Synthesis method of 3-hydroxyquinoline derivative

Abstract

The invention relates to the technical field of organic synthesis, in particular to a synthesis method of a 3-hydroxyquinoline derivative, which comprises the following steps: adding reactants 1, 2, 3, 4-tetrahydroquinoline compound, a catalyst and a solvent into a reactor, reacting under stirring and heating conditions, and after the reaction is finished, performing post-treatment to obtain the target product 3-hydroxyquinoline derivative. According to the novel method for synthesizing the 3-hydroxyquinoline derivative, the hybrid material synthesized through coordination of the Mn-containing hydrotalcite and the organic acid is used as the catalyst, the 3-hydroxyquinoline derivative can be synthesized under the mild condition, and the method has the advantages of being low in raw material price, short in reaction process, mild in reaction condition and the like.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for synthesizing a 3-hydroxyquinoline derivative. Background Art

[0002] 3-Hydroxyquinoline derivatives are important intermediates for the synthesis of organic drugs. For example, 3,8-dihydroxyquinoline has antioxidant and anti-tumor effects. The development of simple and efficient strategies for the synthesis of 3-hydroxyquinoline derivatives has attracted much attention from organic chemists. The traditional methods for the synthesis of 3-hydroxyquinoline mainly include the following:

[0003] Functional group conversion preparation method: This method usually prepares 3-hydroxyquinoline by functionalizing a substituent with a hydroxyl precursor. Although this method has certain flexibility and can functionalize different substituents, it requires multi-step reactions and involves complex protection and deprotection steps, resulting in a cumbersome synthesis process, low yield, and high cost. Therefore, the economic efficiency is greatly affected when large-scale production is carried out on an industrial scale.

[0004] 2-aminobenzaldehyde and chloroacetaldehyde reaction method: This method utilizes 2-aminobenzaldehyde and chloroacetaldehyde to react to synthesize 3-hydroxyquinoline. Although the reaction steps of this method are relatively simple, its raw materials (especially chloroacetaldehyde) are relatively expensive, and there are high requirements for the safety of the environment and operators during operation. In addition, this method will produce some by-products that are difficult to separate in some cases, affecting the subsequent purification process.

[0005] Doebner-Miller reaction: This reaction is one of the classic quinoline synthesis reactions, which converts the precursor into the target product through oxidation. Although this method has a long research history and is widely used in laboratories, the yield of this reaction is usually low, about 40%, resulting in a large amount of waste of reactants. The low yield not only increases the consumption of raw materials, but also increases the difficulty of subsequent purification operations, which in turn leads to a significant decrease in production efficiency and economy.

[0006] Pinacol borate and indole reaction method: This method synthesizes 3-hydroxyquinoline by reacting pinacol borate with indole. This method utilizes some new technologies and new catalysts in modern organic synthesis and has high reaction activity, but its reaction steps are complicated, involving multiple intermediates and complex catalyst systems, which restricts its practical application in industry. In addition, pinacol borate is a key raw material and its price is high, which further affects the economic efficiency of this method.

[0007] These methods all have certain limitations, such as cumbersome reaction steps, low overall efficiency due to multi-step reactions, complex or expensive catalysts, low yields, and difficulty in subsequent purification, etc. These problems make the process of synthesizing 3-hydroxyquinoline derivatives not ideal in industry and difficult to achieve large-scale economic production.

[0008] The information disclosed in this background technology section is only intended to deepen the understanding of the overall background technology of the present invention, and should not be regarded as acknowledging or suggesting in any form that the information constitutes the prior art known to those skilled in the art. Summary of the invention

[0009] The technical problem to be solved by the present invention is to provide a method for synthesizing 3-hydroxyquinoline derivatives, adopt a heterogeneous catalyst, and develop a new method for catalytically synthesizing 3-hydroxyquinoline with simple raw materials, which has the advantages of cheap raw material price, short reaction process, mild reaction conditions, etc.

