Synthesis process of a safety agent to detoxify quinine

Abstract

This invention discloses a synthetic process for the safetyant antidote quinone, comprising the following steps: reacting 5-chloro-8-hydroxyquinoline and 2-heptyl chloroacetate as raw materials to generate the target product in the presence of a composite catalyst and an acid-binding agent. This invention uses a composite catalyst for the synthesis of the safetyant antidote quinone, significantly shortening the reaction cycle and reducing byproduct formation. The synthetic process features mild reaction conditions, simple operation, reduced emissions of waste, lower production costs, and improved product yield and content, thus facilitating the industrial production of the safetyant antidote quinone.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, specifically relating to a synthesis process for a safer antidote, quinine. Background Technology

[0002] Quizalofop-P-ethyl, also known as quizalofop-P-ethyl, has the chemical name 1-methylhexyl-(5-chloro-8-quinolinoxy)acetate. Quizalofop-P-ethyl was first discovered by J. Amrein et al., and later marketed by Syngenta, primarily used as a safener for the herbicide quizalofop-P-ethyl. When mixed with quizalofop-P-ethyl in a certain proportion, it is applied to cereal crops and provides excellent control of grassy weeds such as sage, wild oat, wild oat, ryegrass, Kentucky bluegrass, and foxtail grass.

[0003] Currently, the main synthetic processes for antidote quinolone include the following:

[0004] Patent CN103193706A discloses a method for synthesizing anti-toxic quinone by condensing methyl chloroacetate with 5-chloro-8-hydroxyquinoline to generate the intermediate methyl 5-chloro-8-quinolineoxyacetate, followed by transesterification with 2-heptanol. However, this method requires high temperatures for synthesizing the intermediate and uses excessive 2-heptanol, which is difficult to remove during post-processing, thus affecting product quality. The process conditions are demanding and the operation is cumbersome.

[0005] Patent CN105001158A discloses a method for synthesizing anti-toxic quinoline from 5-chloro-8-hydroxyquinoline and chloroacetic acid-2-heptyl ester using 4-methyl-2-pentanone as both a reaction solvent and a recrystallization solvent. However, this method involves high reaction temperatures, long reaction times, and the generation of moisture in the system, which easily degrades 4-methyl-2-pentanone and chloroacetic acid-2-heptyl ester, affecting product quality. Furthermore, it results in significant solvent loss, difficult waste treatment, and increased production costs.

[0006] Patents CN1568314A and CN103930402A both disclose a method for preparing antidote quinoline by reacting 5-chloro-8-hydroxyquinoline with an aqueous solution of sodium hydroxide in N-methylpyrrolidone (NMP), followed by reflux of toluene to remove excess water, and then adding potassium carbonate and 2-heptyl chloroacetate to react. The disadvantages of this reaction are high temperature, cumbersome operation, and long reaction cycle; the mixed solvent of toluene and N-methylpyrrolidone (NMP) results in a variety of wastes that are difficult to treat, low product content, and poor properties; and high equipment requirements and production costs.

[0007] Patent CN113461610A discloses a method of salting 5-chloro-8-hydroxyquinoline with potassium carbonate and sodium carbonate in dimethyl sulfoxide, then removing excess water with toluene, followed by the addition of methyl chloroacetate to generate methyl 5-chloro-8-hydroxyquinolineoxyacetate, which then undergoes an transesterification reaction with 2-heptanol to generate detoxifying quinoline. However, this method cannot achieve one-step preparation of the target product. The resulting mixed solvent of toluene and dimethyl sulfoxide is difficult to handle; it also suffers from problems such as difficulty in separating the mixed sodium and potassium salts and difficulty in controlling water entrainment; the synthesis temperature of the intermediate is high, and the use of excessive 2-heptanol requires high-temperature desolventizing and separation, resulting in low product content, poor properties, and high cost, which also increases the difficulty of industrial production.

