阅读说明：本技术 一种在含水介质中制备多取代喹喔啉的光催化方法 (Photocatalytic method for preparing polysubstituted quinoxaline in aqueous medium ) 是由 王翠苹 齐林 侯娜 张志强 李晓 孟庆涛 卢公昊 迟海军 董岩 代爽 张智 张 于 2020-11-13 设计创作，主要内容包括：本发明提供了一种在含水介质中制备多取代喹喔啉的光催化方法,属于有机合成技术领域。本方法以R～1-取代喹喔啉和R～2-取代苯甲酰甲酸为原料,将光催化剂、氧化剂、添加剂和含水溶剂置于反应管中,于蓝光光照条件下室温照射12h,得到产物多取代喹喔啉衍生物。本发明采用了铱配合物作为光敏催化剂,在含水介质中直接进行脱羧酰基化反应,具有反应条件温和,收率高等优点,为该类化合物的制备提供了新的方法指导。(The invention provides a photocatalysis method for preparing polysubstituted quinoxaline in an aqueous medium, belonging to the technical field of organic synthesis. The process uses R 1 -substituted quinoxalines and R 2 And (3) taking substituted benzoic acid as a raw material, placing a photocatalyst, an oxidant, an additive and a water-containing solvent into a reaction tube, and irradiating for 12 hours at room temperature under the condition of blue light illumination to obtain the product, namely the polysubstituted quinoxaline derivative. The invention adopts the iridium complex as the photosensitive catalyst, directly carries out decarboxylation acylation reaction in an aqueous medium, has the advantages of mild reaction conditions, high yield and the like, and provides a new method guide for the preparation of the compounds.)

1. A method for preparing polysubstituted quinoxaline derivatives, which is characterized in that: the reaction formula is as follows:

wherein R is¹、R²Is a substituted or unsubstituted aryl group.

2. The method of claim 1, wherein: r is to be¹-substituted quinoxalines, R²Placing substituted benzoic acid, photocatalyst, oxidant, additive and aqueous solvent in a reaction tube, irradiating at room temperature under blue light irradiation condition, extracting to obtainOrganic phase, solvent is removed by evaporation, and column chromatography is carried out to obtain the polysubstituted quinoxaline derivative, wherein R¹-substituted quinoxalines, R²The molar ratio of the substituted benzoic acid to the photocatalyst to the oxidant to the additive is 1 (2-3): 0.01-0.02): 0.1/3-0.2/3): 2.

3. The method of claim 2, wherein: the room temperature irradiation time under the blue light irradiation condition is 12h, and R is¹-substituted quinoxalines, R²-the molar ratio of substituted benzoic acid, photocatalyst, oxidant and additive is 1:2:0.02:0.2/3: 2.

4. The production method according to any one of claims 1 to 3, characterized in that: the photocatalyst is dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer, dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, bis (2-phenylpyridine) iridium acetylacetonate, (4,4 '-di-tert-butyl-2, 2' -bipyridine) bis [ (2-pyridyl) phenyl ] iridium (III) hexafluorophosphate, acid red, eosin B, eosin Y and rose bengal.

5. The production method according to any one of claims 1 to 3, characterized in that: the oxidant is a mixed oxidant of silver hexafluoroantimonate/potassium persulfate, silver nitrate/potassium persulfate, silver acetate/potassium persulfate, silver oxide/potassium persulfate and silver carbonate/potassium persulfate.

6. The production method according to any one of claims 1 to 3, characterized in that: the additive is glacial acetic acid and trifluoroacetic acid.

7. The production method according to any one of claims 1 to 3, characterized in that: the aqueous solvent is one or more of acetonitrile/water, N-dimethylacetamide/water, dimethyl sulfoxide/water, N-dimethylformamide/water, 1, 4-dioxane/water, tetrahydrofuran/water mixed solvent and single solvent water.

8. The production method according to any one of claims 1 to 3, characterized in that: the blue light is a 24W blue LED lamp.

Technical Field

The invention belongs to the technical field of organic synthesis, and particularly relates to a photocatalytic method for preparing polysubstituted quinoxaline in an aqueous medium.

Background

The polysubstituted quinoxaline is an important organic chemical raw material and intermediate in the fields of natural products, medicines and pesticides, and is widely used as an antibacterial agent, an antitumor agent, an anticoagulant, a hypoglycemic agent, an antidepressant and the like. Research on novel methods for preparing polysubstituted quinoxaline derivatives is of great value and has been receiving attention from researchers in this field.

