阅读说明：本技术 一种3-胺烷基色酮化合物及其制备方法 (3-amine alkyl chromone compound and preparation method thereof ) 是由 祝志强 胡家榆 程宏丽 谢宗波 乐长高 汤娟 于 2021-09-16 设计创作，主要内容包括：本发明公开了一种3-胺烷基色酮化合物及其制备方法,制备方法包括以下实验步骤：在室温下混合溶剂中,2-羟基苯基烯胺酮和N-芳基甘氨酸为反应底物,在18W蓝光照射下搅拌反应8-12小时,至TLC检测原料转化完全,反应混合液经柱层析分离,可制得产物3-胺烷基色酮化合物。(The invention discloses a 3-amine alkyl chromone compound and a preparation method thereof, wherein the preparation method comprises the following experimental steps: in a mixed solvent at room temperature, 2-hydroxyphenyl enaminone and N-aryl glycine are used as reaction substrates, the mixture is stirred and reacted for 8 to 12 hours under the irradiation of 18W blue light until the TLC detection raw material is completely converted, and the reaction mixed liquid is separated by column chromatography to obtain the product 3-aminoalkyl chromone compound.)

1. A3-amine alkyl chromone compound and a preparation method thereof are characterized in that the structural formula is shown as the formula (I):

in the formula, R¹Is hydrogen, an electron donating or electron withdrawing group, R¹Is connected with a benzene ring; r²Is hydrogen, an electron donating or electron withdrawing group, R²Is connected with a benzene ring.

2. The 3-aminoalkylchromonic compound of claim 1 wherein R is¹When the electron donating group is selected, the electron donating group is 5-methyl, 5-methoxy, 4-methoxy or 4, 5-dimethyl; r¹When selected as an electron withdrawing group, saidThe electron-withdrawing group of (a) is a halogen atom.

3. The 3-aminoalkylchromonic compound of claim 2 wherein R is¹When the electron-withdrawing group is selected, the electron-withdrawing group is fluorine, chlorine and bromine atoms.

4. A3-aminoalkylchromonic compound in accordance with claim 2 or 3 wherein R is¹When the electron-withdrawing group is selected, the electron-withdrawing group is 4-fluorine, 4-chlorine, 4-bromine, 5-fluorine, 5-chlorine or 5-bromine.

5. The 3-aminoalkylchromonic compound of claim 1 wherein R is the number¹Selected as hydrogen, R²When the electron donating group is selected, the electron donating group is methyl, tert-butyl or 3, 4-dimethyl.

6. The 3-aminoalkylchromonic compound of claim 4 wherein R is the number¹Selected as hydrogen, R²When the electron donating group is selected, the electron donating group is 3-methyl, 4-methyl, 3, 4-dimethyl and 4-tertiary butyl.

7. A3-amine alkyl chromone compound and a preparation method thereof comprise the following steps: in a volume ratio of 20:1, irradiating 2-hydroxyphenyl enaminone and N-aryl glycine by adopting 18W blue light at room temperature, stirring and reacting for 8-12 hours until TLC detection reaction is complete, and separating reaction mixed liquor by column chromatography to obtain a product 3-aminoalkyl chromone compound (I), wherein the reaction general formula is as follows:

8. the method of claim 4, wherein the solvent used in the step (A) is acetonitrile, 1, 2-dichloroethane, tetrahydrofuran, dimethylsulfoxide, or a mixture of ethanol and water.

9. The 3-aminoalkylchromone compound and the preparation method thereof as claimed in claim 5, wherein the temperature in the step is 25-35 ℃.

10. The 3-aminoalkyl chromone compound and the preparation method thereof as claimed in claim 6, wherein the light source used for the visible light irradiation is LED blue light with a wavelength of 450-460nm, and the time for irradiating the reaction solution with the visible light is 8-12 hours.

Technical Field

The invention belongs to the field of organic synthesis, relates to synthesis of a 3-aminoalkyl chromone compound, and particularly relates to a synthesis method of a visible light catalytic 3-aminoalkyl chromone compound.

