Continuous flow process for synthesizing phenylhydrazine hydrochloride

Abstract

The invention provides a continuous flow process for synthesizing phenylhydrazine hydrochloride. The continuous flow process is a whole-process continuous synthesis method. The aniline hydrochloride solution and the sodium nitrite solution are pumped into the micro-channel reaction module I and are mixed and reacted to obtain the benzene diazonium chloride solution. The reduction solution and a diazobenzene chloride solution generated by the reaction module I are mixed and react in the micro-channel reaction module II, a concentrated hydrochloric acid solution enters the micro-channel reaction module III to react and synthesize phenylhydrazine hydrochloride, and finally, the phenylhydrazine hydrochloride is obtained through cooling crystallization and centrifugal separation. The land cost and the construction cost of a factory workshop are greatly saved, meanwhile, better production safety and process stability are achieved, and the production scale larger than that of an intermittent process can be achieved.

Description

Technical Field

[0001] The invention relates to a diazotization reaction continuous flow process, in particular to a method for preparing phenylhydrazine hydrochloride by using an aniline diazotization reaction continuous flow process. Background Art

[0002] Phenylhydrazine hydrochloride is a pink solid powder with a foul and pungent smell at room temperature and is a highly toxic substance. It is mainly used as an organic intermediate in the dye, pharmaceutical and pesticide industries. For example, it can produce phenol AS-G, the drug antipyrine, cationic dyes, developers, etc. For some small and medium-sized enterprises, due to the limitations of production process conditions, the purity of the product is not high, so that the product is mainly used in the pesticide industry. Moreover, due to improper determination of certain synthetic process conditions, the reaction often occurs abnormally, which has a certain impact on the product yield and quality.

[0003] At present, there are many methods for synthesizing phenylhydrazine hydrochloride. Most of them use aniline as the main raw material, which undergoes a diazotization reaction with sodium nitrite in an acidic medium at low temperature to generate a diazonium salt of diazonium chloride, which is then reduced and acid-precipitated to produce phenylhydrazine hydrochloride.

[0004] The above-mentioned synthetic route mainly adopts an intermittent process to produce phenylhydrazine salt and substituted phenylhydrazine salt. The first step of diazotization reaction is completed in a reactor. A large amount of diazonium salt will be stored in the reactor during and after the diazotization reaction. Since the diazonium salt has poor thermal stability and is easily decomposed and exploded, there are great safety hazards in the production process, which also limits the production capacity of phenylhydrazine salt and substituted phenylhydrazine salt, and it is impossible to further expand the production scale. To ensure production safety, most of the diazotization reactions of the intermittent process are controlled at low temperatures (for example, 0 to 10° C.), which increases the energy consumption of the production process. The multiple temperature rise and fall operations not only make the operation cumbersome, but also reduce the production efficiency.

[0005] In recent years, there have been some reports on attempts to produce phenylhydrazine salts and substituted phenylhydrazine salts using a "continuous" reaction. By improving existing equipment and process methods, or using continuous operations in certain steps, the high risks faced by the diazotization reaction and the cumbersome production operations in certain steps have only been solved to a certain extent. However, since the entire process (diazotization, reduction and acid hydrolysis to form salts) cannot be continuous, the entire process is essentially still an intermittent process, so the effect is not ideal. Summary of the invention

[0006] In view of the deficiencies in the prior art, the technical problem to be solved by the present invention is to provide a new full-process continuous flow synthesis process for phenylhydrazine hydrochloride that is safe, flexible, simple to operate, efficient and easy to mass produce.

[0007] The production process of phenylhydrazine salts includes four steps of reaction: diazotization, reduction, acidolysis to form salts, and cooling crystallization. Only when these four steps are realized in a continuous "assembly line" manner can it be a continuous flow process. If any one or two steps are realized in a continuous manner, it is only a semi-continuous process, not a continuous flow process. The acidolysis to form salts reaction must be carried out at high temperatures. When the temperature is too low, phenylhydrazine hydrochloride will cool and crystallize, which poses a potential risk of blockage. Therefore, after acidolysis to form salts, it needs to flow into the collection kettle for cooling and crystallization to effectively avoid crystallization blockage.

