阅读说明：本技术 一种邻硝基苯甲醛的制备方法 (Preparation method of o-nitrobenzaldehyde ) 是由 程先波 于 2018-07-11 设计创作，主要内容包括：本发明涉及一种邻硝基苯甲醛的制备方法,以所需的产品硝基苯甲醛和硝基甲苯为原料来制备1,2-二(邻硝基苯基)乙烯,然后以适当浓度的臭氧进行高效率氧化得到最终的产品硝基苯甲醛。本发明的有益效果：本发明的制备方法在缩合反应中仅用到适量的碱催化,用常规溶剂进行带水反应即可高效率得到中间产物1,2-二(邻硝基苯基)乙烯；以微通道反应器进行气液反应,最终得到所需的硝基苯甲醛。所用原料少,反应收率高,副产物及杂质带入少,纯化操作简单易行,便于车间工业化生产。(The invention relates to a method for preparing o-nitrobenzaldehyde, which takes the required products of nitrobenzaldehyde and nitrotoluene as raw materials to prepare 1, 2-di (o-nitrophenyl) ethylene, and then carries out high-efficiency oxidation by ozone with proper concentration to obtain the final product of nitrobenzaldehyde. The invention has the beneficial effects that: the preparation method of the invention only uses a proper amount of alkali for catalysis in the condensation reaction, and uses the conventional solvent for carrying out water-carrying reaction to obtain the intermediate product 1, 2-di (o-nitrophenyl) ethylene with high efficiency; and carrying out gas-liquid reaction by using a microchannel reactor to finally obtain the required nitrobenzaldehyde. The method has the advantages of less raw materials, high reaction yield, less byproducts and impurities, simple and easy purification operation and convenient industrial production in a workshop.)

1. A preparation method of o-nitrobenzaldehyde is characterized in that o-nitrotoluene and o-nitrobenzaldehyde are used as raw materials to react to generate 1, 2-di (o-nitrophenyl) ethylene, and then ozone is used to oxidize the ethylene into the o-nitrobenzaldehyde, wherein the reaction equation is as follows:

2. the method for preparing o-nitrobenzaldehyde according to claim 1, wherein the molar ratio of o-nitrotoluene to o-nitrobenzaldehyde is 1: 1.

3. The method for preparing o-nitrobenzaldehyde according to claim 1, wherein the reaction solvent of o-nitrotoluene and o-nitrobenzaldehyde is benzene, toluene or xylene, the reaction time is 6-24 hours, and TLC tracking detection is performed until the reaction is completed.

4. The process for producing o-nitrobenzaldehyde according to claim 3, wherein the reaction temperature when benzene is used as the reaction solvent is 80 to 90 ℃; the reaction temperature is 110-120 ℃ when toluene is used as a reaction solvent; the reaction temperature when xylene was used as the reaction solvent was 130-140 ℃.

5. The method for preparing o-nitrobenzaldehyde according to claim 3, characterized in that o-nitrotoluene and o-nitrobenzaldehyde are used as raw materials for reaction, benzene, toluene or xylene are used as reaction solvents, the temperature is raised, reflux dehydration is carried out, and then the solvents are recovered by distillation; adding ethanol into the product, cooling, crystallizing, filtering, washing and drying to obtain the 1, 2-di (o-nitrophenyl) ethylene.

6. The method for preparing o-nitrobenzaldehyde according to claim 1, wherein the o-nitrotoluene and o-nitrobenzaldehyde are subjected to Knoevenagel condensation reaction in the presence of a base to obtain 1, 2-bis (o-nitrophenyl) ethylene.

7. The method for preparing o-nitrobenzaldehyde according to claim 6, wherein said base is piperidine, sodium alkoxide, sodium hydride.

8. The preparation method of o-nitrobenzaldehyde according to claim 1, characterized in that in the ozone oxidation process, the reaction solvent is halogenated alkane, the reaction temperature is-50 ℃ to 25 ℃, the reaction equipment is a microchannel gas-liquid reaction device, tail gas is collected through a gas-liquid separator and absorbed, the reaction liquid is collected, distilled and recovered, the solvent is then added with ethyl acetate for recrystallization, and the o-nitrobenzaldehyde is obtained after filtration, washing and drying.

9. The method for preparing o-nitrobenzaldehyde according to claim 8, wherein said haloalkane is dichloromethane, chloroform or carbon tetrachloride.

10. The method for preparing o-nitrobenzaldehyde according to claim 1, wherein said method is suitable for the synthesis of p-nitrobenzaldehyde or polynitrobenzaldehyde, and also for the synthesis of aminobenzaldehyde from nitro group and amino group by Knoevenagel condensation reaction.

Technical Field

The invention relates to a synthesis method of pharmaceutical and chemical intermediates, in particular to a preparation method of o-nitrobenzaldehyde.