[0008] Patents CN113135851A and CN113123431A both disclose a method of forming a salt of 5-chloro-8-hydroxyquinoline and potassium carbonate in N,N-dimethylformamide (DMF), followed by the addition of methyl chloroacetate to generate methyl 5-chloro-8-hydroxyquinolineoxyacetate, which then undergoes an transesterification reaction with 2-heptanol to generate detoxifying quinone. However, this method cannot achieve one-step preparation of the target product. The synthesis intermediates require high temperatures and excessive 2-heptanol, necessitating high-temperature solvent removal and separation, resulting in poor product content and properties, and difficulty in solvent recovery. Furthermore, it generates ammonia nitrogen wastewater and waste gas, which are difficult to treat, leading to high production costs and long production cycles, making it unsuitable for the industrial production of detoxifying quinone.

[0009] Therefore, the key to achieving the further large-scale and economical production of the safety agent detoxifying quinine lies in solving the problems of harsh reaction conditions, cumbersome operation, excessive waste and difficulty in treatment, high equipment requirements and production costs in the existing technology. Summary of the Invention

[0010] In order to overcome the shortcomings of the prior art, the present invention aims to provide a synthesis process for the safe agent detoxifying quinine.

[0011] The technical solution of the present invention to solve the above-mentioned technical problems is as follows:

[0012] The first aspect of the present invention provides a process for synthesizing a safe agent, quinine, characterized by comprising the following steps: reacting 5-chloro-8-hydroxyquinoline and 2-heptyl chloroacetate as raw materials to generate compound I in the presence of a composite catalyst and an acid-binding agent;

[0013] The specific reaction route is as follows:

[0014]

[0015] Furthermore, the composite catalyst is prepared from potassium bromide, 18-crown ether-6 and quaternary ammonium salt; the mass ratio of potassium bromide, 18-crown ether-6 and quaternary ammonium salt is 1-2:1-2:1-2, preferably 1-1.2:1-1.2:1-1.2;

[0016] Furthermore, the quaternary ammonium salt is one or more of tetraalkylammonium chloride, tetraalkylammonium bromide, tetraalkylammonium iodide, aryltrialkylammonium chloride, aryltrialkylammonium bromide or aryltrialkylammonium iodide, preferably tetrabutylammonium bromide, benzyltriethylammonium chloride, tetramethylammonium chloride or tridecyltrimethylammonium bromide;

[0017] Furthermore, the molar ratio of 2-heptyl chloroacetate to 5-chloro-8-hydroxyquinoline is 1 to 1.5:1, preferably 1 to 1.3:1;

[0018] Furthermore, the molar ratio of the acid-binding agent to 5-chloro-8-hydroxyquinoline is 1 to 1.5:1, preferably 1 to 1.3:1; the mass ratio of 5-chloro-8-hydroxyquinoline to the composite catalyst is 10 to 40:1, preferably 15 to 35:1; wherein, the acid-binding agent is preferably potassium carbonate;

[0019] Furthermore, the reaction solvent is one or more of 4-methyl-2-pentanone, butanone, 2-pentanone, 3-pentanone, acetylacetone, 3-methyl-2-butanone, 2-hexanone, 3-hexanone, 2-methyl-3-pentanone, 3,3-dimethyl-2-butanone, 2-heptanone, 3-heptanone, 4-heptanone, 2,4-dimethyl-3-pentanone, or cyclohexanone, preferably 4-methyl-2-pentanone;

[0020] Furthermore, the reaction temperature is 50–100°C, preferably 50–80°C; the reaction time is 2–10 h, preferably 3–6 h.

[0021] Furthermore, after the reaction is complete, the process includes filtration, washing, vacuum concentration, recrystallization, and / or drying steps; wherein the recrystallization solvent is preferably methylcyclohexane;

[0022] The second aspect of the present invention provides a method for preparing a composite catalyst for the above-mentioned synthesis process of detoxifying quinine with a safety agent, characterized by comprising the following steps: dissolving 18-crown ether-6, potassium bromide and quaternary ammonium salt in methanol in a certain proportion, performing a first cooling filtration, concentrating the filtrate, and then performing a second cooling filtration and drying to obtain the composite catalyst;

[0023] Furthermore, the first cooling is to 40-60°C, and the second cooling is to 0-20°C.

