CN107602462B - Method for preparing hydroxy-2 (1H) -quinolinone - Google Patents
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Abstract
The invention discloses a method for preparing hydroxy-2 (1H) -quinolinone, which belongs to the field of organic chemistry.an aminophenylboronic acid compound and trans- β -aryl acryloyl chloride react in the presence of triethylamine or pyridine to generate a trans-amide intermediate, then in an organic solvent, in the presence of anhydrous aluminum trichloride and B (C6F5)3, the temperature is raised for reaction, the reaction is finished and the temperature is reduced, hydrogen peroxide is added for oxidation to obtain the hydroxy-2 (1H) -quinolinone.
Description
The technical field is as follows:
the invention relates to a preparation method of hydroxy-2 (1H) -quinolinone, belonging to the technical field of organic chemistry.
Background art:
the hydroxy-2 (1H) -quinolinone compounds have good biological activity, show various pharmaceutical activities in different drug molecules, are considered as potential anti-tumor structures, and are widely applied to medicines. 6-hydroxy-2 (1H) -quinolinone is an important intermediate in the synthesis of cilostazol for the treatment of stable intermittent claudication. Also is an important intermediate for synthesizing antithrombotic drug, anticoagulant kinase, antiphlogistic drug, ulcer drug, asthma drug, heart-strengthening drug, cerebral circulation treatment drug and herbicide; the 7-hydroxy-2 (1H) -quinolinone is an important intermediate for synthesizing the atypical antipsychotic aripiprazole, and compared with the typical and atypical antipsychotics on the market, the drug has completely different action mechanisms, obvious advantages and good prospects.
In the research of new quinolones and the acquisition of compounds with good pharmacological effects, hydroxy-2 (1H) -quinolinone is often the most critical precursor in the synthesis process. There are many methods for synthesizing hydroxy-2 (1H) -quinolinone, mainly including the following four methods:
(1) the nitro group of 2-nitrocinnamic acid in which the benzene ring is substituted by hydroxyl group is reduced to amino group, and then cyclization reaction is carried out, which is not suitable for industrial mass production because the method is limited by production cost, production equipment and production scale.
(2) The quinoline compound with benzene ring substituted by hydroxyl or alkoxy is used as a raw material to synthesize a target product through oxidation, acetylation, hydrolysis and dealkylation, the synthetic route is simple and convenient to operate, but the total yield is only about 17%, the application of the quinoline compound is limited, the reaction raw material price is high, and the raw material source is limited.
(3) Methoxy aniline and acryloyl chloride are used as raw materials, and hydroxyl-2 (1H) -quinolinone is synthesized through bromination, acylation and intramolecular Heck reaction.
(4) The hydroxy-2 (1H) -quinolinone is synthesized by intramolecular Friedel-Crafts reaction of amino anisole or aminophenol and 3-chloropropionyl chloride or cinnamoyl chloride, and has the advantages of wide raw material source, simpler synthetic route and high product yield. However, the use of a large excess anhydrous aluminum trichloride catalytic system has the disadvantages of difficult post-treatment, large amount of waste water, waste residues and waste gases generated in the reaction process and serious environmental pollution.
In conclusion, it is still necessary to research the preparation method of hydroxy-2 (1H) -quinolinone, search a suitable synthetic route thereof, and complete the path search of the industrial production process.
The invention content is as follows:
in order to overcome the defects, the invention aims to provide a method for preparing the hydroxy-2 (1H) -quinolinone (1), which is beneficial to large-scale industrial production and achieves the purposes of energy conservation, emission reduction and environmental friendliness.
A method for preparing hydroxy-2 (1H) -quinolinone is obtained by two-step reaction, and adopts the technical scheme that:
in the first step, an aminobenzene boric acid compound (2) and trans- β -aryl acryloyl chloride (3) react in the presence of triethylamine or pyridine to generate a trans-amide intermediate (4), wherein aryl is an electron-rich phenyl.
