CN107266321B - A kind of method of trifluoromethoxybenzene nitration - Google Patents

Abstract

The invention belongs to the technical field of microchemical industry, and in particular relates to a method for nitration of trifluoromethoxybenzene. Using pure trifluoromethoxybenzene as the raw material, using the mixed acid of fuming nitric acid and concentrated sulfuric acid as the nitrating agent, the two are strongly mixed in the microchannel reactor through continuous conveying equipment, preferably, the mixed material is further Mix and react in the second reactor at the back of the microchannel reactor to obtain the product trifluoromethoxynitrobenzene. The method of the present invention utilizes the high-efficiency mass and heat transfer characteristics of a microchannel reactor, and can realize more than 99% of raw material conversion and generate p- and ortho-nitrotrifluoromethoxy with high selectivity under optimized microreactor structure and operating parameters Benzene, meta and dinitration by-products are less than 0.1% and 1%, respectively.

Description

A kind of method of trifluoromethoxybenzene nitration

technical field

The invention belongs to the technical field of microchemical industry, and in particular relates to a method for highly selective nitration of trifluoromethoxy substituted benzene.

Background technique

p-Nitrotrifluoromethoxybenzene is the raw material for the synthesis of p-trifluoromethoxyaniline, and p-trifluoromethoxyaniline, as a fluorine-containing organic intermediate, can be widely used in pesticides, medicines, and liquid crystal materials. It is used in the synthesis of various insecticides, herbicides, electrophotographic materials, active optical fibers, and in the synthesis of medicines for the treatment of cardiovascular diseases and diabetes. With the continuous development of these downstream products, the demand for trifluoromethoxyaniline will gradually increase. At present, the industrialized product production still stays in the tank-type nitration-hydrogenation reduction process stage. Due to the restriction of the reaction process and the performance of the reactor, the production of high-quality nitrotrifluoromethoxybenzene needs to consume a large amount of concentrated sulfuric acid. Slowly add mixed acid to carry out the nitrification step under low temperature (-30°C cold medium to transfer heat), and the annual output of most enterprises is only several hundred tons. Therefore, there is an urgent need to adopt new technologies to improve poor product quality or make up for the insufficient capacity of traditional reaction processes.

Microreactor is a kind of chemical process intensification equipment, which has a microchannel structure with a characteristic scale of several microns to several millimeters. It has the characteristics of fast mass and heat transfer, uniform mixing, and high specific surface area. It has been widely concerned and applied in the nitration and sulfonation of aromatic hydrocarbons. Aromatic hydrocarbon nitration is a kind of strong exothermic reaction (benzene nitration reaction heat is 145kJ/mol), if the heat of reaction cannot be removed in time, the temperature rise of the reaction system will increase the reaction temperature and the rate of side reactions, especially the increase of dinitride content and isomer ratio changes. The nitration product of trifluoromethoxybenzene requires that the meta-site concentration is lower than 0.2%, and the dinitrification compound is controlled below 2%. At this time, the kettle-type process must transfer heat in an extremely low-temperature cooling medium and adopt a slow drop method to achieve Product indicators, a production batch generally takes tens of hours. Shi Zuopan of Nanjing University of Science and Technology added polyphosphoric acid to nitrate trifluoromethoxybenzene in the nitrating agent, and used the "polyphosphoric acid-NO ₂ ⁺ " ion nitration formed by polyphosphoric acid and nitric acid with a steric hindrance effect to improve the nitration. Regioselectivity, the product yield is up to 90%, the to-ortho ratio is 91:9, and the rest are dinitration by-products and meta-products. The Dalian Institute of Chemical Physics, Chinese Academy of Sciences has conducted many years of experimental research on reactions such as nitration of alcohols, aromatics, and sulfonation of aromatics in microreactors, and has applied for related patented technologies. Patents CN101544567B and CN101544568B use low-water-content nitric-sulfur mixed acid to nitrate toluene and chlorobenzene to synthesize dinitro compounds. Among them, the toluene conversion rate is 97.5% when the dinitration of toluene is about 50000h ^-1 in space time, and the conversion rate of 2,4-DNT and 2, The total selectivity of 6-DNT is higher than 95% (there are other site dinitrates). In the patent CN101613285B, a combined nitration process of microreactor and tank reactor was proposed. Under the condition of high water content and mixed acid, the dinitrate is less than 0.3%. Since there are no substituents on the benzene ring, the mononitration product has no regioselectivity problem. Process optimization only needs to control the dinitration rate, which is different from the regioselectivity of trifluoromethoxy-substituted benzene in the mononitration process, and the nitration of aromatics with regioselectivity has more stringent requirements on the process.

In order to develop micro-reaction technology for the mononitration of substituted benzene and product selectivity, the applicant conducted in-depth research and found that this type of reaction is different from the dinitration of substituted benzene, and also different from the mononitration of benzene. The micro-reaction nitration process is not suitable for the mononitration of substituted benzene. For example, the use of highly aqueous nitrating acids for the nitration of benzene in the mononitration of substituted benzene will significantly increase the selectivity for meta-position products, which are not the desired structural products for this type of reaction.

