Preparation method of p-toluenesulfonylurea

Abstract

The invention particularly relates to a preparation method of paratoluensulfonylurea. The preparation method comprises the following steps: jointly adding paratoluensulfonyl chloride and urea into a solvent containing an acid-binding agent, and sufficiently and uniformly mixing; adding p-toluene sulfonamide and 4-dimethylaminopyridine, sealing the reaction system, heating to 100-130 DEG C, and reacting for 2-4 hours; and adding alkali liquor into the cooled reaction system to adjust the pH value to be neutral, continuously stirring for a period of time, and filtering to obtain a solid, namely p-toluenesulfonylurea. According to the method, p-toluene sulfonamide and 4-dimethylaminopyridine are adopted as the composite catalyst, the reaction activity of urea is remarkably improved, the reaction yield is increased, in addition, the acid-binding agent can be regenerated after being treated by alkali liquor, recycling of waste filtrate and the composite catalyst in production is achieved, wastewater discharge is remarkably reduced, and the production cost is reduced.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical synthesis, and particularly relates to a method for preparing p-toluenesulfonylurea. Background Art

[0002] The information disclosed in this background technology section is only intended to enhance the understanding of the overall background of the invention, and should not necessarily be regarded as an admission or any form of suggestion that the information constitutes the prior art already known to a person skilled in the art.

[0003] Toluenesulfonyl urea can be used to synthesize hypoglycemic drugs such as gliclazide. In the prior art, the synthesis method of toluenesulfonyl urea is reported more, mainly using toluenesulfonamide and toluenesulfonyl chloride as starting materials. Invention patent CN111747872A relates to a synthesis method of toluenesulfonyl urea, wherein toluenesulfonamide and sodium cyanate are dissolved in a mixed solution of water and ethanol for reaction, filtered after the reaction is completed, and the mother liquor obtained after filtration is acidified and filtered again to finally obtain toluenesulfonyl urea. The above method has no by-products and ammonia production, and the yield of the target product reaches more than 90%, purity>99%, simple process, no waste gas production, but the cost of using sodium cyanate is relatively high. Patent CN110372545A proposes a method and process for preparing a high-purity gliclazide intermediate p-toluenesulfonyl urea, and the reaction steps are as follows: first, fill the reaction vessel with nitrogen, add an organic solvent and p-toluenesulfonyl isocyanate, charge ammonia, react at low temperature under stirring conditions to generate a crude p-toluenesulfonyl urea, then filter and add acetonitrile / water to reflux, centrifuge, and dry to obtain a white crystalline p-toluenesulfonyl urea. The invention uses p-toluenesulfonyl isocyanate to ammonolyze with ammonia in toluene to obtain p-toluenesulfonyl urea, with a yield of up to 96.3% and a product purity of more than 99.9%. The method is simple to operate, mild in conditions, easy to post-process, high in purity and yield, but the raw material p-toluenesulfonyl isocyanate is expensive and not competitive in the market. At present, the industrial production process mainly adopts the invention technology similar to CN102557997A, with p-toluenesulfonamide, inorganic base and urea as raw materials, first reacting p-toluenesulfonamide and inorganic base in an organic solvent to obtain p-toluenesulfonamido sodium, then adding urea to react with p-toluenesulfonamido sodium to obtain p-toluenesulfonylurea sodium, then acidifying the obtained p-toluenesulfonylurea sodium to obtain a crude p-toluenesulfonylurea product, and further purifying the crude product to obtain p-toluenesulfonylurea, the method is simple in process, high in raw material utilization rate and short in reaction cycle. Its raw material p-toluenesulfonamide is generally obtained by reacting p-toluenesulfonyl chloride and ammonia water. In order to reduce costs, most companies currently use a two-step method to prepare p-toluenesulfonylurea, first using p-toluenesulfonyl chloride to react with ammonia water to obtain toluenesulfonamide, which is further reacted with urea to obtain p-toluenesulfonylurea; in the first step, the ammonium chloride generated by adding ammonia water is dissolved in dilute ammonia water, and the ammonia gas generated in the second step is mixed with the alkali solution used for neutralization and will also remain in the water phase, resulting in a large amount of high-salt ammonia nitrogen wastewater in both steps, and evaporation treatment will consume a lot of energy. Therefore, although the above method has a high product yield and the quality meets the requirements of drug synthesis, the treatment cost of the wastewater generated by the reaction is high, resulting in low overall economic benefits.

