A method for synthesizing sulfonamide-6-methoxymelamine

Abstract

The application provides a synthesis method of sulfanilamide-6-methoxy pyrimidine, and relates to the technical field of medicine preparation. 4-chloro-6-methoxypyrimidine, sulfanilamide alkali metal salt and an organic solvent are mixed to carry out a condensation reaction to obtain sulfanilamide-6-methoxy pyrimidine. The synthesis method has the advantages of high product yield (greater than 91.5%), high purity, good quality, cheap and easily obtained raw materials, simple, safe, stable, efficient, environmental protection, mild reaction conditions, simple operation and convenience for industrial production. The sulfanilamide alkali metal salt used in the application is obtained by salification of alkali metal hydroxide and sulfanilamide, and the sulfanilamide alkali metal salt does not need to be purified and separated, thereby reducing the production cost and reducing the amount of waste liquid. The sulfanilamide-6-methoxy pyrimidine obtained by the post-treatment method has high purity, and the organic solvent and sulfanilamide recovered in the post-treatment process can be recycled, thereby reducing the production cost of sulfanilamide-6-methoxy pyrimidine and greatly reducing the amount of sewage.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medicine preparation, in particular to a synthesis method of sulfonamide-6-methoxy pyrimidine. BACKGROUND

[0002] Sulfonamides are the earliest synthetic antibacterial drugs, usually white or light yellow crystalline powder. Since the invention and application in the 1930s, sulfonamides have been widely valued and researched as the most valuable antibacterial drugs due to their easy production, easy storage, good efficacy, convenient use, low price and other advantages. Sulfonamides have a history of more than 80 years, and more than 8500 kinds of sulfonamides have been synthesized, of which more than 20 kinds such as sulfadiazine, sulfisoxazole, sulfisomidine and sulfadimidine are commonly used in clinic. With the continuous discovery and development of various antibiotics, antibiotics and quinolones gradually replace sulfonamides, but sulfonamides still have their unique advantages, such as wide antibacterial spectrum, stable properties, convenient use, low price, no consumption of grain in drug production, and large-scale production. The discovery of antibacterial synergists such as trimethoprim (TMP) and dihydroxybenzylamine (DVD) greatly enhances the antibacterial spectrum and activity of sulfonamides when they are used in combination with antibacterial synergists. Therefore, sulfonamides are still one of the important drugs for the treatment of infections in livestock and poultry.

[0003] Among them, sulfonamide-6-methoxy pyrimidine is a kind of sulfonamide, which is a white powder solid composed of aniline connected by a sulfonamide group and a methoxy pyrimidine. It belongs to broad-spectrum antibacterial drugs, has the characteristics of small toxicity, easy absorption by oral administration, and has inhibitory effect on many gram-positive bacteria and some gram-negative bacteria.

[0004] At present, the synthesis process of sulfonamide-6-methoxy pyrimidine mainly includes two steps: 4,6-dichloropyrimidine is condensed with sodium sulfonamide in dimethylformamide (DMF) for 4-6 hours to obtain sulfonamide chloropyrimidine; and then the refined sulfonamide chloropyrimidine is reacted with sodium methoxide to obtain sulfonamide-6-methoxy pyrimidine. However, 4,6-dichloropyrimidine is unstable in the condensation reaction, and the generated sodium sulfonamide chloropyrimidine is also prone to degradation under this condition, resulting in low yield (75-80%) of the product. SUMMARY

[0005] Therefore, the purpose of the present application is to provide a synthesis method of sulfonamide-6-methoxy pyrimidine. The synthesis method provided by the present application has high yield of sulfonamide-6-methoxy pyrimidine.

[0006] In order to achieve the above-mentioned purpose of the application, the present application provides the following technical solutions:

[0007] The present application provides a synthesis method of sulfonamide-6-methoxy pyrimidine, comprising the following steps:

[0008] 4-Chloro-6-methoxypyrimidine, sulfonamide alkali metal salt, and organic solvent are mixed and subjected to a condensation reaction to obtain sulfa-6-methoxypyrimidine.

