CN108689941B - Method for synthesizing 1, 2-dimethyl-5-nitroimidazole - Google Patents
Method for synthesizing 1, 2-dimethyl-5-nitroimidazole Download PDFInfo
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Abstract
The invention discloses a method for synthesizing 1, 2-dimethyl-5-nitroimidazole, which sequentially comprises a methylation reaction, a neutralization and a refining process, wherein the methylation reaction is carried out by uniformly mixing methanol and sulfuric acid to obtain a first mixed solution, heating the first mixed solution to 30-40 ℃, adding 2-methyl-5-nitroimidazole and dimethyl sulfate to react at 80-130 ℃ to obtain a second mixed solution, preserving the second mixed solution at 120-130 ℃ for 1.5-2.5 h, diluting the second mixed solution, hydrolyzing the diluted second mixed solution at 95-102 ℃ for 2.5-4 h, and diluting a hydrolysis product to obtain a first neutralized solution. The invention provides a safe, stable and high-yield synthesis process of 1, 2-dimethyl-5-nitroimidazole, the reaction yield can reach 81.3-86.5%, and the synthesis process has good industrial application value.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis, and particularly relates to a method for synthesizing 1, 2-dimethyl-5-nitroimidazole.
Background
1, 2-dimethyl-5-nitroimidazole is also called dimezole, the molecular formula is C5H7N3O2, the melting point is 138-141 ℃, and the appearance is white or yellowish crystalline powder. The 1, 2-dimethyl-5-nitroimidazole is mainly used as a veterinary antibacterial agent, is an effective drug for preventing and treating black head disease of turkeys and swine dysentery, and has remarkable inhibition effect on various protozoa and various bacteria; can also be used as a feed additive for promoting the growth of pigs and chickens and improving the feed conversion rate, and is widely used in poultry and livestock feeds at home and abroad.
The existing synthesis method of 1, 2-dimethyl-5-nitroimidazole mainly comprises the following two steps: (1) 2-methyl-5-nitroimidazole and dimethyl sulfate are used as raw materials, the raw materials react for 1h at 100 ℃, the reaction solution is cooled to room temperature, hydrochloric acid is added into the reaction solution, and the finished product is prepared through subsequent treatment processes such as neutralization, centrifugal separation and the like. The single pass yield of the 2-methyl-5-nitroimidazole prepared by the method is 51.3 percent. (2) Adding formic acid into a three-neck flask, then sequentially and dropwise adding concentrated sulfuric acid and anhydride, carrying out dehydration reaction for 2 hours, adding 2-methyl-5-nitroimidazole into the mixed solution, heating to dissolve nitrites, cooling, dropwise adding dimethyl sulfate, carrying out reaction for 2 hours, and carrying out subsequent treatment processes such as neutralization, centrifugal separation and the like to obtain a finished product. The single pass yield of the 2-methyl-5-nitroimidazole prepared by the method is 12.5 percent. The acid used in the first method is hydrochloric acid, so that the material requirement on equipment of a production system is high, and the wastewater contains chloride ions, so that the difficulty and the production cost of subsequent wastewater treatment are increased; in the second method, the acetic anhydride has larger potential safety hazard in the use process, is inflammable and explosive, and greatly reduces the safety of the reaction. In addition, the yield of the 2-methyl-5-nitroimidazole prepared by the two methods is less than 60 percent, and the yield is low.
Disclosure of Invention
The invention aims to overcome the technical defects, and provides a method for synthesizing 1, 2-dimethyl-5-nitroimidazole, which solves the technical problems of lower yield and lower safety in the existing method for synthesizing 1, 2-dimethyl-5-nitroimidazole.
In order to achieve the technical purpose, the technical scheme of the invention provides a method for synthesizing 1, 2-dimethyl-5-nitroimidazole, which comprises the following reaction equation:
the method specifically comprises the following steps:
s1, methylation reaction: uniformly mixing methanol and sulfuric acid to obtain a first mixed solution, heating the first mixed solution to 30-40 ℃, adding 2-methyl-5-nitroimidazole and dimethyl sulfate to react at 80-130 ℃ to obtain a second mixed solution, preserving the heat of the second mixed solution at 120-130 ℃ for 1.5-2.5 h, diluting the second mixed solution, hydrolyzing the diluted second mixed solution at 95-102 ℃ for 2.5-4 h, and diluting the hydrolysate to obtain a first neutralization solution;
s2, neutralization: cooling the first neutralization liquid to 30-40 ℃, adjusting the pH value of the first neutralization liquid to 1.9-2.1, cooling to 20-30 ℃ for crystallization, and performing solid-liquid separation after crystallization to obtain a neutralization mother liquid;
s3, neutralizing: cooling the first neutralization mother liquor to 25-40 ℃, adjusting the pH value of the first neutralization mother liquor to 7-8, cooling to 15-20 ℃ for crystallization, and carrying out solid-liquid separation after crystallization to obtain a 1, 2-dimethyl-5-nitroimidazole crude product;
s4, refining: and decoloring, crystallizing, separating solid from liquid and drying the 1, 2-dimethyl-5-nitroimidazole crude product to obtain a finished product.
