A method for synthesizing 8-hydroxyquinoline

Abstract

The application discloses a synthesis method of 8-hydroxyquinoline, and relates to the technical fields of pesticides and organic synthesis. The method is characterized in that 8-hydroxyquinoline is prepared from o-amino phenol and propylene aldehyde as main raw materials, o-nitrophenol as an oxidant and hydrochloric acid as a catalyst. The method is suitable for industrial production of 8-hydroxyquinoline. The reaction of o-amino phenol and propylene aldehyde is realized through static mixing continuous reaction, the utilization rate of propylene aldehyde is improved, the generation of three wastes is reduced, and the method is environment-friendly. The 8-hydroxyquinoline is prepared through oxidation of an intermediate by o-nitrophenol, o-amino phenol is obtained at the same time, propylene aldehyde is continuously added to synthesize 8-hydroxyquinoline, the side reaction of excessive propylene aldehyde and the intermediate is avoided, the yield of 8-hydroxyquinoline is improved, the generation of polymers is reduced, the utilization rate of propylene aldehyde is high in the whole process, and the yield of 8-hydroxyquinoline is high.

Description

Technical Field

[0001] This invention relates to the fields of pesticide and organic synthesis technology, specifically a method for synthesizing 8-hydroxyquinoline. Background Technology

[0002] 8-Hydroxyquinoline, also known as hydroxyquinoline or quinolinol, is an important intermediate in pharmaceuticals, dyes, and pesticides. It is mainly used in the production of pharmaceutical intermediates such as quinoline and chloroquinoline, as well as intermediates in dyes and pesticides. Its sulfate and copper salts are excellent preservatives, disinfectants, and antitoxic agents, and are also complexometric titration indicators in chemical analysis. It is a key raw material for low-toxicity, high-efficiency pesticides and certain pharmaceuticals.

[0003] Currently, the main methods for producing 8-hydroxyquinoline are the quinoline sulfonation alkali fusion method and the Skraup synthesis method.

[0004] Alkali fusion methods for 8-quinoline sulfonic acid include atmospheric pressure high-temperature alkali fusion and medium-temperature alkali fusion. The fusion temperature is 230~360℃, the reaction rate is fast and the time is short, but some 8-quinoline sulfonic acid decomposes, and the quinoline odor is relatively strong during the alkali fusion process. During atmospheric pressure alkali fusion, because the generated 8-hydroxyquinoline is easily oxidized by air, steam protection is required. The quinoline sulfonation alkali fusion method is relatively mature, but it consumes a lot of steam, requires a high reaction temperature, and if the temperature is not well controlled, the reaction is slow, the yield is low, and the material flowability is poor. The sulfonation alkali fusion process requires a large amount of acid and alkali, resulting in a large amount of wastewater. Quinoline as a raw material itself is a limited resource, thus restricting the application of the sulfonation alkali fusion method.

[0005] The Skraup synthesis method uses o-aminophenol, concentrated sulfuric acid, glycerol, and o-nitrophenol to produce 8-hydroxyquinoline upon co-heating. Patent CN 105777630 A uses sufficient formic acid to pre-dilute acrolein, and also incorporates zeolite molecular sieves, resulting in high amounts of o-nitrophenol and acrolein. CN 109053569 B uses a cobalt oxime chelate photocatalyst and eosin Y photosensitizer, making it unsuitable for industrial production. While the Skraup synthesis method uses low-cost, non-toxic, or low-toxicity raw materials, it produces a large amount of waste salt from sulfuric acid dehydration, and often results in excess glycerol, significant polymerization, and difficult-to-treat reactor residue.

[0006] Therefore, it is of great significance to find a method for preparing 8-hydroxyquinoline that is easy to control, has a short reaction time, few byproducts, and a high yield. Summary of the Invention

[0007] To address the problems of low yield, numerous side reactions, and large amounts of waste in the preparation of 8-hydroxyquinoline in existing technologies, the present invention aims to provide a method for synthesizing 8-hydroxyquinoline.

[0008] To achieve the above objectives, the present invention employs the following technical solution:

[0009] A synthetic method for 8-hydroxyquinoline, the synthetic route is as follows:

[0010]

[0011] A method for synthesizing 8-hydroxyquinoline includes the following steps:

[0012] ① Dissolve o-aminophenol and hydroquinone in acetic acid-hydrochloric acid solution to obtain solution A; dissolve acrolein in acetic acid to obtain solution B; add solution A and solution B to a static mixer and obtain intermediate 1,2-dihydro-8-hydroxyquinoline at 90~110℃.

