2-chloro-4-fluorotrichlorotoluene and preparation method thereof

Abstract

The invention provides 2-chloro-4-fluorotrichlorotoluene and a preparation method thereof, and belongs to the technical field of chemical synthesis.The preparation method comprises the steps that a catalyst and 2-chloro-4-fluorotoluene are mixed, heated and then subjected to ultrasonic treatment, and a clear solution is obtained; the clear solution and chlorine are subjected to a chlorination reaction in the micro-channel reactor, and 2-chloro-4-fluorotrichlorotoluene is obtained in a product. According to the technical scheme provided by the invention, the 2-chloro-4-fluorotrichlorotoluene is obtained by a one-step method without special treatment on the catalyst.

Description

Technical Field

[0001] The invention relates to the technical field of chemical synthesis, and in particular to 2-chloro-4-fluorotoluene trichloride and a preparation method thereof. Background Art

[0002] Aromatic fluorinated intermediates are a class of organic compounds with a benzene ring structure and containing fluorine atoms. They have important application value in the fields of organic synthesis, medicine, pesticides, etc. Aromatic fluorinated intermediates play an important role in organic synthesis. They can be used as raw materials or intermediates for synthesizing other complex organic compounds. Since the introduction of fluorine atoms can change the electron cloud distribution and reaction activity of molecules, aromatic fluorinated intermediates often have unique reactivity and selectivity in organic synthesis. Aromatic fluorinated intermediates can be mainly divided into benzene series and toluene series.

[0003] The main compounds of the benzene series include fluorobenzene, 2,4-dichlorofluorobenzene, p-fluorophenol, p-fluorobenzoyl chloride, 3-chloro-4-fluoroaniline, 4-bromo-2-fluoroaniline, 4-chloro-4-fluorobenzophenone and 2-chloro-4-fluorobenzotrichloride. These compounds are widely used in the fields of medicine, pesticides, dyes, etc. For example, fluorobenzene is an important raw material for the preparation of a variety of fluorine-containing drugs, such as norfloxacin and fluconazole; 2,4-dichlorofluorobenzene can be used to prepare pesticide intermediates; 2-chloro-4-fluorobenzotrichloride is widely used in the synthesis of pesticide intermediates, such as benzylsulfuron.

[0004] The patent with the publication number CN113416114A and the name of a method for preparing 2-chloro-4-fluoro-trichlorotoluene by photochlorination of 2-chloro-4-fluorotoluene catalyzed by loaded phosphorus trichloride is published, wherein 2-chloro-4-fluorotoluene and loaded phosphorus trichloride catalyst are added to a chlorination kettle equipped with a reflux condenser, dry chlorine is introduced into the chlorination kettle, the light source is turned on, the reaction is stirred, and a crude 2-chloro-4-fluoro-trichlorotoluene is obtained, and the target product is obtained after distillation. However, the above technical solution has cumbersome steps, requires the loading of phosphorus trichloride catalyst, and the content of the synthesized product is low, and distillation operation is also required.

[0005] Therefore, it is necessary to provide a 2-chloro-4-fluorobenzotrichloride and a preparation method thereof to solve the problems existing in the above-mentioned prior art. Summary of the invention

[0006] In view of this, the present invention provides a 2-chloro-4-fluorobenzotrichloride and a preparation method thereof, which can obtain 2-chloro-4-fluorobenzotrichloride in one step without special treatment of the catalyst.

[0007] To achieve the above object, the present invention provides a method comprising the following steps: The catalyst is mixed with 2-chloro-4-fluorotoluene, and the mixture is heated and ultrasonicated to obtain a clear solution; the clear solution and chlorine gas undergo a chlorination reaction in a microchannel reactor to obtain 2-chloro-4-fluorotrichlorotoluene as a product.

[0008] Optionally, the catalyst includes one of benzoyl peroxide, azobisisobutyronitrile and polyethylene glycol 800.

[0009] Optionally, the weight ratio of the catalyst to 2-chloro-4-fluorotoluene is 1-1.2:40.

[0010] Optionally, the temperature rising end point is 52-60°C.

[0011] Optionally, the injection volume of the clarified solution into the microchannel reactor is 2-6 ml / min.

[0012] Optionally, the flow rate of chlorine gas entering the microchannel reactor is 0.5~0.8L / min.

[0013] Optionally, the temperature during the chlorination reaction in the microchannel reactor is 110-130° C. and the pressure is 0.15-0.25 MPa.

