CN114920670B - Preparation method of 5-chloro-2-aminobenzenesulfonamide - Google Patents

Preparation method of 5-chloro-2-aminobenzenesulfonamide Download PDF

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CN114920670B
CN114920670B CN202210844821.8A CN202210844821A CN114920670B CN 114920670 B CN114920670 B CN 114920670B CN 202210844821 A CN202210844821 A CN 202210844821A CN 114920670 B CN114920670 B CN 114920670B
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aminobenzenesulfonamide
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chlorosulfonyl
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CN114920670A (en
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乔红运
许峰
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Zesheng Technology Guangzhou Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
    • C07C303/38—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reaction of ammonia or amines with sulfonic acids, or with esters, anhydrides, or halides thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/02—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof
    • C07C303/22—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof from sulfonic acids, by reactions not involving the formation of sulfo or halosulfonyl groups; from sulfonic halides by reactions not involving the formation of halosulfonyl groups
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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Abstract

The invention discloses a preparation method of 5-chloro-2-aminobenzenesulfonamide, relating to the technical field of organic compound preparation and comprising the following two steps: firstly, taking 4-chloro-2- (chlorosulfonyl) benzoic acid and sodium azide as raw materials, adding the 4-chloro-2- (chlorosulfonyl) benzoic acid into a solvent, adding the sodium azide into the system, keeping the temperature for reaction for a period of time, adding sodium nitrite and sulfuric acid into a mixed solution, adding sodium hydroxide into the mixed solution after ice bath for a period of time, adding an organic reagent for extraction after water washing, and recrystallizing and purifying an organic layer after rotary evaporation to obtain an intermediate 2-amino-5-chlorobenzenesulfonyl chloride; secondly, adding an intermediate 2-amino-5-chlorobenzenesulfonyl chloride into water, and slowly adding ammonia water into the system; filtering after reaction, and extracting a filter cake by an alcohol-water method to obtain white powder, namely a pure product of the 5-chloro-2-aminobenzenesulfonamide. The method has the advantages of simple equipment, no pressure operation, easy product purification, simple operation and good yield.

Description

Preparation method of 5-chloro-2-aminobenzenesulfonamide
Technical Field
The invention belongs to the technical field of organic compound preparation, and particularly relates to a preparation method of 5-chloro-2-aminobenzenesulfonamide.
Background
5-chloro-2-aminobenzenesulfonamide is an important medical intermediate, and downstream products of benzothiadiazine derivatives of the aminobenzenesulfonamide are widely applied to different medical fields.
The current preparation method of 5-chloro-2-aminobenzenesulfonamide comprises the following steps: firstly, 5-chlorobenzothiadiazine is used as a raw material for hydrolysis, so that the raw material cost is high and the economic benefit is poor; secondly, the o-aminobenzenesulfonamide is prepared by chlorination of the o-aminobenzenesulfonamide, so that the reaction time is long and the yield is low; the p-chloroaniline reacts with nitromethane and sulfuric acid under the catalysis of aluminum trichloride, and the method has the advantages of low yield and harsh reaction conditions; fourthly, p-chlorodiphenylamine is directly sulfonylated, and the operation of sulfonation by sulfur dioxide has large corrosion to equipment, more steps and low yield; fifthly, the catalyst is obtained by catalytic hydrogenation reduction of 5-chloro-2-nitrobenzenesulfonamide nickel, the reaction conditions are harsh, and the catalyst is not suitable for industrial production; sixthly, iron mud formed by reducing 5-chloro-2-aminobenzene sulfonyl chloride and nitro is difficult to treat, and the product is difficult to purify.
Disclosure of Invention
The invention aims to provide a preparation method of 5-chloro-2-aminobenzenesulfonamide, which has the advantages of simple and easily obtained raw materials, wide sources, short reaction route, low production cost and convenience for industrial production; the yield of the prepared 5-chloro-2-aminobenzene sulfonamide product is obviously increased, and the product purity is good.