Contents of the invention

In order to solve the problem of regioselectivity and avoid overnitration during the nitration of trifluoromethoxybenzene, the present invention provides a method for nitration of trifluoromethoxybenzene, which can make the concentration of meta-nitration by-products lower than 0.2% , can be lower than 0.08% under optimal conditions; the concentration of dinitration by-products is lower than 2%, lower than 0.6% under optimal conditions.

The present invention takes following technical scheme:

Using pure trifluoromethoxybenzene as the raw material, using the mixed acid of fuming nitric acid and concentrated sulfuric acid as the nitrating agent, the two are strongly mixed in the microchannel reactor through continuous conveying equipment, and the mixed material is further in the Mix and react in the second reactor at the rear of the microchannel reactor to obtain the product nitrotrifluoromethoxybenzene; the nitration reaction is carried out within the following parameter ranges:

In terms of mass, the water content in the mixed acid is not higher than 5%, and the concentration of nitric acid is 8-30%;

Wherein, the water content in the concentrated sulfuric acid is 2-5%, and the water content in the fuming nitric acid is 2.5-10%.

In terms of molar weight, the feeding ratio of nitric acid to trifluoromethoxybenzene is not less than 1.00 and not higher than 1.20; the reaction temperature is -10 to 40°C; the residence time of raw materials and nitrating agent in the microchannel reactor is 0.1 ～10 seconds, the preferred time is 1～10 seconds, 5～50% of the raw materials are converted; the residence time in the second reactor (as a reaction residence device) at the rear of the microchannel is not less than 30 seconds, and preferably the The residence time is no greater than 30 minutes to achieve at least 98% conversion of the feedstock.

After nitrification, slowly add water or discarded dilute sulfuric acid (such as dilute sulfuric acid with a water concentration exceeding 50%) to extract the nitration products in the waste acid. The amount of water or dilute sulfuric acid added generally does not exceed 5% of the total mass of the reaction mixed acid. 20% to reduce the amount of waste acid. The temperature in the extraction process is not higher than 40°C, preferably not higher than 20°C, more preferably not higher than 10°C, but optionally not lower than -10°C.

The microchannel reactor can be plate-shaped or microtubular and include any structure of heat exchange channels or equipment, and the second reactor at the rear of the microchannel reactor can be microreactor or microtubular and include heat exchange Any configuration of channels or heat removal devices. The heat exchange channel they contain can control the nitrification reaction temperature in the mixing or reaction channel between -10 and 40°C with very high heat transfer efficiency, and there is no hot spot area.

Structurally, microchannel reactors have submillimeter-level mixing or reaction channels, which are usually measured by hydraulic diameter. The range of hydraulic diameters is generally 0.1-2mm. Chemical etching methods generally obtain microchannels less than 1mm; mixing or reaction channels Multiple lines are distributed in parallel, with a certain volume, so that the residence time of the raw material trifluoromethoxybenzene and the nitrating agent in the channel reaches 0.1 to 10 seconds, to maximize the nitrated conversion of the raw material, because there is a large heat of solution when the two phases are mixed With part of the heat of reaction, the structure of the microchannel reactor must be equipped with heat exchange channels to control the temperature. The second reactor equipment has mixing or reaction channels from submillimeter to several millimeters, and can be in the form of a microreactor. At this time, a slightly larger internal volume of the microreactor needs to be constructed; stainless steel or other metals with an inner diameter of 4 to 15mm can also be used. The round tube is used as a reaction residence device. Preferably, its interior can be filled with any corrosion-resistant and good thermal conductivity filler as a mixing element. The gap of the mixing element is from submillimeter to several millimeters; preferably, it is made of high-purity quartz material The round tubes are filled, and the round tubes containing the mixing elements are arranged in parallel to form a tubular structure, and a cooling medium is passed through the outside of the tubes, and the temperature of the cooling medium is -10 to 10°C.

Beneficial effects of the present invention:

The present invention can convert nearly 100% of the raw material trifluoromethoxybenzene in the microchannel reactor as the core reactor technology and within a reaction time that is two orders of magnitude smaller than that of the traditional process. In the method of the present invention, the microchannel is used alone It is difficult to achieve a good nitrification effect in the reactor or the second reactor. The larger internal volume of the second reactor makes up for the defects in the residence time control of the microchannel reactor, and the microchannel reactor is the raw material for the nitrification process. Mixing and product selectivity provide the best solution and guarantee.

According to the nitration method of the present invention, the concentration of mononitration by-products in the middle of the product is lower than 0.2%, preferably lower than 0.08%; the concentration of dinitration by-products is lower than 2%, and lower than 0.6% under preferable conditions. The invention provides a more advanced nitration technology for simplifying the subsequent separation of the nitration process and improving product quality.