[0010] In order to achieve the above object, the technical solution adopted by the present invention is:

[0011] The method for synthesizing 3-hydroxyquinoline derivatives proposed by the present invention comprises the following steps:

[0012] Add reactant 1, catalyst and solvent into the reactor, introduce oxygen-containing gas (air, oxygen, or a certain content of O2 / N2 mixed gas) under normal pressure, react under stirring and heating conditions, and after the reaction is completed, remove the catalyst by filtration, and confirm the target product 2 by liquid chromatography and nuclear magnetic resonance analysis. The reaction formula is as follows:

[0013]

[0014] In the reaction formula, the reactant 1 is a 1,2,3,4-tetrahydroquinoline compound; the target product 2 is a 3-hydroxyquinoline derivative;

[0015] In the reaction formula, R 1 represents one, two, three or four substituents at the 5-, 6-, 7- and 8-positions of the aromatic ring to which it is attached, R 2 represents one, two or three substituents at the 1-, 2- and 4-positions of a nitrogen-containing saturated ring, each R 1 and R 2 The substituents are independently selected from H, halogen, C 1-3 The alkyl, methoxy, hydroxyl, methyl formate, aryl, p-tolyl, 3,5-dimethylphenyl or aryl containing heteroatoms. The aryl group is conducive to the reaction, while the sterically hindered group will reduce the activity of the reaction. In order to increase the yield of the target product 1, R 1 Benzene and its derivative substituents are preferred.

[0016] Specifically, at the beginning of the reaction, reactant 1 (1,2,3,4-tetrahydroquinoline derivative) is activated under the conditions of catalyst and heating, and the catalyst can promote the formation of imine intermediate; further, in the presence of oxygen, the catalyst can catalyze the oxidation of C-3 to form a carbonyl structure; finally, the target product 3-hydroxyquinoline derivative is obtained through tautomerism reaction, and the reaction formula is as follows: After the reaction is completed, the catalyst is removed by filtration, and the obtained reaction mixture contains the target product.

[0017]

[0018] Liquid chromatography (HPLC) was used to analyze the reaction conversion rate and product selectivity; nuclear magnetic resonance (NMR) was used to confirm the structure of the target product 3-hydroxyquinoline derivative.

[0019] The reactant 1 is selected from one of the compounds shown in the following 1a-1z.

[0020]

[0021] Preferably, the catalyst is an organic-inorganic hybrid material synthesized by reacting a Mn-containing hydrotalcite (LDH) with an organic acid. The metal in the catalyst structure also includes one or more of Ni, Mg, Al, Cu, and Fe, and the organic acid includes n-hexanoic acid, n-valeric acid, benzoic acid, acetic acid, propionic acid, butyric acid, and benzoic acid substituted with one or more groups. The proton coupled electron transfer (PCET) process is one of the important pathways for the oxidation activation of C–H bonds. The present invention uses a manganese-containing organic-inorganic hybrid material as a catalyst, and increases the central Mn by the coordination of organic carboxylic acid molecules. 3+ The oxidation potential and electron transfer ability of the carboxylic acid molecule are improved by the reaction coordination with the hexacoordinated (hydr)oxide central metal to increase the positive charge density of the central metal, thereby constructing a M with strong alkalinity. n+ -O 2- (H) site, effectively improving the surface alkalinity and proton transfer ability of the material, and finally obtaining a catalytic material that can efficiently catalyze the PCET reaction process, thereby realizing the oxidation activation of the C–H bond. Further preferably, the catalyst containing Ni and Mg, as well as hexanoic acid, valeric acid, butyric acid and benzoic acid has better catalytic activity, mainly because Ni and Mg can better stabilize high-valent Mn species and improve the surface alkalinity of the catalyst, thereby improving its activity in catalyzing the PCET process; and the surface of the manganese-based material formed by hexanoic acid, valeric acid, butyric acid and benzoic acid has good compatibility with substrates and oxygen molecules, which can effectively promote the reaction of the present invention.