[0024] In this invention, if there is a conflict between the Chinese name and the structural formula of a compound, the structural formula shall prevail, unless the structural formula is obviously incorrect.

[0025] The beneficial effects of this invention are as follows:

[0026] This invention utilizes a composite catalyst for the synthesis of the safener antitoxin quinine, significantly shortening the reaction cycle and reducing byproduct formation. The synthesis process features mild reaction conditions, simple operation, reduced emissions of waste, lower production costs, and improved product yield and content, making it more suitable for the industrial production of the safener antitoxin quinine. Attached Figure Description

[0027] Figure 1 : Hydrogen spectrum of detoxifying quinine in Example 1 Detailed Implementation

[0028] The present invention is illustrated below with reference to examples, but is not intended to limit the invention. Any simple substitutions or modifications made to the present invention by those skilled in the art are within the scope of the technical solutions protected by this invention.

[0029] Example 1:

[0030] At room temperature, 500g of methanol, 25g of potassium bromide, 30g of 18-crown ether-6, and 30g of tetrabutylammonium bromide were added to a reactor equipped with a thermometer, a dryer, and a stirring device. The mixture was heated to 65-70°C, refluxed and stirred for 1 hour, cooled to 50-55°C, and filtered. The filter cake was undissolved. The filtrate was concentrated to about 100g of concentrate, cooled to 10-15°C, filtered, and dried to obtain 22.8g of the compound catalyst.

[0031] At room temperature, in a reactor equipped with a thermometer, desiccator, and stirrer, 700 g of 4-methyl-2-pentanone, 104.3 g (0.575 mol) of 5-chloro-8-hydroxyquinoline, and 115.7 g (0.592 mol) of chloro-acetic acid-2-heptyl ester were added, along with 3 g of a compound catalyst. The temperature was raised to 50 °C, and 96 g (0.696 mol) of potassium carbonate was added. The mixture was stirred and the temperature was maintained at 70–80 °C. After reacting for 3–5 hours, samples were taken for analysis: 0.05% 5-chloro-8-hydroxyquinoline and 0.592 mol chloro-acetic acid-2-heptyl ester were present. 2.10% heptyl ester, 97.22% antidote quinone, reaction ended; filtered while hot, the filtrate was washed with 100g of water, separated into layers, the organic phase was kept under negative pressure of 0.095-0.1MPa and temperature of 50-85℃, 4-methyl-2-pentanone was recovered completely, cooled to 50℃, 250g of methylcyclohexane was added, the temperature was raised to 60-75℃ to dissolve completely, stirred for 1 hour, slowly cooled to 0-5℃ to precipitate solid, filtered, washed to obtain wet product, dried to obtain 182.65g of antidote quinone product, content 99.3%, yield 94%. 1H-NMR(CDCl3,500MHz)δ0.84(t,J=7.0Hz,3H),1.19-1.23(m,9H),1.43-1.57(m,2H),4.96(s,2H),5.03(m,1H),6.90(d,J =8.0Hz,1H),7.51(d,J=8.5Hz,1H),7.58(dd,J=4.0,8.5Hz,1H),8.56(dd,J=2.0,8.5Hz,1H),9.02(dd,J=1.5,4.0Hz,1H).

[0032] Example 2:

[0033] At room temperature, 500g of methanol, 25g of potassium bromide, 30g of 18-crown ether-6, and 30g of tetrabutylammonium bromide were added to a reactor equipped with a thermometer, a dryer, and a stirring device. The mixture was heated to 65-70°C, refluxed and stirred for 1 hour, cooled to 50-55°C, and filtered. The filter cake was undissolved. The filtrate was concentrated to about 100g of concentrate, cooled to 10-15°C, filtered, and dried to obtain 22.8g of the compound catalyst.

