CN119841748B - A kind of preparation method of toluenesulfonylurea - Google Patents
A kind of preparation method of toluenesulfonylurea Download PDFInfo
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- 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
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Abstract
The invention particularly relates to a preparation method of p-toluenesulfonyl urea, which comprises the steps of adding p-toluenesulfonyl chloride and urea into a solvent containing an acid binding agent, fully and uniformly mixing, adding p-toluenesulfonamide and 4-dimethylaminopyridine, then sealing a reaction system, heating to 100-130 ℃ for reacting for 2-4 hours, adding alkali liquor into the reaction system after cooling to adjust the pH value to be neutral, continuously stirring for a period of time, and filtering to obtain a solid, namely the p-toluenesulfonyl urea. According to the invention, p-toluenesulfonamide and 4-dimethylaminopyridine are adopted as the composite catalyst, so that the reaction activity of urea is obviously improved, the reaction yield is improved, and in addition, the acid binding agent is renewable through alkali liquor treatment, so that the recycling of waste filtrate and the composite catalyst in production is realized, the waste water emission is obviously reduced, and the production cost is reduced.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis, and particularly relates to a preparation method of p-toluenesulfonyl urea.
Background
The disclosure of this background section is only intended to increase the understanding of the general background of the invention and is not necessarily to be construed as an admission or any form of suggestion that this information forms the prior art already known to those of ordinary skill in the art.
The p-toluenesulfonylurea can be used for synthesizing hypoglycemic gliclazide (gliclazide) and the like. In the prior art, many synthetic methods of p-toluenesulfonyl urea are reported, and p-toluenesulfonamide and p-toluenesulfonyl chloride are mainly used as starting materials. The invention patent CN111747872A relates to a method for synthesizing p-toluenesulfonyl urea, which comprises the steps of dissolving p-toluenesulfonamide and sodium cyanate in a mixed solution of water and ethanol for reaction, filtering after the reaction is finished, acidizing mother liquor obtained after the filtration, and filtering again to finally obtain the p-toluenesulfonyl urea. The method has the advantages of no byproducts and ammonia gas production, the yield of the target product reaching more than 90 percent, the purity of the target product being more than 99 percent, simple process, no waste gas production, and higher cost of sodium cyanate. The patent CN110372545A proposes a preparation method and a process of high-purity gliclazide intermediate p-toluenesulfonyl urea, which comprises the following steps of firstly filling nitrogen into a reaction vessel, adding an organic solvent and p-toluenesulfonyl isocyanate, filling ammonia gas, reacting at a low temperature under stirring to generate a p-toluenesulfonyl urea crude product, filtering, adding acetonitrile/water for reflux, centrifuging, and drying to obtain white crystal p-toluenesulfonyl urea. The invention prepares the p-toluenesulfonyl urea by ammonolysis of the p-toluenesulfonyl isocyanate and ammonia gas in toluene, the yield can reach 96.3 percent, the purity of the product is over 99.9 percent, the method has simple operation, mild condition, easy post-treatment, high purity and high yield, but the raw material p-toluenesulfonyl isocyanate is expensive and does not have market competitiveness. The present industrial production process mainly adopts the technology similar to CN102557997A, takes p-toluenesulfonamide, inorganic base and urea as raw materials, firstly reacts the p-toluenesulfonamide and the inorganic base in an organic solvent to obtain sodium p-toluenesulfonamide, then adds urea and sodium p-toluenesulfonamide to react to obtain sodium p-toluenesulfonamide, then acidizes the obtained sodium p-toluenesulfonamide to obtain a crude p-toluenesulfonamide product, and further purifies the crude p-toluenesulfonamide to obtain the p-toluenesulfonamide. The raw material of the p-toluenesulfonamide is generally obtained by reacting p-toluenesulfonyl chloride with ammonia water. In the first step, ammonium chloride generated by adding ammonia water is dissolved in dilute ammonia water, and ammonia gas generated in the second step is mixed with alkali liquor used in neutralization to remain in an aqueous phase, so that a large amount of high-salt ammonia nitrogen wastewater is generated in both steps, and a large amount of energy is consumed for evaporating the high-salt ammonia nitrogen wastewater. Therefore, although the method has high product yield and high quality, and meets the requirement of drug synthesis, the wastewater generated by the reaction has high treatment cost, so that the overall economic benefit is not high.