[0004] The inventor believes that direct reaction of p-toluenesulfonyl chloride with urea is an ideal synthetic route. CN102219718A discloses a novel method for synthesizing p-toluenesulfonyl urea, wherein p-toluenesulfonyl chloride is added to a urea and ethylene dichloride system for condensation reaction, and ethylene dichloride can also be replaced by toluene, xylene, benzene, dichloromethane, chloroform, etc., to generate p-toluenesulfonyl urea, and after the condensation reaction is completed, sodium hydroxide solution is added to neutralize the generated hydrogen chloride, and p-toluenesulfonyl urea is freed and precipitated, and p-toluenesulfonyl urea is obtained by filtration. However, after multiple tests, no product was obtained even when heated to 140 degrees, indicating that it is not feasible to directly mix the two for reaction. Summary of the invention

[0005] In view of the above research status, the present invention aims to provide a method for synthesizing p-toluenesulfonyl urea with high product yield, simple process and no obvious waste products. In order to achieve the above technical objectives, the present invention is designed to provide a preparation process for one-step synthesis using p-toluenesulfonyl chloride and urea as raw materials, which overcomes the defect of low yield of the reaction of p-toluenesulfonyl chloride and urea by introducing a composite catalyst, and also provides a recycling solution for the wastewater produced by the above reaction, thereby achieving efficient synthesis while reducing production costs and maximizing the production benefits of enterprises.

[0006] Based on the above technical effects, the present invention provides the following technical solutions: The present invention provides a method for preparing p-toluenesulfonylurea, comprising the following steps: (1) adding p-toluenesulfonyl chloride and urea to a solvent containing an acid binding agent and mixing them thoroughly; wherein the weight of the solvent is 3-10 times the weight of p-toluenesulfonyl chloride, and the molar ratio of p-toluenesulfonyl chloride, urea and acid binding agent is 1-1.2:1-1.2:1-1.5; (2) After adding the composite catalyst, the reaction system is sealed and heated to 100-130° C. for reaction for 2-4 hours; the composite catalyst is a mixture of p-toluenesulfonamide and 4-dimethylaminopyridine in a molar ratio of 1:0.8-1.2; (3) Adding alkaline solution to the reaction system after cooling to adjust the pH to neutral and continue stirring for a period of time. The solid obtained by filtering is p-toluenesulfonylurea.

[0007] The present invention uses p-toluenesulfonyl chloride and urea as raw materials to synthesize p-toluenesulfonylurea through a one-step reaction, and the reaction route is shown in the following formula: However, urea will undergo a decomposition reaction when heated to about 160°C, and a condensation reaction will occur when heated further to produce biuret, triuret and cyanuric acid. When heated below 160°C, urea is not active, so the yield of the above reaction is very low. In order to solve this problem, the present invention first introduces a composite catalyst of p-toluenesulfonamide and 4-dimethylaminopyridine (DMAP). The pyridine ring of DMAP has significantly enhanced alkalinity due to its dimethylamino group (strong electron-donating group) at the 4th position, making it a strong nucleophilic reagent. When sulfonyl chloride (RSO2Cl) participates in the reaction, the pyridine nitrogen atom of DMAP nucleophilically attacks the sulfur atom of sulfonyl chloride to form a highly active N-sulfonylpyridinium salt intermediate (RSO 2- DMAP⁺Cl⁻), the sulfonyl group of the intermediate is significantly activated (SO bond polarization, the positive charge of sulfur atom is enhanced). Urea attacks the positive center of sulfur atom in active intermediate through nitrogen lone electron pair, replaces DMAP, and generates sulfonylurea product (RSO2NHCONH2). DMAP regenerates (restores free state) after completing the transfer, and continues to catalyze the next sulfonyl transfer process (catalytic cycle). When DMAP catalyzes sulfonylation reaction, it is usually necessary to use alkaline reagent (such as triethylamine) to neutralize the released HCl to avoid HCl protonating DMAP and inhibiting the reaction. DMAP can also activate p-toluenesulfonamide, and urea molecules are more likely to attack to form p-toluenesulfonylurea. The ammonia released by the reaction reacts rapidly with p-toluenesulfonic chloride to generate p-toluenesulfonamide again, and the cyclic catalysis realizes the acceleration of the reaction rate. In some embodiments verified by the present invention, the p-toluenesulfonamide and 4-dimethylaminopyridine are mixed in a molar ratio of 1:1.

