Green and environment-friendly sulfonamide amidation preparation method

Abstract

The invention belongs to the technical field of sulfonamide synthesis, and particularly relates to a green and environment-friendly sulfonamide amidation preparation method. Comprising the following steps: adding chlorosulfonic acid into a reactor, stirring, heating, adding o-nitrochlorobenzene, carrying out staged heat preservation, cooling, and adding thionyl chloride to obtain 2-nitro-4-chlorine sulfonate-chlorobenzene; the method comprises the following steps: separating and filtering 2-nitro-4-chlorine sulfonate-chlorobenzene, adding ammonia water, stirring, preserving heat, and carrying out filter pressing to obtain 2-nitro-4-amine sulfonate-chlorobenzene; the preparation method comprises the following steps: adding liquid caustic soda into 2-nitro-4-amine sulfonate-chlorobenzene, stirring, heating, and adjusting the pH value to obtain 2-nitro-4-amine sulfonate-phenol; the method comprises the following steps: adding water, a catalyst and hydrazine hydrate into 2-nitro-4-amine sulfonate-phenol, heating, stirring, and carrying out filter pressing to obtain 4-sulfonamide-2-amino-phenol. According to the preparation method of sulfonamide, generated tail gas is subjected to falling film absorption treatment, and the product prepared by the preparation method is high in purity.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of sulfonamide synthesis, and particularly relates to a green and environmentally-friendly sulfonamide amidation preparation method. BACKGROUND

[0002] Sulfonamide compounds are a kind of functional materials with important industrial value, and are widely used in hydrometallurgy, engineering plastics, medicine and other fields. However, the traditional synthesis method of sulfonamide compounds has many drawbacks, the synthesis process is seriously polluted, the synthesis method has low yield, and the product has low purity, which cannot meet the requirements of modern industry for green environmental protection, high efficiency and low cost. SUMMARY

[0003] In view of the above problems, the application provides a green and environmentally-friendly sulfonamide amidation preparation method, which can perform falling film absorption treatment on the generated tail gas, and the product prepared by the preparation method has high purity.

[0004] In order to achieve the above purpose, the application provides a green and environmentally-friendly sulfonamide amidation preparation method, which comprises the following steps:

[0005] S1, chlorosulfonic acid is added to a reactor, stirred, and heated to 60-65 DEG C, then o-nitrochlorobenzene is added, and stage-by-stage heat preservation reaction is performed, then cooling is performed, and then thionyl chloride is added to react, so as to obtain 2-nitro-4-sulfonic acid chloro-chlorobenzene, and the tail gas generated in the reaction is introduced into a falling film absorption tower for absorption treatment;

[0006] In the above reaction, o-nitrochlorobenzene undergoes an electrophilic substitution reaction under the action of chlorosulfonic acid, and SO 3+ attacks the benzene ring as an electrophilic reagent, the nitro group is a strong electron-withdrawing group, which activates the deprotonation ability of the hydrogen in the meta position, promotes the sulfonic acid group to replace the hydrogen atom in the meta position of the nitro group, and generates 2-nitro-4-sulfonic acid chlorobenzene, thionyl chloride is used as a chlorinating agent, and through a nucleophilic substitution reaction, Cl - attacks the sulfur atom in 2-nitro-4-sulfonic acid chlorobenzene to generate 2-nitro-4-sulfonic acid chloro-chlorobenzene.

[0007] S2, 2-nitro-4-sulfonic acid chloro-chlorobenzene is isolated and filtered, ammonia water is added and stirred to react, heat preservation is performed, and pressure filtration is performed, so as to obtain 2-nitro-4-sulfonic acid amine-chlorobenzene, and the tail gas generated in the reaction is introduced into a falling film absorption tower for absorption treatment;

[0008] In the above reaction process, 2-nitro-4-sulfonic acid chloro-chlorobenzene undergoes a nucleophilic substitution reaction with ammonia water, the sulfamoyl group in 2-nitro-4-sulfonic acid chloro-chlorobenzene is replaced by an amino group, and 2-nitro-4-sulfonic acid amine-chlorobenzene is generated.