[0014] In order to achieve the above object, the present invention also provides 2-chloro-4-fluorotrichlorotoluene obtained by the above preparation method.

[0015] The above technical solution of the present invention includes at least the following beneficial effects: The catalyst used in the preparation method of 2-chloro-4-fluorobenzotrichloride provided by the present invention is uniformly mixed with 2-chloro-4-fluorobenzotrichloride through temperature-raising ultrasound, thereby improving the efficiency of chlorination reaction, and realizing one-step preparation of high-content 2-chloro-4-fluorobenzotrichloride through a microchannel reactor, thereby eliminating the subsequent distillation and purification steps and reducing the cost.

[0016] The catalyst used in the present invention does not need to be subjected to secondary treatment and can function after being uniformly mixed with the raw materials. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 It is a reaction diagram in an embodiment of the present invention; Figure 2 This is the gas phase detection spectrum of the product 2-chloro-4-fluorotrichlorotoluene in Example 1 of the present invention. DETAILED DESCRIPTION

[0018] To make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the following will be combined with the appended drawings of the embodiments of the present invention. Figure 1~2, the technical scheme of the embodiment of the present invention is clearly and completely described. Obviously, the described embodiment is a part of the embodiment of the present invention, not all of the embodiments. Based on the described embodiment of the present invention, all other embodiments obtained by ordinary technicians in this field belong to the scope of protection of the present invention.

[0019] Example 1 Take a 1000mL beaker, add 400g of 2-chloro-4-fluorotoluene and 12g of benzoyl peroxide, heat to 52°C and ultrasonicate until the solution is clear and transparent. Put the above clear liquid into a microchannel reactor, then introduce chlorine into the microchannel reactor, the microchannel injection volume is 5ml / min, the pressure is set to 0.2MPa, the chlorine flow rate is 0.6L / min, and the reaction temperature is set to 120°C to obtain the product.

[0020] Example 2 Take a 1000mL beaker, add 400g of 2-chloro-4-fluorotoluene and 12g of benzoyl peroxide, heat to 52°C and ultrasonicate until the solution is clear and transparent. Put the above clear liquid into a microchannel reactor, then introduce chlorine into the microchannel reactor, the microchannel injection volume is 5ml / min, the pressure is set to 0.2MPa, the chlorine flow rate is 0.6L / min, and the reaction temperature is set to 110°C to obtain the product.

[0021] Example 3 Take a 1000mL beaker, add 400g of 2-chloro-4-fluorotoluene and 12g of benzoyl peroxide, heat to 52°C and ultrasonicate until the solution is clear and transparent. Put the above clear liquid into a microchannel reactor, then introduce chlorine into the microchannel reactor, the microchannel injection volume is 5ml / min, the pressure is set to 0.2MPa, the chlorine flow rate is 0.6L / min, and the reaction temperature is set to 130°C to obtain the product.

[0022] Example 4 Take a 1000mL beaker, add 400g of 2-chloro-4-fluorotoluene and 12g of benzoyl peroxide, heat to 52°C and ultrasonicate until the solution is clear and transparent. Put the above clear liquid into a microchannel reactor, then introduce chlorine gas into the microchannel reactor, the microchannel injection volume is 2ml / min, the pressure is set to 0.2MPa, the chlorine flow rate is 0.6L / min, and the reaction temperature is set to 120°C to obtain the product.

[0023] Example 5 Take a 1000mL beaker, add 400g of 2-chloro-4-fluorotoluene and 12g of benzoyl peroxide, heat to 52°C and ultrasonicate until the solution is clear and transparent. Put the above clear liquid into a microchannel reactor, then introduce chlorine into the microchannel reactor, the microchannel injection volume is 3ml / min, the pressure is set to 0.2MPa, the chlorine flow rate is 0.6L / min, and the reaction temperature is set to 120°C to obtain the product.

[0024] Example 6 Take a 1000mL beaker, add 400g of 2-chloro-4-fluorotoluene and 12g of benzoyl peroxide, heat to 52°C and ultrasonicate until the solution is clear and transparent. Put the above clear liquid into a microchannel reactor, then introduce chlorine into the microchannel reactor, the microchannel injection volume is 4ml / min, the pressure is set to 0.2MPa, the chlorine flow rate is 0.6L / min, and the reaction temperature is set to 120°C to obtain the product.