The technical scheme adopted by the invention for realizing the purpose is as follows:
a preparation method of 5-chloro-2-aminobenzenesulfonamide comprises the following steps:
the method comprises the following steps: 4-chloro-2- (chlorosulfonyl) benzoic acid and sodium azide are used as raw materials, carboxyl in a structure of the 4-chloro-2- (chlorosulfonyl) benzoic acid is converted into amino in a solvent system, and an intermediate 2-amino-5-chlorobenzenesulfonyl chloride is obtained;
step two: ammoniating sulfonyl chloride in the intermediate 2-amino-5-chlorobenzenesulfonyl chloride structure under the condition of ammonia water, and then extracting and purifying by an alcohol-water method to obtain the pure 5-chloro-2-aminobenzenesulfonamide. The invention adopts a two-step method, takes 4-chlorine-2- (chlorosulfonyl) benzoic acid as a raw material, prepares 2-amino-5-chlorobenzene sulfonyl chloride under the action of sodium azide, and prepares 5-chlorine-2-aminobenzene sulfonamide through ammonia water amination, and the raw material is simple and easy to obtain, the source is wide, the reaction route is short, and the production cost is low. Meanwhile, the preparation method of the 5-chloro-2-aminobenzenesulfonamide provided by the invention has the advantages that the required equipment for the reaction is simple, the operation is carried out under normal pressure, high temperature is not required, and the reaction condition is not harsh; and the intermediate product and the target product of the preparation method are easy to purify, the operation is simple and convenient, the yield is good, and the product purity is high.
Specifically, the preparation method of the 5-chloro-2-aminobenzenesulfonamide comprises the following reaction steps:
the method comprises the following steps: taking 4-chloro-2- (chlorosulfonyl) benzoic acid and sodium azide as raw materials, adding the 4-chloro-2- (chlorosulfonyl) benzoic acid into a solvent, adding sodium azide into the system, keeping the temperature for reaction for a period of time, adding sodium nitrite and sulfuric acid into a mixed solution, carrying out ice bath for a period of time, adding sodium hydroxide into the mixed solution, washing, adding an organic reagent for extraction, carrying out rotary evaporation on an organic layer, and then recrystallizing and purifying to obtain an intermediate 2-amino-5-chlorobenzenesulfonyl chloride;
step two: adding the intermediate 2-amino-5-chlorobenzenesulfonyl chloride into water, and slowly adding ammonia water into the system; filtering after reaction, and extracting a filter cake by an alcohol-water method to obtain white powder, namely a pure product of the 5-chloro-2-aminobenzenesulfonamide.
In an embodiment of the present invention, the reaction route of the preparation method of 5-chloro-2-aminobenzenesulfonamide includes:
Figure DEST_PATH_IMAGE002
。
in a specific embodiment of the present invention, the solvent in the first step is selected from one of acetone and DMF.
In one embodiment of the present invention, the organic solvent in the first step is an alcohol solvent.
Further, the alcohol solvent is selected from one of ethanol, methanol and n-butanol.
In the specific embodiment of the invention, in the first step, the molar ratio of 4-chloro-2- (chlorosulfonyl) benzoic acid to sodium azide, sodium nitrite and sulfuric acid is 1.03 to 1.12.
In the specific embodiment of the invention, the molar ratio of the 4-chloro-2- (chlorosulfonyl) benzoic acid to the sodium hydroxide in the first step is 1.5 to 2.5.
In the specific embodiment of the invention, in the first step, the sodium azide is added and then the temperature is raised to 50 to 80 ℃.
In the specific embodiment of the invention, the heat preservation time in the step one is 1 to 2.5 hours.
In a specific embodiment of the invention, the molar ratio of the 2-amino-5-chlorobenzenesulfonyl chloride to the ammonia water in the second step is 1 to 2.5-5.