[0009] S3, stirring in liquid alkali in 2-nitro-4-sulfonamide-chlorobenzene, and heating to 100-103℃ for 2-3h, adjusting pH value by adding hydrochloric acid to obtain 2-nitro-4-sulfonamide-phenol, and the tail gas generated in the reaction is absorbed in a falling film absorption tower;

[0010] In the above reaction process, the nitro group and the sulfonamide group are strong electron-withdrawing groups, which significantly activate the chlorine atom on the chlorobenzene ring through conjugation effect and induction effect. The activated chlorine atom is a good leaving group, which is easily attacked by nucleophiles. In strong base conditions, hydroxyl ion as a nucleophile attacks the activated site of the chlorobenzene ring to form a phenoxy negative ion intermediate, and chloride ion as a leaving group is removed to generate 2-nitro-4-sulfonamide-phenol salt. Adding hydrochloric acid to generate 2-nitro-4-sulfonamide-phenol through acid-base reaction.

[0011] S4, adding water, catalyst and hydrazine hydrate in 2-nitro-4-sulfonamide-phenol, heating to 70-72℃ for 2-3h, pressure filtration to obtain 4-sulfonamide-2-amino-phenol.

[0012] In the above reaction process, hydrazine hydrate has strong reducing property. Under the catalysis of catalyst, the nitrogen element in hydrazine hydrate loses electrons to generate an active intermediate, and the nitrogen element in nitro group is reduced to -3 valence in amino group to generate amino group, and 4-sulfonamide-2-amino-phenol is generated. The structural formula of 4-sulfonamide-2-amino-phenol is:

[0013]

[0014] Further, the o-nitrochlorobenzene is added, and the molar ratio of o-nitrochlorobenzene to chlorosulfonic acid is 1:1.2-1.3.

[0015] Further, the reaction is kept at 80-90℃ for 2-3h, and kept at 105-110℃ for 4-5h.

[0016] Further, the thionyl chloride is added, and the molar ratio of thionyl chloride to o-nitrochlorobenzene is 1.1-1.2:1.

[0017] Further, the 2-nitro-4-sulfonamide-chlorobenzene is separated by adding 0-5℃ water with a mass of 1.5-2 times of 2-nitro-4-sulfonamide-chlorobenzene.

[0018] Further, the ammonia water is added, and the concentration of ammonia water is 25-30%, and the molar ratio of ammonia water to 2-nitro-4-sulfonamide-chlorobenzene is 1.1-1.2:1.

[0019] Further, the liquid alkali is 30-35% sodium hydroxide or 30-35% potassium hydroxide.

[0020] Further, the liquid alkali is added, and the molar ratio of the liquid alkali to 2-nitro-4-sulfonamide-chlorobenzene is 1.1-1.2:1.

[0021] Further, the pH value is adjusted to 6-7.

[0022] Further, the catalyst is composed of ferric chloride, copper chloride, activated carbon and 30% hydrochloric acid, the ferric chloride and the copper chloride are dissolved in the hydrochloric acid, the activated carbon is added and soaked for 2-3 hours, then filtered and dried to obtain the catalyst, the mass ratio of the ferric chloride, the copper chloride, the activated carbon and the 30% hydrochloric acid is 1:0.2-0.3:2-3:2-3, and the catalyst dosage is 5-8% of the mass of 2-nitro-4-sulfonamide-phenol.

[0023] Further, the hydrazine hydrate has a water content of >36%, and the molar ratio of the hydrazine hydrate to 2-nitro-4-sulfonamide-phenol is 2.5-3:1.