[0034] At room temperature, in a reactor equipped with a thermometer, desiccator, and stirrer, 700 g of 4-methyl-2-pentanone, 104.3 g (0.575 mol) of 5-chloro-8-hydroxyquinoline, and 115.7 g (0.592 mol) of chloro-2-heptyl acetate were added, along with 6 g of a compound catalyst. The temperature was raised to 50°C, and 96 g (0.696 mol) of potassium carbonate was added. The mixture was stirred and the temperature was maintained at 50–60°C. After reacting for 3–5 hours, samples were taken for analysis: 0.01% 5-chloro-8-hydroxyquinoline and 0.592 mol chloro-2-heptyl acetate were present. 1.68% heptyl ester and 98.12% antidote quinone were added, and the reaction was completed. The mixture was filtered while hot, and the filtrate was washed with 100g of water. The layers were separated, and the organic phase was kept under negative pressure of 0.095-0.1MPa and temperature of 50-85℃. 4-Methyl-2-pentanone was recovered completely. The temperature was lowered to 50℃, and 250g of methylcyclohexane was added. The mixture was heated to 60-75℃ and completely dissolved. The mixture was stirred for 1 hour, and then slowly cooled to 0-5℃ to precipitate a solid. The solid was filtered, washed to obtain a wet product, and dried to obtain 187.72g of antidote quinone product with a purity of 99.2% and a yield of 96.5%.

[0035] Example 3:

[0036] At room temperature, in a reactor equipped with a thermometer, desiccator, and stirrer, 700 g of 4-methyl-2-pentanone, 104.3 g (0.575 mol) of 5-chloro-8-hydroxyquinoline, and 115.7 g (0.592 mol) of chloro-acetic acid-2-heptyl ester were added, along with 6 g of a compound catalyst. The temperature was raised to 50 °C, and 83.3 g (0.603 mol) of potassium carbonate was added. The mixture was stirred and the temperature was maintained at 60–65 °C. After reacting for 3–5 hours, samples were taken for analysis: 0.01% 5-chloro-8-hydroxyquinoline and 0.592 mol chloro-acetic acid-2-heptyl ester were present. 1.89% heptyl ester, 97.48% antidote quinone, reaction ended; filtered while hot, the filtrate was washed with 100g of water, separated into layers, the organic phase was kept under negative pressure of 0.095-0.1MPa and temperature of 50-85℃, 4-methyl-2-pentanone was recovered completely, cooled to 50℃, 250g of methylcyclohexane was added, the temperature was raised to 60-75℃ to dissolve completely, stirred for 1 hour, slowly cooled to 0-5℃ to precipitate solid, filtered, washed to obtain wet product, dried to obtain 185.95g of antidote quinone product, content 99.1%, yield 95.5%.

[0037] Example 4:

[0038] At room temperature, 500g of methanol, 20g of potassium bromide, 20g of 18-crown ether-6, and 20g of benzyltriethylammonium chloride were added to a reactor equipped with a thermometer, a dryer, and a stirring device. The mixture was heated to 65-70°C, refluxed and stirred for 1 hour, cooled to 50-55°C, and filtered. The filter cake was undissolved. The filtrate was concentrated to about 100g of concentrate, cooled to 10-15°C, filtered, and dried to obtain 17.5g of the compound catalyst.

