CN112552242B - Method for synthesizing cinnoline salt compound - Google Patents
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- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
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Abstract
The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing a cinnoline salt compound, which is characterized in that a compound shown in a formula (I) and a compound shown in a formula (II) are subjected to catalytic cyclization reaction under the action of a composite catalytic system consisting of a metal catalyst and an auxiliary substance to obtain the cinnoline salt compound shown in the formula (III). The invention provides a synthetic method of a nitrogenous inner salt structure, which can obtain a target product with good yield through a unique composite catalytic system and the mutual synergy and promotion effect among all components and conditions, provides a brand new method for synthesizing nitrogenous inner salt compounds, and provides corresponding products with certain optical properties and good research value and application potential.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing cinnoline salt compounds.
Background
Quaternary ammonium salts are a class of compounds that are widely used and are gaining increasing attention due to their reactivity and biological activity. Among them, the silhouette of cinnoline salt structure is often found in some compounds, drug molecules, alkaloids, receptors and inhibitors having biological activity.
In the conventional studies on the synthesis of cinnoline salt compounds, the most common approach is to use S of cinnoline and an alkyl halideN2, but the method is not applicable to nitrogen-containing heterocyclic compounds with high application value.
Transition metal catalyzed C-H functionalization and cross-coupling reactions are of widespread interest due to their advantages in atom economy and steps. Azobenzene is a widely used compound which can be used as a food additive, a dye, an indicator, a light reaction conversion agent, a pharmaceutical product, etc. Among them, the transition metal has been widely studied for catalyzing the cyclization reaction of aromatic azobenzene C-H bond activation. For example: cheng et al (org. Lett.2019,21,2565-2568.) reported that azobenzene and nitrosobenzene synthesized various cinnolines in moderate reaction yields under the condition of [ Cp. RhCl2]2 as a catalyst; chuang topic group (Angew. chem. int. Ed.2020,59, 689-694) developed a palladium (II) -catalyzed reaction of copper chloride to oxidize 2-azoaryl compounds and olefins to synthesize cinnoline compounds with moderate reaction yield; the Li topic group (adv. synth. catal.2018,360, 2836-2842) catalyzed the reaction of the C-H bond of azobenzene with diazo compounds using rhodium (III) and zinc trifluoromethanesulfonate to synthesize cinnoline salts; wang research group (j.org.chem.2018,83,10845-10854) reported that rh (iii) catalyzes an oxidative coupling-cyclization reaction to produce a cinnoline salt from a t-butoxycarbonyl-protected arylhydrazine and an alkyne in a mixed solvent of chlorobenzene and dichloromethane.
However, in many cases, these methods require the use of large amounts of strong oxidizers, expensive additives, and noble metal catalysts, which greatly reduces the utility of these methods. Therefore, it is still of great importance to develop a convenient and practical method for obtaining a cinnoline salt skeleton from a stable and easily available substrate.
Disclosure of Invention
The invention aims to overcome the defects and shortcomings of the prior art and provides a method for synthesizing a cinnoline salt compound.
The technical scheme adopted by the invention is as follows: a process for synthesizing cinnoline salt compound with the reaction formula
Under the action of a composite catalytic system consisting of a metal catalyst and an auxiliary substance, carrying out catalytic cyclization reaction on a compound shown in a formula (I) and a compound shown in a formula (II) to obtain a cinnoline salt compound shown in a formula (III);
wherein R1 is selected from H, halogen, nitro, ester group, alkyl and cyano; r2 is selected from aryl, alkyl, cyano, ester, halogen, nitro, methoxy and heterocycle; r3 is selected from halogen, alkyl and methoxy.
Preferably, the metal catalyst is any one or more of cuprous chloride, cuprous bromide, cupric acetate and copper trifluoromethanesulfonate.
Preferably, the metal catalyst is cuprous chloride.
Preferably, the amount of cuprous chloride used is 0.05 to 0.5 equivalent based on the compound represented by the formula (I) as the raw material.