Detailed ways

Example 1

Pure trifluoromethoxybenzene is used as a raw material, and a mixed acid of fuming nitric acid and concentrated sulfuric acid is used as a nitrating agent, wherein the mass concentration of nitric acid in the nitrating agent is 23.6%, and the mass concentration of water is 3%. The raw material and nitrifying acid are fed at a flow rate of 1.0mL/min and 1.4mL/min respectively through two continuous conveying equipment Series II digital pumps, that is, the feed ratio of nitric acid to trifluoromethoxybenzene is 1.17 in terms of molar weight . Raw materials and nitrating acid are strongly mixed in a parallel microchannel reactor with a channel equivalent diameter of 0.6mm and a liquid holding volume of 0.4mL and undergo an initial reaction (46% to 51% conversion of the tested reactant), and then the mixed material Further mixing and reacting in the second reactor (packing tube) of the reaction residence device at the rear of the microchannel reactor, the packing tube is a tube with a porosity of 38.4% to 40% (a tube reactor with a mixing element), The reaction mass was allowed to dwell in the second reactor for 30 seconds. Simultaneously, the microchannel reactor and the tube reactor are controlled to have a reaction temperature of 20°C, and the product nitrotrifluoromethoxybenzene and waste acid are obtained at the outlet of the tube, and the two phases are separated, and the organic matter in the acid phase is extracted with 10% water, The upper layer products were combined, and the product was washed alternately with water and alkaline water until neutral. Agilent 7890 gas chromatograph was used for detection, and the chromatographic column was DB-1701. The concentration of meso-, para-, ortho-mono-nitride and di-nitrate of the product was quantified by peak area.

After analysis: the conversion rate of raw materials is 99.8%, the m-, p-, and ortho-mono-nitrides are 0.07%, 91.5%, and 7.4% respectively, and the di-nitrides are 0.5%.

Example 2

Adopt the same micro-reactor system nitration as in Example 1, adjust the mass concentration of nitric acid to 19.8% in the nitrating agent, and the mass concentration of water is 3%, and the mol ratio of fixed nitric acid and trifluoromethoxybenzene is 0.99～1.05, the total The reaction residence time was 60 seconds, and the temperature of the microreactor system was changed to 18°C, 28°C, and 42°C, and the product results are shown in Table 1.

Table 1. Microreactor system performance at different reaction temperatures

Embodiment 3-5

The microchannel reactor used in Example 1 was tested individually. The mass concentration of nitric acid in the nitrating agent is 13.4%, and the mass concentration of water is still 3%; In terms of molar weight, the feed ratio of nitric acid and trifluoromethoxybenzene is 1.05; the reaction temperature is 5～10°C; raw material and nitrating agent are in micro The residence times in the channel reactor were 1.0, 3.5 and 10 seconds, respectively. The product results are shown in Table 2.

Table 2. Partial nitrification performance of microchannel reactor

Embodiment 6-8

The tube reactor used in Example 1 (the second reactor) was tested separately. The mass concentration of nitric acid in the nitrating agent is 10.8%, and the mass concentration of water is 5%; in terms of molar weight, the feed ratio of nitric acid and trifluoromethoxybenzene is 1.00; the reaction temperature is 5-10°C; The residence times in the reactor were 15, 20 and 40 seconds, respectively. The product results are shown in Table 3.

Table 3. Partial nitrification performance of the tube reactor

Claims (6)

1. a method for the nitration of trifluoromethoxybenzene is characterized in that: taking trifluoromethoxybenzene as raw material, taking the mixed acid of fuming nitric acid and the vitriol oil as nitrating agent, raw material and nitrating agent are in microchannel successively Mix and react in the second reactor connected to the rear of the reactor I and the microchannel reactor I, to obtain product nitrotrifluoromethoxybenzene; In terms of mass, the water content in the mixed acid is not higher than 5%, and the concentration of nitric acid is 8-30%; On a molar basis, the feed ratio of nitric acid to trifluoromethoxybenzene is 1.00 to 1.20; The reaction temperature is -10～40℃; The residence time of the raw material and the nitrating agent in the microchannel reactor I is 0.1 to 10 seconds, and the residence time in the second reactor is not less than 30 seconds; the second reactor is a tube reactor, and the inner diameter of the tubes is 4~15mm. 2. The method according to claim 1, characterized in that: the nitrated material is slowly added to water or dilute sulfuric acid to extract the nitrated product in the waste acid, the temperature of the extraction process is -10 ~ 40 ° C; the combined nitrated product is mixed with water Wash with alkaline water until neutral. 3. method according to claim 1, is characterized in that: the residence time of raw material and nitrating agent in microchannel reactor 1 makes the raw material conversion of 5～50%; The residence time in the second reactor makes raw material complete At least 98% conversion. 4. method according to claim 1, is characterized in that: microchannel reactor 1 has the mixing-reaction channel of submillimeter order; Described microchannel reactor 1 and the second reactor all comprise heat exchange structure or heat removal The equipment, heat exchange structure or heat transfer equipment can control the temperature of the reaction process at -10-40°C. 5. The method according to claim 1 or 4, characterized in that: the microchannel reactor I is a plate-shaped or micro-tubular structure with a hydraulic diameter of 0.1 to 2 mm. 6. The method according to claim 1, characterized in that: The tubes of the tube reactor are filled with mixing elements, the mixing elements are selected from high-purity quartz materials, and the circular tubes containing the mixing elements are arranged in parallel, and the cooling medium is passed through the outside of the tubes, and the temperature of the cooling medium is -10~ 10°C.