Aryl amide derivative containing quaternary carbon center by taking aryl amide and Grignard reagent as raw materials and preparation method of aryl amide derivative

Abstract

The invention provides an aryl amide derivative containing a quaternary carbon center, which takes aryl amide and a Grignard reagent as raw materials, and a preparation method of the aryl amide derivative, and solves the problems that the existing aryl amide para-quaternary carbon center synthesis strategy is low in synthesis efficiency, isomerized byproducts are difficult to avoid, the product separation and purification difficulty is high, and the reaction conditions are harsh. The method comprises the following steps: in an inert atmosphere, by taking aryl amide and a tert-butylmagnesium chloride Grignard reagent as raw materials, chloralkane as an additive and tetrahydrofuran, 2-methyltetrahydrofuran, n-hexane or 1, 4-dioxane as a reaction solvent, stirring at normal temperature to react under the action of an iron catalyst, quenching after the reaction is completed, and separating to obtain the aryl amide and tert-butylmagnesium chloride compound. And separating and purifying to obtain the aryl amide derivative of which the para-position is the quaternary carbon center.

Description

Technical Field

[0001] The present invention belongs to the technical field of the construction of quaternary carbon compounds of arylamides, and particularly relates to an arylamide derivative containing a quaternary carbon center with arylamide and Grignard reagent as raw materials and a preparation method thereof. Background Art

[0002] Aryl amide compounds, as important pharmaceutical synthetic intermediates, are widely used in the fields of medicinal chemistry, material chemistry, organic synthetic chemistry, etc. In the development of arylamide drugs, C-H bond functionalization often requires pre-functionalization, which is cumbersome and costly, and has obvious deficiencies in constructing complex molecular structures. If the C-H bond can be directly activated by a catalyst, the functionalization of arylamide can be achieved without pre-functionalization. However, the current synthetic strategies using transition metal catalytic systems to construct the para quaternary carbon center of arylamide have problems such as low synthetic efficiency, inevitable isomerization by-products, difficult separation and purification of products, and harsh reaction conditions. Therefore, it is of great practical significance to develop a method for highly selective construction of the para quaternary carbon center of arylamide with atom economy, step economy, high selectivity, and mild reaction conditions. Summary of the Invention

[0003] In order to solve the deficiencies of the prior art, the purpose of the present invention is to provide an arylamide derivative containing a quaternary carbon center with arylamide and Grignard reagent as raw materials and a preparation method thereof. This method is a method for constructing a para quaternary carbon center by the reaction of iron-catalyzed C-H bond cleavage of arylamide with tert-butylmagnesium chloride Grignard reagent.

[0004] To achieve the above purpose, the technical solution provided by the present invention is as follows:

[0005] A preparation method of an arylamide derivative containing a quaternary carbon center, which is characterized in that:

[0006] Under an inert atmosphere, using arylamide and tert-butylmagnesium chloride Grignard reagent as raw materials (wherein, arylamide is the substrate, and Grignard reagent is the quaternary carbon source, also serving as an alkylating agent and a reducing agent), using chloroalkane as an additive (participating in the iron-catalyzed cycle), using tetrahydrofuran, 2-methyltetrahydrofuran, n-hexane or 1,4-dioxane as the reaction solvent, reacting under the action of an iron catalyst with stirring at room temperature, quenching after the reaction is completed, and separating and purifying to obtain an arylamide derivative with a quaternary carbon center at the para position (i.e., the product of constructing the para quaternary carbon center of arylamide).

[0007] The synthesis general formula is as follows:

[0008]

[0009] Wherein, both R1 and R2 are aliphatic groups or aromatic groups.

[0010] Further, the molar ratio of the arylamide, chloroalkane, and Grignard reagent is 1:3:4 - 6, preferably 1:3:5;

[0011] The dosage ratio of the reaction solvent to the arylamide is 2.5 - 5:1 (mL:mmol), that is, 2.5 - 5 mL of the reaction solvent is required for each millimole of the arylamide, preferably 5:1 (mL:mmol);

[0012] The dosage of the iron catalyst is 5 - 10% of the amount of substance of the arylamide, preferably 5%.