Preferably, the auxiliary substance is one or more of triethylamine, 4-dimethylaminopyridine, pyridine and tetramethylethylenediamine.
Preferably, the adjuvant is 4-dimethylaminopyridine; the amount of the compound represented by the formula (I) is 0.2 to 1.0 equivalent based on the amount of the compound represented by the formula (I).
Preferably, the reaction is a reaction under an air atmosphere or an oxygen atmosphere.
Preferably, any one or more of dimethyl sulfoxide, chlorobenzene, acetonitrile and toluene are used as reaction solvents. The amount of solvent is not particularly limited, and those skilled in the art can select an appropriate amount, which is within the ordinary skill of the art and will not be described in detail herein.
Preferably, the reaction temperature is 60-120 ℃, and the reaction time is 24-48 h.
Preferably, after the reaction is completed, transferring the reaction solution, adding a proper amount of ethyl acetate for washing, mixing the reaction stock solution with a washing solution, concentrating, and directly performing silica gel column chromatography separation, wherein the volume ratio of the ethyl acetate to the washing solution is 1: 0.2-1 of a mixture of dichloromethane and ethyl acetate as an eluent, collecting the eluent, and concentrating by distillation under reduced pressure again to obtain the compound shown in the formula (III). The amount of ethyl acetate added after the reaction is completed is not particularly limited, as long as it can completely transfer the reaction solution and facilitate subsequent treatment, and those skilled in the art can make verification selection and determination, and will not be described again.
The invention has the following beneficial effects: the cuprous chloride and 4-dimethylamino pyridine composite system provided by the invention can be used for synthesizing an inner salt structure, and can obtain good product yield, so that the cuprous chloride and 4-dimethylamino pyridine composite system has good application in the synthesis of the inner salt structure.
The invention provides a synthetic method of a nitrogenous inner salt structure, which can obtain a target product with good yield through a unique composite catalytic system and the mutual synergy and promotion effect among all components and conditions, provides a brand new method for synthesizing nitrogenous inner salt compounds, and provides corresponding products with certain optical properties and good research value and application potential.
Detailed Description
Implementation 1: 2, 3-diphenyl-4-oxocinnoline ylide
To a 100mL Schlenk reaction tube were added 2-phenylethynylaniline (96.6mg, 0.5mmol), nitrosobenzene in that order(80.3mg, 0.75mmol), CuCl (5.0mg, 0.05mmol), 4-dimethylaminopyridine (24.4mg, 0.2mmol), toluene (1.5mL), and then the tube was sealed. And (2) putting the reaction mixture into an oil bath kettle at the temperature of 100 ℃, stirring for 24 hours, taking out and cooling to room temperature, transferring the reaction stock solution, adding a proper amount of ethyl acetate for washing, mixing the stock solution with a washing solution, concentrating under reduced pressure, adsorbing on silica gel, and directly performing silica gel chromatographic separation, wherein the volume ratio of the mixture is 50: 1 as eluent, and by column chromatography, the yield was 74%.1H-NMR(500MHz,DMSO):δ8.25(d,J＝8.0Hz,1H),7.95(d,J＝8.5Hz,1H),7.88(t,J＝6.5Hz,1H),7.65(t,J＝7.0Hz,1H),7.58-7.57(m,2H),7.40(t,J＝3.5Hz,3H),7.35(d,J＝7.5Hz,2H),7.30-7.26(m,3H).13C-NMR(500MHz,DMSO):δ168.6,148.1,145.7,144.6,132.8,131.3,131.0,129.3,128.6,128.4,127.7,127.6,126.5,126.0,125.5,123.7.
