A method for synthesizing a 3-hydroxyquinoline derivative

Abstract

The application relates to the technical field of organic synthesis, in particular to a synthesis method of 3-hydroxyquinoline derivatives, wherein a reactant 1,2,3,4-tetrahydroquinoline compound, a catalyst and a solvent are added into a reactor, and then the reaction is carried out under the conditions of stirring and heating; after the reaction is completed, the target product 3-hydroxyquinoline derivative is obtained through post-treatment. The new synthesis method of 3-hydroxyquinoline derivatives provided by the application uses a hybrid material synthesized by coordination of Mn-containing hydrotalcite and an organic acid as a catalyst, can synthesize 3-hydroxyquinoline derivatives under mild conditions, and has the advantages of low price of raw materials, short reaction flow and mild reaction conditions.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and specifically to a method for synthesizing a 3-hydroxyquinoline derivative. Background Technology

[0002] 3-Hydroxyquinoline derivatives are important intermediates in the synthesis of organic drugs. For example, 3,8-dihydroxyquinoline possesses antioxidant and antitumor effects. Developing simple and efficient strategies for the synthesis of 3-hydroxyquinoline derivatives has attracted considerable attention from organic chemists. Traditional methods for synthesizing 3-hydroxyquinoline mainly include the following:

[0003] Functional group transformation method: This method typically prepares 3-hydroxyquinoline by functionalizing substituents containing hydroxyl precursors. Although this method offers some flexibility, allowing for the functionalization of different substituents, it requires multiple reaction steps involving complex protection and deprotection processes, resulting in a cumbersome synthesis, low yield, and high cost. Therefore, its economic viability is significantly hampered when implementing large-scale industrial production.

[0004] 2-Aminobenzaldehyde and Chloroacetaldehyde Reaction Method: This method utilizes the reaction of 2-aminobenzaldehyde with chloroacetaldehyde to synthesize 3-hydroxyquinoline. Although the reaction steps are relatively simple, the raw materials (especially chloroacetaldehyde) are expensive, and the operation requires high standards of environmental and personnel safety. Furthermore, this method can sometimes generate difficult-to-separate byproducts, affecting subsequent purification processes.

[0005] The Doebner-Miller reaction: This is a classic quinoline synthesis reaction that converts a precursor into the target product through oxidation. Although this method has a long history of research and is widely used in laboratories, the yield is typically low, around 40%, leading to significant waste of reactants. Low yields not only increase raw material consumption but also complicate subsequent purification operations, resulting in a significant decrease in production efficiency and economics.

[0006] Pinarylboronic acid ester and indole reaction: This method synthesizes 3-hydroxyquinoline by reacting pinarylboronic acid ester with indole. This method utilizes some new technologies and catalysts in modern organic synthesis, resulting in high reactivity. However, its reaction steps are complex, involving multiple intermediates and a complex catalyst system, which limits its practical industrial application. Furthermore, pinarylboronic acid ester, as a key raw material, is expensive, further impacting the economic viability of this method.

[0007] These methods all have certain limitations, such as cumbersome reaction steps, low overall efficiency due to multiple reaction steps, complex or expensive catalysts, low yields, and difficulties in subsequent purification. These problems make the synthesis of 3-hydroxyquinoline derivatives less than ideal for industrial use, hindering large-scale economic production.

[0008] The information disclosed in this background section is intended only to enhance the understanding of the overall background of the present invention and should not be construed as an admission or in any way implying that the information constitutes 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. A new method for synthesizing 3-hydroxyquinoline from simple raw materials by catalysis using a heterogeneous catalyst has been developed, which has the advantages of inexpensive raw materials, short reaction process and mild reaction conditions.

