阅读说明：本技术 邻硝基苯磺酰氯制备方法 (Preparation method of o-nitrobenzenesulfonyl chloride ) 是由 马春江 刘国先 李慧鹏 于 2021-08-18 设计创作，主要内容包括：本发明涉及医药中间体生产技术领域,提供了一种邻硝基苯磺酰氯制备方法,包括硫化：溶液配制,加入预定摩尔比的水、硫化碱及硫磺；反应；洗涤离心；二、氯化：向反应釜内加入预定配比的盐酸、硫化料以及催化剂,搅拌；反应釜内温度升至30℃以上,通入氯气并且在不超过65℃情况下完成通氯气反应；之后降温至35～38℃放料；三、后处理：氯化反应完毕后,将料放入离心机进行离心处理；对离心后的物料烘干。借此,本发明通过硫化、氯化以及后处理等工序,实现了邻硝基苯磺酰氯的制备。本发明生产过程连续,生产效率高,反应充分,产品纯度高,能够满足生产需求。(The invention relates to the technical field of production of medical intermediates, and provides a preparation method of o-nitrobenzenesulfonyl chloride, which comprises the following steps: preparing a solution, and adding water, sodium sulfide and sulfur in a predetermined molar ratio; carrying out reaction; washing and centrifuging; II, chlorination: adding hydrochloric acid, a vulcanizing material and a catalyst in a preset ratio into a reaction kettle, and stirring; raising the temperature in the reaction kettle to be above 30 ℃, introducing chlorine gas and completing chlorine gas introduction reaction under the condition that the temperature is not more than 65 ℃; then, cooling to 35-38 ℃ and discharging; thirdly, post-treatment: after the chlorination reaction is finished, putting the material into a centrifugal machine for centrifugal treatment; and drying the centrifuged material. Therefore, the preparation of the o-nitrobenzenesulfonyl chloride is realized through the working procedures of vulcanization, chlorination, post-treatment and the like. The method has the advantages of continuous production process, high production efficiency, full reaction and high product purity, and can meet the production requirements.)

1. The preparation method of the o-nitrobenzenesulfonyl chloride is characterized by comprising the following steps:

first, sulfurize

1. Solution preparation

Adding water, sodium sulfide and sulfur with a preset ratio into a reaction kettle, stirring for 4 +/-0.5 hours, and precipitating for 27-33 hours at the temperature of 55 ℃; removing residues to obtain a solution; the molar ratio of the added water, the sodium sulfide and the sulfur is as follows: 6-9:2-4: 1;

2. reaction of

Adding ethanol and o-nitrochlorobenzene in a predetermined amount into a reaction kettle and stirring; when the temperature in the kettle reaches 63 ℃, dropwise adding a sodium polysulfide solution into the kettle until the content of the o-nitrochlorobenzene is lower than 5%; after the dripping is finished, preserving the heat for 1.5 plus or minus 0.1 hour;

the molar ratio of the added ethanol to the added o-nitrochlorobenzene to the added sulfur is as follows: 1-1.5: 1;

3. washing centrifuge

Transferring the reacted solution into a washing kettle; raising the temperature in the kettle to 65-70 ℃ by adopting steam or hot water and stirring for 1 hour;

then, carrying out pressure filtration by using nitrogen; then opening a liquid inlet of the washing kettle, adding 1500-1600L ethanol into the kettle, heating the temperature in the kettle to 55-70 ℃, and stirring for 2 hours; then, introducing nitrogen for filter pressing;

then adding 1000L of hot water into the washing kettle, stirring for 60 minutes at 85-95 ℃, and then transferring the materials into a centrifuge for centrifugal treatment;

di, chlorination

Adding hydrochloric acid, a vulcanizing material and a catalyst in a preset ratio into a reaction kettle, and stirring; when the temperature in the reaction kettle rises to 40-45 ℃, introducing 450 +/-30 kg of chlorine; then, cooling to 35-38 ℃ and discharging;

third, post-treatment

After the chlorination reaction is finished, putting the material into a centrifugal machine for centrifugal treatment;

and drying the centrifuged material in a boiling drying mode.