The inventors believe that direct reaction of p-toluenesulfonyl chloride with urea is an ideal synthetic route. CN102219718a discloses a new method for synthesizing p-toluenesulfonyl urea, adding p-toluenesulfonyl chloride into urea and dichloroethane system to make condensation reaction, and the dichloroethane can be substituted by one of toluene, xylene, benzene, dichloromethane and chloroform to produce p-toluenesulfonyl urea, after the condensation reaction is completed, adding sodium hydroxide solution, and neutralizing the produced hydrogen chloride, the p-toluenesulfonyl urea can be separated out, and filtered so as to obtain p-toluenesulfonyl urea. However, after many experiments, no product was obtained even when heated to 140 degrees, indicating that it was not feasible to directly mix the two.
Disclosure of Invention
Aiming at the current research situation, the invention aims to provide a p-toluenesulfonyl urea synthesis method which has high product yield, simple process and no obvious waste products. In order to achieve the technical aim, the invention provides a preparation process for one-step synthesis by taking the p-toluenesulfonyl chloride and urea as raw materials, overcomes the defect of low reaction yield of the p-toluenesulfonyl chloride and the urea by introducing a composite catalyst, and also provides a recycling scheme for wastewater produced by the reaction, thereby realizing efficient synthesis, reducing production cost and maximally improving the production benefit of enterprises.
Based on the technical effects obtained, the invention provides the following technical scheme:
the invention provides a preparation method of p-toluenesulfonyl urea, which comprises the following steps:
(1) Adding p-toluenesulfonyl chloride and urea into a solvent containing an acid binding agent, and fully and uniformly mixing, wherein the weight of the solvent is 3-10 times of that of the p-toluenesulfonyl chloride, and the molar ratio of the p-toluenesulfonyl chloride to the urea to the acid binding agent is 1-1.2:1-1.5;
(2) Adding a composite catalyst, and then sealing a reaction system, and heating to 100-130 ℃ to react for 2-4 hours, wherein the composite catalyst is a mixture of p-toluenesulfonamide and 4-dimethylaminopyridine according to a molar ratio of 1:0.8-1.2;
(3) 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 solid, namely the p-toluenesulfonyl urea.
The invention designs the method for synthesizing the p-toluenesulfonyl urea by taking the p-toluenesulfonyl chloride and the urea as raw materials through one-step reaction, wherein the reaction route is shown as the following formula:
However, urea undergoes decomposition reaction when heated to about 160 ℃, and further undergoes condensation reaction to give biuret, triurea, cyanuric acid, etc., and when heated to less than 160 ℃, urea is inactive and thus the reaction yield is very low. In order to solve the problem, the invention firstly introduces the composite catalyst of p-toluenesulfonamide and 4-Dimethylaminopyridine (DMAP), and the pyridine ring of the DMAP becomes a strong nucleophile because the alkalinity of dimethylamino (strong electron donating group) at the 4-position of the pyridine ring of the DMAP is obviously enhanced. When sulfonyl chloride (RSO 2 Cl) is involved in the reaction, the pyridine nitrogen atom of DMAP nucleophilic attacks the sulfur atom of the sulfonyl chloride, forming a highly reactive N-sulfonylpyridinium salt intermediate (RSO 2- dmap+cl-), whose sulfonyl group is significantly activated (S-O bond polarized, sulfur atom electropositivity enhanced). Urea attacks the positive center of the sulfur atom in the reactive intermediate through a nitrogen lone pair, replacing DMAP, yielding a sulfonylurea product (RSO 2NHCONH2). DMAP regenerates after transfer is completed (reverts to the free state) and continues to catalyze the next sulfonyl transfer process (catalytic cycle). In catalyzing the sulfonylation reaction, the DMAP is usually matched with an alkaline reagent (such as triethylamine) to neutralize the released HCl, so that the reaction is prevented from being inhibited by protonating the DMAP by the HCl. DMAP can activate p-toluenesulfonamide, urea molecules are easier to attack and form p-toluenesulfonyl urea, ammonia released by the reaction rapidly reacts with p-toluenesulfonyl chloride to generate p-toluenesulfonamide, and the cyclic catalysis realizes the acceleration of the reaction speed. In some embodiments of the present invention, the p-toluenesulfonamide and 4-dimethylaminopyridine are mixed in a molar ratio of 1:1.
