51 results about "Dimethyl sulfate" patented technology

The invention discloses a continuous kettle type nitromethane production process, and relates to the technical field of basic chemical raw material synthesis and flow chemical reaction process control, which comprises the following steps: quantitatively and continuously pumping a temperature-regulated sodium nitrite mixed solution into a raw material mixer in a closed-loop automatic control mode through a variable-frequency feeding pump matched with a mass flow meter; synchronously, quantitatively and continuously pumping dimethyl sulfate into the raw material mixer in a closed-loop automatic control manner by matching a feeding pump with a stop valve and a mass flow meter, and uniformly mixing the two raw materials in the raw material mixer according to the stoichiometric molar ratio of the dimethyl sulfate to the sodium nitrite, according to the tandem type segmented design, each reaction kettle can be subjected to customized temperature field control and heat transfer design specially aiming at the special thermodynamic and dynamic requirements of the reaction stage where the reaction kettle is located, the heat transfer efficiency of the whole system is greatly improved, and due to the fact that reaction heat is taken away timely and accurately, the heat transfer efficiency is greatly improved. And a by-product generation path induced by local abnormal high temperature is effectively restrained.

The invention relates to an L-proline heterocyclic intermediate, alpha-methyl-L-proline hydrochloride and a preparation method thereof, which comprises the following steps: step 01, cyclization upper protection: taking L-proline as a raw material, which is shown in a formula (1), to react with trichloracetic aldehyde hydrate under an acidic condition, and performing upper protection to obtain a heterocyclic intermediate as shown in a formula (2); the molar weight of chloral hydrate is 1-2.5 times of the molar weight of the L-proline shown in the formula (1), preferably 1.5 times of the molar weight of the L-proline shown in the formula (1). 02, methylation: reacting the heterocyclic intermediate as shown in the formula (2) obtained in the step 01 with lithium diisopropylamide, and after the reaction is completed, adding dimethyl sulfate for methylation to obtain an intermediate as shown in a formula (3); 03, deprotection: adding the intermediate as shown in the formula (3) obtained in the step 02 into a deprotection reagent for hydrolysis so as to obtain the alpha-methyl-L-proline hydrochloride as shown in the formula (4), so that the problems that the preparation cost of the existing alpha-methyl-L-proline hydrochloride is relatively high and the yield is relatively low can be solved.

The invention provides a method for detecting trace dimethyl sulfate in nicergoline, which comprises the following steps of: carrying out derivatization reaction on an azacyclo-compound serving as a derivatization agent and dimethyl sulfate in nicergoline to generate a derivatization product, and determining the amount of the derivatization product by using a high performance liquid chromatograph-mass spectrometer, therefore, the content of dimethyl sulfate in nicergoline is obtained. Compared with the prior art, the detection method provided by the invention has the characteristics of good specificity, high sensitivity, good reproducibility and the like, and makes up the vacancy of how to detect trace dimethyl sulfate in nicergoline in the prior art.

The present application relates to a kind of preparation method of trifluoromethyl pyrazole compound, belong to the technical field of organic synthesis.The specific method is: (1) trifluoroacetyl ethyl acetate is first with hydrazine hydrate cyclization reaction and generates compound of formula III;(2) under the catalysis of base, compound of formula III is reacted with difluoromethylation reagent and generates compound of formula II;(3) compound of formula II is reacted with methylating agent and obtains compound of formula I;The difluoromethylation reagent is difluoro-monochloromethane or sodium difluoro-monochloroacetate;The methylating agent is chloromethane, bromomethane, iodomethane, dimethyl sulfate or dimethyl carbonate.The present application is prepared by changing reaction route, and the higher-priced raw material methylhydrazine is replaced, and isomer impurity is no longer generated in the product prepared.Not only raw material cost is reduced, but also the purity of product is improved.

The present application relates to a kind of preparation methods of 2-methylamino-3-formylpyridine, comprising the following steps: 3-cyanopyridine and dimethyl sulfate are heated to reflux reaction in organic solvent I, then base is added, continue to react under heating reflux condition, and obtain intermediate product 2-methylamino-3-formylpyridine.The raw material used in the preparation method of the present application is cheap and easy to obtain, the preparation process has few side reactions, and is easy to purify.Only the steps of extraction and heavy crystallization are needed to achieve high purity, and strict control of anhydrous reaction conditions is not required.The yield and purity are high, and the prepared 2-methylamino-3-formylpyridine is suitable for industrial large-scale production of 2-methylamino-3-hydroxymethylpyridine, and further preparation of eslicarbazepine acetate and / or eslicarbazepine acetate sulfate.

