A method for synthesizing 8-hydroxyquinoline

Abstract

This invention discloses a method for synthesizing 8-hydroxyquinoline, using o-aminophenol and acrolein as raw materials, o-nitrophenol as an oxidant, hydroquinone as a polymerization inhibitor, and hydrochloric acid / ionic liquid as a mixed solvent. Under heating conditions, acrolein is vaporized by heating and then slowly and uniformly added to the reaction system. The reaction solution is subjected to phase separation, neutralization, and steam distillation to obtain the product 8-hydroxyquinoline. This invention proposes a method for synthesizing 8-hydroxyquinoline that utilizes hydrochloric acid and ionic liquid as a mixed solvent and adopts a gas-phase feeding method for acrolein, effectively inhibiting the polymerization of acrolein, improving the reaction yield, and overcoming the problems of low acrolein utilization, low product yield, and large amount of waste in existing technologies. Compared with existing synthesis methods, it has the advantages of higher product yield, less waste, and milder reaction conditions.

Description

Technical Field

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

[0002] 8-Hydroxyquinoline is an important pharmaceutical intermediate used in the synthesis of drugs such as cloiodriquinoline and chlorpheniramine maleate. Simultaneously, 8-hydroxyquinoline is also used as a metal ion chelating agent for the analysis, monitoring, extraction, and enrichment of metal ions. Its derived metal ion complexes have been extensively studied in catalysis, materials science, biological and pharmacological activities. For example, the complex formed by 8-hydroxyquinoline and aluminum exhibits excellent properties in organic electroluminescence and can be used as a material for organometallic light-emitting diodes (OLEDs). Therefore, developing efficient and safe methods for the synthesis of 8-hydroxyquinoline is of great significance.

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

[0004] The quinoline sulfonation alkaline fusion method uses quinoline as a raw material, first synthesizing 8-sulfonoquinoline with fuming sulfuric acid under heating conditions, and then reacting it with solid sodium hydroxide under heating for alkaline hydrolysis and neutralization to obtain 8-hydroxyquinoline. The regioselectivity of the reaction is difficult to control; quinoline sulfonation produces 5-sulfonoquinoline along with 8-sulfonoquinoline. Furthermore, the reaction process consumes large amounts of acid and alkali, resulting in significant amounts of waste. The second alkaline fusion step is also carried out at high temperatures, generating a large amount of tar byproducts, leading to a low yield of 8-hydroxyquinoline.

[0005] The Skraup synthesis method uses o-aminophenol, glycerol, and o-nitrophenol as main raw materials to synthesize 8-hydroxyquinoline via cothermal reaction in a concentrated sulfuric acid system. The Skraup method utilizes readily available, inexpensive, and non-toxic or low-toxic raw materials. However, it requires a large amount of concentrated sulfuric acid, resulting in significant waste. Furthermore, the high glycerol content increases the likelihood of side reactions such as acrolein polymerization, generating tar as a byproduct, making product purification difficult and reducing yield. Patents and literature have reported reaction systems that use acrolein instead of glycerol to synthesize 8-hydroxyquinoline in an acid-catalyzed system. However, these systems still suffer from problems such as easy polymerization of acrolein, high tar content, and low product yield.

[0006] In summary, suppressing side reactions such as acrolein polymerization is one of the effective methods to improve the yield of 8-hydroxyquinoline in current synthesis methods. Finding a synthetic method for 8-hydroxyquinoline that produces fewer byproducts, is cleaner and safer, and allows for easier control of the reaction process remains of great significance. Summary of the Invention

[0007] To address the problems of numerous side reactions, difficulty in controlling the reaction process, low reaction yield, and large amounts of waste that pollute the environment associated with 8-hydroxyquinoline, 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 method for synthesizing 8-hydroxyquinoline includes the following steps:

[0010] ① Preparation of reaction solution: Dissolve o-aminophenol, o-nitrophenol and hydroquinone in a mixed solution to obtain the reaction solution;

[0011] The molar ratio of o-aminophenol to o-nitrophenol is 1:0.4~0.6;

[0012] The mixed solution is obtained by mixing concentrated hydrochloric acid aqueous solution and ionic liquid at a mass ratio of 4~5:2~3; the ionic liquid is 1-butyl-3-methylimidazolium hexafluorophosphate.