[0013] The mass ratio of o-aminophenol to hydroquinone in solution A is 1:0.005~0.02;

[0014] The molar ratio of o-aminophenol to acrolein is 1:1 to 1.05;

[0015] ② Add o-nitrophenol to the first reaction vessel, then add second acetic acid, start stirring to dissolve o-nitrophenol, heat to 110~130℃, add the intermediate 1,2-dihydro-8-hydroxyquinoline obtained in step ① to the first reaction vessel to obtain a reaction solution containing the product 8-hydroxyquinoline and o-aminophenol.

[0016] The molar ratio of o-nitrophenol to o-aminophenol in step ① is 0.4~0.6:1;

[0017] ③ Dissolve the second acrolein in the second acetic acid and add it to the reaction solution of step ② in several portions. React at 110~130℃. The o-aminophenol obtained in step ② reacts with the second acrolein, and then continues to react with o-nitrophenol to obtain 8-hydroxyquinoline.

[0018] The mass ratio of the second acrolein to the second acetic acid is 1:3~6;

[0019] The molar ratio of acrolein to o-nitrophenol in the second step is 1.05~1.1:1.

[0020] Preferably, the acetic acid-hydrochloric acid solution is obtained by mixing an aqueous solution of acetic acid and hydrochloric acid in a mass ratio of 5~10:2.2~3.5; the mass concentration of the aqueous solution of hydrochloric acid is 30~35%.

[0021] Preferably, the mass ratio of o-aminophenol to acetic acid-hydrochloric acid solution in solution A is 1:7.2~13.5.

[0022] Preferably, the mass ratio of the first acrolein to the first acetic acid in solution B is 1:3~6.

[0023] Preferably, the reaction temperature of the first reactor in steps ② and ③ is 115~125℃.

[0024] Preferably, the mass ratio of the first acrolein to the first acetic acid in solution B is 1:4~5.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] This invention discloses a method for synthesizing 8-hydroxyquinoline, using o-aminophenol and acrolein as main raw materials. Under hydrochloric acid catalysis, o-nitrophenol is used as an oxidant to prepare 8-hydroxyquinoline, providing a method suitable for industrial-scale synthesis. This method reduces the problem of high polymer yield due to excess acrolein, simplifies the separation of 8-hydroxyquinoline, results in high product quality, and minimizes waste. In this technical solution, the yield in the first step reaches 96%, the yield in the third step reaches 92%, the total yield of 8-hydroxyquinoline reaches 94.6%, the utilization rate of acrolein reaches 90.4%, and the final reaction of o-aminophenol and o-nitrophenol is complete.

[0027] The reaction steps of this invention are ingeniously designed, significantly improving the utilization rate of acrolein. Experiments revealed that acrolein and o-aminophenol undergo an addition reaction to obtain an intermediate; this step has a relatively fast reaction rate, approaching seconds. The intermediate, under the action of an oxidant, yields 8-hydroxyquinoline. This step is a rate-controlled step, and the intermediate is highly susceptible to further addition reactions due to the influence of acrolein. Therefore, in a batch reactor, the excess acrolein reacts with the intermediate, leading to a reduced acrolein utilization rate, higher polymer yield, and a lower 8-hydroxyquinoline yield.

[0028] Therefore, this invention, through analysis and experimental verification of the reaction process, proposes a stepwise reaction scheme. The reaction of o-aminophenol and acrolein is achieved through continuous static mixing, improving the utilization rate of acrolein, reducing the generation of waste, and making it environmentally friendly. 8-Hydroxyquinoline is prepared by oxidizing the o-nitrophenol intermediate, simultaneously obtaining o-aminophenol. Further addition of acrolein avoids side reactions from excess acrolein and intermediates, improving the yield of 8-hydroxyquinoline and reducing polymer formation. The entire process exhibits high acrolein utilization and a high yield of 8-hydroxyquinoline. Detailed Implementation

[0029] The purpose of this invention is to provide a method for synthesizing 8-hydroxyquinoline. The invention will be further described below with reference to specific embodiments.

[0030] The concentrations of the raw materials listed in this embodiment are all mass concentrations. Example 1

[0031] A method for synthesizing 8-hydroxyquinoline, characterized by comprising the following steps:

[0032] ① Dissolve 222.7g of o-aminophenol (wt%=98%) and 17.8g of hydroquinone in a solution of 1560g acetic acid and 600g hydrochloric acid (wt%=32%) to obtain solution A. Dissolve 120.4g of acrolein (wt%=95%) in a solution of 600g acetic acid to obtain solution B. In a static mixer, solutions A and B are reacted at 100℃ to obtain intermediate 1,2-dihydro-8-hydroxyquinoline.