The invention relates to a catalyst for preparing anisole through phenol methanol etherification as well as a preparation method and application of the catalyst. The catalyst takes aluminum phosphate as a carrier and is doped with zirconium oxide; on the basis of the mole number of Al, the mole ratio of P to Al is (0.05-2): 1, and the mole ratio of Zr to Al is (0.08-0.20): 1. Dropwise adding the aluminum-zirconium mixed aqueous solution into the phosphorus source aqueous solution, stirring, standing and washing to obtain a solid sample; and drying and roasting the solid sample to obtain the aluminum phosphate catalyst. Under the action of the catalyst, phenol and methanol are catalyzed to generate anisole. Compared with the prior art, the phenol conversion rate is greater than or equal to 50%, the anisole selectivity is greater than or equal to 85%, highly toxic dimethyl sulfate and a large amount of alkali are not needed, the process is green, the cost is low, separation is simple, and the method is suitable for large-scale industrial production of anisole.

The invention discloses modified lignin as well as a preparation method and application thereof, the preparation method comprises the following steps: adding lignin into a reaction kettle, adding an organic solvent, and stirring and dispersing; the preparation method comprises the following steps: adding an alkaline agent into a reaction kettle, stirring, condensing, refluxing, heating to 80-110 DEG C, adding a modifier A which is dimethyl carbonate or dimethyl sulfate, and reacting for 3-6 hours; after the reaction is finished, a modifier B is added for continuous reaction, negative pressure distillation is performed to remove the organic solvent, modified lignin is obtained, and the modifier B is epichlorohydrin. According to the method, the polarity of the lignin is remarkably reduced through two-step modification, the compatibility and dispersity of the lignin and a rubber matrix are enhanced, meanwhile, introduced active groups can be chemically bonded with rubber molecules, and the reinforcing effect is improved. The prepared modified lignin can be used as a rubber reinforcing agent, the tensile strength and hardness of a rubber product are effectively improved, the process is environment-friendly, the solvent can be recycled, and the method is suitable for preparing a green high-performance rubber material.

The application discloses a preparation method of triclabendazole, and relates to the technical field of raw medicine synthesis. The method comprises the following steps: taking 4-chloro-5-(2,3-dichlorophenoxy)-2-nitroaniline as raw material, and sequentially performing reduction in an iron powder ethanol system, ring closure with a sulfur-containing ring closure reagent, methylation with dimethyl sulfate, and crystallization and purification in ethanol to obtain triclabendazole finished products. In the reaction process, iron mud is removed through pressure filtration, ethanol is recovered through distillation, and the ring closure intermediate is precipitated under acidic conditions. The process condition is clear, the operation is simple, the emission of hazardous waste can be reduced, the utilization rate of solvents and the purity of products can be improved, and the method is suitable for industrialized production of triclabendazole raw medicine.

The invention relates to a method for efficiently preparing flurbiprofen based on a Suzuki-Miyaura coupling reaction. The preparation method comprises the following steps: taking ethyl cyanoacetate as a raw material, and carrying out methylation reaction on the ethyl cyanoacetate and methyl iodide or dimethyl sulfate to prepare racemic ethyl 2-cyanopropionate; the racemic ethyl 2-cyanopropionate and 4-bromine-2-fluorobiphenyl are subjected to a similar Suzuki-Miyaura reaction under the combined action of a zero-valent palladium metal catalyst, a metal stabilizer phosphine ligand and alkali, and the racemic ethyl 2-cyano-2-(2-fluoro4-biphenyl) propionate is obtained; and carrying out hydrolysis and decarboxylation on the racemic 2-cyano-2-(2-fluoro-4-biphenyl) ethyl propionate to obtain racemic 2-(2-fluoro-4-biphenyl) propionic acid, namely, the flurbiprofen. The process route comprises three steps of reaction, materials are cheap and easy to obtain, operation is simple, aftertreatment is convenient, and the obtained product is high in purity.