[0008] In order to solve the problems existing in the prior art, the reaction formula designed by the present invention is as follows:

[0009] The invention provides a continuous flow synthesis process of phenylhydrazine hydrochloride. In a microchannel reactor, an aniline hydrochloride solution reacts with a sodium nitrite solution in a first reaction module to generate phenyldiazonium chloride; the phenyldiazonium chloride reacts with a reducing liquid in a second reaction module to generate phenylhydrazine NN disulfonate; the phenylhydrazine NN disulfonate is acid-precipitated into a salt in a third reaction module, flows out of the microchannel reactor for continuous cooling and crystallization, and generates phenylhydrazine hydrochloride.

[0010] Generally, in the continuous flow synthesis process, aniline hydrochloride solution, sodium nitrite solution, reducing solution and concentrated hydrochloric acid solution are respectively pumped into a microchannel reactor through different feed pumps; diazotization, reduction, acid precipitation and cooling crystallization are fully continuous reactions to synthesize phenylhydrazine hydrochloride.

[0011] Furthermore, the feed flow rate of the aniline hydrochloride solution is controlled at 1-30 mL / min, the flow rate of the sodium nitrite solution is controlled at 1-20 mL / min, the flow rate of the reducing solution is controlled at 1-100 mL / min, and the feed flow rate of the concentrated hydrochloric acid solution is controlled at 1-100 mL / min.

[0012] Furthermore, the reaction temperature of the first reaction module is 0-30° C., and the reaction time is 10-200 s.

[0013] Furthermore, the reaction temperature of the second reaction module is 60-95° C., and the reaction time is 1-30 min.

[0014] Furthermore, the acid precipitation temperature of the third reaction module is 60-95° C., and the acid precipitation pH is 1-3.

[0015] Furthermore, the mass concentration of the sodium nitrite solution is 20%-40%.

[0016] Furthermore, the reducing solution is a mixed solution of sodium (ammonium) bisulfite and sodium (ammonium) sulfite, wherein the molar ratio of aniline to the mixed reducing solution is aniline: sodium (ammonium) bisulfite: sodium (ammonium) sulfite = 1:1-4:1-3.5.

[0017] Furthermore, the temperature range of the cooling crystallization is 0-25°C.

[0018] The benefit of the present invention is that the present invention innovatively breaks through the limitations of traditional processes, develops a highly integrated integrated reactor, and realizes the full-process continuous flow synthesis of phenylhydrazine hydrochloride. That is, four reaction raw materials (aniline, sodium nitrite solution, reducing agent and hydrochloric acid) are continuously added to the reactor, and the reaction products are continuously collected for cooling and crystallization, and only one compact device is needed to solve the three-step reaction. At the same time, due to the significant improvement in mass transfer and heat transfer effects, there is no need for slow dropwise addition operation on the reaction device, which greatly improves the efficiency of the process; the reactor has a small liquid holding capacity, a small device volume, and a small footprint, which greatly saves the land cost and construction cost of the factory workshop compared to the traditional reactor; because the continuous flow process has better production safety and process stability than the traditional intermittent process, a larger production scale than the intermittent process can be achieved. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 The present invention is a flow chart of a method for synthesizing phenylhydrazine hydrochloride by continuous flow reaction according to an embodiment of the present invention. Implementation

[0020] The present invention will be further described below in conjunction with specific embodiments and accompanying drawings. It should be understood that these embodiments are only used to illustrate the present invention and are not intended to limit the scope of the present invention. In addition, it should be understood that after reading the content of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms fall within the scope limited by the appended claims of the application equally. Example 1

[0021] Weigh 365.4g of water and pour it into 1L beaker A, weigh 290g of 36% hydrochloric acid solution and add it into beaker A and mix well, then pour it into 500mL flask A. Weigh 136g of aniline solution and add it dropwise into the hydrochloric acid solution in flask A through a 250mL dropping funnel at a temperature of 10-15℃ to obtain aniline hydrochloride solution.