The traditional preparation method of the polysubstituted quinoxaline mostly adopts the reaction of o-phenylenediamine compounds, 1, 2-dicarbonyl compounds, alpha-hydroxy ketones, alpha, beta-dihydroxy compounds, alpha-bromoketone, epoxy compounds and the like. The method has the problems of more reaction steps, difficult raw material obtaining, harsh reaction conditions and the like. In recent years, photocatalytic methods have been developed and used in various fields of organic synthesis due to their advantages of room temperature, high efficiency and high selectivity. At present, although the examples of the application of the photocatalytic method to the synthesis of the polysubstituted quinoxaline have been reported, most of the examples of the preparation of the polysubstituted quinoxaline by the photocatalytic method in an aqueous medium using an organic solvent as a medium have been reported. As a green solvent, water has the characteristics of no toxicity, no harm, low price and the like, and the water serving as an organic reaction medium meets the requirement of green chemistry. Therefore, there is an important value and significance in developing a method for preparing a polysubstituted quinoxaline derivative in an aqueous medium.

Disclosure of Invention

The invention aims to solve the technical problem of developing a photocatalytic method for preparing polysubstituted quinoxaline derivatives in an aqueous medium.

In order to solve the above problems, the present invention provides a method for preparing polysubstituted quinoxaline derivatives, which has the following reaction formula:

wherein R is¹、R²Is a substituted or unsubstituted aryl group.

The preparation method is to mix R¹-substituted quinoxalines, R²Placing substituted benzoic acid, photocatalyst, oxidant, additive and solvent in a reaction tube, irradiating at room temperature under blue light illumination condition, extracting organic phase after reaction, evaporating to remove solvent, and performing column chromatography to obtain polysubstituted quinoxaline derivative, wherein R is¹-substituted quinoxalines, R²The molar ratio of the substituted benzoic acid to the photocatalyst to the oxidant to the additive is 1 (2-3): 0.01-0.02): 0.1/3-0.2/3): 2.

In the preferable preparation method, the irradiation time at room temperature under the blue light illumination condition is 12h, and R is¹-substituted quinoxalines, R²-the molar ratio of substituted benzoic acid, photocatalyst, oxidant and additive is 1:2:0.02:0.2/3: 2.

The photocatalyst in the preferred preparation method is dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer, dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, bis (2-phenylpyridine) iridium acetylacetonate, (4,4 '-di-tert-butyl-2, 2' -bipyridine) bis [ (2-pyridyl) phenyl ] iridium (III) hexafluorophosphate, acid red, eosin B, eosin Y, rose bengal.

The preferred preparation method is that the oxidant is a mixed oxidant of silver hexafluoroantimonate/potassium persulfate, silver nitrate/potassium persulfate, silver acetate/potassium persulfate, silver oxide/potassium persulfate and silver carbonate/potassium persulfate.

The additives mentioned in the preferred preparation method are glacial acetic acid and trifluoroacetic acid.

The aqueous solvent in the preferred preparation method is one or more of acetonitrile/water, N-dimethylacetamide/water, dimethyl sulfoxide/water, N-dimethylformamide/water, 1, 4-dioxane/water, tetrahydrofuran/water mixed solvent and single solvent water.

The blue light in the preferred preparation method is a 24W blue LED lamp.

Compared with the prior art of the same type, the invention has the following remarkable beneficial effects:

the invention provides a method for preparing polysubstituted quinoxaline in an aqueous medium, which adopts a photocatalytic preparation method, adopts the substituted quinoxaline and the substituted benzoylformic acid as raw materials, is simple and easy to obtain, can carry out the reaction at room temperature, has milder reaction conditions and higher reaction yield in the aqueous medium, and provides new method guidance for the preparation of the compounds.

Detailed Description

Reference will now be made in detail to the various embodiments of the present invention, and while the invention will be described in conjunction with the exemplary embodiments, it will be understood that the description is not intended to limit the invention to these exemplary embodiments. On the contrary, the invention is intended to cover not only these exemplary embodiments, but also various alternatives, modifications, equivalents and other embodiments, which may be included within the spirit and scope of the invention as defined by the appended claims.