[0008] In addition, the above preparation method also has the following preferred embodiments: In step (1): The acid binding agent is preferably an organic amine, more preferably a triamine, and further includes but is not limited to one or a combination of triethylamine, tributylamine, and trioctylamine.

[0009] The solvent is an aromatic hydrocarbon with a boiling point above 100 degrees, further selected from substituted benzene reagents, and further includes but is not limited to one or a combination of toluene, xylene, trimethylbenzene, chlorobenzene, and dichlorobenzene.

[0010] In step (2): The molar ratio of the composite catalyst to p-toluenesulfonyl chloride is 0.01-0.10:1.

[0011] The heating temperature is more preferably 110-120°C.

[0012] In step (3): The alkali solution is preferably an inorganic alkali, such as one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate or an aqueous solution of potassium bicarbonate. The concentration of the alkali solution can be adjusted by technicians based on factors such as the reaction volume and reaction conditions. A feasible mass fraction is, for example, 5% to 40%.

[0013] In addition, in order to reduce the reagent consumption in the above preparation method and reduce the production cost, the present invention also optimizes the filtrate produced by filtration in step (3) and provides a solution for recycling the filtrate. In a more preferred embodiment, step (3) is as follows: After the reaction system is adjusted to neutral, stirring is continued for 20-60 minutes to obtain a feed liquid, the feed liquid is filtered to obtain a filter residue 1 and a filtrate 1, 5-10 times the weight of hot water (85-95° C.) is added to the filter residue 1, stirred and filtered to obtain a filter residue 2 and a filtrate 2, and the filter residue 2 is dried to obtain the p-toluenesulfonyl urea; the filtrate 1 is allowed to stand for stratification and separation, the separated upper layer part replaces the solvent and the acid binding agent in step (1), and the separated lower layer is partially prepared with alkali to replace the alkali solution in step (3); the filtrate 2 is cooled to below 40° C. for crystallization, and the crystals obtained by filtering are put into step (2) for further use.

[0014] In the above step (3), after the pH of the feed solution is adjusted to neutral, the product p-toluenesulfonyl urea and the composite catalyst are precipitated at this pH. Since the composite catalyst has better solubility in water, it can be dissolved by hot water, and the composite catalyst can be separated from the product p-toluenesulfonyl urea, and precipitated after cooling and reused in step (2). The filtrate 1 mainly includes solvent, acid binding agent and alkaline water. The alkaline environment promotes the regeneration of the acid binding agent. Therefore, the solvent and the acid binding agent are separated as the organic phase (upper phase) and can be reused in step (1).

[0015] Compared with the prior art, the present invention has the following beneficial effects: The invention adopts a one-step reaction of p-toluenesulfonyl chloride and urea, which meets the atomic economy and utilizes the raw materials to the maximum extent; p-toluenesulfonyl chloride and urea are difficult to react below 130 degrees, and high temperature will lead to the polymerization reaction of urea. The invention solves the problem of the reaction of p-toluenesulfonyl chloride and urea by catalysis; the invention adopts an organic acid-binding agent to be regenerated and recycled by alkali solution, and no waste water is discharged in the production process, and the environmental protection benefit is obvious. The invention not only reduces the operation steps, but also greatly reduces the raw material, operation and waste water treatment costs. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] The accompanying drawings in the specification, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0017] Figure 1This is the infrared spectrum of the p-toluenesulfonylurea product prepared in Example 1; Figure 2 This is the hydrogen nuclear magnetic resonance spectrum of the p-toluenesulfonylurea product prepared in Example 1; Figure 3 The liquid chromatogram of the toluenesulfonylurea product prepared in Example 1 is shown. DETAILED DESCRIPTION

[0018] It should be noted that the following detailed descriptions are all illustrative and intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used herein have the same meanings as those commonly understood by those skilled in the art to which the present invention belongs.

