A process for the synthesis of high purity sulfonamide chlorodiazine sodium

Abstract

The application discloses a synthesis process of high-purity sulfonamide chlorodiazine sodium, and belongs to the technical field of medicine industry synthesis, which comprises the following steps: synthesizing a condensate, synthesizing sulfonamide chlorodiazine, and synthesizing sulfonamide chlorodiazine sodium finished product; the condensate is synthesized by mixing an aromatic hydrocarbon solvent, 3,6-dichloropyridazine, p-acetamidobenzenesulfonamide, an acid-binding agent and a catalyst at 20-30 DEG C, and then performing a reflux water separation reaction at 100-120 DEG C; after 6-10 hours of reaction, the temperature is lowered to obtain a condensate liquid; and the catalyst is one of cuprous bromide, cuprous iodide and cuprous chloride. The synthesis process has the advantages of safety and environmental protection, cheap and easily available raw materials, simple process and low production cost, and the prepared sulfonamide chlorodiazine sodium has high yield and high purity.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of synthetic technology in the pharmaceutical industry, in particular to a synthesis process of high-purity sulfachloropyridazine sodium. BACKGROUND

[0002] Sulfonamides, such as sulfamethoxazole, sulfadiazine, etc. are the earliest synthetic antibacterial drugs discovered in human history, and have a history of nearly a hundred years. In recent years, in the field of veterinary antibacterial drugs, sulfonamides stand out with their unique broad-spectrum antibacterial and antiparasitic properties, and play a decisive role in the field of veterinary drugs.

[0003] Sulfachloropyridazine sodium is a new type of sulfonamide drug, and its chemical name is N- (6-chloro-pyridazinyl) -4-aminobenzenesulfonamide sodium salt. Its drug chemical structure contains p-aminobenzenesulfonamide nucleus, which can compete with p-aminobenzoic acid for bacterial dihydrofolate synthetase in vivo, hinder the synthesis of dihydrofolate and reduce the amount of tetrahydrofolate, ultimately affect the synthesis of nucleic acid, thereby inhibiting the growth and reproduction of bacteria. Its chemical structural formula is as follows:

[0004]

[0005] As an anti-inflammatory and antibacterial drug for poultry and livestock, sulfachloropyridazine sodium is often used in combination with the antibacterial synergist-methoxybenzyl lactate (lactic acid TMP). It is mainly used for the treatment of bacterial diseases and some protozoal diseases in poultry and livestock, such as chicken coccidiosis, cholera, chicken white dysentery, chicken E. coli disease, piglet white dysentery, piglet yellow dysentery, swine plague, swine toxoplasmosis, etc. Its outstanding antibacterial properties, convenient administration method and potential research and development direction continue to play a decisive role in the field of veterinary drugs.

[0006] The industrial synthesis routes of sulfachloropyridazine sodium reported in the literature are all based on p-aminobenzenesulfonamide (industrial sulfanilamide) and 3,6-dichloropyridazine as starting materials. For example, CN101914064B discloses a preparation method of sulfachloropyridazine sodium, CN113666876B discloses a production process of sulfachloropyridazine, CN111303044A discloses a synthesis method of sulfachloropyridazine sodium, and sulfachloropyridazine sodium synthesis experimental research. Shangping, Zhang Wei, Bu Xinli, Yang Yong. Hebei Chemical Industry. December 2005 discloses using o-dichlorobenzene instead of p-dichlorobenzene for condensation reaction. The above patents or documents all disclose that in the presence of a solvent or a high-boiling solvent (dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, o-dichlorobenzene, tri-n-propylamine, etc.), a base metal carbonate (such as potassium carbonate) is used as an acid-binding agent for condensation reaction, and sulfachloropyridazine base metal salt is first generated, and after neutralization of the base metal salt with inorganic acid such as hydrochloric acid, sulfachloropyridazine is obtained, and sulfachloropyridazine is further salted with sodium hydroxide in water to obtain sulfachloropyridazine sodium.