[0009] Preferably, the molar ratio of 4-chloro-6-methoxypyrimidine to sulfanilamide alkali metal salt is 1:2.05 to 2.15; the sulfanilamide alkali metal salt includes sodium sulfanilamide or potassium sulfanilamide.

[0010] Preferably, the organic solvent includes dimethylformamide and / or dimethylacetamide.

[0011] Preferably, the condensation reaction is carried out at a temperature of 90–100°C for 3.5–4 hours.

[0012] Preferably, the method for synthesizing the sulfonamide alkali metal salt includes the following steps: mixing an alkali metal hydroxide, sulfonamide, and water to carry out a salt-forming reaction to obtain the sulfonamide alkali metal salt.

[0013] Preferably, the condensation reaction further includes a post-processing step, the post-processing step including:

[0014] The condensation reaction solution obtained from the condensation reaction is concentrated to obtain a concentrated solution and a recovered organic solvent; the recovered organic solvent is reused in the condensation reaction step.

[0015] The concentrated solution, first water, and first activated carbon are mixed, and after first decolorization and first solid-liquid separation, a first liquid component is obtained. The mixture is cooled to room temperature, and the pH value of the first liquid component is adjusted to 7.5-8, causing solid to precipitate. A second solid-liquid separation is then performed to obtain a second liquid component and a solid component. The solid component is dried to obtain recovered sulfonamide. The recovered sulfonamide is used to prepare sulfonamide alkali metal salts.

[0016] The second liquid component was cooled to room temperature, the pH was adjusted to 5-6, crystallization occurred, and the third solid-liquid separation was performed, the solid component being crude sulfamethoxypyrimidine;

[0017] The crude sulfamethoxypyrimidine, second water, and alkaline reagent are thermally dissolved, and second activated carbon is added for second decolorization. Thermal solid-liquid separation is then performed to obtain the thermal liquid component.

[0018] The pH value of the hot liquid component is adjusted to 5-6, cooled to crystallize, and then subjected to a fourth solid-liquid separation. The resulting solid component is dried to obtain refined sulfamethoxypyrimidine.

[0019] Preferably, the mass ratio of the sulfonamide alkali metal salt to the first activated carbon is 100:1 to 2;

[0020] The mass ratio of the sulfonamide alkali metal salt to the first water is 1:1.4 to 1.6;

[0021] The first decolorization temperature is 90-95℃, and the time is 1.5-2 hours.

[0022] Preferably, the crystallization temperature is 20-25°C and the time is 1.5-2 hours.

[0023] Preferably, the mass ratio of the crude sulfamethoxypyrimidine to the second water is 1:4.75 to 5.25;

[0024] The molar ratio of the crude sulfamethoxypyrimidine to the alkaline reagent is 1:0.5 to 0.51; the alkaline reagent includes one or more of calcium hydroxide, sodium hydroxide, and potassium hydroxide.

[0025] The mass ratio of the crude sulfamethoxypyrimidine to the second activated carbon is 100:3-5;

[0026] The temperatures for the thermal dissolution, the second decolorization, and the thermal solid-liquid separation are independently 90–95°C, and the time for the second decolorization is 1.5–2 hours.

[0027] Preferably, the cooling and crystallization temperature is 5–15°C, and the holding time is 1.5–2 hours.

[0028] This invention involves mixing 4-chloro-6-methoxypyrimidine, a sulfonamide alkali metal salt, and an organic solvent to undergo a condensation reaction, yielding sulfa-6-methoxypyrimidine. The synthetic method provided by this invention offers high product yield, high purity, and good quality. The raw materials are inexpensive and readily available, the preparation process is simple, safe, stable, efficient, and environmentally friendly, with mild reaction conditions and easy operation, facilitating industrial production. As shown in the test results of the examples, the synthetic method provided by this invention achieves a sulfa-6-methoxypyrimidine yield greater than 91.5%, which is high.