The application belongs to the technical field of compound synthesis, and particularly relates to a preparation method of dipyrone with controlled content of 4-N methylene sulfonic acid sodium dipyrone impurity, which comprises the following steps: dissolving 4-formylaminoantipyrine in water, and then adding dimethyl sulfate and lye to react to obtain a methylation liquor; the obtained methylation liquor is hydrolyzed and neutralized, and then is left to stand and separate into layers, the upper 4-methylaminoantipyrine oil is cooled and crystallized to obtain 4-methylaminoantipyrine solid; the obtained 4-methylaminoantipyrine solid, ethanol, sodium pyrosulfite, activated carbon and formaldehyde are mixed to react to obtain dipyrone; the mass percentage of 4-aminoantipyrine in the 4-formylaminoantipyrine is not more than 1.5%. The content of 4-N methylene sulfonic acid sodium dipyrone (unknown impurity) in the prepared dipyrone is less than or equal to 0.05%, which meets the requirements of the European Pharmacopoeia.

The invention discloses a continuous preparation technology of O-methyl-N-nitroisourea, and belongs to the technical field of fine chemical engineering. The O-methyl-N-nitroisourea is prepared by using the continuous flow reactor, compared with the prior art, the whole reaction process is completely sealed, the phenomena of running, emitting, dripping and leaking in the reaction process can be completely eradicated, meanwhile, the dosage of dimethyl sulfate is reduced, and personnel injury caused by leakage of highly toxic dimethyl sulfate can be effectively avoided; according to the invention, all the materials are fed in a liquid phase form, the preparation process of a sulfuric acid solution and a mixed acid solution is avoided, the operation procedures are reduced, the dissolution heat of sulfuric acid is effectively utilized, and the temperature rise is accelerated; the reaction can be completed by using a relatively low amount of concentrated nitric acid, and compared with fuming nitric acid, the cost of the concentrated nitric acid is greatly reduced; the whole operation process is simple, side reactions are few, the yield is high, the method is suitable for industrial production, and compared with a traditional intermittent kettle reaction, the method has great advantages.

The invention provides a method for catalytic continuous synthesis of aryl methyl ether, and belongs to the field of aryl methyl ether. The method for catalytically and continuously synthesizing the aryl methyl ether is carried out in a manner of combining continuous reaction and continuous rectification. According to the method for catalytically and continuously synthesizing the aryl methyl ether, the continuous production of the aryl methyl ether can be realized while dimethyl sulfate is not adopted and a large amount of high-toxicity wastewater and solid wastes are prevented from being generated in the production process, and the continuous production of the aryl methyl ether is mild in reaction condition, low in requirement on production equipment, small in production risk and high in production efficiency; the yield of the aryl methyl ether prepared through large-scale production is high, and large-scale industrial production is facilitated.

The present application relates to a kind of preparation methods of 3,4-dihydroxy-5-methoxybenzoic acid methyl ester, with gallic acid as raw material, it is reacted with trimethyl orthoformate or trimethyl orthoacetate, trimethyl orthoformate or trimethyl orthoacetate can realize the protection of adjacent diphenol hydroxyl on one hand, on the other hand, carboxyl esterification and 5-hydroxyl are methylated, form the methyl ester of 5-phenolic hydroxyl methylation and 3,4-orthoester protection benzoic acid shown in formula 1a or formula 1b, further by acidic solution treatment, deprotection is carried out, and the target product 3,4-dihydroxy-5-methoxybenzoic acid methyl ester is prepared.The preparation method is mild in reaction condition, process is simple, easy to operate, product yield and purity are high, solve the wastewater problem in borax protection method, and avoid using toxic dimethyl sulfate for methylation, process condition is simple, easy to operate, convenient for industrialization, with very high application value.

The invention belongs to the field of synthesis of drug intermediates, and discloses a process for industrially producing 2-allyl-3-methoxybenzaldehyde. The synthesis method comprises the following three steps: 1, alkylation reaction: reacting a raw material 3-hydroxybenzaldehyde with allyl bromide under an alkaline condition to obtain an allyl ether intermediate (3-allyl ether benzaldehyde); and 2, Claisen rearrangement reaction of the allyl ether intermediate: under a brand new flowing chemical reaction device (240 DEG C, 2MPa back pressure), dissolving the raw materials in a solvent, pumping the solvent into a microchannel, carrying out rearrangement reaction, and recrystallizing to remove an isomer, so as to obtain the intermediate 2-allyl-3-hydroxybenzaldehyde. And 3, methylation reaction: enabling the 2-allyl-3-hydroxybenzaldehyde to react with dimethyl sulfate under an alkaline condition, so as to obtain the product 2-allyl-3-methoxybenzaldehyde. The total yield of the three steps is 40%. According to the process, the raw materials are low in price and easy to obtain, the process operation is simple and convenient, and the process is suitable for industrial production of the 2-allyl-3-methoxybenzaldehyde.