[0039] At room temperature, in a reactor equipped with a thermometer, desiccator, and stirrer, 700 g of 4-methyl-2-pentanone, 104.3 g (0.575 mol) of 5-chloro-8-hydroxyquinoline, and 115.7 g (0.592 mol) of chloro-2-heptyl acetate were added, along with 6 g of a compound catalyst. The temperature was raised to 50°C, and 96 g (0.696 mol) of potassium carbonate was added. The mixture was stirred and the temperature was maintained at 50–60°C. After reacting for 3–5 hours, samples were taken for analysis: 0.03% 5-chloro-8-hydroxyquinoline and 0.592 mol / L chloro-2-heptyl acetate were present. 1.87% heptyl ester and 97.92% antidote quinone were added, and the reaction was completed. The mixture was filtered while hot, and the filtrate was washed with 100g of water. The layers were separated, and the organic phase was kept under negative pressure of 0.095-0.1MPa and temperature of 50-85℃. 4-Methyl-2-pentanone was recovered completely. The temperature was lowered to 50℃, and 250g of methylcyclohexane was added. The mixture was heated to 60-75℃ and completely dissolved. The mixture was stirred for 1 hour, and then slowly cooled to 0-5℃ to precipitate a solid. The solid was filtered, washed to obtain a wet product, and dried to obtain 186.75g of antidote quinone product with a purity of 99.4% and a yield of 96.2%.

[0040] Example 5:

[0041] At room temperature, 500g of methanol, 20g of potassium bromide, 20g of 18-crown ether-6, and 20g of tetramethylammonium chloride were added to a reactor equipped with a thermometer, a dryer, and a stirring device. The mixture was heated to 65-70°C, refluxed and stirred for 1 hour, cooled to 50-55°C, and filtered. The filter cake was undissolved. The filtrate was concentrated to about 100g of concentrate, cooled to 10-15°C, filtered, and dried to obtain 19.3g of the compound catalyst.

[0042] At room temperature, in a reactor equipped with a thermometer, desiccator, and stirrer, 700 g of 4-methyl-2-pentanone, 104.3 g (0.575 mol) of 5-chloro-8-hydroxyquinoline, and 115.7 g (0.592 mol) of chloro-2-heptyl acetate were added, along with 5 g of a compound catalyst. The temperature was raised to 50°C, and 96 g (0.696 mol) of potassium carbonate was added. The mixture was stirred and the temperature was maintained at 50–60°C. After reacting for 3–5 hours, samples were taken for analysis: 0.03% 5-chloro-8-hydroxyquinoline and 0.592 mol chloro-2-heptyl acetate were present. 2.10% heptyl ester, 97.62% antidote quinone, reaction ended; filtered while hot, the filtrate was washed with 100g of water, separated into layers, the organic phase was kept under negative pressure of 0.095-0.1MPa and temperature of 50-85℃, 4-methyl-2-pentanone was recovered completely, cooled to 50℃, 250g of methylcyclohexane was added, the temperature was raised to 60-75℃ to dissolve completely, stirred for 1 hour, slowly cooled to 0-5℃ to precipitate solid, filtered, washed to obtain wet product, dried to obtain 187.97g of antidote quinone product, with a content of 99.3% and a yield of 96.7%.

[0043] Example 6:

[0044] At room temperature, 500g of methanol, 20g of potassium bromide, 20g of 18-crown ether-6, and 20g of tridecyltrimethylammonium bromide were added to a reactor equipped with a thermometer, a dryer, and a stirring device. The mixture was heated to 65-70°C, refluxed and stirred for 1 hour, cooled to 50-55°C, and filtered. The filter cake was undissolved. The filtrate was concentrated to about 100g of concentrate, cooled to 10-15°C, filtered, and dried to obtain 15.6g of the compound catalyst.

[0045] At room temperature, in a reactor equipped with a thermometer, desiccator, and stirrer, 700 g of 4-methyl-2-pentanone, 104.3 g (0.575 mol) of 5-chloro-8-hydroxyquinoline, and 115.7 g (0.592 mol) of chloro-2-heptyl chloroacetate were added, along with 5 g of a compound catalyst. The temperature was raised to 50°C, and 96 g (0.696 mol) of potassium carbonate was added. The mixture was stirred and the temperature was maintained at 50–60°C. After reacting for 3–5 hours, samples were taken for analysis: 0.08% 5-chloro-8-hydroxyquinoline and 0.592 mol / L chloro-2-heptyl chloroacetate were present. 1.90% heptyl ester and 98.02% antidote quinone were added, and the reaction was completed. The mixture was filtered while hot, and the filtrate was washed with 100g of water. The layers were separated, and the organic phase was kept under negative pressure of 0.095-0.1MPa and temperature of 50-85℃. 4-Methyl-2-pentanone was recovered completely. The temperature was lowered to 50℃, and 250g of methylcyclohexane was added. The mixture was heated to 60-75℃ and completely dissolved. The mixture was stirred for 1 hour, and then slowly cooled to 0-5℃ to precipitate a solid. The solid was filtered, washed to obtain a wet product, and dried to obtain 187.33g of antidote quinone product with a purity of 99.3% and a yield of 96.4%.