[0022] The manganese-based catalytic material is prepared according to the following steps: Mn-based hydrotalcite, organic acid and solvent (dodecane) are added to a reactor, oxygen is introduced, and the reaction is heated at 110-130° C. under stirring conditions. After the reaction is completed, the catalyst is washed with ethyl acetate and then dried in an oven at 80° C. for 12 hours to obtain a manganese-based catalytic material.

[0023] Preferably, the amount of the catalyst is 40-120 g / mol relative to the amount of the reactant 1. If the amount of the catalyst is too low, the efficiency of the 3-hydroxyquinoline synthesis reaction is low; while if the amount of the catalyst is too high, the economic efficiency of the reaction will be reduced.

[0024] Preferably, the amount of the solvent is 1 to 5 L / mol relative to the amount of the reactant 1. Too low a solvent amount makes the system unevenly dispersed, resulting in poor selectivity of the target product; while a large amount of solvent reduces the economy of the reaction and causes unnecessary waste.

[0025] Preferably, the reaction temperature of the preparation method of the present invention is 50-150° C. Low reaction temperature is not conducive to the oxidative activation of 1,2,3,4-tetrahydroquinoline, and at high temperature, reactant 1 is prone to dehydrogenation to generate quinoline byproducts, reducing the selectivity of the target product.

[0026] Preferably, the stirring rate of the preparation method of the present invention is 400-1000 r / min. If the stirring rate is too low, the mass transfer performance of the reaction system will be affected and the reaction rate will be reduced.

[0027] In summary, the present invention has the following beneficial effects:

[0028] (1) The present invention uses 1,2,3,4-tetrahydroquinoline compounds as raw materials to achieve a simple synthesis of 3-hydroxyquinoline derivatives, which has the advantages of a simple reaction system, cheap raw materials, good product selectivity, mild reaction conditions, etc., and has good application prospects.

[0029] (2) The present invention uses a hybrid material synthesized by coordination of Mn-containing hydrotalcite and organic acid as a catalyst to efficiently synthesize 3-hydroxyquinoline derivatives under mild conditions. The catalyst is easy to separate and recover, and has the advantages of simple reaction process operation, good economy, and easy separation and purification of the product. DETAILED DESCRIPTION

[0030] In order to further explain the technical means and effects adopted by the present invention to achieve the predetermined invention purpose, the synthesis method of 3-hydroxyquinoline derivatives proposed by the present invention, its specific implementation method, characteristics and effects are described in detail as follows.

[0031] In a specific embodiment of the present invention, the sources of various commercially available materials are as follows:

[0032]

[0033] Example 1

[0034] 100 mg of Ni2Mn-LDH, 0.7 mmol of n-hexanoic acid and 2 mL of dodecane were added to the reactor and reacted for 12 h under stirring at 120 ° C. After the reaction, the catalyst was washed with ethyl acetate and then dried in an oven at 80 ° C for 12 h to obtain a manganese-based catalytic material HA-Ni2Mn.

[0035] 50mg HA-Ni2Mn catalyst was added to the reaction system, 1mmol of 1,2,3,4-tetrahydroquinoline (1a), oxygen was introduced, the temperature was 120℃, the stirring rate was 400r / min, 2mL of p-tert-butyltoluene was added, and the reaction was stirred for 5h. After the reaction was completed, the catalyst was removed by filtration, and the contents of the reactant 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC analysis, and the conversion rate and selectivity of the reaction were calculated. It can be seen that the conversion rate of 1,2,3,4-tetrahydroquinoline is 100%, and the selectivity of the target product 3-hydroxyquinoline is 73%.

[0036] Example 2

[0037] 100 mg of Ni2Mn hydrotalcite, 0.4 mmol of p-bromobenzoic acid and 2 mL of dodecane were added to the reactor and reacted for 12 hours under stirring at 120°C. After the reaction, the catalyst was washed with ethyl acetate and then dried in an oven at 80°C for 12 hours to obtain a manganese-based catalytic material BBA-Ni2Mn.