[0007] The synthesis route is as follows:

[0008]

[0009] However, the above synthesis route has obvious defects. First, the reaction temperature is too high (140-180℃), which is difficult to achieve directly using steam insulation in industry; in addition, the high temperature accelerates the rate of side reactions, i.e. when the main reaction proceeds to a certain extent, the unreacted raw material 3,6-dichloropyridazine and the amine group on the product sulfachloropyridazine continue to condense, producing polymeric impurities (3,6-di-p-aminobenzenesulfonamidyl pyridazine) (content more than 0.8%), which makes the purity of sulfachloropyridazine sodium crude product only 96%. This polymeric impurity has similar properties to the product sulfachloropyridazine, and is difficult to remove by the usual "alkali dissolution and acid precipitation method", resulting in low purity of the subsequent sulfachloropyridazine sodium product, which is difficult to meet the requirements of the latest version of the Chinese Pharmacopoeia for maximum single impurity less than 0.3% and total impurities less than 1%, as well as the requirements of high-end markets at home and abroad. The reaction principle of the polymeric impurity is as follows:

[0010]

[0011] In addition, p-aminobenzenesulfonamide will produce a yellow by-product with strong color under high temperature oxidation during the reaction, which is also difficult to remove effectively by the above "alkali dissolution and acid precipitation method", and white or white sulfachloropyridazine sodium product cannot be obtained.

[0012] Therefore, in order to solve the defects of high reaction temperature, many impurities, poor refining effect, yellow appearance, etc. in the above technical route, and obtain high-quality and high-yield products, improvements need to be made in various aspects of the existing route. SUMMARY

[0013] The application provides a synthesis process of high-purity sulfonamide chlorodiazine sodium, which has the advantages of safety, environmental protection, cheap and easily available raw materials, simple process and low production cost.

[0014] The application adopts the following technical scheme:

[0015] A synthesis process of high-purity sulfonamide chlorodiazine sodium, the route is as follows:

[0016]

[0017] A synthesis process of high-purity sulfonamide chlorodiazine sodium, comprising: synthesizing a condensate, synthesizing sulfonamide chlorodiazine, and synthesizing sulfonamide chlorodiazine sodium finished product;

[0018] In the synthesis of the condensate, aromatic hydrocarbon solvent, 3, 6-dichloropyridazine, p-acetamidobenzenesulfonamide, acid binding agent and catalyst are mixed at 20-30 DEG C, and then subjected to reflux and water separation reaction at 100-120 DEG C, after reaction for 6-10 h, cooling is carried out, and the condensate liquid is obtained;

[0019] In the synthesis of the condensate, the aromatic hydrocarbon solvent is one of toluene, mixed xylene and m-xylene;

[0020] The acid binding agent is one of sodium hydroxide, potassium carbonate and sodium carbonate;

[0021] The catalyst is one of cuprous bromide, cuprous iodide and cuprous chloride;

[0022] The mass ratio of the aromatic hydrocarbon solvent, 3, 6-dichloropyridazine, p-acetamidobenzenesulfonamide, acid binding agent and catalyst is 447-894:148.98:214-235.4:40-138:0.99-4.95;

[0023] In the synthesis of sulfonamide chlorodiazine, an alkaline aqueous solution is added to the condensate liquid, reflux reaction is carried out at 90-120 DEG C, reaction is carried out for 6-10 h, cooling is carried out to 50-60 DEG C, the pH value is adjusted to 7-8, a reducing agent and activated carbon are added, heat preservation reaction is carried out for 0.5-1 h, filtration is carried out, the pH value of the filtrate is adjusted to 5-7, cooling is carried out to 10-20 DEG C, and post-treatment is carried out, so as to obtain sulfonamide chlorodiazine;

[0024] In the synthesis of sulfonamide chlorodiazine, the alkaline aqueous solution is sodium hydroxide aqueous solution or potassium hydroxide aqueous solution, and the mass fraction is 10-20%;

[0025] When the pH value is adjusted to 7-8, dilute acid is used for adjustment, the dilute acid is dilute sulfuric acid or dilute hydrochloric acid, and the mass fraction is 10-20%;

[0026] The post-processing includes filtration, washing, and drying.

[0027] The reducing agent is thiourea dioxide or sodium dithionite;

[0028] The activated carbon is pharmaceutical-grade activated carbon;

[0029] The mass ratio of 3,6-dichloropyridazine in the synthetic condensate to the alkaline aqueous solution in the synthetic sulfachlorpyridazine is 148.98:220-400;

[0030] The mass ratio of 3,6-dichloropyridazine in the synthetic condensate to the reducing agent and activated carbon in the synthetic sulfachlorpyridazine is 148.98:7.45-14.9:7.45-14.9;

[0031] The process for synthesizing sodium sulfachlorpyridazine involves adjusting the pH of sulfachlorpyridazine to 7.5-9.5 at 5-15℃, stirring, and then adding it dropwise to a lower alcohol. After the addition is complete, the mixture is kept at 4-6℃ for 1-2 hours, followed by post-treatment to obtain the sodium sulfachlorpyridazine product.