[0033] ② Add 142g of o-nitrophenol (wt%=98%) to the first reaction vessel, add 426g of acetic acid to dissolve the o-nitrophenol, heat to 120℃, and then continuously add the intermediate obtained in step ① to the first reaction vessel to obtain a reaction solution containing the products 8-hydroxyquinoline and o-aminophenol. After liquid phase analysis, the yield of 8-hydroxyquinoline was 96%.

[0034] ③ Dissolve 63.7g of acrolein in 318g of acetic acid solution, and slowly add the acrolein solution to the reaction solution in step ②. The newly generated o-aminophenol reacts with acrolein, and then continues to react with o-nitrophenol to obtain 8-hydroxyquinoline. The total yield of 8-hydroxyquinoline was determined by liquid chromatography to be 90.5%, and the reaction of o-aminophenol and o-nitrophenol was complete. Example 2

[0035] A method for synthesizing 8-hydroxyquinoline, characterized by comprising the following steps:

[0036] ① Dissolve 222.7g of o-aminophenol (wt%=98%) and 11.1g of hydroquinone in a solution of 1560g of acetic acid and 617g of hydrochloric acid (wt%=30%) to obtain solution A. Dissolve 119.2g of acrolein (95%) in a solution of 596g of acetic acid to obtain solution B. In a static mixer, solutions A and B are reacted at 110℃ to obtain intermediate 1,2-dihydro-8-hydroxyquinoline.

[0037] ② Add 142g of o-nitrophenol (wt%=98%) to the first reaction vessel, add 426g of acetic acid to dissolve the o-nitrophenol, heat to 115℃, and then continuously add the intermediate obtained in step ① to the first reaction vessel to obtain a reaction solution containing the products 8-hydroxyquinoline and o-aminophenol. After liquid chromatography, the yield of 8-hydroxyquinoline was 95.2%.

[0038] ③ Dissolve 62g of acrolein in 310g of acetic acid solution, and slowly add the acrolein solution to the reaction solution in step ②. The newly generated o-aminophenol reacts with acrolein, and then continues to react with o-nitrophenol to obtain 8-hydroxyquinoline. The total yield of 8-hydroxyquinoline was determined by liquid chromatography to be 89.7%, and the reaction of o-aminophenol and o-nitrophenol was complete. Example 3

[0039] ① A method for synthesizing 8-hydroxyquinoline, characterized by comprising the following steps:

[0040] 222.7 g of o-aminophenol (wt%=98%) and 22 g of hydroquinone were dissolved in 1780 g of acetic acid and 548 g of hydrochloric acid (wt%=35%) to obtain solution A. 121.6 g of acrolein (wt%=95%) was dissolved in 607.8 g of acetic acid to obtain solution B. Solutions A and B were fed into a static mixer in a specific ratio and reacted at 100 °C to obtain intermediate 1,2-dihydro-8-hydroxyquinoline.

[0041] ② Add 142g of o-nitrophenol (wt%=98%) to the first reaction vessel, add 426g of acetic acid to dissolve the o-nitrophenol, heat to 125℃, and then continuously add the intermediate obtained in step ① to the first reaction vessel to obtain a reaction solution containing the products 8-hydroxyquinoline and o-aminophenol. After liquid phase analysis, the yield of 8-hydroxyquinoline was 96.5%.

[0042] ③ Dissolve 64.9g of acrolein in 325g of acetic acid solution, and slowly add the acrolein solution to the reaction solution in step ②. The newly generated o-aminophenol reacts with acrolein, and then continues to react with o-nitrophenol to obtain 8-hydroxyquinoline. The total yield of 8-hydroxyquinoline was determined by liquid chromatography to be 91.3%, and the reaction between o-aminophenol and o-nitrophenol was complete. Example 4

[0043] ① Dissolve 222.7g of o-aminophenol (wt%=98%) and 22g of hydroquinone in 1550g of acetic acid and 690g of hydrochloric acid (wt%=32%) to obtain solution A. Dissolve 120.4g of acrolein (wt%=95%) in 607.8g of acetic acid to obtain solution B. In a static mixer, solutions A and B are reacted at 90℃ to obtain intermediate 1,2-dihydro-8-hydroxyquinoline.

[0044] ② Add 142g of o-nitrophenol (wt%=98%) to the first reaction vessel, add 426g of acetic acid to dissolve the o-nitrophenol, heat to 120℃, and then continuously add the intermediate obtained in step ① to the first reaction vessel to obtain a reaction solution containing the products 8-hydroxyquinoline and o-aminophenol. After liquid chromatography, the yield of 8-hydroxyquinoline was 95.9%.