[0029] The sulfonamide alkali metal salt used in this invention is obtained by mixing alkali metal hydroxide, sulfonamide and water to carry out a salt formation reaction. There is no need to purify and separate the sulfonamide alkali metal salt, the post-processing is simple, and the production cost of sulfa-6-methoxypyrimidine is further reduced, and less waste liquid is generated.

[0030] The post-treatment method provided by this invention yields sulfamethoxypyrimidine with high purity, has simple post-treatment steps, and allows for the recycling of organic solvents and sulfonamides recovered during the post-treatment process, thereby reducing the production cost of sulfamethoxypyrimidine and significantly reducing wastewater generation. Attached Figure Description

[0031] Figure 1 The infrared spectrum of sulfa-6-methoxypyrimidine prepared in Example 1;

[0032] Figure 2 The infrared spectrum of the sulfa-6-methoxypyrimidine standard sample is shown. Detailed Implementation

[0033] This invention provides a method for synthesizing sulfa-6-methoxypyrimidine, comprising the following steps:

[0034] 4-Chloro-6-methoxypyrimidine, sulfonamide alkali metal salt, and organic solvent are mixed and subjected to a condensation reaction to obtain sulfa-6-methoxypyrimidine.

[0035] Unless otherwise specified, the materials and equipment used in this invention are all commercially available products in the field.

[0036] In this invention, the molar ratio of the 4-chloro-6-methoxypyrimidine to the sulfanilamide alkali metal salt is preferably 1:2.05 to 2.15, more preferably 1:2.1; the sulfanilamide alkali metal salt preferably includes sodium sulfanilamide or potassium sulfanilamide, more preferably sodium sulfanilamide.

[0037] In this invention, the method for synthesizing the sulfanilamide alkali metal salt includes the following steps: mixing an alkali metal hydroxide, sulfanilamide, and water to perform a salt-forming reaction to obtain the sulfanilamide alkali metal salt. In this invention, the alkali metal hydroxide preferably includes sodium hydroxide or potassium hydroxide; the mass ratio of sulfanilamide to alkali metal hydroxide is preferably 1:0.227–0.232, more preferably 1:0.023. In this invention, the mass ratio of sulfanilamide to water is preferably 1:2.75–3.25, more preferably 1:2.8–3. In this invention, the temperature of the salt-forming reaction is preferably 90–100°C, more preferably 93–95°C; the time of the salt-forming reaction is preferably 20–40 min, more preferably 30 min; the salt-forming reaction is preferably carried out under stirring conditions.

[0038] After the salt-forming reaction is completed, the present invention preferably further includes evaporating the salt-forming reaction solution obtained from the salt-forming reaction to dryness, thereby obtaining a sulfonamide alkali metal salt. In the present invention, the evaporation to dryness is preferably carried out by vacuum distillation until all water is removed.

[0039] In this invention, the organic solvent preferably includes dimethylformamide and / or dimethylacetamide; the organic solvent is preferably an anhydrous organic solvent. In this invention, the solid-liquid ratio of the 4-chloro-6-methoxypyrimidine to the organic solvent is preferably 1 g: 3-4 mL, more preferably 1 g: 3.5 mL.

[0040] In this invention, the temperature of the condensation reaction is preferably 90-100°C, more preferably 95°C; the time of the condensation reaction is preferably 3.5-4 hours; and the condensation reaction is preferably carried out under stirring conditions.

[0041] After the condensation reaction is completed, the present invention preferably further includes a post-processing step, wherein the post-processing preferably includes:

[0042] The condensation reaction solution obtained from the condensation reaction is concentrated to obtain a concentrated solution and a recovered organic solvent; the recovered organic solvent is reused in the condensation reaction step.