[0013] Further, the reaction time is 24 - 48 h; thin-layer chromatography is used for tracking during the reaction process.

[0014] Further, the chloroalkane is chloro-isobutane, chloro-n-butane, chloro-isopropane, or chloro-neopentane;

[0015] The iron catalyst is ferric chloride, ferrous chloride, iron(III) trifluoromethanesulfonate, or iron(III) acetylacetonate.

[0016] Further, the specific operation of separation and purification is to first extract with ethyl acetate, then dry with anhydrous Na2SO4, filter, reduce the pressure, and finally purify by column chromatography to obtain arylamide derivatives containing a quaternary carbon center at the para position.

[0017] Further, when the arylamide is a compound of formula I, the product is a compound of formula I';

[0018]

[0019] In formula I and I', R1 is 2-methoxy, 2-dimethylamino, 1,4-benzodioxane.

[0020] Further, when the arylamide is a compound of formula II, the product is a compound of formula II';

[0021]

[0022] In formula II and II', R2 is 2-methoxy, 3-fluoro, 3-methoxy, 3-oxophenyl, 3-oxobenzyl, 2-methoxy-5-fluoro, 2,3-dimethoxy, 2,3-methylenedioxy.

[0023] Further, when the arylamide is a compound of formula III, the product is a compound of formula III';

[0024]

[0025] Among them, R3 is 2-methoxy, 3-methoxy.

[0026] Meanwhile, the present invention also provides arylamide derivatives containing a quaternary carbon center prepared by the above method.

[0027] The advantages of the present invention are as follows:

[0028] 1. For the first time, the present invention realizes the construction of a quaternary carbon center with high selectivity at the para-position C-H bond of arylamide by reacting for 24 - 48 h at room temperature under the action of a cheap metal iron catalyst. The low-spin state and spin crossover effect of the iron catalyst enable it to rapidly achieve redox reactions under mild conditions. After the arylamide molecule reacts with the Grignard reagent to form an imine intermediate, the strong adsorption ability and orbital interaction of the iron catalyst can coordinate with the imine intermediate, activate the para-position C-H bond, thereby increasing the collision probability with the Grignard reagent molecule, and thus improving the reaction selectivity and yield. This reaction system has the advantages of low cost, mild reaction conditions, easy separation and purification of products, high reaction yield, high selectivity, etc., and avoids the use of precious metal catalysts and additional ligands.

[0029] 2. Various raw materials of the present invention are easily available, the operation is simple, the yield is considerable, and it has good application prospects.

[0030] 3. Using arylamide and tert-butylmagnesium chloride Grignard reagent as raw materials, the present invention synthesizes arylamide compounds containing a quaternary carbon structure at the para-position, which play an important role in medicinal chemistry and organic synthetic chemistry, and can be applied to the construction of a quaternary carbon center with high selectivity at the para-position of arylamide derivatives with different substituents. Specific Embodiments

[0031] The following further describes the content of the present invention in detail with specific embodiments:

[0032] The present invention realizes the construction reaction of a quaternary carbon center at the para-position of arylamide by using an iron catalyst. The specific synthesis method of arylamide derivatives containing a quaternary carbon center is as follows:

[0033] Under an inert atmosphere, 0.4 mmol of arylamide, 5 - 10% of the amount of substance of the iron catalyst (such as ferric chloride, ferrous chloride, iron trifluoromethanesulfonate, ferrous acetylacetonate) based on the amount of substance of arylamide, 1.2 mmol of chloroalkane (such as chloro-isobutane, chloro-n-butane, chloro-isopropane, chloro-neopentane), 1.6 - 2.4 mmol of tert-butylmagnesium chloride Grignard reagent, and 2 mL of reaction solvent (such as tetrahydrofuran, 2-methyltetrahydrofuran, n-hexane, 1,4-dioxane) are reacted at room temperature for 24 - 48 h, and the reaction is monitored by TLC.

