CN108863890B - 4-pyrroline-2-ketone derivative and preparation method thereof - Google Patents
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Abstract
The invention belongs to the technical field of medicines, and particularly relates to a 4-pyrroline-2-ketone derivative and a preparation method thereof, wherein the method comprises the following reaction steps: is represented by formula (1)Pyrrole compound reacts in the presence of solvent, alkali and oxygen to obtain 4-pyrroline-2-ketone derivative shown in formula (2),
the preparation method disclosed by the invention has the advantages of readily available raw materials, mild reaction conditions, high product yield, wide substrate application range, strong reaction specificity and simple, convenient, green and environment-friendly post-treatment, and is a novel and efficient method for synthesizing the 4-pyrroline-2-one derivative.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a 4-pyrroline-2-ketone derivative and a preparation method thereof.
Background
The synthesis of nitrogen-containing heterocyclic compounds with various structures by using simple and easily available raw materials is always the focus of attention of the organic chemistry community. Among them, compounds having a pyrroline core structure are widely used in medicines, and can be used as medicines or organic synthetic intermediates due to the presence of a C ═ C unsaturated bond in a molecule, and further undergo a functionalization reaction, and thus have an important effect on modification of pyrrolidones having pharmacological activities such as anti-inflammation, anti-senile dementia, anti-tumor, and anti-HIV. The 4-pyrroline-2-ketone derivative is an important nitrogen-containing heterocyclic compound and has wide biological activity, and a natural product, namely the Violacein, and some antibacterial and anti-inflammatory drugs and dye molecules all contain 4-pyrroline-2-ketone structures. Therefore, research on a new synthesis method of the 4-pyrroline-2-one compound and the analogues thereof has important application value and is concerned by researchers in related fields.
The traditional synthesis of 4-pyrroline-2-one compounds is mainly obtained by intramolecular or intermolecular cyclization reaction of pre-functionalized acyclic substrates, and the synthesis method has the defects of long reaction steps and low reaction efficiency, such as 1, 3-dihydro-2H-pyrroline compounds and the synthesis method thereof in Chinese patent application CN 106008304. To date, few methods have been reported for the oxidative synthesis of 4-pyrrolin-2-one compounds based on pyrrole. Even in the synthesis strategy based on pyrrole oxidative dearomatization developed in recent years, the use of hostile oxidation reagents such as ozone, high-valent iodine compounds, singlet oxygen, electrocatalytic oxidation and the like is often adopted, and side reactions such as decomposition, polymerization and the like are often generated in the reaction process. Therefore, the development of a green, environment-friendly, novel and efficient method for synthesizing the 4-pyrroline-2-ketone compound is very important and has important medicinal research value.
Disclosure of Invention
Summary of The Invention
The invention provides a preparation method of a 4-pyrroline-2-ketone derivative.
In another aspect, the invention provides a 4-pyrroline-2-one derivative.
Definition of terms
The term "aryl" denotes monocyclic, bicyclic and tricyclic carbon ring systems containing 6 to 14 ring atoms, or 6 to 12 ring atoms, or 6 to 10 ring atoms, wherein at least one ring system is aromatic, wherein each ring system contains 3 to 7 atoms. The aryl group is typically, but not necessarily, attached to the parent molecule through an aromatic ring of the aryl group. The term "aryl" may be used interchangeably with the terms "aromatic ring" or "aromatic ring". Examples of the aryl group may include phenyl, naphthyl, and anthracene.
The term "heteroaryl" denotes monocyclic, bicyclic and tricyclic ring systems containing 5 to 12 ring atoms, or 5 to 10 ring atoms, or 5 to 6 ring atoms, wherein at least one ring system is aromatic and at least one ring system contains one or more heteroatoms, wherein each ring system contains a ring of 5 to 7 atoms. The heteroaryl group is typically, but not necessarily, attached to the parent molecule through an aromatic ring of the heteroaryl group. The term "heteroaryl" may be used interchangeably with the terms "heteroaromatic ring", "aromatic heterocycle" or "heteroaromatic compound". The heteroaryl group is optionally substituted with one or more substituents described herein. In one embodiment, a heteroaryl group of 5-10 atoms contains 1, 2,3, or 4 heteroatoms independently selected from O, S, and N.
Detailed Description
The invention aims to provide a 4-pyrroline-2-ketone derivative and a preparation method thereof aiming at the defects of the prior art.
