Preparation of tetrachlorocyclohexanone by micro-reaction continuous flow process

Abstract

The present application belongs to the technical field of fine chemical industry, and efficiently prepares tetrachlorocyclohexanone through a micro-reaction continuous flow process, solves the heat release problem in the amplification process. The process has the characteristics of simplicity, continuity and high efficiency, greatly reduces the production risk coefficient, improves the production yield, and provides more solid technical support for large-scale production of tetrachlorocyclohexanone.

Description

[Technical Field]

[0001] This invention belongs to the field of fine chemical technology and efficiently prepares tetrachlorocyclohexanone through a micro-reaction continuous flow process. This process solves the exothermic problem during scale-up. The invention features a simple, continuous, and efficient process, significantly shortening the reaction cycle, reducing production risks, and improving production efficiency; thus providing stronger technical support for the large-scale production of tetrachlorocyclohexanone. [Background Technology]

[0002] Tetrachlorocyclohexanone, short for 2,2,6,6-tetrachlorocyclohexanone, is a white crystalline solid with a melting point of 81–83°C. It is an important intermediate in organic functional materials (such as pyrogallol, diclofenac sodium, and 2,6-dichloroaniline), and is mainly used in pharmaceuticals, pesticides, liquid crystal materials, environmental protection materials, plastics and rubber industries, solar energy, and anti-corrosion and antibacterial applications.

[0003] The synthesis of tetrachlorocyclohexanone can be broadly categorized into two methods. One method uses cyclohexanol as a starting material, with peroxides, organic nitrogen, or organic phosphorus as catalysts, reacting with chlorine under ultraviolet light or mercury lamp irradiation. This process suffers from low yield and complex post-processing. The second method uses cyclohexanone as a starting material, reacting with chlorine in the liquid phase under the action of a catalyst. The reaction temperature needs to be controlled at around 110℃. This method features high yield, high product purity, and short reaction time, and is currently the main process for producing tetrachlorocyclohexanone. From the reaction mechanism, cyclohexanone accelerates to form an enol form under the action of a catalyst, then undergoes electrophilic addition with chlorine, followed by deprotonation to obtain an alpha-chloroketone. The resulting alpha-chloroketone rapidly forms a more stable enol structure in the system, undergoing another electrophilic addition reaction. Theoretically, as long as there is sufficient chlorine, tetrachlorocyclohexanone can be generated.

[0004] As can be seen from the reaction process, the chlorination process in the preparation of tetrachlorocyclohexanone is a rapidly exothermic reaction, which is a hazardous process. In industrial production, it poses potential safety hazards such as material overflow and chlorine leakage compared to batch reactors. Microchannel reactors, with their large specific surface area, heat exchange efficiency 100-200 times that of general industrial equipment, high mass and heat transfer efficiency, and short reaction time, offer significant advantages over batch reactors, especially considering the reaction characteristics of tetrachlorocyclohexanone. Therefore, using a micro-reaction continuous flow process to replace batch reactors has substantial advantages. [Summary of the Invention]

[0005] This application utilizes a micro-reaction continuous flow apparatus to effectively solve the exothermic problem in the production of tetrachlorocyclohexanone and improve the chemical reaction rate of the chlorination reaction. The specific optimized process flow is shown below:

[0006]

[0007] The preparation process is carried out in a microreactor continuous flow device, which includes various types of tubular reactors and microchannel reactors.

[0008] The reaction conditions include, but are not limited to, one or more of dichloroethane, benzene, chlorobenzene, toluene, mixed xylene, mesitylene, dichlorobenzene, tetrachlorobenzene, carbon tetrachloride, chloroform, cyclopentane, cyclohexane, n-pentane, n-hexane, n-heptane, and petroleum ether, or a solvent-free reaction method may be adopted. The volume ratio of cyclohexanone to solvent is 1:0 to 1:1000, preferably 1:0 to 1:20, and more preferably 1:1 to 1:10.

[0009] The reaction temperature is 60℃-250℃, preferably 80℃-200℃, and more preferably 90℃-150℃.

