CN114292230B - Palladium catalyzed N-H carbonylation of N-phenylpyridine-2-amine with DMF as methyl source - Google Patents

Palladium catalyzed N-H carbonylation of N-phenylpyridine-2-amine with DMF as methyl source Download PDF

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CN114292230B
CN114292230B CN202210000719.XA CN202210000719A CN114292230B CN 114292230 B CN114292230 B CN 114292230B CN 202210000719 A CN202210000719 A CN 202210000719A CN 114292230 B CN114292230 B CN 114292230B
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CN114292230A (en
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及方华
李璇
徐嘉伟
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Guilin University of Technology
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Abstract

The invention relates to a palladium-catalyzed N-H carbonylation reaction of N-phenylpyridine-2-amine with DMF as a methyl source. Adding N-phenylpyridine-2-amine, a catalyst, an oxidant, an additive, a ligand and a solvent into a glass test tube, sleeving a balloon filled with carbon monoxide on a reactor, stirring and reacting for 1-40 hours at 40-150 ℃, cooling to room temperature after the reaction is finished, removing the balloon, filtering a reaction solution, decompressing and evaporating the solvent to obtain a crude product, and purifying by column chromatography to obtain the N-H carbonylation product of the N-phenylpyridine-2-amine. The invention realizes the N-H carbonylation process of N-phenylpyridine-2-amine by using carbonylation reaction, and has the characteristics of simple operation, easily obtained raw materials, good functional group tolerance, good yield and the like.

Description

Palladium catalyzed N-H carbonylation of N-phenylpyridine-2-amine with DMF as methyl source
Technical Field
The invention relates to the technical fields of medicinal chemistry, pesticide science, dye chemistry, organic synthesis and the like, in particular to a palladium-catalyzed N-H carbonylation reaction of N-phenylpyridine-2-amine with DMF as a methyl source.
Background
Acetylation of amines is one of the most fundamental transformations in organic chemistry. The reaction is widely applied in the fields of pharmaceutical industry and agriculture. Acetylation of amines typically occurs with acetic acid/acetic anhydride/acetyl chloride under basic or acidic conditions. The reaction conditions are harsh, and the applicability of the substrate is limited. The carbonylation reaction serves as a key reaction for introducing carbonyl groups, and provides more synthesis paths for the acetylation reaction of amines. At the same time, research work with the industrial solvent N, N-Dimethylformamide (DMF) as a methyl source has also attracted considerable attention from scientists. The study of how to introduce carbonyl groups by means of carbonylation reactions while using N, N-Dimethylformamide (DMF) as a methyl source envisages a great deal of innovation, both as solvent and as reactant, while meeting the development requirements of green chemistry.
Disclosure of Invention
The invention provides a palladium-catalyzed N-H carbonylation reaction of N-phenylpyridine-2-amine with DMF as a methyl source, which has the advantages of excellent yield, simple operation, easily obtained raw materials, high step economy and novel synthetic route for the N-H carbonylation reaction of N-phenylpyridine-2-amine by using carbon monoxide as a carbonyl source and N, N-Dimethylformamide (DMF) as a solvent and a methyl source. The synthetic route is as follows:
the principle of the invention is that N-phenylpyridine-2-amine, carbon monoxide and DMF are used as reaction raw materials, and under the guiding action of pyridine nitrogen atoms, target products are generated through carbon monoxide migration and insertion, nucleophilic attack, reduction elimination and single electron transfer.
The aim of the invention is achieved by the following technical scheme:
palladium catalyzed N-H carbonylation of N-phenylpyridine-2-amine with DMF as a methyl source: adding N-phenylpyridine-2-amine, a catalyst, an oxidant, an additive, a ligand and a solvent into a glass test tube, sleeving a balloon filled with carbon monoxide on a reactor, stirring and reacting for 1-40 hours at 40-150 ℃, cooling to room temperature after the reaction is finished, removing the balloon, filtering a reaction solution, decompressing and evaporating the solvent to obtain a crude product, and purifying by column chromatography to obtain an N-H carbonylation product of the N-phenylpyridine-2-amine;
the above reaction is shown in the following formula:
wherein R is 1 Or R is 2 Including H, F, cl,3, 4-dimethyl, methyl, methoxy, tert-butyl, trifluoromethyl, nitro, 3, 5-dimethyl, naphthyl or ester groups.
