006] The invention provides a method for preparing alpha-tetralone by continuous flow. The method is carried out in a continuous flow reaction device. In the continuous flow reaction device, a mixed solution of tetralin, a solvent and a catalyst is connected to a metering pump, and the metering pump is connected to a continuous flow preheater; an oxygen cylinder is connected to a flow meter, and the flow meter and the continuous flow preheater are both connected to a continuous flow mixer, and the continuous flow mixer is connected to a continuous flow photoreactor, and the continuous flow photoreactor is connected to a continuous flow gas-liquid separator, and the continuous flow gas-liquid separator is connected to a continuous flow post-processing module;

[0007] The reaction route of the method is:

[0008]

[0009] The method comprises the following steps: opening a continuous flow photoreactor, an oxygen cylinder valve and a metering pump, reacting, collecting liquid in a continuous flow gas-liquid separator after the reaction is completed, and treating the liquid in a continuous flow post-treatment module to obtain α-tetralone.

[0010] Furthermore, the catalyst is an aromatic ketone catalyst or an aromatic quinone catalyst, and the solvent is an organic solvent.

[0011] Furthermore, the catalyst is α-tetralone, benzophenone, acetophenone, anthraquinone or 9-thioxanthone, preferably α-tetralone; and the organic solvent is an alcohol solvent, preferably methanol.

[0012] Furthermore, the mass volume ratio of the tetralin to the solvent is 1:(6-10) g / mL, and the equivalent ratio of the tetralin to the catalyst is 1:(0.1-2).

[0013] Furthermore, the mass volume ratio of the tetralin to the solvent is 1:8 g / mL, and the equivalent ratio of the tetralin to the catalyst is 1:0.2.

[0014] Furthermore, the flow rate of the metering pump is set to 5.0-20.0 mL / min, the flow rate of the flow meter is set to 0.21-0.84 L / min; and the reaction time is 40-80 min.

[0015] Furthermore, the flow rate of the metering pump is set to 10.0 mL / min, the flow rate of the flow meter is set to 0.42 L / min; and the reaction time is 60 min.

[0016] Furthermore, the continuous flow photoreactor comprises a reaction tube, a light source, a reaction tube circulation jacket and a light source circulation jacket.

[0017] Furthermore, the circulation temperature of the continuous flow preheater is set to 5-55°C, the circulation temperature of the continuous flow mixer is set to 5-55°C, the circulation temperature of the reaction tube is set to 5-55°C, the circulation temperature of the light source is 5-20°C; the wavelength of the light source is 254-365nm, the power is 400

[0018] -450W.

[0019] Furthermore, the circulation temperature of the continuous flow preheater is set to 45°C, the circulation temperature of the continuous flow mixer is set to 45°C, the circulation temperature of the reaction tube is set to 45°C, the circulation temperature of the light source is 10°C; the wavelength of the light source is 365nm, and the power is 420W.

[0020] Compared with the prior art, the method for continuous flow synthesis of α-tetralone of the present invention has the following beneficial effects:

[0021] 1) The present invention adopts the α-tetralone autocatalytic method, which has a single reaction, fewer impurities and simpler purification;

[0022] 2) The present invention significantly improves the yield of α-tetralone;

[0023] 3) The present invention simplifies the reaction process and shortens the reaction time;

[0024] 4) The present invention adopts a continuous flow reaction device to replace the traditional reactor, which is safer;

[0025] 5) In the continuous flow reaction device of the present invention, the whole process is a continuous process, which avoids other problems encountered in traditional kettle reactions, such as: dust or solvent volatilization generated during manual feeding, inaccurate local temperature control, long feeding time, running, bubbling, dripping, leakage during material transfer, occupational dangerous diseases caused by manual operation and contact with materials, etc., realizes automatic control, reduces the risk and cost of manual operation, and thus realizes safe, environmentally friendly, healthy and efficient green chemical production.

[0026] Obviously, according to the above contents of the present invention, in accordance with common technical knowledge and customary means in the art, without departing from the above basic technical ideas of the present invention, other various forms of modification, replacement or change may be made.

[0027] The above contents of the present invention are further described in detail below through specific implementation methods in the form of embodiments. However, this should not be understood as the scope of the above subject matter of the present invention being limited to the following examples. All technologies realized based on the above contents of the present invention belong to the scope of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1Schematic diagram of the continuous flow reaction device for continuous flow synthesis of α-tetralone. DETAILED DESCRIPTION

[0029] The reagents and raw materials used in the following examples and experimental examples are all commercially available unless otherwise specified.

[0030] The structure of the continuous flow reaction device used in the following examples is the prior art, and the schematic diagram is shown in FIG. Figure 1 In the continuous flow reaction device, the mixed solution of raw materials, solvents and catalysts is connected to a metering pump, which is connected to a continuous flow preheater; an oxygen cylinder is connected to a flow meter, which is connected to a continuous flow mixer, which is connected to a continuous flow photoreactor, which is connected to a continuous flow gas-liquid separator, which is connected to a continuous flow post-processing module.