Examples 1 to 9: preparation of product 1

The structural formula of the product 1 is:

0.1mmol of 2-phenylquinoxaline, 0.3mmol of benzoylformic acid, different photocatalysts, silver carbonate/potassium persulfate (0.2/3, equiv), and an aqueous solvent CH₃CN/H₂O (2mL,0.5/1.5, v/v) was added to the reaction tube and sealed. The reaction tube was placed in a light reaction tube and irradiated with 24W blue LED lamp at room temperature for 12 h. After the reaction, the solution is extracted by dichloromethane (3X 10mL) and water, an organic phase is dried by anhydrous magnesium sulfate, a drying agent is removed by suction filtration, reduced pressure concentration and column chromatography purification are carried out to obtain a target product 1, and the specific contents are shown in Table 1:

TABLE 1 yield results of polysubstituted quinoxalines under different photocatalysts

Examples 10 to 14:

0.1mmol of 2-phenylquinoxaline, 0.3mmol of benzoylcarboxylic acid and Ir (ppy)₂(dtbbpy)PF₆(2 mol%), different oxidants, aqueous solvent CH₃CN/H₂O (2mL,0.5/1.5, v/v) was added to the reaction tube and sealed. The reaction tube was placed in a light reaction tube and irradiated with 24W blue LED lamp at room temperature for 12 h. After the reaction, the solution is extracted by dichloromethane (3X 10mL) and water, an organic phase is dried by anhydrous magnesium sulfate, a drying agent is removed by suction filtration, reduced pressure concentration and column chromatography purification are carried out to obtain a target product 1, and the specific contents are shown in Table 2:

TABLE 2 results of yields of polysubstituted quinoxalines with different oxidizing agents

Examples	Oxidant (equiv)	Yield (%)
			10	AgSbF6/K2S2O8(0.2/3)	77
11	AgNO3/K2S2O8(0.2/3)	79
			12	AgOAc/K2S2O8(0.2/3)	89
13	Ag2O/K2S2O8(0.2/3)	59
			14	Ag2CO3/K2S2O8(0.1/3)	66

Examples 15 to 26:

0.1mmol of 2-phenylquinoxaline, 0.3mmol of benzoylcarboxylic acid and Ir (ppy)₂(dtbbpy)PF₆(2mol％)、Ag₂CO₃/K₂S₂O₈(0.2/3equiv), various organic solvents and aqueous solvents were put into the reaction tube and sealed. The reaction tube was placed in a light reaction tube and irradiated with 24W blue LED lamp at room temperature for 12 h. After the reaction, the solution is extracted by dichloromethane (3X 10mL) and water, an organic phase is dried by anhydrous magnesium sulfate, a drying agent is removed by suction filtration, reduced pressure concentration and column chromatography purification are carried out to obtain a target product 1, and the specific contents are shown in Table 3:

TABLE 3 yield results of polysubstituted quinoxalines in different solvents

Example 27:

reducing the dosage of 2-phenylquinoxaline to 0.1mmol, the dosage of benzoylformic acid to 0.2mmol, Ir (ppy)₂(dtbbpy)PF₆(2mol％)、Ag₂CO₃/K₂S₂O₈(0.2/3equiv), aqueous solvent CH₃CN/H₂O (2mL,0.5/1.5, v/v) was added to the reaction tube and sealed. The reaction tube was placed in a photoreactor and irradiated with 24W blue LED lamp at room temperature for 12 h. After the reaction, the solution was extracted with dichloromethane (3 × 10mL) and water, the organic phase was dried over anhydrous magnesium sulfate, the drying agent was removed by suction filtration, concentrated under reduced pressure, and purified by column chromatography to obtain the target product 1 with a yield of 71%.

Examples 28 to 29:

0.1mmol of 2-phenylquinoxaline, 0.2mmol of benzoylcarboxylic acid and Ir (ppy)₂(dtbbpy)PF₆(2mol％)、Ag₂CO₃/K₂S₂O₈(0.2/3equiv), an additive, and an aqueous solvent CH₃CN/H₂O (2mL,0.5/1.5, v/v) was added to the reaction tube and sealed. The reaction tube was placed in a light reaction tube and irradiated with 24W blue LED lamp at room temperature for 12 h. After the reaction, the solution is extracted by dichloromethane (3X 10mL) and water, an organic phase is dried by anhydrous magnesium sulfate, a drying agent is removed by suction filtration, reduced pressure concentration and column chromatography purification are carried out to obtain a target product 1, and the specific contents are shown in Table 4:

TABLE 4 yield results of polysubstituted quinoxalines with different additives

Examples	Additive (equiv)	Yield (%)
			28	HOAc(2)	92
29	TFA(2)	87

Note: in the table [ Cp RuCl₂]₂、[Cp*IrCl₂]₂、Ir(ppy)₂acac、Ir(ppy)₂(dtbbpy)PF₆The Chinese names of Acid Red, Eosin B, Eosin Y and rose bengal are dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer, dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, bis (2-phenylpyridine) iridium acetylacetonate, (4,4 '-di-tert-butyl-2, 2' -bipyridyl) bis [ (2-pyridyl) phenyl ] iridium]Iridium (III) hexafluorophosphate, acid red, eosin B, eosin Y, rose bengal; AgSbF₆、AgNO₃、AgOAc、Ag₂O、Ag₂CO₃And K₂S₂O₈The Chinese names of the compounds are respectively silver hexafluoroantimonate, silver nitrate, silver acetate, silver oxide, silver carbonate and potassium persulfate; CH (CH)₃CN, DMAc, DMSO, DMF, Dioxane, THF, HOAc, TFA and H₂The Chinese names of O are acetonitrile, N-dimethylacetamide, dimethyl sulfoxide, N-dimethylformamide, dioxane, tetrahydrofuran, glacial acetic acid, trifluoroacetic acid and water respectively.

Examples 30 to 49:

R¹0.1mmol of-substituted quinoxaline, R²0.2mmol of substituted benzoic acid, Ir (ppy)₂(dtbbpy)PF₆(2mol％)、Ag₂CO₃/K₂S₂O₈(0.2/3equiv), HOAc (2equiv), aqueous solvent CH₃CN/H₂O (2mL,0.5/1.5, v/v) was placed in the reaction tube and irradiated with 24W blue LED lamp at room temperature for 12 h. Extracting the reacted solution with dichloromethane (3X 10mL) and water, drying the organic phase with anhydrous magnesium sulfate, filtering to remove the drying agent, concentrating under reduced pressure, and purifying by column chromatography to obtain the final productThe specific contents of the series of polysubstituted quinoxaline derivatives are shown in the table 5:

TABLE 5 Structure and yield of different products

The structural characterization data for the product obtained in example 1 are:

White solid,m.p.:136.6-138.3℃.¹H NMR(500MHz,CDCl₃):δ8.25(d,J＝8.5Hz,1H),8.17(d,J＝8.5Hz,1H),7.95(d,J＝7.5Hz,2H),7.88(dd,J＝7.5,8.0Hz,1H),7.82(dd,J＝7.5,7.5Hz,1H),7.71-7.69(m,2H),7.61(dd,J＝7.5,7.5Hz,1H),7.47(dd,J＝7.5,8.0Hz,2H),7.39-7.38(m,3H)；¹³C NMR(125MHz,CDCl₃)δ193.30,152.15,150.71,141.48,139.05,136.62,135.03,133.39,130.77,129.88,129.80,128.97,128.84,128.50,128.06.HRMS(APCI)calcd for C₂₁H₁₅N₂O[M+H]⁺311.1184,found m/z 311.1182.

the structural characterization data for the product obtained in example 30 are:

Light yellow solid,m.p.:145.7-146.9℃.¹H NMR(500MHz,CDCl₃):δ8.25(d,J＝8.0Hz,1H),8.16(d,J＝8.5Hz,1H),7.99(dd,J＝7.0,6.5Hz,2H),7.89(dd,J＝7.5,7.5Hz,1H),7.83(dd,J＝7.5,8.0Hz,1H),7.69-7.68(m,2H),7.40-7.39(m,3H),7.14(dd,J＝8.0,8.5Hz,2H)；¹³C NMR(125MHz,CDCl₃)δ191.71,165.67(d,J＝255.00Hz),152.15,150.29,141.51,138.98,136.54,132.62(d,J＝8.75Hz),131.47,130.93,129.92,129.05,128.83(d,J＝6.25Hz),128.45,128.11,115.37(d,J＝22.5Hz).HRMS(APCI)calcd for C₂₁H₁₄NO₂F[M+H]⁺329.1090,found m/z 329.1086.

the structural characterization data for the product obtained in example 31 are:

Light yellow solid,m.p.:146.0-147.6℃.¹H NMR(500MHz,CDCl₃):δ8.27(d,J＝7.5Hz,1H),8.18(d,J＝7.0Hz,1H),7.93-7.92(m,3H),7.86(dd,J＝8.0,7.5Hz,1H),7.70-7.69(m,2H),7.47(d,J＝7.0Hz,2H),7.43-7.20(m,3H)；¹³C NMR(125MHz,CDCl₃)δ192.05,152.17,150.09,141.55,140.07,138.97,136.52,133.37,131.20,130.97,129.94,129.07,128.88,128.82,128.47,128.45,128.14.HRMS(APCI)calcd for C₂₁H₁₄N₂OCl[M+H]⁺345.0795,347.0765,found m/z 345.0791,347.0771.