[0025] Example 7 Take a 1000mL beaker, add 400g of 2-chloro-4-fluorotoluene and 12g of benzoyl peroxide, heat to 52°C and ultrasonicate until the solution is clear and transparent. Put the above clear liquid into a microchannel reactor, then introduce chlorine into the microchannel reactor, the microchannel injection volume is 6ml / min, the pressure is set to 0.2MPa, the chlorine flow rate is 0.6L / min, and the reaction temperature is set to 120°C to obtain the product.

[0026] Example 8 Compared with Example 1, the only difference is that azobisisobutyronitrile is used instead of benzoyl peroxide as a catalyst, and the other raw materials and steps are the same as those in Example 1.

[0027] Example 9 Compared with Example 2, the only difference is that azobisisobutyronitrile is used instead of benzoyl peroxide as a catalyst, and the other raw materials and steps are the same as those in Example 2.

[0028] Example 10 Compared with Example 3, the only difference is that azobisisobutyronitrile is used instead of benzoyl peroxide as a catalyst, and the other raw materials and steps are the same as those in Example 3.

[0029] Embodiment 11 Compared with Example 4, the only difference is that azobisisobutyronitrile is used instead of benzoyl peroxide as a catalyst, and the other raw materials and steps are the same as those of Example 4.

[0030] Example 12 Compared with Example 5, the only difference is that azobisisobutyronitrile is used instead of benzoyl peroxide as a catalyst, and the other raw materials and steps are the same as those in Example 5.

[0031] Example 13 Compared with Example 6, the only difference is that azobisisobutyronitrile is used instead of benzoyl peroxide as a catalyst, and the other raw materials and steps are the same as those in Example 6.

[0032] Embodiment 14 Compared with Example 7, the only difference is that azobisisobutyronitrile is used instead of benzoyl peroxide as a catalyst, and the other raw materials and steps are the same as those in Example 7.

[0033] Embodiment 15 Compared with Example 1, the only difference is that polyethylene glycol 800 is used instead of benzoyl peroxide as a catalyst, and the other raw materials and steps are consistent with Example 1.

[0034] Example 16 Compared with Example 2, the only difference is that polyethylene glycol 800 is used instead of benzoyl peroxide as a catalyst, and the other raw materials and steps are consistent with Example 2.

[0035] Embodiment 17 Compared with Example 3, the only difference is that polyethylene glycol 800 is used instead of benzoyl peroxide as a catalyst, and the other raw materials and steps are consistent with Example 3.

[0036] Embodiment 18 Compared with Example 4, the only difference is that polyethylene glycol 800 is used instead of benzoyl peroxide as a catalyst, and the other raw materials and steps are consistent with Example 4.

[0037] Embodiment 19 Compared with Example 5, the only difference is that polyethylene glycol 800 is used instead of benzoyl peroxide as a catalyst, and the other raw materials and steps are consistent with Example 5.

[0038] Embodiment 20 Compared with Example 6, the only difference is that polyethylene glycol 800 is used instead of benzoyl peroxide as a catalyst, and the other raw materials and steps are consistent with Example 6.

[0039] Embodiment 21 Compared with Example 7, the only difference is that polyethylene glycol 800 is used instead of benzoyl peroxide as a catalyst, and the other raw materials and steps are consistent with Example 7.

[0040] Comparative Example 1 Take a 1000mL beaker, add 400g of 2-chloro-4-fluorotoluene and 12g of benzoyl peroxide, heat to 52°C and ultrasonicate until the solution is clear and transparent. Put the above clear liquid into a microchannel reactor, then introduce chlorine into the microchannel reactor, the microchannel injection volume is 5ml / min, the pressure is set to 0.2MPa, the chlorine flow rate is 0.6L / min, and the reaction temperature is set to 100°C to obtain the product.

[0041] Comparative Example 2 Take a 1000mL beaker, add 400g of 2-chloro-4-fluorotoluene and 12g of benzoyl peroxide, heat to 52°C and ultrasonicate until the solution is clear and transparent. Put the above clear liquid into a microchannel reactor, then introduce chlorine into the microchannel reactor, the microchannel injection volume is 7ml / min, the pressure is set to 0.2MPa, the chlorine flow rate is 0.6L / min, and the reaction temperature is set to 120°C to obtain the product.

