A method for continuously preparing a m-trifluoromethylaniline diazonium salt

Abstract

The application discloses a method for continuously preparing m-trifluoromethylaniline diazonium salt, belongs to the technical field of pesticide intermediate synthesis, and utilizes the characteristics that the reaction rate is still very fast at low temperature in general diazotization reaction, realizes pre-cooling of the reaction through rapid cooling and crystallization, the flowability of the precipitated solid particles is good, the reaction temperature and the decomposition of the diazonium salt can be safely controlled, the diazotization reaction is continuously, safely and stably operated, and the yield of the prepared m-trifluoromethylaniline diazonium salt is above 99%.

Description

Technical Field

[0001] This invention belongs to the field of pesticide intermediate synthesis technology, specifically a method for the continuous preparation of m-trifluoromethylaniline diazonium salt. Background Technology

[0002] m-Trifluoromethylaniline is an important fine chemical intermediate. Its core value lies in the synergistic effect of its trifluoromethyl and amino groups, which can significantly alter molecular polarity, stability, and bioactivity, leading to its wide application in pharmaceuticals, pesticides, functional materials, and electronic chemicals. A key step in the synthesis of m-trifluoromethylphenol, a crucial intermediate in pharmaceuticals and pesticides, involves the synthesis of its diazonium salt from m-trifluoromethylaniline. The reaction equation is shown below:

[0003]

[0004] Currently, the main process used is a semi-batch reactor process. This process suffers from drawbacks such as poor process stability, high liquid holdup, long reaction time, low yield, and high risk. The general synthesis steps for diazonium salts involve first reacting the aromatic primary amine with a dilute acid (hydrochloric acid, sulfuric acid, etc.) to form a salt, then gradually heating until the solution is completely dissolved, thus protecting the amine groups and reducing the occurrence of coupling side reactions. Because diazonium salts generally have poor stability, in a semi-batch reactor reaction, it is usually necessary to cool the dissolved aromatic primary amine salt. Cooling is typically done using a jacket, which is slow. Furthermore, during the precipitation of the aromatic primary amine salt, the crystals gradually grow, leading to poor stirring. This significantly affects mass transfer during the reaction with the diazotizing reagents sodium nitrite or nitrososulfuric acid, easily causing localized overheating and prolonged retention of the diazonium salt in the reactor with a large liquid holdup. If the diazonium salt decomposes at high temperatures, it can easily pose a safety risk. Summary of the Invention

[0005] To address the above problems, the present invention aims to provide a method for the continuous preparation of m-trifluoromethylaniline diazonium salt.

[0006] To achieve the above objectives, the present invention employs the following technical solution:

[0007] A method for the continuous preparation of m-trifluoromethylaniline diazonium salt includes the following steps:

[0008] 1) Mix m-trifluoromethylaniline with a preheated dilute sulfuric acid aqueous solution through a static mixer-1 and then enter a heat exchanger-3. Heat the mixture to dissolve it until it becomes transparent to obtain an aqueous solution of m-trifluoromethylaniline sulfate.

[0009] 2) The pure water that has been cooled by the precooler is rapidly mixed and cooled with the aqueous solution of m-trifluoromethylaniline sulfate prepared in step 1) through static mixer-2 to obtain reaction solution A;

[0010] 3) The reaction solution A obtained in step 2) is mixed with the diazotizing reagent in static mixer-3. The resulting diazotizing reaction solution is passed into heat exchanger-4 to cool down, and m-trifluoromethylaniline diazonium salt is obtained.

[0011] The temperature of the preheated dilute sulfuric acid aqueous solution in step 1) is 40–120°C, and the mass concentration of the dilute sulfuric acid aqueous solution is 10–30%.

[0012] The temperature at which the substance enters the heat exchanger-3 and is heated to a transparent state, as described in step 1), is 40–100°C.

[0013] The molar ratio of dilute sulfuric acid to m-trifluoromethylaniline in step 1) is 1 to 4:1.

[0014] The temperature of the pure water cooled by the precooler in step 2) is 1-10°C, and the amount of pure water added is 2-10 times the amount of trifluoromethylaniline used in step 1).

[0015] The temperature of reaction solution A in step 2) is 30–80°C.

[0016] The reaction solution A and the diazotizing reagent described in step 3) are held in the static mixer-3 for 1 to 10 seconds.

[0017] The outlet temperature of the static mixer-3 mentioned in step 3) is 40-80℃.

[0018] In step 3), the obtained diazotization reaction solution is passed into heat exchanger-4 to cool it to 20-60°C.