[0046] Example 7:

[0047] At room temperature, 70 g of 4-methyl-2-pentanone, 10.43 g (0.0575 mol) of 5-chloro-8-hydroxyquinoline, and 13.46 g (0.0696 mol) of chloro-acetic acid-2-heptyl ester were added to a reactor equipped with a thermometer, desiccator, and stirring device. 0.5 g of a compound catalyst was added, the temperature was raised to 50 °C, and 9.6 g (0.0696 mol) of potassium carbonate was added. The mixture was stirred and slowly heated to 50–60 °C. After reacting for 3–5 hours, samples were taken for analysis: 0.08% 5-chloro-8-hydroxyquinoline, 1.90% chloro-acetic acid-2-heptyl ester, and 98.02% detoxifying quinoline. The reaction was completed; the mixture was filtered while hot, and the filtrate was washed with 10g of water. The layers were separated, and the organic phase was kept under a negative pressure of 0.095-0.1MPa and a temperature of 50-85℃. 4-Methyl-2-pentanone was recovered completely. The temperature was lowered to 50℃, and 25g of petroleum ether was added. The mixture was heated to 60-75℃ to dissolve completely and stirred for 1 hour. The temperature was slowly lowered to 0-5℃ to precipitate a solid. The solid was filtered, washed to obtain a wet product, and dried to obtain 18.52g of antidote quinolone product with a purity of 99.2% and a yield of 95.2%.

[0048] Example 8:

[0049] At room temperature, 70 g of 4-methyl-2-pentanone, 10.43 g (0.0575 mol) of 5-chloro-8-hydroxyquinoline, 11.57 g (0.0592 mol) of chloro-acetic acid-2-heptyl ester, and 0.5 g of benzyltriethylammonium chloride were added to a reactor equipped with a thermometer, desiccator, and stirring device. The temperature was raised to 50 °C, and 9.6 g (0.0696 mol) of potassium carbonate was added. The mixture was stirred and the temperature was slowly raised to 60-70 °C. After reacting for 3-5 hours, samples were taken for analysis: 5-chloro-8-hydroxyquinoline 18.4%, chloro-acetic acid-2-heptyl ester 26.7%, and detoxifying quinoline 54.6%.

[0050] Example 9:

[0051] At room temperature, 70 g of 4-methyl-2-pentanone, 10.43 g (0.0575 mol) of 5-chloro-8-hydroxyquinoline, 11.57 g (0.0592 mol) of chloro-acetic acid-2-heptyl ester, and 0.5 g of 18-crown ether-6 were added to a reactor equipped with a thermometer, desiccator, and stirring device. The temperature was raised to 50 °C, and 9.6 g (0.0696 mol) of potassium carbonate was added. The mixture was stirred and the temperature was slowly raised to 60–70 °C. After reacting for 3–5 hours, samples were taken for analysis: 5-chloro-8-hydroxyquinoline 21.3%, chloro-acetic acid-2-heptyl ester 28.7%, and detoxifying quinoline 49.8%.