Background

The o-nitrobenzaldehyde and polynitrobenzaldehyde are important medical intermediates and organic synthesis raw materials, have very wide application, and the existing synthesis method mainly comprises the following steps:

1. the method is a direct oxidation method of o-nitrotoluene or polynitrotoluene, and because products of methyl oxidation comprise three products of alcohol, aldehyde and acid, the oxidation degree needs to be controlled, the method generates more impurities and has lower yield.

2. Firstly, carrying out halogenation reaction on methyl by using o-nitrotoluene or polynitrotoluene to generate benzyl monohalide or benzyl dihalide, then hydrolyzing to obtain alcohol or aldehyde, and then oxidizing the alcohol into aldehyde to obtain the final product of aldehyde. The method needs a large amount of halogenating reagents, and although some halogenating reagents used in the process can be well recycled, the operation process is complicated and the yield is not high.

3. The Chinese patent CN105859562 takes 1, 2-bis (o-nitrophenyl) ethane as a raw material, benzoquinone is used for oxidation to obtain o-nitrotoluene, the raw material is not easy to obtain in the method, a preparation method of the raw material is not mentioned in the text, benzoquinone is introduced in the oxidation process, and is changed into hydroquinone after reaction, so that the purification difficulty of the final product is increased, a relatively pure product can be obtained only by high vacuum rectification, and the energy consumption and the labor cost in the production process of the product are greatly increased.

Claro I.Sainz-Diaz and Alfonso Hernandez-Laguna et al, in Trans-2,2' -Dinitrostilbene as a previous of o-nitrobenzaldehyde, a key inter mediate medicines: reactivities and molecular structures [ J ] Chem.Soc.Perkin Trans,1999,2:1489-1495, proposed the oxidation of 1, 2-bis (o-nitrophenyl) ethylene by ozone in the presence of dimethyl sulfide to give o-nitrobenzaldehyde, but also in the case of ethylene feedstocks obtained by post-halogenation condensation and use of dimethyl sulfide in the course of ozonization, which is environmentally friendly and safe.

5. The o-nitrobenzaldehyde can be obtained by adopting an electrochemical oxidation method, but the electrochemical oxidation method has the problems of low yield, serious equipment corrosion and the like, and limits the industrial production of the electrochemical method.

Disclosure of Invention

In order to solve the problems in the prior art, the invention provides a preparation method of o-nitrobenzaldehyde, which has the advantages of less raw materials, high reaction yield, less introduction of byproducts and impurities, simple and easy purification operation and convenient industrial production in a workshop.

The invention aims to provide a preparation method of o-nitrobenzaldehyde.

According to the preparation method of the o-nitrobenzaldehyde, the o-nitrobenzaldehyde is prepared by taking o-nitrotoluene and o-nitrobenzaldehyde as raw materials to react to generate 1, 2-di (o-nitrophenyl) ethylene, and then oxidizing the o-nitrobenzaldehyde into the o-nitrobenzaldehyde by ozone, wherein the reaction equation is as follows:

according to the preparation method of the o-nitrobenzaldehyde, the molar ratio of the o-nitrotoluene to the o-nitrobenzaldehyde is 1: 1. 1mol of o-nitrotoluene and 1mol of o-nitrobenzaldehyde react to generate 1mol of 1, 2-di (o-nitrophenyl) ethylene, and then the 1mol of 1, 2-di (o-nitrobenzyl) ethylene is oxidized into 2mol of o-nitrobenzaldehyde by ozone.

According to the preparation method of the o-nitrobenzaldehyde, the reaction solvent of the o-nitrotoluene and the o-nitrobenzaldehyde is benzene, toluene or xylene, the reaction time is 6-24 hours, and TLC tracking detection is carried out until the reaction is finished.

According to the preparation method of the o-nitrobenzaldehyde, provided by the embodiment of the invention, further, the reaction temperature is 80-90 ℃ when benzene is used as a reaction solvent; the reaction temperature is 110-120 ℃ when toluene is used as a reaction solvent; the reaction temperature when xylene was used as the reaction solvent was 130-140 ℃.

According to the preparation method of the o-nitrobenzaldehyde, provided by the specific embodiment of the invention, further, o-nitrotoluene and o-nitrobenzaldehyde are used as raw materials to react, benzene, toluene or xylene are used as reaction solvents, the temperature is raised, reflux dehydration is carried out, and then the solvents are recovered by distillation; adding ethanol into the product, cooling, crystallizing, filtering, washing and drying to obtain the 1, 2-di (o-nitrophenyl) ethylene.

According to the preparation method of o-nitrobenzaldehyde, provided by the specific embodiment of the invention, o-nitrotoluene and o-nitrobenzaldehyde are subjected to Knoevenagel condensation reaction in the presence of alkali to obtain 1, 2-di (o-nitrophenyl) ethylene.