Compared with the prior art, the invention has the beneficial effects that: compared with the method which uses concentrated sulfuric acid and acid anhydride as solvents, the method has the advantages that the reaction process is milder, and the safety of using methanol is higher; in the traditional method, the dimethyl sulfate is hydrolyzed to different degrees, so that the concentration of the reaction raw materials is reduced, and the hydrolysis of the dimethyl sulfate is inhibited by adopting sulfuric acid and methanol, so that the reaction yield is improved; in addition, 2-methyl-5-nitroimidazole and dimethyl sulfate are added at the temperature of 30-40 ℃, so that on one hand, methylation reaction can be stimulated, and the reaction is milder; the methylation reaction is carried out at the temperature of 80-130 ℃, so that a large amount of heat is prevented from being released after dimethyl sulfate is added, the reaction is safer, the reaction can be moved forward, and the reaction yield is improved; the temperature is kept for a period of time at 120-130 ℃, so that the raw materials can be fully reacted, and the final yield is improved; the invention makes the reaction move to the direction of generating 1, 2-dimethyl-5-nitroimidazole by adjusting the reaction technological process and parameters, and makes the 1, 2-dimethyl-5-nitroimidazole crystal fully separated out, thus improving the yield of the final product. The invention provides a safe, stable and high-yield synthesis process of 1, 2-dimethyl-5-nitroimidazole, the reaction yield can reach 81.3-86.5%, and the synthesis process has good industrial application value.
Drawings
FIG. 1 is a flow chart of a method for producing 1, 2-dimethyl-5-nitroimidazole according to the present invention.
Detailed Description
The invention provides a method for synthesizing 1, 2-dimethyl-5-nitroimidazole, which comprises the following steps:
(1) Methylation reaction: 15-25 parts of methanol and 70-90 parts of sulfuric acid are sequentially added into a reaction kettle in parts by weight, the reaction kettle is started to stir and mix uniformly, wherein the mass concentration of the sulfuric acid is more than or equal to 98%, steam is started to heat the mixed solution in the reaction kettle to 30-40 ℃, 528-583 parts of 2-methyl-5-nitroimidazole with the mass concentration of more than or equal to 98% and 423-517 parts of dimethyl sulfate with the mass concentration of more than or equal to 98.5% are added into the reaction kettle, and in order to control the reaction rate and ensure the stable reaction, the 2-methyl-5-nitroimidazole and the dimethyl sulfate are added for three times to participate in the reaction, and the method specifically comprises the following steps: adding 2-methyl-5-nitroimidazole into a reaction kettle for the first time, slowly dropwise adding dimethyl sulfate, wherein the adding of the dimethyl sulfate is an exothermic reaction, the speed of dropwise adding the dimethyl sulfate is based on the condition that the reaction temperature of a mixed solution in the reaction kettle is 90-100 ℃, and after the dropwise adding is finished, the temperature of the mixed solution in the reaction kettle is reduced to 80-90 ℃ to prepare a second material feeding; 2-methyl-5-nitroimidazole is added into the reaction kettle for the second time, dimethyl sulfate is slowly added dropwise, the reaction temperature of the mixed solution in the reaction kettle is controlled to be 105-130 ℃, and after the dropwise addition is finished, the temperature of the mixed solution in the reaction kettle is reduced to be 100-105 ℃ for preparing a third material feeding; thirdly, adding 2-methyl-5-nitroimidazole into the reaction kettle, slowly dropwise adding dimethyl sulfate, and controlling the reaction temperature of the mixed solution in the reaction kettle to be 90-105 ℃; then raising the temperature of the mixed solution in the reaction kettle to 120-130 ℃, preserving heat for 1.5-2.5 hours, reducing the temperature of the mixed solution to below 105 ℃, adding 100-200 parts of purified water or refined mother liquor (if the refined mother liquor is insufficient and is supplemented to 100-200 parts by the purified water), adjusting the temperature of the mixed solution in the reaction kettle to 95-102 ℃ and hydrolyzing for 2.5-4 hours, so as to ensure that the unreacted and completely hydrolyzed dimethyl sulfate is completely hydrolyzed, and avoid the toxicity of the mixed solution increasing the danger in the reaction process; after the hydrolysis is finished, adding 1000-1200 parts of purified water or refined mother liquor (if the refined mother liquor is insufficient, supplementing 1000-1200 parts of purified water) into the hydrolysate in the reaction kettle, and transferring the mixed solution in the reaction kettle into a first neutralization kettle;
in the steps, 2-methyl-5-nitroimidazole and dimethyl sulfate are added in three times, and the mass ratio of the three times of adding 2-methyl-5-nitroimidazole is 3:5:3, a step of; the mass ratio of the dimethyl sulfate added for three times is 16:21:10. before and after hydrolysis, purified water or refined mother liquor can be added into the reaction kettle for dilution, preferably, the refined mother liquor is added into the reaction kettle, on one hand, materials contained in the mother liquor can be fully utilized, the production cost is reduced, and in addition, the treatment and discharge of wastewater can be reduced.
