A kind of 4-sulfonamide phenylhydrazine hydrochloride and preparation method thereof

Abstract

The invention belongs to the technical field of organic synthesis, and in particular to a kind of p-sulfonamide phenylhydrazine hydrochloride and preparation method thereof. The present invention provides a kind of preparation method of p-sulfonamide phenylhydrazine hydrochloride, comprise the following steps:Nitrite solution and sulfanilamide hydrochloric acid solution are mixed sequentially through diazotization reaction, reduction reaction, hydrolysis reaction, salt-forming reaction, obtain p-sulfonamide phenylhydrazine hydrochloride;In the diazotization reaction step, reaction temperature is 40 60 DEG C;In the diazotization reaction step, the sulfanilamide hydrochloric acid solution and nitrite enter the bottom of the reactor, under the effect of stirring, feed liquid turns up from the bottom, arrives at discharge port, makes the diazonium salt generated enter into reduction tank.The present invention adopts medium temperature diazotization, and reaction conditions are mild, easy to operate, good product quality, and few impurities.

Description

Technical Field

[0001] The invention belongs to the technical field of organic compound synthesis, and particularly relates to p-sulfonamide phenylhydrazine hydrochloride and a preparation method thereof. Background Art

[0002] Sulfonamidophenylhydrazine hydrochloride is an important intermediate in the synthesis of the nonsteroidal anti-inflammatory drug celecoxib. Celecoxib is a new type of selective COX-2 inhibitor that achieves anti-inflammatory, analgesic and antipyretic effects by selectively inhibiting COX-2 and preventing the synthesis of prostaglandins. It is now widely used in the treatment of diseases such as rheumatoid arthritis and rheumatic arthritis.

[0003] The conventional preparation process of p-sulfonamidophenylhydrazine hydrochloride generally adopts a kettle reaction, in which a sodium nitrite solution is added dropwise to a sulfonamide hydrochloric acid solution for diazotization. The temperature is relatively low, generally controlled at -5 to 5°C, which consumes too much energy and takes a long time to react. The generated diazonium salt cannot be removed from the reactor in time and is prone to coupling reaction with the raw materials, resulting in an increase in by-products. Although the tubular reaction has a short residence time and few coupling by-products, the pipeline reactor is not satisfactory in terms of production capacity. Summary of the Invention

[0004] In response to the above-mentioned deficiencies in the prior art, the present invention provides a para-sulfonamide phenylhydrazine hydrochloride and a preparation method thereof. The preparation method is mild, has a short reaction time, high production capacity (referring to the output of para-sulfonamide phenylhydrazine hydrochloride produced per unit time), and a stable process (stable yield and purity). The subsequently produced para-sulfonamide phenylhydrazine hydrochloride has few impurities and high purity.

[0005] In view of the above technical deficiencies, one of the purposes of the present invention is to provide a method for preparing p-sulfonamide phenylhydrazine hydrochloride. A second purpose of the present invention is to provide p-sulfonamide phenylhydrazine hydrochloride prepared by the above preparation method.

[0006] In a first aspect, the present invention provides a method for preparing p-sulfonamide phenylhydrazine hydrochloride, comprising the following steps:

[0007] The nitrite solution and the sulfonamide hydrochloric acid solution are mixed and subjected to diazotization reaction, reduction reaction, hydrolysis reaction and salt formation reaction in sequence to obtain p-sulfonamide phenylhydrazine hydrochloride;

[0008] In the diazotization reaction step, the reaction temperature is 40-60°C;

[0009] In the diazotization reaction step, the sulfonamide hydrochloric acid solution and nitrite enter the bottom of the reactor. Under the action of stirring, the liquid turns upward from the bottom and reaches the discharge port, so that the generated diazonium salt enters the reduction tank.