Example 2: 2-phenyl-3- (4- (methoxycarbonyl) phenyl) -4-oxocinnoline ylide
To a 100mL Schlenk reaction tube were added methyl 4- ((2-aminophenyl) ethynyl) benzoate (125.6mg, 0.5mmol), nitrosobenzene (80.3mg, 0.75mmol), CuCl (5.0mg, 0.05mmol), 4-dimethylaminopyridine (24.4mg, 0.2mmol), toluene (1.5mL) in that order, and the tube was sealed. And (2) putting the reaction mixture into an oil bath kettle at the temperature of 100 ℃, stirring for 24 hours, taking out and cooling to room temperature, transferring the reaction stock solution, adding a proper amount of ethyl acetate for washing, mixing the stock solution with a washing solution, concentrating under reduced pressure, adsorbing on silica gel, and directly performing silica gel chromatographic separation, wherein the volume ratio of the mixture is 50: 1 as eluent, and column chromatography, in 86% yield.1H-NMR(500MHz,CDCl3):δ8.42(d,J＝8.0Hz,1H),7.91(d,J＝8.0Hz,3H),7.76(t,J＝8.0Hz,1H),7.58(t,J＝7.5Hz,1H),7.35(d,J＝9.5Hz,7H),3.87(s,3H).13C-NMR(500MHz,CDCl3):δ169.2,166.4,148.5,145.6,142.7,135.4,132.9,131.0,130.0,129.8,129.1,129.1,128.5,126.9,126.3,125.7,124.5.
Example 3: 2, 3-diphenyl-4-oxo-7-chlorocinnoline ylide
To a 100mL Schlenk reaction tube were added 5-chloro-2- (phenylethynyl) aniline (113.8mg, 0.5mmol), nitrosobenzene (80.3mg, 0.75mmol), CuCl (5.0mg, 0.05mmol), 4-dimethylaminopyridine (24.4mg, 0.2mmol), and toluene (1.5mL) in that order. Then, the tube is sealed. And (2) putting the reaction mixture into an oil bath kettle at the temperature of 100 ℃, stirring for 24 hours, taking out and cooling to room temperature, transferring the reaction stock solution, adding a proper amount of ethyl acetate for washing, mixing the stock solution with a washing solution, concentrating under reduced pressure, adsorbing on silica gel, and directly performing silica gel chromatographic separation, wherein the volume ratio of the mixture is 50: 1 as eluent, and by column chromatography, the yield was 73%.1H-NMR(500MHz,CDCl3):δ8.18(d,J＝9.0Hz,1H),7.76(d,J＝1.5Hz,1H),7.36(dd,J＝8.5Hz,J＝2.0Hz,1H),7.27-7.24(m,5H),7.18-7.15(m,5H).13C-NMR(500MHz,CDCl3):δ169.4,149.6,146.2,145.5,139.1,131.3,131.2,129.9,129.3,129.3,128.8,128.4,126.6,126.1,125.7,124.8.
Example 4: 2-phenyl-3- (4-biphenyl) yl-4-oxocinnoline ylide
2- ([1, 1-Biphenyl) was added to a 100mL Schlenk reaction tube in sequence]-4-phenylene) aniline (202.0mg, 0.5mmol), nitrosobenzene (80.3mg, 0.75mmol), CuCl (5.0mg, 0.05mmol), 4-dimethylaminopyridine (24.4mg, 0.2mmol), toluene (1.5 mL). Then, the tube is sealed. And (2) putting the reaction mixture into an oil bath kettle at the temperature of 100 ℃, stirring for 24 hours, taking out and cooling to room temperature, transferring the reaction stock solution, adding a proper amount of ethyl acetate for washing, mixing the stock solution with a washing solution, concentrating under reduced pressure, adsorbing on silica gel, and directly performing silica gel chromatographic separation, wherein the volume ratio of the mixture is 50: 1 mixture of dichloromethane and ethyl acetateAs eluent, obtained after column chromatography separation in 71% yield.1H-NMR(500MHz,CDCl3):δ8.45(dd,J＝10.5Hz,1.0Hz,1H),7.92(d,J＝11.0Hz,1H),7.76(t,J＝10.5Hz,1H),7.59-7.53(m,3H),7.50(d,J＝10.5Hz,2H),7.43-7.39(m,4H),7.38-7.33(m,6H).13C-NMR(500MHz,CDCl3):δ159.6,148.6,146.0,143.7,141.3,140.1,132.7,131.3,129.6,129.5,129.0,128.7,128.1,127.6,127.0,126.7,126.6,126.1,125.8,124.6.