[0013] The mass ratio of hydroquinone, o-aminophenol, and the mixed solution is 0.5~2:100:600~800;

[0014] ② Heat the reaction solution obtained in step ① to 110~130℃, and introduce the heated and vaporized acrolein into it. After the introduction is complete, keep the reaction at the temperature for 1~2 hours, and then cool it to 25~35℃ to obtain the reaction mixture.

[0015] The molar ratio of o-aminophenol to acrolein is 1:1.7~2;

[0016] ③ The reaction mixture obtained in step ② is allowed to stand and separate into an aqueous phase and an organic phase. The pH of the aqueous phase is adjusted to 6.5~7.5 with sodium hydroxide aqueous solution. The final product 8-hydroxyquinoline is obtained by steam distillation.

[0017] Preferably, the mass concentration of the sodium hydroxide aqueous solution is 30-35%.

[0018] Preferably, the mass concentration of the concentrated hydrochloric acid aqueous solution is 30-35%.

[0019] Preferably, the mass ratio of hydroquinone, o-aminophenol, and the mixed solution is 1:100:700.

[0020] Preferably, the molar ratio of o-aminophenol to acrolein is 1:1.75.

[0021] Preferably, the reaction temperature in step ② is 115~125℃.

[0022] Preferably, the molar ratio of o-aminophenol to o-nitrophenol is 1:0.5.

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] (1) The present invention improves the reaction yield by vaporizing acrolein and passing it below the surface of the reaction solution, so that the acrolein gas can be added evenly and effectively transferred, thereby effectively slowing down the rapid polymerization of acrolein due to excessively high local concentration during the addition process.

[0025] (2) By using a two-phase solvent system of hydrochloric acid / ionic liquid (1-butyl-3-methylimidazolium hexafluorophosphate), the present invention can reduce the occurrence of side reactions such as acrolein self-polymerization and improve the yield of 8-hydroxyquinoline.

[0026] (3) The ionic liquid used in this invention is a green solvent with a high boiling point and high thermodynamic stability. After the reaction is completed, the ionic liquid phase can be separated from the acidic aqueous phase by simple phase separation, so that the reaction medium can be recycled multiple times.

[0027] (4) The method for synthesizing 8-hydroxyquinoline of the present invention has few side reactions, simple post-processing, high yield, high product purity, and low amount of waste that is easy to treat, making it suitable for industrial production. Detailed Implementation

[0028] 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.

[0029] A method for synthesizing 8-hydroxyquinoline, the reaction equation is as follows:

[0030]

[0031] The reaction process uses o-aminophenol and acrolein as raw materials, o-nitrophenol as an oxidant, hydroquinone as a polymerization inhibitor, and hydrochloric acid / ionic liquid as a mixed solvent. Under heating conditions, acrolein is vaporized by heating and then slowly and uniformly added to the reaction system. The reaction solution is subjected to phase separation, neutralization, and steam distillation to obtain the product 8-hydroxyquinoline.

[0032] The ionic liquid of this invention is 1-butyl-3-methylimidazolium hexafluorophosphate, with the molecular formula C8H12H2O. 15 F6N2P has a molecular weight of 284.0877 and its structural formula is shown in the figure below.

[0033] . Example 1

[0034] A method for synthesizing 8-hydroxyquinoline includes the following steps:

[0035] ① Preparation of reaction solution: Dissolve 1.09 kg of o-aminophenol, 556 g of o-nitrophenol and 5.45 g of hydroquinone in 6.54 kg of mixed solution to obtain the reaction solution;

[0036] The mixed solution was obtained by mixing concentrated hydrochloric acid aqueous solution and ionic liquid at a mass ratio of 4:2; the ionic liquid was 1-butyl-3-methylimidazolium hexafluorophosphate.