And secondly, adding the trans-amide intermediate (4) into an organic solvent, heating to react in the presence of anhydrous aluminum trichloride and B (C6F5)3, quenching, layering, and adding hydrogen peroxide into an organic layer to react to obtain the hydroxy-2 (1H) -quinolinone (1).
The reaction route is as follows:
in the first step trans- β -aryl acryloyl chloride, the aryl or Ar is selected from 4-methoxyphenyl, 4, 5-dimethoxyphenyl, 3,4, 5-trimethoxyphenyl, 4-methylphenyl, 4, 5-dimethylphenyl or 3,4, 5-trimethylphenyl.
In the first step amino phenyl boronic acid compound, an amino group is selected from an o-, m-or p-amino group; the boronic acid compound is selected from boronic acid, boronic acid pinacol ester or boronic acid neopentyl glycol ester.
In the first step, the molar ratio of the aminophenylboronic acid compound (2) to the trans- β -arylacryloyl chloride (3) is 1: 1, and the amount of triethylamine or pyridine added is 1.5 to 2.5 equivalents of 2.
In the second step, the organic solvent is toluene, xylene, anisole, diphenyl ether and the like.
In the second step, the trans-amide intermediate (4), anhydrous aluminum chloride and B (C)6F5)3In a molar ratio of 1: 1-1.4: 0.05-0.15.
In the second step, the reaction temperature is 60-90 ℃.
Further research shows that during the Friedel-crafts reaction of the second step of intramolecular ring closure condensation, the ring closure reaction is difficult to carry out, and when the ring closure reaction is carried out with a substituent group on a substituted aromatic ring, the substituent group is an electron-withdrawing group, the electrophilic reaction of the aromatic ring is passivated; when the substituent is an electron donating group, electrophilic reaction of the aromatic ring is facilitated. In the process of obtaining 7-hydroxy-2 (1H) -quinolinone by intramolecular Friedel-Crafts reaction under the condition of the invention, the reaction mechanism is presumed as follows (taking aryl as 4, 5-dimethoxyphenyl as an example):
in conclusion, the beneficial results of the invention are as follows:
(1) the design route is novel, the process does not need the process of removing the alkoxy protecting group, and the operation is simple and easy.
(2) Compared with the traditional process, the method adopts trans- β -aryl acryloyl chloride which is more rich in electronic groups as a raw material to ensure that Friedel-Crafts reaction is easier to occur in molecules so as to obtain 2(1H) -quinolinone boride through ring closure, so that the reaction can be carried out at 60-90 ℃, high temperature is avoided, energy is saved, and (3) the catalytic amount of B (C6F5)3 and 1-1.4 equivalent of AlCl3 are used, so that the production cost is reduced, and the problems of difficult post-treatment, large amount of waste water, waste residues and waste gases and serious environmental pollution caused by large excess of AlCl3 are solved.
(4) The reaction solvent is organic solvent with low toxicity to replace chlorobenzene with high toxicity.
Detailed Description
Example 1
Synthesis of Compound (3):
in a 100mL three-necked flask equipped with a gas absorption device and a reflux condenser, trans-4-methoxyphenylacrylic acid (17.8g, 0.10mol) and toluene (55mL) were charged, and thionyl chloride (11.9g, 0.10mol) was added dropwise, and the mixture was slowly heated to 70 ℃ and reacted at a constant temperature for 4 hours. After cooling, the excess thionyl chloride was removed by concentration under reduced pressure, and the residue was frozen to precipitate a pale yellow solid which was recrystallized from methylene chloride to give 17.3g of white crystals in 88.0% yield.