[0024] In summary, the present application has the following beneficial effects:

[0025] The preparation method of the sulfonamide in the present application adopts a staged heat preservation method, the reaction is preserved at 80-90 DEG C, the decomposition of chlorosulfonic acid to generate SO3 has a moderate rate, the concentration of the electrophilic reagent matches the reactivity of the benzene ring, the single sulfonation reaction occurs, after the sulfonation reaction, the sulfonic acid group in 2-nitro-4-sulfonamide-chlorobenzene is a strong electron-withdrawing group, which further reduces the electron cloud density of the benzene ring and inhibits the occurrence of polysulfonation reaction, the reaction is preserved at 105-110 DEG C, which promotes the further reaction of the unreacted ortho-nitrochlorobenzene, the thermodynamic stable product is generated under the high temperature condition of the sulfonation reaction, the reverse reaction is inhibited, the purity and yield of the main product are improved; the ferric chloride is reduced to Fe 2+ by the hydrazine hydrate in the initial stage of the reaction, Fe 2+ acts as an intermediate active species to transfer electrons with the nitro compound, and Cu 2+ stabilizes the intermediate, such as nitroso and hydroxylamine, by coordination, reduces the reaction energy barrier, improves the reaction rate, reduces the occurrence of side reactions, the copper chloride and the ferric chloride form Fe-Cu bimetallic active sites, increase the adsorption sites of the reactants, improve the contact efficiency of the substrate and the catalyst, accelerate the reduction reaction process and improve the yield; the activated carbon has a porous structure and a large specific surface area, can uniformly disperse the ferric chloride and the copper chloride on the surface of the activated carbon, effectively avoids the agglomeration of the catalyst particles, and thus significantly improves the catalytic activity, at the same time, the adsorption performance of the activated carbon can adsorb the reaction substrate, such as the organic compound containing nitro group, on the surface thereof, so that the substrate molecules fully contact with the catalyst and the reducing agent, increases the effective collision frequency, and ensures that the reaction is more complete and efficient; the preparation method of the present application performs falling film absorption treatment on the generated tail gas, and achieves the effect of green production. BRIEF DESCRIPTION OF DRAWINGS

[0026] To more clearly illustrate the technical solutions of the embodiments of this application, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0027] Figure 1 This is the high-performance liquid chromatogram of Example 1;

[0028] Figure 2 This is the high-performance liquid chromatogram of Example 2;

[0029] Figure 3 This is the high-performance liquid chromatogram of Example 3;

[0030] Figure 4 This is the high performance liquid chromatogram of control example 1;

[0031] Figure 5 This is the high performance liquid chromatogram of control example 2. Detailed Implementation

[0032] The technical solutions in the embodiments of this application will be clearly and completely described below with reference to the embodiments of this application. Obviously, the described embodiments are only some embodiments of this invention, and not all embodiments. Based on the embodiments of this invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of this invention.

[0033] The raw materials involved in the specific embodiments of this application are analytical grade.

[0034] Example 1

[0035] A green and environmentally friendly method for preparing sulfonamides by amidation includes the following steps:

[0036] S1. Add chlorosulfonic acid to the reactor, stir (100 rpm) and heat to 60°C, add o-nitrochlorobenzene, the molar ratio of o-nitrochlorobenzene to chlorosulfonic acid is 1:1.2, keep at 80°C for 3 h, keep at 105°C for 5 h, cool to 70°C, add thionyl chloride to react, the molar ratio of thionyl chloride to o-nitrochlorobenzene is 1.1:1, to obtain 2-nitro-4-sulfonic acid chloro-chlorobenzene, and the tail gas generated by the reaction enters the falling film absorption tower for absorption treatment;

[0037] S2. Place 2-nitro-4-sulfonic acid chloro-chlorobenzene into a separation vessel, add 0℃ water at twice the mass of 2-nitro-4-sulfonic acid chloro-chlorobenzene for separation, and filter the precipitated material into a tubular filter. The filtered material is then fed into an ammoniation reactor, where 28% ammonia water is added and stirred (at 120 rpm). The molar ratio of ammonia water to 2-nitro-4-sulfonic acid chloro-chlorobenzene is 1.1:1. The mixture is kept at 40℃ for 3 hours. After the heat treatment, the material is fed into an ammoniation filter press for filtration to obtain 2-nitro-4-sulfonic acid ammonium chlorobenzene. The tail gas generated by the reaction is absorbed and treated in a falling film absorption tower.