[0037] ② Heat the reaction solution obtained in step ① to 110°C, and introduce 952g of heated and vaporized acrolein into it. After the introduction is complete, keep the reaction at the temperature for 2 hours, and then cool it to 25°C to obtain the reaction mixture.

[0038] ③ The reaction mixture obtained in step ② was allowed to stand and separate into an aqueous phase and an organic phase. The pH of the aqueous phase was adjusted to 6.5 with a 30% sodium hydroxide aqueous solution. The final product 8-hydroxyquinoline was obtained by steam distillation, with a yield of 95.17% and a purity of 99.1%. Example 2

[0039] A method for synthesizing 8-hydroxyquinoline includes the following steps:

[0040] ① Preparation of reaction solution: Dissolve 1.09 kg of o-aminophenol, 834 g of o-nitrophenol and 21.8 g of hydroquinone in 8.72 kg of mixed solution to obtain the reaction solution;

[0041] The mixed solution was obtained by mixing concentrated hydrochloric acid aqueous solution and ionic liquid at a mass ratio of 5:3; the ionic liquid was 1-butyl-3-methylimidazolium hexafluorophosphate.

[0042] ② Heat the reaction solution obtained in step ① to 130°C, and introduce 1.12 kg of heated and vaporized acrolein into it. After the introduction is complete, keep the reaction at this temperature for 1 hour, and then cool it to 35°C to obtain the reaction mixture.

[0043] ③ The reaction mixture obtained in step ② was allowed to stand and separate into an aqueous phase and an organic phase. The pH of the aqueous phase was adjusted to 7.5 with a 35% sodium hydroxide aqueous solution. The final product 8-hydroxyquinoline 1.40 kg was obtained by steam distillation, with a yield of 96.55% and a purity of 99.0%. Example 3

[0044] A method for synthesizing 8-hydroxyquinoline includes the following steps:

[0045] ① Preparation of reaction solution: Dissolve 1.09 kg of o-aminophenol, 764.5 g of o-nitrophenol and 10.9 g of hydroquinone in 7.08 kg of mixed solution to obtain the reaction solution;

[0046] The mixed solution was obtained by mixing concentrated hydrochloric acid aqueous solution and ionic liquid at a mass ratio of 4:3; the ionic liquid was 1-butyl-3-methylimidazolium hexafluorophosphate.

[0047] ② Heat the reaction solution obtained in step ① to 115°C, and introduce 1.01 kg of heated and vaporized acrolein into it. After the introduction is complete, keep the reaction at the temperature for 1.5 hours, and then cool it to 30°C to obtain the reaction mixture.

[0048] ③ The reaction mixture obtained in step ② was allowed to stand and separate into an aqueous phase and an organic phase. The pH of the aqueous phase was adjusted to 7.0 with a 32% sodium hydroxide aqueous solution. The final product 8-hydroxyquinoline was obtained by steam distillation, with a yield of 97.24% and a purity of 99.2%. Example 4

[0049] A method for synthesizing 8-hydroxyquinoline includes the following steps:

[0050] ① Preparation of reaction solution: Dissolve 1.09 kg of o-aminophenol, 625.5 g of o-nitrophenol and 16.35 g of hydroquinone in 8.175 kg of mixed solution to obtain the reaction solution;

[0051] The mixed solution was obtained by mixing concentrated hydrochloric acid aqueous solution and ionic liquid at a mass ratio of 5:2; the ionic liquid was 1-butyl-3-methylimidazolium hexafluorophosphate.

[0052] ② Heat the reaction solution obtained in step ① to 125°C, and introduce 1.06 kg of heated and vaporized acrolein into it. After the introduction is complete, keep the reaction at this temperature for 1.5 hours, and then cool it to 28°C to obtain the reaction mixture.