[0022] Weigh 175.7 g of sodium nitrite and 500 g of water in beaker B and mix them evenly; weigh 301.8 g of sodium bisulfite, 397.08 g of sodium sulfite, and 1650 g of water in beaker C and mix them evenly as a reducing agent.

[0023] Connect the aniline hydrochloride solution in flask A to feed pump A, and connect the sodium nitrite solution to feed pump B. Adjust the flow rate of feed pump A to 17.9 mL / min, and the flow rate of feed pump B to 8.7 mL / min. Start pumps A and B at the same time, and pump the two solutions into reaction module I.

[0024] Solutions A and B are mixed and reacted in microchannel reaction module I at a reaction temperature of 17° C. and a residence time of 23 s to generate a diazonium chloride solution.

[0025] Solution C is connected to feed pump C (47.8 mL / min), mixed with the diazonium chloride solution generated by reaction module I, and enters the microchannel reaction module II preheated to 90°C. In reaction module II, the diazonium chloride solution reacts with reducing solution C for 5 minutes.

[0026] The 36% hydrochloric acid solution is connected to the feed pump D (50 mL / min) and is acid-precipitated into salt with the solution flowing out of the microchannel reaction module II in the microchannel reaction module III, the acid precipitation temperature is 60°C, and the acid precipitation pH is 1. Then it flows into the continuous crystallizer.

[0027] The product was cooled to 0°C in a continuous crystallizer and crystallized, and then separated by centrifugation to obtain phenylhydrazine hydrochloride. Example 2

[0028] Weigh 320g of water and pour it into 1L beaker A, weigh 290g of 36% hydrochloric acid solution and add it into beaker A and mix well, then pour it into 500mL flask A. Then weigh 136g of aniline solution and add it dropwise into the hydrochloric acid solution in flask A through a 250mL dropping funnel at a temperature of 10-15℃ to obtain aniline hydrochloride solution.

[0029] Weigh 86.8g of sodium nitrite and 250g of water into beaker B; weigh 301.8g of sodium bisulfite, 397.08g of sodium sulfite, and 1650g of water into beaker C and mix well as a reducing agent;.

[0030] Connect the aniline hydrochloride solution in flask A to feed pump A, and connect the sodium nitrite solution to feed pump B. Adjust the flow rate of feed pump A to 25 mL / min, and the flow rate of feed pump B to 12.1 mL / min. Start pumps A and B at the same time, and pump the two solutions into microchannel reaction module I.

[0031] Solutions A and B are mixed and reacted in a microchannel reaction module I at a reaction temperature of 10° C. and a residence time of 30 s to generate a diazonium chloride solution.

[0032] The reducing liquid C is connected to the feed pump C (68 mL / min), mixed with the diazonium chloride solution generated by the microchannel reaction module I, and enters the microchannel reaction module II preheated to 95°C. The diazonium chloride solution reacts with the reducing liquid C in the microchannel reaction module II, and the reaction time is 10 minutes.

[0033] The 36% hydrochloric acid solution is connected to the feed pump D (62 mL / min), and the solution flowing out of the microchannel reaction module II is acid-precipitated into hydrochloric acid in the microchannel reaction module III at a temperature of 70°C and a pH of 1. Then it flows into the continuous crystallizer.

[0034] The product was cooled to 5°C in a continuous crystallizer and crystallized, and then separated by centrifugation to obtain phenylhydrazine hydrochloride. Example 3

[0035] Weigh 365.4g of water and pour it into 1L beaker A, weigh 290g of 36% hydrochloric acid solution and add it into beaker A and mix well, then pour it into 500mL flask A. Weigh 136g of aniline solution and add it dropwise into the hydrochloric acid solution in flask A through a 250mL dropping funnel at a temperature of 10-15℃ to obtain aniline hydrochloride solution.