In the specific embodiment of the invention, the reaction time of the second step in the second step is 1.0 to 3h.
In a specific embodiment of the present invention, the alcohol used in the alcohol-water process in step two comprises ethanol; the water is deionized water.
In the alcohol-water method, the 5-chloro-2-aminobenzenesulfonamide crude product is dissolved by using ethanol, deionized water is added into the 5-chloro-2-aminobenzenesulfonamide crude product, a white-like solid is precipitated after standing, and the pure 5-chloro-2-aminobenzenesulfonamide product is obtained after filtration and drying.
Furthermore, the volume ratio of the ethanol to the water in the alcohol-water method is 1 to 5 to 10.
The yield of the 5-chloro-2-aminobenzenesulfonamide prepared by the preparation method is more than or equal to 85.0 percent; more preferably, the yield of the 5-chloro-2-aminobenzenesulfonamide prepared by the preparation method is more than 90.0 percent.
The purity of the 5-chloro-2-aminobenzenesulfonamide prepared by the preparation method is more than 98.00 percent; more preferably, the purity of the 5-chloro-2-aminobenzenesulfonamide prepared by the preparation method is more than 99.00 percent.
Compared with the prior art, the invention has the following beneficial effects:
the 5-chloro-2-aminobenzenesulfonamide is synthesized by taking 4-chloro-2- (chlorosulfonyl) benzoic acid as a raw material, the raw material is simple and easy to obtain, the source is wide, and the production cost can be effectively reduced; the method has the advantages of short reaction route, simple required equipment, mild operation conditions, easy purification of the prepared intermediate product and the target product, simple and convenient operation, high yield of the obtained target product, good purity and guaranteed product quality.
Therefore, the invention provides a preparation method of 5-chloro-2-aminobenzenesulfonamide, which has the advantages of simple and easily obtained raw materials, wide sources, short reaction route, low production cost and convenience for industrial production; the yield of the prepared 5-chloro-2-aminobenzene sulfonamide product is obviously increased, and the product purity is good.
Detailed Description
The technical solutions of the present invention are described in further detail below with reference to specific embodiments, but it should be understood that these examples are only for illustrating the disclosure of the present invention to assist understanding, and do not limit the scope of the present invention, and the scope of the present invention is not limited to the following examples.
The present invention is not particularly limited with respect to the sources of the raw materials in the following examples, and they may be prepared by a preparation method known to those skilled in the art or commercially available.
The 4-chloro-2- (chlorosulfonyl) benzoic acid used in the embodiment of the invention is obtained by market order, and the preparation method comprises the following steps: adding 1.4 equivalent of LiOH into a THF/water (v/v, 1:1) mixed medium, reacting at room temperature, performing rotary evaporation after TLC monitoring reaction is finished, adding a small amount of water, washing for 3 times by using dichloromethane, adding 1M hydrochloric acid to adjust the pH to 5, performing suction filtration, adding a filter cake into methyl tert-butyl ether, pulping for 3 hours, performing suction filtration, and drying to obtain 4-chloro-2- (chlorosulfonyl) benzoic acid. The nuclear magnetic data are as follows: 1 H NMR (400 MHz, DMSO-d 6 ), δ ppm ：12.47(s，1H，-COOH)，8.39、8.27、7.93 (3H, Ar-H)。
the concentration of the ammonia water used in the embodiment of the invention is 22%.