[0043] The concentrated solution, first water, and first activated carbon are mixed, and after first decolorization, first solid-liquid separation is performed to obtain a first liquid component. The mixture is cooled to room temperature, and the pH value of the first liquid component is adjusted to 7.5-8 to precipitate a solid. Second solid-liquid separation is performed to obtain a second liquid component and a solid component. The solid component is dried to obtain recovered sulfonamide.

[0044] The second liquid component was cooled to room temperature, the pH was adjusted to 5-6, crystallization occurred, and the third solid-liquid separation was performed, the solid component being crude sulfamethoxypyrimidine;

[0045] The crude sulfamethoxypyrimidine, second water, and alkaline reagent are thermally dissolved, and second activated carbon is added for second decolorization. Thermal solid-liquid separation is then performed to obtain the thermal liquid component.

[0046] The pH value of the hot liquid component is adjusted to 5-6, cooled to crystallize, and then subjected to a fourth solid-liquid separation. The resulting solid component is dried to obtain refined sulfamethoxypyrimidine.

[0047] This invention concentrates the condensation reaction solution obtained from the condensation reaction to obtain a concentrated solution and a recovered organic solvent; the recovered organic solvent is reused in the condensation reaction step. In this invention, the concentration is preferably carried out under reduced pressure. This invention does not have specific limitations on the concentration conditions, as long as the organic solvent can be completely recovered.

[0048] After obtaining the concentrated solution, the present invention mixes the concentrated solution, first water, and first activated carbon, performs a first decolorization followed by a first solid-liquid separation to obtain a first liquid component. The liquid component is then cooled to room temperature (20-25°C), and its pH is adjusted to 7.5-8, causing solid precipitation. A second solid-liquid separation is performed to obtain a second liquid component and a solid component. The solid component is then dried to obtain recovered sulfonamide. In this invention, the mass ratio of the sulfonamide alkali metal salt to the first activated carbon is preferably 100:1-2, more preferably 100:1.5. In this invention, the mass ratio of the sulfonamide alkali metal salt to the first water is preferably 1:1.4-1.6, more preferably 1:1.5; the first water is preferably hot water, and the temperature of the hot water is preferably 85-100°C, more preferably 90-95°C. In this invention, the temperature of the first decolorization is preferably 90-95°C, more preferably 93-95°C; the time of the first decolorization is preferably 1.5-2 hours, more preferably 2 hours. In this invention, the first solid-liquid separation and the second solid-liquid separation preferably independently include filtration, vacuum filtration, or centrifugation. In this invention, the acid used to adjust the pH value of the first liquid component to 7.5-8 preferably includes one or more of acetic acid, hydrochloric acid, sulfuric acid, and phosphoric acid; the pH value is more preferably 7.6-7.9, and even more preferably 7.7-7.8. In this invention, the drying temperature is preferably 95-105°C, more preferably 100°C. This invention does not have a specific limitation on the drying time; drying to constant weight is sufficient.

[0049] After obtaining the second liquid component, the present invention cools the second liquid component to room temperature (20-25°C), adjusts the pH value to 5-6, induces crystallization, and performs a third solid-liquid separation. The solid component is crude sulfamethoxypyrimidine. In the present invention, the acid used to adjust the pH value to 5-6 preferably includes one or more of acetic acid, hydrochloric acid, sulfuric acid, and phosphoric acid; the pH value is more preferably 5.2-5.8, and even more preferably 5.4-5.6. In the present invention, the crystallization temperature is preferably 20-25°C (room temperature), and the crystallization time is preferably 1.5-2 hours. In the present invention, the third solid-liquid separation preferably includes filtration, vacuum filtration, or centrifugation.