[0042] Comparative Example 3 Take a 1000mL beaker, add 400g of 2-chloro-4-fluorotoluene and 12g of benzoyl peroxide, heat to 52°C and ultrasonicate until the solution is clear and transparent. Put the above clear liquid into a microchannel reactor, then introduce chlorine into the microchannel reactor, the microchannel injection volume is 8ml / min, the pressure is set to 0.2MPa, the chlorine flow rate is 0.6L / min, and the reaction temperature is set to 120°C to obtain the product.

[0043] Comparative Example 4 Compared with Comparative Example 1, the only difference is that azobisisobutyronitrile is used instead of benzoyl peroxide as a catalyst, and the other raw materials and steps are the same as those of Comparative Example 1.

[0044] Comparative Example 5 Compared with Comparative Example 2, the only difference is that azobisisobutyronitrile is used instead of benzoyl peroxide as a catalyst, and the other raw materials and steps are the same as those of Comparative Example 2.

[0045] Comparative Example 6 Compared with Comparative Example 3, the only difference is that azobisisobutyronitrile is used instead of benzoyl peroxide as a catalyst, and the other raw materials and steps are the same as those of Comparative Example 3.

[0046] Comparative Example 7 Compared with Comparative Example 1, the only difference is that polyethylene glycol 800 is used instead of benzoyl peroxide as a catalyst, and the other raw materials and steps are the same as those of Comparative Example 1.

[0047] Comparative Example 8 Compared with Comparative Example 2, the only difference is that polyethylene glycol 800 is used instead of benzoyl peroxide as a catalyst, and the other raw materials and steps are the same as those of Comparative Example 2.

[0048] Comparative Example 9 Compared with Comparative Example 3, the only difference is that polyethylene glycol 800 is used instead of benzoyl peroxide as a catalyst, and the other raw materials and steps are the same as those of Comparative Example 3.

[0049] Comparative Example 10 Compared with Example 1, the only difference is that tetrabutylammonium bromide is used instead of benzoyl peroxide as a catalyst, and the other raw materials and steps are the same as those in Example 1.

[0050] The test was repeated on Examples 1 to 3 and Comparative Example 1, and the prepared products were tested to obtain Table 1.

[0051] Table 1 Yields of products prepared in Examples 1 to 3 and Comparative Example 1

[0052] Note: In the table, dichloro refers to 2-chloro-4-fluorotoluene dichloride, and trichloro refers to 2-chloro-4-fluorotoluene trichloride.

[0053] As can be seen from Table 1, the only difference between Examples 1 to 3 and Comparative Example 1 is the temperature. When the temperature is 100 to 130° C., the product yield is greater than 90%, especially when the temperature is 120° C., the reaction yield can reach more than 99.1%.

[0054] The products prepared in Examples 1, 4, 5, 6, 7 and Comparative Examples 2 and 3 were tested to obtain the results shown in Table 2.

[0055] Table 2 Yields of products prepared in Examples 1, 4, 5, 6, 7 and Comparative Examples 2 and 3

[0056] Note: In the table, dichloro refers to 2-chloro-4-fluorotoluene dichloride, and trichloro refers to 2-chloro-4-fluorotoluene trichloride.

[0057] As can be seen from Table 2, the difference between Examples 1, 4, 5, 6, 7 and Comparative Examples 2 and 3 is only the injection volume, and the product yield of Examples 1, 4, 5, 6, 7 is higher than that of Comparative Examples 2 and 3. When the injection volume is 2-6 ml / min, the product yield is significantly higher than the yield when the injection volume is 7-8 ml / min.

[0058] The test was repeated on Examples 8, 9, 10 and Comparative Example 4, and the prepared products were tested to obtain Table 3.

[0059] Table 3 Yields of the products prepared in Examples 8, 9, 10 and Comparative Example 4

[0060] Note: In the table, dichloro refers to 2-chloro-4-fluorotoluene dichloride, and trichloro refers to 2-chloro-4-fluorotoluene trichloride.

[0061] As can be seen from Table 3, the only difference between Examples 8, 9 and 10 and Comparative Example 4 is the temperature. The product yield at a temperature of 110-130° C. is significantly higher than the product yield at a temperature of 100° C.

[0062] The products prepared in Examples 8, 11, 12, 13, 14 and Comparative Examples 5 and 6 were tested to obtain the results shown in Table 4.

[0063] Table 4 Yields of the products prepared in Examples 8, 11, 12, 13, 14 and Comparative Examples 5 and 6

[0064] Note: In the table, dichloro refers to 2-chloro-4-fluorotoluene dichloride, and trichloro refers to 2-chloro-4-fluorotoluene trichloride.