[0038] 80 mg of BBA-Ni2Mn catalyst was added to the reaction system, 1 mmol of 1,2,3,4-tetrahydroquinoline (1a), oxygen was introduced, the temperature was 120°C, the stirring rate was 500 r / min, 2 mL of mesitylene was added, and the reaction was stirred for 4 hours. After the reaction was completed, the catalyst was removed by filtration, and the contents of the reactant 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC analysis, and the conversion rate and selectivity of the reaction were calculated. It was found that the conversion rate of 1,2,3,4-tetrahydroquinoline was 83%, and the selectivity of the target product 3-hydroxyquinoline was 44%.

[0039] Example 3

[0040] 100 mg of Ni2Mg2Mn hydrotalcite, 0.5 mmol of 2,4,5-trimethylbenzoic acid and 2 mL of dodecane were added to the reactor and reacted for 12 hours under stirring at 120°C. After the reaction, the catalyst was washed with ethyl acetate and then dried in an oven at 80°C for 12 hours to obtain a manganese-based catalytic material TBA-Ni2Mg2Mn.

[0041] 80mg TBA-Ni2Mg2Mn catalyst was added to the reaction system, 1mmol of 1,2,3,4-tetrahydroquinoline (1a), oxygen was introduced, the temperature was 120℃, the stirring rate was 400r / min, 2mL of mesitylene was added, and the reaction was stirred for 4h. After the reaction was completed, the catalyst was removed by filtration, and the contents of the reactant 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC analysis, and the conversion rate and selectivity of the reaction were calculated. It was found that the conversion rate of 1,2,3,4-tetrahydroquinoline was 98%, and the selectivity of the target product 3-hydroxyquinoline was 67%.

[0042] Example 4

[0043] 100 mg of Mn2Al hydrotalcite, 0.3 mmol of propionic acid and 2 mL of dodecane were added to the reactor and reacted for 12 h under stirring at 120 ° C. After the reaction, the catalyst was washed with ethyl acetate and then dried in an oven at 80 ° C for 12 h to obtain a manganese-based catalytic material PA-Mn2Al.

[0044] 50mg PA-Mn2Al catalyst was added to the reaction system, 1mmol of 1,2,3,4-tetrahydroquinoline (1a), oxygen was introduced, the temperature was 100℃, the stirring rate was 600r / min, 2mL of p-xylene was added, and the reaction was stirred for 10h. After the reaction was completed, the catalyst was removed by filtration, and the contents of the reactant 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC analysis, and the conversion rate and selectivity of the reaction were calculated. It was found that the conversion rate of 1,2,3,4-tetrahydroquinoline was 92%, and the selectivity of the target product 3-hydroxyquinoline was 69%.

[0045] Example 5

[0046] 100 mg of CuMgMn hydrotalcite, 0.4 mmol of benzoic acid and 2 mL of dodecane were added to the reactor and reacted for 12 h under stirring at 120° C. After the reaction, the catalyst was washed with ethyl acetate and then dried in an oven at 80° C. for 12 h to obtain a manganese-based catalyst material BA-CuMgMn.

[0047] 100 mg of BA-CuMgMn catalyst was added to the reaction system, 1 mmol of 1,2,3,4-tetrahydroquinoline (1a), oxygen was introduced, the temperature was 120°C, the stirring rate was 400 r / min, 2 mL of 4-isopropyltoluene was added, and the reaction was stirred for 3 hours. After the reaction was completed, the catalyst was removed by filtration, and the contents of the reactant 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC analysis, and the conversion rate and selectivity of the reaction were calculated. It was found that the conversion rate of 1,2,3,4-tetrahydroquinoline was 96%, and the selectivity of the target product 3-hydroxyquinoline was 67%.

