Method for continuously preparing m-trifluoromethylaniline diazonium salt

Abstract

The invention discloses a method for continuously preparing m-trifluoromethylaniline diazonium salt, which belongs to the technical field of synthesis of pesticide intermediates, utilizes the characteristic that the reaction rate of general diazotization reaction is still high at low temperature, and realizes pre-cooling of the reaction through rapid cooling crystallization and good flowability of precipitated solid particles, so that the yield of the m-trifluoromethylaniline diazonium salt is improved. The reaction temperature and the decomposition of the diazonium salt can be safely controlled, the continuous, safe and stable operation of the diazotization reaction is realized, and the yield of the m-trifluoromethylaniline diazonium salt prepared by the method is more than 99%.

Description

Technical Field

[0001] The invention belongs to the technical field of pesticide intermediate synthesis, and in particular relates to a method for continuously preparing diazonium salt of m-trifluoromethylaniline. Background Art

[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 the molecular polarity, stability, and biological activity. It is widely used in pharmaceuticals, pesticides, functional materials, and electronic chemicals. In the synthesis of m-trifluoromethylphenol, a key intermediate in pharmaceuticals and pesticides, the key step is to use m-trifluoromethylaniline to synthesize the diazonium salt. The reaction equation is shown below:

[0003]

[0004] Current existing technique is mainly semi-batch still process, has the shortcomings such as process stability is poor, liquid holdup is large, reaction time is long, output is low, danger is large for semi-batch process.The general synthesis step of diazonium salt is that aromatic primary amine is first salified with dilute acid (hydrochloric acid, sulfuric acid etc.), then gradually be warming up to molten clear, fully protect the generation of amido reducing coupling side reaction.Due to the generally poor stability of diazonium salt, therefore in semi-batch still reaction, generally need to molten clear aromatic primary amine diluted acid salt cooling, the mode of cooling is generally jacket cooling, this kind of cooling mode is slower, and in the process that aromatic primary amine diluted acid salt is separated out, crystal grows up gradually, cause stirring effect poor, in the reaction process with diazotizing agent sodium nitrite or nitrosylsulfuric acid, significantly affect mass transfer effect, easily cause local temperature too high and diazonium salt to stay in reactor for a long time, liquid holdup is larger, if diazonium salt decomposes at high temperature, easily cause safety risk. Summary of the Invention

[0005] To solve the above problems, the present invention aims to provide a method for continuously preparing diazonium salt of trifluoromethylaniline.

[0006] To achieve the above-mentioned purpose, the present invention is implemented through the following technical solutions:

[0007] A method for continuously preparing diazonium salt of m-trifluoromethylaniline comprises the following steps:

[0008] 1) m-Trifluoromethylaniline and preheated dilute sulfuric acid aqueous solution are mixed in static mixer-1 and then enter heat exchanger-3, where they are heated and dissolved until transparent to obtain a m-Trifluoromethylaniline sulfate aqueous solution;

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

[0010] 3) The reaction solution A obtained in step 2) is mixed with a diazotization reagent in a static mixer-3 for reaction, and the obtained diazotization reaction solution is passed into a heat exchanger-4 for cooling to obtain m-trifluoromethylaniline diazonium salt.

[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 of entering the heat exchanger-3 and being heated and dissolved until transparent is 40-100°C in step 1).

[0013] The molar ratio of the dilute sulfuric acid to the 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 the reaction solution A in step 2) is 30-80°C.

[0016] In step 3), the reaction solution A and the diazotizing agent reside in the static mixer-3 for a time period of 1 to 10 seconds.

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

[0018] The diazotization reaction solution obtained in step 3) is passed into heat exchanger-4 and cooled to 20-60°C.

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

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

[0021] In step 2), the pure water is cooled in a precooler and then rapidly mixed with the aqueous solution of m-trifluoromethylaniline sulfate prepared in step 1) in a static mixer-2 to cool the mixture, thereby precipitating small crystals with good fluidity. The static mixer is insulated, so there is no possibility of solid precipitation on the inner wall of the static mixer-2. At this time, a mixture of m-trifluoromethylaniline sulfate crystals and water with a good mobile phase after cooling is obtained.