[0065] It can be seen from Table 4 that the difference between Examples 8, 11, 12, 13, 14 and Comparative Examples 5 and 6 is only the injection volume. The product yields of Examples 8, 11, 12, 13, and 14 are higher than those of Comparative Examples 5 and 6. When the injection volume is 2 to 6 ml / min, the product yield is significantly higher than the yield when the injection volume is 7 to 8 ml / min.

[0066] The test was repeated on Examples 15, 16, 17 and Comparative Example 7, and the prepared products were tested to obtain Table 5.

[0067] Table 5 Yields of the products prepared in Examples 15, 16, 17 and Comparative Example 7

[0068] Note: In the table, dichloro refers to 2-chloro-4-fluorotoluene dichloride, and trichloro refers to 2-chloro-4-fluorotoluene trichloride.

[0069] As can be seen from Table 5, the only difference between Examples 15, 16 and 17 and Comparative Example 7 is the temperature. When the temperature is 110-130°C, the product yield is greater than the product yield at 100°C.

[0070] The products prepared in Examples 15, 18, 19, 20, 21 and Comparative Examples 8 and 9 were tested and the results are shown in Table 6.

[0071] Table 6 Yields of products prepared in Examples 15, 18, 19, 20, 21 and Comparative Examples 8 and 9

[0072] Note: In the table, dichloro refers to 2-chloro-4-fluorotoluene dichloride, and trichloro refers to 2-chloro-4-fluorotoluene trichloride.

[0073] It can be seen from Table 6 that the difference between Examples 15, 18, 19, 20, 21 and Comparative Examples 8 and 9 is only the injection volume. The product yields of Examples 15, 18, 19, 20 and 21 are higher than those of Comparative Examples 8 and 9. When the injection volume is 2 to 6 ml / min, the product yield is significantly higher than the yield when the injection volume is 7 to 8 ml / min.

[0074] The products prepared in Examples 1, 8, 15 and Comparative Example 10 were tested and the results are shown in Table 7.

[0075] Table 7 Yields of products prepared in Examples 1, 8, 15 and Comparative Example 10

[0076] It can be seen from Table 7 that the difference between Examples 1, 8, 15 and Comparative Example 10 is only the catalyst, and the product yields of Examples 1, 8, 15 are significantly higher than that of Comparative Example 10. It can be seen that the catalyst used in the present invention promotes the improvement of product yield.

[0077] The gas phase detection spectrum of the product 2-chloro-4-fluorotrichlorotoluene in Example 1 can verify the product structure.

[0078] The above are preferred embodiments of the present invention. It should be pointed out that, for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A method for preparing 2-chloro-4-fluorobenzotrichloride, characterized in that: The following steps are involved: The catalyst is mixed with 2-chloro-4-fluorotoluene, and the mixture is heated and ultrasonicated to obtain a clear solution; the clear solution and chlorine gas undergo a chlorination reaction in a microchannel reactor to obtain 2-chloro-4-fluorotrichlorotoluene as a product.

2. The method for preparing 2-chloro-4-fluorobenzotrichloride according to claim 1, characterized in that: The catalyst includes one of benzoyl peroxide, azobisisobutyronitrile and polyethylene glycol 800.

3. The method for preparing 2-chloro-4-fluorobenzotrichloride according to claim 1, characterized in that: The weight ratio of the catalyst to 2-chloro-4-fluorotoluene is 1-1.2:

40.

4. The method for preparing 2-chloro-4-fluorobenzotrichloride according to claim 1, characterized in that: The temperature rise end point is 52-60°C.

5. The method for preparing 2-chloro-4-fluorobenzotrichloride according to claim 1, characterized in that: The injection volume of the clarified solution into the microchannel reactor is 2-6 ml / min.

6. The method for preparing 2-chloro-4-fluorobenzotrichloride according to claim 1, characterized in that: The flow rate of the chlorine gas entering the microchannel reactor is 0.5-0.8 L / min.

7. The method for preparing 2-chloro-4-fluorobenzotrichloride according to claim 1, characterized in that: The temperature during the chlorination reaction in the microchannel reactor is 110-130° C. and the pressure is 0.15-0.25 MPa.

8. 2-Chloro-4-fluorobenzotrichloride obtained by the method for preparing 2-chloro-4-fluorobenzotrichloride as claimed in any one of claims 1 to 7.

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