The preparation method of the invention can use oxygen in the air as an oxygen source, the used raw materials are easy to obtain, the reaction condition is mild, the product yield is high, the cost is low, the substrate application range is wide, the reaction specificity is strong, the post-treatment is simple, convenient, green and environment-friendly, and the method is a novel and efficient method for synthesizing the 4-pyrroline-2-one derivative.
The invention provides a preparation method of a 4-pyrroline-2-ketone derivative shown in a formula (2), which comprises the following steps of reacting a pyrrole compound shown in the formula (1) in the presence of a solvent, alkali and oxygen to obtain the 4-pyrroline-2-ketone derivative shown in the formula (2),
wherein the content of the first and second substances,
R1is hydrogen, halogen, alkyl, acyl, amino, nitro or alkoxy; or, R1Is a substituted or unsubstituted group: aryl or heteroaryl;
R2is hydrogen, halogen, acyl, amino or nitro; or, R2Is a substituted or unsubstituted group: alkyl, aryl or heteroaryl;
R3is hydrogen, halogen, acyl or nitro; or, R3Is a substituted or unsubstituted group: amino, alkyl, aryl or heteroaryl.
The method can be used for preparing the 4-pyrroline-2-ketone derivative, and has the advantages of mild reaction conditions, high product yield and wide substrate application range.
In some embodiments, the R1 is a substituted or unsubstituted group selected from: phenyl, thienyl, furyl, piperazinyl, or pyridyl.
In some embodiments, the R2 is a substituted or unsubstituted group selected from: C1-C6 alkyl, phenyl or naphthyl.
In some embodiments, the R3 is a substituted or unsubstituted group selected from: phenyl, naphthyl, thienyl, furyl, piperazinyl, or pyridyl.
In some embodiments, the solvent is one or more of dimethylsulfoxide, acetonitrile, N-dimethylformamide, N-dimethylacetamide, or N-methylpyrrolidone. The preparation method using the solvent has the advantages of mild reaction conditions, low cost, high yield and environmental protection.
In some embodiments, the base is one or more of sodium hydroxide, potassium tert-butoxide, sodium methoxide or sodium ethoxide. The preparation method of the alkali has mild reaction conditions, low cost and high yield.
In some embodiments, the oxygen is oxygen in air. Air is used as an oxygen source, the reaction condition is mild, the cost is low, and the yield is high.
In some embodiments, the molar ratio of the pyrrole compound of formula (1) to the base is from 1:1 to 1: 5; or the molar ratio of the pyrrole compound shown in the formula (1) to the base is 1:1-1: 3; or the molar ratio of the pyrrole compound shown in the formula (1) to the base is 1:1-1: 1. The preparation method using the molar ratio has low cost and high yield.
In some embodiments, the reaction temperature is from 10 ℃ to 75 ℃; or the reaction temperature is 25-60 ℃. The preparation method using the reaction temperature has mild reaction conditions, low cost and high yield.
In some embodiments, the reaction time is from 0.5h to 20 h; or the reaction time is 1h-10 h; or the reaction time is 1h-5 h.
In some embodiments, the concentration of the compound represented by the formula (1) in the reaction solution is from 0.5mol/L to 15 mol/L; or the concentration of the compound represented by the formula (1) in the reaction solution is 2mol/L to 12 mol/L. The preparation method using the above concentration has high yield.
In another aspect of the invention, there is provided a compound of the formula:
drawings
FIG. 1 shows a hydrogen-nuclear magnetic resonance spectrum of a compound represented by the formula (2a) ((1H-NMR)。
FIG. 2 is a carbon-core of a compound of formula (2a)Magnetic resonance spectrum diagram (13C-NMR)。
Detailed Description
In order to make the technical solutions of the present invention better understood by those skilled in the art, the following further discloses some non-limiting examples to further explain the present invention in detail.
The reagents used in the present invention are either commercially available or can be prepared by the methods described herein.
In the present invention, min represents min, h represents h, g represents g, mL represents mL, and mmol represents mmol.