[0048] Example 6

[0049] 100 mg of Mn2Fe hydrotalcite, 0.5 mmol of n-hexanoic acid and 2 mL of dodecane were added to the reactor and reacted for 12 hours under stirring at 120°C. After the reaction, the catalyst was washed with ethyl acetate and then dried in an oven at 80°C for 12 hours to obtain a manganese-based catalytic material HA-Mn2Fe.

[0050] 50mg HA-Mn2Fe catalyst was added to the reaction system, 1mmol of 1,2,3,4-tetrahydroquinoline (1a), oxygen was introduced, the temperature was 120℃, the stirring rate was 600r / min, 2mL of p-tert-butyltoluene was added, and the reaction was stirred for 7h. After the reaction was completed, the catalyst was removed by filtration, and the contents of the reactant 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC analysis, and the conversion rate and selectivity of the reaction were calculated. It was found that the conversion rate of 1,2,3,4-tetrahydroquinoline was 95%, and the selectivity of the target product 3-hydroxyquinoline was 51%.

[0051] Example 7

[0052] 100 mg of Ni3MnAl hydrotalcite, 0.6 mmol of n-hexanoic acid and 2 mL of dodecane were added to the reactor and reacted for 12 h under stirring at 120° C. After the reaction, the catalyst was washed with ethyl acetate and then dried in an oven at 80° C. for 12 h to obtain a manganese-based catalytic material HA-Ni3MnAl.

[0053] 80 mg of HA-Ni3MnAl catalyst was added to the reaction system, 1 mmol of 1,2,3,4-tetrahydroquinoline (1a), oxygen was introduced, the temperature was 120°C, the stirring rate was 400 r / min, 2 mL of p-tert-butyltoluene was added, and the reaction was stirred for 3 hours. After the reaction was completed, the catalyst was removed by filtration, and the contents of the reactant 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC analysis, and the conversion rate and selectivity of the reaction were calculated. It was found that the conversion rate of 1,2,3,4-tetrahydroquinoline was 94%, and the selectivity of the target product 3-hydroxyquinoline was 63%.

[0054] Example 8

[0055] 100 mg of Ni2Mn hydrotalcite, 0.3 mmol of benzoic acid and 2 mL of dodecane were added to the reactor and reacted for 12 h under stirring at 120° C. After the reaction, the catalyst was washed with ethyl acetate and then dried in an oven at 80° C. for 12 h to obtain a manganese-based catalyst material BA-Ni2Mn.

[0056] 60mg BA-Ni2Mn catalyst was added to the reaction system, 1mmol 1,2,3,4-tetrahydroquinoline (1a), oxygen was introduced, the temperature was 120℃, the stirring rate was 500r / min, 2mL mesitylene was added, and the reaction was stirred for 5h. After the reaction was completed, the catalyst was removed by filtration, and the contents of the reactant 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC analysis, and the conversion rate and selectivity of the reaction were calculated. It was found that the conversion rate of 1,2,3,4-tetrahydroquinoline was 98%, and the selectivity of the target product 3-hydroxyquinoline was 67%.

[0057] Example 9

[0058] The catalyst in Example 1 was used.

[0059] Add 20mg HA-Ni2Mn catalyst, 0.5mmol 1,2,3,4-tetrahydroquinoline (1a) to the reaction system, introduce oxygen, oxygen / 1,2,3,4-tetrahydroquinoline molar ratio is 30:1, temperature is 150℃, stirring rate is 400r / min, 1mL p-tert-butyltoluene, and stir for 2h. After the reaction is completed, the catalyst is removed by filtration, and the content of the reactant 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution is analyzed by LC analysis, and the conversion rate and selectivity of the reaction are calculated. It can be seen that the conversion rate of 1,2,3,4-tetrahydroquinoline is 95%, and the yield of the target product 3-hydroxyquinoline is 51%.

[0060] Example 10

[0061] The catalyst in Example 1 was used.