[0010] In the present invention, the diazotization reaction temperature is too high, which can cause the diazonium salt to be easily decomposed, and the output and quality of sulfonamidophenylhydrazine hydrochloride can be affected. The diazotization reaction temperature is too low, and the time is long, and the yield productive rate is low. In the diazotization reaction process, sulfanilamide and nitrite enter the reactor bottom, and under the effect of stirring, the feed liquid turns up from the bottom, arrives at the discharge port, and makes the diazonium salt enter the reduction tank. In the whole diazotization reaction process, the material reaction is complete, and the time is short, and the diazonium salt can be timely shifted out of the reaction system, thereby avoiding the use of low temperature.

[0011] In the above preparation method, as a preferred embodiment, the sulfanilamide hydrochloric acid solution and the nitrite enter the bottom of the reactor simultaneously or the sulfanilamide hydrochloric acid solution enters the bottom of the reactor 2-5 seconds later than the sodium nitrite enters the bottom of the reactor.

[0012] In the present invention, by controlling the flow rate ratio of nitrite solution and sulfanilamide hydrochloride solution, the molar ratio of sodium nitrite and sulfanilamide hydrochloride is regulated. However, the flow rate is too low, which will cause the material to stay in the reactor for a long time, and back-mixing phenomenon will occur, thereby leading to the increase of by-products. The flow rate is too large, which will cause the reaction to be incomplete, and the yield of the product to be reduced. When nitrite is excessive, the nitrite solution flow meter is first opened, and the sulfanilamide hydrochloride solution flow meter is opened again after 3 seconds. This is because in the diazotization reaction process, nitrite is excessive. In order to make the sulfanilamide that has just entered react completely, it is necessary to allow nitrite to enter the reaction system first. If opened at the same time, sulfanilamide may not react completely at the beginning and have a residue. Opening salt water to control the temperature is a routine operation of the factory. The diazotization reactor is jacketed, and the material reacts in the reactor. The jacket is used to control the reaction temperature at 40-60°C with salt water. This is because the diazotization reaction is an exothermic reaction. If salt water is not used to cool the temperature, the reaction will be overheated, causing the decomposition of diazonium salt.

[0013] In the above preparation method, as a preferred embodiment, in the diazotization reaction step, the reaction time is 3-5 min;

[0014] And / or, in the reduction reaction step, the temperature of the reduction reaction is 80-100° C., and the pH environment of the reduction reaction is 6-7.

[0015] In the present invention, the temperature of the reduction reaction is low, which will lead to a slow reduction reaction, thereby reducing the yield of sulfonamide phenylhydrazine hydrochloride. In addition, the reduction reaction needs to be carried out in an acidic environment (pH 6-7), but the pH cannot be too low. If it is too low, sulfite will turn into sulfur dioxide gas, further affecting the amount of reducing agent used.

[0016] In the above preparation method, as a preferred embodiment, in the hydrolysis reaction step, a hydrochloric acid solution is added to carry out the reaction, and the mass ratio of the hydrochloric acid solution to sulfonamide is (2-4):1;

[0017] In the salt-forming reaction step, a hydrochloric acid solution is added to carry out stirring reaction, and the mass ratio of the hydrochloric acid solution to sulfonamide is (1.5-3.5):1;

[0018] In the present invention, the hydrolysis reaction is carried out in an acidic environment by adding hydrochloric acid. However, if the amount of hydrochloric acid solution added is too much, waste will be caused. If the amount of hydrochloric acid solution added is too low, sodium sulfite cannot be further neutralized, resulting in incomplete hydrolysis. In the salt-forming reaction, the hydrochloric acid solution is added at the end of the reaction. The purpose is to allow 4-sulfonylaminophenylhydrazine to be salified and crystals to be fully precipitated. Therefore, when the amount of hydrochloric acid added is too much or too little, the 4-sulfonylaminophenylhydrazine hydrochloride finished product cannot be precipitated from the aqueous phase, resulting in a low yield. The amount of hydrochloric acid added is relatively large, and the precipitated 4-sulfonylaminophenylhydrazine hydrochloride is water-soluble and can be dissolved in water, resulting in a reduced yield of the 4-sulfonylaminophenylhydrazine hydrochloride.