Preparation of the starting Material
The pyrrole compounds represented by the formula (1a) -formula (1l) as the starting materials for use in the present invention can be prepared by the following reaction scheme, with reference to Chemical Communications (Cambridge, United Kingdom) (2013),49(90), 10641-10643:
raw material example 1: preparation of 2,3, 5-triphenylpyrrole compound shown in formula (1a)
Benzylamine (10mmol), 1, 3-diphenyl-prop-2-yn-1-one (10mmol), potassium phosphate (10mmol) and dimethyl sulfoxide (30mL) were added to a 100 mL round-bottom flask and stirred at room temperature for 2 h. After 12h of reaction in an oil bath at 140 ℃ under nitrogen protection, the reaction was stopped by adding an appropriate amount of water or sodium chloride solution. The reaction solution was diluted with ethyl acetate, washed with water three times, and the organic phase was washed with anhydrous Na2SO4Drying, filtering, concentrating and purifying by column chromatography to obtain 2.68g of target product with the yield of 91%.
Preparation of 4-pyrroline-2-one derivatives
Example 1: preparation of compound 3,3, 5-triphenyl-1H-pyrrole-2 (3H) -ketone shown as formula (2a)
2,3, 5-Triphenylpyrrole (1a) (0.5mmol), potassium hydroxide (1mmol) and dimethylsulfoxide (10mL) were placed in an oil bath at 50 ℃ and reacted for 1 h. The reaction was stopped by adding an appropriate amount of water or sodium chloride solution and cooled to room temperature. The reaction solution was diluted with ethyl acetate, washed with water three times, and the organic phase was washed with anhydrous Na2SO4Drying, filtering, concentrating and purifying by column chromatography to obtain 132.2mg of target product with the yield of 85%. The nuclear magnetic characterization of the compound is as follows:1H NMR(400MHz,CDCl3)δ8.97(s,1H),7.55(dd,J＝8.1,1.3Hz,2H),7.49–7.36(m,7H),7.36–7.31(m,4H),7.30–7.26(m,2H),6.14(d,J＝2.0Hz,1H)；13C NMR(100MHz,CDCl3)δ181.6,141.2,139.6,129.5,129.2,128.9,128.5,128.0,127.2,124.8,110.5,63.8。
example 2: preparation of Compound 3, 3-Diphenyl-5- (p-tolyl) -1H-pyrrol-2 (3H) -one represented by the formula (2b)
2, 3-Diphenyl-5- (p-tolyl) -1H-pyrrole (1b) (0.5mmol), sodium t-butoxide (1.5mmol) and N-methylpyrrolidone (2mL) were placed in a reaction vessel at room temperature and reacted for 10H. The reaction was stopped by adding an appropriate amount of water or sodium chloride solution and cooled to room temperature. The reaction solution was diluted with ethyl acetate, washed with water three times, and the organic phase was washed with anhydrous Na2SO4Drying, filtering, concentrating and purifying by column chromatography to obtain 149.5mg of target product with a yield of 92%. The nuclear magnetic characterization of the compound is as follows:1H NMR(400MHz,CDCl3)δ8.40(s,1H),7.44–7.36(m,6H),7.34–7.28(m,4H),7.27(dd,J＝3.7,2.4Hz,1H),7.25(s,1H),7.21(d,J＝8.0Hz,2H),6.06(d,J＝2.1Hz,1H),2.38(s,3H)；13C NMR(100MHz,CDCl3)δ181.1,141.3,139.4,129.6,128.5,128.0,127.1,126.8,124.7,109.6,63.7,21.3。
example 3: preparation of Compound 3, 3-Diphenyl-5- (o-tolyl) -1H-pyrrol-2 (3H) -one represented by the formula (2c)
2, 3-Diphenyl-5- (o-tolyl) -1H-pyrrole (1c) (0.5mmol), potassium tert-butoxide (1mmol) and dimethyl sulfoxide (3mL) were placed in an oil bath at 50 ℃ and reacted for 1H. The reaction was stopped by adding an appropriate amount of water or sodium chloride solution and cooled to room temperature. The reaction solution was diluted with ethyl acetate, washed with water three times, and the organic phase was washed with anhydrous Na2SO4Drying, filtering, concentrating and purifying by column chromatography to obtain 112.1mg of target product with the yield of 69%. The nuclear magnetic characterization of the compound is as follows:1H NMR(400MHz,CDCl3)δ7.92(s,1H),7.40(d,J＝7.3Hz,4H),7.36–7.22(m,10H),5.82(d,J＝2.0Hz,1H),2.43(s,3H)；13C NMR(100MHz,CDCl3)δ180.6,141.2,139.4,136.2,131.1,130.6,129.1,128.5,128.0,128.0,127.2,126.2,114.3,63.6,20.8。