(2) And (3) neutralizing: the temperature of the mixed solution in the first neutralization kettle in the step (1) is reduced to 30-40 ℃, ammonia water is added into the mixed solution, and the pH value of the mixed solution is regulated to 1.9-2.1; then the temperature of the mixed solution is reduced to 20-30 ℃ for crystallization, after crystallization, solid-liquid separation is carried out to obtain a neutralized mother solution and unreacted completely 2-methyl-5-nitroimidazole, the unreacted completely 2-methyl-5-nitroimidazole is dried for 2.5-4 hours at 65-75 ℃, and the dried 2-methyl-5-nitroimidazole can be used as a raw material for the next synthesis;
(3) And II, neutralizing: transferring the first neutralization mother liquor obtained in the step (2) into a second neutralization kettle, reducing the temperature of the first neutralization mother liquor to 25-40 ℃, adding ammonia water into the mixed liquor, and adjusting the pH value of the mixed liquor to 7.0-8.0; then the temperature of the mixed solution is reduced to 15-20 ℃ for crystallization, after crystallization, solid-liquid separation is carried out to obtain a second neutralization mother solution and a 1, 2-dimethyl-5-nitroimidazole crude product, and the second neutralization mother solution is discharged after treatment in a purification workshop;
(4) Refining: sequentially adding purified water, the crude 1, 2-dimethyl-5-nitroimidazole product obtained in the step (3) and active carbon into a refining kettle, increasing the temperature of the mixed solution in the refining kettle to 97-103 ℃, decoloring for 0.3-0.5 h, performing filter pressing, and transferring the filtrate into a crystallization kettle; and (3) reducing the temperature of filtrate in the crystallization kettle to 35-40 ℃, adding alkali into the filtrate to adjust the pH of the filtrate to 10-11.5, reducing the temperature of the filtrate to 15-20 ℃ for crystallization, and performing solid-liquid separation to obtain a 1, 2-dimethyl-5-nitroimidazole refined product and refined mother liquor after crystallization, wherein the refined mother liquor can be used in hydrolysis reaction of methylation reaction, and drying the 1, 2-dimethyl-5-nitroimidazole refined product at 65-75 ℃ for 2-3 hours to obtain a finished product.
In order to sufficiently crystallize and separate out the 1, 2-dimethyl-5-nitroimidazole and improve the yield, the mass ratio of the 1, 2-dimethyl-5-nitroimidazole crude product, purified water and active carbon is 1400-1750: 650-750: 1-4.
To avoid mixing impurities and to reduce the purity of 1, 2-dimethyl-5-nitroimidazole, a liquid alkali is added to the filtrate after press filtration, and the liquid alkali may be a liquid alkali commonly used in the art, and is not particularly limited as long as the pH of the filtrate can be adjusted to be alkaline, and may be an alkaline solution such as sodium hydroxide solution, potassium hydroxide or aqueous ammonia.