Synthesis of Compound (4):
adding 60mL of tetrahydrofuran (12.1g, 88.0mmol) and triethylamine (13.3g, 132.0mmol) into a 250mL three-necked flask, dropping a compound (3) (17.3g, 88.0mmol) dissolved in tetrahydrofuran (70mL) at the temperature of-5-0 ℃, stirring at room temperature for 2 hours after dropping, acidifying the reaction solution by using concentrated hydrochloric acid to obtain a large amount of white solid, filtering, washing with water to be neutral, and drying to obtain 24.6g of a white solid product with the yield of 94.1%.
Synthesis of 6-hydroxy-2 (1H) -quinolinone Compound (1):
adding the product (24.6g, 82.7mmol) and 250mL of toluene in a 500mL three-necked bottle, cooling to 0 ℃, and adding B (C) in batches6F5)32.2g (4.2mmol) and 15.4g (115.8mmol) of anhydrous aluminum trichloride, slowly raising the temperature to 90 ℃, continuing stirring for 2 hours, pouring the reaction liquid into 800mL of ice hydrochloric acid solution to enable the pH value to be 2-3, stirring for 1 hour, layering, and keeping an organic layer. To the organic layer was added dropwise acetic acid (49.6g, 0.827mol) and 30% H at 0-10 deg.C2O2(9.4g, 82.7mmol) solution, preserving the temperature at 0-10 ℃ for 1 hour after dripping, continuing stirring at room temperature for 1 hour, dripping sodium bisulfite solution to quench peroxide, separating an organic layer, washing with saturated salt water once, concentrating the organic layer under reduced pressure to obtain a crude solid, and recrystallizing the crude solid with methanol to obtain 10.8g of a white solid product, namely 6-hydroxy-2 (1H) -quinolinone, wherein the yield is 80.7 percent, and mp is mp>The purity is 99.2 percent at 300 ℃.
Example 2
Synthesis of Compound (3):
into a 100mL three-necked flask equipped with a gas absorption device and a reflux condenser, trans-3, 4-dimethylphenylacrylic acid (17.6g, 0.10mol) and toluene (55mL) were added, and thionyl chloride (11.9g, 0.10mol) was added dropwise, followed by slow heating to 70 ℃ and isothermal reaction for 4 hours. After cooling, the excess thionyl chloride was removed by concentration under reduced pressure, and the residue was frozen to precipitate a pale yellow solid which was recrystallized from methylene chloride to give 17.2g of white crystals in 88.6% yield.
Synthesis of Compound (4):
adding 60mL of tetrahydrofuran (12.1g, 88.6mmol) and triethylamine (22.4g, 0.22mol) into a 250mL three-necked flask, dropping a compound (3) (17.2g, 88.6mmol) dissolved in tetrahydrofuran (70mL) at the temperature of-5-0 ℃, stirring at room temperature for 2 hours after dropping, acidifying the reaction solution by using concentrated hydrochloric acid to obtain a large amount of white solid, filtering, washing with water to be neutral, and drying to obtain 24.8g of a white solid product with the yield of 94.7%.
Synthesis of 6-hydroxy-2 (1H) -quinolinone Compound (1):
adding the product (24.8g, 83.9mmol) and xylene (250 mL) into a 500mL three-necked flask, cooling to 0 deg.C, and adding B (C) in portions6F5)3(6.4g, 12.6mmol) and anhydrous aluminum trichloride (11.2g, 83.9mmol), slowly raising the temperature to 60 ℃, continuing stirring for 2 hours, pouring the reaction solution into 800mL of ice hydrochloric acid solution to enable the pH value to be 2-3, stirring for 1 hour, demixing, and keeping an organic layer. To the organic layer was added dropwise acetic acid (50.3g, 0.839mol) and 30% H at 0-10 deg.C2O2(9.5g, 83.9mmol) solution, after the dripping is finished, keeping the temperature at 0-10 ℃ for 1 hour, continuing stirring at room temperature for 1 hour, dripping sodium bisulfite solution to quench peroxide, separating an organic layer, washing the organic layer with saturated salt water once, decompressing and concentrating the organic layer to obtain a crude solid, and recrystallizing the crude solid with methanol to obtain 10.8g of a white solid product, namely 6-hydroxy-2 (1H) -quinolinone, wherein the yield is 80.2 percent, and mp is mp>300 ℃ and the purity is 99.0 percent.
