A method for continuous synthesis of crotonic acid

Abstract

This invention discloses a method for the continuous synthesis of crotonic acid, comprising the following steps: sodium chlorite and acidic hydrogen peroxide are rapidly mixed in a microreactor, and then directly introduced into the next microreactor to be mixed with an organic solution containing crotonaldehyde. The oxidation reaction is completed under high temperature and high pressure conditions. The reaction solution is then cooled, depressurized, and subjected to continuous gas-liquid separation. The resulting liquid reacts with a reducing agent in a tubular reactor to quench excess oxides. The resulting reaction solution is then subjected to vacuum distillation to recover the organic solvent. The remaining liquid is decolorized and recrystallized to obtain a high-purity crotonic acid product. This method effectively solves the problems of cumbersome process, low production efficiency, dangerous reaction, and process instability in existing batch-type crotonaldehyde oxidation processes. It significantly improves the conversion rate and selectivity of the reaction, shortens the reaction time, and has the advantages of simple process, short production cycle, continuous production, and intrinsic safety.

Description

Technical Field

[0001] This invention belongs to the field of fine chemical raw material synthesis technology, specifically relating to a method for the continuous synthesis of crotonic acid. Background Technology

[0002] Crotonic acid, a short-chain α,β-unsaturated fatty acid, has wide applications in functional materials and medicine.

[0003] Currently, crotonic acid is mainly synthesized through the oxidation of crotonaldehyde, using both gaseous and liquid oxidants. Industrially, gaseous oxidants, such as oxygen and air, are more commonly used. Cheng Shaoguo et al. (CN1415594A) reported a process using precious metal silver as a catalyst to oxidize crotonaldehyde in a tower with air, achieving a yield of 75%. However, this process suffers from high catalyst costs, cumbersome operation steps, and long reaction cycles. Currently, reaction systems using gaseous oxidants consistently struggle to address the slow gas-liquid two-phase reaction rate and low feed conversion rate, requiring additional feed recovery stages, significantly increasing production costs and equipment investment. While liquid oxidants such as organic peroxides can effectively improve the reaction rate, reaction selectivity is typically poor, and batch processes pose significant process hazards, making industrial scale-up difficult.

[0004] For the selective oxidation of α,β-unsaturated aldehydes to unsaturated acids, the modified Pinnick reaction, using chlorite as the oxidant and hydrogen peroxide as the hypochlorous acid scavenger, is a promising choice for small-scale trials. The mainstream reaction mechanism (R.Soc.OpenSci.,7,2020,191568) involves the protonation of the aldehyde carbonyl group under acidic conditions, simultaneously triggering the attack of the carbonyl group by the chlorite ion, forming a one-molecule six-membered ring intermediate. With ring cleavage, a one-molecule unsaturated acid and the byproduct hypochlorite ion are generated. The hypochlorite ion can be reduced to chloride ions by hydrogen peroxide, thus reducing its damaging effect on the double bond. However, this reaction process is highly hazardous due to the presence of chlorite and the generation of oxygen. Traditional batch reactor processes have poor controllability and require slow, low-temperature operation, resulting in low reaction efficiency. Existing literature (J.Org.Chem.,51,1986,567) reports that this reaction has high conversion and selectivity for substrates with poor water solubility, but poor reaction effect and selectivity for substrates with good water solubility such as crotonaldehyde. Summary of the Invention

[0005] The purpose of this invention is to provide a method for the continuous preparation of crotonic acid using a liquid-phase oxidant, aiming to solve the problems of complex process, low production efficiency and poor selectivity in the existing crotonic acid synthesis process, improve process controllability and safety, and achieve process enhancement in crotonic acid synthesis.

[0006] The technical solution of this invention is as follows:

[0007] A method for the continuous preparation of crotonic acid includes the following steps:

[0008] (1) The hydrogen peroxide-containing solution A and the sodium chlorite-containing solution B are continuously fed into microreactor No. 1 to obtain reaction solution C;

[0009] (2) The reaction solution C is directly mixed and reacted with the crotonaldehyde-containing feed solution D by continuously passing it into the No. 2 microreactor to obtain the reaction solution E containing gas.