[0010] Catalysts include, but are not limited to, organic peroxides (such as: di-tert-butyl peroxide, benzoyl peroxide, diisopropyl percarbonate, tert-butyl peroxide, methyl ethyl ketone peroxide, cyclohexanone peroxide, benzoyl peroxide, lauroyl peroxide, cumene hydroperoxide, tert-butyl hydroperoxide, tert-butyl peroxide, and tert-butyl pervalerate, etc.); inorganic peroxides (such as: potassium persulfate, sodium persulfate, and ammonium persulfate, etc.); and azo compounds (such as azobisisobutyronitrile, azobisisobutyronitrile, etc.). Diisopropyl dicarbonate, azobisisoheptanenitrile, azobisisovaleratenitrile, dimethyl azobisisobutyrate, azobisisobutyramidine hydrochloride, azobisisobutyramidoline hydrochloride, azoisobutyroxycyanoformamide, azodimethyl N-2-hydroxybutylpropionamide, azobiscyclohexylformamide, and azobiscyanopentanoic acid, etc.; nitrogen-containing heterocyclic chlorinated compounds (such as pyridine chloride); nitrogen- or phosphorus-containing compounds (such as pyridine, triphenylphosphine, acetamide, N,N-dimethylformamide, triethanolamine, ammonium chloride, etc.).

[0011] The chlorine gas flow rate is 0.05-100 L / min, preferably 1-50 L / min.

[0012] If a tubular reactor is used for the reaction, the reactor rotation speed is 0-500 r / min, preferably 50-200 r / min; the retention time is 0-5 h, preferably 0.2-3 h.

[0013] If a microchannel continuous flow reactor is used for the reaction, the reaction liquid flow rate is 0.1-5000 mL / min, preferably 2-700 mL / min.

[0014] The materials used in tubular reactors and microchannel reactors include, but are not limited to, silicon carbide, Hastelloy, and stainless steel such as 304, 316, and 316L.

[0015] The microchannel and tubular reaction process flows are respectively as shown in the attached instruction manual. Figure 1 and attached Figure 2 As shown.

[0016] We will explain further in the embodiments. [Attached Image Description]

[0017] For detailed illustrations of this invention, please refer to the accompanying drawings in the specification.

[0018] Figure 1 pyrogallol microchannel process flow

[0019] Figure 2 Flowchart of pyrogallol tubular reaction

Detailed Implementation Methods

[0020] The essence of the invention is further illustrated below with reference to specific embodiments:

[0021] Example 1:

[0022]

[0023] Weigh 100g of cyclohexanone and 2.4g of catalyst and dissolve them in 600mL of chlorobenzene to prepare a liquid mobile phase. Turn on the integrated heating and cooling system and adjust the temperature to stabilize at 120℃. Using chlorobenzene as the solvent, adjust the peristaltic pump flow rate to 4mL / min. After the flow rate stabilizes, adjust the chlorine gas flow rate to 0.5L / min. Once the gas flow rate stabilizes, use the peristaltic pump to pump the prepared liquid mobile phase into the microchannel device. Collect the reaction solution at the end of the microchannel; the gas phase analysis showed a yield of 94.6%.

[0024] Example 2:

[0025]

[0026] Weigh 100g of cyclohexanone and 2.4g of catalyst and dissolve them in 600mL of chlorobenzene to prepare a liquid mobile phase. Turn on the integrated heating and cooling system and adjust the temperature to stabilize at 130℃. Using chlorobenzene as the solvent, adjust the flow rate of the peristaltic pump to 4mL / min. After the flow rate stabilizes, adjust the chlorine gas flow rate to 0.5L / min. After the gas flow rate stabilizes, use the peristaltic pump to pump the prepared liquid mobile phase into the microchannel device. Collect the reaction solution at the end of the microchannel; the gas phase analysis showed a yield of 92.1%.

[0027] Example 3:

[0028]

[0029] 1 kg of cyclohexanone and 24 g of catalyst were dissolved in 6 L of chlorobenzene to prepare a liquid mobile phase. The integrated heating and cooling system was turned on and the temperature was stabilized at 120 °C. Using chlorobenzene as the solvent, the peristaltic pump flow rate was adjusted to 4 mL / min. After the flow rate stabilized, the chlorine gas flow rate was adjusted to 0.5 L / min. Once the gas flow rate stabilized, the prepared liquid mobile phase was pumped into the microchannel device using the peristaltic pump. The reaction solution was collected at the end of the microchannel, and the yield was 95.8% as determined by gas chromatography.

