A kind of synthetic method of pirenoxine

Abstract

The invention discloses a method for synthesizing pyrenoxine in the field of drug synthesis technology. The method comprises the following steps: (1) dehydrating 2,4,5-trimethoxyaniline and diethyl oxaloacetate to obtain diethyl 2,4,5-trimethoxyphenyliminobutyrate; (2) subjecting the diethyl 2,4,5-trimethoxyphenyliminobutyrate to dealcoholization and cyclization by heating to obtain ethyl 4-hydroxy-5,6,8-trimethoxyquinoline-2-carboxylate; (3) adding tribromophenol to ethyl 4-hydroxy-5,6,8-trimethoxyquinoline-2-carboxylate; Boron, demethoxyl reaction at room temperature to obtain 4,5,6,8-tetrahydroxyquinoline-2-carboxylic acid; (4) 4,5,6,8-tetrahydroxyquinoline-2-carboxylic acid is oxidized with potassium persulfate to obtain 4,6-dihydroxy-5,8-diquinone-2-carboxylic acid; (5) 4,6-dihydroxy-5,8-diquinone-2-carboxylic acid is cyclized with o-aminophenol to obtain crude pyrenoxine; (6) the crude pyrenoxine is refined to obtain pyrenoxine fine product. The advantages of the present invention are reducing three wastes, improving safety factor, and being suitable for large-scale production.

Description

Technical Field

[0001] The invention relates to the technical field of drug synthesis, and in particular to a method for synthesizing pirenoxine. Background Art

[0002] Pirenoxine, whose chemical name is 1-hydroxy-5-oxo-5H-pyrido[3,2-A]phenazine-3-carboxylic acid, is a drug for preventing and treating cataracts. It can improve the metabolic abnormalities of aromatic amino acids and inhibit the production of quinone compounds, thereby stabilizing or delaying the development of lens opacities. It is mainly used to treat senile cataracts, diabetic cataracts, and can also treat traumatic cataracts and congenital cataracts. In addition, it has a certain effect on the regulatory function and has the effect of inhibiting vision loss or improving vision.

[0003] The prior art on the synthesis of pyrenoxine mainly comprises hydroquinone being oxidized with sodium dichromate, acetylated with acetic anhydride, methylated with dimethyl sulfate, nitrated with nitric acid, reduced with metallic tin, cyclized with 5-amino-1,2,4-trimethoxybenzene, hydrolyzed with hydrobromic acid, oxidized with sodium bicarbonate and potassium ferrocyanide solution, and condensed with o-aminophenol in acetic acid to obtain the product; the main problems are as follows:

[0004] 1. Using hydrobromic acid gas for hydrolysis requires controlling the reaction temperature to 110-120°C. The reaction conditions are harsh and increase the cost. In addition, the reaction process will cause the leakage of hydrobromic acid, which is toxic and has an impact on the environment.

[0005] 2. Oxidation with sodium bicarbonate and potassium ferrocyanide solution will generate hydrocyanic acid gas and potassium cyanide, both of which are highly toxic. Not only does it affect the environment, but the safety of the operators cannot be guaranteed.

[0006] In summary, the above-mentioned synthesis method is not suitable for large-scale production. Summary of the invention

[0007] The purpose of the present invention is to provide a synthesis method of pirenoxine suitable for large-scale production. The reaction conditions of the present invention are mild and the cost is low. At the same time, the generation of three wastes is reduced and the safety factor is improved.

[0008] In order to achieve the above-mentioned object of the invention, the synthesis method of pirenoxine of the present invention adopts the following technical scheme:

[0009] A method for synthesizing pirenoxine comprises the following steps:

[0010] (1) subjecting 2,4,5-trimethoxyaniline to a dehydration reaction with diethyl oxaloacetate to obtain diethyl 2,4,5-trimethoxyphenyliminosuccinate;

[0011] (2) 2,4,5-trimethoxyphenyliminobutyric acid diethyl ester is subjected to dealcoholization cyclization by heating to obtain 4-hydroxy-5,6,8-trimethoxyquinoline-2-carboxylic acid ethyl ester;

[0012] (3) adding boron tribromide to ethyl 4-hydroxy-5,6,8-trimethoxyquinoline-2-carboxylate to carry out a demethoxylation reaction at room temperature to obtain 4,5,6,8-tetrahydroxyquinoline-2-carboxylic acid;

[0013] (4) subjecting 4,5,6,8-tetrahydroxyquinoline-2-carboxylic acid to an oxidation reaction with potassium persulfate to obtain 4,6-dihydroxy-5,8-diquinone-2-carboxylic acid;

[0014] (5) completing a cyclization reaction of 4,6-dihydroxy-5,8-diquinone-2-carboxylic acid with o-aminophenol to obtain a crude product of pyrenoxine;

[0015] (6) The crude product of pirenoxine is purified to obtain a refined product of pirenoxine.