Background

Chromones are an important class of oxygen-containing heterocyclic compounds, which are widely found in many natural products, drugs, and functional materials. Chromone is the core skeleton structure of flavonoid, and molecules containing the chromone structure have various biological and pharmacological activities, such as anticancer, antibacterial and anti-inflammatory effects. Among them, 3-substituted chromones have great application value in the fields of biochemistry, pharmaceutical chemistry and the like due to wide physiological activity. Therefore, the preparation of 3-substituted chromone compounds has attracted considerable interest to researchers.

Conventional synthetic strategies for 3-substituted chromones, which are typically obtained by coupling halogenated chromones under transition metal catalysis, require pre-functionalization of the reaction substrate, thereby limiting their application in industrial production. In addition, in recent years, the application of intermolecular coupling and intramolecular cyclization reactions to the construction of 3-substituted chromone compounds has also made remarkable progress. Nevertheless, there is still a need and a need to find a simpler, more efficient, convenient, practical and environmentally friendly method for preparing 3-substituted chromone compounds with potential biological activity.

Visible light is a green, clean, abundant and easily available renewable resource, and the catalytic reaction condition is mild, and the chemical selectivity and the functional group compatibility are good. In recent years, visible light-induced organic synthesis has developed into a very important approach. Amino acid is an important biomass raw material, and has important research significance and application value when being used as an effective synthesis building block for constructing functional organic molecules. Based on the method, green, clean, abundant, cheap and sustainable visible light is adopted to promote decarboxylation, coupling and cyclization of 2-hydroxyphenyl enaminone and N-aryl glycine to prepare a series of 3-amine alkyl chromone compounds. To our knowledge, no patent or literature report has been found on the synthesis of 3-aminoalkylchromone compounds by using visible light-induced 2-hydroxyphenyl enaminones and N-aryl glycines.

Disclosure of Invention

The invention provides a 3-amine alkyl chromone compound and a preparation method thereof. According to the method, 2-hydroxyphenyl enaminone and N-aryl glycine are used as reaction substrates, a reaction mixture of the 2-hydroxyphenyl enaminone and the N-aryl glycine is irradiated by 18W blue light at room temperature in air, intermolecular decarboxylation coupling cyclization is carried out, and the 3-aminoalkyl chromone compound is efficiently prepared in one step. The synthesis method of the 3-amine alkyl chromone compound provided by the invention does not need a photosensitizer or an additive, and has the advantages of simple and convenient reaction operation, mild conditions and good chemical selectivity.

The invention adopts the following technical scheme: a3-aminoalkylchromone compound has the structural formula shown in formula (I):

wherein R is¹May be hydrogen, electron donating groups or electron withdrawing groups. Preferably, the electron donating group can be methyl, methoxy, preferably, the electron donating group is 5-methyl, 5-methoxy, 4-methoxy or 4, 5-dimethyl; the electron-withdrawing group may be a halogen atom, preferably a fluorine, chlorine, bromine atom, and further preferably 4-fluorine, 4-chlorine, 4-bromine, 5-fluorine, 5-chlorine or 5-bromine. .

R²Is hydrogen, electron donating group or electron withdrawing group, when R²In the case of the electron-donating group, the electron-donating group is not particularly limited, and is preferably a methyl group, a tert-butyl group, or a 3, 4-dimethyl group, and further preferably a 3-methyl group, a 4-methyl group, a 3, 4-dimethyl group, or a 4-tert-butyl group.

The invention relates to a 3-amine alkyl chromone compound and a preparation method thereof, comprising the following experimental steps: in a mixed solvent at room temperature, taking 2-hydroxyphenyl enaminone and N-aryl glycine as reaction substrates, stirring and reacting for 8-12 hours under the irradiation of 18W blue light until TLC detection raw materials are completely converted, and performing column chromatography separation on reaction mixed liquid to obtain the product 3-aminoalkyl chromone compound (I). The reaction formula is as follows:

in the preparation method of the invention:

preferably, the solvent in said step is acetonitrile, 1, 2-dichloroethane, tetrahydrofuran, dimethyl sulfoxide or a solvent of ethanol mixed with water, most preferably tetrahydrofuran: water (20: 1 by volume).