[0030] Example 4:

[0031]

[0032] Weigh 200g of cyclohexanone and 4.8g of catalyst to prepare a liquid mobile phase. Turn on the integrated heating and cooling system and adjust the temperature to stabilize at 120℃. Adjust the peristaltic pump flow rate to 3mL / min, and after the flow rate stabilizes, adjust the chlorine gas flow rate to 0.3L / min. After the gas flow rate stabilizes, use the peristaltic pump to pump the prepared liquid mobile phase into the microchannel device. Collect the reaction solution at the end of the microchannel; the gas phase analysis showed a yield of 93.2%.

[0033] It should be emphasized that the above embodiments are merely exemplary and not limiting. Based on the disclosure of this application, any adjustments or changes to the reaction conditions or parameters that a person skilled in the art might normally adopt will not deviate from the spirit of the invention. The scope of protection of this patent shall be determined by the relevant claims.

Claims

1. The preparation process of tetrachlorocyclohexanone is shown in reaction formula (I). Tetrachlorocyclohexanone (B) is prepared from cyclohexanone (A) under the action of chlorine and catalyst.

2. According to the process method described in claim (1), the preparation process is carried out in a micro-reaction continuous flow device, which includes various types of tubular reactors and microchannel reactors.

3. According to the process method of claim (1), the conditions solvent includes, but is not limited to, one or more of dichloroethane, benzene, chlorobenzene, toluene, mixed xylene, mesitylene, dichlorobenzene, tetrachlorobenzene, carbon tetrachloride, chloroform, cyclopentane, cyclohexane, n-pentane, n-hexane, n-heptane, and petroleum ether, or the reaction is carried out by a solvent-free method, wherein the volume ratio of cyclohexanone to solvent is 1:0 to 1:1000, preferably 1:0 to 1:20, and more preferably 1:1 to 1:

10.

4. According to the process method of claim (1), the reaction temperature of Conditions is 60℃-250℃, preferably 80℃-200℃, and more preferably 90℃-150℃.

5. According to the process method of claim (1), the Conditions catalyst includes, but is not limited to, organic peroxides (such as: di-tert-butyl peroxide, benzoyl peroxide, diisopropyl percarbonate, tert-butyl peroxide, methyl ethyl ketone peroxide, cyclohexanone peroxide, benzoyl peroxide, lauroyl peroxide, cumene hydroperoxide, tert-butyl hydroperoxide, tert-butyl peroxide, and tert-butyl pervalerate, etc.); and inorganic peroxides (such as: potassium persulfate, sodium persulfate, and ammonium persulfate, etc.). Azo compounds (such as azobisisobutyronitrile, diisopropyl azobiscarbonate, azobisisoheptanenitrile, azobisisovalerate, dimethyl azobisisobutyrate, azobisisobutyramidine hydrochloride, azobisisobutyramidazole hydrochloride, azoisobutyramidocyanoformamide, azodimethyl N-2-hydroxybutylpropionamide, azobiscyclohexylformitrile, and azobiscyanopentanoic acid, etc.); nitrogen-containing heterocyclic chlorinated compounds (such as pyridine chloride); nitrogen- or phosphorus-containing compounds (such as pyridine, triphenylphosphine, acetamide, N,N-dimethylformamide, triethanolamine, ammonium chloride, etc.).

6. According to the process method of claim (1), the chlorine gas rate is 0.05-100 L / min, preferably 1-50 L / min.

7. According to the process method described in claim (1), if a tubular reactor is used for the reaction, the reactor rotation speed is 0-500 r / min, preferably 50-200 r / min; the retention time is 0-5 h, preferably 0.2-3 h.

8. According to the process method described in claim (1), if a microchannel continuous flow reactor is used for the reaction, the flow rate of the reaction liquid is 0.1-5000 mL / min, preferably 2-700 mL / min.

9. The micro-reaction continuous flow apparatus according to claim (2), wherein the tubular reactor and the microchannel reactor are made of materials including but not limited to silicon carbide, Hastelloy and stainless steel such as 304, 316, and 316L.

10. The microchannel reaction process according to claims (1) and (2) is shown in Figure 1 of the specification.

11. The tubular reaction process flow according to claims (1) and (2) is shown in Figure 1 of the specification.

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