[0010] (3) The reaction liquid E enters the continuous gas-liquid separator after passing through the condenser and pressure relief valve to remove the gas and obtain the feed liquid F;

[0011] (4) After continuous mixing of feed solution F and feed solution G containing reducing agent, the mixture is directly introduced into a tubular reactor to react and obtain reaction solution H;

[0012] (5) The reaction solution H enters the evaporator, and after the organic solvent is recovered, the feed solution I is obtained. Then, after post-treatment and purification, the product crotonic acid is obtained.

[0013] In step (1), the feed solution A is an acidic solution of hydrogen peroxide, with a mass fraction of 20-50 wt.% and a pH of 0.1-5.0, more preferably 1.0-4.7. The acidity regulator is one or more of phosphoric acid, sodium dihydrogen phosphate, potassium dihydrogen sulfate, sulfuric acid, hydrochloric acid, and nitric acid.

[0014] In step (1), the feed solution B is an aqueous solution of sodium chlorite, and the mass fraction of sodium chlorite is 30-50 wt.%.

[0015] In step (1), the characteristic size of the No. 1 microreactor is less than 1 mm, and more preferably between 0.1 and 0.6 mm, the mixing time is 0.1 s to 1 s, the residence time is 1 s to 30 s, and the reaction temperature is -10℃ to 20℃.

[0016] In step (2), the feed solution C is an organic solution of crotonaldehyde, with a mass fraction of 30-70 wt.%. The organic solvent in the organic solution is a water-soluble organic solvent, preferably one of acetonitrile, methanol, ethanol, isopropanol, tert-butanol, etc.; as a further preferred option, the organic solvent is acetonitrile or tert-butanol.

[0017] The molar ratio of hydrogen peroxide, sodium chlorite and crotonaldehyde is (1.0-3.0):(1.0-2.0):1, preferably (1.1-2.0):(1.0-1.2):1.

[0018] In step (2), the characteristic size of the No. 2 microreactor is less than 1.5 mm, the mixing time is 0.1 s to 1 s, the reaction residence time is 1 min to 20 min, the reaction temperature is 60 ℃ to 120 ℃, and the system pressure is 1 MPa to 3 MPa.

[0019] In step (4), the reducing agent contained in the liquid G is one of sodium sulfite, sodium bisulfite, and sodium thiosulfate.

[0020] In step (4), the reaction temperature of the tubular reactor is 10-30℃ and the reaction residence time is 0.1-5min.

[0021] In step (5), the post-processing steps include activated carbon decolorization and recrystallization.

[0022] Compared with the prior art, the present invention has the following advantages and outstanding technical effects:

[0023] This invention utilizes the advantages of rapid mixing and continuous reaction in microreactors to achieve "on-demand production" of the hazardous reactive substance chlorophyll, effectively solving the problems of cumbersome operation steps, low reagent utilization, and significant safety hazards caused by the slow addition of reaction reagents in traditional batch reactor processes. Based on the characteristic that the activation energy of the main reaction is greater than that of the side reactions, and leveraging the advantages of high heat and mass transfer efficiency and process control in microreactors, this method significantly increases the reaction temperature and shortens the reaction time from several hours to just a few minutes, effectively improving reaction selectivity and yield. The raw material conversion rate (>95%) of this continuous process is far higher than that of traditional gas oxidation processes, eliminating the need to recover crotonaldehyde raw material and simplifying the process steps. The use of a continuous gas-liquid separation unit for oxygen and the reaction liquid, as well as a continuous hydrogen peroxide quenching unit, effectively reduces the safety risks of the process. Attached Figure Description

[0024] Figure 1 This is a process flow diagram for synthesizing crotonic acid according to the present invention. Detailed Implementation

[0025] This invention provides a method for the continuous preparation of crotonic acid, and the invention will be further illustrated below with reference to the embodiments.