Example 5: 2-phenyl-3- (4-cyano) phenyl-4-oxocinnoline ylide
To a 100mL Schlenk reaction tube were added sequentially 4- ((2-aminophenyl) ethynyl) benzonitrile (109.13mg, 0.5mmol), nitrosobenzene (80.3mg, 0.75mmol), CuCl (5.0mg, 0.05mmol), 4-dimethylaminopyridine (24.4mg, 0.2mmol), and toluene (1.5 mL). Then, the tube is sealed. And (2) putting the reaction mixture into an oil bath kettle at the temperature of 100 ℃, stirring for 24 hours, taking out and cooling to room temperature, transferring the reaction stock solution, adding a proper amount of ethyl acetate for washing, mixing the stock solution with a washing solution, concentrating under reduced pressure, adsorbing on silica gel, and directly performing silica gel chromatographic separation, wherein the volume ratio of the mixture is 50: 1 as eluent, and column chromatography, in 72%.1H-NMR(500MHz,CDCl3):δ8.41(dd,J＝8.0,0.5Hz,1H),7.93(d,J＝8.5Hz,1H),7.79(t,J＝7.0Hz,1H),7.61(t,J＝7.0Hz,1H),7.53(d,J＝8.5Hz),7.42-7.37(m,4H),7.35-7.33(m,2H).13C-NMR(500MHz,CDCl3):δ169.0,148.4,145.4,141.4,135.6,133.1,131.7,131.6,130.1,129.3,129.0,127.0,126.4,125.7,124.5,118.2,112.3.
Example 6: 2-phenyl-3- (4-methyl) phenyl-4-oxocinnoline ylide
2 + into a 100mL Schlenk reaction tube(p-tolyl) aniline (103.6mg, 0.5mmol), nitrosobenzene (80.3mg, 0.75mmol), CuCl (5.0mg, 0.05mmol), 4-dimethylaminopyridine (24.4mg, 0.2mmol), and toluene (1.5 mL). Then, the tube is sealed. And (2) putting the reaction mixture into an oil bath kettle at the temperature of 100 ℃, stirring for 24 hours, taking out and cooling to room temperature, transferring the reaction stock solution, adding a proper amount of ethyl acetate for washing, mixing the stock solution with a washing solution, concentrating under reduced pressure, adsorbing on silica gel, and directly performing silica gel chromatographic separation, wherein the volume ratio of the mixture is 50: 1 as eluent, and by column chromatography, the yield was 78%.1H-NMR(500MHz,CDCl3):δ8.43(d,J＝8.0Hz,1H),7.89(d,J＝8.5Hz,1H),7.74(t,J＝8.0Hz,1H),7.54(t,J＝8.0Hz,1H),7.35(s,5H),7.15(d,J＝8.0Hz,2H),7.06(d,J＝8.0Hz),2.28(s,3H).13C-NMR(500MHz,CDCl3):δ169.6,148.6,146.1,144.3,138.8,132.6,130.7,129.3,129.0,128.8,127.9,127.7,126.6,126.0,125.7,124.6,21.3.