[0053] ③ The reaction mixture obtained in step ② was allowed to stand and separate into an aqueous phase and an organic phase. The pH of the aqueous phase was adjusted to 6.8 with a 34% sodium hydroxide aqueous solution. The final product 8-hydroxyquinoline was obtained by steam distillation, with a yield of 97.24% and a purity of 99.0%. Example 5

[0054] A method for synthesizing 8-hydroxyquinoline includes the following steps:

[0055] ① Preparation of reaction solution: Dissolve 1.09 kg of o-aminophenol, 695 g of o-nitrophenol and 10.9 g of hydroquinone in 7.63 kg of mixed solution to obtain the reaction solution;

[0056] The mixed solution was obtained by mixing concentrated hydrochloric acid aqueous solution and ionic liquid at a mass ratio of 9:5; the ionic liquid was 1-butyl-3-methylimidazolium hexafluorophosphate.

[0057] ② Heat the reaction solution obtained in step ① to 120°C, and introduce 980g of heated and vaporized acrolein into it. After the introduction is complete, keep the reaction at the temperature for 1.5 hours, and then cool it to 30°C to obtain the reaction mixture.

[0058] ③ The reaction mixture obtained in step ② was allowed to stand and separate into an aqueous phase and an organic phase. The pH of the aqueous phase was adjusted to 7.0 with a 35% sodium hydroxide aqueous solution. The final product 8-hydroxyquinoline 1.43 kg was obtained by steam distillation, with a yield of 98.62% and a purity of 99.2%.

Claims

1. A method of synthesizing 8-hydroxyquinoline, characterized by: The method comprises the following steps: ① Preparing a reaction solution: dissolving o-aminophenol, o-nitrophenol and p-dihydroxybenzene in a mixed solution to obtain the reaction solution; The molar ratio of the o-aminophenol and the o-nitrophenol is 1:0.4-0.6; The mixed solution is obtained by mixing a concentrated hydrochloric acid aqueous solution and an ionic liquid at a mass ratio of 4-5:2-3; the ionic liquid is 1-butyl-3-methylimidazolium hexafluorophosphate; The mass ratio of the p-dihydroxybenzene, the o-aminophenol and the mixed solution is 0.5-2:100:600-800; ② Heating the reaction solution obtained in step ① to 110-130 ℃, and then introducing heated and vaporized propenal into the reaction solution; after the introduction is completed, the reaction is maintained for 1-2 hours, and then the reaction solution is cooled to 25-35 ℃ to obtain a reaction mixture; The molar ratio of the o-aminophenol and the propenal is 1:1.7-2; ③ The reaction mixture obtained in step ② is allowed to stand and is separated into an aqueous phase and an organic phase; the pH of the aqueous phase is adjusted to 6.5-7.5 by using a sodium hydroxide aqueous solution, and then the aqueous phase is subjected to water vapor distillation to obtain the final product 8-hydroxyquinoline.

2. The method for synthesizing 8-hydroxyquinoline according to claim 1, characterized in that: The mass concentration of the sodium hydroxide aqueous solution is 30-35%.

3. The method for synthesizing 8-hydroxyquinoline according to claim 1, characterized in that: The mass concentration of the concentrated hydrochloric acid aqueous solution is 30-35%.

4. The method for synthesizing 8-hydroxyquinoline according to claim 1, characterized in that: The mass ratio of the p-dihydroxybenzene, the o-aminophenol and the mixed solution is 1:100:

700.

5. The method for synthesizing 8-hydroxyquinoline according to claim 1, characterized in that: The molar ratio of the o-aminophenol and the propenal is 1:1.

75.

6. The method for synthesizing 8-hydroxyquinoline according to claim 1, characterized in that: The reaction temperature in step ② is 115-125 ℃.

7. The method for synthesizing 8-hydroxyquinoline according to claim 1, characterized in that: The molar ratio of the o-aminophenol and the o-nitrophenol is 1:0.5.

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