In addition, the above preparation method has the following preferred embodiments:
in step (1):
The acid-binding agent is preferably an organic amine, more preferably a triamine, and even more preferably one or a combination of several of triethylamine, tributylamine and trioctylamine.
The solvent is aromatic hydrocarbon with boiling point of above 100 degrees, and is further selected from substituted benzene reagent, and further comprises one or a combination of more than one of toluene, xylene, trimethylbenzene, chlorobenzene and dichlorobenzene.
In the step (2):
the molar ratio of the composite catalyst to the p-toluenesulfonyl chloride is 0.01-0.10:1.
The heating temperature is further preferably 110-120 ℃.
In the step (3):
The alkali liquor is preferably an inorganic alkali, such as one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate or aqueous solution of potassium bicarbonate, and the concentration of the alkali liquor can be adjusted by a technician according to factors such as the amount of a reaction body, the reaction condition and the like, and the feasible mass fraction is 5% -40%.
In addition, in order to reduce the reagent consumption and the production cost in the preparation method and optimize the filtrate generated by filtering in the step (3), the invention provides a scheme for recycling the filtrate, and in a more preferred embodiment, the step (3) is as follows:
And (3) continuously stirring for 20-60min after the reaction system is regulated to be neutral to obtain a feed liquid, filtering the feed liquid to obtain a first filter residue and a first filter liquid, adding hot water (85-95 ℃) which is 5-10 times the weight of the first filter residue, stirring and filtering to obtain a second filter residue and a second filter liquid, drying the second filter residue to obtain the p-toluenesulfonyl urea, standing and layering the first filter liquid, separating an upper layer part which is separated out to replace a solvent and an acid binding agent in the step (1), adding an alkali-adding modulating part which is separated out to replace an alkali liquid in the step (3), cooling the second filter liquid to below 40 ℃, crystallizing, and filtering to obtain crystals, and continuously using the crystals in the step (2).
In the step (3), after the pH of the feed liquid is adjusted to be neutral, the p-toluenesulfonyl urea product and the composite catalyst are separated out at the pH, and the composite catalyst can be separated from the p-toluenesulfonyl urea product by hot water dissolution due to better solubility of the composite catalyst in water and is separated out after being cooled and reused in the step (2). The first filtrate mainly comprises a solvent, an acid binding agent and alkali water, and the alkaline environment can promote the regeneration of the acid binding agent, so that the solvent and the acid binding agent are separated as an organic phase (upper phase) and can be put into the step (1) for repeated use.
Compared with the prior art, the invention has the beneficial effects that:
The invention adopts one-step reaction of the tosyl chloride and the urea, accords with atom economy, furthest utilizes raw materials, is difficult to react at the temperature of below 130 ℃ and can lead to the polymerization reaction of the urea, the invention solves the difficult problem of the reaction of the tosyl chloride and the urea through catalysis, and the invention adopts an organic acid binding agent to recycle through alkali liquor regeneration, and the production process does not discharge waste water, has obvious environmental protection benefit, reduces operation steps, and greatly reduces the cost of raw materials, operation and waste water treatment.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the invention.
FIG. 1 is an infrared spectrum of the p-toluenesulfonyl urea product prepared in example 1;
FIG. 2 is a nuclear magnetic resonance hydrogen spectrum of the p-toluenesulfonyl urea product prepared in example 1;
FIG. 3 is a liquid chromatogram of the p-toluenesulfonylurea product prepared in example 1.
Detailed Description
It should be noted that the following detailed description is illustrative and is intended to provide further explanation of the invention. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of exemplary embodiments according to the present invention. As used herein, the singular is also intended to include the plural unless the context clearly indicates otherwise, and furthermore, it is to be understood that the terms "comprises" and/or "comprising" when used in this specification are taken to specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof.
In order to enable those skilled in the art to more clearly understand the technical scheme of the present invention, the technical scheme of the present invention will be described in detail below with reference to specific examples and comparative examples.