[0016] Preferably, the specific steps of the refining treatment are as follows: potassium acetate is added to the crude pyrenoxic acid to form potassium salt precipitation, and then acidification is performed to obtain the pyrenoxic acid fine product. The present invention uses potassium acetate to directly form potassium salt precipitation, which is convenient for separating impurities.

[0017] Preferably, the present invention comprises the following steps:

[0018] (1) under nitrogen protection, 2,4,5-trimethoxyaniline and diethyl oxaloacetate are added to ethyl acetate, stirred, heated to reflux, and after the dehydration reaction is completed, the temperature is reduced and concentrated to obtain diethyl 2,4,5-trimethoxyimino succinate;

[0019] (2) under nitrogen protection, adding liquid paraffin to diethyl 2,4,5-trimethoxyimino succinate, stirring, removing ethanol and performing cyclization reaction at elevated temperature, cooling after the reaction is completed to precipitate solids, adding the solids to anhydrous ethanol for recrystallization, and obtaining ethyl 4-hydroxy-5,6,8-trimethoxyquinoline-2-carboxylate;

[0020] (3) under nitrogen protection, ethyl 4-hydroxy-5,6,8-trimethoxyquinoline-2-carboxylate is added to dichloromethane, and then boron tribromide is added, and the mixture is stirred at room temperature to complete the demethoxylation reaction, and then the temperature is lowered to 0-5° C., water is added dropwise and stirred to complete the hydrolysis, and then post-treated to obtain 4,5,6,8-tetrahydroxyquinoline-2-carboxylic acid;

[0021] (4) under nitrogen protection, 4,5,6,8-tetrahydroxyquinoline-2-carboxylic acid is added to dichloromethane, stirred, heated to slight reflux, and then potassium persulfate is added in multiple portions, and water is added to continue oxidation reaction, and finally post-processed to obtain 4,6-dihydroxy-5,8-diquinone-2-carboxylic acid;

[0022] (5) under nitrogen protection, adding 4,6-dihydroxy-5,8-diquinone-2-carboxylic acid to anhydrous acetic acid, then adding o-aminophenol, stirring, heating, completing the cyclization reaction, and obtaining a crude product of pyrrolidine octanoic acid;

[0023] (6) Under nitrogen protection, the crude product of pyrenoxic acid is added to a sodium dihydrogen phosphate aqueous solution, dissolved and filtered, and then potassium acetate is added to precipitate pyrenoxic acid potassium, and then the pyrenoxic acid potassium is acidified with dilute hydrochloric acid, and the temperature is lowered to precipitate pyrenoxic acid fine product.

[0024] Preferably, the molar ratio of 2,4,5-trimethoxyaniline to diethyl oxaloacetate in step (1) is 1:1.25-2.0.

[0025] Preferably, the molar ratio of ethyl 4-hydroxy-5,6,8-trimethoxyquinoline-2-carboxylate to boron tribromide in step (3) is 1:1.5-3.0.

[0026] Preferably, the molar ratio of 4,5,6,8-tetrahydroxyquinoline-2-carboxylic acid to potassium persulfate in step (4) is 1:2-5.

[0027] Preferably, the dehydration reaction time in step (1) is 1-2 hours, and the dehydration reaction temperature is 80-85°C; the cyclization reaction time in step (2) is 1-2 hours, and the cyclization reaction temperature is 235-240°C.

[0028] Preferably, the demethoxylation reaction time in step (3) is 24 hours.

[0029] Preferably, the potassium persulfate in step (4) is added in three times, and the oxidation reaction time is 2-3 hours.

[0030] Preferably, the cyclization reaction time in step (5) is 5-6 hours, and the cyclization reaction temperature is 50-55°C.

[0031] Compared with the prior art, the present invention has the following beneficial effects:

[0032] 1. The present invention adds boron tribromide to ethyl 4-hydroxy-5,6,8-trimethoxyquinoline-2-carboxylate and performs a demethoxylation reaction at room temperature. Compared with the prior art, firstly, the reaction temperature is reduced from 110-120° C. to room temperature, so that the reaction conditions are mild, no temperature increase is required, and the cost is reduced. Secondly, the overflow caused by the generation of hydrogen bromide gas in the prior art is avoided. The present invention reduces the generation of toxic gases and better protects the environment.