[0062] 30 mg HA-Ni2Mn catalyst, 0.5 mmol 1,2,3,4-tetrahydroquinoline (1a) were added to the reaction system, oxygen was introduced, the molar ratio of oxygen / 1,2,3,4-tetrahydroquinoline was 50:1, the temperature was 130°C, the stirring rate was 400 r / min, 2 mL o-xylene was added, and the reaction was stirred for 4 hours. After the reaction was completed, the catalyst was removed by filtration, and the contents of the reactant 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC analysis, and the conversion rate and selectivity of the reaction were calculated. It was found that the conversion rate of 1,2,3,4-tetrahydroquinoline was 99%, and the yield of the target product 3-hydroxyquinoline was 63%.

[0063] Embodiment 11

[0064] The catalyst in Example 1 was used.

[0065] 40 mg HA-Ni2Mn catalyst, 0.5 mmol 1,2,3,4-tetrahydroquinoline (1a) were added to the reaction system, oxygen was introduced, the molar ratio of oxygen / 1,2,3,4-tetrahydroquinoline was 60:1, the temperature was 110°C, the stirring rate was 400 r / min, 1 mL of p-tert-butyltoluene was added, and the reaction was stirred for 5 h. After the reaction was completed, the catalyst was removed by filtration, and the contents of the reactant 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC analysis, and the conversion rate and selectivity of the reaction were calculated. It was found that the conversion rate of 1,2,3,4-tetrahydroquinoline was 92%, and the yield of the target product 3-hydroxyquinoline was 56%.

[0066] Example 12

[0067] The catalyst in Example 1 was used.

[0068] Add 60mg HA-Ni2Mn catalyst, 0.5mmol 1,2,3,4-tetrahydroquinoline (1a) to the reaction system, introduce oxygen, oxygen / 1,2,3,4-tetrahydroquinoline molar ratio is 80:1, temperature is 100℃, stirring rate is 400r / min, 2mL 1,2,4,5-tetramethylbenzene, and stir for 6h. After the reaction is completed, the catalyst is removed by filtration, and the content of the reactant 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution is analyzed by LC analysis, and the conversion rate and selectivity of the reaction are calculated. It can be seen that the conversion rate of 1,2,3,4-tetrahydroquinoline is 84%, and the yield of the target product 3-hydroxyquinoline is 50%.

[0069] Embodiment 13

[0070] The catalyst in Example 1 was used.

[0071] 100 mg HA-Ni2Mn catalyst, 1 mmol 1,2,3,4-tetrahydroquinoline (1a) were added to the reaction system, oxygen was introduced, the molar ratio of oxygen / 1,2,3,4-tetrahydroquinoline was 60:1, the temperature was 120°C, the stirring rate was 400 r / min, 2 mL of mesitylene was added, and the reaction was stirred for 3 h. After the reaction was completed, the catalyst was removed by filtration, and the contents of the reactant 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC analysis, and the conversion rate and selectivity of the reaction were calculated. It can be seen that the conversion rate of 1,2,3,4-tetrahydroquinoline is >99%, and the yield of the target product 3-hydroxyquinoline is 55%.

[0072] Embodiment 14

[0073] The catalyst in Example 1 was used.

[0074] 80 mg HA-Ni2Mn catalyst, 1 mmol 1,2,3,4-tetrahydroquinoline (1a) were added to the reaction system, oxygen was introduced, the molar ratio of oxygen / 1,2,3,4-tetrahydroquinoline was 30:1, the temperature was 80°C, the stirring rate was 1000 r / min, 2 mL of p-tert-butyltoluene was added, and the reaction was stirred for 8 hours. After the reaction was completed, the catalyst was removed by filtration, and the contents of the reactant 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC analysis, and the conversion rate and selectivity of the reaction were calculated. It was found that the conversion rate of 1,2,3,4-tetrahydroquinoline was 79%, and the yield of the target product 3-hydroxyquinoline was 47%.

[0075] Embodiment 15

[0076] The catalyst in Example 1 was used.