[0010] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0011] The method for synthesizing 3-hydroxyquinoline derivatives proposed in this invention includes the following steps:

[0012] Reactant 1, catalyst, and solvent were added to the reactor. An oxygen-containing gas (air, oxygen, or a mixture of O2 / N2 with a certain content) was introduced under normal pressure. The reaction was carried out under stirring and heating conditions. After the reaction was completed, the catalyst was removed by filtration. The target product 2 was confirmed by liquid chromatography and nuclear magnetic resonance analysis. The reaction formula is as follows:

[0013]

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

[0015] In the reaction formula, R 1 R indicates one, two, three, or four substituents at the 5-, 6-, 7-, and 8- positions on the connected aromatic ring. 2 This indicates one, two, or three substituents at the 1-, 2-, and 4- positions on a nitrogen-containing saturated ring, with each R... 1 and R 2 The substituents are independently selected from H, halogens, and C. 1-3 The alkyl, methoxy, hydroxy, methyl formate, aryl, p-tolyl, 3,5-dimethylphenyl, or aryl groups containing heteroatoms are preferred for the reaction. Aryl groups favor the reaction, while sterically hindered groups reduce its reactivity. To improve the yield of target product 1, R in this invention... 1 Preferred to be benzene and its derivatives are substituents.

[0016] Specifically, at the start of the reaction, reactant 1 (1,2,3,4-tetrahydroquinoline derivative) is activated under the conditions of a catalyst and heating. The catalyst promotes the formation of an imine intermediate. Furthermore, in the presence of oxygen, the catalyst catalyzes the oxidation at the C-3 position to form a carbonyl structure. Finally, the target product, 3-hydroxyquinoline derivative, is obtained through a tautomerism reaction, as shown in the following reaction formula: After the reaction is completed, the catalyst is removed by filtration, and the resulting reaction mixture contains the target product.

[0017]

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

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

[0020]

[0021] Preferably, the catalyst is an organic-inorganic hybrid material synthesized by reacting Mn-containing hydrotalcite (LDH) with organic acids. The metal in the catalyst structure may also include one or more of Ni, Mg, Al, Cu, and Fe, and the organic acid may include hexanoic acid, valeric acid, benzoic acid, acetic acid, propionic acid, butyric acid, or benzoic acid with single or multiple substituted groups. Proton-coupled electron transfer (PCET) is one of the important pathways for the oxidative activation of C–H bonds. This invention uses a manganese-containing organic-inorganic hybrid material as a catalyst to enhance the central Mn content through the coordination of organic carboxylic acid molecules. 3+ The oxidation potential and electron transfer ability of the carboxylic acid molecule are utilized to coordinate with the central metal of the six-coordinate (hydrogen) oxide, thereby increasing the positive charge density of the central metal and constructing a strongly basic M. n+ -O 2- (H) sites effectively enhance the surface basicity and proton transfer ability of the material, ultimately yielding a catalytic material capable of efficiently catalyzing the PCET reaction process, thereby achieving the oxidative activation of C–H bonds. Further preferred catalysts containing Ni and Mg, as well as hexanoic acid, valeric acid, butyric acid, and benzoic acid, exhibit superior catalytic activity. This is primarily because Ni and Mg can effectively stabilize high-valence Mn species and enhance the surface basicity of the catalyst, thereby improving its activity in catalyzing the PCET process. Furthermore, the manganese-based material formed by hexanoic acid, valeric acid, butyric acid, and benzoic acid exhibits good substrate and oxygen molecule compatibility, effectively promoting the reaction of this invention.

[0022] Manganese-based catalysts were prepared according to the following steps: Mn-based hydrotalcite, organic acid, and solvent (dodecane) were added to a reactor, oxygen was introduced, and the reaction was carried out at 110–130 °C with stirring. After the reaction was completed, the catalyst was washed with ethyl acetate and then dried in an oven at 80 °C for 12 h to obtain the manganese-based catalyst.

[0023] Preferably, the amount of catalyst used is 40–120 g / mol relative to the amount of reactant 1. Too low a catalyst amount results in low efficiency in the synthesis of 3-hydroxyquinoline; while too high a catalyst amount reduces the economics of the reaction.