[0022] Compared with the prior art, the present invention has the following advantages:

[0023] The method for continuously preparing m-trifluoromethylaniline diazonium salt of the present invention, m-trifluoromethylaniline has a strong electron-withdrawing group (trifluoromethyl) in its structure itself, has a strong passivation effect, and the diazonium salt aqueous solution has good thermal stability within a temperature of 100°C, and has good chemical stability within a short residence time of 80°C. The m-trifluoromethylaniline sulfate obtained after m-trifluoromethylaniline is salified with dilute sulfuric acid is rapidly mixed with a stream of cold pure water in a static mixer for cooling and crystallization, and the obtained smaller solid particles are conducive to flow dispersion; the obtained m-trifluoromethylaniline salt crystals and a mixed solution of water and a diazotizing agent (nitrosylsulfuric acid or sodium nitrite aqueous solution) are instantaneously and uniformly mixed through a static mixer, and then enter a heat exchanger for rapid cooling. The present invention innovatively adopts a segmented temperature control strategy, realizes pre-cooling by forced heat exchange before the diazotization reaction, and effectively regulates the temperature of the reaction system. At the same time, combined with the endothermic characteristics of the crystal dissolution process, it successfully solves the technical difficulties such as the poor thermal stability of the diazonium salt and the limited heat exchange efficiency of the reactor existing in the traditional preparation process. The supporting equipment realizes the continuous operation of salt formation reaction - rapid cooling and crystallization - diazotization reaction - rapid heat exchange through modular design, which significantly improves the process safety and stability.

[0024] The method for continuously preparing m-trifluoromethylaniline diazonium salt of the present invention utilizes the characteristic that a general diazotization reaction has a high reaction rate at low temperatures, and through rapid cooling and crystallization, precipitated solid particles have good fluidity, thereby achieving pre-cooling of the reaction, safely controlling the reaction temperature and decomposition of the diazonium salt, and realizing continuous, safe and stable operation of the diazotization reaction. The yield of the m-trifluoromethylaniline diazonium salt prepared by the present invention is above 99%. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 The present invention is a process flow chart for continuously preparing diazonium salt of m-trifluoromethylaniline;

[0026] In the figure: Pump-1—dilute sulfuric acid feed pump, Pump-2—m-trifluoromethylaniline feed pump, Pump-3—pure water feed pump, Pump-4—diazotization 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—diazotization reaction liquid cooling heat exchanger, Static mixer-1—dilute sulfuric acid and m-trifluoromethylaniline salt-forming mixing reactor, Static mixer-2—m-trifluoromethylaniline sulfate aqueous solution and cold pure water rapid mixing cooling crystallization heat exchanger, Static mixer-3—diazotization reaction static mixing reactor. DETAILED DESCRIPTION

[0027] In order to better understand the technical solutions of the present invention, the following is a further detailed description of the above content of the present invention through specific implementation methods in the form of examples. However, this should not be construed as limiting the scope of the above subject matter of the present invention to the following examples. All technologies implemented based on the above 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 in heat exchanger-1, the mixture is mixed with m-trifluoromethylaniline in static mixer-1. After mixing, the mixture enters heat exchanger-3 and is heated to 40-100°C to dissolve until transparent, thereby obtaining a m-trifluoromethylaniline sulfate aqueous solution.

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

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

[0031] Example 2 161 g of m-trifluoromethylaniline and 1715 g of a 20% dilute sulfuric acid aqueous solution preheated to 50° C. were mixed in a static mixer-1 and then introduced into a heat exchanger-3 where the mixture was heated to 53° C. and dissolved until transparent to obtain a m-trifluoromethylaniline sulfate aqueous solution.

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

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

[0034] Example 3 161 g of m-trifluoromethylaniline and 1307 g of a 30% dilute sulfuric acid aqueous solution preheated to 40° C. were mixed in a static mixer-1 and then introduced into a heat exchanger-3 where the mixture was heated to 52° C. and dissolved until transparent to obtain a m-trifluoromethylaniline sulfate aqueous solution.

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

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

[0037] Example 4 161 g of m-trifluoromethylaniline and 816.7 g of a 30% dilute sulfuric acid aqueous solution preheated to 60° C. were mixed in a static mixer-1 and then introduced into a heat exchanger-3 where the mixture was heated to 70° C. and dissolved until transparent to obtain a m-trifluoromethylaniline sulfate aqueous solution.

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

[0039] The obtained reaction solution A was mixed with 331 g of a 25% mass concentration of sodium nitrite aqueous solution as a diazotizing agent in a static mixer-3 for 6 seconds. The obtained diazotization reaction solution was passed into a heat exchanger-4 and cooled to 35°C to obtain m-trifluoromethylaniline diazonium salt in a yield of 99.3%.