2. The method for producing o-nitrobenzenesulfonyl chloride according to claim 1, wherein the sodium sulfide is replaced with an aqueous solution of sodium sulfide having a concentration of 20% in the step of preparing the solution.

3. The method for preparing o-nitrobenzenesulfonyl chloride according to claim 1, wherein the time period for dropping the sodium polysulfide solution is 7 to 8 hours.

4. The method for preparing o-nitrobenzenesulfonyl chloride according to claim 1, wherein the purity of ethanol added in the reaction step in the solution preparation is not less than 92%.

5. The method for preparing o-nitrobenzenesulfonyl chloride according to claim 1, wherein the pressure in the reaction kettle during the nitrogen pressure filtration process is not more than 0.25 MPa.

6. The method for preparing o-nitrobenzenesulfonyl chloride according to claim 1, wherein the cooling mode in the chlorination step is water-cooled cooling.

7. The method for preparing o-nitrobenzenesulfonyl chloride according to claim 1, wherein the concentration of hydrochloric acid in said chlorination step is between 20 and 31%.

Technical Field

The invention belongs to the technical field of production of medical intermediates, and particularly relates to a preparation method of o-nitrobenzenesulfonyl chloride.

Background

The o-nitrobenzenesulfonyl chloride is used as a medical intermediate for synthesizing drugs such as sulfanilamide and the like.

The existing production process of o-nitrobenzenesulfonyl chloride has low production efficiency and a plurality of product impurities, and is difficult to meet the use requirement.

In view of the above, the prior art is obviously inconvenient and disadvantageous in practical use, and needs to be improved.

Disclosure of Invention

Aiming at the defects, the invention aims to provide a method for preparing o-nitrobenzenesulfonyl chloride, which realizes the preparation of o-nitrobenzenesulfonyl chloride through the working procedures of vulcanization, chlorination, post-treatment and the like. The method has the advantages of continuous production process, high production efficiency, full reaction and high product purity, and can meet the production requirements.

In order to realize the purpose, the invention provides a preparation method of o-nitrobenzenesulfonyl chloride, which comprises the following steps:

first, sulfurize

1. Solution preparation

Adding water, sodium sulfide and sulfur with a preset ratio into a reaction kettle, stirring for 4 +/-0.5 hours, and precipitating for 27-33 hours at the temperature of 55 ℃; removing residues to obtain a solution; the molar ratio of the added water, the sodium sulfide and the sulfur is as follows: 6-9:2-4: 1;

2. reaction of

Adding ethanol and o-nitrochlorobenzene in a predetermined amount into a reaction kettle and stirring; when the temperature in the kettle reaches 63 ℃, dropwise adding a sodium polysulfide solution into the kettle until the content of the o-nitrochlorobenzene is lower than 5%; after the dripping is finished, preserving the heat for 1.5 plus or minus 0.1 hour;

the molar ratio of the added ethanol to the added o-nitrochlorobenzene to the added sulfur is as follows: 1-1.5: 1;

3. washing centrifuge

Transferring the reacted solution into a washing kettle; raising the temperature in the kettle to 65-70 ℃ by adopting steam or hot water and stirring for 1 hour;

then, carrying out pressure filtration by using nitrogen; then opening a liquid inlet of the washing kettle, adding 1500-1600L ethanol into the kettle, heating the temperature in the kettle to 55-70 ℃, and stirring for 2 hours; then, introducing nitrogen for filter pressing;

then adding 1000L of hot water into the washing kettle, stirring for 60 minutes at 85-95 ℃, and then transferring the materials into a centrifuge for centrifugal treatment;

di, chlorination

Adding hydrochloric acid, a vulcanizing material and a catalyst in a preset ratio into a reaction kettle, and stirring; when the temperature in the reaction kettle rises to 40-45 ℃, introducing 450 +/-30 kg of chlorine; then, cooling to 35-38 ℃ and discharging;

third, post-treatment

After the chlorination reaction is finished, putting the material into a centrifugal machine for centrifugal treatment;

and drying the centrifuged material in a boiling drying mode.

According to the preparation method of the o-nitrobenzenesulfonyl chloride, the sodium sulfide is replaced by a sodium sulfide aqueous solution with a concentration value of 20% in the solution preparation step.