The present application relates to a kind of preparation methods of 4-acetamido-5-chloro-2-methoxybenzoic acid methyl ester, steps include: S1, m-amino phenol is reacted with acetic anhydride to generate m-acetylamino phenol;S2, the m-acetylamino phenol is reacted with carbon dioxide to generate 4-acetylamino salicylic acid;S3, the 4-acetylamino salicylic acid is reacted with dimethyl sulfate to generate 2-methoxy-4-acetylamino benzoic acid methyl ester;S4, the 2-methoxy-4-acetylamino benzoic acid methyl ester is reacted with hydrochloric acid to generate 4-acetamido-5-chloro-2-methoxybenzoic acid methyl ester.The preparation method of the present application not only improves product quality and production efficiency, but also reduces cost, simplifies operation, and is friendly to environment, with significant industrial application prospect and market competitiveness.

The invention provides a method for treating excessive halogen in an ionic photoacid generator, which comprises the following steps: adding a crude product of the ionic photoacid generator to be treated into a reactor, adding a solvent, stirring, then adding a sulfate reagent, reacting, then adding an anion raw material, continuing reacting, and after the reaction is completed, carrying out post-treatment to obtain the excessive halogen in the ionic photoacid generator. The ionic photoacid generator with qualified halogen content is obtained. The halogen content is less than or equal to 10 ppm. And the sulfate reagent is dimethyl sulfate, diethyl sulfate, dipropyl sulfate or dibutyl sulfate. The method for treating the residual halogen in the ionic photoacid generator is mild in reaction condition, simple in technological process, environment-friendly and high in yield, and can be widely applied to preparation of iodonium salt and sulfonium salt photoacid generators.

This invention discloses a continuous flow synthesis method for nitromethane. The method includes mixing dimethyl sulfate, nitrite, a catalyst, and water to obtain a mixture; continuously feeding the mixture into a first reactor and reacting it at a first temperature to obtain a first reaction solution; continuously feeding the first reaction solution into a second reactor and reacting it at a second temperature to obtain a second reaction solution; continuously feeding the second reaction solution into a distillation column to obtain crude nitromethane, which is then purified by distillation to obtain the final nitromethane product. Both the first and second reactors are plug flow reactors, and the first temperature is lower than the second temperature. This method provides milder reaction conditions, easier process control, and by refining and precisely controlling the reaction temperatures of the two stages, it reduces the generation of byproducts and energy costs, avoids the safety hazards caused by violent foaming and material surges during the reaction, and significantly improves both process safety and efficiency.

The invention relates to the technical field of detection of dimethyl sulfate, in particular to a gas chromatography-mass spectrometry detection method of dimethyl sulfate in soil and sediment, which at least comprises the following steps: (1) collecting a sample, and measuring moisture in the sample; (2) adding an extracting agent into the sample, and carrying out vortex oscillation, ultrasonic extraction and solid-liquid separation to obtain supernate; and (3) filtering the supernate through a needle filter into a chromatographic sampling bottle, testing by adopting a gas chromatograph-mass spectrometer, comparing the retention time, characteristic ions and abundance of the sample and the standard solution to determine whether the dimethyl sulfate exists in the sample, quantifying by adopting an external standard method, and calculating the content of the dimethyl sulfate in the sample through a formula. According to the method, matching of all steps in the method is optimized, interference caused by complex environment matrixes is effectively overcome, accurate detection of the dimethyl sulfate in the soil and the sediments is achieved, and the method is simple and easy to promote daily monitoring of the DMS in the soil and the sediments.

The invention relates to a synthesis method of an azoxystrobin intermediate, and belongs to the technical field of organic synthesis.The synthesis method comprises the steps that benzofuranone serves as a raw material and is directly condensed with formate under the action of alkali, then dimethyl sulfate is methylated, and 3-(alpha-methoxyl) methylene benzofuranone is obtained. The use of expensive trimethyl orthoformate is avoided, and the cheap and easily available formate is adopted, so that the raw material cost of the azoxystrobin intermediate is greatly reduced, and the method is simple in process route, high in yield and suitable for industrial production.

The utility model discloses an efficient contact spray type tail gas recovery device, which comprises a filter box and a tower body, the left side of the filter box is fixedly connected with a gas inlet pipe, and the right end of the inner cavity of the filter box is fixedly connected with a fixed frame. Through the arrangement of the spraying pipe, a sodium hydroxide absorbent can be sprayed into the tower body in the tail gas treatment process, and under the action of the activated carbon filler layer, the sodium hydroxide absorbent sprayed in the tower body can be in full contact with dimethyl sulfate in tail gas and can be recycled; meanwhile, by arranging a film-coated polyester cloth bag in the filter box, impurities in the tail gas can be effectively filtered in the process of conveying the tail gas into the tower body, the situation that the impurities enter the tower body and cause blockage of a porous structure of the activated carbon filler layer is avoided, and the replacement frequency and the use cost of the activated carbon filler layer are reduced.