[0050] After obtaining crude sulfamethoxypyrimidine, the present invention thermally dissolves the crude sulfamethoxypyrimidine, a second water, and an alkaline reagent, adds a second activated carbon for a second decolorization, and performs thermal solid-liquid separation to obtain a hot liquid component. In the present invention, the mass ratio of the crude sulfamethoxypyrimidine to the second water is preferably 1:4.75–5.25, more preferably 1:4.8–5. In the present invention, the molar ratio of the crude sulfamethoxypyrimidine to the alkaline reagent is preferably 1:0.5–0.51, more preferably 1:0.55; the alkaline reagent preferably includes one or more of calcium hydroxide, sodium hydroxide, and potassium hydroxide, more preferably calcium oxide. In the present invention, the mass ratio of the crude sulfamethoxypyrimidine to the second activated carbon is preferably 100:3–5, more preferably 100:4. In this invention, the temperatures for the thermal dissolution, the second decolorization, and the thermal solid-liquid separation are preferably 90–95°C, more preferably 92–93°C; the time for the second decolorization is preferably 1.5–2 hours, more preferably 2 hours. In this invention, the thermal solid-liquid separation preferably includes thermal filtration, thermal vacuum filtration, or thermal centrifugation.

[0051] After obtaining the hot liquid component, the present invention adjusts the pH value of the hot liquid component to 5-6, cools it to crystallize, performs a fourth solid-liquid separation, and dries the resulting solid component to obtain refined sulfamethoxypyrimidine. In the present invention, the acid used to adjust the pH value to 5-6 preferably includes one or more of acetic acid, hydrochloric acid, sulfuric acid, and phosphoric acid; the pH value is more preferably 5.2-5.8, and even more preferably 5.4-5.6. In the present invention, the cooling and crystallization temperature is preferably 5-15°C, more preferably 10°C; the holding time is preferably 1.5-2 hours.

[0052] To further illustrate the present invention, the synthesis method of sulfa-6-methoxypyrimidine provided by the present invention will be described in detail below with reference to the embodiments, but these should not be construed as limiting the scope of protection of the present invention.

[0053] Example 1

[0054]

[0055] Add 950g of purified water to the reaction vessel, add 78.5g of sodium hydroxide while controlling the temperature at 30℃, then add 345g of sulfanilamide. Under stirring, raise the temperature to 95℃ and keep the reaction at that temperature for 0.5h. Evaporate the water to obtain sodium sulfanilamide.

[0056] Add 350 mL of DMF, 100 g of 4-chloro-6-methoxypyrimidine, and 276.5 g of sodium sulfamethamide to a reaction vessel. Heat to 100 °C under stirring and maintain the temperature for 4 h. Recover DMF under reduced pressure (this DMF is used for the next batch of condensation reaction). Add 390 mL of hot water at 95 °C and 5 g of activated carbon. Decolorize at 95 °C for 2 h. Hot filter. Cool the filtrate to 25 °C and adjust the pH to 7.5 with acetic acid. The solid precipitates. Filter to obtain the filtrate and filter cake. Dry the filter cake to obtain recovered sulfamethamide (this sulfamethamide is used for the next batch of sodium sulfamethamide preparation).

[0057] The filtrate was adjusted to pH 5.0 with acetic acid at 20–25 °C for 2 h to allow crystallization. After filtration, the filter cake was dried to obtain crude sulfa-6-methoxypyrimidine (182.7 g, crude molar yield 94.3%).

[0058] 100g of crude sulfamethoxypyrimidine, 500g of purified water, and 13.3g of calcium hydroxide were added to a reaction vessel and heated to 95℃ to dissolve. 5g of activated carbon was added, and the mixture was decolorized at 95℃ for 2 hours. After hot filtration, the pH of the filtrate was adjusted to 5.0 with acetic acid at 95℃. After cooling to 5℃, crystallization was carried out for 2 hours. The mixture was then filtered, and the filter cake was dried to obtain purified sulfamethoxypyrimidine (97.2g, purity 99.61%, purification yield 97.2%).

[0059] Example 2

[0060] Add 1120g of purified water to the reaction vessel, control the temperature at 30℃, add 80g of sodium hydroxide, then add 345g of sulfanilamide, heat to 95℃ under stirring and keep the temperature for 0.5h, evaporate the water to obtain sodium sulfanilamide.