Example 3
Synthesis of Compound (3):
trans-3, 4, 5-trimethylphenylacrylic acid (19.0g, 0.10mol) and toluene (55mL) were added to a 100mL three-necked flask equipped with a gas absorption apparatus and a reflux condenser, and thionyl chloride (11.9g, 0.10mol) was added dropwise, slowly heated to 70 ℃ and reacted at a constant temperature for 4 hours. After cooling, the excess thionyl chloride was removed by concentration under reduced pressure, and the residue was frozen to precipitate a pale yellow solid which was recrystallized from dichloromethane to give 18.4g of white crystals in 88.3% yield.
Synthesis of Compound (4):
60mL of tetrahydrofuran, 4-aminobenzeneboronic acid pinacol ester (19.3g, 88.3mmol) and pyridine (17.5g, 0.22mol) are added into a 250mL three-necked flask, the temperature is reduced to-5 to 0 ℃, a compound (3) (18.4g, 88.3mmol) dissolved in tetrahydrofuran (75mL) is dripped, the mixture is stirred for 2 hours at room temperature after dripping, the pH value of a reaction solution is acidified by concentrated hydrochloric acid to be 2 to 3, a large amount of white solid is separated out, the mixture is filtered, washed to be neutral by water, and 32.9g of a white solid product is obtained after drying, and the yield is 95.2%.
Synthesis of 6-hydroxy-2 (1H) -quinolinone Compound (1):
adding the product (32.9g, 84.1mmol) and 330mL diphenyl ether into a 500mL three-necked bottle, cooling to 0 deg.C, and adding B (C) in portions6F5)3(4.3g, 8.41mmol) and anhydrous aluminum trichloride (13.5g, 0.101mol), slowly raising the temperature to 80 ℃, continuing stirring for 2 hours, pouring the reaction liquid into 1000mL of ice hydrochloric acid solution to enable the pH value to be 2-3, stirring for 1 hour, demixing, and keeping an organic layer. To the organic layer was added dropwise acetic acid (50.5g, 0.841mol) and 30% H at 0-10 deg.C2O2(9.5g, 84.1mmol) solution, preserving the temperature at 0-10 ℃ for 1 hour after dripping, continuing stirring at room temperature for 1 hour, dripping sodium bisulfite solution to quench peroxide, separating an organic layer, washing with saturated salt water once, concentrating the organic layer under reduced pressure to obtain a crude solid, and recrystallizing with methanol to obtain 11.0g of a white solid product, namely 6-hydroxy-2 (1H) -quinolinone, with the yield of 81.1 percent and mp>The purity is 99.1 percent at 300 ℃.
Example 4
Synthesis of Compound (3):
in a 100mL three-necked flask equipped with a gas absorption apparatus and a reflux condenser, trans-3, 4-dimethoxyphenylacrylic acid (20.8g, 0.10mol) and toluene (60mL) were added, and thionyl chloride (11.9g, 0.10mol) was added dropwise, and the mixture was slowly heated to 70 ℃ and reacted at a constant temperature for 4 hours. After cooling, the excess thionyl chloride was removed by concentration under reduced pressure, and the residue was frozen to precipitate a pale yellow solid which was recrystallized from dichloromethane to give 19.9g of white crystals with a yield of 87.8%.
Synthesis of Compound (4):
adding 60mL of tetrahydrofuran, 3-aminobenzeneboronic acid (12.0g, 87.8mmol) and triethylamine (17.8g, 0.176mol) into a 250mL three-necked flask, dropping the compound (3) (19.9g, 87.8mmol) dissolved in tetrahydrofuran (80mL) at the temperature of-5-0 ℃, stirring for 2 hours at room temperature after dropping, acidifying the reaction solution by using concentrated hydrochloric acid to obtain a large amount of white solid, filtering, washing with water to be neutral, and drying to obtain 27.3g of a white solid product with the yield of 95.0%.