The application discloses a method for removing half ester in bisphenol A bis(diphenyl phosphate), relates to the technical field of organic synthesis, and has the following steps: mixing bisphenol A bis(diphenyl phosphate) material containing half ester with a methylating agent in the presence of a Lewis acid catalyst to make P-OH groups in the half ester undergo a methylation reaction, wherein the methylating agent is selected from one or more of dimethyl phosphate, dimethyl carbonate and dimethyl sulfate; and performing vacuum distillation on the reaction material after the reaction is completed to remove unreacted methylating agent and by-products, and further performing solvent dissolution, acid washing, alkali washing, water washing and desolvent treatment. The method has the beneficial effects that the half ester impurities containing acidic P-OH groups are converted into corresponding phosphate esters through the methylation reaction, and the half ester content and acid value in the BDP product are reduced.

The invention discloses a preparation method for preparing methoxyamine hydrochloride by using 2, 3-butanedione, which comprises the following steps: S1, adding 2, 3-butanedione and hydroxylamine hydrochloride into water, and carrying out oximation reaction under the action of alkali to prepare 2, 3-butanedioxime; s2, 2, 3-dimethylglyoxime and dimethyl sulfate are subjected to a methylation reaction, 2, 3-bis (methoxyimino) butane is prepared, and in the reaction process, alkali liquor is adopted to control the pH of a reaction system to be 7-9; s3, the 2, 3-bis (methoxyimino) butane is subjected to an acidolysis reaction, and methoxyamine hydrochloride is prepared. According to the method, 2, 3-butanedione and hydroxylamine hydrochloride are taken as raw materials, so that the conversion rate of methylation reaction is increased, the generation of polymethylation impurities (O, N-dimethyl hydroxylamine hydrochloride) is reduced, the yield is relatively high, meanwhile, the reaction condition is mild, the operation is simple, synthesis is easy, the byproduct 2, 3-butanedione can be recycled, the material utilization rate is high, and the method is suitable for industrial production. And the cost and the energy consumption can be reduced.

The invention relates to the technical field of chemical synthesis, in particular to a synthesis method and a purification method of DMI (isosorbide dimethyl ether). The DMI synthesis step comprises the following steps: mixing isosorbide, alkali and a high-boiling-point solvent, then adding DMS (dimethyl sulfate) for reaction, and collecting an organic phase after the reaction is finished to obtain a reaction product containing the DMI; the molar weight ratio of the isosorbide to the DMS to the alkali is 1: (0.5-3): (2-5). According to the method, the isosorbide is used as a starting raw material of a DMI synthesis route, the utilization rate of the isosorbide is remarkably increased by optimizing synthesis reaction raw materials and process conditions, preferably selecting NaOH or an aqueous solution thereof as alkali and limiting a feeding sequence and a formula dosage, and a brand new thought is provided for batch production of the DMI by virtue of natural properties of the isosorbide.

The invention discloses a preparation method of 2, 4-dinitroanisole. According to the method, phenol is taken as a starting raw material, in the first step, phenol reacts with nitrate under photocatalysis to obtain 2, 4-dinitrophenol, and in the second step, the target product 2, 4-dinitroanisole is prepared from 2, 4-dinitrophenol and dimethyl sulfate under the action of alkali. The synthesis technical route is different from the traditional synthesis method. The method does not need to use a large amount of excessive acid and alkali, and is simple to operate, mild in condition, environment-friendly, free of the problem of corrosivity and high in yield.

The invention relates to a preparation method of ketoprofen, and belongs to the technical field of synthesis of drug intermediates. In order to solve the problems of low yield and difficulty in removing impurities in the prior art, the invention provides a preparation method of ketoprofen, which comprises the following steps: in the presence of alkali metal alkoxide, reacting 3-benzoylbenzyl cyanide with a methyl esterification reagent to obtain a compound as shown in a formula II; carrying out methylation reaction on the compound as shown in the formula II and dimethyl sulfate; carrying out selective ester hydrolysis reaction under the action of an ester hydrolysis catalyst to obtain salt of a compound as shown in a formula IV; after the reaction is finished, enabling a reaction solution to contain water and a water-insoluble organic solvent, standing for layering, collecting a water phase, and adding acid into the water phase for acidification to obtain a compound shown as a formula IV; and under acidic or alkaline conditions, carrying out cyano hydrolysis and decarboxylation reaction on the compound as shown in the formula IV to obtain ketoprofen. Through route improvement, the product purity is more effectively guaranteed, and the effects of high product purity and yield are achieved.