[0061] Add 350 mL of DMF, 100 g of 4-chloro-6-methoxypyrimidine, and 290 g of sodium sulfamethamide to a reaction vessel. Heat to 100 °C under stirring and maintain the temperature for 3.5 h. Recover DMF under reduced pressure (this DMF is used for the next batch of condensation reaction), add 460 mL of hot water at 95 °C and 5 g of activated carbon, and decolorize at 90–95 °C for 2 h. Hot filter, cool the filtrate to 25 °C, adjust the pH to 8.0 with acetic acid, precipitate a solid, filter, and obtain filtrate and filter cake respectively. Dry the filter cake to obtain recovered sulfamethamide (this sulfamethamide is used for the next batch of sodium sulfamethamide preparation).

[0062] The filtrate was further adjusted to pH 6.0 with acetic acid at 20–25 °C, and crystallized for 2 hours. After filtration, the filter cake was dried to obtain crude sulfamethoxypyrimidine (184.7 g, crude molar yield 95.0%).

[0063] 100g of crude sulfamethoxypyrimidine, 500g of purified water, and 13.5g of calcium hydroxide were added to a reaction vessel and heated to 95℃ to dissolve. 5g of activated carbon was added, and the mixture was decolorized at 95℃ for 2 hours. After hot filtration, the pH of the filtrate was adjusted to 6.0 with acetic acid at 95℃. After cooling to 15℃, crystallization was carried out for 2 hours. The mixture was then filtered, and the filter cake was dried to obtain purified sulfamethoxypyrimidine (98.3g, purity 99.59%, purification yield 98.3%).

[0064] Example 3

[0065] Add 1120g of purified water to the reaction vessel, control the temperature at 15℃, add 110g of potassium hydroxide, and then add 345g of sulfanilamide. Under stirring, raise the temperature to 95℃ and keep the reaction at that temperature for 0.5h. Evaporate the water to obtain potassium sulfanilamide.

[0066] Add 350 mL of DMF, 100 g of 4-chloro-6-methoxypyrimidine, and 299 g of potassium sulfamethoxide to a reaction vessel. Heat to 100 °C under stirring and maintain the temperature for 4 h. Recover DMF under reduced pressure (this DMF is used for the next batch of condensation reaction). Add 400 mL of hot water at 95 °C and 6 g of activated carbon. Decolorize at 95 °C for 2 h. Hot filter. After the filtrate is cooled to 25 °C, adjust the pH to 7.8 with acetic acid to precipitate a solid. Filter and dry the filter cake to obtain recovered sulfamethoxide (this sulfamethoxide is used for the preparation of the next batch of potassium sulfamethoxide or sodium sulfamethoxide).

[0067] The filtrate was adjusted to pH 5.5 with acetic acid at 20–25 °C, crystallized for 2 hours, filtered, and the filter cake was dried to obtain crude sulfa-6-methoxypyrimidine (184.3 g, crude molar yield 94.8%).

[0068] 100g of crude sulfamethoxypyrimidine, 500g of purified water, and 13.3g of calcium hydroxide were added to a reaction vessel and heated to 95℃ to dissolve. 5g of activated carbon was added, and the mixture was decolorized at 95℃ for 2 hours and then hot-filtered. The filtrate was adjusted to pH 5.5 with acetic acid at 95℃, cooled to 10℃, and crystallized for 2 hours. The filtrate was then filtered, and the filter cake was dried to obtain purified sulfamethoxypyrimidine (97.8g, purity 99.69%, purification yield 97.8%).

[0069] Figure 1 The infrared spectrum of sulfa-6-methoxypyrimidine prepared in Example 1 is shown below. Figure 2 The infrared spectrum of the sulfa-6-methoxypyrimidine standard sample (purchased from the China Institute of Veterinary Drug Control) was compared. Figure 1 and Figure 2 As can be seen, the infrared spectra of the two are consistent, indicating that the synthesis method provided by the present invention can successfully prepare sulfa-6-methoxypyrimidine.