[0034] After the reaction is complete, pour the reactants into 10 - 30 mL of saturated ammonium chloride aqueous solution, and extract with 20 - 30 mL of ethyl acetate in portions. Then dry over anhydrous Na2SO4, filter, remove the solvent under reduced pressure, and purify by flash silica gel column chromatography (ethyl acetate / petroleum ether = 1∶10 - 20) to obtain the product.

[0035] Example 1

[0036] 4-tert-Butyl-N-phenylbenzamide

[0037]

[0038] Under an argon atmosphere, add ferrous chloride (0.02 mmol), N-phenylbenzamide (0.4 mmol), and chloro-iso-butane (1.2 mmol) to tetrahydrofuran (2 mL). Slowly add dropwise 1.0 mL of a 2 mol / L solution of tert-butylmagnesium chloride in tetrahydrofuran at room temperature. After the addition is complete, stir the reaction at room temperature for 48 hours. Add 30 mL of saturated ammonium chloride aqueous solution to quench the reaction. Extract with ethyl acetate (10 mL each time, 3 times). Combine the extracts, add anhydrous sodium sulfate for drying, and separate the product by column chromatography using petroleum ether∶ethyl acetate = 10∶1 as the eluent to obtain 4-tert-butyl-N-phenylbenzamide with a yield of 97%.

[0039] The spectral data of the obtained product are as follows:

[0040] 1 H NMR(500MHz,CDCl3):δ=8.01(s,1H),7.81(d,J=8.4Hz,2H),7.65(d,J=8.0Hz,2H),7.46(d,J=8.3Hz,2H),7.35(t,J=7.9Hz,2H),7.14(t,J=7.4Hz,1H),1.35(s,9H).

[0041] 13 C NMR(125MHz,CDCl3):δ=165.8,155.3,138.1,132.0,129.0,126.9,125.6,124.4,120.2,34.9,31.1.

[0042] Example 2

[0043] 4-tert-Butyl-N-(4-methoxyphenyl)-benzamide

[0044]

[0045] Under an argon atmosphere, (0.02 mmol) iron(III) chloride, (0.4 mmol) N-(4-methoxyphenyl)-benzamide, and (1.2 mmol) chloro-isobutane were added to tetrahydrofuran (2 mL). A 0.8 mL tetrahydrofuran solution of 2 mol / L tert-butylmagnesium chloride was slowly added dropwise at room temperature. After the addition was complete, the reaction mixture was stirred at room temperature for 24 hours. The reaction was quenched by adding 10 mL of saturated ammonium chloride aqueous solution. The mixture was extracted with ethyl acetate (10 mL each time, 3 times). The combined extracts were dried over anhydrous sodium sulfate and separated by column chromatography using petroleum ether∶ethyl acetate = 10∶1 as the eluent to obtain 4-tert-butyl-N-(4-methoxyphenyl)-benzamide.

[0046] The spectral data of the obtained product are as follows:

[0047] 1 1H NMR (400 MHz, CDCl3): δ = 8.09 (s, 1H), 7.79 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 9.0 Hz, 2H), 7.42 (d, J = 8.5 Hz, 2H), 6.85 (d, J = 8.9 Hz, 2H), 3.78 (s, 3H), 1.33 (s, 9H).

[0048] 13 13C NMR (100 MHz, CDCl3): δ = 165.7, 156.4, 155.1, 132.0, 131.2, 126.9, 125.5, 122.2, 114.1, 55.4, 34.9, 31.1.