Preferably, the temperature in said step is 25-35 ℃, most preferably 35 ℃.

Preferably, the light source used for visible light irradiation is 18W LED blue light with the wavelength of 450-460nm, and the time for irradiating the reaction solution with the blue light is 8-12 hours.

The method of the invention has the following advantages and beneficial effects: the 3-aminoalkyl chromone compound and the preparation method thereof have the advantages of practicability, high efficiency, simple operation, mild reaction conditions, good chemical selectivity and the like. The invention can prepare a series of 3-amine alkyl chromone compounds by directly irradiating reaction liquid with 18W blue light in the air at room temperature. The method is practical, simple and convenient, is easy to operate, is suitable for large-scale synthesis, and has wide application prospect.

Detailed Description

The present invention will be described in more detail with reference to specific examples and experimental examples, but the embodiments of the present invention are not limited thereto.

Detailed description of the invention

The invention is implemented in the following way: a3-aminoalkylchromone compound has the structural formula shown in formula (I):

wherein R is¹May be hydrogen, electron donating groups or electron withdrawing groups. Preferably, the electron donating group can be methyl, methoxy, preferably, the electron donating group is 5-methyl, 5-methoxy, 4-methoxy or 4, 5-dimethyl; the electron-withdrawing group may be a halogen atom, preferably a fluorine, chlorine, bromine atom, and further preferably 4-fluorine, 4-chlorine, 4-bromine, 5-fluorine, 5-chlorine or 5-bromine. .

R²Is hydrogen, electron donating group or electron withdrawing group, when R²When the electron-donating group is used, the electron-donating group may be non-limiting, and is preferablyMethyl, tert-butyl and 3, 4-dimethyl are selected, and 3-methyl, 4-methyl, 3, 4-dimethyl and 4-tert-butyl are further preferred.

The invention relates to a 3-amine alkyl chromone compound and a preparation method thereof, comprising the following experimental steps: in a mixed solvent at room temperature, taking 2-hydroxyphenyl enaminone and N-aryl glycine as reaction substrates, stirring and reacting for 8-12 hours under the irradiation of 18W blue light until TLC detection raw materials are completely converted, and performing column chromatography separation on reaction mixed liquid to obtain the product 3-aminoalkyl chromone compound (I). The reaction formula is as follows:

in the preparation method of the invention:

preferably, the solvent in said step is acetonitrile, 1, 2-dichloroethane, tetrahydrofuran, dimethyl sulfoxide or a solvent of ethanol mixed with water, most preferably tetrahydrofuran: water (20: 1 by volume).

Preferably, the temperature in said step is 25-35 ℃, most preferably 35 ℃.

Preferably, the light source used for visible light irradiation is 18W LED blue light with the wavelength of 450-460nm, and the time for irradiating the reaction solution with the blue light is 8-12 hours.

Experimental example 1

5-methyl-2-hydroxyphenyl-enaminone (0.2mmol) and N-4-methyl-arylglycine (0.6mmol) were added to a dry reaction tube with stirring magnetons. Tetrahydrofuran and water (2mL, volume ratio 20:1) were added as a reaction solvent to a test tube, and the reaction mixture was left to react for 12 hours at room temperature under an air atmosphere. After TLC detection reaction is finished, the reaction solvent is removed by reduced pressure distillation of a rotary evaporator, and the residue is separated and purified by column chromatography to obtain pure yellow solid 3aa with the yield of 67%. The structural characterization data for the 3aa compound is as follows:

Yellow solid；m.p.132.3-136.4℃；¹HNMR(400MHz,CDCl₃)δ8.01-7.98(m,1H),7.87(d,J＝1.1Hz,1H),7.45(dd,J＝8.6,2.2Hz,1H),7.30(d,J＝8.5Hz,1H),6.97(d,J＝8.1Hz,2H),6.58-6.54(m,2H),4.23(d,J＝1.1Hz,2H),2.44(s,3H),2.21(s,3H)；¹³C NMR(100MHz,CDCl₃)δ178.1,154.8,153.1,145.2,135.1,134.9,129.8,127.3,124.9,123.5,121.2,117.9,113.7,40.9,20.9,20.4；HRMS(ESI)calcd for C₁₈H₁₈NO₂(M+H)⁺280.1332,found 280.1334.

experimental example 2

5-methoxy-2-hydroxyphenyl-enaminone (0.2mmol) and N-4-methyl-arylglycine (0.6mmol) were added to a dry reaction tube with stirring magnetons. Tetrahydrofuran and water (2mL, volume ratio 20:1) were added as a reaction solvent to a test tube, and the reaction mixture was left to react for 12 hours at room temperature under an air atmosphere. After TLC detection reaction is finished, the reaction solvent is removed by reduced pressure distillation of a rotary evaporator, and the residue is separated and purified by column chromatography to obtain pure yellow solid 2b with the yield of 56%. The structural characterization data for the 2b compound is as follows:

Yellowsolid；m.p.157.8-160.2℃；¹HNMR(400MHz,CDCl₃)δ7.88(d,J＝1.1Hz,1H),7.57(d,J＝3.1Hz,1H),7.34(d,J＝9.1Hz,1H),7.24(dd,J＝9.1,3.0Hz,1H),6.97(d,J＝8.1Hz,2H),6.60-6.55(m,2H),4.24(d,J＝1.1Hz,2H),3.88(s,3H),2.22(s,3H)；¹³C NMR(100MHz,CDCl₃)δ177.8,156.9,153.0,151.4,145.2,129.8,127.3,124.4,123.8,120.6,119.6,113.7,104.6,55.9,40.9,20.4；HRMS(ESI)calcd for C₁₈H₁₈NO₂(M+H)⁺296.1281,found 296.1282.

experimental example 3

4-methoxy-2-hydroxyphenyl-enaminone (0.2mmol) and N-4-methyl-arylglycine (0.6mmol) were added to a dry reaction tube with stirring magnetons. Tetrahydrofuran and water (2mL, volume ratio 20:1) were added as a reaction solvent to a test tube, and the reaction mixture was left to react for 12 hours at room temperature under an air atmosphere. After TLC detection reaction is finished, the reaction solvent is removed by reduced pressure distillation of a rotary evaporator, and the residue is separated and purified by column chromatography to obtain pure yellow solid 2c with the yield of 66%. The structural characterization data for the 2c compound is as follows:

Yellow solid；m.p.147.0-153.6℃；¹H NMR(400MHz,CDCl₃)δ8.11(d,J＝8.9Hz,1H),7.81(d,J＝1.2Hz,1H),6.97(d,J＝2.4Hz,1H),6.97-6.93(m,2H),6.78(d,J＝2.4Hz,1H),6.59-6.55(m,2H),4.20(d,J＝1.2Hz,2H),3.87(s,3H),2.21(s,3H)；¹³C NMR(100MHz,CDCl₃)δ177.4,164.1,158.3,152.7,145.2,129.8,127.3,127.0,121.2,117.8,114.6,113.7,100.2,55.8,40.8,20.4；HRMS(ESI)calcd for C₁₈H₁₈NO₂(M+H)⁺296.1281,found 296.1280.

experimental example 4

4, 5-dimethyl-2-hydroxyphenyl-enaminone (0.2mmol) and N-4-methyl-arylglycine (0.6mmol) were added to a dry reaction tube with stirring magnetons. Tetrahydrofuran and water (2mL, volume ratio 20:1) were added as a reaction solvent to a test tube, and the reaction mixture was left to react for 12 hours at room temperature under an air atmosphere. After TLC detection reaction is finished, the reaction solvent is removed by reduced pressure distillation of a rotary evaporator, and the residue is separated and purified by column chromatography to obtain pure yellow solid 2d with the yield of 65%. The structural characterization data for the 2d compound is as follows:

Yellowsolid；m.p.138.2-142.5℃；¹HNMR(400MHz,CDCl₃)δ7.94(s,1H),7.84(d,J＝1.2Hz,1H),7.18(s,1H),6.97(d,J＝8.0Hz,2H),6.60-6.56(m,2H),4.22(d,J＝1.2Hz,2H),2.35(d,J＝6.5Hz,6H),2.22(s,3H)；¹³C NMR(100MHz,CDCl₃)δ177.9,155.2,152.8,145.1,144.1,134.4,129.8,127.4,125.2,121.8,121.0,118.2,113.8,41.1,20.4,19.3；HRMS(ESI)calcd for C₁₉H₂₀NO₂(M+H)⁺294.1489,found 294.1487.

experimental example 5

4-fluoro-2-hydroxyphenyl-enaminone (0.2mmol) and N-4-methyl aryl glycine (0.6mmol) were added to a dry reaction tube with stirring magnetons. Tetrahydrofuran and water (2mL, volume ratio 20:1) were added as a reaction solvent to a test tube, and the reaction mixture was left to react for 12 hours at room temperature under an air atmosphere. After TLC detection reaction is finished, the reaction solvent is removed by reduced pressure distillation of a rotary evaporator, and the residue is separated and purified by column chromatography to obtain pure yellow solid 2e with the yield of 72%. The structural characterization data for the 2e compound is as follows:

Yellow solid；m.p.141.4-143.1℃；¹HNMR(400MHz,CDCl₃)δ8.23(dd,J＝8.8,6.3Hz,1H),7.86(d,J＝1.2Hz,1H),7.14-7.07(m,2H),6.97(d,J＝8.1Hz,2H),6.59-6.51(m,2H),4.23(d,J＝1.2Hz,2H),2.22(s,3H)；¹³C NMR(100MHz,CDCl₃)δ177.0,165.6(d,J＝255.2Hz,2C),157.5(d,J＝13.4Hz,2C),153.2,145.0,129.8,128.2(d,J＝10.7Hz,2C),127.4,121.7,120.8(d,J＝2.2Hz,2C),114.0(d,J＝23.0Hz),113.6,104.7(d,J＝25.2Hz),40.6,20.3；HRMS(ESI)calcd for C₁₇H₁₅FNO₂(M+H)⁺284.1081,found 284.1080.

experimental example 6

4-chloro-2-hydroxyphenyl-enaminone (0.2mmol) and N-4-methyl aryl glycine (0.6mmol) were added to a dry reaction tube with stirring magnetons. Tetrahydrofuran and water (2mL, volume ratio 20:1) were added as a reaction solvent to a test tube, and the reaction mixture was left to react for 12 hours at room temperature under an air atmosphere. After TLC detection reaction is finished, the reaction solvent is removed by reduced pressure distillation of a rotary evaporator, and the residue is separated and purified by column chromatography to obtain pure yellow solid 2f with the yield of 70%. The structural characterization data for the 2f compound is as follows:

Yellowsolid；m.p.150.2-154.3℃；¹HNMR(400MHz,CDCl₃)δ8.14(d,J＝8.6Hz,1H),7.85(d,J＝1.2Hz,1H),7.42(d,J＝1.9Hz,1H),7.34(dd,J＝8.6,1.9Hz,1H),6.97(d,J＝8.2Hz,2H),6.57-6.54(m,2H),4.22(d,J＝1.1Hz,2H),2.22(s,3H)；¹³C NMR(100MHz,CDCl₃)δ176.8,154.9,153.3,145.0,133.9,131.1,129.8,127.5,125.0,124.7,121.6,119.9,113.6,40.7,20.4；HRMS(ESI)calcd for C₁₇H₁₅ClNO₂(M+H)⁺300.0786,found 300.0786.