the structural characterization data for the product obtained in example 32 are:

Light yellow solid,m.p.:155.3-157.1℃.¹H NMR(500MHz,CDCl₃):δ8.27(d,J＝8.0Hz,1H),8.18(d,J＝8.5Hz,1H),7.92(dd,J＝7.0,8.0Hz,1H),7.87-7.84(m,3H),7.00-7.69(d,J＝5.0Hz,2H),7.64(d,J＝8.0Hz,2H),7.43-7.42(m,3H)；¹³C NMR(125MHz,CDCl₃)δ192.23,152.17,150.06,141.56,138.98,136.52,133.79,131.46,131.27,130.97,129.93,129.07,128.92,128.89,128.82,128.47,128.13.HRMS(APCI)calcd for C₂₁H₁₄N₂OBr[M+H]⁺389.0290,391.0269,found m/z 389.0285,391.0262.

the structural characterization data for the product obtained in example 33 are:

White solid,m.p.:163.3-165.2℃.¹H NMR(500MHz,CDCl₃):δ8.26(d,J＝8.5Hz,1H),8.17(d,J＝8.5Hz,1H),7.91(dd,J＝7.5,7.0Hz,1H),7.88-7.84(m,3H),7.70-7.68(d,J＝6.5Hz,4H),7.44-7.42(m,3H)；¹³C NMR(125MHz,CDCl₃)δ192.57,152.20,150.01,141.58,138.95,137.46,136.53,134.30,131.08,130.97,129.92,129.07,128.89,128.82,128.45,128.14,102.02.HRMS(APCI)calcd for C₂₁H₁₄N₂OI[M+H]⁺437.0151,found m/z 437.0150.

the structural characterization data for the product obtained in example 34 are:

White solid,m.p.:134.7-136.2℃.¹H NMR(500MHz,CDCl₃):δ8.29(d,J＝8.0Hz,1H),8.19(d,J＝8.0Hz,1H),8.13(d,J＝8.0Hz,2H),7.95(dd,J＝7.0,8.0Hz,1H),7.88(dd,J＝7.5,7.5Hz,1H),7.79(d,J＝8.0Hz,2H),7.71-7.69(m,2H),7.46-7.44(m,3H)；¹³C NMR(125MHz,CDCl₃)δ192.10,152.32,149.64,141.63,138.91,137.68,136.45,134.45(q,J＝31.25Hz),131.20,130.17,130.05,129.70,129.13,128.92,128.85,128.33(d,J＝33.75Hz),125.10(q,J＝3.75Hz),122.86(q,J＝271.25Hz).HRMS(APCI)calcd for C₂₁H₁₄N₂OF₃[M+H]⁺379.1058,found m/z 379.1055.

the structural characterization data for the product obtained in example 35 are:

Yellow solid,m.p.:97.9-98.4℃.¹H NMR(500MHz,CDCl₃):δ8.24(d,J＝8.5Hz,1H),8.13(d,J＝8.5Hz,1H),7.89(dd,J＝7.5,7.5Hz,1H),7.83-7.79(m,4H),7.49(dd,J＝7.0,7.0Hz,1H),7.46-7.44(m,3H),7.41-7.38(m,2H)；¹³C NMR(125MHz,CDCl₃)δ193.10,152.22,150.20,142.57,139.24,136.83,135.57,132.98,132.86,131.81,131.05,130.08,129.70,129.07,128.80,128.71,127.93,126.35.HRMS(APCI)calcd for C₂₁H₁₄N₂OCl[M+H]⁺345.0795,347.0765,found m/z 345.0796,347.0773.

the structural characterization data for the product obtained in example 36 are:

White solid,m.p.:105.9-107.0℃.¹H NMR(500MHz,CDCl₃):δ8.24(d,J＝8.0Hz,1H),8.18(d,J＝8.5Hz,1H),7.96(d,J＝8.0Hz,2H),7.91(dd,J＝7.0,8.0Hz,1H),7.85(dd,J＝7.5,7.5Hz,1H),7.73-7.70(m,2H),7.65(dd,J＝7.5,7.5Hz,1H),7.50(dd,J＝7.0,6.5Hz,2H),7.10(dd,J＝8.5,8.5Hz,2H)；¹³C NMR(125MHz,CDCl₃)δ193.31,163.06(d,J＝248.75Hz),151.02,150.41,141.44,139.01,134.87,133.59,130.93,130.50(d,J＝8.75Hz),129.94,129.89,128.81(d,J＝7.5Hz),128.16,115.24(d,J＝22.5Hz).HRMS(APCI)calcd for C₂₁H₁₄NOF[M+H]⁺329.1090,found m/z 329.1086.