[0036] Weigh 175.7 g of sodium nitrite and 500 g of water in beaker B and mix them evenly; weigh 301.8 g of sodium bisulfite, 397.08 g of sodium sulfite, and 1650 g of water in beaker C and mix them evenly as a reducing agent.

[0037] The aniline hydrochloride solution in flask A is connected to feed pump A, and the sodium nitrite solution is connected to feed pump B. The flow rate of feed pump A is adjusted to 17.9 mL / min, and the flow rate of feed pump B is adjusted to 8.8 mL / min. Pump A and pump B are started at the same time to pump the two solutions into microchannel reaction module I.

[0038] Solutions A and B are mixed and reacted in a microchannel reaction module I at a reaction temperature of 15° C. and a residence time of 28 s to generate a diazonium chloride solution.

[0039] Solution C was connected to feed pump C (72.6 mL / min) and mixed with the diazonium chloride solution generated by microchannel reaction module I into microchannel reaction module II preheated to 90° C. for reaction for 5 min.

[0040] The 36% hydrochloric acid solution is connected to the feed pump D (68 mL / min), and the solution flowing out of the microchannel reaction module II is acid-precipitated into hydrochloric acid in the microchannel reaction module III at an acid precipitation temperature of 80°C and an acid precipitation pH of 1. Then it flows into the continuous crystallizer.

[0041] The product was cooled to -2°C in a continuous crystallizer and crystallized, and then separated by centrifugation to obtain phenylhydrazine hydrochloride. Example 4

[0042] Weigh 365.4g of water and pour it into 1L beaker A, weigh 290g of 36% hydrochloric acid solution and add it into beaker A and mix well, then pour it into 500mL flask A. Weigh 136g of aniline solution and add it dropwise into the hydrochloric acid solution in flask A through a 250mL dropping funnel at a temperature of 10-15℃ to obtain aniline hydrochloride solution.

[0043] Weigh 175.7 g of sodium nitrite and 500 g of water in beaker B and mix them evenly; weigh 301.8 g of sodium bisulfite, 397.08 g of sodium sulfite, and 1650 g of water in beaker C and mix them evenly as a reducing agent.

[0044] The aniline hydrochloride solution in flask A is connected to feed pump A, and the sodium nitrite solution is connected to feed pump B. The flow rate of feed pump A is adjusted to 17.9 mL / min, and the flow rate of feed pump B is adjusted to 8.8 mL / min. Pump A and pump B are started at the same time to pump the two solutions into microchannel reaction module I.

[0045] Solutions A and B are mixed and reacted in a microchannel reaction module I at a reaction temperature of 15° C. and a residence time of 28 s to generate a diazonium chloride solution.

[0046] Solution C was connected to feed pump C (72.6 mL / min) and mixed with the diazonium chloride solution generated by microchannel reaction module I into microchannel reaction module II preheated to 90° C. for reaction for 30 min.

[0047] The 36% hydrochloric acid solution is connected to the feed pump D (68 mL / min), and the solution flowing out of the microchannel reaction module II is acid-precipitated into hydrochloric acid in the microchannel reaction module III at a temperature of 90°C and a pH of 1. Then it flows into the continuous crystallizer.

[0048] The product was cooled to -2°C in a continuous crystallizer and crystallized, and then separated by centrifugation to obtain phenylhydrazine hydrochloride. Example 5

[0049] Weigh 365.4g of water and pour it into 1L beaker A, weigh 290g of 36% hydrochloric acid solution and add it into beaker A and mix well, then pour it into 500mL flask A. Weigh 136g of aniline solution and add it dropwise into the hydrochloric acid solution in flask A through a 250mL dropping funnel at a temperature of 10-15℃ to obtain aniline hydrochloride solution.

[0050] Weigh 175.7 g of sodium nitrite and 500 g of water in beaker B and mix them evenly; weigh 301.8 g of sodium bisulfite, 397.08 g of sodium sulfite, and 1650 g of water in beaker C and mix them evenly as a reducing agent.