Example 7: 2, 3-diphenyl-4-oxo-6-fluorocinnolin ylium salt
To a 100mL Schlenk reaction tube were added 4-fluoro-2-phenylethynylaniline (105.6mg, 0.5mmol), nitrosobenzene (80.3mg, 0.75mmol), CuCl (5.0mg, 0.05mmol), 4-dimethylaminopyridine (24.4mg, 0.2mmol), and toluene (1.5mL) in that order. Then, the tube is sealed. And (2) putting the reaction mixture into an oil bath kettle at the temperature of 100 ℃, stirring for 24 hours, taking out and cooling to room temperature, transferring the reaction stock solution, adding a proper amount of ethyl acetate for washing, mixing the stock solution with a washing solution, concentrating under reduced pressure, adsorbing on silica gel, and directly performing silica gel chromatographic separation, wherein the volume ratio of the mixture is 50: 1 as eluent, and by column chromatography, yield was 79%. Confirmation of structural data using nuclear magnetic resonance was:1H-NMR(500MHz,CDCl3):δ8.03(dd,J＝9.0Hz,J＝3.0Hz,1H),7.94(q,J＝4.5Hz,1H),7.53-7.49(m,1H),7.34(s,5H),7.25(s,1H).13C-NMR(500MHz,CDCl3):δ168.8,168.8,163.0,161.0,145.8,145.7,142.7,130.9,130.5,129.9,129.9,129.5,129.0,128.8,128.1,127.8,127.7,125.7,123.2,123.0,108.3,108.1.
example 8: 2, 3-diphenyl-4-oxo-6-methylcinnoline ylide
To a 100mL Schlenk reaction tube were added 4-methyl-2-phenylethynylaniline (103.6mg, 0.5mmol), nitrosobenzene (80.3mg, 0.75mmol), CuCl (5.0mg, 0.05mmol), 4-dimethylaminopyridine (24.4mg, 0.2mmol), and toluene (1.5mL) in that order. Then, the tube is sealed. And (2) putting the reaction mixture into an oil bath kettle at the temperature of 100 ℃, stirring for 24 hours, taking out and cooling to room temperature, transferring the reaction stock solution, adding a proper amount of ethyl acetate for washing, mixing the stock solution with a washing solution, concentrating under reduced pressure, adsorbing on silica gel, and directly performing silica gel chromatographic separation, wherein the volume ratio of the mixture is 50: 1 as eluent, and by column chromatography, the yield was 77%.1H-NMR(500MHz,CDCl3):δ8.22(s,1H),7.83(d,J＝9.0Hz,1H),7.59(dd,J＝8.5Hz,J＝2.0Hz,1H),7.34(s,5H),7.26-7.23(m,5H).13C-NMR(500MHz,CDCl3):δ169.0,147.1,146.0,143.5,139.0,134.9,131.1,131.0,129.3,128.9,128.6,128.0,126.6,126.3,125.8,123.3,21.8.
Example 9: 2, 3-diphenyl-4-oxo-6-methoxycarbonylcinnoline ylide
To a 100mL SchlenK reaction tube were added methyl 4-amino-3- (phenylethynyl) benzoate (125.6mg, 0.5mmol), nitrosobenzene (80.3mg, 0.75mmol), CuCl (5.0mg, 0.05mmol), 4-dimethylaminopyridine (24.4mg, 0.2mmol), and toluene (1.5mL) in that order. Then, the tube is sealed. Placing the reaction mixture into an oil bath kettle at 100 deg.C, stirring for 24 hr, cooling to room temperature, transferring the reaction stock solution, adding appropriate amount of ethyl acetate for washing, mixing the stock solution with the washing solution, concentrating under reduced pressure for adsorptionDirectly chromatographing on silica gel, the ratio by volume of 50: 1 as eluent, and column chromatography gave 61% after separation.1H-NMR(500MHz,CDCl3):δ9.09(s,1H),8.32(d,J＝8.5Hz,1H),7.90(dd,J＝9.0Hz,J＝2.0Hz,1H),7.36(s,5H),7.27(d,J＝2.0Hz,5H),3.99(d,J＝2.0Hz).13C-NMR(500MHz,CDCl3):δ169.9,166.3,150.5,145.8,145.5,132.3,130.8,130.2,129.6,129.1,129.0,128.6,128.1,127.7,127.7,126.7,125.6,125.1,52.4.
