Process for synthesizing m-nitrobenzaldehyde by using fixed bed reactor
By combining a fixed-bed reactor with a solid acid catalyst and a microchannel reactor, the problems of numerous ortho- and para-position byproducts, low yield, and significant safety hazards in the production of m-nitrobenzaldehyde have been solved, achieving high-purity, high-yield, and safe industrial production.
Patent Information
- Application Number
- CN202510998864.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-07-21
- Publication Date
- 2025-11-11
AI Technical Summary
Existing technologies for producing intermediate nitrobenzaldehyde suffer from problems such as numerous ortho- and para-position byproducts, low yield and purity, significant safety hazards, and high costs, making it difficult to achieve safe, economical, and efficient industrial production.
A fixed-bed reactor packed with a solid acid catalyst was used to synthesize m-nitrobenzaldehyde through a continuous production system. The nitration reaction was carried out in conjunction with a microchannel reactor, using fuming nitric acid and benzaldehyde as raw materials. The reaction conditions were controlled to reduce the formation of by-products and improve purity and yield.
It significantly reduces the formation of ortho- and para-side byproducts, improves product purity and yield, reduces energy consumption, lowers safety risks, is suitable for industrial continuous production, reduces pollution, and lowers production costs.
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Figure CN120923352A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of organic synthesis technology. More specifically, it relates to a process for synthesizing m-nitrobenzaldehyde using a fixed-bed reactor. Background Technology
[0002] m-Nitrobenzaldehyde is an important organic synthesis intermediate used in the pharmaceutical industry to synthesize calcium iodosporate, iodopanic acid, m-hydroxylamine bitartrate, nimodipine, nicardipine, nifedipine, niludipine, etc. It is also widely used in the dye industry, photosensitive materials and surfactants.
[0003] Traditional methods for producing m-nitrobenzaldehyde are primarily carried out in stirred tanks, using benzaldehyde as a raw material and nitrating it with potassium nitrate, sodium nitrate, or nitric acid in the presence of sulfuric acid. These methods generally have low yields, typically only about 60%–80%, and generate numerous ortho- and para-position byproducts during the reaction, making purification of the m-nitrobenzaldehyde product difficult and resulting in low purity. Furthermore, the nitration reaction is highly exothermic, posing significant safety hazards such as temperature runaway and even explosions within the reactor.
[0004] In a 2005 article published in the *Journal of Zhejiang University of Technology*, Ding Chengrong et al. described a method using benzaldehyde as a raw material. The benzaldehyde reacted with isopropylamine to generate the intermediate benzaldehyde imide, which was then nitrated with mixed acid and followed by hydrolysis to obtain the target product, m-nitrobenzaldehyde, with a total yield of 88.4%. While this method reduced the formation of byproducts and improved the yield and purity, the high cost of isopropylamine made it less economically viable.
[0005] In a 2008 article published in *Petrochemical Technology*, Huang Yinhua et al. described the synthesis of m-nitrobenzaldehyde by condensing benzaldehyde with ammonia to produce tribenzaldehyde diamine (TBDA), followed by nitration with mixed acid and hydrolysis, with a total yield of 76.4%. The overall yield remains relatively low.
[0006] The nitration reaction in both of the above routes is still carried out in a traditional stirred tank. It requires the addition of amine reagents to first carry out a condensation reaction before the nitration reaction occurs. Furthermore, the problem of overheating or even explosion has not been solved, and safety hazards still exist.
[0007] In 2017, Russo et al. achieved a one-step direct nitration reaction from a mixed acid solution of benzyl alcohol and concentrated nitric acid / concentrated sulfuric acid via a microchannel reactor (Org. Process Res.Dev. 2017, 21, 357-364). Leveraging the efficient heat and mass transfer capabilities of the microchannel reactor, the selectivity of the resulting m-nitrobenzaldehyde product could reach up to 95%. Simultaneously, the continuous flow strategy effectively mitigated the safety risks of temperature runaway and explosion. However, this strategy is highly dependent on the reaction concentration. When the substrate concentration exceeds 5% w / w, the reaction system transitions from a homogeneous to a heterogeneous reaction, resulting in a large amount of unreacted benzaldehyde feedstock remaining. To maintain a homogeneous reaction, a significant excess of sulfuric acid is required, leading to increased costs and wastewater volume.
[0008] In addition, Russo, D. et al. achieved a one-step direct nitration reaction using a microchannel reactor starting from a mixed acid solution of benzaldehyde and concentrated nitric acid / concentrated sulfuric acid in 2019 (Chemical Engineering Journal, 2019, 377, 120346). However, this reaction had low selectivity, with the purity of the crude m-nitrobenzaldehyde product being 65%–75%, and the proportion of ortho-byproducts being about 25%–35%. After purification, the yield of the product was only 40%–55%.