[0077] 110 mg HA-Ni2Mn catalyst, 1 mmol 1,2,3,4-tetrahydroquinoline (1a) were added to the reaction system, oxygen was introduced, the molar ratio of oxygen / 1,2,3,4-tetrahydroquinoline was 100:1, the temperature was 50°C, the stirring rate was 800 r / min, 2 mL of p-tert-butyltoluene was added, and the reaction was stirred for 40 hours. After the reaction was completed, the catalyst was removed by filtration, and the contents of the reactant 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC analysis, and the conversion rate and selectivity of the reaction were calculated. It was found that the conversion rate of 1,2,3,4-tetrahydroquinoline was 69%, and the yield of the target product 3-hydroxyquinoline was 49%.

[0078] Comparative Example 1

[0079] Compared with the precursor of manganese-based catalytic material. 30mg Ni2Mn-LDH catalyst, 0.5mmol 1,2,3,4-tetrahydroquinoline (1a) were added to the reaction system, oxygen was introduced, the molar ratio of oxygen / 1,2,3,4-tetrahydroquinoline was 50:1, and the reaction was carried out at a temperature of 120°C and a speed of 400r / min for 7h. The content of the reactant 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution was analyzed by LC analysis, and the conversion rate and selectivity of the reaction were calculated. It can be seen that the conversion rate of 1,2,3,4-tetrahydroquinoline is 82%, and the yield of the target product 3-hydroxyquinoline is 5%.

[0080] Comparative Example 2

[0081] Verify the role of the catalyst. Add 0.5mmol of 1,2,3,4-tetrahydroquinoline (1a) to the reaction system, introduce oxygen, and stir at 120°C, 400r / min, 2mL of tert-butyltoluene, and stir for 5h. After the reaction, remove the catalyst by filtration, and analyze the contents of the reactant 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution by LC analysis, and calculate the conversion rate and selectivity of the reaction. It can be seen that the conversion rate of 1,2,3,4-tetrahydroquinoline is 7%, and the yield of the target product 3-hydroxyquinoline is 0.

[0082] Comparative Example 3

[0083] Verify the difference between air and oxygen. Add 30mg HA-Ni2Mn catalyst, 0.5mmol 1,2,3,4-tetrahydroquinoline (1a) to the reaction system, introduce air, temperature at 120℃, stirring rate 400r / min, 2mL p-tert-butyltoluene, and stir for 5h. After the reaction, the catalyst was removed by filtration, and the content of the reactant 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution was analyzed by LC analysis, and the conversion rate and selectivity of the reaction were calculated. It can be seen that the conversion rate of 1,2,3,4-tetrahydroquinoline is 69%, and the yield of the target product 3-hydroxyquinoline is 37%.

[0084] Substrate extension experiment

[0085] Using the reaction conditions of Example 1, various types of reaction substrates were further expanded to investigate the adaptability of the method to different types of reaction substrates. Due to different reaction substrates, the most suitable reaction conditions will also be different. Therefore, the following reaction yields of the present invention are only for the reaction conditions of Example 1, and do not represent the best effects of various reaction substrates of the present invention. The reaction results are as follows:

[0086] Table 2 Reaction results of different substrates

[0087]

[0088]

[0089]

[0090]

[0091] Performance Results

[0092] It can be seen from the results of substrate expansion experiments that the catalyst and preparation method of the present invention have good substrate expansion properties and a wide range of applications.

[0093] Comparative Example 1 Compared with Example 1, Ni2Mn-LDH was used as a catalyst. The results showed that the conversion rate of 1,2,3,4-tetrahydroquinoline was significantly reduced, indicating that the catalytic activity of Ni2Mn-LDH was not as good as that of HA-Ni2Mn, indicating that the material generated by hybridization of organic acid and Ni2Mn-LDH has a significant promoting effect on the conversion of 1,2,3,4-tetrahydroquinoline.