Synthesis of 7-hydroxy-2 (1H) -quinolinone Compound (1):
adding the product (27.3g, 83.5mmol) and 270mL of toluene in a 500mL three-necked bottle, cooling to 0 ℃, and adding B (C) in batches6F5)3(4.3g, 8.35mmol) and anhydrous aluminum trichloride (15.6g, 0.117mol), slowly raising the temperature to 90 ℃, continuing stirring for 2 hours, pouring the reaction liquid into 800mL of ice hydrochloric acid solution to enable the pH value to be 2-3, stirring for 1 hour, demixing, and keeping an organic layer. Dripping acetic acid (50.1g, 0.835mol) into the obtained organic layer, and dripping 30% H at 0-10 deg.C2O2(9.5g, 83.5mmol) solution, preserving the temperature at 0-10 ℃ for 1 hour after dripping, continuing stirring at room temperature for 1 hour, dripping sodium bisulfite solution to quench peroxide, separating an organic layer, washing with saturated salt water once, concentrating the organic layer under reduced pressure to obtain a crude solid, and recrystallizing with methanol to obtain 10.9g of a white solid product, namely 7-hydroxy-2 (1H) -quinolinone, with the yield of 81.3%, mp>The purity is 99.2 percent at 300 ℃.
Example 5
Synthesis of Compound (3):
in a 100mL three-necked flask equipped with a gas absorption apparatus and a reflux condenser, trans-3, 4, 5-trimethoxyphenylacrylic acid (23.8g, 0.10mol) and toluene (70mL) were added, and thionyl chloride (11.9g, 0.10mol) was added dropwise, slowly heated to 70 ℃ and reacted at a constant temperature for 4 hours. After cooling, the excess thionyl chloride was removed by concentration under reduced pressure, and the residue was frozen to precipitate a pale yellow solid which was recrystallized from methylene chloride to give 22.6g of white crystals in 88.2% yield.
Synthesis of Compound (4):
adding 60mL of tetrahydrofuran, 3-aminobenzeneboronic acid (12.1g, 88.2mmol) and pyridine (14.0g, 0.176mol) into a 250mL three-necked flask, dropping the mixture into the tetrahydrofuran (90mL) dissolved compound (3) (22.6g, 88.2mmol) at a temperature of-5-0 ℃, stirring the mixture at room temperature for 2 hours after dropping, acidifying the reaction solution by using concentrated hydrochloric acid to obtain a large amount of white solid, filtering, washing the white solid with water to be neutral, and drying to obtain 29.9g of a white solid product with the yield of 94.7%.
Synthesis of 7-hydroxy-2 (1H) -quinolinone Compound (1):
adding the product (29.9g, 83.6mmol) and 300mL of xylene into a 500mL three-necked bottle, cooling to 0 deg.C, and adding B (C) in portions6F5)3(6.5g, 12.6mmol) and anhydrous aluminum trichloride (11.1g, 83.6mmol), slowly raising the temperature to 70 ℃, continuing stirring for 2 hours, pouring the reaction solution into 1000mL of ice hydrochloric acid solution to enable the pH value to be 2-3, stirring for 1 hour, demixing, and keeping an organic layer. To the organic layer was added dropwise acetic acid (50.2g, 0.836mol) and 30% H at 0-10 deg.C2O2(9.5g, 83.6mmol) solution, after the dripping is finished, keeping the temperature at 0-10 ℃ for 1 hour, continuing stirring at room temperature for 1 hour, dripping sodium bisulfite solution to quench peroxide, separating an organic layer, washing the organic layer with saturated salt water once, decompressing and concentrating the organic layer to obtain a crude solid, and recrystallizing the crude solid with methanol to obtain 11.1g of a white solid product, namely 7-hydroxy-2 (1H) -quinolinone, wherein the yield is 82.2 percent, and mp is mp>300 ℃ and the purity is 99.0 percent.