[0019] The molar ratio of the diazotizing reagent in step 3) to the m-trifluoromethylaniline in step 1) is 1 to 1.4:1.

[0020] The diazotizing reagent mentioned in step 3) is a sodium nitrite aqueous solution with a mass concentration of 15-30% or a nitrososulfuric acid solution with a mass concentration of 40%.

[0021] In step 2), after the pure water is cooled by a precooler, it is rapidly mixed and cooled with the aqueous solution of m-trifluoromethylaniline sulfate prepared in step 1) through a static mixer-2, resulting in the precipitation of small crystals with good fluidity. Since the static mixer is insulated, there is no possibility of solid precipitation on the inner wall of the static mixer-2. At this point, a mixture of m-trifluoromethylaniline sulfate crystals and water with good fluidity after cooling is obtained.

[0022] The present invention has the following advantages over the prior art:

[0023] This invention discloses a method for the continuous preparation of m-trifluoromethylaniline diazonium salt. m-Trifluoromethylaniline itself possesses a strong electron-withdrawing group (trifluoromethyl), exhibiting a strong passivating effect. The diazonium salt aqueous solution demonstrates good thermal stability up to 100°C and good chemical stability within a short residence time up to 80°C. The method involves rapidly mixing the m-trifluoromethylaniline salt obtained by salting with dilute sulfuric acid with a stream of cold pure water in a static mixer to cool and crystallize, resulting in smaller solid particles that facilitate flow and dispersion. The resulting m-trifluoromethylaniline salt crystals, a mixture of water and a diazotizing reagent (nitrososulfuric acid or sodium nitrite aqueous solution), are then instantaneously and uniformly mixed in a static mixer before being rapidly cooled in a heat exchanger. This invention innovatively employs a segmented temperature control strategy, using forced heat exchange to achieve pre-cooling before the diazotization reaction, effectively regulating the reaction system temperature. Combined with the endothermic characteristics of the crystal dissolution process, this successfully solves the technical challenges of poor thermal stability of diazonium salts and limited reactor heat exchange efficiency in traditional preparation processes. The supporting equipment, through modular design, enables continuous operation of salt formation reaction, rapid cooling and crystallization, diazotization reaction, and rapid heat exchange, significantly improving process safety and stability.

[0024] The method for continuous preparation of m-trifluoromethylaniline diazonium salt of the present invention utilizes the characteristic that the reaction rate of general diazotization reaction is still very fast at low temperature. By rapidly cooling and crystallizing, the precipitated solid particles have good fluidity, realizing the pre-cooling of the reaction. The reaction temperature and decomposition of diazonium salt can be safely controlled, realizing the continuous, safe and stable operation of the diazotization reaction. The yield of m-trifluoromethylaniline diazonium salt prepared by the present invention is above 99%. Attached Figure Description

[0025] Figure 1 This is a process flow diagram for the continuous preparation of m-trifluoromethylaniline diazonium salt according to the present invention;

[0026] In the diagram: Pump-1—Dilute sulfuric acid feed pump, Pump-2—m-trifluoromethylaniline feed pump, Pump-3—Pure water feed pump, Pump-4—Diazotizing reagent feed pump, Heat exchanger-1—Dilute sulfuric acid preheater, Heat exchanger-2—Pure water precooling heat exchanger, Heat exchanger-3—m-trifluoromethylaniline sulfate aqueous solution heater, Heat exchanger-4—Diazotizing reaction liquid cooling heat exchanger, Static mixer-1—Dilute sulfuric acid and m-trifluoromethylaniline salt formation mixing reactor, Static mixer-2—m-trifluoromethylaniline sulfate aqueous solution and cold pure water rapid mixing cooling crystallization heat exchanger, Static mixer-3—Diazotizing reaction static mixing reactor. Detailed Implementation

[0027] To better understand the technical solution of the present invention, the following detailed embodiments further illustrate the above-mentioned content of the present invention. However, this should not be construed as limiting the scope of the above-mentioned subject matter of the present invention to the following examples. All technologies implemented based on the above-mentioned content of the present invention fall within the scope of the present invention.

[0028] Example 1 Figure 1 As shown, m-trifluoromethylaniline is fed through pump-2, and dilute sulfuric acid is fed through pump-1. After being preheated to 40-120°C by heat exchanger-1, it is mixed with m-trifluoromethylaniline in static mixer-1. After mixing, it enters heat exchanger-3 and is heated to 40-100°C to dissolve until transparent, thus obtaining an aqueous solution of m-trifluoromethylaniline sulfate.