[0049] Example 3

[0050] 4-tert-butyl-N-(4-fluorophenyl)-benzamide

[0051]

[0052] Under an argon atmosphere, (0.02 mmol) iron(II) chloride, (0.4 mmol) N-(4-fluorophenyl)-benzamide, and (1.2 mmol) chloro-isobutane were added to n-hexane (2 mL). A 1.2 mL tetrahydrofuran solution of 2 mol / L tert-butylmagnesium chloride was slowly added dropwise at room temperature. After the addition was complete, the reaction mixture was stirred at room temperature for 48 hours. The reaction was quenched by adding 20 mL of saturated ammonium chloride aqueous solution. The mixture was extracted with ethyl acetate (10 mL each time, 3 times). The combined extracts were dried over anhydrous sodium sulfate and separated by column chromatography using petroleum ether∶ethyl acetate = 10∶1 as the eluent to obtain 4-tert-butyl-N-(4-fluorophenyl)-benzamide with a yield of 55%.

[0053] The spectral data of the obtained product are as follows:

[0054] 1 1H NMR (500 MHz, CDCl3): δ = 8.00 (s, 1H), 7.79 (d, J = 8.2 Hz, 2H), 7.58 (dd, J = 8.9, 4.8 Hz, 2H), 7.46 (d, J = 8.2 Hz, 2H), 7.02 (t, J = 8.6 Hz, 2H), 1.34 (s, 9H).

[0055] 13 13C NMR (125 MHz, CDCl3): δ = 165.9, 160.4, 158.5, 155.5, 134.0, 131.7, 126.9, 125.6, 122.2, 115.7, 115.5, 34.9, 31.1.

[0056] 19 19F NMR (471 MHz, CDCl3): δ = -117.82.

[0057] Example 4

[0058] 4-tert-Butyl-N-(1-naphthyl)-benzamide

[0059]

[0060] Under an argon atmosphere, ferrous chloride (0.02 mmol), N-(1-naphthyl)-benzamide (0.4 mmol), and chloro-isobutane (1.2 mmol) were added to tetrahydrofuran (2 mL). A 2-methyltetrahydrofuran solution of 1.2 mL of 2 mol / L tert-butylmagnesium chloride was slowly added dropwise at room temperature. After the addition was complete, the reaction was stirred at room temperature for 48 hours. The reaction was quenched by adding 30 mL of saturated aqueous ammonium chloride solution. The mixture was extracted with ethyl acetate (10 mL each time, 3 times). The combined extracts were dried over anhydrous sodium sulfate. The product was separated by column chromatography using petroleum ether∶ethyl acetate = 10∶1 as the eluent to obtain 4-tert-butyl-N-(1-naphthyl)-benzamide with a yield of 63%.

[0061] The spectral data of the obtained product are as follows:

[0062] 1 1H NMR (400 MHz, CDCl3): δ = 8.56 (s, 1H), 7.86 (d, J = 8.6 Hz, 4H), 7.81 (d, J = 7.4 Hz, 1H), 7.69 (d, J = 8.2 Hz, 1H), 7.49–7.37 (m, 5H), 1.38 (s, 9H).

[0063] 1313C NMR (100 MHz, CDCl3): δ = 166.2, 155.5, 134.1, 132.5, 131.9, 128.8, 127.5, 127.1, 126.3, 126.0, 125.8, 121.2, 120.8, 35.0, 31.1.

[0064] Example 5

[0065] 4-tert-Butyl-N-(2-naphthyl)-benzamide

[0066]

[0067] Under an argon atmosphere, ferrous chloride (0.02 mmol), N-(2-naphthyl)-benzamide (0.4 mmol), and n-butyl chloride (1.2 mmol) were added to tetrahydrofuran (2 mL). A 1.2 mL tetrahydrofuran solution of 2 mol / L tert-butylmagnesium chloride was slowly added dropwise at room temperature. After the addition was complete, the reaction mixture was stirred at room temperature for 48 hours. The reaction was quenched by adding 30 mL of saturated aqueous ammonium chloride solution. The mixture was extracted with ethyl acetate (10 mL each time, 3 times). The combined extracts were dried over anhydrous sodium sulfate and separated by column chromatography using petroleum ether∶ethyl acetate = 10∶1 as the eluent to obtain 4-tert-butyl-N-(2-naphthyl)-benzamide with a yield of 50%.