[0033] 2. The present invention conducts an oxidation reaction between 4,5,6,8-tetrahydroxyquinoline-2-carboxylic acid and potassium disulfate, thereby avoiding the formation of hydrocyanic acid gas and potassium cyanide due to the use of potassium ferrocyanide in the prior art. The present invention not only reduces the generation of toxic gases and protects the environment, but also reduces the generation of other toxic byproducts, thereby improving the safety of operators and the yield;

[0034] 3. The present invention optimizes the process steps, reduces production costs, reduces the generation of three wastes, and is suitable for industrial-scale production. DETAILED DESCRIPTION

[0035] The present invention is further explained below in conjunction with specific implementation methods. It should be understood that these implementation methods are only used to illustrate the present invention and are not used to limit the scope of the present invention. After reading the present invention, various equivalent forms of modifications to the present invention by those skilled in the art all fall within the scope defined by the claims attached to this application.

[0036] Example 1

[0037] A method for synthesizing pirenoxine comprises the following steps:

[0038] (1) under nitrogen protection, 18.3 g (0.1 mol) of 2,4,5-trimethoxyaniline and 25 ml (0.15 mol) of diethyl oxaloacetate were added to 200 ml of ethyl acetate, stirred, heated to 80° C., refluxed and dehydrated for 2 hours, then cooled and concentrated to obtain ethyl acetate, and then further heated to remove diethyl oxaloacetate to obtain a brown liquid of 2,4,5-trimethoxyphenylimine succinate diethyl ester; then 150 ml of liquid paraffin was added, stirred and heated to 235-240° C., ethanol was removed and a cyclization reaction was carried out, and after the reaction was completed, the temperature was cooled and solids were precipitated, the solids were added to anhydrous ethanol, stirred and heated to reflux for 1 hour, cooled to room temperature, filtered, washed and dried to obtain 21.5 g of light yellow crystalline 4-hydroxy-5,6,8-trimethoxyquinoline-2-carboxylic acid ethyl ester, with a yield of 70%;

[0039] (2) Under nitrogen protection, 30.7 g (0.1 mol) of ethyl 4-hydroxy-5,6,8-trimethoxyquinoline-2-carboxylate was added to 150 ml of dichloromethane, and then 37.5 g (0.15 mol) of boron tribromide was added, and the mixture was stirred at room temperature for 24 hours to complete the demethylation reaction. The mixture was then cooled to 0-5° C., 50 ml of water was added dropwise and stirred for 2 hours to complete the hydrolysis. The mixture was then allowed to stand for stratification, and then washed with sodium bicarbonate and sodium chloride aqueous solutions. The dichloromethane organic layer was combined and concentrated to obtain 20 g of 4,5,6,8-tetrahydroxyquinoline-2-carboxylic acid, with a yield of 85%;

[0040] (3) Under nitrogen protection, 23.7 g of 4,5,6,8-tetrahydroxyquinoline-2-carboxylic acid was added to 200 ml of 50% dichloromethane-water, and then 81 g of potassium persulfate was added in three batches under stirring and slight reflux, and 50 ml of water was added to maintain the reaction for 3 hours. Finally, the temperature was cooled to room temperature, and dichloromethane was removed after separation, washing, and combining the organic layers to obtain 20.5 g of 4,6-dihydroxy-5,8-diquinone-2-carboxylic acid with a yield of 88%;

[0041] (4) Under nitrogen protection, 20.5 g of 4,6-dihydroxy-5,8-diquinone-2-carboxylic acid was added to 150 ml of anhydrous acetic acid, and then 12 g of o-aminophenol was added. The mixture was stirred and heated to 50-55° C. for 6 hours to complete the cyclization reaction. The crude product of pyrenoxine was obtained. The crude product was then added to 150 ml of a 1% sodium dihydrogen phosphate aqueous solution to dissolve it. After filtering the insoluble matter, 15 g of potassium acetate was added to precipitate solid pyrenoxine potassium. The pyrenoxine potassium was then acidified with dilute hydrochloric acid. After cooling, 25 g of pyrenoxine fine product was precipitated, with a yield of 83%.