[0024] Preferably, the amount of solvent used is 1 to 5 L / mol relative to the amount of reactant 1. Too little solvent results in uneven dispersion of the system, leading to poor selectivity of the target product; while too much solvent reduces the economic efficiency 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 temperatures are unfavorable for the oxidative activation of 1,2,3,4-tetrahydroquinoline, while at higher temperatures, reactant 1 is prone to dehydrogenation to generate quinoline byproducts, reducing the selectivity of the target product.

[0026] Preferably, the stirring rate in the preparation method of the present invention is 400–1000 r / min. A stirring rate that is too low will affect the mass transfer performance of the reaction system and reduce the reaction rate.

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

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

[0029] (2) This invention uses a hybrid material synthesized by coordination of Mn-containing hydrotalcite with 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 operation, good economy and easy separation and purification of products. Detailed Implementation

[0030] To further illustrate the technical means and effects adopted by the present invention to achieve the intended purpose, the specific implementation methods, features and effects of the synthesis method of 3-hydroxyquinoline derivatives proposed according to the present invention are described in detail below.

[0031] In specific embodiments of the present invention, the sources of each commercially available material are as follows:

[0032]

[0033] Example 1

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

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

[0036] Example 2

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

[0038] 80 mg of BBA-Ni2Mn catalyst was added to the reaction system, along with 1 mmol of 1,2,3,4-tetrahydroquinoline (1a). Oxygen was introduced, the temperature was maintained at 120 °C, the stirring rate was 500 r / min, and 2 mL of mesitylene was added. The reaction was stirred for 4 h. After the reaction was completed, the catalyst was removed by filtration. The contents of the reactants 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC. 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-type hydrotalcite, 0.5 mmol of 2,4,5-trimethylbenzoic acid, and 2 mL of dodecane were added to a reactor, and the reaction was carried out at 120 °C with stirring for 12 h. After the reaction was completed, the catalyst was washed with ethyl acetate and then dried in an oven at 80 °C for 12 h to obtain the manganese-based catalyst TBA-Ni2Mg2Mn.

[0041] 80 mg of TBA-Ni2Mg2Mn catalyst was added to the reaction system, along with 1 mmol of 1,2,3,4-tetrahydroquinoline (1a). Oxygen was introduced, the temperature was maintained at 120 °C, the stirring rate was 400 r / min, and 2 mL of mesitylene was added. The reaction was stirred for 4 h. After the reaction was completed, the catalyst was removed by filtration. The contents of the reactants 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC. 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-based hydrotalcite, 0.3 mmol of propionic acid, and 2 mL of dodecane were added to a reactor, and the reaction was carried out at 120 °C with stirring for 12 h. After the reaction was completed, the catalyst was washed with ethyl acetate and then dried in an oven at 80 °C for 12 h to obtain the manganese-based catalyst PA-Mn2Al.

[0044] 50 mg of PA-Mn2Al catalyst and 1 mmol of 1,2,3,4-tetrahydroquinoline (1a) were added to the reaction system. Oxygen was introduced, the temperature was maintained at 100 °C, the stirring rate was 600 r / min, and 2 mL of p-xylene was added. The reaction was stirred for 10 h. After the reaction was completed, the catalyst was removed by filtration. The contents of the reactants 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC. 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-based hydrotalcite, 0.4 mmol of benzoic acid, and 2 mL of dodecane were added to a reactor, and the reaction was carried out at 120 °C with stirring for 12 h. After the reaction was completed, the catalyst was washed with ethyl acetate and then dried in an oven at 80 °C for 12 h to obtain the manganese-based catalyst BA-CuMgMn.

[0047] 100 mg of BA-CuMgMn catalyst and 1 mmol of 1,2,3,4-tetrahydroquinoline (1a) were added to the reaction system. Oxygen was introduced, the temperature was maintained at 120 °C, the stirring rate was 400 r / min, and 2 mL of 4-isopropyltoluene was added. The reaction was stirred for 3 h. After the reaction was completed, the catalyst was removed by filtration. The contents of the reactants 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC. 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-based hydrotalcite, 0.5 mmol of hexanoic acid, and 2 mL of dodecane were added to a reactor, and the reaction was carried out at 120 °C with stirring for 12 h. After the reaction was completed, the catalyst was washed with ethyl acetate and then dried in an oven at 80 °C for 12 h to obtain the manganese-based catalyst HA-Mn2Fe.