[0051] The aniline hydrochloride solution in flask A is connected to feed pump A, and the sodium nitrite solution is connected to feed pump B. The flow rate of feed pump A is adjusted to 26.8 mL / min, and the flow rate of feed pump B is adjusted to 13.2 mL / min. Pump A and pump B are started at the same time to pump the two solutions into microchannel reaction module I.

[0052] Solutions A and B are mixed and reacted in a microchannel reaction module I at a reaction temperature of 15° C. and a residence time of 28 s to generate a diazonium chloride solution.

[0053] Solution C was connected to feed pump C (72.6 mL / min) and mixed with the diazonium chloride solution generated by microchannel reaction module I into microchannel reaction module II preheated to 90° C. for reaction for 25 min.

[0054] The 36% hydrochloric acid solution is connected to the feed pump D (68 mL / min), and the solution flowing out of the microchannel reaction module II is acid-precipitated into hydrochloric acid in the microchannel reaction module III at a temperature of 90°C and a pH of 1. Then it flows into the continuous crystallizer.

[0055] The product was cooled to -2°C in a continuous crystallizer and crystallized, and then separated by centrifugation to obtain phenylhydrazine hydrochloride.

[0056] By comparison, the present invention develops an efficient continuous flow synthesis process for phenylhydrazine hydrochloride, which greatly saves the land cost and construction cost of the factory workshop through the continuous flow production process, and at the same time has better production safety and process stability, and can achieve a larger production scale than the intermittent process.

Claims

1. A continuous flow synthesis process for phenylhydrazine hydrochloride, characterized in that, In the microchannel reactor, aniline hydrochloride solution reacts with sodium nitrite solution in the first reaction module to generate benzene diazonium chloride; benzene diazonium chloride then reacts with reducing solution in the second reaction module to generate phenylhydrazine NN disulfonate; phenylhydrazine NN disulfonate is acid-precipitated into salt in the third reaction module, flows out of the microchannel reactor for continuous cooling and crystallization, and generates phenylhydrazine hydrochloride.

2. The continuous flow synthesis process according to claim 1, characterized in that: Aniline hydrochloride solution, sodium nitrite solution, reducing solution and concentrated hydrochloric acid solution are respectively pumped into the microchannel reactor through different feed pumps; Phenylhydrazine hydrochloride is synthesized by a fully continuous reaction of diazotization, reduction, acid precipitation to form salt and cooling crystallization.

3. The continuous flow synthesis process according to claim 2, characterized in that: The feed flow rate of aniline hydrochloride solution is controlled at 1-30 mL / min, the flow rate of sodium nitrite solution is controlled at 1-20 mL / min, the flow rate of reducing solution is controlled at 1-100 mL / min, and the feed flow rate of concentrated hydrochloric acid solution is controlled at 1-100 mL / min.

4. The continuous flow synthesis process according to claim 1, characterized in that: The reaction temperature of the first reaction module is 0-30°C, and the reaction time is 10-200s.

5. The continuous flow synthesis process according to claim 1, characterized in that: The reaction temperature of the second reaction module is 60-95° C., and the reaction time is 1-30 min.

6. The continuous flow synthesis process according to claim 1, characterized in that: The acid precipitation temperature of the third reaction module is 60-95°C, and the acid precipitation pH is 1-3.

7. The continuous flow synthesis process according to claim 1, 2 or 3, characterized in that: The mass concentration of the sodium nitrite solution is 20%-40%.

8. The continuous flow synthesis process according to claim 1, 2 or 3, characterized in that: The reducing solution is a mixed solution of sodium (ammonium) bisulfite and sodium (ammonium) sulfite, wherein the molar ratio of aniline to the mixed reducing solution is aniline: sodium (ammonium) bisulfite: sodium (ammonium) sulfite = 1:1-4:1-3.

5.

9. The continuous flow synthesis process according to claim 1, 2 or 3, characterized in that: The temperature range of cooling crystallization is 0-25℃.

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