Example 1:
the preparation method of the 5-chloro-2-aminobenzenesulfonamide comprises two steps, and the specific reaction steps are as follows:
the method comprises the following steps: taking 4-chloro-2- (chlorosulfonyl) benzoic acid and sodium azide as raw materials, adding 100g of 4-chloro-2- (chlorosulfonyl) benzoic acid into 200mL of DMF, adding 26.25g of sodium azide into a solution system, heating to 55 ℃ after the sodium azide is added, preserving heat for 1h, adding 28.40g of sodium nitrite into a mixed solution, slowly adding 31.39g of 98% concentrated sulfuric acid after sodium sulfite is completely added, then adding 23.52g of sodium hydroxide into the mixed solution after ice bath for a period of time, adding methanol for extraction after water washing, adding methanol for recrystallization and purification after organic layer rotary evaporation, slowly adding methanol until the methanol is dissolved at a reflux temperature, cooling and crystallizing to obtain an intermediate 2-amino-5-chlorobenzenesulfonyl chloride, wherein the yield is 76.0%; the nuclear magnetic data are as follows: 1 H NMR (500 MHz, DMSO-d 6 ), δ ppm ：7.90、7.37、6.89 (3H, Ar-H)，5.43(s，2H，-NH 2 )；
step two: adding 2-amino-5-chlorobenzene sulfonyl chloride of 79.28g of an intermediate into 500L of water, slowly adding 104.44g of ammonia water into the system, reacting at normal temperature for 1.0h, filtering after the reaction, adding a filter cake into ethanol at reflux temperature, then adding deionized water into the ethanol, wherein the volume ratio of ethanol to water is 1; the nuclear magnetic data are as follows: 1 H NMR (500 MHz, DMSO-d 6 ), δ ppm ：7.23(s，2H，-NH 2 )，7.93、7.41、6.95 (3H, Ar-CH)，5.54(s，2H，-NH 2 )。
example 2:
the preparation method of 5-chloro-2-aminobenzenesulfonamide is different from that of example 1: the method changes the experimental conditions such as the dosage of each raw material, the reaction temperature and the like, and comprises the following specific reaction processes:
the method comprises the following steps: taking 4-chloro-2- (chlorosulfonyl) benzoic acid and sodium azide as raw materials, adding 100g of 4-chloro-2- (chlorosulfonyl) benzoic acid into 200mL of DMF, adding 27.02g of sodium azide into a solution system, heating to 70 ℃ after adding the sodium azide, keeping the temperature for reaction for 1.6h, adding 29.21g of sodium nitrite into a mixed solution, slowly adding 39.23g of 98% concentrated sulfuric acid after completely adding sodium sulfite, then adding 28.23g of sodium hydroxide into the mixed solution after ice bath for a period of time, adding ethanol after washing for extraction, carrying out rotary evaporation on an organic layer, adding ethanol for recrystallization and purification, slowly adding ethanol until the ethanol is dissolved at a reflux temperature, cooling and crystallizing to obtain an intermediate 2-amino-5-chlorobenzenesulfonyl chloride, wherein the yield is 80.2%;
step two: adding 83.66g of intermediate 2-amino-5-chlorobenzenesulfonyl chloride into 500mL of water, slowly adding 131.92g of ammonia water into the system, reacting at normal temperature for 2h, filtering after the reaction, adding filter cakes into ethanol at the reflux temperature, then adding deionized water into the mixture, wherein the volume ratio of ethanol to water is 1.
Example 3:
the preparation method of 5-chloro-2-aminobenzenesulfonamide is different from that of example 1: the method changes the experimental conditions such as the dosage of each raw material, the reaction temperature and the like, and comprises the following specific reaction processes:
the method comprises the following steps: taking 4-chloro-2- (chlorosulfonyl) benzoic acid and sodium azide as raw materials, adding 100g of 4-chloro-2- (chlorosulfonyl) benzoic acid into 250mL of acetone, adding 28.04g of sodium azide into a solution system, heating to 64 ℃ after the sodium azide is added, carrying out heat preservation reaction for 1.5h, adding 29.75g of sodium nitrite into a mixed solution, slowly adding 35.3g of 98% concentrated sulfuric acid after sodium sulfite is completely added, then adding 31.36g of sodium hydroxide into the mixed solution after ice bath for a period of time, washing with water, adding ethanol for extraction, carrying out rotary evaporation on an organic layer, adding ethanol for recrystallization and purification, slowly adding ethanol until the ethanol is dissolved at a reflux temperature, cooling and crystallizing to obtain an intermediate 2-amino-5-chlorobenzenesulfonyl chloride, wherein the yield is 82.0%;
step two: adding 85.54g of intermediate 2-amino-5-chlorobenzenesulfonyl chloride into 400mL of water, slowly adding 157.76 ammonia water into the system, reacting at normal temperature for 2.5h, filtering after the reaction, adding filter cakes into ethanol at the reflux temperature, then adding deionized water into the mixture, wherein the volume ratio of ethanol to water is 1:8, standing to precipitate a white-like solid, filtering and drying to obtain white-like powder, namely a pure 5-chloro-2-aminobenzenesulfonamide product, wherein the yield of the step is 91.8%.