[0050] 50 mg of HA-Mn2Fe catalyst and 1 mmol of 1,2,3,4-tetrahydroquinoline (1a) were added to the reaction system. Oxygen was introduced, the temperature was maintained at 120 °C, the stirring rate was 600 r / min, and 2 mL of p-tert-butyltoluene was added. The reaction was stirred for 7 h. After the reaction was completed, the catalyst was removed by filtration. The contents of the reactants 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC. 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-based hydrotalcite, 0.6 mmol of hexanoic acid, and 2 mL of dodecane were added to a reactor, and the reaction was carried out at 120 °C with stirring for 12 h. After the reaction was completed, the catalyst was washed with ethyl acetate and then dried in an oven at 80 °C for 12 h to obtain the manganese-based catalyst HA-Ni3MnAl.

[0053] 80 mg of HA-Ni3MnAl catalyst, 1 mmol of 1,2,3,4-tetrahydroquinoline (1a), and oxygen were introduced into the reaction system. The temperature was maintained at 120 °C, the stirring rate at 400 r / min, and 2 mL of p-tert-butyltoluene were added. The reaction was stirred for 3 h. After the reaction was completed, the catalyst was removed by filtration. The contents of the reactants 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC. 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-based hydrotalcite, 0.3 mmol of benzoic acid, and 2 mL of dodecane were added to a reactor, and the reaction was carried out at 120 °C with stirring for 12 h. After the reaction was completed, the catalyst was washed with ethyl acetate and then dried in an oven at 80 °C for 12 h to obtain the manganese-based catalyst BA-Ni2Mn.

[0056] 60 mg of BA-Ni2Mn catalyst and 1 mmol of 1,2,3,4-tetrahydroquinoline (1a) were added to the reaction system. Oxygen was introduced, the temperature was maintained at 120 °C, the stirring rate was 500 r / min, and 2 mL of mesitylene was added. The reaction was stirred for 5 h. After the reaction was completed, the catalyst was removed by filtration. The contents of the reactants 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC. 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 from Example 1 was used.

[0059] 20 mg of HA-Ni2Mn catalyst and 0.5 mmol of 1,2,3,4-tetrahydroquinoline (1a) were added to the reaction system. Oxygen was introduced, with an oxygen / 1,2,3,4-tetrahydroquinoline molar ratio of 30:1. The temperature was maintained at 150 °C, the stirring rate at 400 r / min, and 1 mL of p-tert-butyltoluene was added. The reaction was stirred for 2 h. After the reaction was completed, the catalyst was removed by filtration. The contents of the reactants 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC. 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 yield of the target product 3-hydroxyquinoline was 51%.

[0060] Example 10

[0061] The catalyst from Example 1 was used.

[0062] 30 mg of HA-Ni2Mn catalyst and 0.5 mmol of 1,2,3,4-tetrahydroquinoline (1a) were added to the reaction system. Oxygen was introduced, with an oxygen / 1,2,3,4-tetrahydroquinoline molar ratio of 50:1. The temperature was maintained at 130 °C, the stirring rate at 400 r / min, and 2 mL of o-xylene was added. The reaction was stirred for 4 h. After the reaction was completed, the catalyst was removed by filtration. The contents of the reactants 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC. 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] Example 11

[0064] The catalyst from Example 1 was used.

[0065] 40 mg of HA-Ni2Mn catalyst and 0.5 mmol of 1,2,3,4-tetrahydroquinoline (1a) were added to the reaction system. Oxygen was introduced, with an oxygen / 1,2,3,4-tetrahydroquinoline molar ratio of 60:1. The temperature was maintained at 110 °C, the stirring rate at 400 r / min, and 1 mL of p-tert-butyltoluene was added. The reaction was stirred for 5 h. After the reaction was completed, the catalyst was removed by filtration. The contents of the reactants 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC. 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 from Example 1 was used.