[0068] Spectral data of the obtained product:

[0069] 1 1H NMR (500 MHz, CDCl3): δ = 8.51 (s, 1H), 8.34 (s, 1H), 7.87 (d, J = 8.4 Hz, 2H), 7.76 (dd, J = 10.7, 8.2 Hz, 2H), 7.70 (d, J = 7.3 Hz, 1H), 7.65 (dd, J = 8.8, 2.2 Hz, 1H), 7.41 (dd, J = 7.8, 5.1 Hz, 4H), 1.33 (s, 9H).

[0070] 13 13C NMR (125 MHz, CDCl3): δ = 166.1, 155.3, 135.6, 133.8, 131.9, 130.6, 128.6, 127.6, 127.4, 127.0, 126.3, 125.5, 124.9, 120.4, 117.2, 34.8, 31.0.

[0071] Example 6

[0072] 2-Dimethylamino-4-tert-butyl-N-phenyl-benzamide

[0073]

[0074] Under an argon atmosphere, ferrous chloride (0.02 mmol), 2-dimethylamino-N-phenylbenzamide (0.4 mmol), and chloro-isobutane (1.2 mmol) were added to tetrahydrofuran (2 mL). A 1.2 mL tetrahydrofuran solution of 2 mol / L tert-butylmagnesium chloride was slowly added dropwise at room temperature. After the addition was complete, the reaction mixture was stirred at room temperature for 48 hours. The reaction was quenched by adding 20 mL of saturated ammonium chloride aqueous solution. The mixture was extracted with ethyl acetate (10 mL each time, 3 times). The combined extracts were dried over anhydrous sodium sulfate. The product was separated by column chromatography using petroleum ether∶ethyl acetate = 10∶1 as the eluent to obtain 2-dimethylamino-4-tert-butyl-N-benzamide with a yield of 64%.

[0075] The spectral data of the obtained product are as follows:

[0076] 1 H NMR(500MHz,CDCl3):δ=12.24(s,1H),8.20(d,J=8.2Hz,1H),7.68(d,J=8.4Hz,2H),7.38–7.34(m,2H),7.30(d,J=9.8Hz,2H),7.11(d,J=8.7Hz,1H),2.84(s,6H),1.35(s,9H).

[0077] 13 C NMR(125MHz,CDCl3):δ=164.1,156.1,151.8,139.0,131.4,129.0,124.9,123.6,122.3,120.0,117.1,45.5,35.1,31.1.

[0078] Example 7

[0079] 2-Methoxy-4-tert-butyl-N-phenylbenzamide

[0080]

[0081] Under an argon atmosphere, (0.02 mmol) ferrous chloride, (0.4 mmol) 2-methoxy-N-phenylbenzamide, and (1.2 mmol) chloro-isobutane were added to tetrahydrofuran (2 mL). At room temperature, 1.2 mL of a 2 mol / L solution of tert-butylmagnesium chloride in tetrahydrofuran was slowly added dropwise. After the addition was complete, the reaction mixture was stirred at room temperature for 48 hours. The reaction was quenched by adding 20 mL of saturated ammonium chloride aqueous solution. The mixture was extracted with ethyl acetate (10 mL each time, 3 times). The combined extracts were dried over anhydrous sodium sulfate and separated by column chromatography using petroleum ether∶ethyl acetate = 10∶1 as the eluent to obtain the product with a yield of 52%.

[0082] The spectral data of the obtained product are as follows:

[0083] 1 H NMR(500MHz,CDCl3):δ=9.73(s,1H),8.13(d,J=8.3Hz,1H),7.60(d,J=7.4Hz,2H),7.27(t,J=7.8Hz,2H),7.08(d,J=8.2Hz,1H),7.05–7.02(m,1H),6.95(s,1H),3.99(s,3H),1.28(s,9H).

[0084] 13 C NMR(125MHz,CDCl3):δ=163.3,157.4,157.0,138.5,132.2,128.9,124.0,120.4,119.1,118.9,108.7,56.1,35.8,31.1.