[0029] Pure water is fed through pump 3, pre-cooled to 1-10°C by heat exchanger-2, and then rapidly mixed with m-trifluoromethylaniline sulfate aqueous solution in static mixer-2 and cooled to 30-80°C to obtain reaction solution A.

[0030] The diazotizing reagent is fed through pump-4 and mixed with reaction solution A in static mixer-3 for 1 to 10 seconds. The resulting diazotizing reaction solution is then passed into heat exchanger-4 to cool to 20 to 60°C to obtain m-trifluoromethylaniline diazonium salt.

[0031] Example 2: 161g of m-trifluoromethylaniline and 1715g of a 20% dilute sulfuric acid aqueous solution preheated to 50°C were mixed in a static mixer-1 and then heated to 53°C in a heat exchanger-3 to dissolve until transparent, thus obtaining an aqueous solution of m-trifluoromethylaniline sulfate.

[0032] 400g of pure water, cooled to 5°C by a precooler, is rapidly mixed with an aqueous solution of m-trifluoromethylaniline sulfate via a static mixer-2 and cooled to 42°C to obtain reaction solution A.

[0033] The obtained reaction solution A was mixed with 303.6 g of sodium nitrite aqueous solution with a mass concentration of 25% in a static mixer-3 for 5 s. The resulting diazotization reaction solution was then passed into a heat exchanger-4 to cool to 40 °C to obtain m-trifluoromethylaniline diazonium salt with a yield of 99.5%.

[0034] Example 3: 161g of m-trifluoromethylaniline and 1307g of a 30% dilute sulfuric acid aqueous solution preheated to 40°C were mixed in a static mixer-1 and then heated to 52°C in a heat exchanger-3 to dissolve until transparent, thus obtaining an aqueous solution of m-trifluoromethylaniline sulfate.

[0035] 500g of pure water, cooled to 5°C by a precooler, is rapidly mixed with an aqueous solution of m-trifluoromethylaniline sulfate via a static mixer-2 and cooled to 41°C to obtain reaction solution A.

[0036] The obtained reaction solution A was mixed with 460g of sodium nitrite aqueous solution with a mass concentration of 15% in a static mixer-3 for 1s. The resulting diazotization reaction solution was then passed into a heat exchanger-4 to cool down to 20°C to obtain m-trifluoromethylaniline diazonium salt with a yield of 99%.

[0037] Example 4: 161g of m-trifluoromethylaniline was mixed with 816.7g of a 30% dilute sulfuric acid aqueous solution preheated to 60°C in a static mixer-1 and then heated to 70°C in a heat exchanger-3 to dissolve until transparent, thus obtaining an aqueous solution of m-trifluoromethylaniline sulfate.

[0038] 600g of pure water, cooled to 10°C by a precooler, is rapidly mixed with an aqueous solution of m-trifluoromethylaniline sulfate via a static mixer-2 and cooled to 50°C to obtain reaction solution A.

[0039] The obtained reaction solution A was mixed with 331g of sodium nitrite aqueous solution with a mass concentration of 25% in a static mixer-3 for 6s. The resulting diazotization reaction solution was then passed into a heat exchanger-4 to cool to 35℃ to obtain m-trifluoromethylaniline diazonium salt with a yield of 99.3%.

[0040] Example 5: 161g of m-trifluoromethylaniline and 392g of a 30% dilute sulfuric acid aqueous solution preheated to 60°C were mixed in a static mixer-1 and then heated to 75°C in a heat exchanger-3 to dissolve until transparent, thus obtaining an aqueous solution of m-trifluoromethylaniline sulfate.

[0041] 1000g of pure water, cooled to 10°C by a precooler, is rapidly mixed with an aqueous solution of m-trifluoromethylaniline sulfate via a static mixer-2 and cooled to 30°C to obtain reaction solution A.

[0042] The obtained reaction solution A was mixed with 381.24 g of 40% nitrososulfuric acid solution in static mixer-3 for 10 s. The resulting diazotization reaction solution was then passed into heat exchanger-4 and cooled to 60 °C to obtain m-trifluoromethylaniline diazonium salt with a yield of 99.1%.

[0043] Example 6: 161g of m-trifluoromethylaniline and 512g of a 25% dilute sulfuric acid aqueous solution preheated to 60°C were mixed in a static mixer-1 and then heated to 70°C in a heat exchanger-3 to dissolve until transparent, thus obtaining an aqueous solution of m-trifluoromethylaniline sulfate.

[0044] 966g of pure water, cooled to 7°C by a precooler, was rapidly mixed with an aqueous solution of m-trifluoromethylaniline sulfate via a static mixer-2 and cooled to 35°C to obtain reaction solution A.