[0070] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for synthesizing sulfa-6-methoxypyrimidine, characterized in that, Includes the following steps: 4-Chloro-6-methoxypyrimidine, sulfonamide alkali metal salt and organic solvent are mixed and subjected to condensation reaction to obtain sulfonamide-6-methoxypyrimidine; The molar ratio of the 4-chloro-6-methoxypyrimidine to the sulfonamide alkali metal salt is 1:2.05 to 2.15; The organic solvent is dimethylformamide and / or dimethylacetamide, and the organic solvent is an anhydrous organic solvent; the solid-liquid ratio of the 4-chloro-6-methoxypyrimidine to the organic solvent is 1g:3-4mL; The condensation reaction is carried out at a temperature of 90–100°C for 3.5–4 hours.

2. The synthesis method according to claim 1, characterized in that, The sulfonamide alkali metal salts include sodium sulfonamide or potassium sulfonamide.

3. The synthesis method according to claim 1 or 2, characterized in that, The method for synthesizing the sulfonamide alkali metal salt includes the following steps: mixing alkali metal hydroxide, sulfonamide and water, and carrying out a salt formation reaction to obtain the sulfonamide alkali metal salt.

4. The synthesis method according to claim 1, characterized in that, The condensation reaction is followed by a post-processing step, which includes: The condensation reaction solution obtained from the condensation reaction is concentrated to obtain a concentrated solution and a recovered organic solvent; the recovered organic solvent is reused in the condensation reaction step. The concentrated solution, first water, and first activated carbon are mixed, and after first decolorization and first solid-liquid separation, a first liquid component is obtained. The mixture is cooled to room temperature, and the pH value of the first liquid component is adjusted to 7.5-8, causing solid to precipitate. A second solid-liquid separation is then performed to obtain a second liquid component and a solid component. The solid component is dried to obtain recovered sulfonamide. The recovered sulfonamide is used to prepare sulfonamide alkali metal salts. The second liquid component was cooled to room temperature, the pH was adjusted to 5-6, crystallization occurred, and the third solid-liquid separation was performed, the solid component being crude sulfamethoxypyrimidine; The crude sulfamethoxypyrimidine, second water, and alkaline reagent are thermally dissolved, and second activated carbon is added for second decolorization. Thermal solid-liquid separation is then performed to obtain the thermal liquid component. The pH value of the hot liquid component is adjusted to 5-6, cooled to crystallize, and then subjected to a fourth solid-liquid separation. The resulting solid component is dried to obtain refined sulfamethoxypyrimidine.

5. The synthesis method according to claim 4, characterized in that, The mass ratio of the sulfonamide alkali metal salt to the first activated carbon is 100:1-2; The mass ratio of the sulfonamide alkali metal salt to the first water is 1:1.4 to 1.6; The first decolorization temperature is 90-95℃, and the time is 1.5-2 hours.

6. The synthesis method according to claim 4, characterized in that, The crystallization temperature is 20–25°C, and the time is 1.5–2 hours.

7. The synthesis method according to claim 4, characterized in that, The mass ratio of the crude sulfamethoxypyrimidine to the second water is 1:4.75 to 5.25; The molar ratio of the crude sulfamethoxypyrimidine to the alkaline reagent is 1:0.5 to 0.51; the alkaline reagent includes one or more of calcium hydroxide, sodium hydroxide, and potassium hydroxide. The mass ratio of the crude sulfamethoxypyrimidine to the second activated carbon is 100:3-5; The temperatures for the thermal dissolution, the second decolorization, and the thermal solid-liquid separation are independently 90–95°C, and the time for the second decolorization is 1.5–2 hours.

8. The synthesis method according to claim 4, characterized in that, The cooling and crystallization temperature is 5–15°C, and the holding time is 1.5–2 hours.

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