[0019] In the above preparation method, as a preferred embodiment, in the diazotization reaction step, the flow rate of the sodium nitrite solution entering the diazotization reaction tank is 0.5-1.0m 3 / h;

[0020] And / or, the flow rate of the sulfanilamide hydrochloric acid solution entering the diazotization reaction tank is 1-2m 3 / h;

[0021] And / or, the pH of the diazonium salt solution obtained after the diazotization reaction is between 1.0 and 1.5.

[0022] In the present invention, the specific steps of the diazotization reaction are: first open the nitrite solution flow meter, then open the sulfonamide hydrochloric acid solution flow meter after 3 seconds, open the brine to control the temperature, adjust the flow rates of the nitrite solution and the sulfonamide hydrochloric acid solution to 0.5-1.0m 3 / h and 1.0-2.0m 3 / h;

[0023] Use starch-potassium iodide solution to measure the end point at the outlet of the diazonium salt solution, and it is appropriate when the color turns blue. Use 0.5-5.0 pH paper to measure the acidity, and the pH value should be between 1.0-1.5.

[0024] In the present invention, pH and starch potassium iodide test paper are both used to verify whether diazotization is complete. After the sulfonamide reaction is complete, excess sodium nitrite reacts with potassium iodide to generate elemental iodine, causing the starch to turn blue. If it does not turn blue, it indicates that the amount of sodium nitrite is insufficient and the sulfonamide may not have reacted completely. pH control is to ensure that acidity is not too strong during the diazotization reaction. If acidity is too strong, sodium nitrite will be converted into nitrous acid, which will decompose into nitric oxide and nitrogen dioxide, causing waste of sodium nitrite.

[0025] In the above preparation method, as a preferred embodiment, the mass content of nitrite in the nitrite solution is 18-21%;

[0026] and / or, in the sulfanilamide hydrochloric acid solution, the mass content of sulfanilamide is 15-23%, and the mass content of HCl is 10.8-16.6%;

[0027] And / or, the mass fraction of the hydrochloric acid is 35-36.5%;

[0028] And / or, the nitrite includes one of sodium nitrite and potassium nitrite, preferably sodium nitrite.

[0029] In the present invention, the sulfanilamide hydrochloric acid solution is prepared by mixing and stirring sulfanilamide, hydrochloric acid and water.

[0030] In the above preparation method, as a preferred embodiment, in the reduction reaction step, the reduction reaction time is 1-2 hours.

[0031] During the reduction reaction, a reducing agent is added;

[0032] and / or, the reducing agent is a sodium sulfite solution;

[0033] And / or, the mass fraction of the sodium sulfite aqueous solution is 25-33%;

[0034] And / or, the molar ratio of the sulfonamide to the sodium sulfite in the sodium sulfite solution is 1:(2.6-4).

[0035] In the above preparation method, in the reduction reaction step, the pH is adjusted by adding sodium hydroxide, sodium carbonate, ammonia water or passing ammonia gas.

[0036] In the present invention, if the pH is less than 6, sulfite will turn into sulfur dioxide gas and will not play a reducing role. If the pH is greater than 7, the reducing agent will not play a role because the reduction reaction requires a weak acid environment.

[0037] In the above preparation method, as a preferred embodiment, in the hydrolysis reaction step, the addition rate of the hydrochloric acid solution is 0.8-1.2m 3 / h;

[0038] And / or, the mass fraction of the hydrochloric acid solution is 35-36.5%.

[0039] In the present invention, the rate of addition of the hydrochloric acid solution is based on the ability of the material to be absorbed without being washed away. This is because when the hydrolysis reaction is carried out after the reduction reaction is completed, the addition of hydrochloric acid will cause sulfite to react with hydrogen ions to produce sulfur dioxide.

[0040] In the above preparation method, as a preferred embodiment, the temperature of the hydrolysis reaction is 80-100°C;

[0041] And / or, the hydrolysis reaction time is 3-5h.