[0032] In the synthesized sodium sulfachlorpyridazine product, when adjusting the pH value of sulfachlorpyridazine to 7.5-9.5, liquid alkali is used for adjustment, and the mass fraction of liquid alkali is 18-22%.

[0033] The lower alcohol is one of methanol, ethanol, and isopropanol;

[0034] When adding to lower alcohols, the dropping time is 3-4 hours;

[0035] The post-processing includes filtration and drying;

[0036] The mass ratio of sulfachlorpyridazine to lower alcohols is 258-266:783-1584.

[0037] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0038] (1) The synthesis process of high-purity sodium sulfachlorpyridazine of the present invention uses p-acetamidobenzenesulfonamide as raw material. P-acetamidobenzenesulfonamide can be protected by acetyl groups, thereby reducing the nucleophilicity of amino groups and blocking the polymer formation pathway from the source to control impurities. Cuprous salt catalysts are used to activate C-Cl bonds, which significantly reduces the reaction energy barrier and lowers the condensation reaction temperature. A suitable aromatic solvent is selected as an azeotropic dehydrating agent to separate the water generated in the system in time to reduce side reactions. Salt formation is carried out in a mixed solvent of water and alcohol to achieve precise separation of impurities. Finally, sodium sulfachlorpyridazine product with high yield, high purity (HPLC > 99.90%, single impurity < 0.1%) and good color (off-white or white) is obtained, which solves the problem of impurities and color that has plagued traditional processes for decades.

[0039] (2) The synthesis process of high-purity sulfachlorpyridazine sodium of the present invention has the following characteristics: the HPLC purity of the synthesized sulfachlorpyridazine sodium is 99.93-99.96 and the yield is 92.7-94.6%; the HPLC purity of the obtained intermediate sulfachlorpyridazine is 99.0-99.1% and the yield is 89.7-92.6%. Attached Figure Description

[0040] Figure 1 The HPLC chromatogram of sulfachlorpyridazine in Example 1 is shown below.

[0041] Figure 2 The HPLC chromatogram of sulfachlorpyridazine in Example 2 is shown below.

[0042] Figure 3 Here is the HPLC chromatogram of sulfachlorpyridazine in Example 3;

[0043] Figure 4 Here is the HPLC chromatogram of the sulfachlorpyridazine sodium product from Example 1;

[0044] Figure 5 Here is the HPLC chromatogram of the sulfachlorpyridazine sodium product from Example 2;

[0045] Figure 6 The image shows the HPLC chromatogram of the sodium sulfachlorpyridazine product from Example 3. Detailed Implementation

[0046] The following embodiments describe and explain the principles and features of the present invention, but do not limit the scope of the present invention.

[0047] The reaction principle in the examples is presumed to be as follows: In the synthesis of the condensate, the catalyst cuprous salt first activates the C-Cl bond of 3,6-dichloropyridazine through oxidative addition to form an aryl-copper intermediate; acetamidobenzenesulfonamide nucleophilically attacks the aryl-copper intermediate and undergoes a condensation reaction with the aryl-copper intermediate to generate a condensation liquid; in the synthesis of sulfachlorpyridazine, the condensation liquid undergoes a hydrolysis reaction with a strong base to generate sulfachlorpyridazine.

[0048] The reaction mechanism of the catalyst cuprous salt participating in the condensation reaction is deduced as follows:

[0049]

[0050] Note: Py represents pyridazine ring, and Ar represents benzene ring.

[0051] The medicinal activated carbon used in the examples has a methylene blue decolorization power ≥9 ml.

[0052] Example 1

[0053] (1) Synthesis of condensate: At 20°C, 447 kg of solvent toluene, 148.98 kg of 3,6-dichloropyridazine, 214 kg of p-acetamide benzenesulfonamide, 40 kg of solid sodium hydroxide, and 1.43 kg of catalyst cuprous bromide were added to the reactor in sequence. After stirring evenly, the temperature was controlled at 100°C for reflux to remove water, and the condensation reaction was carried out at the same time. After 6 h of reaction, the reaction was confirmed by TLC to be completed (3,6-dichloropyridazine concentration was less than 0.5%). The temperature was then lowered to obtain the condensate liquid.