In the method, the metal palladium catalyst is palladium chloride, palladium iodide, palladium bromide, palladium acetate, dichlorodiacetonitrile palladium, trifluoroacetate palladium or bis-triphenylphosphine palladium dichloride.
In the method, the copper salt is copper acetate, cuprous bromide, cupric oxide, cuprous chloride, cupric bromide, cupric chloride, cupric sulfate, cuprous iodide, copper triflate or cupric nitrate.
In the method, the solvent is a mixed solvent of dimethyl sulfoxide (DMSO) and N, N-Dimethylformamide (DMF), wherein the mixed volume ratio of the dimethyl sulfoxide (DMSO) to the N, N-Dimethylformamide (DMF) is 1: 100-100:1.
In the above method, the balloon pressure filled with carbon monoxide gas is 1 atm.
In the above method, the reaction temperature is 40 to 150 ℃.
In the method, after the reaction is finished, the product is separated and purified by column chromatography; the column chromatography eluent is a mixed solvent of petroleum ether and ethyl acetate, and the ratio range value between petroleum ether and ethyl acetate is 1-40:1.
Compared with the prior art, the invention has the following advantages and effects:
the palladium-catalyzed N-H carbonylation reaction of the N-phenylpyridine-2-amine with DMF as a methyl source has the advantages of simple and safe operation, easily obtained raw materials, excellent yield and good functional group tolerance, and improves a novel synthesis means for N-H carbonylation of the N-phenylpyridine-2-amine.
Drawings
FIG. 1 is a hydrogen spectrum of the products obtained in examples 1-18;
FIG. 2 is a graph of the carbon spectra of the products obtained in examples 1-18;
FIG. 3 is a hydrogen spectrum of the product of example 19;
FIG. 4 is a carbon spectrum of the product of example 19;
FIG. 5 is a hydrogen spectrum of the product of example 20;
FIG. 6 is a carbon spectrum of the product of example 20;
FIG. 7 is a hydrogen spectrum of the product of example 21;
FIG. 8 is a carbon spectrum of the product of example 21;
FIG. 9 is a hydrogen spectrum of the product of example 22;
FIG. 10 is a carbon spectrum of the product of example 22;
Detailed Description
The invention will now be described in further detail with reference to specific examples and figures, but embodiments of the invention and adapted substrates are not limited thereto.
Example 1
To a 25mL test tube, 0.2 mmol of N-phenylpyridin-2-amine, 0.03 mmol of palladium acetate, 0.22 mmol of copper acetate, 0.04 mmol of potassium iodide were added 3 mL of N, N-Dimethylformamide (DMF) as a solvent, a balloon containing carbon monoxide gas was set as a carbonyl source, and the mixture was stirred at 100 ℃. After completion of the reaction, TLC (thin layer chromatography) was used to cool the reaction mixture to room temperature, the balloon was removed, and unreacted carbon monoxide was slowly purged. The reaction solution is filtered, the filtrate is decompressed and distilled to remove the solvent, and then the target product is obtained through column chromatography separation and purification, and the yield is 30%.
Example 2
To a 25mL test tube, 0.2 mmol of N-phenylpyridin-2-amine, 0.03 mmol of palladium trifluoroacetate, 0.22 mmol of copper acetate, 0.04 mmol of potassium iodide were added 3 mL of N, N-Dimethylformamide (DMF) as a solvent, a balloon containing carbon monoxide gas was set as a carbonyl source, and the mixture was stirred at 100 ℃. After completion of the reaction, TLC (thin layer chromatography) was used to cool the reaction mixture to room temperature, the balloon was removed, and unreacted carbon monoxide was slowly purged. The reaction solution is filtered, the filtrate is decompressed and distilled to remove the solvent, and then the target product is obtained through column chromatography separation and purification, and the yield is 25%.