example 4: preparation of compound 3, 3-diphenyl-5- (p-methoxyphenyl) -1H-pyrrol-2 (3H) -one shown as formula (2d)
2, 3-Diphenyl-5- (p-methoxyphenyl) -1H-pyrrole (1d) (0.5mmol), sodium hydroxide (1mmol) and N, N-dimethylformamide (10mL) were put in an oil bath at 60 ℃ and reacted for 10 hours. The reaction was stopped by adding an appropriate amount of water or sodium chloride solution and cooled to room temperature. The reaction solution was diluted with ethyl acetate, washed with water three times, and the organic phase was washed with anhydrous Na2SO4Drying, filtering, concentrating and purifying by column chromatography to obtain 93.8mg of target product with the yield of 55%. The nuclear magnetic characterization of the compound is as follows:1H NMR(400MHz,CDCl3)δ7.91(s,1H),7.47–7.36(m,6H),7.32(dd,J＝8.2,6.5Hz,4H),7.27(s,2H),6.93(d,J＝8.8Hz,2H),5.97(d,J＝2.1Hz,1H),3.84(s,3H)；13C NMR(100MHz,CDCl3)δ180.8,160.4,141.4,138.9,128.5,128.0,127.1,126.2,122.3,114.4,108.6,63.7,55.4。
example 5: preparation of compound 3, 3-diphenyl-5- (p-chlorophenyl) -1H-pyrrol-2 (3H) -one of formula (2e)
2, 3-Diphenyl-5- (p-chlorophenyl) -1H-pyrrole (1e) (0.5mmol), sodium methoxide (1.5mmol) and N, N-dimethylacetamide (2mL) were put in an oil bath at 60 ℃ and reacted for 3 hours. The reaction was stopped by adding an appropriate amount of water or sodium chloride solution and cooled to room temperature. The reaction solution was diluted with ethyl acetate, washed with water three times, and the organic phase was washed with anhydrous Na2SO4Drying, filtering, concentrating and purifying by column chromatography to obtain 131.1mg of target product with the yield of 76%. The nuclear magnetic characterization of the compound is as follows:1H NMR(400MHz,CDCl3)δ9.18(s,1H),7.50–7.44(m,2H),7.41–7.36(m,5H),7.36–7.25(m,7H),6.12(d,J＝2.1Hz,1H)；13C NMR(100MHz,CDCl3)δ181.7,141.0,138.7,135.1,129.1,128.6,128.1,128.0,127.3,126.2,111.0,63.9。
example 6: preparation of compound 3, 3-diphenyl-5- (3-thienyl) -1H-pyrrole-2 (3H) -ketone shown as formula (2f)
0.5mmol of 2, 3-diphenyl-5- (3-thienyl) -1H-pyrrole (1f), 1.5mmol of sodium hydroxide and 5mL of dimethyl sulfoxide are put in an oil bath at 60 ℃ for reaction for 3H. The reaction was stopped by adding an appropriate amount of water or sodium chloride solution and cooled to room temperature. The reaction solution is diluted by ethyl acetate, washed by water for three times, and the organic phase is added with anhydrous Na2SO4Drying, filtering, concentrating and purifying by column chromatography gave 109.4mg of the desired product in 69% yield. The nuclear magnetic characterization of the compound is as follows:1H NMR(400MHz,CDCl3)δ8.88(s,1H),7.43(d,J＝1.6Hz,1H),7.40–7.29(m,9H),7.27(d,J＝7.6Hz,3H),5.97(d,J＝2.0Hz,1H)；13C NMR(100MHz,CDCl3)δ181.4,141.2,135.5,131.5,128.5,128.0,127.2,127.0,124.7,122.0,109.9,63.7。
example 7: preparation of 3, 5-Diphenyl-3- (p-tolyl) -1H-pyrrol-2 (3H) -one, a compound represented by the formula (2g)