[0031] The above-mentioned continuous flow photoreactor consists of a reaction tube, a light source, a reaction tube circulation jacket and a light source circulation jacket, wherein the reaction tube circulation temperature refers to the set temperature of the reaction tube circulation jacket, and the light source circulation temperature refers to the set temperature of the light source circulation jacket.

[0032] Example 1: Method for continuous flow synthesis of α-tetralone

[0033]

[0034] A mixed solution of tetralin (20 g), methanol (160 mL, 8 V) and catalyst α-tetralone (4.42 g, 0.2 eq) was prepared, and a metering pump was connected, and the metering pump was connected to a continuous flow preheater; an oxygen cylinder was connected to a flow meter, and the flow meter and the continuous flow preheater were both connected to a continuous flow mixer;

[0035] Set the continuous flow preheater circulation temperature to 45°C and reach stability;

[0036] Set the continuous flow mixer circulation temperature to 45°C and reach stability;

[0037] The cycle temperature of the reaction tube of the continuous flow photoreactor was set to 45°C and stabilized, the cycle temperature of the light source was set to 10°C and stabilized, the wavelength of the light source was 365nm, and the power was 420W.

[0038] Set the continuous flow gas-liquid separator circulation temperature to 0°C and reach stability;

[0039] Set the metering pump flow rate to 10.0 mL / min.

[0040] Adjust the oxygen cylinder valve so that the flow meter indicates a flow rate of 0.42L / min.

[0041] Turn on the light source of the continuous photoreactor, open the oxygen cylinder valve, start the metering pump, run for 60 minutes, perform gas-liquid separation in the continuous flow gas-liquid separator, and the reaction liquid enters the continuous flow post-processing module for concentration and distillation to obtain 21.3 g of α-tetralone product with HPLC purity of 99.2% and a yield of 95.6%.

[0042] Example 2: Screening experiment of continuous flow synthesis of α-tetralone

[0043] Referring to the method of Example 1, the only difference is that the wavelength of the light source, the catalyst and the reaction temperature are controlled according to Table 1, and the purity and yield of the α-tetralone obtained under different conditions are tested.

[0044] Table 1. Screening experimental conditions and results for continuous flow synthesis of α-tetralone

[0045]

[0046]

[0047] Note: The “reaction temperature” in Table 1 refers to the temperature of the reaction tube circulation in the continuous flow photoreactor.

[0048] It can be seen from Table 1 that in the method for continuous flow synthesis of α-tetralone of the present invention, when the wavelength of the light source is controlled to be 365 nm, the catalyst is α-tetralone, and the reaction temperature is 45° C., the HPLC purity of the obtained α-tetralone is as high as 99.2%, and the yield is as high as 95.6%. In addition, the α-tetralone autocatalytic method is adopted, the reaction is single, the impurities are less, and the purification is simpler.

Claims

1. A method for preparing α-tetralone by continuous flow, characterized in that: The method is carried out in a continuous flow reaction device, in which a mixed solution of tetralin, a solvent and a catalyst is connected to a metering pump, which is connected to a continuous flow preheater; an oxygen cylinder is connected to a flow meter, the flow meter and the continuous flow preheater are both connected to a continuous flow mixer, the continuous flow mixer is connected to a continuous flow photoreactor, the continuous flow photoreactor is connected to a continuous flow gas-liquid separator, and the continuous flow gas-liquid separator is connected to a continuous flow post-processing module; The reaction route of the method is: The method comprises the following steps: opening a continuous flow photoreactor, an oxygen cylinder valve, and a metering pump, reacting, collecting liquid in a continuous flow gas-liquid separator after the reaction is completed, and treating the liquid in a continuous flow post-treatment module to obtain α-tetralone; The catalyst is α-tetralone, and the solvent is methanol; The mass volume ratio of the tetralin to the solvent is 1:(6-10) g / mL, and the equivalent ratio of the tetralin to the catalyst is 1:(0.1-2); The continuous flow photoreactor comprises a reaction tube, a light source, a reaction tube circulation jacket and a light source circulation jacket; The circulation temperature of the continuous flow preheater is set to 45°C, the circulation temperature of the continuous flow mixer is set to 45°C, the circulation temperature of the reaction tube is set to 45°C, the circulation temperature of the light source is 10°C; the wavelength of the light source is 365nm, and the power is 420W.

2. The method according to claim 1, characterized in that: The mass volume ratio of the tetralin to the solvent is 1:8 g / mL, and the equivalent ratio of the tetralin to the catalyst is 1:0.

2.

3. The method according to claim 1, characterized in that: The flow rate of the metering pump is set to 5.0-20.0 mL / min, and the flow rate of the flow meter is set to 0.21-0.84 L / min; the reaction time is 40-80 min.

4. The method according to claim 3, characterized in that: The flow rate of the metering pump was set to 10.0 mL / min, and the flow rate of the flow meter was set to 0.42 L / min; the reaction time was 60 min.

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