the structural characterization data for the product obtained in example 37 are:

White solid,m.p.:139.2-142.1℃.¹H NMR(500MHz,CDCl₃):δ8.24(d,J＝8.0Hz,1H),8.16(d,J＝8.0Hz,1H),7.92-7.89(m,3H),7.85(dd,J＝8.0,7.5Hz,1H),7.69-7.67(m,2H),7.47(d,J＝8.5Hz,2H),7.10(dd,J＝8.5,8.5Hz,2H)；¹³C NMR(125MHz,CDCl₃)δ187.24,158.35(d,J＝250.0Hz),146.28,145.05,136.72,135.54,134.18,128.47,127.90(d,J＝3.75Hz),126.48,126.38,125.72(d,J＝7.5Hz),125.31,124.08,124.05,123.82,110.56(d,J＝22.5Hz).HRMS(APCI)calcd for C₂₁H₁₃N₂OClF[M+H]⁺363.0700,365.0671,found m/z 363.0797,365.0675.

the structural characterization data for the product obtained in example 38 are:

White solid,m.p.:148.3-150.0℃.¹H NMR(500MHz,CDCl₃):δ8.25(d,J＝8.0Hz,1H),8.15(d,J＝8.5Hz,1H),8.10(d,J＝8.0Hz,2H),7.92(dd,J＝7.5,7.5Hz,1H),7.86(dd,J＝8.0,7.0Hz,1H),7.77(d,J＝8.0,2H),7.67(dd,J＝6.5,5.5Hz,2H),7.11(dd,J＝8.5,7.5Hz,2H)；¹³C NMR(125MHz,CDCl₃)δ192.03,163.13(d,J＝248.75Hz),151.19,149.34,141.56,138.87,137.55,134.61(q,J＝32.5Hz),132.57,131.36,130.49(d,J＝8.75Hz),130.21,130.17,128.86,125.20,125.17,122.83(d,J＝271.25Hz),115.38(d,J＝22.5Hz).HRMS(APCI)calcd for C₂₂H₁₃N₂OF₄[M+H]⁺397.0964,found m/z 397.0962.

the structural characterization data for the product obtained in example 39 are:

Light yellow solid,m.p.:147.4-149.1℃.¹H NMR(500MHz,CDCl₃):δ8.20(d,J＝8.5Hz,1H),8.09(d,J＝8.0Hz,1H),7.87(dd,J＝7.0,8.0Hz,1H),7.81-7.77(m,4H),7.50(dd,J＝7.5,8.0Hz,1H),7.40(d,J＝7.0Hz,2H),7.13(dd,J＝8.0,8.5Hz,2H)；¹³C NMR(125MHz,CDCl₃)δ193.10,163.00(d,J＝248.75Hz),151.07,149.95,141.44,139.21,135.58,132.97,132.90,131.76,131.19,130.76(d,J＝6.25Hz),130.08,129.81,129.07,128.69,126.44,115.05(d,J＝22.5Hz).HRMS(APCI)calcd for C₂₁H₁₃N₂OClF[M+H]⁺363.0700,365.0671,found m/z 363.0707,365.0678.

the structural characterization data for the product obtained in example 40 are:

Yellow solid,m.p.:140.8-142.0℃.¹H NMR(500MHz,CDCl₃):δ8.22(d,J＝8.5Hz,1H),8.16(d,J＝8.5Hz,1H),7.92(d,J＝8.5Hz,2H),7.88(dd,J＝7.5,7.5Hz,1H),7.82(dd,J＝7.5,7.5Hz,1H),7.72(dd,J＝6.0,6.5Hz,2H),7.08(dd,J＝8.5,8.5Hz,2H),6.95(d,J＝8.5Hz,2H),3.88(s,3H)；¹³C NMR(125MHz,CDCl₃)δ187.11,159.12,158.30(d,J＝247.5Hz),146.12(d,J＝18.75Hz),136.58,134.30,128.09,128.07,127.58,125.98,125.73(d,J＝8.75Hz),125.09,124.04,123.98,123.21,110.44(d,J＝21.25Hz),108.77,50.21.HRMS(APCI)calcd for C₂₂H₁₆N₂O₂F[M+H]⁺359.1196,found m/z 359.1192.