2, 5-Diphenyl-3- (p-tolyl) -1H-pyrrole (1g) (0.5mmol), sodium hydroxide (1mmol) and N, N-dimethylacetamide (12mL) were placed in an oil bath at 50 ℃ and reacted for 10H. The reaction was stopped by adding an appropriate amount of water or sodium chloride solution and cooled to room temperature. The reaction solution was diluted with ethyl acetate, washed with water three times, and the organic phase was washed with anhydrous Na2SO4Drying, filtering, concentrating, and purifying by column chromatography to obtain 120.3mg of target product with a yield of 74%. The nuclear magnetic characterization of the compound is as follows:1H NMR(400MHz,CDCl3)δ8.80(s,1H),7.53(d,J＝7.0Hz,2H),7.47–7.19(m,10H),7.12(d,J＝7.9Hz,2H),6.11(s,1H),2.32(s,3H)；13C NMR(100MHz,CDCl3)δ181.6,141.3,139.4,138.2,136.9,129.7,129.2,129.2,128.9,128.5,128.0,127.9,127.1,124.8,110.6,63.5,21.0。
example 8: preparation of compound 3, 5-diphenyl-3- (p-tert-butylphenyl) -1H-pyrrol-2 (3H) -one of formula (2H)
3, 5-Diphenyl-2- (p-tert-butylphenyl) -1H-pyrrole (1H) (0.5mmol), potassium hydroxide (1mmol) and dimethyl sulfoxide (2mL) were placed in an oil bath at 50 ℃ and reacted for 3H. The reaction was stopped by adding an appropriate amount of water or sodium chloride solution and cooled to room temperature. The reaction solution was diluted with ethyl acetate, washed with water three times, and the organic phase was washed with anhydrous Na2SO4Drying, filtering, concentrating and purifying by column chromatography to obtain 148.6mg of target product with the yield of 81%. The nuclear magnetic characterization of the compound is as follows:1H NMR(400MHz,CDCl3)δ9.58(s,1H),7.62(dd,J＝8.1,1.3Hz,2H),7.50(dd,J＝5.2,3.4Hz,2H),7.46–7.35(m,9H),7.33–7.28(m,1H),6.19(d,J＝2.1Hz,1H),1.35(s,9H)；13C NMR(100MHz,CDCl3)δ182.2,149.9,141.3,139.6,138.1,129.6,129.0,128.8,128.4,128.1,127.6,127.1,125.4,124.9,110.7,63.5,34.4,31.3。
example 9: preparation of compound 3, 5-diphenyl-3- (2-thienyl) -1H-pyrrole-2 (3H) -ketone shown as formula (2i)
2, 5-Diphenyl-3- (2-thienyl) -1H-pyrrole (1i) (0.5mmol) was reacted with sodium tert-butoxide (1mmol) and dimethylsulfoxide (5mL) at room temperature for 10H. The reaction was stopped by adding an appropriate amount of water or sodium chloride solution and cooled to room temperature. The reaction solution was diluted with ethyl acetate, washed with water three times, and the organic phase was washed with anhydrous Na2SO4Drying, filtering, concentrating and purifying by column chromatography to obtain 125.2mg of target product with the yield of 79 percent. The nuclear magnetic characterization of the compound is as follows:1H NMR(400MHz,CDCl3)δ8.88(s,1H),7.56(d,J＝7.6Hz,2H),7.41(ddd,J＝10.1,7.5,3.3Hz,5H),7.34–7.25(m,4H),7.15(d,J＝3.5Hz,1H),7.00(dd,J＝4.9,3.8Hz,1H),6.15(d,J＝1.9Hz,1H)；13C NMR(100MHz,CDCl3)δ180.6,143.7,140.7,140.1,129.5,129.4,129.0,128.6,127.6,127.2,126.7,126.0,125.4,125.0,110.4,60.5。
example 10 preparation of 3, 5-Diphenyl-3- (2-naphthyl) -1H-pyrrol-2 (3H) -one compounds of the formula (2j)
2, 5-Diphenyl-3- (2-naphthyl) -1H-pyrrole (1j) (0.5mmol), sodium tert-butoxide (1.5mmol) and dimethyl sulfoxide (2mL) were placed in an oil bath at 60 ℃ and reacted for 1H. The reaction was stopped by adding an appropriate amount of water or sodium chloride solution and cooled to room temperature. The reaction solution was diluted with ethyl acetate, washed with water three times, and the organic phase was washed with anhydrous Na2SO4Drying, filtering, concentrating and purifying by column chromatography gave 149.8mg of the desired product in 83% yield. The nuclear magnetic characterization of the compound is as follows:1H NMR(400MHz,CDCl3)δ8.54(s,1H),7.91(s,1H),7.87–7.71(m,3H),7.60–7.53(m,2H),7.50–7.27(m,11H),6.21(d,J＝2.0Hz,1H)；13C NMR(100MHz,CDCl3)δ181.1,141.1,139.7,138.4,133.2,132.5,129.6,129.3,129.0,128.6,128.4,128.2,128.1,127.5,127.3,126.5,126.3,126.2,126.1,124.9,110.3,63.9。