[0045] ③ Dissolve 63.7g of acrolein in 319g of acetic acid solution, and slowly add the acrolein solution to the reaction solution in step ②. The newly generated o-aminophenol reacts with acrolein, and then continues to react with o-nitrophenol to obtain 8-hydroxyquinoline. The total yield of 8-hydroxyquinoline was determined by liquid chromatography to be 90.2%, and the reaction of o-aminophenol and o-nitrophenol was complete. Example 5

[0046] ① Dissolve 222.7g of o-aminophenol (wt%=98%) and 17.8g of hydroquinone in 1560g of acetic acid and 600g of hydrochloric acid (32%) solution to obtain solution A. Dissolve 120.4g of acrolein (wt%=95%) in 600g of acetic acid solution to obtain solution B. In a static mixer, solutions A and B are reacted at 110℃ to obtain intermediate 1,2-dihydro-8-hydroxyquinoline.

[0047] ② Add 142g of o-nitrophenol (wt%=98%) to the first reaction vessel, add 426g of acetic acid to dissolve the o-nitrophenol, heat to 130℃, and then continuously add the intermediate obtained in step ① to the first reaction vessel to obtain a reaction solution containing the products 8-hydroxyquinoline and o-aminophenol. After liquid phase analysis, the yield of 8-hydroxyquinoline was 94.8%.

[0048] ③ Dissolve 63.7g of acrolein in 318g of acetic acid solution, and slowly add the acrolein solution to the reaction solution in step ②. The newly generated o-aminophenol reacts with acrolein, and then continues to react with o-nitrophenol to obtain 8-hydroxyquinoline. The total yield of 8-hydroxyquinoline was determined by liquid chromatography to be 89.1%, and the reaction of o-aminophenol and o-nitrophenol was complete.

[0049] In step ② of Examples 1-5, the raw material o-nitrophenol does not react completely, and only about 1 / 3 is consumed. Then, an equimolar amount of o-aminophenol is generated. Step ③ is an iterative reaction, that is, the generated o-aminophenol reacts with the newly added acrolein to obtain an intermediate, which then reacts with o-nitrophenol to regenerate o-aminophenol. This cycle continues until the o-nitrophenol is completely consumed, which improves the utilization rate of acrolein and results in a higher yield of 9-hydroxyquinoline.

Claims

1. A method for synthesizing 8-hydroxyquinoline, characterized in that: Includes the following steps: ① Dissolve o-aminophenol and hydroquinone in acetic acid-hydrochloric acid solution to obtain solution A; dissolve acrolein in acetic acid to obtain solution B; add solution A and solution B to a static mixer and obtain intermediate 1,2-dihydro-8-hydroxyquinoline at 90~110℃. The mass ratio of o-aminophenol to hydroquinone in solution A is 1:0.005~0.02; The molar ratio of o-aminophenol to acrolein is 1:1 to 1.05; ② Add o-nitrophenol to the first reaction vessel, then add second acetic acid, start stirring to dissolve o-nitrophenol, heat to 110~130℃, add the intermediate 1,2-dihydro-8-hydroxyquinoline obtained in step ① to the first reaction vessel to obtain a reaction solution containing the product 8-hydroxyquinoline and o-aminophenol. The molar ratio of o-nitrophenol to o-aminophenol in step ① is 0.4~0.6:1; ③ Dissolve the second acrolein in the second acetic acid and add it to the reaction solution of step ② in several portions. React at 110~130℃. The o-aminophenol obtained in step ② reacts with the second acrolein, and then continues to react with o-nitrophenol to obtain 8-hydroxyquinoline. The mass ratio of the second acrolein to the second acetic acid is 1:3~6; The molar ratio of acrolein to o-nitrophenol in the second step is 1.05~1.1:

1.

2. The method for synthesizing 8-hydroxyquinoline according to claim 1, characterized in that: The acetic acid-hydrochloric acid solution is obtained by mixing acetic acid and hydrochloric acid aqueous solution in a mass ratio of 5~10:2.2~3.5; the mass concentration of the hydrochloric acid aqueous solution is 30~35%.

3. The method for synthesizing 8-hydroxyquinoline according to claim 1, characterized in that: The mass ratio of o-aminophenol to acetic acid-hydrochloric acid solution in solution A is 1:7.2~13.

5.

4. The method for synthesizing 8-hydroxyquinoline according to claim 1, characterized in that: The mass ratio of acrolein to acetic acid in solution B is 1:3~6.

5. The method for synthesizing 8-hydroxyquinoline according to claim 1, characterized in that: The reaction temperature of the first reactor in steps ② and ③ is 115~125℃.

6. The method for synthesizing 8-hydroxyquinoline according to claim 4, characterized in that: The mass ratio of acrolein to acetic acid in solution B is 1:4~5.

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