Example 1
In this embodiment, a method for preparing p-toluenesulfonyl urea is provided, which includes the following steps:
(1) 100g of toluene and 15g of triethylamine (0.1 mol) are added into a reaction device and uniformly mixed, and then 20g of p-toluenesulfonyl chloride (0.105 mol) and 6.3g of urea (0.105 mol) are added into the reaction device in sequence and stirred and mixed for half an hour;
(2) Adding 1g of composite catalyst (0.58 g of p-toluenesulfonamide and 0.42 g of 4-dimethylaminopyridine) into a reaction device, uniformly mixing, sealing the reaction device, heating to 110 ℃ under stirring, preserving heat for 3h, and cooling to room temperature;
(3) Adding 32% sodium hydroxide solution into the reaction mixture to adjust the reaction mixture to be neutral, continuously stirring for 30min, filtering the neutralized feed liquid to obtain first filter residue and first filter residue, adding 10 times of hot water (90 ℃) into the first filter residue, stirring, filtering for the second time to obtain second filter residue and second filter residue, drying the second filter residue to obtain 21.5g of p-toluenesulfonyl urea product, obtaining the yield of 95.5%, crystallizing the second filter residue at a temperature of 35 ℃ or below, filtering for the third time, returning the crystallized solid obtained by filtering to the step (2), reusing filtered water obtained by filtering for the third time, standing and layering the first filter residue, separating the separated upper layer, using the separated upper layer in the step (1) to replace a solvent and an acid binding agent, and adding alkali to the separated lower layer for modulating in the step (3) to replace alkali liquor.
The purity of the obtained p-toluenesulfonyl urea product is 99.4% by liquid chromatography, the infrared spectrum is shown in figure 1, the nuclear magnetic hydrogen spectrum is shown in figure 2, and the liquid chromatography is shown in figure 3.
Example 2
In this embodiment, there is provided a method for producing p-toluenesulfonyl urea, comprising the steps of:
(1) Adding 60g of chlorobenzene and 15g of triethylamine into a reaction device, uniformly mixing, sequentially adding 20g of p-toluenesulfonyl chloride and 6.3g of urea into the reaction device, and stirring and mixing for half an hour;
(2) Adding 2g of composite catalyst (1.16 g of p-toluenesulfonamide and 0.84 g of 4-dimethylaminopyridine) into a reaction device, uniformly mixing, sealing the reaction device, heating to 100 ℃ under stirring, preserving heat for 4 hours, and cooling to room temperature;
(3) Adding 28% sodium hydroxide solution into the reaction mixture to adjust the reaction mixture to be neutral, continuously stirring for 30min, filtering the neutralized feed liquid to obtain first filter residue and first filter residue, adding 10 times of hot water (90 ℃) into the first filter residue, stirring, performing secondary filtration to obtain second filter residue and second filter residue, drying the second filter residue to obtain 21.7g of product with the yield of 96.4%, cooling (35 ℃) the second filter residue for crystallization, performing tertiary filtration, returning the crystallized solid filtered in the tertiary filtration to the step (2), repeatedly using filtered water filtered in the tertiary filtration, standing and layering the filtrate, separating the separated upper layer, using the separated upper layer in the step (1) to replace a solvent and an acid binding agent, and adding alkali into the separated lower layer for modulation in the step (3) to replace alkali liquor.
The purity of the obtained product was 99.2% as determined by liquid chromatography.
Example 3
In this embodiment, there is provided a method for producing p-toluenesulfonyl urea, comprising the steps of:
(1) Adding 200g of dimethylbenzene and 27.5g of tributylamine into a reaction device, uniformly mixing, sequentially adding 20g of p-toluenesulfonyl chloride and 6.3g of urea into the reaction device, and stirring and mixing for half an hour;
(2) Adding 0.5g of composite catalyst (0.29 g of p-toluenesulfonamide and 0.21 g of 4-dimethylaminopyridine) into a reaction device, uniformly mixing, sealing the reaction device, heating to 120 ℃ under stirring, preserving heat for 2h, and cooling to room temperature;
(3) Adding 40% potassium hydroxide solution into the reaction mixture to adjust the reaction mixture to be neutral, continuously stirring for 30min, filtering the neutralized feed liquid to obtain first filter residue and first filter residue, adding 8 times of hot water (90 ℃) into the first filter residue, stirring, performing secondary filtration to obtain second filter residue and second filter residue, drying the second filter residue to obtain 21.3g of product with the yield of 94%, cooling (35 ℃) the second filter residue for crystallization, performing tertiary filtration, returning the crystallized solid filtered for the tertiary time to the step (2), repeatedly using filtered water filtered for the tertiary time, standing and layering the first filter residue, separating the separated upper layer, and adding alkali into the separated lower layer for modulating the alkali solution in the step (3) for replacing alkali solution.