According to the preparation method of the o-nitrobenzenesulfonyl chloride, the dropping time of the sodium polysulfide solution is 7-8 hours.

According to the preparation method of the o-nitrobenzenesulfonyl chloride, the purity of ethanol added in the reaction step in the solution preparation is more than or equal to 92 percent.

According to the preparation method of the o-nitrobenzenesulfonyl chloride, the pressure in the reaction kettle is not more than 0.25MPa in the nitrogen pressure filtration process.

According to the preparation method of the o-nitrobenzenesulfonyl chloride, the cooling mode in the chlorination step is water-cooled cooling.

According to the preparation method of the o-nitrobenzenesulfonyl chloride, the concentration of hydrochloric acid in the chlorination step is 22-23%.

The invention aims to provide a method for preparing o-nitrobenzenesulfonyl chloride, which realizes the preparation of the o-nitrobenzenesulfonyl chloride through the working procedures of vulcanization, chlorination, post-treatment and the like. The method has the advantages of continuous production process, high production efficiency, full reaction and high product purity, and can meet the production requirements.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention. The above-mentioned directions or positions of the upper, lower, left, right, etc. are referred to in this specification for better describing the technical solution, so that the reader can understand that the practical implementation includes but is not limited to this description.

The invention provides a preparation method of o-nitrobenzenesulfonyl chloride, which comprises the following steps:

first, sulfurize

1. Solution preparation

Adding water, sodium sulfide and sulfur into a reaction kettle in predetermined amounts, stirring for 4 +/-0.5 hours, and precipitating for 27-33 hours at 55 ℃; the molar ratio of the added water, the sodium sulfide and the sulfur is as follows: 6-9:2-4: 1;

the purity of the added sodium sulfide is not less than 60%.

Then the residue is discharged, and after stirring for 0.5 hour, the precipitate is precipitated for 18 to 22 hours at the temperature of 55 ℃; then discharging the residue again;

then, the temperature in the kettle is raised to 60 ℃, the mixture is stirred for 3 +/-0.2 hours again, and then a solution is obtained after sampling and detection;

and if the content of the sodium sulfide is detected to be lower than 20%, supplementing the sodium sulfide into the kettle until the content reaches the standard.

Example (b): 3440kg of water, 1575kg of sodium sulfide and about 424kg of sulfur are added (according to the concentration of the sodium sulfide, the ratio of sodium sulfide to sulfur is 1.05 mol). Preferably, water is added to the dissolution kettle, and then the sodium sulfide is added in a stirring state. Naturally heating, stirring for 4 hours, stopping stirring, keeping the temperature at 55 ℃, and precipitating for 30 hours;

after the residue was left, stirring was stopped for 30 minutes, and the mixture was kept at 55 ℃ for 20 hours to precipitate, and then the residue was left.

Stirring and heating to 60 ℃, stirring for 3 hours, and sampling and detecting.

2. Reaction of

Adding ethanol and o-nitrochlorobenzene in a predetermined amount into a reaction kettle and stirring; when the temperature in the kettle reaches 63 ℃, dropwise adding a sodium polysulfide solution into the kettle until the content of the o-nitrochlorobenzene is lower than 5%; after the dripping is finished, preserving the heat for 1.5 plus or minus 0.1 hour;

the dripping time is preferably 7-8 hours;

the molar ratio of the added ethanol, the added o-nitrochlorobenzene and the added sulfur is as follows: 1-1.5: 1;

preferably, the purity of the added ethanol is more than or equal to 92 percent.

Example (b): 565kg of ethanol was placed in the reaction vessel. The stirring was started. Heating to 30 ℃, adding 500kg of melted o-nitrochlorobenzene into the reaction kettle in a vacuum mode, and stirring and heating to 65 ℃; and dropwise adding the sodium polysulfide solution, wherein the adding is completed within 7.5 hours, the temperature is 65-67 ℃, the later-stage temperature is slightly higher, keeping the temperature for 1.5 hours after the adding is completed, detecting that the content of the o-nitrochlorobenzene is lower than 5%, and otherwise, supplementing the sodium polysulfide solution.