[0042] In the above preparation method, as a preferred embodiment, the temperature of the salt-forming reaction is 80-100°C;

[0043] And / or, the salt-forming reaction time is 10-20 min;

[0044] And / or, the mass fraction of the hydrochloric acid solution added in the salt-forming reaction is 35-36.5%.

[0045] In the above preparation method, as a preferred embodiment, after the salt-forming reaction is completed, the temperature is lowered;

[0046] And / or, the average rate of cooling is 0.1-1°C / min;

[0047] And / or, the temperature after cooling is 15-25°C.

[0048] In the above preparation method, as a preferred embodiment, after the salt-forming reaction, it also includes the steps of purification, centrifugation and drying.

[0049] In the above preparation method, as a preferred embodiment, in the refining step, the p-sulfonamide phenylhydrazine hydrochloride solid is slurried.

[0050] In the refining step, the beating temperature is 60-80°C and the beating time is 10-20 minutes;

[0051] And / or, the beating is performed using an alcohol solvent, wherein the alcohol solvent includes one of anhydrous ethanol, methanol, and isopropanol;

[0052] and / or, the mass ratio of the sulfonamide to anhydrous ethanol is 1:(5-8);

[0053] And / or, the drying temperature is 50-60°C.

[0054] In the present invention, solid p-sulfonamide phenylhydrazine hydrochloride is added to ethanol for pulping. Taking advantage of the fact that p-sulfonamide phenylhydrazine hydrochloride is insoluble in alcohol solvents while organic impurities are soluble in alcohol solvents, the organic impurities and pigments are washed away without affecting the yield, thereby improving the purity of p-sulfonamide phenylhydrazine hydrochloride. If impurities are removed by high-temperature dissolution in an aqueous phase and crystallization by cooling, the yield will be reduced.

[0055] In a second aspect, the present invention provides a p-sulfonamide phenylhydrazine hydrochloride, which is prepared by the preparation method of p-sulfonamide phenylhydrazine hydrochloride provided in the first aspect.

[0056] Compared with the prior art, the present invention has at least one of the following beneficial effects:

[0057] 1. The present invention provides a method for preparing p-sulfonamide phenylhydrazine hydrochloride, comprising the following steps: mixing a nitrite solution and a sulfonamide hydrochloric acid solution, sequentially undergoing a diazotization reaction, a reduction reaction, a hydrolysis reaction, and a salt-forming reaction to obtain p-sulfonamide phenylhydrazine hydrochloride; in the diazotization reaction step, the reaction temperature is 40-60°C; in the diazotization reaction step, the sulfonamide hydrochloric acid solution and the nitrite enter the bottom of the reactor, and under the action of stirring, the feed liquid is turned up from the bottom to the discharge port, allowing the generated diazonium salt to enter the reduction tank. The present invention uses sulfonamide as the raw material, adds sodium nitrite under the action of hydrochloric acid to carry out a diazotization reaction, and then uses sodium sulfite for thermal reduction; then adds hydrochloric acid for hydrolysis, adds hydrochloric acid after hydrolysis to form a salt, and finally cools and crystallizes, and centrifuges to obtain the finished product p-sulfonamide phenylhydrazine hydrochloride. The present invention adopts medium-temperature diazotization, which has mild reaction conditions, is easy to operate, and has good product quality and few impurities.

[0058] 2. The diazotization reaction of the present invention does not need to be carried out at low temperature. Generally, the diazotization reaction is carried out at -5 to 5°C. The present invention is carried out at 40-60°C, which has low energy consumption, short reaction time, large production capacity and stable process (stable yield and purity).

[0059] 3. The diazotization reaction of the present invention comprises the following steps: sodium nitrite solution and sulfanilamide hydrochloric acid solution enter the reaction tank and flow into the reduction tank from the discharge port; the feeding and discharging are carried out simultaneously; and the reaction time and temperature are controllable. This avoids the occurrence of the phenomenon of foaming when the sodium nitrite solution is added dropwise to sulfanilamide hydrochloric acid in the traditional process, and discoloration and decomposition when the sodium nitrite solution is added dropwise too quickly or too slowly.