example 11: preparation of compound 3, 5-diphenyl-3-cyclohexyl-1H-pyrrol-2 (3H) -one of formula (2k)
2, 5-Diphenyl-3-cyclohexyl-1H-pyrrole (1k) (0.5mmol) was added with sodium hydroxide (1.5mmol) and dimethyl sulfoxide (2mL), and reacted for 6H in an oil bath at 60 ℃. The reaction was stopped by adding an appropriate amount of water or sodium chloride solution and cooled to room temperature. The reaction solution was diluted with ethyl acetate, washed with water three times, and the organic phase was washed with anhydrous Na2SO4Drying, filtering, concentrating and purifying by column chromatography to obtain 141.1mg of target product, with the yield of 89%. The nuclear magnetic characterization of the compound is as follows:1H NMR(400MHz,CDCl3)δ9.23(s,1H),7.65(dd,J＝14.4,7.4Hz,4H),7.48(t,J＝7.4Hz,2H),7.41(t,J＝7.3Hz,1H),7.35(t,J＝7.6Hz,2H),7.28(d,J＝6.6Hz,1H),6.01(d,J＝1.9Hz,1H),2.31–2.22(m,1H),1.79–1.64(m,4H),1.54(d,J＝12.4Hz,1H),1.33–1.01(m,5H)；13C NMR(100MHz,CDCl3)δ183.3,140.8,140.0,129.9,128.9,128.8,128.2,127.3,126.9,124.8,106.0,62.9,46.8,28.3,28.1,26.7,26.3,26.3。
example 12: preparation of 2-butyl-3- (3-pyridyl) -3-hydroxyisoindol-1-one compound represented by the formula (2l)
3, 5-Diphenyl-2-methyl-1H-pyrrole (1l) (0.5mmol), potassium tert-butoxide (1mmol) and N-methylpyrrolidone (5mL) were placed in an oil bath at 80 ℃ and reacted for 2H. The reaction was stopped by adding an appropriate amount of water or sodium chloride solution and cooled to room temperature. The reaction solution was extracted with ethyl acetateDiluting, washing with water for three times, and mixing the organic phase with anhydrous Na2SO4Drying, filtering, concentrating and purifying by column chromatography to obtain 78.4mg of target product with the yield of 63%. The nuclear magnetic characterization of the compound is as follows:1H NMR(400MHz,CDCl3)δ9.11(s,1H),7.54(d,J＝7.1Hz,2H),7.52–7.48(m,2H),7.40(t,J＝7.4Hz,2H),7.37–7.30(m,3H),7.27–7.23(m,1H),5.89(s,1H)；13C NMR(100MHz,CDCl3)δ184.3,140.6,139.6,139.6,129.9,129.0,128.9,128.6,127.1,126.4,124.8,124.8,111.6,54.5,23.6。
the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (7)
1. A preparation method of 4-pyrroline-2-ketone derivatives shown in formula (2) comprises the steps of reacting pyrrole compounds shown in formula (1) in the presence of a solvent, alkali and oxygen to obtain the 4-pyrroline-2-ketone derivatives shown in formula (2),
wherein the content of the first and second substances,
R1is a substituted or unsubstituted group: aryl or heteroaryl;
R2is a substituted or unsubstituted group: alkyl, aryl or heteroaryl;
R3is a substituted or unsubstituted group: amino, alkyl, aryl or heteroaryl;
the alkali is one or more of sodium hydroxide, potassium tert-butoxide, sodium methoxide or sodium ethoxide.
2. The method according to claim 1, wherein R1 is a substituted or unsubstituted group selected from: phenyl, thienyl, furyl, piperazinyl, or pyridyl.
3. The method according to claim 1, wherein R2 is a substituted or unsubstituted group selected from: C1-C6 alkyl, phenyl or naphthyl.
4. The method according to claim 1, wherein R3 is a substituted or unsubstituted group selected from: phenyl, naphthyl, thienyl, furyl, piperazinyl, or pyridyl.
5. The method according to claim 1, wherein the solvent is one or more of dimethylsulfoxide, N-dimethylformamide, N-dimethylacetamide, or N-methylpyrrolidone.
6. The production method according to claim 1, wherein the oxygen is oxygen in air.
7. The process according to claim 1, wherein the molar ratio of the azole compound represented by the formula (1) to the base is from 1:1 to 1: 3.
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