[0042] Example 2

[0043] A method for synthesizing pirenoxine comprises the following steps:

[0044] (1) under nitrogen protection, 18.3 g (0.1 mol) of 2,4,5-trimethoxyaniline and 33 ml (0.2 mol) of diethyl oxaloacetate were added to 200 ml of ethyl acetate, stirred, heated to 80° C., refluxed for dehydration reaction for 2 hours, then cooled and concentrated to obtain ethyl acetate, and then further heated to remove diethyl oxaloacetate to obtain a brown liquid of 2,4,5-trimethoxyphenylimine succinate diethyl ester; then 150 ml of liquid paraffin was added, stirred and heated to 235-240° C., ethanol was removed and a cyclization reaction was carried out, and after the reaction was completed, the temperature was cooled and solids were precipitated, the solids were added to anhydrous ethanol, stirred, heated and refluxed for 1 hour, cooled to room temperature, filtered, washed, and dried to obtain 20 g of light yellow crystalline 4-hydroxy-5,6,8-trimethoxyquinoline-2-carboxylic acid ethyl ester, with a yield of 65%;

[0045] (2) Under nitrogen protection, 30.7 g (0.1 mol) of ethyl 4-hydroxy-5,6,8-trimethoxyquinoline-2-carboxylate was added to 150 ml of dichloromethane, and then 50 g (0.2 mol) of boron tribromide was added, and the mixture was stirred at room temperature for 24 hours to complete the demethylation reaction. The mixture was then cooled to 0-5° C., 50 ml of water was added dropwise and stirred for 2 hours to complete the hydrolysis, and then the mixture was allowed to stand for stratification, and then washed with sodium bicarbonate and sodium chloride aqueous solutions. The dichloromethane organic layer was combined and concentrated to obtain 18.8 g of 4,5,6,8-tetrahydroxyquinoline-2-carboxylic acid, with a yield of 80%;

[0046] (3) Under nitrogen protection, 23.7 g of 4,5,6,8-tetrahydroxyquinoline-2-carboxylic acid was added to 200 ml of 50% dichloromethane-water, and then 100 g of potassium persulfate was added in three batches under stirring and slight reflux, and 50 ml of water was added to maintain the reaction for 3 hours. Finally, the temperature was cooled to room temperature, and dichloromethane was removed after separation, washing, and combining the organic layers to obtain 19.5 g of 4,6-dihydroxy-5,8-diquinone-2-carboxylic acid with a yield of 84%;

[0047] (4) Under nitrogen protection, 20.5 g of 4,6-dihydroxy-5,8-diquinone-2-carboxylic acid was added to 150 ml of anhydrous acetic acid, and then 11 g of o-aminophenol was added. The mixture was stirred and heated to 50-55° C. for 6 hours to complete the cyclization reaction. The crude product of pyrenoxine was obtained. The crude product was then added to 150 ml of a 1% sodium dihydrogen phosphate aqueous solution to dissolve it. After filtering the insoluble matter, 15 g of potassium acetate was added to precipitate solid pyrenoxine potassium. The pyrenoxine potassium was then acidified with dilute hydrochloric acid. After cooling, 23 g of pyrenoxine fine product was precipitated, with a yield of 76%.

[0048] Example 3

[0049] A method for synthesizing pirenoxine comprises the following steps:

[0050] (1) under nitrogen protection, 18.3 g (0.1 mol) of 2,4,5-trimethoxyaniline and 25 ml (0.15 mol) of diethyl oxaloacetate were added to 200 ml of ethyl acetate, stirred, heated to 80° C., refluxed for dehydration reaction for 1 hour, then cooled and concentrated to obtain ethyl acetate, and then further heated to remove diethyl oxaloacetate to obtain a brown liquid of 2,4,5-trimethoxyphenylimine succinate diethyl ester; then 150 ml of liquid paraffin was added, stirred and heated to 235-240° C., ethanol was removed and a cyclization reaction was carried out, and after the reaction was completed, the temperature was cooled and solids were precipitated, the solids were added to anhydrous ethanol, stirred, heated and refluxed for 2 hours, cooled to room temperature, filtered, washed, and dried to obtain 20.5 g of light yellow crystalline 4-hydroxy-5,6,8-trimethoxyquinoline-2-carboxylic acid ethyl ester, with a yield of 68%;

[0051] (2) Under nitrogen protection, 30.7 g (0.1 mol) of ethyl 4-hydroxy-5,6,8-trimethoxyquinoline-2-carboxylate was added to 150 ml of dichloromethane, and then 45 g (0.18 mol) of boron tribromide was added, and the mixture was stirred at room temperature for 24 hours to complete the demethylation reaction. The mixture was then cooled to 0-5° C., 50 ml of water was added dropwise and stirred for 1 hour to complete the hydrolysis. The mixture was then allowed to stand for stratification, and then washed with sodium bicarbonate and sodium chloride aqueous solutions. The dichloromethane organic layer was combined and concentrated to obtain 20 g of 4,5,6,8-tetrahydroxyquinoline-2-carboxylic acid, with a yield of 85%;