[0019] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit exemplary embodiments according to the present invention. As used herein, unless the context clearly indicates otherwise, the singular form is also intended to include the plural form. In addition, it should be understood that when the terms "comprising" and / or "including" are used in this specification, it indicates the presence of features, steps, operations, devices, components and / or combinations thereof.

[0020] In order to enable those skilled in the art to more clearly understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below in combination with specific embodiments and comparative examples.

[0021] Example 1 In this embodiment, a method for preparing p-toluenesulfonylurea is provided, comprising the following steps: (1) Add 100 g of toluene and 15 g of triethylamine (0.1 mol) to the reaction device and mix them evenly. Then add 20 g of p-toluenesulfonyl chloride (0.105 mol) and 6.3 g of urea (0.105 mol) to the reaction device in sequence and stir and mix for half an hour. (2) Add 1 g of composite catalyst (0.58 g of p-toluenesulfonamide and 0.42 g of 4-dimethylaminopyridine) to the reaction device and mix well. Seal the reaction device, heat to 110 °C while stirring, keep warm for 3 h, and then cool to room temperature. (3) Add 32% by mass sodium hydroxide solution to the reaction mixture to adjust the reaction mixture to neutrality, and then continue stirring for 30 minutes; filter the neutralized feed liquid to obtain a filter residue and a filtrate; add 10 times the weight of hot water (90°C) to the filter residue to stir, and filter it twice to obtain a filter residue and a filtrate; dry the filter residue to obtain 21.5 g of a toluenesulfonyl urea product with a yield of 95.5%; cool the filtrate to 35°C or below for crystallization, and filter it for the third time; filter the obtained crystalline solid and return it to step (2) for use; reuse the filtered water from the third filtration; let the filtrate stand for stratification and separation, and the separated upper layer is used to replace the solvent and the acid binding agent in step (1); and the separated lower layer is prepared with alkali and used to replace the alkali solution in step (3).

[0022] The purity of the obtained p-toluenesulfonylurea product was 99.4% as determined by liquid chromatography. The infrared spectrum is shown in the attached Figure 1 , see the attached H NMR spectrum Figure 2 , the liquid chromatography spectrum is as follows Figure 3 .

[0023] Example 2 In this embodiment, another method for preparing p-toluenesulfonylurea is provided, comprising the following steps: (1) Add 60 g of chlorobenzene and 15 g of triethylamine to the reaction device and mix them evenly. Then, add 20 g of p-toluenesulfonyl chloride and 6.3 g of urea to the reaction device in sequence and stir for half an hour. (2) Add 2 g of composite catalyst (1.16 g of p-toluenesulfonamide and 0.84 g of 4-dimethylaminopyridine) to the reaction device and mix well. Seal the reaction device, heat to 100 °C while stirring, keep warm for 4 h, and then cool to room temperature. (3) Add 28% by mass of sodium hydroxide solution to the reaction mixture to adjust the reaction mixture to neutrality, and then continue stirring for 30 minutes; filter the neutralized feed liquid to obtain a filter residue and a filtrate; add 10 times the weight of hot water (90° C.) to the filter residue to obtain a filter residue and a filtrate; dry the filter residue to obtain 21.7 g of the product with a yield of 96.4%; cool the filtrate to 35° C. for crystallization, filter for the third time, and return the crystallized solid from the third filtration to step (2); reuse the filtered water from the third filtration; let the filtrate stand for stratification and separation, and the separated upper layer is used to replace the solvent and the acid binding agent in step (1); and the separated lower layer is prepared with alkali and used to replace the alkali solution in step (3).

[0024] The purity of the obtained product was 99.2% as determined by liquid chromatography.

[0025] Example 3 In this embodiment, another method for preparing p-toluenesulfonylurea is provided, comprising the following steps: (1) Add 200 g of xylene and 27.5 g of tributylamine to the reaction device and mix them evenly. Then, add 20 g of p-toluenesulfonyl chloride and 6.3 g of urea to the reaction device in sequence and stir and mix for half an hour. (2) Add 0.5 g of composite catalyst (0.29 g of p-toluenesulfonamide and 0.21 g of 4-dimethylaminopyridine) to the reaction device and mix well. Seal the reaction device, heat to 120 °C while stirring, keep warm for 2 h, and then cool to room temperature. (3) Add 40% by mass potassium hydroxide solution to the reaction mixture to adjust the reaction mixture to neutrality, and then continue stirring for 30 minutes; filter the neutralized feed liquid to obtain a filter residue and a filtrate; add 8 times the weight of hot water (90° C.) to the filter residue to obtain a filter residue and a filtrate; dry the filter residue to obtain 21.3 g of the product with a yield of 94%; cool the filtrate to 35° C. for crystallization, and filter it for the third time; return the crystallized solid from the third filtration to step (2); reuse the filtered water from the third filtration; let the filtrate stand for stratification and separation; the separated upper layer is used to replace the solvent and the acid binding agent in step (1); and the separated lower layer is prepared with alkali and used to replace the alkali solution in step (3).