According to the preparation method of the o-nitrobenzaldehyde, the alkali is piperidine, sodium alkoxide and sodium hydrogen.

According to the preparation method of the o-nitrobenzaldehyde, provided by the specific embodiment of the invention, in the ozone oxidation process, a reaction solvent is halogenated alkane, the reaction temperature is-50 ℃ to 25 ℃, a reaction device is a microchannel gas-liquid reaction device, tail gas is collected through a gas-liquid separator and absorbed, a reaction liquid is collected, distilled and recovered, the solvent is then added with ethyl acetate for recrystallization, and the o-nitrobenzaldehyde is obtained after filtration, washing and drying. Wherein, the reaction equipment can adopt a corning microchannel reactor, and the time of the reaction channel is 1 minute to 2 hours.

During the specific operation, on a microchannel reactor for gas-liquid reaction, reducing the working temperature to about-10 ℃ and stabilizing for about 10 minutes, firstly opening an ozone generator to lead ozone into the microchannel, leading the concentration of the ozone to be 5-10 g/L, adjusting a back pressure valve to lead the speed and the pressure of ozone gas with constant concentration into the microchannel to be stable, then pumping 25 g of dichloromethane solution of 1, 2-di (o-nitrophenyl) ethylene into a constant flow pump through a check valve to lead the molar ratio of the ozone to the 1, 2-di (o-nitrophenyl) ethylene to be 1.2-1.5:1, controlling the pumping speed to achieve the optimal oxidation effect, collecting tail gas at an outlet of the microchannel through a gas-liquid separator to carry out absorption treatment, collecting reaction liquid to evaporate and recover dichloromethane to dryness, adding ethyl acetate for recrystallization, filtering and washing by adopting 0-5 ℃ ethyl acetate, then drying the mixture under the conditions that the vacuum degree is between-0.07 and-0.08 MPa and the temperature is between 35 and 40 ℃ to obtain the o-nitrobenzaldehyde.

According to the preparation method of o-nitrobenzaldehyde of the embodiment of the invention, furthermore, the halogenated alkane is dichloromethane, trichloromethane or carbon tetrachloride.

The method for preparing o-nitrobenzaldehyde according to the embodiment of the invention is suitable for synthesizing p-nitrobenzaldehyde or polynitrobenzaldehyde, and also suitable for synthesizing aminobenzaldehyde by Knoevenagel condensation reaction of nitro and amino. The synthesis of polynitrobenzaldehyde, such as the preparation of 2, 6-dinitrobenzaldehyde and the synthesis of 2,4, 6-trinitrobenzaldehyde; synthesis of a combination of a nitro group and an amino group, such as 2, 6-dinitro-4-aminobenzaldehyde.

The invention has the beneficial effects that: the invention provides a preparation method of o-nitro and polynitrobenzaldehyde, which utilizes Knoevenagel condensation reaction to prepare 1, 2-di (o-nitrophenyl) ethylene by taking needed nitrobenzaldehyde and nitrotoluene as raw materials, and then carries out high-efficiency oxidation by ozone with proper concentration to obtain the final product nitrobenzaldehyde.

A microchannel gas-liquid reaction device is adopted in the ozone oxidation process, so that the ozone oxidation process is more efficient;

in the condensation reaction of the method, only a proper amount of alkali is used for catalysis, and the intermediate product 1, 2-di (o-nitrophenyl) ethylene can be efficiently obtained by carrying out water-carrying reaction with a conventional solvent; and carrying out gas-liquid reaction by using a micro-channel reactor to finally obtain the required nitrobenzaldehyde. The method has the advantages of less raw materials, high reaction yield, less byproducts and impurities, simple and easy purification operation and convenient industrial production in a workshop. Under the conditions of environmental protection and severe safety situation of the current chemical industry, the process route can perform stable supply of the important chemical intermediates of the category in a green and environment-friendly way with extremely high atom utilization rate. Compared with the prior art of halogenation and hydrolysis, the method can avoid the corrosion of chlorine or bromine to equipment. The oxidation method of 1, 2-di (o-nitrophenyl) ethane benzoquinone introduces benzoquinone and hydroquinone product after reduction of the benzoquinone, and has great influence on product quality. Compared with the original 1, 2-di (o-nitrophenyl) ethylene ozone oxidation method, the method improves the synthesis method of the 1, 2-di (o-nitrophenyl) ethylene, and in addition, the original oxidation solvent and equipment are adjusted, so that the safety of the process is also improved.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the technical solutions of the present invention will be described in detail below. It is to be understood that the described embodiments are merely exemplary of the invention, and not restrictive of the full scope of the invention. All other embodiments, which can be derived by a person skilled in the art from the examples given herein without any inventive step, are within the scope of the present invention.