[0052] (3) Under nitrogen protection, 23.7 g of 4,5,6,8-tetrahydroxyquinoline-2-carboxylic acid was added to 200 ml of 50% dichloromethane-water, and then 75 g of potassium persulfate was added in three batches under stirring and slight reflux, and 50 ml of water was added to maintain the reaction for 2 hours. Finally, the temperature was cooled to room temperature, and the dichloromethane was removed after layering, washing, and combining the organic layers to obtain 17.4 g of 4,6-dihydroxy-5,8-diquinone-2-carboxylic acid with a yield of 75%;

[0053] (4) Under nitrogen protection, 20.5 g of 4,6-dihydroxy-5,8-diquinone-2-carboxylic acid was added to 150 ml of anhydrous acetic acid, and then 13 g of o-aminophenol was added. The mixture was stirred and heated to 50-55° C. for 5 hours to complete the cyclization reaction. The crude product of pyrenoxine was obtained. The crude product was then added to 150 ml of a 1% sodium dihydrogen phosphate aqueous solution to dissolve the crude product. After filtering the insoluble matter, 15 g of potassium acetate was added to precipitate solid pyrenoxine potassium. The pyrenoxine potassium was then acidified with dilute hydrochloric acid. After cooling, 22 g of pyrenoxine fine product was precipitated, with a yield of 77.5%.

[0054] Comparative Example 1

[0055] Under nitrogen protection, 30.7 g of ethyl 4-hydroxy-5,6,8-trimethoxyquinoline-2-carboxylate was added to 300 ml of glacial acetic acid, and then 1760 ml of 46-48% hydrobromic acid was added, and the temperature was slowly raised to 110-120° C. with stirring to complete the demethylation reaction, and then post-treatment such as silica gel column chromatography was performed to obtain 10.5 g of 4,5,6,8-tetrahydroxyquinoline-2-carboxylic acid with a yield of 45%.

[0056] The yields of the intermediate product 4,5,6,8-tetrahydroxyquinoline-2-carboxylic acid of pirenoxine obtained by the methods of Examples 1-3 and Comparative Example 1 are shown in Table 1 below.

[0057] Table 1

[0058] Yield of 4,5,6,8-tetrahydroxyquinoline-2-carboxylic acid Example 1 85％ Example 2 80％ Example 3 85％ Comparative Example 1 45％

[0059] Comparative Example 2

[0060] Under nitrogen protection, 23.7 g of 4,5,6,8-tetrahydroxyquinoline-2-carboxylic acid was added to 500 ml of 50% dichloromethane-water, 16.8 g of sodium bicarbonate was added, stirred and dissolved, and then 330 g of 50% potassium ferrocyanide solution was added dropwise at 25°C to perform a staged temperature increase oxidation reaction. The oxidation was considered complete when 5% of the substrate remained, and hydrochloric acid was added dropwise at 0-5°C for acidification. Finally, 13.9 g of 4,6-dihydroxy-5,8-diquinone-2-carboxylic acid was obtained after post-treatment, with a yield of 60%.

[0061] The yields of the intermediate product 4,6-dihydroxy-5,8-diquinone-2-carboxylic acid of pirenoxine obtained by the methods of Examples 1-3 and Comparative Example 2 are shown in Table 2 below.

[0062] Table 2

[0063] Yield of 4,6-dihydroxy-5,8-diquinone-2-carboxylic acid Example 1 88％ Example 2 84％ Example 3 75％ Comparative Example 2 60％

Claims

1. A method for synthesizing pirenoxine, characterized in that: The steps include: (1) subjecting 2,4,5-trimethoxyaniline to a dehydration reaction with diethyl oxaloacetate to obtain diethyl 2,4,5-trimethoxyphenyliminosuccinate; (2) 2,4,5-trimethoxyphenyliminobutyric acid diethyl ester is subjected to dealcoholization cyclization by heating to obtain 4-hydroxy-5,6,8-trimethoxyquinoline-2-carboxylic acid ethyl ester; (3) adding boron tribromide to ethyl 4-hydroxy-5,6,8-trimethoxyquinoline-2-carboxylate to carry out a demethoxylation reaction at room temperature to obtain 4,5,6,8-tetrahydroxyquinoline-2-carboxylic acid; (4) subjecting 4,5,6,8-tetrahydroxyquinoline-2-carboxylic acid to an oxidation reaction with potassium persulfate to obtain 4,6-dihydroxy-5,8-diquinone-2-carboxylic acid; (5) completing a cyclization reaction of 4,6-dihydroxy-5,8-diquinone-2-carboxylic acid with o-aminophenol to obtain a crude product of pyrenoxine; (6) The crude product of pirenoxine is purified to obtain a refined product of pirenoxine.