[0054] (2) Synthesis of sulfachlorpyridazine: 400 kg of 10% sodium hydroxide aqueous solution was added to the condensed material obtained in step (1), and the mixture was refluxed at 90°C. The solvent was separated while hydrolysis was carried out. After 6 hours of reaction, the reaction was confirmed to be complete (pH value 10). The temperature was lowered to 50°C, and the pH was adjusted to 8 with 10% dilute sulfuric acid. Then, 7.45 kg each of the reducing agent thiourea dioxide and pharmaceutical activated carbon were added. The mixture was kept warm for 0.5 hours, filtered, and the filtrate was further adjusted to pH 7 with 10% dilute sulfuric acid. The temperature was lowered to 10°C, filtered, washed, and dried to obtain 261 kg of sulfachlorpyridazine, with a yield of 90.9% (calculated as 3,6-dichloropyridazine). The HPLC chromatogram of the obtained sulfachlorpyridazine is shown in [reference needed]. Figure 1 ,Depend on Figure 1 It can be seen that the HPLC purity of the obtained sulfachlorpyridazine is 99.1% (theoretical dry product yield is 284.7 kg).

[0055] (3) Synthesis of sodium sulfachlorpyridazine: At a controlled temperature of 5℃, 20% liquid alkali was added dropwise to 261 kg of sulfachlorpyridazine obtained in step (2) until the pH reached 7.5. After stirring and dissolving, the solution was added dropwise to 783 kg of methanol over a period of 3 hours. After the addition was complete, the solution was kept at 5℃ for 1 hour, filtered, and dried to obtain 258.4 kg of sodium sulfachlorpyridazine, with a yield of 92.7% (calculated based on sulfachlorpyridazine). The product was off-white in appearance. The HPLC chromatogram of the obtained sodium sulfachlorpyridazine is shown in [reference needed]. Figure 4 ,Depend on Figure 4 It can be seen that the HPLC purity of the obtained sulfachlorpyridazine sodium product is 99.95% (theoretical dry product 278.64 kg).

[0056] Example 2

[0057] (1) Synthesis of condensate: At 30°C, 894 kg of solvent mixed xylene, 148.98 kg of 3,6-dichloropyridazine, 235.4 kg of p-acetamide benzenesulfonamide, 44 kg of solid sodium hydroxide, and 1.90 kg of catalyst cuprous iodide were added to the reactor in sequence. After stirring evenly, the temperature was controlled at 110°C for reflux to remove water, and the condensation reaction was carried out at the same time. After 10 h, the reaction was monitored by TLC to complete (the concentration of 3,6-dichloropyridazine was less than 0.5%). Then, the temperature was lowered to obtain the condensate liquid.

[0058] (2) Synthesis of sulfachlorpyridazine: 242 kg of 20% sodium hydroxide aqueous solution was added to the above condensed material solution, and the mixture was refluxed at 110°C. Hydrolysis was carried out simultaneously with solvent separation. After 10 hours, the reaction was monitored to be complete (pH value was 11). The temperature was lowered to 60°C, and the pH was adjusted to 7 with 10% dilute hydrochloric acid. 14.9 kg each of sodium dithionite and pharmaceutical activated carbon were added, and the mixture was kept at this temperature for 1 hour. After filtration, the pH of the filtrate was further adjusted to 5 with 10% dilute hydrochloric acid. The temperature was lowered to 20°C, and the mixture was filtered, washed, and dried to obtain 266 kg of sulfachlorpyridazine, with a yield of 92.6% (calculated as 3,6-dichloropyridazine). The HPLC chromatogram of the obtained sulfachlorpyridazine is shown in [reference needed]. Figure 2 ,Depend on Figure 2 It can be seen that the HPLC purity of the obtained sulfachlorpyridazine is 99.1% (theoretical dry product 284.7 kg).

[0059] (3) Synthesis of sulfachlorpyridazine sodium product: At a controlled temperature of 15℃, 20% alkali solution was added dropwise to 266 kg of sulfachlorpyridazine until the pH reached 9.5. After stirring and dissolving, the solution was added dropwise to 798 kg of ethanol over 3 hours. After the addition was complete, the solution was kept at 5℃ for 2 hours, filtered, and dried to obtain 268.7 kg of sulfachlorpyridazine sodium product, with a yield of 94.6% (calculated based on sulfachlorpyridazine). The product was off-white in appearance. The HPLC chromatogram of the obtained sulfachlorpyridazine sodium product is shown below. Figure 5 ,Depend on Figure 5 It can be seen that the HPLC purity of the obtained sulfachlorpyridazine sodium product is 99.96% (theoretical dry product yield: 283.98 kg).