[0085] Example 8

[0086] 3-Oxo-phenyl-4-tert-butyl-N-(1-naphthyl)-benzamide

[0087]

[0088] Under an argon atmosphere, (0.02 mmol) ferrous chloride, (0.4 mmol) 3-oxo-phenyl-N-(1-naphthyl)-benzamide, and (1.2 mmol) chloro-isobutane were added to tetrahydrofuran (2 mL). At room temperature, 1.2 mL of a 2 mol / L solution of tert-butylmagnesium chloride in tetrahydrofuran was slowly added dropwise. After the addition was complete, the reaction mixture was stirred at room temperature for 48 hours. The reaction was quenched by adding 20 mL of saturated ammonium chloride aqueous solution. The mixture was extracted with ethyl acetate (10 mL each time, 3 times). The combined extracts were dried over anhydrous sodium sulfate and separated by column chromatography using petroleum ether∶ethyl acetate = 10∶1 as the eluent to obtain 3-oxo-phenyl-4-tert-butyl-N-(1-naphthyl)-benzamide with a yield of 69%.

[0089] Spectral data of the obtained product:

[0090] 1 H NMR (500 MHz, CDCl3): δ = 8.12 (s, 1H), 7.97 (d, J = 7.4 Hz, 1H), 7.87 (d, J = 9.3 Hz, 1H), 7.77 (d, J = 9.1 Hz, 1H), 7.71 (d, J = 7.5 Hz, 1H), 7.62 (d, J = 6.0 Hz, 1H), 7.54 (d, J = 8.2 Hz, 1H), 7.48 (dd, J = 8.6, 5.2 Hz, 3H), 7.45 (d, J = 5.3 Hz, 1H), 7.37 (t, J = 7.8 Hz, 2H), 7.15–7.11 (m, 1H), 7.05 (d, J = 7.6 Hz, 2H), 1.50 (s, 9H).

[0091] 13 C NMR (125 MHz, CDCl3): δ = 165.4, 156.9, 156.6, 145.0, 134.1, 133.9, 132.3, 130.0, 128.8, 127.8, 127.2, 126.3, 126.0, 125.9, 125.7, 123.4, 121.2, 120.9, 120.5, 119.1, 118.4, 35.2, 29.9.

[0092] Example 9

[0093] 2,3-Dimethoxy-4-tert-butyl-N-(1-naphthyl)-benzamide

[0094]

[0095] Under an argon atmosphere, ferrous chloride (0.02 mmol), 2,3-dimethoxy-N-(1-naphthyl)-benzamide (0.4 mmol), and chloro-iso-butane (1.2 mmol) were added to tetrahydrofuran (2 mL). A 0.8 mL tetrahydrofuran solution of 2 mol / L tert-butylmagnesium chloride was slowly added dropwise at room temperature. After the addition was complete, the reaction was stirred at room temperature for 48 hours. The reaction was quenched by adding 10 mL of saturated ammonium chloride aqueous solution. The mixture was extracted with ethyl acetate (10 mL each time, 3 times). The combined extracts were dried over anhydrous sodium sulfate and separated by column chromatography using petroleum ether∶ethyl acetate = 10∶1 as the eluent to obtain 2,3-dimethoxy-4-tert-butyl-N-(1-naphthyl)-benzamide.

[0096] Spectral data of the obtained product:

[0097] 11H NMR (500 MHz, CDCl3): δ = 10.62 (s, 1H), 8.46 (d, J = 8.7 Hz, 1H), 8.03 (d, J = 8.8 Hz, 1H), 7.98 (d, J = 8.5 Hz, 1H), 7.92 (d, J = 6.6 Hz, 1H), 7.71 (d, J = 7.0 Hz, 1H), 7.60 (t, J = 6.9 Hz, 1H), 7.56 (t, J = 7.2 Hz, 2H), 7.27 (d, J = 3.1 Hz, 1H), 4.11 (s, 3H), 4.04 (s, 3H), 1.45 (s, 9H).