Example 10: 2-phenyl-3- (2-chloro) phenyl-4-oxocinnoline ylide
To a 100mL Schlenk reaction tube were added in order 2- ((2-chlorophenyl) ethynyl) aniline (113.8mg, 0.5mmol), nitrosobenzene (80.3mg, 0.75mmol), CuCl (5.0mg, 0.05mmol), 4-dimethylaminopyridine (24.4mg, 0.2mmol), and toluene (1.5 mL). Then, the tube is sealed. And (2) putting the reaction mixture into an oil bath kettle at the temperature of 100 ℃, stirring for 24 hours, taking out and cooling to room temperature, transferring the reaction stock solution, adding a proper amount of ethyl acetate for washing, mixing the stock solution with a washing solution, concentrating under reduced pressure, adsorbing on silica gel, and directly performing silica gel chromatographic separation, wherein the volume ratio of the mixture is 50: 1 as eluent, and column chromatography, in 49% yield.1H-NMR(500MHz,CDCl3):δ8.35(d,J＝8.0Hz,1H),7.84(d,J＝8.5Hz,1H),7.68(t,J＝7.0Hz,1H),7.49(t,J＝7.5Hz,1H),7.36(d,J＝5.0Hz,2H),7.25(s,4H),7.13-7.07(m,3H),13C-NMR(500MHz,CDCl3):δ168.9,148.6,145.2,142.3,134.4,132.7,132.5,130.9,130.5,129.8,129.5,128.8,128.3,126.7,126.6,126.1,124.8,124.4.
Example 11: 3-phenyl-2- (4-chloro) phenyl-4-oxocinnoline ylide
To a 100mL Schlenk reaction tube were added 2-phenylethynylaniline (96.6mg, 0.5mmol), 4-chloronitrosobenzene (106.2mg, 0.75mmol), CuCl (5.0mg, 0.05mmol), 4-dimethylaminopyridine (24.4mg, 0.2mmol), and toluene (1.5mL) in that order. Then, the tube is sealed. And (2) putting the reaction mixture into an oil bath kettle at the temperature of 100 ℃, stirring for 24 hours, taking out and cooling to room temperature, transferring the reaction stock solution, adding a proper amount of ethyl acetate for washing, mixing the stock solution with a washing solution, concentrating under reduced pressure, adsorbing on silica gel, and directly performing silica gel chromatographic separation, wherein the volume ratio of the mixture is 50: 1 as eluent, and column chromatography, in 58% yield.1H-NMR(500MHz,CDCl3):δ8.41(d,J＝8.5Hz,1H),7.87(d,J＝9.0Hz,1H),7.75(t,J＝7.5Hz,1H),7.55(t,J＝8.0Hz,1H),7.31(s,4H),7.27(t,J＝6.5Hz,5H),13C-NMR(500MHz,CDCl3):δ169.4,148.6,144.4,144.0,135.5,132.8,130.9,130.5,129.2,129.0,128.2,128.2,127.1,126.6,124.6.
Example 12: 3-phenyl-2- (4-methoxy) phenyl-4-oxocinnoline ylide
To a 100mL Schlenk reaction tube were added 2-phenylethynylaniline (96.6mg, 0.5mmol), 4-methoxynitrosobenzene (102.9mg, 0.75mmol), CuCl (5.0mg, 0.05mmol), 4-dimethylaminopyridine (24.4mg, 0.2mmol), and toluene (1.5mL) in that order. Then, the tube is sealed. And (2) putting the reaction mixture into an oil bath kettle at the temperature of 100 ℃, stirring for 24 hours, taking out and cooling to room temperature, transferring the reaction stock solution, adding a proper amount of ethyl acetate for washing, mixing the stock solution with a washing solution, concentrating under reduced pressure, adsorbing on silica gel, and directly performing silica gel chromatographic separation, wherein the volume ratio of the mixture is 50: 1 as eluent, and column chromatography, in 69%.1H-NMR(500MHz,CDCl3):δ8.417(d,J＝8.0Hz,1H),7.89(d,J＝8.5Hz,1H),7.74(t,J＝7.0Hz,1H),7.75(t,J＝7.5Hz,1H),7.27(s,8H),6.81(d,J＝8.5Hz,2H),3.78(s,3H).13C-NMR(500MHz,CDCl3):δ139.5,159.9,132.6,130.8,128.6,128.0,127.9,126.9,126.6,124.5,114.0,55.5.