[0060] 4. The present invention pulps the crude p-sulfonamide phenylhydrazine hydrochloride in hot anhydrous ethanol, which is beneficial to the removal of organic impurities and pigments, and the product purity is higher. BRIEF DESCRIPTION OF THE DRAWINGS

[0061] Figure 1 This is a process flow chart of Example 1 of this application;

[0062] Figure 2The reaction device of the examples and comparative examples of the present application;

[0063] Figure 3 This is the liquid phase spectrum of Example 1 of this application.

[0064] 1. Sulfanilamide hydrochloric acid solution high-level tank; 2. Sodium nitrite solution high-level tank; 3. Sodium nitrite solution flowmeter; 4. Sulfanilamide hydrochloric acid solution flowmeter; 5. Diazotization reaction tank; 6. Reduction tank. DETAILED DESCRIPTION

[0065] In order to make the purpose, technical solutions and advantages of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. It should be understood by those skilled in the art that the embodiments are merely to help understand the present invention and should not be regarded as specific limitations of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative work are within the scope of protection of the present invention.

[0066] The embodiments of the present invention are implemented on the premise of the technical solution of the present invention, and detailed implementation methods and processes are given. However, the protection scope of the present invention is not limited to the following embodiments. The process parameters in the following embodiments that do not specify specific conditions are generally based on conventional conditions.

[0067] The endpoints of the ranges and any values disclosed herein are not limited to the precise ranges or values, and these ranges or values should be understood to include values close to these ranges or values. For numerical ranges, the endpoints of each range, the endpoints of each range and individual point values, and the individual point values can be combined with each other to form one or more new numerical ranges, and these numerical ranges should be considered to be specifically disclosed in the present invention.

[0068] In the present invention, unless otherwise specified and / or explained, all numerical values involving the amounts of components are "parts by weight". The process parameters in the following examples that are not specified in specific conditions are generally based on conventional conditions.

[0069] The following examples further describe a method for preparing sulfonamide phenylhydrazine hydrochloride of the present invention. The examples are provided only to illustrate the present invention and are not intended to limit the scope of the present invention. The examples provided below can serve as a basis for further improvement or application by those skilled in the art and do not constitute a specific limitation of the present invention in any way.

[0070] The following examples and comparative examples provide a method for preparing sulfonamide phenylhydrazine hydrochloride. Figure 2 The reaction was carried out in the reaction apparatus shown.

[0071] Example 1

[0072] This embodiment provides a method for preparing sulfonamide phenylhydrazine hydrochloride, the process flow chart is as follows: Figure 1 As shown, the specific steps include:

[0073] (1) 200 kg of sodium nitrite was added to a sodium nitrite solution high-level tank 2, and water was added and stirred to obtain a sodium nitrite solution with a mass content of 20%;

[0074] 400 kg of sulfanilamide and 800 kg of concentrated hydrochloric acid with a mass fraction of 36% are put into the sulfanilamide hydrochloric acid solution high-level tank 1, and water is added and stirred to obtain a sulfanilamide hydrochloric acid solution (the solution contains 20% by mass of sulfanilamide and 14.4% by mass of hydrochloric acid).

[0075] (2) First open the sodium nitrite solution flow meter 3, and then open the sulfanilamide hydrochloric acid solution flow meter 4 after 3 seconds, turn on the brine to control the temperature, and adjust the flow rates of the sodium nitrite solution and sulfanilamide hydrochloric acid solution to 0.63m 3 / h and 1.25m 3 / h;

[0076] After 4 minutes, the reaction liquid reaches the discharge port. The endpoint is measured at the outlet of the diazonium salt solution with starch-potassium iodide solution. The color turns blue. The acidity is measured with a 0.5-5.0 pH test paper. The pH value at the outlet of the diazotization reaction tank is controlled between 1.0-1.5.