[0052] Example 10:

[0053] At room temperature, 70 g of 4-methyl-2-pentanone, 10.43 g (0.0575 mol) of 5-chloro-8-hydroxyquinoline, 11.57 g (0.0592 mol) of chloro-acetic acid-2-heptyl ester, and 0.5 g of potassium bromide were added to a reactor equipped with a thermometer, desiccator, and stirring device. The temperature was raised to 50 °C, and 9.6 g (0.0696 mol) of potassium carbonate was added. The mixture was stirred and the temperature was slowly raised to 60–70 °C. After reacting for 3–5 hours, samples were taken for analysis: 11.3% of 5-chloro-8-hydroxyquinoline, 17.4% of chloro-acetic acid-2-heptyl ester, and 70.5% of detoxifying quinoline.

[0054] Example 11:

[0055] At room temperature, 70 g of 4-methyl-2-pentanone, 10.43 g (0.0575 mol) of 5-chloro-8-hydroxyquinoline, and 11.57 g (0.0592 mol) of chloro-acetic acid-2-heptyl ester were added to a reactor equipped with a thermometer, desiccator, and stirring device. The temperature was raised to 50 °C, and 9.6 g (0.0696 mol) of potassium carbonate was added. The mixture was stirred and the temperature was slowly raised to 60–70 °C. After reacting for 3–5 hours, samples were taken for analysis: 38.4% of 5-chloro-8-hydroxyquinoline, 51.7% of chloro-acetic acid-2-heptyl ester, and 9.23% of detoxifying quinoline.

[0056] The above description is only a preferred embodiment of the present invention. It should be noted that those skilled in the art can make several modifications and improvements without departing from the inventive concept of the present invention, and these all fall within the protection scope of the present invention.

Claims

1. A process for the synthesis of the safener clomazone, characterized in that, The synthesis process comprises the following steps: reacting 5-chloro-8-hydroxyquinoline and chloroacetic acid-2-heptyl ester in the presence of a composite catalyst and an acid-binding agent to form a compound of formula I; the composite catalyst is prepared from potassium bromide, 18-crown-6 and a quaternary ammonium salt; the mass ratio of the potassium bromide, 18-crown-6 and the quaternary ammonium salt is 1-2:1-2:1-2; the reaction solvent is one or more of 4-methyl-2-pentanone, butanone, 2-pentanone, 3-pentanone, acetylacetone, 3-methyl-2-butanone, 2-hexanone, 3-hexanone, 2-methyl-3-pentanone, 3,3-dimethyl-2-butanone, 2-heptanone, 3-heptanone, 4-heptanone, 2,4-dimethyl-3-pentanone or cyclohexanone; the reaction temperature is 50-100℃, and the reaction time is 2-10h; the mass ratio of the 5-chloro-8-hydroxyquinoline and the composite catalyst is 10-40:1; the preparation method of the composite catalyst of the synthesis process comprises the following steps: dissolving 18-crown-6, potassium bromide and a quaternary ammonium salt in methanol at a certain ratio, performing first cooling and filtration, concentrating the filtrate, and then performing second cooling and filtration and drying to obtain the composite catalyst; the first cooling is to 40-60℃, and the second cooling is to 0-20℃; the quaternary ammonium salt is tetrabutylammonium bromide, benzyltriethylammonium chloride, tetramethylammonium chloride or tridecyltrimethylammonium bromide; and the acid-binding agent is potassium carbonate. The specific reaction route is as follows:

2. The synthesis process of claim 1, wherein, The molar ratio of the chloroacetic acid-2-heptyl ester and the 5-chloro-8-hydroxyquinoline is 1-1.5:

1.

3. The synthesis process of claim 1, wherein, The molar ratio of the acid-binding agent and the 5-chloro-8-hydroxyquinoline is 1-1.5:

1.

4. The synthesis process of claim 1, wherein, After the reaction is completed, the process further comprises the steps of filtration, washing, concentration under reduced pressure, recrystallization and / or drying. The molar ratio of the chloroacetic acid-2-heptyl ester and the 5-chloro-8-hydroxyquinoline is 1-1.5:

1. The molar ratio of the acid-binding agent and the 5-chloro-8-hydroxyquinoline is 1-1.5:

1. After the reaction is completed, the process further comprises the steps of filtration, washing, concentration under reduced pressure, recrystallization and / or drying.

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