The present invention will be described in further detail with reference to the drawings and examples, in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
Example 1:
(1) Methylation reaction: adding 20kg of methanol and 75kg of sulfuric acid with the mass concentration of 98% into a reaction kettle, starting the reaction kettle, stirring and mixing uniformly, then opening steam to heat the mixed solution in the reaction kettle to 30 ℃, adding 150kg of 98.5wt% of 2-methyl-5-nitroimidazole into the reaction kettle for the first time, slowly dropwise adding 144kg of 98.5wt% of dimethyl sulfate, controlling the reaction temperature of the mixed solution in the reaction kettle to 90 ℃ when the dimethyl sulfate is dropwise added, and opening a jacket to reduce the temperature of the mixed solution in the reaction kettle to 85 ℃ after the dimethyl sulfate is dropwise added; 250kg of 98.5wt% 2-methyl-5-nitroimidazole is added into the reaction kettle for the second time, 189kg of 98.5wt% dimethyl sulfate is slowly added dropwise, the reaction temperature of the mixed solution in the reaction kettle is controlled at 110 ℃, and after the dropwise addition of the dimethyl sulfate, jacket brine is opened to reduce the temperature of the mixed solution in the reaction kettle to 100 ℃; thirdly, 150kg of 98.5wt% 2-methyl-5-nitroimidazole is added into a reaction kettle, 90kg of 98.5wt% dimethyl sulfate is slowly added dropwise, the reaction temperature of the mixed solution in the reaction kettle is controlled at 90 ℃, after the reaction temperature is observed to be no more rise within 5min, the temperature of the mixed solution in the reaction kettle is raised to 130 ℃, after the temperature is kept for 1.5h, the temperature of the mixed solution is lowered to 105 ℃, 150kg of purified water or refined mother solution in the previous cycle (if the refined mother solution is insufficient, the purified water is used for supplementing to 150 kg), the temperature of the mixed solution in the reaction kettle is raised to 100 ℃ for hydrolysis for 3h, after the hydrolysis is finished, 1000kg of purified water or refined mother solution in the previous cycle is added into hydrolysate in the reaction kettle (if the refined mother solution is insufficient, the purified water is used for supplementing to 1000 kg), and the mixed solution in the reaction kettle is transferred into the first middle and the kettle;
(2) And (3) neutralizing: reducing the temperature of the mixed solution in the first neutralization kettle in the step (1) to 40 ℃, adding ammonia water into the mixed solution, and adjusting the pH value of the mixed solution to 2.0; then the temperature of the mixed solution is reduced to 25 ℃ for crystallization, after crystallization, the mixed solution is centrifugally separated to obtain a neutralization mother solution and unreacted and completely 2-methyl-5-nitroimidazole, and the unreacted and completely 2-methyl-5-nitroimidazole is dried for 4 hours at 65 ℃ and then recovered;
(3) And II, neutralizing: transferring the first neutralization mother liquor obtained in the step (2) into a second neutralization kettle, reducing the temperature of the first neutralization mother liquor to 38 ℃, adding ammonia water into the mixed liquor, and adjusting the pH value of the mixed liquor to 7.0; then the temperature of the mixed solution is reduced to 18 ℃ for crystallization, after crystallization, the mixed solution is centrifugally separated to obtain a second neutralization mother solution and a 1, 2-dimethyl-5-nitroimidazole crude product, and the second neutralization mother solution is discharged after being treated by a purification workshop;
(4) Refining: adding 3000kg of purified water, 1500kg of 1, 2-dimethyl-5-nitroimidazole crude product and 2kg of activated carbon into a refining kettle in sequence, raising the temperature of mixed liquor in the refining kettle to 97 ℃, decoloring for 0.4h, press-filtering the mixed liquor in the refining kettle, and transferring filtrate into a crystallization kettle; and (3) reducing the temperature of filtrate in the crystallization kettle to 37 ℃, adding sodium hydroxide solution into the filtrate to adjust the pH of the filtrate to 11, reducing the temperature of the filtrate to 18 ℃ for crystallization, carrying out solid-liquid separation after crystallization to obtain a 1, 2-dimethyl-5-nitroimidazole fine product and refined solution, and drying the 1, 2-dimethyl-5-nitroimidazole fine product at 70 ℃ for 2 hours to obtain a finished product.
By adopting the method, 382.9kg of 1, 2-dimethyl-5-nitroimidazole is obtained, the content is 99.8%, the yield is 86%, and 149kg of 2-methyl-5-nitroimidazole which is not reacted completely is obtained.