Example 4:
the preparation method of 5-chloro-2-aminobenzenesulfonamide is different from that of example 1: the method changes the experimental conditions such as the dosage of each raw material, the reaction temperature and the like, and comprises the following specific reaction processes:
the method comprises the following steps: taking 4-chloro-2- (chlorosulfonyl) benzoic acid and sodium azide as raw materials, adding 100g of 4-chloro-2- (chlorosulfonyl) benzoic acid into 300mL of acetone, adding 27.78g of sodium azide into a solution system, heating to 72 ℃ after the sodium azide is added, carrying out heat preservation reaction for 2.0 hours, adding 29.75g of sodium nitrite into a mixed solution, slowly adding 58.34g of 98% concentrated sulfuric acid after sodium sulfite is completely added, then adding 31.36g of sodium hydroxide into the mixed solution after ice bath for a period of time, washing with water, adding ethanol for extraction, carrying out rotary evaporation on an organic layer, adding ethanol for recrystallization and purification, slowly adding ethanol until the ethanol is dissolved at a reflux temperature, cooling and crystallizing to obtain an intermediate 2-amino-5-chlorobenzenesulfonyl chloride, wherein the yield is 84.0%;
and secondly, adding 87.62g of intermediate 2-amino-5-chlorobenzene sulfonyl chloride into 600mL of water, slowly adding 161.6g of ammonia water into the system, reacting at normal temperature for 2.5h, filtering after the reaction, adding deionized water into a filter cake at the ethanol reflux temperature, standing to precipitate a white-like solid, filtering and drying to obtain white-like powder, namely a pure 5-chloro-2-aminobenzenesulfonamide product, wherein the volume ratio of ethanol to water is 1:6, and the yield of the step is 92.1%.
Example 5:
the preparation method of 5-chloro-2-aminobenzenesulfonamide is different from that of example 1: the method changes the experimental conditions such as the dosage of each raw material, the reaction temperature and the like, and comprises the following specific reaction processes:
the method comprises the following steps: taking 4-chloro-2- (chlorosulfonyl) benzoic acid and sodium azide as raw materials, adding 100g of 4-chloro-2- (chlorosulfonyl) benzoic acid into 150mL of DMF, adding 28.55g of sodium azide into a solution system, heating to 80 ℃ after the sodium azide is added, carrying out heat preservation reaction for 2.5 hours, adding 31.11g of sodium nitrite into a mixed solution, slowly adding 43.15g of 98% concentrated sulfuric acid after sodium sulfite is completely added, then adding 39.2g of sodium hydroxide into the mixed solution after ice bath for a period of time, washing with water, adding n-butanol for extraction, carrying out rotary evaporation on an organic layer, adding n-butanol for recrystallization and purification, slowly adding the n-butanol until the n-butanol is dissolved at a reflux temperature, cooling and crystallizing to obtain an intermediate 2-amino-5-chlorobenzenesulfonyl chloride, wherein the yield is 80.8%;
step two: adding 2-amino-5-chlorobenzene sulfonyl chloride of 84.28g of an intermediate into 350mL of water, slowly adding 178.08 ammonia water into the system, reacting at normal temperature for 3h, filtering after the reaction, adding a filter cake into ethanol at the reflux temperature, then adding deionized water into the filter cake, wherein the volume ratio of ethanol to water is 1:6, standing to precipitate a white-like solid, filtering, and drying to obtain white-like powder, namely a pure 5-chloro-2-aminobenzenesulfonamide product, wherein the yield of the step is 89.0%.