The purity of the obtained product was 99.3% as determined by liquid chromatography.
Example 4
In this embodiment, there is provided a method for producing p-toluenesulfonyl urea, comprising the steps of:
(1) Adding 100g of toluene and 27.5g of tributylamine into a reaction device, uniformly mixing, sequentially adding 20g of p-toluenesulfonyl chloride and 6.3g of urea into the reaction device, and stirring and mixing for half an hour;
(2) Adding 0.5g of composite catalyst (0.29 g of p-toluenesulfonamide and 0.21 g of 4-dimethylaminopyridine) into a reaction device, uniformly mixing, sealing the reaction device, heating to 120 ℃ under stirring, preserving heat for 3h, and cooling to room temperature;
(3) Adding 32% sodium hydroxide solution into the reaction mixture to adjust the reaction mixture to be neutral, continuously stirring for 30min, filtering the neutralized feed liquid to obtain filter residues and filtrate, adding 10 times of hot water (95 ℃) into the filter residues, stirring, filtering for the second time to obtain filter residues II and filtrate II, drying the filter residues II to obtain 21.0g of a product with the yield of 93.3%, cooling (40 ℃) the filtrate II for crystallization, filtering for the third time, returning the crystallized solid filtered for the third time to the step (2), repeatedly using filtered water filtered for the third time, standing and layering the filtrate I, separating the separated upper layer, and adding alkali into the separated lower layer for modulating the lower layer in the step (3) to replace alkali liquor.
The purity of the obtained product was 99.5% as determined by liquid chromatography.
Example 5
In this embodiment, there is provided a method for producing p-toluenesulfonyl urea, comprising the steps of:
(1) Adding the upper layer (organic phase) of the filtrate recovered in the example 4 into a reaction device, sequentially adding 20g of tosyl chloride and 6.3g of urea into the reaction device, and stirring and mixing for half an hour;
(2) Adding the crystalline solid (composite catalyst) recovered in the example 4 into a reaction device, uniformly mixing, sealing the reaction device, heating to 110 ℃ under stirring, preserving heat for 3 hours, and then cooling to room temperature;
(3) Adding a lower water phase of the filtrate into the reaction mixture, regulating the reaction mixture to be neutral by using a sodium hydroxide solution with the mass fraction of 40%, continuously stirring for 30min, filtering the neutralized feed liquid to obtain a first filter residue and a first filter residue, adding 10 times of hot water (85 ℃), stirring, filtering for the second time to obtain a second filter residue and a second filter residue, drying the second filter residue to obtain 21.1g of a product with the yield of 93.8%, crystallizing the second filter residue at the temperature of 35 ℃, carrying out third filtering, returning the crystallized solid filtered for the third time to the step (2), repeatedly using the filtered water filtered for the third time, standing and layering the first filter residue, separating the upper layer separated from the first filter residue, using the upper layer separated from the first filter residue to replace a solvent and an acid binding agent in the step (1), and adding alkali to prepare the lower layer separated from the first filter residue for replacing alkali liquid in the step (3).
The purity of the obtained product was 99.2% as determined by liquid chromatography.
Comparative example
The control was performed according to a method provided by CN102219718a for direct reaction of p-toluenesulfonyl chloride with urea. Adding 39g (0.65 mol) of urea and 79g (0.8 mol) of dichloroethane into a condensation reaction tank, heating to 60 ℃, starting to dropwise add 95g (0.5 mol) of p-toluenesulfonyl chloride and 79g (0.8 mol) of dichloroethane, keeping the temperature at about 60-65 ℃, heating to 70-72 ℃ after the dropwise addition is completed, carrying out heat preservation reaction for 3.5h, cooling to room temperature, adding a prepared sodium hydroxide aqueous solution to make the reaction solution neutral, then distilling and recovering dichloroethane until no dichloroethane is distilled out, cooling for crystallization, centrifuging, washing with water, and obtaining a p-toluenesulfonyl urea crude wet product, and detecting by liquid chromatography, wherein no product is found. The reaction mixture was heated to reflux at a temperature of 110,120,130,140 degrees and no product was detected.