Example 2:
(1) Methylation reaction: adding 15kg of methanol and 80kg of sulfuric acid with the mass concentration of 98% into a reaction kettle, starting the reaction kettle, stirring and mixing uniformly, then starting steam to heat the mixed solution in the reaction kettle to 35 ℃, adding 144kg of 98.5wt% of 2-methyl-5-nitroimidazole into the reaction kettle for the first time, slowly dropwise adding 176kg of 99wt% of dimethyl sulfate, controlling the reaction temperature of the mixed solution in the reaction kettle to 95 ℃ when the dimethyl sulfate is dropwise added, and opening a jacket brine after the dimethyl sulfate is dropwise added to reduce the temperature of the mixed solution in the reaction kettle to 80 ℃; adding 240kg of 98.5wt% 2-methyl-5-nitroimidazole into the reaction kettle for the second time, slowly dropwise adding 231kg of 99wt% dimethyl sulfate, controlling the reaction temperature of the mixed solution in the reaction kettle to be 120 ℃, and opening jacket brine after the dropwise adding of the dimethyl sulfate is finished to reduce the temperature of the mixed solution in the reaction kettle to 100 ℃; adding 144kg of 98.5wt% 2-methyl-5-nitroimidazole into the reaction kettle for the third time, slowly dripping 110kg of 99wt% dimethyl sulfate, controlling the reaction temperature of the mixed solution in the reaction kettle at 95 ℃, observing that the reaction temperature is not increased any more within 5 minutes after the reaction, raising the temperature of the mixed solution in the reaction kettle to 125 ℃, keeping the temperature for 2 hours, reducing the temperature of the mixed solution to 100 ℃, adding 120kg of purified water or refining mother liquor in the previous cycle into the reaction kettle (if the refining mother liquor is insufficient, supplementing 120kg of purified water), raising the temperature of the mixed solution in the reaction kettle to 102 ℃ for hydrolysis for 4 hours, adding 1100kg of purified water or refining mother liquor in the previous cycle into a hydrolysate in the reaction kettle after the hydrolysis is finished (if the refining mother liquor is insufficient, supplementing 1100kg of purified water), and transferring the mixed solution in the reaction kettle into the first middle and the kettle;
(1) And (3) neutralizing: reducing the temperature of the mixed solution in the first neutralization kettle in the step (1) to 35 ℃, adding ammonia water into the mixed solution, and adjusting the pH value of the mixed solution to 1.9; then the temperature of the mixed solution is reduced to 30 ℃ for crystallization, after crystallization, the mixed solution is centrifugally separated to obtain a neutralization mother solution and unreacted and completely 2-methyl-5-nitroimidazole, and the unreacted and completely 2-methyl-5-nitroimidazole is dried for 2.5 hours at 70 ℃ and then recovered;
(2) And II, neutralizing: transferring the first neutralization mother liquor obtained in the step (2) into a second neutralization kettle, reducing the temperature of the first neutralization mother liquor to 36 ℃, adding ammonia water into the mixed liquor, and regulating the pH value of the mixed liquor to 7.5; then the temperature of the mixed solution is reduced to 20 ℃ for crystallization, after crystallization, the mixed solution is centrifugally separated to obtain a second neutralization mother solution and a 1, 2-dimethyl-5-nitroimidazole crude product, and the second neutralization mother solution is discharged after being treated by a purification workshop;
(3) Refining: sequentially adding 3200kg of purified water, 1300kg of 1, 2-dimethyl-5-nitroimidazole crude product and 4kg of activated carbon into a refining kettle, increasing the temperature of mixed liquor in the refining kettle to 100 ℃, decoloring for 0.3h, press-filtering the mixed liquor in the refining kettle, and transferring filtrate into a crystallization kettle; and (3) reducing the temperature of filtrate in the crystallization kettle to 35 ℃, adding potassium hydroxide solution into the filtrate to adjust the pH of the filtrate to 10, reducing the temperature of the filtrate to 16 ℃ for crystallization, carrying out solid-liquid separation after crystallization to obtain a 1, 2-dimethyl-5-nitroimidazole fine product and refined solution, and drying the 1, 2-dimethyl-5-nitroimidazole fine product at 65 ℃ for 2.5 hours to obtain a finished product.
By adopting the method, 370kg of 1, 2-dimethyl-5-nitroimidazole is obtained, the content is 99.8%, the yield is 86.5%, and 143kg of 2-methyl-5-nitroimidazole is not reacted completely.
Example 3:
(1) Methylation reaction: adding 18kg of methanol and 70kg of sulfuric acid with the mass concentration of 98% into a reaction kettle, starting the reaction kettle, stirring and mixing uniformly, then starting steam to heat the mixed solution in the reaction kettle to 33 ℃, firstly adding 150kg of 99wt% of 2-methyl-5-nitroimidazole into the reaction kettle, slowly dropwise adding 160kg of 99wt% of dimethyl sulfate, controlling the reaction temperature of the mixed solution in the reaction kettle to 98 ℃ when the dimethyl sulfate is dropwise added, and opening a jacket brine after the dimethyl sulfate is dropwise added to reduce the temperature of the mixed solution in the reaction kettle to 88 ℃; 250kg of 99wt% 2-methyl-5-nitroimidazole is added into the reaction kettle for the second time, 210kg of 99wt% dimethyl sulfate is slowly added dropwise, the reaction temperature of the mixed solution in the reaction kettle is controlled to be 105 ℃, and jacket brine is opened after the dropwise addition of the dimethyl sulfate is completed to reduce the temperature of the mixed solution in the reaction kettle to 100 ℃; thirdly, 150kg of 99wt% 2-methyl-5-nitroimidazole is added into a reaction kettle, 100kg of 99wt% dimethyl sulfate is slowly added dropwise, the reaction temperature of the mixed solution in the reaction kettle is controlled at 100 ℃, after the reaction temperature is observed to be no longer increased within 5min, the temperature of the mixed solution in the reaction kettle is increased to 120 ℃, the temperature is kept for 2.5h, the temperature of the mixed solution is reduced to 95 ℃, 100kg of purified water or refined mother solution in the previous cycle (if the refined mother solution is insufficient, the purified water is used for supplementing 100 kg), the temperature of the mixed solution in the reaction kettle is increased to 102 ℃ for hydrolysis for 2.5h, after the hydrolysis is finished, 1200kg of purified water or refined mother solution in the previous cycle is added into hydrolysate in the reaction kettle (if the refined mother solution is insufficient, the purified water is used for supplementing to 1200 kg), and then the mixed solution in the reaction kettle is transferred into the first and the kettle;
(2) And (3) neutralizing: reducing the temperature of the mixed solution in the first neutralization kettle in the step (1) to 37 ℃, adding ammonia water into the mixed solution, and adjusting the pH value of the mixed solution to 2.1; then the temperature of the mixed solution is reduced to 28 ℃ for crystallization, after crystallization, the mixed solution is centrifugally separated to obtain a neutralization mother solution and unreacted and completely 2-methyl-5-nitroimidazole, and the unreacted and completely 2-methyl-5-nitroimidazole is dried for 3 hours at 75 ℃ and then recovered;
(3) And II, neutralizing: transferring the first neutralization mother liquor obtained in the step (2) into a second neutralization kettle, reducing the temperature of the first neutralization mother liquor to 25 ℃, adding ammonia water into the mixed liquor, and regulating the pH value of the mixed liquor to 7.5; then the temperature of the mixed solution is reduced to 16 ℃ for crystallization, after crystallization, the mixed solution is centrifugally separated to obtain a second neutralization mother solution and a 1, 2-dimethyl-5-nitroimidazole crude product, and the second neutralization mother solution is discharged after being treated by a purification workshop;
(4) Refining: sequentially adding 3500kg of purified water, 1400kg of 1, 2-dimethyl-5-nitroimidazole crude product and 8kg of activated carbon into a refining kettle, raising the temperature of the mixed solution in the refining kettle to 103 ℃, decoloring for 0.3h, press-filtering the mixed solution in the refining kettle, and transferring the filtrate into a crystallization kettle; and (3) reducing the temperature of filtrate in the crystallization kettle to 40 ℃, adding sodium hydroxide solution into the filtrate to adjust the pH of the filtrate to 11.5, reducing the temperature of the filtrate to 16 ℃ for crystallization, separating solid from liquid after crystallization to obtain a 1, 2-dimethyl-5-nitroimidazole fine product and refined solution, and drying the 1, 2-dimethyl-5-nitroimidazole fine product at 70 ℃ for 2 hours to obtain a finished product.
By adopting the method, 375kg of 1, 2-dimethyl-5-nitroimidazole is obtained, the content is 99.8%, the yield is 82.4%, and 140kg of 2-methyl-5-nitroimidazole is not reacted completely.
Example 4:
(1) Methylation reaction: adding 23kg of methanol and 90kg of sulfuric acid with the mass concentration of 98% into a reaction kettle, starting the reaction kettle, stirring and mixing uniformly, then opening steam to heat the mixed solution in the reaction kettle to 37 ℃, adding 153kg of 98.5wt% of 2-methyl-5-nitroimidazole into the reaction kettle for the first time, slowly dropwise adding 152kg of 99wt% of dimethyl sulfate, controlling the reaction temperature of the mixed solution in the reaction kettle to 100 ℃ when the dimethyl sulfate is dropwise added, and opening a jacket brine after the dimethyl sulfate is dropwise added to reduce the temperature of the mixed solution in the reaction kettle to 84 ℃; 255kg of 98.5wt% 2-methyl-5-nitroimidazole is added into the reaction kettle for the second time, 199.5kg of 99wt% dimethyl sulfate is slowly added dropwise, the reaction temperature of the mixed solution in the reaction kettle is controlled at 115 ℃, and jacket brine is opened after the dropwise addition of the dimethyl sulfate is finished to reduce the temperature of the mixed solution in the reaction kettle to 105 ℃; adding 153kg of 98.5wt% 2-methyl-5-nitroimidazole into a reaction kettle for the third time, slowly dripping 95kg of 99wt% dimethyl sulfate, controlling the reaction temperature