[0009] Therefore, developing an industrial production method for m-nitrobenzaldehyde that produces fewer ortho- and para-byproducts, has high yield and purity, is simple to operate, produces less pollution, and is highly safe is an urgent problem to be solved. Summary of the Invention
[0010] The technical problem to be solved by the present invention is to overcome the defects and deficiencies of the existing technology and provide a process for synthesizing m-nitrobenzaldehyde using a fixed-bed reactor. This process provides a stable, rapid, and scale-up solution that can effectively reduce the formation of ortho- and para-side byproducts, improve reaction yield, significantly reduce energy consumption, is environmentally friendly, and is suitable for industrial production.
[0011] The purpose of this invention is to provide a process for synthesizing m-nitrobenzaldehyde using a fixed-bed reactor.
[0012] The above-mentioned objective of this invention is achieved through the following technical solution:
[0013] A process for synthesizing m-nitrobenzaldehyde using a fixed-bed reactor comprises a continuous production system consisting of a fixed-bed reactor packed with a solid acid catalyst. The specific steps are as follows:
[0014] Step 1: Benzaldehyde and fuming nitric acid are introduced into a fixed-bed reactor at a certain flow rate ratio to carry out a nitration reaction and obtain a nitration reaction solution;
[0015] Step 2: Pass the nitration reaction solution into water to precipitate crude m-nitrobenzaldehyde. After filtration and washing, recrystallize with an organic solvent to obtain the final product m-nitrobenzaldehyde.
[0016] Its chemical reaction formula is:
[0017]
[0018] Preferably, in step one, the flow rate of the material being fed into the fixed-bed reactor is controlled so that the molar ratio of benzaldehyde to nitric acid is 1:(1.0 to 3.0), wherein the nitric acid is fuming nitric acid with a concentration of 98%. More preferably, the molar ratio of benzaldehyde to nitric acid is 1:(1.5 to 2.0).
[0019] Preferably, the nitration reaction temperature in the fixed-bed reactor in step one is 20–80°C, more preferably, the temperature is controlled at 50–70°C. Preferably, the residence time of the mixed reactants in the fixed-bed reactor is 0.1–10 min, more preferably, the residence time is 1–3 min.
[0020] Preferably, the solid acid catalyst in step one is selected from any one of silicotungstic acid, phosphotungstic acid, or phosphomolybdic acid; more preferably, the solid acid catalyst is selected from silicotungstic acid.
[0021] Preferably, the organic solvent in step two is any one of methanol, ethanol, isopropanol, and dichloromethane; more preferably, the organic solvent is any one of methanol and ethanol.
[0022] Preferably, the first microchannel reactor and the second continuous reactor are made of any one of 304L, 316L, 904L stainless steel, Hastelloy, silicon carbide, PTFE, and PEEK; more preferably, they are made of any one of 304L, 316L, 904L stainless steel, and Hastelloy. Preferably, the inner diameter of the pipe is in the range of 1–50 mm; more preferably, it is in the range of 4–20 mm.
[0023] The present invention has the following beneficial effects:
[0024] This invention utilizes a solid acid catalyst to replace traditional liquid concentrated sulfuric acid, which not only improves the selectivity of the reaction, reduces the formation of ortho and para byproducts, shortens the reaction time, and improves the purity and yield of the product, but also reduces the pollution problems caused by the use of liquid concentrated sulfuric acid. At the same time, the solid acid is less corrosive and can be repeatedly recycled, further reducing pollution emissions.
[0025] Because the heat transfer efficiency is significantly improved compared to a batch reactor, and the material retention in the reactor is significantly reduced, for nitration reactions that are highly exothermic and involve inherently hazardous materials, the risk of runaway temperatures is reduced, and the serious consequences of accidents such as material spills and explosions are mitigated, making the process inherently safe. The continuous operation of the microchannel reactor also improves operational convenience, making it suitable for industrial continuous production.
[0026] Using a fixed-bed reactor for continuous synthesis allows for uninterrupted production, a high degree of automation, and eliminates the need for external intervention. This results in high spatial and temporal efficiency, significantly reducing the number of operators and labor intensity, and substantially lowering production costs. Attached Figure Description
[0027] Figure 1 This is a flowchart. Detailed Implementation
[0028] The present invention will be further illustrated below with reference to specific embodiments, but the embodiments do not limit the present invention in any way. Unless otherwise specified, the reagents, methods, and equipment used in the present invention are conventional reagents, methods, and equipment in this technical field.
[0029] Unless otherwise specified, all reagents and materials used in the following examples are commercially available.