Example 6:
the preparation method of 5-chloro-2-aminobenzenesulfonamide is different from that of example 1: the method changes the experimental conditions such as the dosage of each raw material, the reaction temperature and the like, and comprises the following specific reaction processes:
the method comprises the following steps: taking 4-chloro-2- (chlorosulfonyl) benzoic acid and sodium azide as raw materials, adding 100g of 4-chloro-2- (chlorosulfonyl) benzoic acid into 200mL of acetone, adding 28.04g of sodium azide into a solution system, heating to 70 ℃ after the sodium azide is added, carrying out heat preservation reaction for 2.5 hours, adding 32.46g of sodium nitrite into mixed solution, slowly adding 46.14g of 98% concentrated sulfuric acid after sodium sulfite is completely added, then adding 31.36g of sodium hydroxide into the mixed solution after ice bath for a period of time, washing with water, adding ethanol for extraction, carrying out rotary evaporation on an organic layer, adding ethanol for recrystallization and purification, slowly adding ethanol until the ethanol is dissolved at a reflux temperature, cooling and crystallizing to obtain an intermediate 2-amino-5-chlorobenzenesulfonyl chloride, wherein the yield is 78.6%;
step two: adding 81.99g of intermediate 2-amino-5-chlorobenzenesulfonyl chloride into 300mL of water, slowly adding 195.4 ammonia water into the system, reacting at normal temperature for 2.0h, filtering after reaction, adding filter cakes into ethanol at the reflux temperature, then adding deionized water into the filter cakes, wherein the volume ratio of the ethanol to the water is 1:6, standing to precipitate a white-like solid, filtering and drying to obtain white-like powder, namely a pure 5-chloro-2-aminobenzenesulfonamide product, wherein the yield of the step is 87.0%.
Example 7:
the preparation method of 5-chloro-2-aminobenzenesulfonamide is different from that of example 1: the method changes the experimental conditions such as the dosage of each raw material, the reaction temperature and the like, and comprises the following specific reaction processes:
the method comprises the following steps: taking 4-chloro-2- (chlorosulfonyl) benzoic acid and sodium azide as raw materials, adding 100g of 4-chloro-2- (chlorosulfonyl) benzoic acid into 200mL of acetone, adding 28.55g of sodium azide into a solution system, heating to 78 ℃ after adding the sodium azide, carrying out heat preservation reaction for 2.5 hours, adding 32.46g of sodium nitrite into a mixed solution, slowly adding 48.06g of 98% concentrated sulfuric acid after completely adding sodium sulfite, then adding 39.20g of sodium hydroxide into the mixed solution after ice bath for a period of time, adding n-butyl alcohol after washing for extraction, carrying out rotary evaporation on an organic layer, adding the n-butyl alcohol again for recrystallization and purification, slowly adding the n-butyl alcohol until the n-butyl alcohol is dissolved at a reflux temperature, and cooling and crystallizing to obtain an intermediate 2-amino-5-chlorobenzene, wherein the yield is 77.1%;
step two: adding 2-amino-5-chlorobenzene sulfonyl chloride of 80.42g of an intermediate into 300mL of water, slowly adding 211.6g of ammonia water into the system, reacting at normal temperature for 1h, filtering after the reaction, adding a filter cake into ethanol at the reflux temperature, then adding deionized water into the ethanol, wherein the volume ratio of the ethanol to the water is 1:5, standing for precipitation of an off-white solid, filtering and drying to obtain off-white powder, namely a pure 5-chloro-2-aminobenzenesulfonamide product, wherein the yield of the step is 85.0%.