Example 3
To a 25mL test tube, 0.2 mmol of N-phenylpyridin-2-amine, 0.03 mmol of dichlorodiacetonitrile palladium, 0.22 mmol of copper acetate, 0.04 mmol of potassium iodide were added 3 mL of N, N-Dimethylformamide (DMF) as a solvent, a balloon containing carbon monoxide gas was set as a carbonyl source, and the mixture was stirred at 100 ℃. After completion of the reaction, TLC (thin layer chromatography) was used to cool the reaction mixture to room temperature, the balloon was removed, and unreacted carbon monoxide was slowly purged. The reaction solution is filtered, the filtrate is decompressed and distilled to remove the solvent, and then the target product is obtained through column chromatography separation and purification, and the yield is 32%.
Example 4
To a 25mL test tube, 0.2 mmol of N-phenylpyridin-2-amine, 0.03 mmol of palladium chloride, 0.22 mmol of copper acetate, 0.04 mmol of potassium iodide were added 3 mL of N, N-Dimethylformamide (DMF) as a solvent, a balloon containing carbon monoxide gas was set as a carbonyl source, and the mixture was stirred at 100 ℃. After completion of the reaction, TLC (thin layer chromatography) was used to cool the reaction mixture to room temperature, the balloon was removed, and unreacted carbon monoxide was slowly purged. The reaction solution is filtered, the filtrate is decompressed and distilled to remove the solvent, and then the target product is obtained through column chromatography separation and purification, and the yield is 50%.
Example 5
To a 25mL test tube, 0.2 mmol of N-phenylpyridin-2-amine, 0.03 mmol of palladium chloride, 0.22 mmol of copper oxide, 0.04 mmol of potassium iodide were added 3 mL of N, N-Dimethylformamide (DMF) as a solvent, a balloon containing carbon monoxide gas was set as a carbonyl source, and the mixture was stirred at 100 ℃. After completion of the reaction, TLC (thin layer chromatography) was used to cool the reaction mixture to room temperature, the balloon was removed, and unreacted carbon monoxide was slowly purged. The reaction solution is filtered, the filtrate is decompressed and distilled to remove the solvent, and then the target product is obtained through column chromatography separation and purification, and the yield is 10%.
Example 6
To a 25mL test tube, 0.2 mmol of N-phenylpyridin-2-amine, 0.03 mmol of palladium chloride, 0.22 mmol of p-benzoquinone, 0.04 mmol of potassium iodide, 3 mL of N, N-Dimethylformamide (DMF) as a solvent, a balloon containing carbon monoxide gas as a carbonyl source and stirring at 100℃were added. The reaction was detected by TLC (thin layer chromatography) and the target product was not detected.
Example 7
To a 25mL test tube, 0.2 mmol of N-phenylpyridin-2-amine, 0.03 mmol of palladium chloride, 0.22 mmol of silver carbonate, 0.04 mmol of potassium iodide were added 3 mL of N, N-Dimethylformamide (DMF) as a solvent, a balloon containing carbon monoxide gas was set as a carbonyl source, and the mixture was stirred at 100 ℃. The reaction was detected by TLC (thin layer chromatography) and the target product was not detected.
Example 8
To a 25mL test tube, 0.2 mmol of N-phenylpyridin-2-amine, 0.03 mmol of palladium chloride, 0.22 mmol of potassium persulfate, 0.04 mmol of potassium iodide, 3 mL of N, N-Dimethylformamide (DMF) as a solvent, a balloon containing carbon monoxide gas as a carbonyl source and stirring at 100℃were added. The reaction was detected by TLC (thin layer chromatography) and the target product was not detected.
Analysis shows that: it can be seen from the reaction effect of examples 5 to 8 that the oxidizing agent of the reaction has a critical effect on the reaction, which has a certain oxidizing agent specificity.