[0030] Example 1
[0031] A process for synthesizing m-nitrobenzaldehyde using a fixed-bed reactor comprises a continuous production system consisting of a fixed-bed reactor packed with a solid acid catalyst. The specific steps are as follows:
[0032] Benzaldehyde (flow rate 30 g / min) and 98% fuming nitric acid (flow rate 27 g / min) were fed into a fixed-bed reactor (0.5 m long, 12 mm inner diameter). The reactor packing material was 50 g of silicotungstic acid. The reactor temperature was controlled at 60 °C, and the residence time of the mixture in the reactor was 1 minute. Subsequently, the obtained nitration reaction solution was introduced into water to precipitate the crude product. The temperature was then lowered to 5 °C, and the reaction was carried out for a total of 30 minutes. The precipitated solid was filtered, washed with water, and dried to obtain crude m-nitrobenzaldehyde. The crude product was recrystallized from ethanol to obtain m-nitrobenzaldehyde product, which was pale yellow in appearance. After drying, 1076 g of m-nitrobenzaldehyde was obtained with a purity of 99.8% and a yield of 84%.
[0033] Example 2
[0034] This embodiment is basically the same as Example 1, except that the temperature of the fixed-bed reactor is set to 50°C. The obtained m-nitrobenzaldehyde weighed 1051 g, with a purity of 99.8% and a yield of 82%.
[0035] Example 3
[0036] This embodiment is basically the same as Embodiment 1, except that the packing material in the fixed bed in this embodiment is phosphomolybdic acid, and the mass of the prepared m-nitrobenzaldehyde is 985g, the purity is 99.8%, and the yield is 77%.
[0037] Example 4
[0038] This embodiment is basically the same as Embodiment 1, except that the packing material in the fixed bed in this embodiment is phosphotungstic acid, and the mass of the prepared m-nitrobenzaldehyde is 974g, the purity is 99.9%, and the yield is 76%.
[0039] Example 5
[0040] To verify the continuous stability of the silicotungstic acid catalyst in Example 1, the catalyst was continuously fed for 24 hours, with each batch consisting of 4 hours. The product yield of each batch is shown in Table 1.
[0041] Table 1. Stability test of catalysts
[0042] batch time Product quality purity yield 1 0～4h 8.72kg 99.7％ 85％ 2 4～8h 8.61kg 99.7％ 84％ 3 8～12h 8.43kg 99.8％ 82％ 4 12～16h 8.39kg 99.6％ 82％ 5 16～20h 8.34kg 99.5％ 81％ 6 20～24h 8.31kg 99.6％ 81％
[0043] As can be seen from Table 1, the purity of the product obtained by using silicotungstic acid catalyst in the fixed-bed reactor for the synthesis of m-nitrobenzaldehyde in this invention is relatively stable, and the yield is consistently above 80%.
[0044] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.
Claims
1. A process for synthesizing m-nitrobenzaldehyde using a fixed-bed reactor, characterized in that, A continuous production system is constructed using a fixed-bed reactor packed with a solid acid catalyst. The specific steps are as follows: Step 1: Benzaldehyde and nitric acid are introduced into a fixed-bed reactor at a certain flow rate ratio to carry out a nitration reaction and obtain a nitration reaction solution; Step 2: Pass the nitration reaction solution into water to precipitate crude m-nitrobenzaldehyde. After filtration and washing, recrystallize with an organic solvent to obtain the final product m-nitrobenzaldehyde. Its chemical reaction formula is:
2. The process as described in claim 1, characterized in that, In step one, the flow rate of the material being fed into the fixed-bed reactor is controlled. The molar ratio of benzaldehyde to nitric acid is 1:(1.0-3.0); the nitric acid is 98% fuming nitric acid.
3. The process as described in claim 2, characterized in that, The molar ratio of benzaldehyde to nitric acid is 1:(1.5 to 2.0).
4. The process as described in claim 1 or 2, characterized in that: In step one, the nitration reaction temperature in the fixed-bed reactor is 20–80℃, and the reaction residence time is 0.1–10 min.
5. The process as described in claim 4, characterized in that: In step one, the nitration reaction temperature in the fixed-bed reactor is 50–70°C, and the reaction residence time is 1–3 min.
6. The process as described in claim 1, characterized in that: In step one, the solid acid catalyst is selected from any one of silicotungstic acid, phosphotungstic acid, or phosphomolybdic acid.
7. The process as described in claim 6, characterized in that: In step one, the solid acid catalyst is selected from silicotungstic acid.
8. The process as described in claim 1, characterized in that, The organic solvent mentioned in step two is any one or a mixture of any two of methanol, ethanol, isopropanol, and dichloromethane.
9. The process as described in claim 8, characterized in that, The organic solvent is either methanol or ethanol.
10. The process as described in claim 1, characterized in that, The fixed-bed reactor is made of any one of the following materials: 304L, 316L, 904L stainless steel, Hastelloy, glass, silicon carbide, PTFE, and PEEK, and the inner diameter of the pipe ranges from 1 to 50 mm.