[0038] S3. Add a 30% sodium hydroxide solution to 2-nitro-4-sulfonic acid amine-chlorobenzene and stir (100 rpm). The molar ratio of sodium hydroxide to 2-nitro-4-sulfonic acid amine-chlorobenzene is 1.1:1. Heat to 100℃ and keep warm for 3 hours. Add hydrochloric acid to adjust the pH to 6 and react to obtain 2-nitro-4-sulfonic acid amine-phenol. The tail gas generated by the reaction enters the falling film absorption tower for absorption treatment.

[0039] S4. Add 5% of the mass of catalyst (ferric chloride, copper chloride, activated carbon, and 30% hydrochloric acid in a mass ratio of 1:0.2:2:2), hydrazine hydrate (molar ratio of hydrazine hydrate to 2-nitro-4-sulfonamide-phenol is 2.5:1), and water equal to twice the total mass of 2-nitro-4-sulfonamide-phenol, catalyst, and hydrazine hydrate to 2-nitro-4-sulfonamide-phenol. Heat to 70°C and stir for 3 hours. Filter using a filter press to obtain 4-sulfonamide-2-amino-phenol.

[0040] Example 2

[0041] A green and environmentally friendly method for preparing sulfonamides by amidation includes the following steps:

[0042] S1. Add chlorosulfonic acid to the reactor, stir (100 rpm) and heat to 65°C, add o-nitrochlorobenzene, the molar ratio of o-nitrochlorobenzene to chlorosulfonic acid is 1:1.3, keep at 85°C for 2 h, keep at 108°C for 4 h, cool to 70°C, add thionyl chloride to react, the molar ratio of thionyl chloride to o-nitrochlorobenzene is 1.2:1, to obtain 2-nitro-4-sulfonic acid chloro-chlorobenzene, the tail gas generated by the reaction enters the falling film absorption tower for absorption treatment;

[0043] S2. Place 2-nitro-4-sulfonic acid chloro-chlorobenzene into a separation vessel, add water at 3°C ​​with a mass twice that of 2-nitro-4-sulfonic acid chloro-chlorobenzene, and separate the precipitate into a tubular filter for filtration. The filtered material is then introduced into an ammoniation reactor, where 28% ammonia water is added and stirred (at 120 rpm). The molar ratio of ammonia water to 2-nitro-4-sulfonic acid chloro-chlorobenzene is 1.2:1. The mixture is kept at 40°C for 3 hours. After the heat treatment, the material is introduced into an ammoniation filter press for filtration to obtain 2-nitro-4-sulfonic acid ammonium chlorobenzene. The tail gas generated by the reaction is absorbed and treated in a falling film absorption tower.

[0044] S3. Add a 35% sodium hydroxide solution to 2-nitro-4-sulfonic acid amine-chlorobenzene and stir (100 rpm). The molar ratio of sodium hydroxide to 2-nitro-4-sulfonic acid amine-chlorobenzene is 1.2:1. Heat to 100℃ and keep warm for 3 hours. Add hydrochloric acid to adjust the pH to 7 and react to obtain 2-nitro-4-sulfonic acid amine-phenol. The tail gas generated by the reaction enters the falling film absorption tower for absorption treatment.