[0040] Example 5 161 g of m-trifluoromethylaniline and 392 g of a 30% dilute sulfuric acid aqueous solution preheated to 60° C. were mixed in a static mixer-1 and then introduced into a heat exchanger-3 where the mixture was heated to 75° C. and dissolved until transparent to obtain a m-trifluoromethylaniline sulfate aqueous solution.

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

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

[0043] Example 6 161 g of m-trifluoromethylaniline and 512 g of a 25% dilute sulfuric acid aqueous solution preheated to 60° C. were mixed in a static mixer-1 and then introduced into a heat exchanger-3 where the mixture was heated to 70° C. and dissolved until transparent to obtain a m-trifluoromethylaniline sulfate aqueous solution.

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

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

[0046] Comparative Example

[0047] 1310g mass concentration is that 24% aqueous sulfuric acid solution and 161.12g m-trifluoromethylaniline are added in reactor, be warming up to 60 ℃ and dissolve clearly, be cooled to 5 ℃ (solid is separated out), dripping mass concentration is 20% sodium nitrite aqueous solution 289.2g wherein, controlling the dropping process reaction temperature is 5~12 ℃, dripping time is about 1h, and dripping is warming up to 20 ℃ of insulation reaction 1h after finishing, obtain m-trifluoromethylaniline diazonium salt, and yield is 97%. In actual industrial production process, semi-batch process exists poor process stability (continuousization is steady-state process, and semi-batch is dynamic process) with respect to the continuous scheme proposed in the application, liquid holdup is large, process risk is large (continuousization liquid holdup is within 1L, and semi-batch is generally more than 1000L), long reaction time (continuousization residence time of about 10s, semi-batch process needs about 2h) shortcomings.

[0048] Although the above describes the specific implementation methods of the present invention, it does not limit the scope of protection of the present invention. Based on the technical solution of the present invention, various modifications or variations that can be made by those skilled in the art without creative work are still within the scope of protection of the present invention.

Claims

1. A method for continuously preparing diazonium salt of m-trifluoromethylaniline, characterized in that: The following steps are involved: 1) m-Trifluoromethylaniline and preheated dilute sulfuric acid aqueous solution are mixed in static mixer-1 and then enter heat exchanger-3, where they are heated and dissolved until transparent to obtain a m-Trifluoromethylaniline sulfate aqueous solution; 2) The pure water cooled by the precooler and the aqueous solution of m-trifluoromethylaniline sulfate prepared in step 1) are rapidly mixed and cooled in a static mixer-2 to obtain a reaction solution A; 3) The reaction solution A obtained in step 2) is mixed with a diazotization reagent in a static mixer-3 for reaction, and the obtained diazotization reaction solution is passed into a heat exchanger-4 for cooling to obtain m-trifluoromethylaniline diazonium salt.

2. The method for continuously preparing diazonium salt of m-trifluoromethylaniline as claimed in claim 1, wherein: 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%.

3. The method for continuously preparing diazonium salt of m-trifluoromethylaniline as claimed in claim 1, wherein: The temperature of entering the heat exchanger-3 and being heated and dissolved until transparent is 40-100°C in step 1).

4. The method for continuously preparing diazonium salt of m-trifluoromethylaniline as claimed in claim 1, wherein: The molar ratio of the dilute sulfuric acid to the m-trifluoromethylaniline in step 1) is 1 to 4:

1.

5. The method for continuously preparing diazonium salt of m-trifluoromethylaniline as claimed in claim 1, wherein: 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).

6. The method for continuously preparing diazonium salt of m-trifluoromethylaniline according to claim 1, wherein: The temperature of the reaction solution A in step 2) is 30-80°C.

7. The method for continuously preparing diazonium salt of m-trifluoromethylaniline according to claim 1, wherein: In step 3), the reaction solution A and the diazotizing agent reside in the static mixer-3 for a time period of 1 to 10 seconds.

8. The method for continuously preparing diazonium salt of m-trifluoromethylaniline according to claim 1, wherein: The outlet temperature of the static mixer-3 in step 3) is 40-80°C.

9. The method for continuously preparing diazonium salt of m-trifluoromethylaniline according to claim 1, wherein: The diazotization reaction solution obtained in step 3) is passed into heat exchanger-4 and cooled to 20-60°C.

10. The method for continuously preparing diazonium salt of m-trifluoromethylaniline according to claim 1, wherein: The molar ratio of the diazotizing agent in step 3) to the m-trifluoromethylaniline in step 1) is 1-1.4:1; the diazotizing agent in step 3) is a sodium nitrite aqueous solution with a mass concentration of 15-30% or a nitrosylsulfuric acid solution with a mass concentration of 40%.

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