[0060] Example 3

[0061] (1) Synthesis of condensate: At 20°C, 888 kg of xylene, 148.98 kg of 3,6-dichloropyridazine, 235.4 kg of p-acetamide benzenesulfonamide, 138 kg of solid potassium carbonate, and 0.99 kg of cuprous chloride catalyst were added to the reactor in sequence. After stirring evenly, the temperature was controlled at 120°C for reflux to remove water, and the condensation reaction was carried out at the same time. After 10 h, the reaction was monitored by TLC to complete (the concentration of 3,6-dichloropyridazine was less than 0.5%). The temperature was then lowered to obtain the condensate liquid.

[0062] (2) Synthesis of sulfachlorpyridazine: 220 kg of 20% sodium hydroxide aqueous solution was added to the above condensed material solution, and the mixture was refluxed at 120°C. The solvent was separated while hydrolysis was carried out. After 10 hours, the reaction was monitored to be complete (pH 12). The temperature was lowered to 60°C, and the pH was adjusted to 7 with 20% dilute sulfuric acid. 14.9 kg each of the reducing agent thiourea dioxide and pharmaceutical activated carbon were added. The mixture was kept at this temperature for 1 hour, filtered, and the pH of the filtrate was further adjusted to 5 with 20% dilute sulfuric acid. The temperature was lowered to 20°C, filtered, washed, and dried to obtain 258 kg of sulfachlorpyridazine, with a yield of 89.7% (calculated as 3,6-dichloropyridazine). The HPLC chromatogram of the obtained sulfachlorpyridazine is shown in [reference needed]. Figure 3 ,Depend on Figure 3 It can be seen that the HPLC purity of the obtained sulfachlorpyridazine is 99.0% (theoretical dry product 284.7 kg).

[0063] (3) Synthesis of sulfachlorpyridazine sodium product: At a controlled temperature of 15℃, 20% (w / w) liquid alkali was added dropwise to 258 kg of sulfachlorpyridazine until the pH reached 9.5. After stirring and dissolving, the solution was added dropwise to 1548 kg of ethanol over 3 hours. After the addition was complete, the solution was kept at 5℃ for 2 hours, filtered, and dried to obtain 257.9 kg of sulfachlorpyridazine sodium product, with a yield of 93.7% (calculated based on sulfachlorpyridazine). The product was off-white in appearance. The HPLC chromatogram of the obtained sulfachlorpyridazine sodium product is shown below. Figure 6 ,Depend on Figure 6 It can be seen that the HPLC purity of the obtained sulfachlorpyridazine sodium product is 99.96% (theoretical dry product 275.16 kg).

[0064] Example 4

[0065] (1) Synthesis of condensate: At 20°C, 894 kg of toluene, 148.98 kg of 3,6-dichloropyridazine, 214 kg of p-acetamide benzenesulfonamide, 106 kg of solid sodium carbonate, and 4.95 kg of cuprous chloride catalyst were added to the reactor in sequence. After stirring evenly, the temperature was controlled at 100°C for reflux to remove water, and the condensation reaction was carried out at the same time. After 10 h, the reaction was monitored by TLC to complete (the concentration of 3,6-dichloropyridazine was less than 0.5%). The temperature was then lowered to obtain the condensate liquid.

[0066] (2) Synthesis of sulfachlorpyridazine: 280 kg of a 20% potassium hydroxide aqueous solution was added to the above condensed material solution, and the mixture was refluxed at 100°C. The solvent was separated while a hydrolysis reaction was carried out. After 10 hours, the reaction was monitored to be complete (pH 11). The temperature was lowered to 60°C, and the pH was adjusted to 7 with 10% dilute hydrochloric acid. 14.9 kg each of sodium dithionite and pharmaceutical activated carbon were added, and the mixture was kept at this temperature for 1 hour. After filtration, the pH of the filtrate was further adjusted to 5 with 10% dilute hydrochloric acid. The temperature was lowered to 20°C, and the mixture was filtered, washed, and dried to obtain 264 kg of sulfachlorpyridazine, with a yield of 91.8% (calculated as 3,6-dichloropyridazine) and an HPLC purity of 99.0%. (Theoretical dry product: 284.7 kg)

[0067] (3) Synthesis of sulfachlorpyridazine sodium product: At a controlled temperature of 15℃, 20% (w / w) liquid alkali was added dropwise to 264 kg of sulfachlorpyridazine until the pH reached 9.5. After stirring and dissolving, the solution was added dropwise to 1584 kg of isopropanol over a period of 3 hours. After the addition was complete, the solution was kept at 5℃ for 2 hours, filtered, and dried to obtain 265.9 kg of sulfachlorpyridazine sodium product, with a yield of 94.4% (calculated based on sulfachlorpyridazine). The product was off-white in appearance and had an HPLC purity of 99.93%. (Theoretical dry product: 281.56 kg)

[0068] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and do not constitute a limitation on the content of the present invention. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solutions of the present invention, including combining various technical features in any other suitable manner. These simple modifications and combinations should also be regarded as the content disclosed in the present invention and all fall within the protection scope of the present invention.