[0026] The purity of the obtained product was 99.3% as determined by liquid chromatography.

[0027] Example 4 In this embodiment, another method for preparing p-toluenesulfonylurea is provided, comprising the following steps: (1) Add 100 g of toluene and 27.5 g of tributylamine to the reaction device and mix them evenly. Then, add 20 g of p-toluenesulfonyl chloride and 6.3 g of urea to the reaction device in sequence and stir and mix for half an hour. (2) Add 0.5 g of composite catalyst (0.29 g of p-toluenesulfonamide and 0.21 g of 4-dimethylaminopyridine) to the reaction device and mix well. Seal the reaction device, heat to 120°C while stirring, keep warm for 3 h, and then cool to room temperature. (3) Add 32% by mass of sodium hydroxide solution to the reaction mixture to adjust the reaction mixture to neutrality, and then continue stirring for 30 minutes; filter the neutralized feed liquid to obtain a filter residue and a filtrate, add 10 times the weight of hot water (95°C) to the filter residue, stir, and filter twice to obtain a filter residue II and a filtrate II, dry the filter residue II to obtain 21.0 g of the product, with a yield of 93.3%; cool the filtrate II to 40°C for crystallization, filter for the third time, and return the crystallized solid from the third filtration to step (2) for use; reuse the filtered water from the third filtration; let the filtrate I stand for stratification and separation, the separated upper layer is used to replace the solvent and the acid binding agent in step (1), and the separated lower layer is prepared with alkali and used in step (3) to replace the alkali solution.

[0028] The purity of the obtained product was 99.5% as determined by liquid chromatography.

[0029] Example 5 In this embodiment, another method for preparing p-toluenesulfonylurea is provided, comprising the following steps: (1) Add the upper layer (organic phase) of the filtrate recovered in Example 4 to the reaction apparatus, then add 20 g of toluenesulfonyl chloride and 6.3 g of urea to the reaction apparatus in sequence, and stir and mix for half an hour; (2) Add the crystalline solid (composite catalyst) recovered in Example 4 into the reaction device and mix well, seal the reaction device, heat to 110° C. under stirring, keep warm for 3 h, and then cool to room temperature; (3) Add the lower aqueous phase of the filtrate to the reaction mixture, adjust the reaction mixture to neutrality with a sodium hydroxide solution having a mass fraction of 40%, and continue stirring for 30 minutes; filter the neutralized feed liquid to obtain a filter residue and a filtrate; add 10 times the weight of hot water (85°C) to the filter residue to stir, filter it twice to obtain a filter residue and a filtrate; dry the filter residue to obtain 21.1 g of the product with a yield of 93.8%; cool the filtrate to 35°C for crystallization, filter it for the third time, and return the crystallized solid from the third filtration to step (2); reuse the filtered water from the third filtration; let the filtrate stand for stratification and separation, and use the separated upper layer to replace the solvent and the acid binding agent in step (1); add alkali to the separated lower layer to replace the alkali solution in step (3).

[0030] The purity of the obtained product was 99.2% as determined by liquid chromatography.

[0031] Comparative Example A method for direct reaction of toluenesulfonyl chloride and urea provided in CN102219718A was used for comparison. 39 g (0.65 mol) of urea and 79 g (0.8 mol) of dichloroethane were added to a condensation reaction tank, heated to 60 ° C, and a solution of 95 g (0.5 mol) of toluenesulfonyl chloride and 79 g (0.8 mol) of dichloroethane was added dropwise, and the temperature was kept at about 60-65 ° C. After the addition was completed, the temperature was raised to 70-72 ° C, and the reaction was kept warm for 3.5 hours, cooled to room temperature, and the prepared sodium hydroxide aqueous solution was added to make the reaction solution neutral, and then distilled to recover dichloroethane until no dichloroethane was evaporated, cooled and crystallized, centrifuged, washed with water, and a crude wet product of toluenesulfonyl urea was obtained. No product was found by liquid chromatography. No product was detected when heated to reflux at the ratio of reactants and the temperature was controlled at 110, 120, 130, and 140 degrees.