[0077] In the diazotization reaction tank 5, the temperature is controlled at 50° C.; the diazotization reaction time is 4 minutes.

[0078] (3) After the diazotization reaction is completed, the diazonium salt solution in the diazotization reaction tank 5 is pumped into the reduction tank 6 for a high-temperature reduction reaction. During the reduction reaction, 3045 kg of sodium sulfite solution is added (the mass fraction of the sodium sulfite solution is 25%, and the molar ratio of sodium sulfite in the sodium sulfite solution to the sulfonamide added in step (1) is 2.6:1). The reaction temperature is controlled at 90°C and the reaction time is 1 hour. During this period, ammonia should be added to adjust the pH value to 6-7.

[0079] (4) After the reduction reaction is completed, 1000 kg of 36% hydrochloric acid solution is added to the 3 / h is added into the reduction tank 6 for hydrolysis reaction. The temperature of the hydrolysis reaction is 90°C and the time is 3h.

[0080] (5) After the hydrolysis reaction is completed, 1200 kg of 36% hydrochloric acid solution is added and stirred at 90° C. for 20 min, and then the temperature is cooled to 25° C. at an average cooling rate of 0.2° C. / min. The obtained solid is p-sulfonamide phenylhydrazine hydrochloride solid.

[0081] (6) The obtained p-sulfonamide phenylhydrazine hydrochloride solid is added to anhydrous ethanol for beating, wherein the mass ratio of anhydrous ethanol to the sulfonamide added in step (1) is 1:5, the beating temperature is 80° C., and the beating time is 20 min.

[0082] (7) After beating, centrifuge and dry at 50°C to obtain p-sulfonamide phenylhydrazine hydrochloride.

[0083] In this embodiment, the yield of p-sulfonamide phenylhydrazine hydrochloride is 90%. Figure 3 As shown, the purity of p-sulfonamide phenylhydrazine hydrochloride detected by UltiMate 3000 high performance liquid chromatography is 99.86%.

[0084] Example 2

[0085] This embodiment provides a method for preparing p-sulfonamide phenylhydrazine hydrochloride, comprising the following steps:

[0086] The difference between this embodiment and embodiment 1 is that the pulping solution in step (6) is isopropyl alcohol, and the remaining steps are the same as those in embodiment 1.

[0087] In this example, the yield of p-sulfonamide phenylhydrazine hydrochloride is 90.1% and the purity is 99.84%.

[0088] Example 3

[0089] This embodiment provides a method for preparing p-sulfonamide phenylhydrazine hydrochloride, comprising the following steps:

[0090] Compared with Example 1, the difference between this embodiment and Example 1 is that the flow rate of the sodium nitrite solution in step (2) is 0.5m 3 / h, the flow rate of sulfanilamide hydrochloric acid solution is 1.0m 3 / h, the diazotization reaction time was 5 min, and the remaining steps were the same as in Example 1.

[0091] In this example, the yield of p-sulfonamide phenylhydrazine hydrochloride is 90.3% and the purity is 99.88%.

[0092] Comparative Example 1

[0093] This comparative example provides a method for preparing sulfonamide phenylhydrazine hydrochloride, comprising the following steps:

[0094] The difference between this comparative example and Example 1 is that the temperature of the diazotization reaction in step (2) is 5° C., and the remaining steps are the same as those in Example 1.

[0095] In this comparative example, the yield of p-sulfonamide phenylhydrazine hydrochloride was 86% and the purity was 96.52%.

[0096] Comparative Example 2

[0097] This comparative example provides a method for preparing sulfonamide phenylhydrazine hydrochloride, comprising the following steps:

[0098] This comparative example differs from Example 1 in that purified water is used for impurity removal in step (6), specifically, the obtained p-sulfonamide phenylhydrazine hydrochloride solid is added to purified water (the mass ratio of sulfonamide to purified water is 1:0.5), dissolved at 70°C, and cooled to 25°C. The remaining steps are the same as in Example 1.