[0045] S4. Add 7% of the mass of catalyst (ferric chloride, copper chloride, activated carbon, and 30% hydrochloric acid in a mass ratio of 1:0.2:2:2), hydrazine hydrate (molar ratio of hydrazine hydrate to 2-nitro-4-sulfonamide-phenol is 2.8:1), and water equal to twice the total mass of 2-nitro-4-sulfonamide-phenol, catalyst, and hydrazine hydrate to 2-nitro-4-sulfonamide-phenol. Heat to 70°C and stir for 3 hours. Filter using a filter press to obtain 4-sulfonamide-2-amino-phenol.

[0046] Example 3

[0047] A green and environmentally friendly method for preparing sulfonamides by amidation includes the following steps:

[0048] S1. Add chlorosulfonic acid to the reactor, stir (100 rpm) and heat to 65°C, add o-nitrochlorobenzene, the molar ratio of o-nitrochlorobenzene to chlorosulfonic acid is 1:1.3, keep at 90°C for 2 h, keep at 110°C for 5 h, cool to 70°C, add thionyl chloride to react, the molar ratio of thionyl chloride to o-nitrochlorobenzene is 1.2:1, to obtain 2-nitro-4-sulfonic acid chloro-chlorobenzene, the tail gas generated by the reaction enters the falling film absorption tower for absorption treatment;

[0049] S2. Place 2-nitro-4-sulfonic acid chloro-chlorobenzene into a separation vessel, add water at 5°C with a mass twice that of 2-nitro-4-sulfonic acid chloro-chlorobenzene, and separate the precipitate into a tubular filter for filtration. The filtered material is then introduced into an ammoniation reactor, where 28% ammonia water is added and stirred (at 120 rpm). The molar ratio of ammonia water to 2-nitro-4-sulfonic acid chloro-chlorobenzene is 1.2:1. The mixture is kept at 40°C for 3 hours. After the heat treatment, the material is introduced into an ammoniation filter press for filtration to obtain 2-nitro-4-sulfonic acid ammonium chlorobenzene. The tail gas generated during the reaction is then absorbed and treated in a falling film absorption tower.

[0050] S3. Add a 35% sodium hydroxide solution to 2-nitro-4-sulfonic acid amine-chlorobenzene and stir (100 rpm). The molar ratio of sodium hydroxide to 2-nitro-4-sulfonic acid amine-chlorobenzene is 1.2:1. Heat to 100℃ and keep warm for 3 hours. Add hydrochloric acid to adjust the pH to 7 and react to obtain 2-nitro-4-sulfonic acid amine-phenol. The tail gas generated by the reaction enters the falling film absorption tower for absorption treatment.

[0051] S4. Add 8% of the mass of catalyst (ferric chloride, copper chloride, activated carbon, and 30% hydrochloric acid in a mass ratio of 1:0.3:3:3), hydrazine hydrate (molar ratio of hydrazine hydrate to 2-nitro-4-sulfonamide-phenol is 3:1), and water equal to twice the total mass of 2-nitro-4-sulfonamide-phenol, catalyst, and hydrazine hydrate to 2-nitro-4-sulfonamide-phenol. Heat to 70°C and stir for 3 hours. Filter using a filter press to obtain 4-sulfonamide-2-amino-phenol.

[0052] Compare with Example 1

[0053] The difference between this comparative example and Example 3 is that this comparative example provides a green and environmentally friendly method for preparing sulfonamides by amidation, which includes the following steps:

[0054] S1. Add chlorosulfonic acid to the reactor, stir (100 rpm) and heat to 65°C, add o-nitrochlorobenzene, the molar ratio of o-nitrochlorobenzene to chlorosulfonic acid is 1:1.3, keep at 110°C for 5 hours, cool down to 70°C, add thionyl chloride to react, the molar ratio of thionyl chloride to o-nitrochlorobenzene is 1.2:1, to obtain 2-nitro-4-sulfonic acid chloro-chlorobenzene, and the tail gas generated by the reaction enters the falling film absorption tower for absorption treatment;