of the mixed solution in the reaction kettle to 98 ℃, observing that the reaction temperature is not increased in 5min after the reaction is no longer carried out, raising the temperature of the mixed solution in the reaction kettle to 125 ℃, keeping the temperature for 2h, reducing the temperature of the mixed solution to 90 ℃, adding 180kg of purified water or refining mother solution in the previous cycle into the reaction kettle (if the refining mother solution is insufficient, supplementing 180kg of purified water), raising the temperature of the mixed solution in the reaction kettle to 98 ℃ for hydrolysis for 3.5h, adding 1000kg of purified water or refining mother solution in the previous cycle into hydrolysate in the reaction kettle after the hydrolysis is finished (if the refining mother solution is insufficient, supplementing 1000kg of purified water), and transferring the mixed solution in the reaction kettle into the first and the kettle;
(2) And (3) neutralizing: reducing the temperature of the mixed solution in the first neutralization kettle in the step (1) to 38 ℃, adding ammonia water into the mixed solution, and adjusting the pH value of the mixed solution to 2.0; then the temperature of the mixed solution is reduced to 26 ℃ for crystallization, after crystallization, the mixed solution is centrifugally separated to obtain a neutralization mother solution and unreacted and completely 2-methyl-5-nitroimidazole, and the unreacted and completely 2-methyl-5-nitroimidazole is dried for 3.5 hours at 70 ℃ and then recovered;
(3) And II, neutralizing: transferring the first neutralization mother liquor obtained in the step (2) into a second neutralization kettle, reducing the temperature of the first neutralization mother liquor to 40 ℃, adding ammonia water into the mixed liquor, and adjusting the pH value of the mixed liquor to 8.0; then the temperature of the mixed solution is reduced to 15 ℃ for crystallization, after crystallization, the mixed solution is centrifugally separated to obtain a second neutralization mother solution and a 1, 2-dimethyl-5-nitroimidazole crude product, and the second neutralization mother solution is discharged after being treated by a purification workshop;
(4) Refining: adding 2800kg of purified water, 1300kg of 1, 2-dimethyl-5-nitroimidazole crude product and 6kg of activated carbon into a refining kettle in sequence, raising the temperature of the mixed solution in the refining kettle to 100 ℃, decoloring for 0.5h, press-filtering the mixed solution in the refining kettle, and transferring the filtrate into a crystallization kettle; and (3) reducing the temperature of filtrate in the crystallization kettle to 35 ℃, adding sodium hydroxide solution into the filtrate to adjust the pH of the filtrate to 10.5, reducing the temperature of the filtrate to 20 ℃ for crystallization, separating solid from liquid after crystallization to obtain a 1, 2-dimethyl-5-nitroimidazole fine product and refined solution, and drying the 1, 2-dimethyl-5-nitroimidazole fine product at 75 ℃ for 3 hours to obtain a finished product.
By adopting the method, 381kg of 1, 2-dimethyl-5-nitroimidazole is obtained, the content is 99.8 percent, and the yield is 81.3 percent, wherein 139kg of unreacted complete 2-methyl-5-nitroimidazole is obtained.
Example 5:
(1) Methylation reaction: 25kg of methanol and 85kg of sulfuric acid with the mass concentration of 98% are put into a reaction kettle, the reaction kettle is started to stir and mix uniformly, then steam is started to heat the mixed solution in the reaction kettle to 40 ℃, 159kg of 99wt% of 2-methyl-5-nitroimidazole is firstly added into the reaction kettle, 160kg of 98.5wt% of dimethyl sulfate is slowly added dropwise, the reaction temperature of the mixed solution in the reaction kettle is controlled to 92 ℃ when the dimethyl sulfate is added dropwise, and jacket-opened brine is opened to reduce the temperature of the mixed solution in the reaction kettle to 90 ℃ after the dimethyl sulfate is added dropwise; 265kg of 99wt% 2-methyl-5-nitroimidazole is added into the reaction kettle for the second time, 210kg of 98.5wt% dimethyl sulfate is slowly added dropwise, the reaction temperature of the mixed solution in the reaction kettle is controlled at 130 ℃, and jacket brine is opened after the dropwise addition of the dimethyl sulfate is completed to reduce the temperature of the mixed solution in the reaction kettle to 102 ℃; thirdly, 159kg of 99wt% 2-methyl-5-nitroimidazole is added into a reaction kettle, 100kg of 98.5wt% dimethyl sulfate is slowly added dropwise, the reaction temperature of the mixed solution in the reaction kettle is controlled at 105 ℃, after the reaction temperature is observed to be no longer increased within 5min, the temperature of the mixed solution in the reaction kettle is increased to 127 ℃, the temperature is kept for 1.5h, the temperature of the mixed solution is reduced to 90 ℃, 200kg of purified water or refining mother solution in the previous cycle is added into the reaction kettle (if the refining mother solution is insufficient, the purified water is used for supplementing to 200 kg), the temperature of the mixed solution in the reaction kettle is increased to 95 ℃ for hydrolysis for 3h, after the hydrolysis is finished, 1200kg of purified water or refining mother solution in the previous cycle is added into hydrolysate in the reaction kettle (if the refining mother solution is insufficient, the purified water is used for supplementing to 1200 kg), and then the mixed solution in the reaction kettle is transferred into the first reaction kettle and the kettle;