[0045] The obtained reaction solution A was mixed with 412g of 40% nitrososulfuric acid solution in static mixer-3 for 8s. The resulting diazotization reaction solution was then passed into heat exchanger-4 and cooled to 50℃ to obtain m-trifluoromethylaniline diazonium salt with a yield of 99.4%.

[0046] Comparative Example

[0047] 1310g of a 24% sulfuric acid aqueous solution and 161.12g of m-trifluoromethylaniline were added to a reactor, heated to 60℃ to dissolve, and then cooled to 5℃ (solid precipitates). 289.2g of a 20% sodium nitrite aqueous solution was then added dropwise, controlling the reaction temperature at 5–12℃ during the dropwise addition process, which lasted approximately 1 hour. After the dropwise addition was completed, the temperature was raised to 20℃ and maintained for 1 hour to obtain the diazonium salt of m-trifluoromethylaniline, with a yield of 97%. In actual industrial production, the semi-batch process, compared to the continuous process proposed in this application, suffers from disadvantages such as poor process stability (continuous process is a steady-state process, while semi-batch is a dynamic process), large liquid holdup, high process risk (continuous process liquid holdup is less than 1L, while semi-batch is generally over 1000L), and long reaction time (continuous process has a residence time of approximately 10 seconds, while semi-batch process requires approximately 2 hours).

[0048] While the specific embodiments of the present invention have been described above, they are not intended to limit the scope of protection of the present invention. Based on the technical solutions of the present invention, various modifications or variations that can be made by those skilled in the art without creative effort are still within the scope of protection of the present invention.

Claims

1. A method for the continuous preparation of m-trifluoromethylaniline diazonium salt, characterized in that: Includes the following steps: 1) Mix m-trifluoromethylaniline with a preheated dilute sulfuric acid aqueous solution through a static mixer-1 and then enter a heat exchanger-3. Heat the mixture to dissolve it until it becomes transparent to obtain an aqueous solution of m-trifluoromethylaniline sulfate. The temperature of the preheated dilute sulfuric acid aqueous solution in step 1) is 40~120℃, and the mass concentration of the dilute sulfuric acid aqueous solution is 10~30%. 2) The pure water that has been cooled by the precooler is rapidly mixed and cooled with the aqueous solution of m-trifluoromethylaniline sulfate prepared in step 1) through static mixer-2 to obtain reaction solution A; The temperature of the pure water cooled by the precooler in step 2) is 1~10℃, and the amount of pure water added is 2~10 times the amount of intermediate trifluoromethylaniline used in step 1); 3) The reaction solution A obtained in step 2) is mixed with the diazotizing reagent in static mixer-3. The resulting diazotizing reaction solution is passed into heat exchanger-4 to cool down, and m-trifluoromethylaniline diazonium salt is obtained.

2. The method for continuous preparation of m-trifluoromethylaniline diazonium salt as described in claim 1, characterized in that: In step 1), the temperature at which the material enters the heat exchanger-3 and is heated to dissolve until it becomes transparent is 40~100℃.

3. The method for continuous preparation of m-trifluoromethylaniline diazonium salt as described in claim 1, characterized in that: The molar ratio of dilute sulfuric acid to m-trifluoromethylaniline in step 1) is 1~4:

1.

4. The method for continuous preparation of m-trifluoromethylaniline diazonium salt as described in claim 1, characterized in that: The temperature of reaction solution A in step 2) is 30~80℃.

5. The method for continuous preparation of m-trifluoromethylaniline diazonium salt as described in claim 1, characterized in that: In step 3), the reaction solution A and the diazotizing reagent are held in the static mixer-3 for 1 to 10 seconds.

6. The method for continuous preparation of m-trifluoromethylaniline diazonium salt as described in claim 1, characterized in that: The outlet temperature of the static mixer-3 mentioned in step 3) is 40~80℃.

7. The method for continuous preparation of m-trifluoromethylaniline diazonium salt according to claim 1, characterized in that: In step 3), the obtained diazotization reaction solution is passed into heat exchanger-4 to cool down to 20~60℃.

8. The method for continuous preparation of m-trifluoromethylaniline diazonium salt as described in claim 1, characterized in that: The molar ratio of the diazotizing reagent in step 3) to the m-trifluoromethylaniline in step 1) is 1~1.4:1; the diazotizing reagent in step 3) is a sodium nitrite aqueous solution with a mass concentration of 15~30% or a nitrososulfuric acid solution with a mass concentration of 40%.

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