Example 6
Synthesis of Compound (3):
in a 100mL three-necked flask equipped with a gas absorption apparatus and a reflux condenser, trans-3, 4-dimethoxyphenylacrylic acid (20.8g, 0.10mol) and toluene (60mL) were added, and thionyl chloride (11.9g, 0.10mol) was added dropwise, and the mixture was slowly heated to 70 ℃ and reacted at a constant temperature for 4 hours. After cooling, the excess thionyl chloride was removed by concentration under reduced pressure, and the residue was frozen to precipitate a pale yellow solid which was recrystallized from methylene chloride to give 19.9g of white crystals with a yield of 88.0%.
Synthesis of Compound (4):
adding 60mL of tetrahydrofuran, 2-aminobenzeneboronic acid (12.1g, 88.0mmol) and triethylamine (17.8g, 0.176mol) into a 250mL three-necked flask, dropping a compound (3) (19.9g, 88.0mmol) dissolved in tetrahydrofuran (80mL) at the temperature of-5-0 ℃, stirring for 2 hours at room temperature after dropping, acidifying the reaction solution by using concentrated hydrochloric acid to obtain a large amount of white solid, filtering, washing with water to be neutral, and drying to obtain 27.4g of a white solid product with the yield of 95.1%.
Synthesis of 8-hydroxy-2 (1H) -quinolinone Compound (1):
adding the product (27.4g, 83.7mmol) and 300mL of anisole into a 500mL three-necked bottle, cooling to 0 ℃, and adding B (C) in batches6F5)3(4.3g, 8.37mmol) and anhydrous aluminum trichloride (14.5g, 0.109mol), slowly raising the temperature to 90 ℃, continuing stirring for 2 hours, pouring the reaction solution into 1000mL of ice hydrochloric acid solution to enable the pH value to be 2-3, stirring for 1 hour, demixing, and keeping an organic layer. To the organic layer was added dropwise acetic acid (50.2g, 0.837mol) and 30% H at 0-10 deg.C2O2(9.5g, 83.7mmol) solution, after the dripping is finished, keeping the temperature at 0-10 ℃ for 1 hour, continuing stirring at room temperature for 1 hour, dripping sodium bisulfite solution to quench peroxide, separating an organic layer, washing the organic layer with saturated salt water once, decompressing and concentrating the organic layer to obtain a crude solid, and recrystallizing the crude solid with methanol to obtain 11.0g of a white solid product, namely 8-hydroxy-2 (1H) -quinolinone, wherein the yield is 81.7 percent, and mp is mp>The purity is 99.2 percent at 300 ℃.
Example 7
Synthesis of Compound (3):
trans-4-methylphenylacrylic acid (16.2g, 0.10mol) and toluene (50mL) were added to a 100mL three-necked flask equipped with a gas absorption device and a reflux condenser, thionyl chloride (11.9g, 0.10mol) was added dropwise, and the mixture was slowly heated to 70 ℃ and reacted at a constant temperature for 4 hours. After cooling, the excess thionyl chloride was removed by concentration under reduced pressure, and the residue was frozen to precipitate a pale yellow solid which was recrystallized from dichloromethane to give 16.2g of white crystals with a yield of 89.6%.
Synthesis of Compound (4):
adding tetrahydrofuran 90mL, 2-amino-benzeneboronic acid neopentyl glycol ester (18.4g, 89.6mmol) and pyridine (10.6g, 0.134mol) into a 250mL three-neck flask, dropping the temperature to be between-5 and 0 ℃ and adding a compound (3) (16.2g, 89.6mmol) dissolved in tetrahydrofuran (65mL) dropwise, stirring the mixture at room temperature for 2 hours after dropping, acidifying the pH value of a reaction solution by concentrated hydrochloric acid to be 2 to 3, precipitating a large amount of white solid, filtering, washing the white solid to be neutral, and drying to obtain 29.8g of a white solid product with the yield of 95.3%.