the structural characterization data for the product obtained in example 41 are:

Light yellow solid,m.p.:168.1-170.0℃.¹H NMR(500MHz,CDCl₃):δ8.22(d,J＝8.5Hz,1H),8.16(d,J＝8.0Hz,1H),7.96(d,J＝7.5Hz,2H),7.89(dd,J＝7.0,8.0Hz,1H),7.84(dd,J＝7.5,8.0Hz,1H),7.64(dd,J＝7.5,7.0Hz,2H),7.58(d,J＝8.5Hz,2H),7.53-7.48(m,4H)；¹³C NMR(125MHz,CDCl₃)δ193.13,151.05,150.30,141.44,139.04,135.57,134.83,133.64,131.77,131.31,130.98,130.04,129.95,128.86,128.83,128.19,123.77.HRMS(APCI)calcd for C₂₁H₁₄N₂OBr[M+H]⁺389.0290,391.0269,found m/z 389.0285,391.0262.

the structural characterization data for the product obtained in example 42 are:

White solid,m.p.:245.3-248.6℃.¹H NMR(500MHz,CDCl₃):δ8.23(d,J＝8.0Hz,1H),8.15(d,J＝8.5Hz,1H),7.93-7.89(m,3H),7.85(dd,J＝7.5,7.5Hz,1H),7.57-7.53(m,4H),7.48(d,J＝8.0Hz,2H)；¹³C NMR(125MHz,CDCl₃)δ191.84,151.08,149.68,141.48,140.36,138.95,135.43,133.17,131.38,131.29,131.20,130.21,130.00,128.85,128.60,123.89.HRMS(APCI)calcd for C₂₁H₁₃N₂OBrCl[M+H]⁺422.9900,424.9879,found m/z 422.9984,424.9865.

the structural characterization data for the product obtained in example 43 are:

White solid,m.p.:209.3-212.0℃.¹H NMR(500MHz,CDCl₃):δ8.23(d,J＝8.0Hz,1H),8.15(d,J＝8.0Hz,1H),7.91(dd,J＝6.5,8.5Hz,1H),7.87-7.84(m,3H),7.65(d,J＝7.0Hz,2H),7.57-7.53(m,4H)；¹³C NMR(125MHz,CDCl₃)δ192.04,151.09,149.63,141.50,138.95,135.44,133.58,131.59,131.38,131.34,131.21,130.21,129.99,129.25,128.85,123.89.HRMS(APCI)calcd for C₂₁H₁₃N₂OBr₂[M+H]⁺466.9395,468.9374,470.9354,found m/z 466.9391,468.9365,470.9347.

the structural characterization data for the product obtained in example 44 are:

White solid,m.p.:233.4-235.5℃.¹H NMR(500MHz,CDCl₃):δ8.23(d,J＝8.0Hz,1H),8.15(d,J＝8.0Hz,1H),7.92-7.83(m,4H),7.68(d,J＝8.0Hz,2H),7.55(m,4H),1.26(s,3H)；¹³C NMR(125MHz,CDCl₃)δ192.36,151.09,149.64,141.48,138.97,137.60,135.42,134.13,131.39,131.22,131.16,130.22,130.02,128.86,123.91,102.35,29.07.HRMS(APCI)calcd for C₂₁H₁₃N₂OBrI[M+H]⁺514.9256,516.9235,found m/z 514.9252,516.9235.

the structural characterization data for the product obtained in example 45 are:

Light yellow solid,m.p.:149.1-150.9℃.¹H NMR(500MHz,CDCl₃):δ8.25(d,J＝8.0Hz,1H),8.18(d,J＝8.0Hz,1H),7.98(d,J＝7.0Hz,2H),7.91(dd,J＝6.5,7.5Hz,1H),7.86(dd,J＝7.5,7.0Hz,1H),7.68-7.65(m,3H),7.51(dd,J＝7.0,6.5Hz,2H),7.39(d,J＝7.0Hz,2H)；¹³C NMR(125MHz,CDCl₃)δ193.17,150.97,150.35,141.43,139.05,135.39,135.10,134.83,133.64,130.97,130.06,129.94,129.81,128.86,128.82,128.36,128.18.HRMS(APCI)calcd for C₂₁H₁₄N₂OCl[M+H]⁺345.0795,347.0765,found m/z 345.0791,347.0763.