[0099] In this comparative example, the yield of p-sulfonamide phenylhydrazine hydrochloride was 50% and the purity was 99.45%.

[0100] Comparative Example 3

[0101] This comparative example provides a method for preparing sulfonamide phenylhydrazine hydrochloride, comprising the following steps:

[0102] The difference between this comparative example and Example 1 is that the temperature of the reduction reaction in step (3) is 70° C., and the remaining steps are the same as those in Example 1.

[0103] In this comparative example, the yield of p-sulfonamide phenylhydrazine hydrochloride was 85% and the purity was 98.78%.

[0104] Comparative Example 4

[0105] This comparative example provides a method for preparing sulfonamide phenylhydrazine hydrochloride, comprising the following steps:

[0106] Compared with Example 1, this comparative example differs in that the amount of hydrochloric acid solution added in step (4) is 400 kg, and the remaining steps are the same as those in Example 1.

[0107] In this comparative example, the yield of p-sulfonamide phenylhydrazine hydrochloride was 78% and the purity was 81.23%.

[0108] Comparative Example 5

[0109] This comparative example provides a method for preparing sulfonamide phenylhydrazine hydrochloride, comprising the following steps:

[0110] Compared with Example 1, this comparative example differs in that the amount of hydrochloric acid solution added in step (5) is 300 kg, and the remaining steps are the same as those in Example 1.

[0111] In this comparative example, the yield of p-sulfonamide phenylhydrazine hydrochloride was 35% and the purity was 99.68%.

[0112] Comparative Example 6

[0113] This comparative example provides a method for preparing sulfonamide phenylhydrazine hydrochloride, comprising the following steps:

[0114] Compared with Example 1, this comparative example differs in that the amount of hydrochloric acid solution added in step (5) is 1600 kg, and the remaining steps are the same as those in Example 1.

[0115] In this comparative example, the yield of p-sulfonamide phenylhydrazine hydrochloride was 84% and the purity was 99.56%.

[0116] Comparative Example 7

[0117] This comparative example provides a method for preparing sulfonamide phenylhydrazine hydrochloride, comprising the following steps:

[0118] Compared with Example 1, the difference between this comparative example and Example 1 is that step (2) adopts tubular reaction for diazotization, the pipe material is 316L, the pipe diameter is DN32, the pipe length is 25m, and the flow rates of sodium nitrite solution and sulfonamide hydrochloric acid solution are 0.096m 3 / h and 0.204m 3 / h, reaction time 4min. The remaining steps are the same as those in Example 1.

[0119] In this comparative example, the yield of p-sulfonamide phenylhydrazine hydrochloride was 89.8% and the purity was 99.23%.

[0120] The preparation methods of Example 1 and Comparative Example 7 were used to produce 467 kg of p-sulfonamide phenylhydrazine hydrochloride. Example 1 required 1.6 h, while Comparative Example 7 required 9.8 h. It can be seen that the time for producing p-sulfonamide phenylhydrazine hydrochloride using Comparative Example 7 was significantly increased, and relatively speaking, the production capacity of p-sulfonamide phenylhydrazine hydrochloride was significantly reduced.

[0121] Comparative Example 8

[0122] This comparative example provides a method for preparing p-sulfonamide phenylhydrazine hydrochloride, comprising the following steps: Compared with Example 1, the reaction liquid reaches the discharge port after 10 minutes, and the time when the reaction liquid reaches the discharge port can be controlled by adjusting the flow rate. The remaining steps are the same as in Example 1.

[0123] In this comparative example, the yield of p-sulfonamide phenylhydrazine hydrochloride is 84% and the purity is 94.58%.

[0124] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention are within the scope of protection of the pending claims of the present invention.