Example 9
To a 25mL test tube, 0.2 mmol of N-phenylpyridin-2-amine, 0.03 mmol of palladium chloride, 0.22 mmol of copper acetate, 0.04 mmol of elemental iodine, 3 mL of N, N-Dimethylformamide (DMF) as a solvent, a balloon containing carbon monoxide gas as a carbonyl source, and stirring at 100℃were added. After completion of the reaction, TLC (thin layer chromatography) was used to cool the reaction mixture to room temperature, the balloon was removed, and unreacted carbon monoxide was slowly purged. The reaction solution is filtered, the filtrate is decompressed and distilled to remove the solvent, and then the target product is obtained through column chromatography separation and purification, and the yield is 45%.
Example 10
To a 25mL test tube, 0.2 mmol of N-phenylpyridin-2-amine, 0.03 mmol of palladium chloride, 0.22 mmol of copper acetate, 0.04 mmol of sodium iodide were added 3 mL of N, N-Dimethylformamide (DMF) as a solvent, a balloon containing carbon monoxide gas was set as a carbonyl source, and the mixture was stirred at 100 ℃. After completion of the reaction, TLC (thin layer chromatography) was used to cool the reaction mixture to room temperature, the balloon was removed, and unreacted carbon monoxide was slowly purged. The reaction solution is filtered, the filtrate is decompressed and distilled to remove the solvent, and then the target product is obtained through column chromatography separation and purification, and the yield is 30%.
Example 11
To a 25mL test tube, 0.2 mmol of N-phenylpyridin-2-amine, 0.03 mmol of palladium chloride, 0.22 mmol of copper acetate, 0.04 mmol of potassium sulfate and 3 mL of N, N-Dimethylformamide (DMF) were added as a solvent, a balloon containing carbon monoxide gas was set as a carbonyl source, and the mixture was stirred at 100 ℃. After completion of the reaction, TLC (thin layer chromatography) was used to cool the reaction mixture to room temperature, the balloon was removed, and unreacted carbon monoxide was slowly purged. The reaction solution is filtered, the filtrate is decompressed and distilled to remove the solvent, and then the target product is obtained through column chromatography separation and purification, and the yield is 23%.
Example 12
To a 25mL test tube, 0.2 mmol of N-phenylpyridin-2-amine, 0.03 mmol of palladium chloride, 0.22 mmol of copper acetate and 0.04 mmol of potassium iodide were added 3 mL of N, N-Dimethylformamide (DMF) as a solvent, a balloon containing carbon monoxide gas was set as a carbonyl source, and the mixture was stirred at 80 ℃. After completion of the reaction, TLC (thin layer chromatography) was used to cool the reaction mixture to room temperature, the balloon was removed, and unreacted carbon monoxide was slowly purged. The reaction solution is filtered, the filtrate is decompressed and distilled to remove the solvent, and then the target product is obtained through column chromatography separation and purification, and the yield is 70%.
Example 13
To a 25mL test tube, 0.2 mmol of N-phenylpyridin-2-amine, 0.03 mmol of palladium chloride, 0.22 mmol of copper acetate, 0.04 mmol of potassium iodide were added 3 mL of N, N-Dimethylformamide (DMF) as a solvent, a balloon containing carbon monoxide gas was set as a carbonyl source, and the mixture was stirred at 120 ℃. After completion of the reaction, TLC (thin layer chromatography) was used to cool the reaction mixture to room temperature, the balloon was removed, and unreacted carbon monoxide was slowly purged. The reaction solution is filtered, the filtrate is decompressed and distilled to remove the solvent, and then the target product is obtained through column chromatography separation and purification, and the yield is 20%.
Example 14
To a 25mL test tube, 0.2 mmol of N-phenylpyridin-2-amine, 0.03 mmol of palladium chloride, 0.22 mmol of copper acetate, 0.04 mmol of potassium iodide, 3 mL of dimethyl sulfoxide (DMSO) as a solvent, a balloon containing carbon monoxide gas as a carbonyl source, and stirring at 80℃were added. After completion of the reaction, TLC (thin layer chromatography) was used to cool the reaction mixture to room temperature, the balloon was removed, and unreacted carbon monoxide was slowly purged. The reaction solution is filtered, the filtrate is decompressed and distilled to remove the solvent, and then the target product is obtained through column chromatography separation and purification, and the yield is 65%.