[0068] 60 mg of HA-Ni2Mn catalyst and 0.5 mmol of 1,2,3,4-tetrahydroquinoline (1a) were added to the reaction system. Oxygen was introduced, with an oxygen / 1,2,3,4-tetrahydroquinoline molar ratio of 80:1. The temperature was maintained at 100 °C, the stirring rate at 400 r / min, and 2 mL of 1,2,4,5-tetramethylbenzene was added. The reaction was stirred for 6 h. After the reaction was completed, the catalyst was removed by filtration. The contents of the reactants 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC. The conversion rate and selectivity of the reaction were calculated. It was found that the conversion rate of 1,2,3,4-tetrahydroquinoline was 84%, and the yield of the target product 3-hydroxyquinoline was 50%.

[0069] Example 13

[0070] The catalyst from Example 1 was used.

[0071] 100 mg of HA-Ni2Mn catalyst and 1 mmol of 1,2,3,4-tetrahydroquinoline (1a) were added to the reaction system. Oxygen was introduced, with an oxygen / 1,2,3,4-tetrahydroquinoline molar ratio of 60:1. The temperature was maintained at 120 °C, the stirring rate at 400 r / min, and 2 mL of mesitylene was added. The reaction was stirred for 3 h. After the reaction was completed, the catalyst was removed by filtration. The contents of the reactants 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC. 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 55%.

[0072] Example 14

[0073] The catalyst from Example 1 was used.

[0074] 80 mg of HA-Ni2Mn catalyst and 1 mmol of 1,2,3,4-tetrahydroquinoline (1a) were added to the reaction system. Oxygen was introduced, with an oxygen / 1,2,3,4-tetrahydroquinoline molar ratio of 30:1. The temperature was maintained at 80 °C, the stirring rate at 1000 r / min, and 2 mL of p-tert-butyltoluene was added. The reaction was stirred for 8 h. After the reaction was completed, the catalyst was removed by filtration. The contents of the reactants 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC. 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] Example 15

[0076] The catalyst from Example 1 was used.

[0077] 110 mg of HA-Ni2Mn catalyst and 1 mmol of 1,2,3,4-tetrahydroquinoline (1a) were added to the reaction system. Oxygen was introduced, with an oxygen / 1,2,3,4-tetrahydroquinoline molar ratio of 100:1. The temperature was maintained at 50 °C, the stirring rate at 800 r / min, and 2 mL of p-tert-butyltoluene was added. The reaction was stirred for 40 h. After the reaction was completed, the catalyst was removed by filtration. The contents of the reactants 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC. 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 manganese-based catalytic precursors, 30 mg of Ni₂Mn-LDH catalyst and 0.5 mmol of 1,2,3,4-tetrahydroquinoline (1a) were added to the reaction system. Oxygen was introduced, and the molar ratio of oxygen to 1,2,3,4-tetrahydroquinoline was 50:1. The reaction was carried out at 120 °C and 400 r / min for 7 h. The content of reactants 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution was analyzed by LC, and the conversion and selectivity of the reaction were calculated. It was found that the conversion rate of 1,2,3,4-tetrahydroquinoline was 82%, and the yield of the target product 3-hydroxyquinoline was 5%.

[0080] Comparative Example 2

[0081] The role of the catalyst was verified. 0.5 mmol of 1,2,3,4-tetrahydroquinoline (1a) was added to the reaction system, oxygen was introduced, the temperature was maintained at 120℃, the stirring rate was 400 r / min, and 2 mL of p-tert-butyltoluene was added. The reaction was stirred for 5 h. After the reaction was completed, the catalyst was removed by filtration. The contents of the reactant 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC, and the conversion rate and selectivity were calculated. It was found that the conversion rate of 1,2,3,4-tetrahydroquinoline was 7%, and the yield of the target product 3-hydroxyquinoline was 0%.