[0094] Comparative Example 2 is relative to Example 1, but no catalyst is added. The results show that the conversion rate and yield of 1,2,3,4-tetrahydroquinoline are significantly reduced, indicating that the catalytic material HA-Ni2Mn has a significant promoting effect on the conversion of 1,2,3,4-tetrahydroquinoline to 3-hydroxyquinoline.

[0095] Comparative Example 3 verifies the difference between air and oxygen relative to Example 1. When air is used as the oxidant, the conversion rate and yield of 1,2,3,4-tetrahydroquinoline are significantly reduced, indicating that molecular oxygen plays a key role as an oxidant in the oxidation process, and the low oxygen concentration in the air affects the conversion rate of 1,2,3,4-tetrahydroquinoline.

[0096] The above description is only a preferred embodiment of the present invention and does not limit the present invention in any form. Although the present invention has been disclosed as a preferred embodiment as above, it is not used to limit the present invention. Any technician familiar with this profession can make some changes or modify the technical contents disclosed above into equivalent embodiments without departing from the scope of the technical solution of the present invention. However, any simple modification, equivalent change and modification made to the above embodiments according to the technical essence of the present invention without departing from the content of the technical solution of the present invention still fall within the scope of the technical solution of the present invention.

Claims

1. A method for synthesizing a 3-hydroxyquinoline derivative, characterized in that: The steps are as follows: Add reactant 1, catalyst and solvent into the reactor, introduce oxygen-containing gas under normal pressure, react under stirring and heating conditions, and after the reaction is completed, obtain the target product 2 through treatment. The reaction formula is as follows: In the reaction formula, the reactant 1 is a 1,2,3,4-tetrahydroquinoline compound; the target product 2 is a 3-hydroxyquinoline derivative; In the reaction formula, R 1 represents one, two, three or four substituents at the 5-, 6-, 7- and 8-positions of the aromatic ring to which it is attached, R 2 represents one, two or three substituents at the 2- and 4-positions of a nitrogen-containing saturated ring, each R 1 and R 2 The substituents are independently selected from H, halogen, C 1-3 The invention can be an alkyl group, a methoxy group, a hydroxyl group, a methyl formate group, an aryl group, a p-tolyl group, a 3,5-dimethylphenyl group or an aryl group containing a heteroatom.

2. The method for synthesizing a 3-hydroxyquinoline derivative according to claim 1, characterized in that: The reactant 1 is selected from one of the compounds shown in the following 1a-1z:

3. The method for synthesizing a 3-hydroxyquinoline derivative according to claim 1, characterized in that: The catalyst is an organic-inorganic hybrid material synthesized by reacting Mn-containing hydrotalcite with an organic acid. The metal in the catalyst structure also includes one or more of Ni, Mg, Al, Cu, and Fe. The organic acid includes n-hexanoic acid, n-valeric acid, benzoic acid, propionic acid, butyric acid, and benzoic acid substituted with a single or multiple groups.

4. The method for synthesizing a 3-hydroxyquinoline derivative according to claim 1, characterized in that: The amount of the catalyst used is 40 to 120 g / mol relative to the amount of the reactant 1 used.

5. The method for synthesizing a 3-hydroxyquinoline derivative according to claim 1, characterized in that: The solvent includes one or more of p-tert-butyltoluene, mesitylene, o-xylene, m-xylene, p-xylene, 4-isopropyltoluene, and 1,2,4,5-tetramethylbenzene.

6. The method for synthesizing a 3-hydroxyquinoline derivative according to claim 5, characterized in that: The amount of the solvent used is 1 to 5 L / mol relative to the amount of the reactant 1 used.

7. The method for synthesizing a 3-hydroxyquinoline derivative according to claim 1, characterized in that: The reaction temperature is 50-150°C.

8. The method for synthesizing 3-hydroxyquinoline derivatives according to claim 1, characterized in that: The reaction time is 2 to 40 hours.

9. The method for synthesizing a 3-hydroxyquinoline derivative according to claim 1, characterized in that: The stirring rate is 400~1000r / min.

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