Example 15
To a 25mL test tube, 0.2 mmol of N-phenylpyridin-2-amine, 0.03 mmol of palladium chloride, 0.22 mmol of copper acetate, 0.04 mmol of potassium iodide, 3 mL of toluene (PhMe) as a solvent, a balloon containing carbon monoxide gas as a carbonyl source, and stirring at 80℃were added. The reaction was detected by TLC (thin layer chromatography) and the target product was not detected.
Example 16
To a 25mL test tube, 0.2 mmol of N-phenylpyridin-2-amine, 0.03 mmol of palladium chloride, 0.22 mmol of copper acetate, 0.04 mmol of potassium iodide were added 3 mL of N, N-Dimethylacetamide (DMA) as a solvent, a balloon containing carbon monoxide gas was set as a carbonyl source, and the mixture was stirred at 80 ℃. The reaction was detected by TLC (thin layer chromatography) and the target product was not detected.
Example 17
To a 25mL test tube, 0.2 mmol of N-phenylpyridine-2-amine, 0.03 mmol of palladium chloride, 0.22 mmol of copper acetate, 0.04 mmol of potassium iodide were added 3 mL of N, N-Dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) as a mixed solvent at a volume ratio of 10:1, a balloon containing carbon monoxide gas was set as a carbonyl source, and the mixture was stirred at 80 ℃. After completion of the reaction, TLC (thin layer chromatography) was used to cool the reaction mixture to room temperature, the balloon was removed, and unreacted carbon monoxide was slowly purged. The reaction solution is filtered, the filtrate is decompressed and distilled to remove the solvent, and then the target product is obtained through column chromatography separation and purification, and the yield is 75%.
Example 18
To a 25mL test tube, 0.2 mmol of N-phenylpyridine-2-amine, 0.03 mmol of palladium chloride, 0.22 mmol of copper acetate, 0.04 mmol of potassium iodide, and 0.03 mmol of triphenylphosphine were added, 3 mL of N, N-Dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) were added as a mixed solvent at a volume ratio of 10:1, and a balloon containing carbon monoxide gas was fitted as a carbonyl source, followed by stirring at 80 ℃. After completion of the reaction, TLC (thin layer chromatography) was used to cool the reaction mixture to room temperature, the balloon was removed, and unreacted carbon monoxide was slowly purged. The reaction solution is filtered, the filtrate is decompressed and distilled to remove the solvent, and then the target product is obtained through column chromatography separation and purification, and the yield is 81%.
Structural characterization data for the products obtained in examples 1-18 are shown below: (see FIGS. 1 and 2)
1 H NMR(500MHz,CDCl 3 )δ8.46–8.40(m,1H),7.71(tdd,J＝7.3,2.0,1.1Hz,1H),7.46(d,J＝8.2Hz,1H),7.41(t,J＝7.9Hz,2H),7.34–7.28(m,3H),7.16–7.10(m,1H),2.11(s,3H)； 13 C{ 1 H}NMR(125MHz,CDCl 3 )δ171.0,155.2,148.8,142.0,138.0,129.5,128.5,127.6,121.5,121.3,24.3.HRMS Calcd(ESI-TOF)m/z for C 13 H 12 N 2 O[M+H] + ,213.1022；Found 213.1026.