[0082] Comparative Example 3

[0083] The difference between air and oxygen was verified. 30 mg of HA-Ni2Mn catalyst, 0.5 mmol of 1,2,3,4-tetrahydroquinoline (1a), and air were added to the reaction system. The temperature was maintained at 120 °C, the stirring rate at 400 r / min, and 2 mL of p-tert-butyltoluene was added. The reaction was stirred for 5 h. After the reaction was complete, the catalyst was removed by filtration. The contents of the reactant 1,2,3,4-tetrahydroquinoline and the target product 3-hydroxyquinoline in the reaction solution were analyzed by LC. 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 37%.

[0084] Substrate Expansion Experiment

[0085] Using the reaction conditions of Example 1, the method was further extended to various types of reaction substrates to examine its adaptability to different types of reaction substrates. Since the optimal reaction conditions vary depending on the reaction substrate, the reaction yields described below are only for the reaction conditions of Example 1 and do not represent the best results for all reaction substrates of this invention. The reaction results are shown below:

[0086] Table 2. Reaction results for different substrates

[0087]

[0088]

[0089]

[0090]

[0091] Performance Results Explanation

[0092] The substrate expansion experiments show that the catalyst and preparation method of this invention have good substrate expansion properties and a wide range of applications.

[0093] Compared to Example 1, Comparative Example 1 used Ni2Mn-LDH 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. This suggests 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] Compared to Example 1, Comparative Example 2 did not add a catalyst, and the results showed that the conversion rate and yield of 1,2,3,4-tetrahydroquinoline were significantly reduced, indicating that the catalyst HA-Ni2Mn has a significant promoting effect on the conversion of 1,2,3,4-tetrahydroquinoline to 3-hydroxyquinoline.

[0095] Comparative Example 3, compared to Example 1, verifies the difference between air and oxygen. Using air as the oxidant significantly reduced the conversion and yield of 1,2,3,4-tetrahydroquinoline, indicating that molecular oxygen plays a crucial role as an oxidant in the oxidation process. The low oxygen concentration in the air affected the conversion rate of 1,2,3,4-tetrahydroquinoline.

[0096] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes, and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A method for synthesizing a 3-hydroxyquinoline derivative, characterized in that, The following steps are included: Reactant 1, catalyst, and solvent were added to the reactor, and oxygen-containing gas was introduced under normal pressure. The reaction was carried out under stirring and heating conditions. After the reaction was completed, the target product 2 was obtained through treatment. The reaction formula is as follows: In the reaction formula, reactant 1 is a 1,2,3,4-tetrahydroquinoline compound; target product 2 is a 3-hydroxyquinoline derivative. In the reaction formula, (R) 1 ) m This represents the substituents at positions 5, 6, 7, and 8 on the connected aromatic ring, where m represents any integer from 1 to 4, (R 2 ) n This represents the substituents at the 2- and 4-positions on the nitrogen-containing ring, where n represents any integer from 1 to 2, and each R... 1 and R 2 The substituents are independently selected from H, halogens, and C. 1-3 Alkyl, methoxy, hydroxy, methyl formate, p-tolyl, or 3,5-dimethylphenyl; The catalyst is an organic-inorganic hybrid material synthesized by reacting Mn-containing hydrotalcite with organic acids. The metal in the catalyst structure also includes one or more of Ni, Mg, Al, Cu, and Fe, and the organic acid is any one of hexanoic acid, valeric acid, benzoic acid, propionic acid, and butyric acid.

2. The method for synthesizing the 3-hydroxyquinoline derivative according to claim 1, characterized in that, The reactant 1 is selected from one of the compounds shown in 1a-1z below: 。 3. The method for synthesizing the 3-hydroxyquinoline derivative according to claim 1, characterized in that, The amount of catalyst used is 40~120 g / mol relative to the amount of reactant 1.

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

5. The method for synthesizing the 3-hydroxyquinoline derivative according to claim 4, characterized in that, The amount of solvent used is 1 to 5 L / mol relative to the amount of reactant 1.

6. The method for synthesizing the 3-hydroxyquinoline derivative according to claim 1, characterized in that, The reaction temperature is 50~150 ℃.

7. The method for synthesizing the 3-hydroxyquinoline derivative according to claim 1, characterized in that, The reaction time is 2 to 40 hours.

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

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