experimental example 7

4-bromo-2-hydroxyphenyl-enaminone (0.2mmol) and N-4-methyl-arylglycine (0.6mmol) were added to a dry reaction tube with stirring magnetons. Tetrahydrofuran and water (2mL, volume ratio 20:1) were added as a reaction solvent to a test tube, and the reaction mixture was left to react for 12 hours at room temperature under an air atmosphere. After TLC detection reaction is finished, the reaction solvent is removed by reduced pressure distillation through a rotary evaporator, and the residue is separated and purified by column chromatography to obtain pure yellow solid 2g, wherein the yield is 63%. The structural characterization data for 2g of compound is as follows:

Yellowsolid；m.p.146.5-150.0℃；¹HNMR(400MHz,CDCl₃)δ8.07(d,J＝8.6Hz,1H),7.84(d,J＝1.2Hz,1H),7.60(d,J＝1.7Hz,1H),7.50(dd,J＝8.5,1.8Hz,1H),6.97(d,J＝8.1Hz,2H),6.57-6.53(m,2H),4.22(d,J＝1.2Hz,2H),2.22(s,3H)；¹³C NMR(100MHz,CDCl₃)δ177.3,156.6,153.1,145.0,129.8,128.8,128.0,127.4,127.1,122.7,121.9,121.2,113.6,40.7,20.4；HRMS(ESI)calcd for C₁₇H₁₅BrNO₂(M+H)⁺344.0281,found 344.0282.

experimental example 8

5-fluoro-2-hydroxyphenyl-enaminone (0.2mmol) and N-4-methyl aryl glycine (0.6mmol) were added to a dry reaction tube with stirring magnetons. Tetrahydrofuran and water (2mL, volume ratio 20:1) were added as a reaction solvent to a test tube, and the reaction mixture was left to react for 12 hours at room temperature under an air atmosphere. After TLC detection reaction is finished, the reaction solvent is removed by reduced pressure distillation of a rotary evaporator, and the residue is separated and purified by column chromatography to obtain pure yellow solid for 2h, wherein the yield is 65%. The structural characterization data for the 2h compound is as follows:

Yellowsolid；m.p.157.3-160.2℃；¹HNMR(400MHz,CDCl₃)δ7.90(d,J＝1.1Hz,1H),7.85(dd,J＝8.2,3.0Hz,1H),7.43(dd,J＝9.2,4.3Hz,1H),7.40-7.36(m,1H),6.98(d,J＝8.1Hz,2H),6.58-6.54(m,2H),4.24(d,J＝1.1Hz,2H),2.22(s,3H)；¹³C NMR(100MHz,CDCl₃)δ177.2,159.5(d,J＝247.0Hz,2C),153.4,152.8(d,J＝1.5Hz,2C),145.0,129.8,127.4,124.9(d,J＝7.2Hz,2C),121.9(d,J＝25.6Hz,2C),120.9,120.3(d,J＝8.1Hz,2C),113.6,110.4(d,J＝23.6Hz,2C),40.7,20.4；HRMS(ESI)calcd for C₁₇H₁₅FNO₂(M+H)⁺284.1081,found 284.1082.

experimental example 9

5-chloro-2-hydroxyphenyl-enaminone (0.2mmol) and N-4-methyl aryl glycine (0.6mmol) were added to a dry reaction tube with stirring magnetons. Tetrahydrofuran and water (2mL, volume ratio 20:1) were added as a reaction solvent to a test tube, and the reaction mixture was left to react for 12 hours at room temperature under an air atmosphere. After TLC detection reaction is finished, the reaction solvent is removed by reduced pressure distillation of a rotary evaporator, and the residue is separated and purified by column chromatography to obtain pure yellow solid 2i with the yield of 65%. The structural characterization data for the 2i compound is as follows:

Yellowsolid；m.p.155.7-158.9℃；¹HNMR(400MHz,CDCl₃)δ8.17(d,J＝2.6Hz,1H),7.88(d,J＝1.1Hz,1H),7.58(dd,J＝8.9,2.7Hz,1H),7.37(d,J＝8.9Hz,1H),6.97(d,J＝8.1Hz,2H),6.57-6.54(m,2H),4.23(d,J＝1.2Hz,2H),2.22(s,3H)；¹³C NMR(100MHz,CDCl₃)δ176.8,154.9,153.3,145.0,133.9,131.1,129.8,127.5,125.0,124.7,121.6,119.9,113.6,40.7,20.4；HRMS(ESI)calcd for C₁₇H₁₅ClNO₂(M+H)⁺300.0786,found 300.0787.

experimental example 10

5-bromo-2-hydroxyphenyl-enaminone (0.2mmol) and N-4-methyl-arylglycine (0.6mmol) were added to a dry reaction tube with stirring magnetons. Tetrahydrofuran and water (2mL, volume ratio 20:1) were added as a reaction solvent to a test tube, and the reaction mixture was left to react for 12 hours at room temperature under an air atmosphere. After TLC detection reaction is finished, the reaction solvent is removed by reduced pressure distillation of a rotary evaporator, and the residue is separated and purified by column chromatography to obtain pure yellow solid 2j with the yield of 73%. The structural characterization data for the 2j compound is as follows:

Yellow solid；m.p.134.7-137.5℃；¹H NMR(400MHz,CDCl₃)δ8.34(d,J＝2.5Hz,1H),7.88(d,J＝1.2Hz,1H),7.71(dd,J＝8.9,2.5Hz,1H),7.31(d,J＝8.9Hz,1H),6.97(d,J＝8.1Hz,2H),6.57-6.53(m,2H),4.23(d,J＝1.2Hz,2H),2.22(s,3H)；¹³C NMR(100MHz,CDCl₃)δ176.6,155.3,153.3,145.0,136.6,129.8,128.3,127.5,125.1,121.7,120.1,118.5,113.6,40.7,20.4；HRMS(ESI)calcd for C₁₇H₁₅BrNO₂(M+H)⁺344.0281,found 344.0283.

experimental example 11

2-Hydroxyphenylenaminone (0.2mmol) and N-4-methylarylglycine (0.6mmol) were added to a dry reaction tube with stirring magnetons. Tetrahydrofuran and water (2mL, volume ratio 20:1) were added as a reaction solvent to a test tube, and the reaction mixture was left to react for 12 hours at room temperature under an air atmosphere. After TLC detection reaction is finished, the reaction solvent is removed by reduced pressure distillation of a rotary evaporator, and the residue is separated and purified by column chromatography to obtain pure yellow solid 2k with the yield of 70%. The structural characterization data for the 2k compound is as follows:

Yellow solid；mp 145.0-149.0℃；¹H NMR(400MHz,CDCl₃)δ8.23(dd,J＝7.9,1.9Hz,1H),7.90(s,1H),7.68-7.63(m,1H),7.44-7.38(m,2H),6.98(d,J＝7.9Hz,2H),6.60-6.55(m,2H),4.25(s,2H),2.22(s,3H)；¹³C NMR(100MHz,CDCl₃)δ178.0,156.5,153.1,145.1,133.6,129.8,127.4,125.7,125.1,123.9,121.4,118.2,113.6,40.8,20.4；HRMS(ESI)calcd for C₁₇H₁₆NO₂(M+H)⁺266.1175,found 266.1178.

experimental example 12

2-Hydroxyphenylenaminone (0.2mmol) and N-3-methylarylglycine (0.6mmol) were added to a dry reaction tube with stirring magnetons. Tetrahydrofuran and water (2mL, volume ratio 20:1) were added as a reaction solvent to a test tube, and the reaction mixture was left to react for 12 hours at room temperature under an air atmosphere. After TLC detection reaction is finished, the reaction solvent is removed by reduced pressure distillation through a rotary evaporator, and the residue is separated and purified by column chromatography to obtain pure yellow solid 2l with the yield of 53%. The structural characterization data for the 2l compound are as follows:

Yellow solid；m.p.109.6-113.3℃；¹H NMR(400MHz,CDCl₃)δ8.23(dd,J＝8.0,1.7Hz,1H),7.91(d,J＝1.2Hz,1H),7.67-7.62(m,1H),7.44-7.37(m,2H),7.08-7.03(m,1H),6.55(d,J＝7.5Hz,1H),6.47(d,J＝6.5Hz,2H),4.26(d,J＝1.2Hz,2H),2.25(s,3H)；¹³C NMR(100MHz,CDCl₃)δ178.0,156.6,153.1,147.5,139.1,133.6,129.2,125.7,125.1,123.9,121.4,119.1,118.2,114.3,110.5,40.5,21.6；HRMS(ESI)calcd for C₁₇H₁₆NO₂(M+H)⁺266.1176,found 266.1173.

experimental example 13

2-Hydroxyphenylenaminone (0.2mmol) and N-3, 4-dimethylarylglycine (0.6mmol) were added to a dry reaction tube with stirring magnetons. Tetrahydrofuran and water (2mL, volume ratio 20:1) were added as a reaction solvent to a test tube, and the reaction mixture was left to react for 12 hours at room temperature under an air atmosphere. After TLC detection reaction is finished, the reaction solvent is removed by reduced pressure distillation of a rotary evaporator, and the residue is separated and purified by column chromatography to obtain pure yellow solid 2m with the yield of 67%. The structural characterization data for the 2m compound is as follows:

Yellow solid；mp 125.7-129.3℃；¹H NMR(400MHz,CDCl₃)δ8.22(dd,J＝8.0,1.7Hz,1H),7.89(d,J＝1.2Hz,1H),7.66-7.61(m,1H),7.44-7.36(m,2H),6.92(d,J＝8.1Hz,1H),6.48-6.40(m,2H),4.24(d,J＝1.1Hz,2H),2.15(d,J＝13.8Hz,6H)；¹³C NMR(100MHz,CDCl₃)δ178.0,156.6,153.1,145.6,137.4,133.6,130.3,126.1,125.7,125.1,123.9,121.5,118.2,115.4,110.8,40.8,20.0,18.7；HRMS(ESI)calcd for C₁₈H₁₈NO₂(M+H)⁺280.1332,found 280.1330.

experimental example 14

2-Hydroxyphenylenaminone (0.2mmol) and N-4-tert-butylarylglycine (0.6mmol) were added to a dry reaction tube with stirring magnetons. Tetrahydrofuran and water (2mL, volume ratio 20:1) were added as a reaction solvent to a test tube, and the reaction mixture was left to react for 12 hours at room temperature under an air atmosphere. After TLC detection reaction is finished, the reaction solvent is removed by reduced pressure distillation of a rotary evaporator, and the residue is separated and purified by column chromatography to obtain pure yellow solid 2n with the yield of 67%. The structural characterization data for the 2n compounds are as follows:

Yellow solid；mp 133.6-137.3℃；¹H NMR(400MHz,CDCl₃)δ8.23(dd,J＝8.0,1.7Hz,1H),7.91(d,J＝1.2Hz,1H),7.66-7.61(m,1H),7.43-7.37(m,2H),7.21-7.17(m,2H),6.62-6.58(m,2H),4.25(d,J＝1.1Hz,2H),1.26(s,9H)；¹³C NMR(100MHz,CDCl₃)δ178.0,156.6,153.2,145.1,140.9,133.6,126.1,125.7,125.1,123.9,121.5,118.1,113.1,40.7,33.9,31.5；HRMS(ESI)calcd for C₂₀H₂₂NO₂(M+H)⁺308.1645,found 308.1644.

the above description is only a preferred embodiment of the present invention, and should not be taken as limiting the invention, and any modifications, equivalents, improvements, etc. made within the spirit and principle of the present invention should be included in the scope of the present invention.