[0032] After consulting the literature, it was found that the reaction activity of urea is very low, and p-toluenesulfonyl chloride cannot react directly with urea without a catalyst.

[0033] In summary, the present invention believes that it is difficult for p-toluenesulfonyl chloride and urea to directly undergo addition reaction below 130°C, and urea is inactive and has a low yield. In the process provided by the present invention, the reaction temperature is controlled at 130°C or below, urea basically does not undergo side reactions, and the introduction of the composite catalyst significantly improves the activity of urea. The product yield of p-toluenesulfonyl urea in the above embodiments is more than 90%, and the product purity is high, which is a product with high market value.

[0034] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for preparing p-toluenesulfonylurea, characterized in that: The steps include: (1) adding p-toluenesulfonyl chloride and urea to a solvent containing an acid binding agent and mixing them thoroughly; wherein the weight of the solvent is 3-10 times the weight of p-toluenesulfonyl chloride, and the molar ratio of p-toluenesulfonyl chloride, urea and acid binding agent is 1-1.2:1-1.2:1-1.5; (2) After adding the composite catalyst, the reaction system is sealed and heated to 100-130° C. for reaction for 2-4 hours; the composite catalyst is a mixture of p-toluenesulfonamide and 4-dimethylaminopyridine in a molar ratio of 1:0.8-1.2; (3) Adding alkaline solution to the reaction system after cooling to adjust the pH to neutral and continue stirring for a period of time. The solid obtained by filtering is p-toluenesulfonylurea.

2. The method for preparing p-toluenesulfonylurea as claimed in claim 1, characterized in that: In step (1): the acid binding agent is selected from one or a combination of triethylamine, tributylamine and trioctylamine.

3. The method for preparing p-toluenesulfonylurea as claimed in claim 1, characterized in that: In step (1): the solvent is selected from one or a combination of toluene, xylene, trimethylbenzene, chlorobenzene and dichlorobenzene.

4. The method for preparing p-toluenesulfonylurea as claimed in claim 1, characterized in that: In step (2): the molar ratio of the composite catalyst to p-toluenesulfonyl chloride is 0.01-0.10:

1.

5. The method for preparing p-toluenesulfonylurea as claimed in claim 1, characterized in that: In step (2): the p-toluenesulfonamide and 4-dimethylaminopyridine are mixed in a molar ratio of 1:

1.

6. The method for preparing p-toluenesulfonylurea as claimed in claim 1, characterized in that: In step (3): the alkali solution is selected from an aqueous solution of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate or potassium bicarbonate.

7. The method for preparing p-toluenesulfonylurea as claimed in claim 6, characterized in that: The mass fraction of the alkali solution is 5% to 40%.

8. The method for preparing p-toluenesulfonylurea as claimed in claim 1, characterized in that: The specific implementation method of step (3) is as follows: After the reaction system is adjusted to neutral, stirring is continued for 20-60 minutes to obtain a feed liquid, the feed liquid is filtered to obtain a filter residue 1 and a filtrate 1, 5-10 times the weight of hot water is added to the filter residue 1, stirred and filtered to obtain a filter residue 2 and a filtrate 2, and the filter residue 2 is dried to obtain the p-toluenesulfonyl urea; the filtrate 1 is allowed to stand for stratification and separation, the separated upper layer part replaces the solvent and the acid binding agent in step (1), and the separated lower layer is partially prepared with alkali to replace the alkali solution in step (3); the filtrate 2 is cooled and crystallized, and the crystals obtained by filtering are put into step (2) for further use.

9. The method for preparing p-toluenesulfonylurea as claimed in claim 8, characterized in that: The hot water temperature is 85-95°C.

10. The method for preparing p-toluenesulfonylurea as claimed in claim 8, characterized in that: The temperature of the cooling crystallization is 40° C. or below.

Images