The present application relates to a kind of 2-methoxy-4-acetylamino-5-iodobenzoic acid methyl ester preparation method, steps include: S1, by p-aminosalicylic acid and acetic anhydride reaction, preparation 4-acetylamino salicylic acid;S2, by the 4-acetylamino salicylic acid and dimethyl sulfate reaction, preparation 2-methoxy-4-acetylamino benzoic acid methyl ester;S3, by the 2-methoxy-4-acetylamino benzoic acid methyl ester and iodine reaction, preparation 2-methoxy-4-acetylamino-5-iodobenzoic acid methyl ester.The preparation method of the present application is compared with prior art, and reaction step is shortened to three steps, and total yield is as high as 70% or so;While the yield of iodine substitution reaction is increased from 29% to more than 90%.

This invention discloses a method for preparing dimethyl tellurium. The method includes the following steps: slowly adding a dimethyl ether solution dropwise into a boron triiodide solution; washing and drying the reaction mixture to obtain an organic phase; adding the organic phase dropwise into a mixture of disodium telluride and an alcohol reagent; separating the reaction product by distillation; and purifying the reaction product to obtain dimethyl tellurium. This invention uses low-toxicity, inexpensive dimethyl ether instead of highly toxic dimethyl sulfate or expensive iodomethane, fundamentally solving the raw material safety bottleneck and significantly reducing production costs. The synthetic route using dimethyl ether, boron triiodide, and disodium telluride as the main raw materials significantly reduces byproducts and impurities in the direct product, simplifies subsequent purification steps, and allows for the acquisition of high-purity dimethyl tellurium through simple distillation, effectively improving the yield and purity of the final product and showing good prospects for industrial application.

The application discloses a preparation method of N1,N2-dimethyl benzene-1,2-diamine and belongs to the technical field of medical intermediate preparation. The method comprises the following steps: taking o-phenylenediamine as a raw material, reacting with ethyl formate, then adopting dimethyl sulfate to perform a nitrogen-methylation reaction, and finally removing a formyl group under the action of an acid to obtain N1,N2-dimethyl benzene-1,2-diamine. In the method, all raw materials can be conveniently purchased on the market, the process of each reaction is simple, there is no expensive catalyst, the yield is high, and the industrialized production is easy.

The invention relates to the technical field of pharmaceutical chemicals, in particular to a preparation method of 4-methylaminoantipyrine, which comprises the following steps: uniformly stirring 4-formylaminoantipyrine and water, dropwise adding dimethyl sulfate and liquid caustic soda at the same time at 10-20 DEG C for methylation reaction, with the pure amount ratio of dimethyl sulfate to FAA being 0.60-0.90 and the pure amount ratio of liquid caustic soda to FAA being 0.20-0.30; after the reaction end point is qualified, adding concentrated sulfuric acid with the pure amount ratio of 0.6-0.8 to the FAA and methanol with the pure amount ratio of 0.1-0.6 to the FAA, heating for hydrolysis, and controlling the hydrolysis top temperature to be lower than 95 DEG C; and after hydrolysis is finished, neutralizing with liquid caustic soda until the pH value is 7.0-7.5, and standing for layering to obtain MAA. Through collaborative optimization of methylation, hydrolysis and neutralization procedures, the consumption of dimethyl sulfate and sulfuric acid is remarkably reduced, the byproduct salt amount and the mother liquor treatment amount are reduced, the liquid caustic soda is used for replacing sodium carbonate to realize pipeline conveying, and the production cost and the labor intensity of workers are effectively reduced.

The application discloses a continuous synthesis process of dimetridazole raw medicine. The application specifically discloses a preparation method of dimetridazole, which comprises the following steps: introducing a heterogeneous suspension into a tubular reactor to prepare dimetridazole through a substitution reaction; and the heterogeneous suspension contains 2-methyl-5-nitroimidazole, dimethyl sulfate and an aromatic hydrocarbon solvent. The preparation method has one or more of the following advantages: high safety, simple operation, high yield, easy control of reaction progress, difficulty in generation of double-substituted impurities and fast reaction speed.