[0055] S2. Place 2-nitro-4-sulfonic acid chloro-chlorobenzene into a separation vessel, add water at 5°C with a mass twice that of 2-nitro-4-sulfonic acid chloro-chlorobenzene, and separate the precipitate into a tubular filter for filtration. The filtered material is then introduced into an ammoniation reactor, where 28% ammonia water is added and stirred (at 120 rpm). The molar ratio of ammonia water to 2-nitro-4-sulfonic acid chloro-chlorobenzene is 1.2:1. The mixture is kept at 40°C for 3 hours. After the heat treatment, the material is introduced into an ammoniation filter press for filtration to obtain 2-nitro-4-sulfonic acid ammonium chlorobenzene. The tail gas generated during the reaction is then absorbed and treated in a falling film absorption tower.

[0056] S3. Add a 35% sodium hydroxide solution to 2-nitro-4-sulfonic acid amine-chlorobenzene and stir (100 rpm). The molar ratio of sodium hydroxide to 2-nitro-4-sulfonic acid amine-chlorobenzene is 1.2:1. Heat to 100℃ and keep warm for 3 hours. Add hydrochloric acid to adjust the pH to 7 and react to obtain 2-nitro-4-sulfonic acid amine-phenol. The tail gas generated by the reaction enters the falling film absorption tower for absorption treatment.

[0057] S4. Add 8% of the mass of catalyst (ferric chloride, copper chloride, activated carbon, and 30% hydrochloric acid in a mass ratio of 1:0.3:3:3), hydrazine hydrate (molar ratio of hydrazine hydrate to 2-nitro-4-sulfonamide-phenol is 3:1), and water equal to twice the total mass of 2-nitro-4-sulfonamide-phenol, catalyst, and hydrazine hydrate to 2-nitro-4-sulfonamide-phenol. Heat to 70°C and stir for 3 hours. Filter using a filter press to obtain 4-sulfonamide-2-amino-phenol.

[0058] Compare with Example 2

[0059] The difference between this comparative example and Example 2 is that this comparative example provides a green and environmentally friendly method for preparing sulfonamides by amidation, which includes the following steps:

[0060] S1. Add chlorosulfonic acid to the reactor, stir (100 rpm) and heat to 65°C, add o-nitrochlorobenzene, the molar ratio of o-nitrochlorobenzene to chlorosulfonic acid is 1:1.3, keep at 85°C for 2 h, keep at 108°C for 4 h, cool to 70°C, add thionyl chloride to react, the molar ratio of thionyl chloride to o-nitrochlorobenzene is 1.2:1, to obtain 2-nitro-4-sulfonic acid chloro-chlorobenzene, the tail gas generated by the reaction enters the falling film absorption tower for absorption treatment;

[0061] S2. Place 2-nitro-4-sulfonic acid chloro-chlorobenzene into a separation vessel, add water at 3°C ​​with a mass twice that of 2-nitro-4-sulfonic acid chloro-chlorobenzene, and separate the precipitate into a tubular filter for filtration. The filtered material is then introduced into an ammoniation reactor, where 28% ammonia water is added and stirred (at 120 rpm). The molar ratio of ammonia water to 2-nitro-4-sulfonic acid chloro-chlorobenzene is 1.2:1. The mixture is kept at 40°C for 3 hours. After the heat treatment, the material is introduced into an ammoniation filter press for filtration to obtain 2-nitro-4-sulfonic acid ammonium chlorobenzene. The tail gas generated by the reaction is absorbed and treated in a falling film absorption tower.

[0062] S3. Add a 35% sodium hydroxide solution to 2-nitro-4-sulfonic acid amine-chlorobenzene and stir (100 rpm). The molar ratio of sodium hydroxide to 2-nitro-4-sulfonic acid amine-chlorobenzene is 1.2:1. Heat to 100℃ and keep warm for 3 hours. Add hydrochloric acid to adjust the pH to 7 and react to obtain 2-nitro-4-sulfonic acid amine-phenol. The tail gas generated by the reaction enters the falling film absorption tower for absorption treatment.