the structural characterization data for the product obtained in example 46 are:

White solid,m.p.:163.6-165.4℃.¹H NMR(500MHz,CDCl₃):δ8.23(d,J＝8.5Hz,1H),8.15(d,J＝8.5Hz,1H),7.93-7.89(m,3H),7.85(dd,J＝7.5,7.0Hz,1H),7.63(d,J＝8.0Hz,2H),7.48(d,J＝8.0Hz,2H),7.39(d,J＝8.0Hz,2H)；¹³C NMR(125MHz,CDCl₃)δ191.88,151.02,149.74,141.50,140.35,138.97,135.52,135.00,133.21,131.59,131.28,131.18,130.19,129.78,128.85,128.60,128.44.HRMS(APCI)calcd for C₂₁H₁₃N₂Ocl₂[M+H]⁺379.0405,381.0375,found m/z 379.0403,381.0371.

the structural characterization data for the product obtained in example 47 are:

Light yellow solid,m.p.:158.3-159.1℃.¹H NMR(500MHz,CDCl₃):δ8.25(d,J＝8.0Hz,1H),8.19(d,J＝8.0Hz,1H),7.96(d,J＝7.5Hz,2H),7.91(dd,J＝7.0,8.0Hz,1H),7.86(dd,J＝7.0,7.0Hz,1H),7.70(d,J＝8.0Hz,2H),7.40(d,J＝8.0Hz,2H),6.99(d,J＝8.5Hz,2H),3.92(s,3H)；¹³C NMR(125MHz,CDCl₃)δ191.17,163.91,150.89,150.72,141.33,139.07,135.35,135.17,132.39,130.80,129.99,129.79,128.80,128.78,128.33,127.91,113.56,54.98.HRMS(APCI)calcd for C₂₂H₁₆N₂O₂Cl[M+H]⁺375.0900,377.0871,found m/z 375.0888,377.0868.

the structural characterization data for the product obtained in example 48 are:

White solid,m.p.:179.1-183.5℃.¹H NMR(500MHz,CDCl₃):δ8.27(d,J＝8.0Hz,1H),8.19-8.15(m,3H),7.95(dd,J＝6.5,8.0Hz,1H),7.89(dd,J＝7.5,6.5Hz,1H),7.80(d,J＝7.5Hz,4H),7.69(d,J＝7.5Hz,2H)；¹³C NMR(125MHz,CDCl₃)δ191.64,151.16,149.16,141.53,140.02,139.02,137.51,134.73(q,J＝32.5Hz),131.59,130.95(q,J＝32.5Hz),130.63,130.66,128.97(d,J＝8.75Hz),125.22(q,J＝3.75Hz),125.10(q,J＝3.75Hz),124.09(q,J＝47.5Hz),121.92(q,J＝47.5Hz).HRMS(APCI)calcd for C₂₃H₁₃N₂OF₆[M+H]⁺447.0932,found m/z 447.0928.

the structural characterization data for the product obtained in example 49 are:

White solid,m.p.:174.5-176.1℃.¹H NMR(500MHz,CDCl₃):δ8.24(d,J＝8.5Hz,1H),8.18(d,J＝8.5Hz,1H),7.97(d,J＝8.5Hz,2H),7.86(dd,J＝8.0,7.0Hz,1H),7.86-7.83(m,3H),7.66(d,J＝7.5,2H),6.98(d,J＝8.5Hz,2H),3.89(s,3H)；¹³C NMR(125MHz,CDCl₃)δ191.49,164.00,150.84,150.65,141.31,140.25,139.18,132.46,131.72,130.97,130.72(q,J＝32.5Hz),130.33,128.89,128.84,127.89,124.98(d,J＝3.75Hz),123.29(q,J＝271.25Hz),113.60,55.00.HRMS(APCI)calcd for C₂₃H₁₆N₂O₂F₃[M+H]⁺409.1164,found m/z 409.1161.

the foregoing descriptions of specific exemplary embodiments of the present invention have been presented for purposes of illustration and description. The foregoing description is not intended to be exhaustive or to limit the invention to the precise form disclosed. Obviously, many modifications and variations are possible in light of the above teaching. The exemplary embodiments were chosen and described in order to explain certain principles of the invention and its practical application to enable one skilled in the art to make and use various exemplary embodiments of the invention, as well as various alternatives and modifications thereof. Indeed, the scope of the invention is defined by the appended claims and equivalents thereof.