[0026] Example 1

[0027] Weigh 60g of sodium dihydrogen phosphate and dissolve it in 170g of 30% hydrogen peroxide (pH≈4.7) to obtain solution A; weigh 136g of sodium chlorite (80%) and dissolve it in 441g of water to obtain solution B; add 180g of acetonitrile to 70g of crotonaldehyde to obtain solution D; weigh 50g of sodium bisulfite and dissolve it in 200g of water to obtain solution G. Feed solutions A and B were pumped into microchannel reactor No. 1 (VICI VALCO, T-type, characteristic dimension 0.5 mm) using a horizontal flow pump. The reaction temperature was 10℃, the flow rate of feed solution A was 6.9 g / min, the flow rate of feed solution B was 16.5 g / min, and the flow rate of feed solution D was 7.5 g / min, with a residence time of 2 s. The resulting reaction solution C was directly fed into microreactor No. 2 (Shenshi, model 0010WR, characteristic dimension 1 mm, material Hastelloy) to mix and react with feed solution D. The reaction temperature was 90℃, the residence time was 4 min, and the pressure was 2.0 MPa. After cooling by a condenser and depressurization by a pressure relief valve, the reaction solution entered the gas-liquid separation unit. The resulting feed solutions F and G were pumped into a 316L reaction coil (outer diameter 3 mm, inner diameter 2 mm, total length 50 m, atmospheric pressure) at flow rates of 30 g / min and 7.5 g / min, respectively, using horizontal flow pumps. The water bath temperature outside the coil was 20℃. The reaction solution H flowing out of the coil was separated from the reaction solution by vacuum distillation to obtain acetonitrile, which was then recycled. The remaining solution I was decolorized with activated carbon and recrystallized to obtain 70.9 g of pure crotonic acid with a GC purity >99% and a yield of 82.5%.

[0028] Example 2

[0029] Weigh 60g of sodium dihydrogen phosphate and dissolve it in 170g of 30% hydrogen peroxide to obtain solution A; weigh 136g of sodium chlorite (80%) and dissolve it in 441g of water to obtain solution B; add 180g of acetonitrile to 70g of crotonaldehyde to obtain solution D; weigh 50g of sodium bisulfite and dissolve it in 200g of water to obtain solution G. Feed solutions A and B were pumped into microchannel reactor No. 1 (VICI VALCO, T-type, characteristic dimension 0.5 mm) using a horizontal flow pump. The reaction temperature was 10℃, the flow rate of feed solution A was 6.9 g / min, the flow rate of feed solution B was 16.5 g / min, and the flow rate of feed solution D was 7.5 g / min, with a residence time of 2 s. The resulting reaction solution C was directly fed into microreactor No. 2 (Shenshi, model 0010WR, characteristic dimension 1 mm, material Hastelloy) to mix and react with feed solution D. The reaction temperature was 70℃, the residence time was 8 min, and the pressure was 2.0 MPa. After cooling by a condenser and depressurization by a pressure relief valve, the reaction solution entered the gas-liquid separation unit. The resulting feed solutions F and G were pumped into a 316L reaction coil (outer diameter 3 mm, inner diameter 2 mm, total length 50 m, atmospheric pressure) at flow rates of 30 g / min and 7.5 g / min, respectively, using horizontal flow pumps. The water bath temperature outside the coil was 20℃. The reaction solution H flowing out of the coil was separated from the reaction solution by vacuum distillation to obtain acetonitrile, which was then recycled. The remaining solution I was decolorized with activated carbon and recrystallized to obtain 65.8 g of pure crotonic acid with a GC purity >99% and a yield of 76.5%.

[0030] Example 3

[0031] Weigh 30g of phosphoric acid and dissolve it in 170g of 30% hydrogen peroxide (pH≈1.0) to make solution A; weigh 136g of sodium chlorite (80%) and dissolve it in 441g of water to make solution B; add 180g of acetonitrile to 70g of crotonaldehyde to make solution D; weigh 50g of sodium bisulfite and dissolve it in 200g of water to make solution G. Feed solutions A and B were pumped into microchannel reactor No. 1 (VICI VALCO, T-type, characteristic dimension 0.5 mm) using a horizontal flow pump. The reaction temperature was 10℃, the flow rate of feed solution A was 6 g / min, the flow rate of feed solution B was 16.5 g / min, and the flow rate of feed solution D was 7.5 g / min, with a residence time of 2 s. The resulting reaction solution C was directly fed into microreactor No. 2 (Shenshi, model 0010WR, characteristic dimension 1 mm, material Hastelloy) to mix and react with feed solution D. The reaction temperature was 90℃, the residence time was 4 min, and the pressure was 2.0 MPa. After cooling by a condenser and depressurization by a pressure relief valve, the reaction solution entered the gas-liquid separation unit. The resulting feed solutions F and G were pumped into a 316L reaction coil (outer diameter 3 mm, inner diameter 2 mm, total length 50 m, atmospheric pressure) at flow rates of 30 g / min and 7.5 g / min, respectively, using horizontal flow pumps. The water bath temperature outside the coil was 20℃. The reaction solution H flowing out of the coil was separated from the reaction solution by vacuum distillation to obtain acetonitrile, which was then recycled. The remaining solution I was decolorized with activated carbon and recrystallized to obtain 67.3 g of pure crotonic acid with a GC purity >99% and a yield of 78.2%.

