阅读说明：本技术 一种邻硝基苯甲醛的制备方法及其应用 (Preparation method and application of o-nitrobenzaldehyde ) 是由 程先波 于 2020-06-02 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,以邻硝基卞基三苯基溴化膦与所需的产品邻硝基苯甲醛为原料进行反应生成1,2-二(邻硝基苯基)乙烯,然后再用臭氧氧化成邻硝基苯甲醛。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,用碱水反应催化即可高效率得到中间产物1,2-二(邻硝基苯基)乙烯；再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。本方法所用原料少,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。在当前化工环保及安全形势严峻的情况下,该工艺路线能以极高的原子利用率绿色环保地进行该类别重要化工中间体的稳定供应。(The invention relates to a preparation method of o-nitrobenzaldehyde, which takes o-nitrobenzyl triphenyl phosphonium bromide and a required product o-nitrobenzaldehyde as raw materials to react to generate 1, 2-di (o-nitrophenyl) ethylene, and then ozone is used for oxidizing the ethylene into the o-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 the intermediate product 1, 2-di (o-nitrophenyl) ethylene can be obtained with high efficiency by using the alkali water for reaction and catalysis; 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.)

1. A preparation method of o-nitrobenzaldehyde is characterized in that o-nitrobenzyl triphenyl phosphonium bromide 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 1, 2-di (o-nitrophenyl) ethylene into the o-nitrobenzaldehyde, wherein the reaction equations are shown as the following formula 1 and formula 2:

2. the preparation method of o-nitrobenzaldehyde according to claim 1, wherein the o-nitrobenzyl triphenylphosphine bromide and o-nitrobenzaldehyde undergo a condensation reaction in the presence of a base to obtain 1, 2-bis (o-nitrophenyl) ethylene.

3. The method for preparing o-nitrobenzaldehyde according to claim 2, wherein said base comprises KOH, NaOH, K₂CO₃Or Na₂CO₃。

4. The preparation method of o-nitrobenzaldehyde according to claim 1 or 2, characterized in that the reaction solvent of o-nitrobenzyl triphenyl phosphine bromide and o-nitrobenzaldehyde is water, and the reaction time is 6-24 hours.

5. The method for preparing o-nitrobenzaldehyde according to claim 1, wherein the molar ratio of o-nitrobenzyl triphenylphosphine bromide to o-nitrobenzaldehyde is 1: 0.8 to 1: 1.2, preferably 1: 1.

6. the method for preparing o-nitrobenzaldehyde according to claim 1, wherein the reaction solvent is halogenated alkane and the reaction temperature is from-50 ℃ to 25 ℃ in the oxidation reaction of 1, 2-bis (o-nitrophenyl) ethylene.

7. The method for preparing o-nitrobenzaldehyde according to claim 6, wherein in the oxidation reaction of 1, 2-bis (o-nitrophenyl) ethylene, the reaction equipment is a microchannel gas-liquid reaction device, and the time passed by the reaction channel is 1 minute to 2 hours.

8. The method for preparing o-nitrobenzaldehyde according to claim 6, wherein said haloalkane is dichloromethane, chloroform or carbon tetrachloride.

9. Use of the process for the preparation of o-nitrobenzaldehyde according to any of claims 1 to 8, characterized in that it is suitable for the synthesis of m-nitrobenzaldehyde, p-nitrobenzaldehyde and polynitrobenzaldehyde, and also for the synthesis of benzaldehydes of the group consisting of nitro groups and other groups.

10. The method for producing o-nitrobenzaldehyde according to claim 9, wherein said polynitrobenzaldehyde is 2,4, 6-trinitrobenzaldehyde, and said benzaldehyde having a nitro group combined with other groups is 2, 6-dinitro-4-aminobenzaldehyde.

Technical Field

The invention relates to a synthesis method of pharmaceutical and chemical intermediates, and in particular relates to a preparation method and application 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. Chinese patent CN105859562 takes 1, 2-bis (o-nitrophenyl) ethane as a raw material, benzoquinone is used for oxidation to obtain o-nitrobenzyl triphenyl phosphonium bromide, 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, hydroquinone is changed after reaction, 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 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.

The invention aims to provide an application of the preparation method.

According to the method for preparing o-nitrobenzaldehyde, which is provided by the specific embodiment of the invention, o-nitrobenzyl triphenyl phosphonium bromide and o-nitrobenzaldehyde are used as raw materials to react to generate 1, 2-di (o-nitrophenyl) ethylene, and then the 1, 2-di (o-nitrophenyl) ethylene is oxidized into o-nitrobenzaldehyde by ozone, wherein the reaction equations are shown as the following formula 1 and formula 2:

according to the preparation method of the o-nitrobenzaldehyde, which is provided by the specific embodiment of the invention, the o-nitrobenzyl triphenylphosphine bromide and the o-nitrobenzaldehyde are subjected to condensation reaction in the presence of alkali to obtain the 1, 2-di (o-nitrophenyl) ethylene.