Synthesis of 8-hydroxy-2 (1H) -quinolinone Compound (1):
adding the product (29.8g, 85.4mmol) and xylene 300mL into a 500mL three-necked bottle, cooling to 0 deg.C, and adding B (C) in portions6F5)3(2.2g, 4.3mmol) and anhydrous aluminum trichloride (15.9g, 0.120mol), slowly raising the temperature to 90 ℃, continuing stirring for 2 hours, pouring the reaction solution into 1000mL of ice hydrochloric acid solution to enable the pH value to be 2-3, stirring for 1 hour, demixing, and keeping an organic layer. Acetic acid (51.2g, 0.854mol) is dripped into the obtained organic layer, and 30% H is dripped at the temperature of 0-10 DEG C2O2(9.7g, 85.4mmol) solution, after the dripping is finished, keeping the temperature at 0-10 ℃ for 1 hour, continuing stirring at room temperature for 1 hour, dripping sodium bisulfite solution to quench peroxide, separating an organic layer, washing the organic layer with saturated salt water once, decompressing and concentrating the organic layer to obtain a crude solid, and recrystallizing the crude solid with methanol to obtain 11.1g of a white solid product, namely 8-hydroxy-2 (1H) -quinolinone, wherein the yield is 80.6 percent, and mp is mp>The purity is 99.1 percent at 300 ℃.
The foregoing shows and describes the general principles and broad features of the present invention and advantages thereof. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are described in the specification and illustrated only to illustrate the principle of the present invention, but that various changes and modifications may be made therein without departing from the spirit and scope of the present invention, which fall within the scope of the invention as claimed. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (3)
1. The method for preparing the hydroxyl-2 (1H) -quinolinone is obtained by two-step reaction and is characterized in that the reaction route is as follows:
the method comprises the following steps:
in the first step, an aminophenylboronic acid compound (2) and trans- β -aryl acryloyl chloride (3) react in the presence of triethylamine or pyridine to generate a trans-amide intermediate (4), wherein aryl is an electron-rich phenyl group, in the aminophenylboronic acid compound (2) in the first step, amino is selected from o-amino, m-amino or p-amino, and a boric acid compound is selected from boric acid, pinacol borate or neopentyl glycol borate;
in the second step, the trans-amide intermediate (4) is added to an organic solvent in the presence of anhydrous aluminum trichloride and B (C)6F5)3In the presence of the solvent, heating to react, quenching, layering, adding hydrogen peroxide into the organic layer to react to obtain hydroxy-2 (1H) -quinolinone (1); in the second step, the organic solvent is toluene, xylene, anisole or diphenyl ether, trans-amide intermediate (4), anhydrous aluminum trichloride and B (C)6F5)3In a molar ratio of 1: 1-1.4: 0.05-0.15, and the reaction temperature is 60-90 ℃.
2. A process for the preparation of hydroxy-2 (1H) -quinolinone according to claim 1, characterized in that: in the first step, the aryl or Ar is selected from 4-methoxyphenyl, 4, 5-dimethoxyphenyl, 3,4, 5-trimethoxyphenyl, 4-methylphenyl, 4, 5-dimethylphenyl or 3,4, 5-trimethylphenyl.
3. The process for preparing hydroxy-2 (1H) -quinolinone of claim 1, wherein the molar ratio of aminobenzeneboronic acid compound (2) to trans- β -arylacryloyl chloride (3) in the first step is 1: 1, and triethylamine or pyridine is added in an amount of 1.5 to 2.5 equivalents based on aminobenzeneboronic acid compound (2).
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