[0032] Example 4

[0033] Weigh 60g of sodium dihydrogen phosphate and dissolve it in 120g of 50% hydrogen peroxide to obtain solution A; weigh 136g of sodium chlorite (80%) and dissolve it in 441g of water to obtain solution B; add 180g of acetonitrile to 70g of crotonaldehyde to obtain solution D; weigh 50g of sodium bisulfite and dissolve it in 200g of water to obtain solution G. Feed solutions A and B were pumped into microchannel reactor No. 1 (VICI VALCO, T-type, characteristic dimension 0.5 mm) using a horizontal flow pump. The reaction temperature was 5℃, the flow rate of feed solution A was 5.4 g / min, the flow rate of feed solution B was 16.5 g / min, and the flow rate of feed solution D was 7.5 g / min. The residence time was 2 s. The resulting reaction solution C was directly fed into microreactor No. 2 (Shenshi, model 0010WR, characteristic dimension 1 mm, material Hastelloy) to mix and react with feed solution D. The reaction temperature was 90℃, the residence time was 4 min, and the pressure was 2.0 MPa. After cooling by a condenser and depressurization by a pressure relief valve, the reaction solution entered the gas-liquid separation unit. The resulting feed solutions F and G were pumped into a 316L reaction coil (outer diameter 3 mm, inner diameter 2 mm, total length 50 m, atmospheric pressure) at flow rates of 28 g / min and 7 g / min, respectively, using horizontal flow pumps. The water bath temperature outside the coil was 20℃. The reaction solution H flowing out of the coil was separated from the reaction solution by vacuum distillation to obtain acetonitrile, which was then recycled. The remaining solution I was decolorized with activated carbon and recrystallized to obtain 73.3 g of pure crotonic acid with a GC purity >99% and a yield of 85.2%.

[0034] Example 5

[0035] 60g of sodium dihydrogen phosphate was dissolved in 120g of 50% hydrogen peroxide to obtain solution A; 136g of sodium chlorite (80%) was dissolved in 441g of water to obtain solution B; 180g of tert-butanol was added to 70g of crotonaldehyde to obtain solution D; 50g of sodium bisulfite was dissolved in 200g of water to obtain solution G. Solutions A and B were pumped into microchannel reactor No. 1 using a horizontal flow pump. The reaction temperature was 10℃, the flow rate of solution A was 5.4g / min, the flow rate of solution B was 16.5g / min, the flow rate of solution D was 7.5g / min, and the residence time was 2s. The resulting reaction solution C was directly introduced into microreactor No. 2 to mix and react with solution D. The reaction temperature was 90℃, the residence time was 4min, and the pressure was 2.0MPa. After cooling by a condenser and depressurization by a pressure relief valve, the reaction solution entered the gas-liquid separation unit. After gas-liquid separation, the resulting feed solutions F and G were pumped into a 316L reaction coil (outer diameter 3mm, inner diameter 2mm, total length 50m, atmospheric pressure) at flow rates of 28g / min and 7g / min, respectively, using a horizontal flow pump. The external water bath temperature of the coil was 20℃. The reaction solution H flowing out of the coil was separated from the reaction solution by vacuum distillation to obtain tert-butanol for recycling. The remaining feed solution I was decolorized with activated carbon and recrystallized to obtain 75.3g of pure crotonic acid with a GC purity >99% and a yield of 87.6%.