The method for preparing o-nitrobenzaldehyde according to an embodiment of the present invention, wherein the base comprises KOH, NaOH, K₂CO₃Or Na₂CO₃。

According to the preparation method of the o-nitrobenzaldehyde, which is a specific embodiment of the invention, the reaction solvent of the o-nitrobenzyl triphenyl phosphine bromide and the o-nitrobenzaldehyde is water, and the reaction time is 6-24 hours.

The preparation method of o-nitrobenzaldehyde according to the specific embodiment of the invention is characterized in that the molar ratio of o-nitrobenzyl triphenylphosphine bromide to o-nitrobenzaldehyde is 1: 0.5 to 1: 1.2.

according to the method for preparing o-nitrobenzaldehyde of the embodiment of the invention, further, the molar ratio of o-nitrobenzyl triphenyl phosphine bromide to o-nitrobenzaldehyde is 1: 1.

according to the preparation method of the o-nitrobenzaldehyde, the reaction solvent is halogenated alkane in the oxidation reaction of the 1, 2-di (o-nitrophenyl) ethylene, and the reaction temperature is-50 ℃ to 25 ℃.

According to the preparation method of o-nitrobenzaldehyde, the reaction equipment is a microchannel gas-liquid reaction device in the oxidation reaction of the 1, 2-di (o-nitrophenyl) ethylene, and the time of the reaction channel is 1 minute to 2 hours.

The method for preparing o-nitrobenzaldehyde according to an embodiment of the present invention, wherein the haloalkane is dichloromethane, chloroform or carbon tetrachloride.

According to the application of the preparation method of the o-nitrobenzaldehyde, the preparation method is suitable for synthesizing m-nitrobenzaldehyde, p-nitrobenzaldehyde or polynitrobenzaldehyde, and is also suitable for synthesizing a combination group of nitro and other groups.

The application of the method for preparing o-nitrobenzaldehyde according to the embodiment of the invention is that the polynitrobenzaldehyde is 2,4, 6-trinitrobenzaldehyde, and the combination group of the nitro and other groups is 2, 6-dinitro-4-aminobenzaldehyde.

More specifically, the raw materials for preparing the 2, 6-dinitrobenzaldehyde are 2, 6-dinitrobenzyl triphenyl phosphonium bromide and 2, 6-dinitrobenzaldehyde.

More specifically, the raw materials for preparing the 2,4, 6-trinitrobenzaldehyde are 2,4, 6-trinitrobenzyl triphenyl phosphonium bromide and 2,4, 6-trinitrobenzaldehyde.

More specifically, the raw materials for preparing the 2, 6-dinitro-4-aminobenzaldehyde are 2, 6-dinitro-4-aminobenzyl triphenylphosphine bromide and 2, 6-dinitro-4-aminobenzaldehyde.

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.

Compared with the prior art, the invention has the beneficial effects that: the invention cancels the dangerous solvent carbon disulfide in the prior art, thereby eliminating potential safety hazard; the microchannel reactor is used on the reaction equipment to replace the original reaction kettle, thereby greatly improving the safety.

The invention provides a preparation method and application of o-nitrobenzaldehyde, which takes the needed products of nitrobenzaldehyde and o-nitrobenzyl triphenyl phosphine bromide as raw materials to prepare 1, 2-di (o-nitrophenyl) ethylene, and then carries out high-efficiency oxidation by ozone with proper concentration in a micro-channel reactor to obtain the final product of nitrobenzaldehyde.

In the ozone oxidation process, a micro-channel reactor is adopted for gas-liquid reaction, so that the efficiency is higher;

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 using alkali water for reaction and catalysis; 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.

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.

In some more specific embodiments, the method for preparing o-nitrobenzaldehyde comprises:

o-nitrobenzyl triphenylphosphine bromide 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 1, 2-di (o-nitrophenyl) ethylene into the o-nitrobenzaldehyde. The reaction equations are shown in the following formulas 1 and 2:

1mol of o-nitrobenzyl triphenyl phosphonium bromide reacts with 1mol of o-nitrobenzaldehyde to generate 1mol of 1, 2-di (o-nitrophenyl) ethylene, and then the 1, 2-di (o-nitrophenyl) ethylene is oxidized into 2mol of o-nitrobenzaldehyde by ozone.