Example 13: 2-phenyl-3- (3-thienyl) -4-oxocinnoline ylide
To a 100mL Schlenk reaction tube were added 2- (thienyl-3-ethynyl) aniline (99.6mg, 0.5mmol), nitrosobenzene (80.3mg, 0.75mmol), CuCl (5.0mg, 0.05mmol), 4-dimethylaminopyridine (24.4mg, 0.2mmol), and toluene (1.5mL) in that order. Then, the tube is sealed. And (2) putting the reaction mixture into an oil bath kettle at the temperature of 100 ℃, stirring for 24 hours, taking out and cooling to room temperature, transferring the reaction stock solution, adding a proper amount of ethyl acetate for washing, mixing the stock solution with a washing solution, concentrating under reduced pressure, adsorbing on silica gel, and directly performing silica gel chromatographic separation, wherein the volume ratio of the mixture is 50: 1 as eluent, and column chromatography, in 66% yield.1H-NMR(500MHz,CDCl3):δ8.43(d,J＝10.0Hz,1H),7.89(d,J＝10.5Hz,1H),7.74(t,J＝10.5Hz,1H),7.66(d,J＝2.5Hz,1H),7.55(t,J＝10.0Hz,1H),7.45-7.41(m,5H),7.13(dd,J＝6.0Hz,3.5Hz,1H),6.80(d,J＝6.0Hz,1H).13C-NMR(500MHz,CDCl3):δ169.4,148.4,146.3,139.4,132.7,129.9,129.8,129.5,129.3,128.8,128.1,126.7,125.8,125.5,124.6,124.4.
Comparative examples 1 to 9: examination of copper Compound
The procedure of example 1 was repeated except that the copper compounds of examples 1 to 9 were replaced with the following copper compounds, respectively, to obtain comparative examples 1 to 13, and the ligands used, the corresponding examples and the product yields are shown in Table 1 below.
TABLE 1 Effect of different copper compounds on reaction yield
It can be seen that cuprous chloride has the best effect among the copper compounds screened.
The above examples 1 to 13 and comparative examples 1 to 9 show that the catalytic reaction method of the present invention can efficiently produce cinnoline ylide compounds by using CuCl as an accelerator, which can provide good reaction effects and high yields, and by analyzing the structure of the product by NMR chromatography, it can be confirmed that the product is a cinnoline ylide compound
In conclusion, the invention provides a method for synthesizing cinnoline salt compound by catalyzing 2-ethynylaniline compound and nitrosobenzene compound through dehydration condensation addition reaction, and the synthesis method can obtain target product with high yield through mutual synergy and promotion of CuCl, 4-dimethylamino pyridine, each component and conditions, provides a brand new method for synthesizing cinnoline salt, and has good research value and application potential.
The above disclosure is only for the purpose of illustrating the preferred embodiments of the present invention, and it is therefore to be understood that the invention is not limited by the scope of the appended claims.
Claims (7)
1. A method for synthesizing cinnoline salt compound is characterized in that: which is of the formula
Under the action of a composite catalytic system consisting of a metal catalyst and an auxiliary substance, carrying out catalytic cyclization reaction on a compound shown in a formula (I) and a compound shown in a formula (II) to obtain a cinnoline salt compound shown in a formula (III);
wherein R1 is selected from H, halogen, nitro, ester group, alkyl and cyano; r2 is selected from aryl, alkyl, cyano, ester, halogen, nitro, methoxy and heterocycle; r3 is selected from halogen, alkyl and methoxy;
the metal catalyst is any one or more of cuprous chloride, cuprous bromide, copper acetate and copper trifluoromethanesulfonate;
the auxiliary substance is 4-dimethylamino pyridine;
the reaction is carried out in an air atmosphere or an oxygen atmosphere.