Example 8:
the preparation method of 5-chloro-2-aminobenzenesulfonamide is different from that of example 1: replacing 1/2 molar mass of ammonia water in the second step with pyrrolidine ammonium dithioformate; the yield in this step was 89.3%. According to the invention, ammonium pyrrolidine dithiocarbamate is used for replacing ammonia water to carry out amination reaction, and the yield of the obtained product is further increased, the purity is higher and the quality is better by increasing the conversion rate of amination reaction.
Example 9:
the preparation method of 5-chloro-2-aminobenzenesulfonamide is different from that of example 1: in the second step, ammonia water is replaced by pyrrolidine ammonium dithioformate with equal molar quantity; the yield in this step was 93.5%.
Test example 1:
purity test results
The 5-chloro-2-aminobenzenesulfonamide prepared in example 1~9 was tested for purity and the results are shown in table 1:
TABLE 1 purity test results for 5-chloro-2-aminobenzenesulfonamide product
Figure DEST_PATH_IMAGE004
As can be seen from the data in the table 1, the purity of the product prepared by the preparation method of 5-chloro-2-aminobenzenesulfonamide provided by the invention is more than 98.00%, the product purity is good, and the product quality is high; moreover, the purity of the product prepared in example 9 can reach more than 99.00%, which is obviously better than that of examples 1 and 8, and the effect of example 8 is better than that of example 1, which shows that by adopting pyrrolidine ammonium dithioformate to replace ammonia water for amination reaction, the purity of the obtained product can be higher and the quality is better by increasing the conversion rate of amination reaction.
Conventional techniques in the above embodiments are known to those skilled in the art, and therefore, will not be described in detail herein.
The above description is only for the specific embodiments of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art can easily conceive of the changes or substitutions within the technical scope of the present invention, and all the changes or substitutions should be covered within the scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the appended claims.

Claims (5)

1. A preparation method of 5-chloro-2-aminobenzenesulfonamide comprises the following steps:
the method comprises the following steps: taking 4-chloro-2- (chlorosulfonyl) benzoic acid and sodium azide as raw materials, adding the 4-chloro-2- (chlorosulfonyl) benzoic acid into a solvent, adding sodium azide into the system, keeping the temperature for reaction for a period of time, adding sodium nitrite and sulfuric acid into a mixed solution, carrying out ice bath for a period of time, adding sodium hydroxide into the mixed solution, washing, adding an organic reagent for extraction, carrying out rotary evaporation on an organic layer, and then recrystallizing and purifying to obtain an intermediate 2-amino-5-chlorobenzenesulfonyl chloride;
step two: adding the intermediate 2-amino-5-chlorobenzenesulfonyl chloride into water, and slowly adding ammonium pyrrolidine dithiocarbamate into the system; filtering after reaction, and extracting a filter cake by an alcohol-water method to obtain white powder, namely a pure 5-chloro-2-aminobenzenesulfonamide product;
in the first step, the molar ratio of 4-chloro-2- (chlorosulfonyl) benzoic acid to sodium azide is 1.03 to 1.12;
the yield of the 5-chloro-2-aminobenzenesulfonamide prepared by the preparation method is more than or equal to 85.0 percent.
2. The process for preparing 5-chloro-2-aminobenzenesulfonamide according to claim 1, wherein: the solvent in the first step is selected from one of acetone and DMF.
3. The process for preparing 5-chloro-2-aminobenzenesulfonamide according to claim 1, wherein: in the first step, after adding sodium azide, heating to 50-80 ℃.
4. The process for preparing 5-chloro-2-aminobenzenesulfonamide according to claim 1, wherein: the alcohol adopted in the alcohol-water method is ethanol.
5. The process according to claim 4, wherein the reaction mixture comprises the following components: the volume ratio of ethanol to water in the alcohol-water method is 1 to 5-10.
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