[0036] Comparative Example 1

[0037] Dissolve 7g of crotonaldehyde in 18g of acetonitrile, add 17g of 30% hydrogen peroxide, and add 6g of sodium dihydrogen phosphate. Cool to approximately 10℃, control the temperature, and add 55g of 20% sodium chlorite aqueous solution dropwise while stirring. Oxygen continuously escapes, and the addition is completed in about 2 hours. Continue stirring until no new bubbles are generated (about 1 hour). Add 5g of sodium bisulfite to quench the reaction. Evaporate the acetonitrile under reduced pressure. After decolorization with activated carbon and recrystallization, 5.6g of pure crotonic acid is obtained, with a GC purity >99% and a yield of 65%.

[0038] The results of the above embodiments and comparative examples show that by using the continuous generation method of the present invention, the product yield is significantly improved, the reaction efficiency is greatly enhanced, and more product is obtained per unit time.

Claims

1. A method for preparing crotonic acid, characterized in that, Includes the following steps: (1) The hydrogen peroxide-containing solution A and the sodium chlorite-containing solution B are continuously fed into microreactor No. 1 to obtain reaction solution C; In step (1), the mixing time in the No. 1 microreactor is 0.1s~1s, the residence time is 1s~30s, and the reaction temperature is -10℃~20℃; The feed solution A is an acidic solution formed by adding an acidity regulator to hydrogen peroxide, with a pH of 0.1-5.0; (2) The reaction solution C is directly and continuously fed into the No. 2 microreactor to mix and react, resulting in a reaction solution E containing gas; In step (2), the reaction temperature in microreactor No. 2 is 60℃~120℃ and the system pressure is 1MPa~3MPa; (3) The reaction liquid E enters the continuous gas-liquid separator after passing through the condenser and pressure relief valve to remove the gas and obtain the feed liquid F; (4) After continuous mixing of feed solution F and feed solution G containing reducing agent, the mixture is directly introduced into a tubular reactor to react and obtain reaction solution H; (5) The reaction solution H enters the evaporator, and after the organic solvent is recovered, the feed solution I is obtained. Then, after post-treatment and purification, the product crotonic acid is obtained.

2. The method according to claim 1, characterized in that, In step (1), the hydrogen peroxide has a mass fraction of 20~50 wt.%; The acidity regulator is one or more of phosphoric acid, sodium dihydrogen phosphate, potassium dihydrogen sulfate, sulfuric acid, hydrochloric acid, and nitric acid.

3. The method according to claim 1, characterized in that, In step (1), the feed solution B is an aqueous solution of sodium chlorite, and the mass fraction of sodium chlorite is 30~50 wt.%.

4. The method according to claim 1, characterized in that, In step (1), the characteristic size of the No. 1 microreactor is less than 1 mm.

5. The method according to claim 1, characterized in that, In step (2), the feed solution C is an organic solution of crotonaldehyde, with a mass fraction of 30~70 wt.% of crotonaldehyde. The organic solvent in the organic solution is one of acetonitrile, methanol, ethanol, isopropanol, and tert-butanol.

6. The method according to claim 1, characterized in that, The molar ratio of hydrogen peroxide, sodium chlorite and crotonaldehyde is (1.0-3.0):(1.0-2.0):

1.

7. The method according to claim 6, characterized in that, The molar ratio of hydrogen peroxide, sodium chlorite and crotonaldehyde is (1.1-2.0):(1.0-1.2):

1.

8. The method according to claim 1, characterized in that, In step (2), the characteristic size of the No. 2 microreactor is less than 1.5 mm, the mixing time is 0.1 s to 1 s, and the reaction residence time is 1 min to 20 min.

9. The method according to claim 1, characterized in that, In step (4), the reducing agent contained in the feed liquid G is one of sodium sulfite, sodium bisulfite, and sodium thiosulfate.

10. The method according to claim 1, characterized in that, In step (4), the inner diameter of the tubular reactor is 1mm-20mm, the reaction temperature is 10~30℃, and the reaction residence time is 0.1~5min.

11. The method according to claim 1, characterized in that, In step (5), the post-processing steps include activated carbon decolorization and recrystallization.

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