2. The method for synthesizing pirenoxine according to claim 1, characterized in that: The specific steps of the refining treatment are as follows: potassium acetate is added to the crude product of pyrenoxic acid to form potassium salt precipitation, and then acidification is performed to obtain the pyrenoxic acid fine product.

3. The method for synthesizing pirenoxine according to claim 2, characterized in that: The steps include: (1) under nitrogen protection, 2,4,5-trimethoxyaniline and diethyl oxaloacetate are added to ethyl acetate, stirred, heated to reflux, and after the dehydration reaction is completed, the temperature is reduced and concentrated to obtain diethyl 2,4,5-trimethoxyimino succinate; (2) under nitrogen protection, adding liquid paraffin to diethyl 2,4,5-trimethoxyimino succinate, stirring, removing ethanol and performing cyclization reaction at elevated temperature, cooling after the reaction is completed to precipitate solids, adding the solids to anhydrous ethanol for recrystallization, and obtaining ethyl 4-hydroxy-5,6,8-trimethoxyquinoline-2-carboxylate; (3) under nitrogen protection, ethyl 4-hydroxy-5,6,8-trimethoxyquinoline-2-carboxylate is added to dichloromethane, and then boron tribromide is added, and the mixture is stirred at room temperature to complete the demethoxylation reaction, and then the temperature is lowered to 0-5° C., water is added dropwise and stirred to complete the hydrolysis, and then post-treated to obtain 4,5,6,8-tetrahydroxyquinoline-2-carboxylic acid; (4) under nitrogen protection, 4,5,6,8-tetrahydroxyquinoline-2-carboxylic acid is added to dichloromethane, stirred, heated to slight reflux, and then potassium persulfate is added in multiple portions, and water is added to continue oxidation reaction, and finally post-processed to obtain 4,6-dihydroxy-5,8-diquinone-2-carboxylic acid; (5) under nitrogen protection, adding 4,6-dihydroxy-5,8-diquinone-2-carboxylic acid to anhydrous acetic acid, then adding o-aminophenol, stirring, heating, completing the cyclization reaction, and obtaining a crude product of pyrrolidine octanoic acid; (6) Under nitrogen protection, the crude product of pyrenoxic acid is added to a sodium dihydrogen phosphate aqueous solution, dissolved and filtered, and then potassium acetate is added to precipitate pyrenoxic acid potassium, and then the pyrenoxic acid potassium is acidified with dilute hydrochloric acid, and the temperature is lowered to precipitate pyrenoxic acid fine product.

4. The method for synthesizing pirenoxine according to claim 3, characterized in that: The molar ratio of 2,4,5-trimethoxyaniline to diethyl oxaloacetate in step (1) is 1:1.25-2.

0.

5. The method for synthesizing pirenoxine according to claim 3, characterized in that: The molar ratio of ethyl 4-hydroxy-5,6,8-trimethoxyquinoline-2-carboxylate to boron tribromide in step (3) is 1:1.5-3.

0.

6. The method for synthesizing pirenoxine according to claim 3, characterized in that: The molar ratio of 4,5,6,8-tetrahydroxyquinoline-2-carboxylic acid to potassium persulfate in step (4) is 1:2-5.

7. The method for synthesizing pirenoxine according to claim 3, characterized in that: The dehydration reaction time in step (1) is 1-2 hours, and the dehydration reaction temperature is 80-85°C; the cyclization reaction time in step (2) is 1-2 hours, and the cyclization reaction temperature is 235-240°C.

8. The method for synthesizing pirenoxine according to claim 3, characterized in that: The demethoxylation reaction time in step (3) is 24 hours.

9. The method for synthesizing pirenoxine according to claim 3, characterized in that: The potassium persulfate in step (4) is added in three portions, and the oxidation reaction time is 2-3 hours.

10. The method for synthesizing pirenoxine according to claim 3, characterized in that: The cyclization reaction time in step (5) is 5-6 hours, and the cyclization reaction temperature is 50-55°C.