3. Washing centrifuge

Transferring the reacted solution into a washing kettle; preferably, the washing kettle is opened and emptied, and the solution after reaction is transferred into the washing kettle by a pump; after the material is transferred, 50 liters of water is used for washing the pipeline and the pipeline is continuously pumped into the washing kettle by a pump, so that the pipeline is prevented from being blocked by the remained material on the line.

Raising the temperature in the kettle to 65-70 ℃ by adopting steam and stirring for 1 hour;

then, the mother liquor is pressed into a receiving tank by using nitrogen for filter pressing (the pressure in the kettle is kept to be not more than 0.25MPa in the process). And after the mother liquor is basically subjected to filter pressing, slowly emptying the washing kettle and releasing pressure.

Then opening a liquid inlet of the washing kettle, adding 1500-1600L ethanol into the kettle, heating the temperature in the kettle to 65-70 ℃, and stirring for 2 hours; then, introducing nitrogen for filter pressing; and after the mother liquor is basically subjected to pressure filtration, slowly opening the filter to empty, and relieving pressure. Transferring the ethanol solution to a temporary storage iron tank for rectification.

Preferably, the concentration of the ethanol is more than or equal to 87 percent;

sampling and detecting, wherein the thioether content is qualified when the thioether content is less than or equal to 0.5%. If not, continuing to add ethanol for washing until qualified.

Then adding 1000L of hot water into the washing kettle, stirring for 60 minutes at the temperature of 90-95 ℃, and then transferring the materials into a centrifugal machine for centrifugal treatment; the material in the centrifuge was washed with hot water during centrifugation.

And (4) allowing the centrifuged water to enter an iron tank, and pumping the water into a sewage tank for treatment after the solid carrying-out condition is detected.

Di, chlorination

Adding 3000 liters of hydrochloric acid, 450kg of vulcanizing material and 5kg of catalyst into a reaction kettle, and stirring; when the temperature in the reaction kettle rises to 40-45 ℃, introducing chlorine for 15 hours; then, cooling to 35-38 ℃ and discharging; preferably, the invention adopts water-cooled cooling

The concentration of hydrochloric acid is preferably 22-23%;

preferably, the chlorine is introduced for 15 hours, the cold water is cooled and kept at 58-59 ℃, and the chlorine is continuously introduced until the end point (the color of the material is suddenly changed into white, the sampling observation shows that few yellow sulfide particles are remained) based on the condition that the buffer bottle does not emit green, and the temperature can reach 60 ℃. And (4) gradually reducing the ammonia amount in the later period, analyzing the end point of the plate layer, and tracking and monitoring the liquid chromatogram until the end point. Circulating water is introduced to cool to 35-38 ℃ for discharging.

Preferably, the chlorine pipeline is checked firstly; the invention adopts ammonia water for leakage detection and simultaneously opens a reaction kettle tail gas recovery system. When chlorine is introduced, the steam frame is firstly opened, the steam valve is preheated, the needle valve is opened, the small chlorine cylinder is opened, the ammonia water leakage test is carried out, the chlorine amount is adjusted to normal flux after the chlorine is normal, and the pressure of the buffer tank cannot exceed 0.2 MPa.

Third, post-treatment

After the chlorination reaction is finished, putting the material into a centrifugal machine for centrifugal treatment;

after the centrifuge finishes feeding, spin-drying at medium speed for 5 minutes, starting washing, adding water at medium speed for 5 minutes, spin-drying at medium speed for 5 minutes after water supply is stopped, adding water at medium speed for washing for 5 minutes, spin-drying at high speed for 6 minutes finally, and measuring the pH value of water at the same time. Should be above 5. And finally scraping the materials by a scraper.

And drying the centrifuged material in a boiling drying mode. The drying temperature is not more than 56 ℃. The purity of the material is not lower than 98%.

And packaging, detecting and warehousing the dried materials. The packaging specification is 25 kg/bag.

In conclusion, the invention provides a preparation method of o-nitrobenzenesulfonyl chloride, which realizes the preparation of the o-nitrobenzenesulfonyl chloride through the working procedures of vulcanization, chlorination, post-treatment and the like. The method has the advantages of continuous production process, high production efficiency, full reaction and high product purity, and can meet the production requirements.

The present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof, and it should be understood that various changes and modifications can be effected therein by one skilled in the art without departing from the spirit and scope of the invention as defined in the appended claims.