[0098] 13 13C NMR (125 MHz, CDCl3): δ = 163.2, 152.6, 151.9, 148.7, 134.1, 133.3, 128.9, 126.3, 126.2, 126.1, 125.8, 125.7, 125.1, 124.8, 122.7, 120.1, 119.2, 61.1, 60.4, 35.5, 30.3.

[0099] In addition to the above embodiments, other arylamides can be used as raw materials to prepare corresponding compounds for constructing quaternary carbon at the para-position of arylamide by the method of the present invention. Specifically, under an inert atmosphere, the arylamide, chloro-isobutane and an iron catalyst are added to a reaction solvent, and tert-butylmagnesium chloride Grignard reagent is dropped in, and the reaction is stirred at room temperature for 24 - 48 h. After the reaction is completed, it is quenched, separated and purified to obtain the corresponding target product.

[0100] As mentioned above, the above are only specific embodiments of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art in the technical field disclosed by the present invention can easily think of various equivalent modifications or substitutions within the technical scope disclosed by the present invention, and these modifications or substitutions should be covered within the protection scope of the present invention.

Claims

1. A method for preparing an arylamide derivative containing a quaternary carbon center, characterized in that: Under an inert atmosphere, using an arylamide and a tert-butylmagnesium chloride Grignard reagent as raw materials, a chloroalkane as an additive, and tetrahydrofuran, 2-methyltetrahydrofuran, n-hexane or 1,4-dioxane as a reaction solvent, reacting with stirring at room temperature under the action of an iron catalyst, quenching after the reaction is completed, and separating and purifying to obtain an arylamide derivative with a quaternary carbon center at the para position.

2. The method for preparing an arylamide derivative containing a quaternary carbon center according to claim 1, characterized in that: The molar ratio of the arylamide, the chloroalkane and the tert-butylmagnesium chloride Grignard reagent is 1∶3∶4-6; The dosage ratio of the reaction solvent to the arylamide is 2.5-5∶1 (mL∶mmol); The dosage of the iron catalyst is 5-10% of the amount of the arylamide substance.

3. The method for preparing an arylamide derivative containing a quaternary carbon center according to claim 1 or 2, characterized in that: The reaction time is 24-48 h, and thin-layer chromatography is used for tracking during the reaction process.

4. The method for preparing an arylamide derivative containing a quaternary carbon center according to claim 3, characterized in that: The chloroalkane is chloro-isobutane, chloro-n-butane, chloro-isopropane or chloro-neopentane; The iron catalyst is ferric chloride, ferrous chloride, iron(III) trifluoromethanesulfonate or iron(III) acetylacetonate.

5. The method for preparing an arylamide derivative containing a quaternary carbon center according to claim 4, characterized in that: The specific operation of separation and purification is to first extract with ethyl acetate, then dry with anhydrous Na2SO4, filter, reduce the pressure, and finally purify by column chromatography to obtain an arylamide derivative with a quaternary carbon center at the para position.

6. The preparation method according to claim 1, characterized in that: When the arylamide is a compound of formula I, the product is a compound of formula I'; Among them, R1 is 2-methoxy, 2-dimethylamino, 1,4-benzodioxane.

7. The preparation method according to claim 1, characterized in that: When the arylamide is a compound of formula II, the product is a compound of formula II'; Among them, R2 is 2-methoxy, 3-fluoro, 3-methoxy, 3-oxophenyl, 3-oxobenzyl, 2-methoxy-5-fluoro, 2,3-dimethoxy, 2,3-methylenedioxy.

8. The preparation method according to claim 1, characterized in that: When the arylamide is a compound of formula III, the product is a compound of formula III'; Among them, R3 is 2-methoxy, 3-methoxy.

9. Aryl amide derivatives containing quaternary carbon centers, characterized in that: Obtained by using the preparation method described in any one of claims 1-8.

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