Through the examination and the reading of the literature, the reaction activity of the urea is very low, and the p-toluenesulfonyl chloride cannot directly react with the urea under the condition of no catalyst.
In summary, the invention considers that the direct addition reaction of the tosyl chloride and the urea is difficult to occur below 130 ℃, and the urea is inactive in nature and low in yield. In the process provided by the invention, the reaction temperature is controlled at 130 ℃ or below, the urea basically does not generate side reaction, the urea activity is obviously improved through the introduction of the composite catalyst, the product yield of the p-toluenesulfonyl urea in the embodiment is more than 90%, and the product purity is higher, so that the process belongs to a product with higher market value.
The above description is only of the preferred embodiments of the present invention and is not intended to limit the present invention, but various modifications and variations can be made to the present invention by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A method for preparing p-toluenesulfonyl urea, which is characterized by comprising the following steps:
(1) Adding p-toluenesulfonyl chloride and urea into a solvent containing an acid binding agent, and fully and uniformly mixing, wherein the weight of the solvent is 3-10 times of that of the p-toluenesulfonyl chloride, and the molar ratio of the p-toluenesulfonyl chloride to the urea to the acid binding agent is 1-1.2:1-1.5;
(2) Adding a composite catalyst, and then sealing a reaction system, and heating to 100-130 ℃ to react for 2-4 hours, wherein the composite catalyst is a mixture of p-toluenesulfonamide and 4-dimethylaminopyridine according to a molar ratio of 1:0.8-1.2;
(3) 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 solid, namely the p-toluenesulfonyl urea.
2. The method for producing p-toluenesulfonylurea according to claim 1, wherein in step (1), the acid-binding agent is one or a combination of several kinds selected from triethylamine, tributylamine and trioctylamine.
3. The method for producing p-toluenesulfonylurea according to claim 1, wherein in step (1), the solvent is selected from one or more of toluene, xylene, trimethylbenzene, chlorobenzene and dichlorobenzene.
4. The method for preparing p-toluenesulfonyl urea according to claim 1, wherein in the step (2), the molar ratio of the composite catalyst to p-toluenesulfonyl chloride is 0.01-0.10:1.
5. The method for producing p-toluenesulfonylurea according to claim 1, wherein in step (2), p-toluenesulfonamide and 4-dimethylaminopyridine are mixed in a molar ratio of 1:1.
6. The process for producing p-toluenesulfonylurea according to claim 1, wherein in step (3), the alkali liquid is one selected from the group consisting of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate and aqueous solutions of potassium hydrogencarbonate.
7. The method for preparing p-toluenesulfonyl urea according to claim 6, wherein the mass fraction of the alkali solution is 5% -40%.
8. The method for producing p-toluenesulfonylurea as claimed in claim 1, wherein the embodiment of step (3) is as follows:
And (3) continuously stirring for 20-60min after the reaction system is regulated to be neutral to obtain a feed liquid, filtering the feed liquid to obtain a first filter residue and a first filter liquid, adding hot water which is 5-10 times the weight of the first filter residue, stirring and filtering to obtain a second filter residue and a second filter liquid, drying the second filter residue to obtain the p-toluenesulfonyl urea, standing and layering and separating the first filter liquid, replacing the solvent and the acid binding agent in the step (1) with the separated upper layer part, replacing the alkali liquor in the step (3) with the separated lower layer alkali adding modulation part, cooling and crystallizing the second filter liquid, and filtering to obtain crystals, and continuously using the crystals in the step (2).
9. The method for producing p-toluenesulfonylurea as claimed in claim 8, wherein the hot water temperature is 85 to 95 ℃.
10. The method for producing p-toluenesulfonylurea according to claim 8, wherein the temperature of the cooling crystallization is 40 ℃ or lower.
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| CN102219718A (en) * | 2010-04-19 | 2011-10-19 | 巨野金岭生物科技发展有限公司 | New synthesis method for p-tolunesulfonyl carbamide |
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| CN102964280A (en) * | 2012-11-27 | 2013-03-13 | 广东逸舒制药有限公司 | Preparation method of toluenesulfonylurea |
| CN111747872A (en) * | 2020-06-23 | 2020-10-09 | 江苏理工学院 | A kind of synthetic method of p-toluenesulfonylurea |
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