Claims

1. A method for preparing sulfonamide phenylhydrazine hydrochloride, characterized in that, The following steps are involved: The nitrite solution and the sulfonamide hydrochloric acid solution are mixed and subjected to diazotization reaction, reduction reaction, hydrolysis reaction and salt formation reaction in sequence to obtain p-sulfonamide phenylhydrazine hydrochloride; In the diazotization reaction step, the reaction temperature is 40-60°C; The sulfanilamide hydrochloric acid solution and the nitrite enter the bottom of the reactor at the same time, or the sulfanilamide hydrochloric acid solution enters the bottom of the reactor 2-5 seconds later than the nitrite; In the diazotization reaction step, the reaction time is 3-5 min; In the diazotization reaction step, the flow rate of the nitrite solution entering the diazotization reaction tank is 0.5-1.0m 3 / h; The flow rate of the sulfanilamide hydrochloric acid solution entering the diazotization reaction tank is 1-2m 3 / h; The pH of the diazonium salt solution obtained after the diazotization reaction is between 1.0 and 1.5; In the diazotization reaction step, the sulfonamide hydrochloric acid solution and nitrite enter the bottom of the reactor, and under the action of stirring, the feed liquid turns upward from the bottom to reach the discharge port, so that the generated diazonium salt enters the reduction tank; In the reduction reaction step, the temperature of the reduction reaction is 80-100° C., and the pH environment of the reduction reaction is 6-7; In the hydrolysis reaction step, a hydrochloric acid solution is added to carry out the reaction, and the mass ratio of the hydrochloric acid solution to sulfonamide is (2-4):1; In the salt-forming reaction step, a hydrochloric acid solution is added to carry out stirring reaction, and the mass ratio of the hydrochloric acid solution to sulfonamide is (1.5-3.5):1; After the salt-forming reaction, the method further comprises the steps of purification, centrifugation and drying; In the refining step, the p-sulfonamide phenylhydrazine hydrochloride solid is slurried; the slurrying adopts an alcohol solvent.

2. The method for preparing sulfonamide phenylhydrazine hydrochloride according to claim 1, wherein The mass content of nitrite in the nitrite solution is 18-21%; and / or, in the sulfanilamide hydrochloric acid solution, the mass content of sulfanilamide is 15-23%, and the mass content of HCl is 10.8-16.6%; And / or, the nitrite includes one of sodium nitrite and potassium nitrite.

3. The preparation method of sulfonamide phenylhydrazine hydrochloride according to claim 1, wherein In the reduction reaction step, the reduction reaction time is 1-2h; During the reduction reaction, a reducing agent is added; The reducing agent is a sodium sulfite solution, and the molar ratio of the sulfonamide to the sodium sulfite solution is 1:(2.6-4); The mass fraction of the sodium sulfite aqueous solution is 25-33%; In the reduction reaction step, the pH is adjusted by adding sodium hydroxide, sodium carbonate, ammonia water or passing ammonia gas.

4. The method for preparing sulfonamide phenylhydrazine hydrochloride according to claim 1, wherein In the hydrolysis reaction step, the addition rate of the hydrochloric acid solution is 0.8-1.2m 3 / h; The mass fraction of the hydrochloric acid solution is 35-36.5%; The temperature of the hydrolysis reaction is 80-100°C; The hydrolysis reaction time is 3-5h; The temperature of the salt-forming reaction is 80-100°C; The salt-forming reaction time is 10-20 min; The mass fraction of the hydrochloric acid solution added to the salt-forming reaction is 35-36.5%; After the salt-forming reaction is completed, cooling is performed; The average rate of cooling is 0.1-1°C / min; The temperature after cooling is 15-25°C.

5. The method for preparing sulfonamide phenylhydrazine hydrochloride according to claim 1, wherein The beating temperature is 60-80°C and the beating time is 10-20 minutes; The alcohol solvent includes one of anhydrous ethanol, methanol, and isopropanol; The drying temperature is 50-60°C.

6. The method for preparing sulfonamide phenylhydrazine hydrochloride according to claim 5, wherein The alcohol solvent is anhydrous ethanol, and the mass ratio of the sulfonamide to anhydrous ethanol is 1:(5-8).

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