The structure of the resulting product is deduced from the above data as follows:
example 19
To a 25mL test tube, 0.2 mmol of N-p-tolylpyridin-2-amine, 0.03 mmol of palladium chloride, 0.22 mmol of copper acetate, 0.04 mmol of potassium iodide, 0.03 mmol of triphenylphosphine were added, 3 mL of N, N-Dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) were added as a mixed solvent at a volume ratio of 10:1, and a balloon containing carbon monoxide gas was set as a carbonyl source and stirred at 80 ℃. After completion of the reaction, TLC (thin layer chromatography) was used to cool the reaction mixture to room temperature, the balloon was removed, and unreacted carbon monoxide was slowly purged. The reaction solution is filtered, the filtrate is decompressed and distilled to remove the solvent, and then the target product is obtained through column chromatography separation and purification, and the yield is 82%.
The structural characterization data of the resulting product are shown below:
1 H NMR(500MHz,CDCl 3 )δ8.42(dd,J＝5.0,1.9Hz,1H),7.69(dd,J＝7.8,2.0Hz,1H),7.48(d,J＝8.2Hz,1H),7.21(q,J＝8.4Hz,4H),7.12(ddd,J＝7.4,4.8,1.0Hz,1H),2.37(s,3H),2.11(s,3H)； 13 C{ 1 H}NMR(125MHz,CDCl 3 )δ171.2,155.3,148.8,139.5,137.9,137.6,130.2,128.2,121.3,121.1,24.3,21.1.HRMS Calcd(ESI-TOF)m/z for C 14 H 14 N 2 O[M+H] + ,227.1179；Found 227.1189.
the structure of the product obtained is deduced from the above data as follows: (see FIGS. 3 and 4)
Example 20
To a 25mL test tube, 0.2 mmol of N-p-fluorophenylpyridin-2-amine, 0.03 mmol of palladium chloride, 0.22 mmol of copper acetate, 0.04 mmol of potassium iodide, 0.03 mmol of triphenylphosphine were added, 3 mL of N, N-Dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) were added as a mixed solvent at a volume ratio of 10:1, and a balloon containing carbon monoxide gas was set as a carbonyl source and stirred at 80 ℃. After completion of the reaction, TLC (thin layer chromatography) was used to cool the reaction mixture to room temperature, the balloon was removed, and unreacted carbon monoxide was slowly purged. The reaction solution is filtered, the filtrate is decompressed and distilled to remove the solvent, and then the target product is obtained through column chromatography separation and purification, and the yield is 67%.
The structural characterization data of the resulting product are shown below: (see FIGS. 5 and 6)
1 H NMR(500MHz,CDCl 3 )δ8.42(dd,J＝4.9,1.9Hz,1H),7.75–7.69(m,1H),7.45(d,J＝8.1Hz,1H),7.30–7.25(m,2H),7.15(ddd,J＝7.3,4.9,1.1Hz,1H),7.09(td,J＝8.4,1.8Hz,2H),2.10(s,3H). 13 C{ 1 H}NMR(125MHz,CDCl 3 )δ171.0,162.6,160.7,155.1,148.8,138.1,137.9,130.1,130.1,121.6,121.1,116.4,116.3,24.2.HRMS Calcd(ESI-TOF)m/z for C 13 H 11 N 2 OF[M+H] + ,231.0928；Found 231.0936.
The structure of the product obtained is deduced from the above data as follows:
example 18
To a 25mL test tube, 0.2 mmol of N-p-bromophenyl-pyridin-2-amine, 0.03 mmol of palladium chloride, 0.22 mmol of copper acetate, 0.04 mmol of potassium iodide, 0.03 mmol of triphenylphosphine were added, 3 mL of N, N-Dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) were added as a mixed solvent at a volume ratio of 10:1, and a balloon containing carbon monoxide gas was set as a carbonyl source and stirred at 80 ℃. After completion of the reaction, TLC (thin layer chromatography) was used to cool the reaction mixture to room temperature, the balloon was removed, and unreacted carbon monoxide was slowly purged. The reaction solution is filtered, the filtrate is decompressed and distilled to remove the solvent, and then the target product is obtained through column chromatography separation and purification, and the yield is 53%.