2. The method of synthesizing a cinnoline salt compound according to claim 1, wherein the cinnoline salt compound is prepared by the following steps: the metal catalyst is cuprous chloride.
3. The method of synthesizing a cinnoline salt compound according to claim 2, wherein: the compound shown in the formula (I) is used as a base number, and the amount of cuprous chloride is 0.05-0.5 equivalent.
4. The method of synthesizing a cinnoline salt compound according to claim 1, wherein the cinnoline salt compound is prepared by the following steps: the auxiliary material takes the compound shown in the formula (I) as a base number, and the using amount of the auxiliary material is 0.2-1.0 equivalent.
5. The method of synthesizing a cinnoline salt compound according to claim 1, wherein the cinnoline salt compound is prepared by the following steps: any one or more of dimethyl sulfoxide, chlorobenzene, acetonitrile and toluene is used as a reaction solvent.
6. The method of synthesizing a cinnoline salt compound according to claim 1, wherein the cinnoline salt compound is prepared by the following steps: the reaction temperature is 60-120 ℃, and the reaction time is 24-48 h.
7. The method of synthesizing a cinnoline salt compound according to claim 1, wherein the cinnoline salt compound is prepared by the following steps: after the reaction is finished, transferring the reaction solution, adding a proper amount of ethyl acetate for washing, mixing the reaction stock solution with a washing solution, concentrating, and directly performing silica gel column chromatographic separation, wherein the volume ratio of the ethyl acetate to the washing solution is 1: 0.2-1 of a mixture of dichloromethane and ethyl acetate as an eluent, collecting the eluent, and concentrating by distillation under reduced pressure again to obtain the compound shown in the formula (III).
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Non-Patent Citations (7)
| Title |
|---|
| A General Method to Diverse Cinnolines and Cinnolinium Salts;Dongbing Zhao，等;《Chem. Eur. J.》;20130328;第19卷;6239-6244 * |
| Cascade One-Pot Synthesis of Orange-Red-Fluorescent Polycyclic Cinnolino[2,3-f]phenanthridin-9-ium Salts by Palladium(II)-Catalyzed C-H Bond Activation of 2-Azobiaryl Compounds and Alkenes;Jayachandran Jayakumar，等;《Angew. Chem. Int. Ed.》;20191119;第59卷;689-694 * |
| Cobalt-Catalyzed Oxidative Annulation of Nitrogen-Containing Arenes with Alkynes: An Atom-Economical Route to Heterocyclic Quaternary Ammonium Salts;Sekar Prakash，等;《Angew. Chem. Int. Ed.》;20151221;第55卷;1844-1848 * |
| Copper-Catalyzed Aerobic Oxidative Cyclization of 2-Alkynylanilines with Nitrosoarenes: Synthesis of Organic Solid Mechanoluminescence Compounds of 4‑Oxo‑4H‑cinnolin-2-ium-1-ide;Xiaolan Fang，等;《Org. Lett.》;20210201;第23卷;1228-1233 * |
| RhodiumACHTUNGTRENUNG(III)-Catalyzed Synthesis of Cinnolinium Salts from Azobenzenes and Alkynes: Application to the Synthesis of Indoles and Cinnolines;Krishnamoorthy Muralirajan，等;《Chem. Eur. J.》;20130415;第19卷;6198-6202 * |
| Substituent Effects on So lvent-Free Synthesis (MWAOS) of Dihydroquinazolinones by the Addition of Isatoic Anhydride to a Series of Phenyl-Substituted N-(Phenylmethylidene) Anilines;Abhilash Mullasseril;《Journal of Chemistry》;20121231;第2013卷;1-4 * |
| 噌啉类化合物的合成研究进展;苏琳，等;《有机化学》;20191231;第39卷;363-376 * |
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