[0063] S4. Add 7% of the mass of catalyst (ferric chloride, activated carbon, and 30% hydrochloric acid in a mass ratio of 1.2:2:2), hydrazine hydrate (molar ratio of hydrazine hydrate to 2-nitro-4-sulfonamide-phenol in a molar ratio of 2.8:1), and water equal to twice the total mass of 2-nitro-4-sulfonamide-phenol, catalyst, and hydrazine hydrate to 2-nitro-4-sulfonamide-phenol. Heat to 70°C and stir for 3 hours. Filter using a filter press to obtain 4-sulfonamide-2-amino-phenol.

[0064] Performance testing

[0065] The 4-sulfonamide-2-amino-phenol prepared by the methods of Examples 1-3 and Comparative Examples 1-2 was tested.

[0066] Table 1: Figure 1 Analysis results table

[0067] Table 2: Figure 2 Analysis results table

[0068] Table 3: Figure 3 Analysis results table

[0069]

[0070] Table 4: Figure 4 Analysis results table

[0071]

[0072] Table 5:Figure 5 Analysis results table

[0073]

[0074] Continued from table:

[0075]

[0076] 4-Sulfanamide-2-aminophenol prepared by the methods in Examples 1-3 and Comparative Examples 1-2 was detected by high-performance liquid chromatography (HPLC). The chromatographic column was a C18 column, the mobile phase was phosphate buffer (pH 2.5)-acetonitrile, the flow rate was 1.0 mL / min, the detector was a UV detector, and the detection wavelength was 270 nm. The detection results are shown in the figure. Figure 1 Table 1 shows the high-performance liquid chromatography (HPLC) analysis report for Example 1. The highest peak, 4-sulfonamide-2-amino-phenol, was observed at a retention time of 6.382 min, with a peak area ratio of 98.65%, indicating a content of 98.65% and very high purity. Figure 2 Table 2 shows the high-performance liquid chromatography (HPLC) analysis report for Example 2. The peak at retention time 6.398 min is 4-sulfonamide-2-amino-phenol, which is the highest peak. The peak area ratio at this point is 99.07%, the content is 99.07%, and the purity reaches over 99%. Figure 3 Table 3 shows the high-performance liquid chromatography (HPLC) analysis report for Example 3. The highest peak is observed at a retention time of 6.400 min, which is the 4-sulfonamide-2-amino-phenol peak. The peak area ratio of this peak is 98.14%, indicating that the 4-sulfonamide-2-amino-phenol prepared in Example 3 has a purity of 98.14%, which is very high. The difference between Control Example 1 and Example 3 is that Control Example 1 was directly incubated at 110℃ for 5 hours, leading to a vigorous reaction, side reactions, and a decrease in purity. Figure 4 Table 4 shows the high-performance liquid chromatography (HPLC) analysis report of Comparative Example 1. The highest peak was observed at a retention time of 7.626 min, with a peak area ratio of 95.32%, indicating that the purity of 4-sulfonamide-2-amino-phenol prepared in Comparative Example 1 was 95.32%, which is lower than that of Example 3. Compared with Example 2, Comparative Example 2 used ferric chloride instead of copper chloride, resulting in a single catalyst with fewer reactive sites, reduced reaction efficiency, and loss of Cu. 2+ Stabilizing intermediates increase side reactions and decrease purity, such as Figure 5 Table 5 shows the high performance liquid chromatography analysis report of Control Example 2. The highest peak was observed at a retention time of 6.354 min, with a peak area ratio of 97.22%, indicating that the purity of 4-sulfonamide-2-amino-phenol prepared in Control Example 2 was 97.22%, which is lower than that of Example 2.

[0077] The above description is merely an example and illustration of the concept of this application. Those skilled in the art can make various modifications or additions to the specific embodiments described or use similar methods to replace them, as long as they do not deviate from the inventive concept or exceed the scope defined in the claims, they should all fall within the protection scope of this application.