The structural characterization data of the resulting product are shown below: (see FIGS. 7 and 8)
1 H NMR(500MHz,CDCl 3 )δ8.46–8.42(m,1H),7.76–7.69(m,1H),7.53(dd,J＝8.3,1.4Hz,2H),7.42(t,J＝8.3Hz,1H),7.20–7.15(m,3H),2.12(s,3H). 13 C{ 1 H}NMR(125MHz,CDCl 3 )δ170.7,155.0,148.9,141.0,138.2,132.6,129.9,129.5,121.8,121.3,24.3.HRMS Calcd(ESI-TOF)m/z for C 13 H 11 N 2 OBr[M+H] + ,291.0128；Found 291.0138.
The structure of the product obtained is deduced from the above data as follows:
example 19
To a 25mL test tube, 0.2 mmol of N-p-trifluoromethylpyridin-2-amine, 0.03 mmol of palladium chloride, 0.22 mmol of copper acetate, 0.04 mmol of potassium iodide, 0.03 mmol of triphenylphosphine were added, 3 mL of N, N-Dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) were added as a mixed solvent at a volume ratio of 10:1, and a balloon containing carbon monoxide gas was set as a carbonyl source and stirred at 80 ℃. After completion of the reaction, TLC (thin layer chromatography) was used to cool the reaction mixture to room temperature, the balloon was removed, and unreacted carbon monoxide was slowly purged. The reaction solution is filtered, the filtrate is decompressed and distilled to remove the solvent, and then the target product is obtained through column chromatography separation and purification, and the yield is 29%.
The structural characterization data of the resulting product are shown below: (see FIGS. 9 and 10)
1 H NMR(500MHz,CDCl 3 )δ8.49(dd,J＝4.9,2.2Hz,1H),7.78(td,J＝7.8,2.0Hz,1H),7.54(ddd,J＝20.7,8.7,6.1Hz,4H),7.42(d,J＝8.0Hz,1H),7.23(dd,J＝7.5,4.8Hz,1H),2.14(d,J＝3.0Hz,3H). 13 C{ 1 H}NMR(125MHz,CDCl 3 )δ170.6,154.9,149.1,142.4,138.4,132.0,131.7,131.5,131.4,129.9,124.9,124.7,124.1,122.5,122.1,121.5,24.2.HRMS Calcd(ESI-TOF)m/z for C 14 H 11 F 3 N 2 O[M+H] + ,281.0896；Found 281.0900.
The structure of the product obtained is deduced from the above data as follows:

Claims (2)

1. the palladium catalyzed N-H carbonylation of N-phenylpyridine-2-amine with DMF as methyl source is characterized by adding N-phenylpyridine-2-amine, catalyst, oxidant, additive, ligand and solvent into a glass test tube, covering a balloon filled with carbon monoxide on a reactor, stirring at 40-150 ℃ for reaction for 1-40 hours, cooling to room temperature after the reaction is finished, removing the balloon, filtering the reaction solution, decompressing and steaming out the solvent to obtain a crude product, and purifying by column chromatography to obtain the N-H carbonylation product of the N-phenylpyridine-2-amine; the additive is potassium iodide; the ligand is triphenylphosphine; the catalyst is palladium chloride, palladium iodide, palladium bromide, palladium acetate, dichlorodiacetonitrile palladium, palladium trifluoroacetate or bis-triphenylphosphine palladium dichloride; the oxidant is copper acetate, copper bromide, copper chloride, copper sulfate, copper triflate or copper nitrate,
the above reaction is shown in the following formula:
wherein R is 1 Or R is 2 Selected from H, F, cl,3, 4-dimethyl, methyl, methoxy, tert-butyl, trifluoromethyl, nitro, 3, 5-dimethyl, naphthyl or ester groups.
2. A palladium-catalyzed N-H carbonylation of N-phenylpyridine-2-amine with DMF as a methyl source according to claim 1, wherein: the solvent is a mixed solvent of dimethyl sulfoxide (DMSO) and N, N-Dimethylformamide (DMF), wherein the mixed volume ratio of the dimethyl sulfoxide (DMSO) to the N, N-Dimethylformamide (DMF) is 1: 100-100:1.
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