(2) And (3) neutralizing: reducing the temperature of the mixed solution in the first neutralization kettle in the step (1) to 30 ℃, adding ammonia water into the mixed solution, and adjusting the pH value of the mixed solution to 2.0; then the temperature of the mixed solution is reduced to 20 ℃ for crystallization, after crystallization, the mixed solution is centrifugally separated to obtain a neutralization mother solution and unreacted and completely 2-methyl-5-nitroimidazole, and the unreacted and completely 2-methyl-5-nitroimidazole is dried for 3 hours at 70 ℃ and then recovered;
(3) And II, neutralizing: transferring the first neutralization mother liquor obtained in the step (2) into a second neutralization kettle, reducing the temperature of the first neutralization mother liquor to 30 ℃, adding ammonia water into the mixed liquor, and adjusting the pH value of the mixed liquor to 7.0; then the temperature of the mixed solution is reduced to 16 ℃ for crystallization, after crystallization, the mixed solution is centrifugally separated to obtain a second neutralization mother solution and a 1, 2-dimethyl-5-nitroimidazole crude product, and the second neutralization mother solution is discharged after being treated by a purification workshop;
(4) Refining: adding 3300kg of purified water, 1400kg of 1, 2-dimethyl-5-nitroimidazole crude product and 6kg of activated carbon into a refining kettle in sequence, raising the temperature of the mixed solution in the refining kettle to 97 ℃, decoloring for 0.4h, press-filtering the mixed solution in the refining kettle, and transferring the filtrate into a crystallization kettle; and (3) reducing the temperature of filtrate in the crystallization kettle to 36 ℃, adding sodium hydroxide solution into the filtrate to adjust the pH of the filtrate to 11, reducing the temperature of the filtrate to 15 ℃ for crystallization, carrying out solid-liquid separation after crystallization to obtain a 1, 2-dimethyl-5-nitroimidazole fine product and refined solution, and drying the 1, 2-dimethyl-5-nitroimidazole fine product at 70 ℃ for 2.5 hours to obtain a finished product.
399kg of 1, 2-dimethyl-5-nitroimidazole with the content of 99.8 percent and the yield of 83 percent are obtained by adopting the method, wherein 150kg of 2-methyl-5-nitroimidazole which is not reacted completely.
The above-described embodiments of the present invention do not limit the scope of the present invention. Any other corresponding changes and modifications made in accordance with the technical idea of the present invention shall be included in the scope of the claims of the present invention.
Claims (1)
1. A method for synthesizing 1, 2-dimethyl-5-nitroimidazole, comprising the steps of:
s1: methylation reaction: uniformly mixing methanol and sulfuric acid to obtain a first mixed solution, heating the first mixed solution to 30-40 ℃, adding 2-methyl-5-nitroimidazole and dimethyl sulfate to react to obtain a second mixed solution, preserving the temperature of the second mixed solution at 120-130 ℃ for 1.5-2.5 h, diluting the second mixed solution, hydrolyzing the diluted second mixed solution at 95-102 ℃ for 2.5-4 h, and diluting the hydrolysate to obtain a first neutralization solution;
s2: and (3) neutralizing: cooling the first neutralization liquid to 30-40 ℃, adjusting the pH value of the first neutralization liquid to 1.9-2.1, cooling to 20-30 ℃ for crystallization, and carrying out solid-liquid separation after crystallization to obtain a neutralization mother liquid;
s3: and II, neutralizing: cooling the first neutralization mother liquor to 25-40 ℃, adjusting the pH value of the first neutralization mother liquor to 7-8, cooling to 15-20 ℃ for crystallization, and carrying out solid-liquid separation after crystallization to obtain a 1, 2-dimethyl-5-nitroimidazole crude product;
s4: refining: decolorizing, crystallizing, solid-liquid separating and drying the 1, 2-dimethyl-5-nitroimidazole crude product to obtain a finished product;
the 2-methyl-5-nitroimidazole and dimethyl sulfate are added into the first mixed solution for reaction in three times, and the reaction is specifically as follows:
adding 2-methyl-5-nitroimidazole and dimethyl sulfate into the first mixed solution for reaction at 90-100 ℃ for the first time, and cooling the mixed solution to 80-90 ℃;
adding 2-methyl-5-nitroimidazole and dimethyl sulfate for the second time, reacting at 105-130 ℃, and cooling the mixed solution to 100-105 ℃;
thirdly adding 2-methyl-5-nitroimidazole and dimethyl sulfate for reaction at 90-105 ℃ to obtain a second mixed solution, wherein the mass ratio of the thirdly adding 2-methyl-5-nitroimidazole is 3:5: and 3, adding dimethyl sulfate for three times, wherein the mass ratio of the dimethyl sulfate to the dimethyl sulfate is 16:21:10.
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