Claims

1. A green and environmentally friendly method for preparing sulfonamides by amidation, characterized in that, Includes the following steps: S1. Add chlorosulfonic acid to the reactor, stir, heat to 60-65℃, add o-nitrochlorobenzene, keep the temperature for reaction in stages, cool down, add thionyl chloride to react, and obtain 2-nitro-4-sulfonic acid chloro-chlorobenzene. The tail gas generated by the reaction enters the falling film absorption tower for absorption treatment. S2. Separate and filter 2-nitro-4-sulfonic acid chloro-chlorobenzene, add ammonia water, stir and react, keep warm, and filter under pressure to obtain 2-nitro-4-sulfonic acid amine-chlorobenzene. The tail gas generated by the reaction enters the falling film absorption tower for absorption treatment. S3. Add liquid alkali to 2-nitro-4-sulfonic acid amine-chlorobenzene and stir. Heat to 100-103℃ and keep warm for 2-3 hours. Add hydrochloric acid to adjust the pH value and react to obtain 2-nitro-4-sulfonic acid amine-phenol. The tail gas generated by the reaction enters the falling film absorption tower for absorption treatment. S4. Add water, catalyst and hydrazine hydrate to 2-nitro-4-sulfonic acid amine-phenol, heat to 70-72℃, stir for 2-3 hours, and filter under pressure to obtain 4-sulfonamide-2-amino-phenol.

2. The green and environmentally friendly sulfonamide amidation preparation method according to claim 1, characterized in that, The o-nitrochlorobenzene is added, and the molar ratio of o-nitrochlorobenzene to chlorosulfonic acid is 1:1.2-1.

3.

3. The green and environmentally friendly sulfonamide amidation preparation method according to claim 1, characterized in that, The phased heat preservation reaction involves maintaining the temperature at 80-90℃ for 2-3 hours and at 105-110℃ for 4-5 hours.

4. The green and environmentally friendly sulfonamide amidation preparation method according to claim 1, characterized in that, The addition of thionyl chloride, wherein the molar ratio of thionyl chloride to o-nitrochlorobenzene is 1.1-1.2:

1.

5. The green and environmentally friendly sulfonamide amidation preparation method according to claim 1, characterized in that, The ammonia solution is added at a concentration of 25-30%, and the molar ratio of ammonia solution to 2-nitro-4-sulfonic acid chloro-chlorobenzene is 1.1-1.2:

1.

6. The green and environmentally friendly sulfonamide amidation preparation method according to claim 1, characterized in that, The added liquid alkali is 30-35% sodium hydroxide or 30-35% potassium hydroxide.

7. The green and environmentally friendly method for preparing sulfonamides by amidation according to claim 1, characterized in that, The added liquid alkali has a molar ratio of 1.1-1.2:1 to the liquid alkali and 2-nitro-4-sulfonamide-chlorobenzene.

8. The green and environmentally friendly method for preparing sulfonamides by amidation according to claim 1, characterized in that, The pH value is adjusted to 6-7.

9. The green and environmentally friendly method for preparing sulfonamides by amidation according to claim 1, characterized in that, The catalyst is composed of ferric chloride, copper chloride, activated carbon, and 30% hydrochloric acid. Ferric chloride and copper chloride are dissolved in hydrochloric acid, activated carbon is added and soaked for 2-3 hours, and then filtered and dried to obtain the catalyst. The mass ratio of ferric chloride, copper chloride, activated carbon, and 30% hydrochloric acid is 1:0.2-0.3:2-3:2-3. The amount of catalyst used is 5-8% of the mass of 2-nitro-4-sulfonic acidamine-phenol.

10. The green and environmentally friendly method for preparing sulfonamides by amidation according to claim 1, characterized in that, The hydrazine hydrate has a water content >36%, and the molar ratio of hydrazine hydrate to 2-nitro-4-sulfonic acid amine-phenol is 2.5-3:1.

Images