Claims

1. A synthesis process for high-purity sulfachlorpyridazine sodium, characterized in that, include: Synthesize condensates, synthesize sulfachlorpyridazine, and synthesize sulfachlorpyridazine sodium as the finished product; The synthetic condensate is prepared by mixing an aromatic solvent, 3,6-dichloropyridazine, p-acetamidobenzenesulfonamide, an acid-binding agent, and a catalyst at 20-30°C, followed by a reflux water separation reaction at 100-120°C for 6-10 hours. After cooling, the condensate is obtained as a liquid condensate. The catalyst is one of cuprous bromide, cuprous iodide, and cuprous chloride. The synthesis of sulfachlorpyridazine involves adding an alkaline aqueous solution to the condensation material solution, refluxing at 90-120℃ for 6-10 hours, cooling to 50-60℃, adjusting the pH to 7-8, adding a reducing agent and activated carbon, maintaining the temperature for 0.5-1 hours, filtering, adjusting the pH of the filtrate to 5-7, cooling to 10-20℃, and post-processing to obtain sulfachlorpyridazine. The process for synthesizing sodium sulfachlorpyridazine involves adjusting the pH of sulfachlorpyridazine to 7.5-9.5 at 5-15℃, stirring, and then adding it dropwise to a lower alcohol. After the addition is complete, the mixture is kept at 4-6℃ for 1-2 hours, followed by post-treatment to obtain the sodium sulfachlorpyridazine product.

2. The synthesis process of high-purity sulfachlorpyridazine sodium according to claim 1, characterized in that, In the synthetic condensate, the aromatic solvent is one of toluene, mixed xylene, and m-xylene; The acid-binding agent is one of sodium hydroxide, potassium carbonate, and sodium carbonate.

3. The synthesis process of high-purity sulfachlorpyridazine sodium according to claim 1, characterized in that, In the synthesized condensate, the mass ratio of aromatic solvent, 3,6-dichloropyridazine, p-acetamidobenzenesulfonamide, acid-binding agent, and catalyst is 447-894:148.98:214-235.4:40-138:0.99-4.

95.

4. The synthesis process of high-purity sulfachlorpyridazine sodium according to claim 1, characterized in that, In the synthesis of sulfachlorpyridazine, the alkaline aqueous solution is a sodium hydroxide aqueous solution or a potassium hydroxide aqueous solution, with a mass fraction of 10-20%. When adjusting the pH value to 7-8, use dilute acid, such as dilute sulfuric acid or dilute hydrochloric acid, with a mass fraction of 10-20%. The post-processing includes filtration, washing, and drying. The reducing agent is thiourea dioxide or sodium dithionite; The activated carbon is pharmaceutical grade activated carbon.

5. The synthesis process of high-purity sulfachlorpyridazine sodium according to claim 1, characterized in that, The mass ratio of 3,6-dichloropyridazine in the synthetic condensate to the alkaline aqueous solution in the synthetic sulfachlorpyridazine is 148.98:220-400; The mass ratio of 3,6-dichloropyridazine in the synthetic condensate to the reducing agent and activated carbon in the synthetic sulfachlorpyridazine is 148.98:7.45-14.9:7.45-14.

9.

6. The synthesis process of high-purity sulfachlorpyridazine sodium according to claim 1, characterized in that, In the synthesized sodium sulfachlorpyridazine product, when adjusting the pH value of sulfachlorpyridazine to 7.5-9.5, liquid alkali is used for adjustment, and the mass fraction of liquid alkali is 18-22%. The lower alcohol is one of methanol, ethanol, and isopropanol; When adding to lower alcohols, the dropping time is 3-4 hours; The post-processing includes filtration and drying.

7. The synthesis process of high-purity sulfachlorpyridazine sodium according to claim 1, characterized in that, In the synthesized sodium sulfachlorpyridazine product, the mass ratio of sulfachlorpyridazine to lower alcohol is 258-266:783-1584.

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