A method for preparing arylamide compounds without catalyst or coupling agent

Abstract

The present invention discloses a method for preparing an arylamide compound without catalyst or coupling agents. In an anhydrous, chlorine-containing organic solvent, an isocyanate and a triarylborane undergo a coupling reaction to obtain the target product. The method uses inexpensive and readily available isocyanate and triarylborane as raw materials and eliminates the need for toxic transition metals and chemically dosed additives such as coupling agents or bases. This reduces production costs and minimizes the emission of environmentally harmful metal salts or halides.

Description

Technical Field

[0001] The invention belongs to the technical field of organic compound synthesis, and particularly relates to a method for preparing an arylamide compound under conditions without a catalyst or a coupling agent. Background Art

[0002] Amide bonds, as important functional groups, are widely present in proteins, peptides, and many bioactive molecules. Two-thirds of candidate drug molecules contain amide bond fragments, and arylamide is also the parent structure of various drugs, such as DEET, remopride, nitazoxanide, indapamide, dexloxicam, nafcillin, bezafibrate, anidulafungin, delavirdine, and cefpiramide. Therefore, the green and efficient preparation of arylamide derivatives using inexpensive and readily available compounds as raw materials has important guiding significance in medicinal chemistry.

[0003]

[0004] In the field of drug synthesis, amidation reactions account for more than 30% of all bond-forming reactions. The current methods for synthesizing arylamide compounds include: (1) dehydration of arylcarboxylic acid and amine under the promotion of chemical dosage of coupling agent to form amide, or activation of carboxylic acid to form carboxylic acid ester, acid anhydride or acid chloride, and then nucleophilic substitution reaction with amine under alkaline conditions to construct amide bond; (2) oxidative coupling reaction of amine with benzyl alcohol (J.Am.Chem.Soc.,2006,128,13064-13065) or aryl aldehyde (Angew.Chem.Int.Ed.,2011,50,8917-8921) under transition metal catalysis to synthesize arylamide derivatives; (3) transition metal catalyzed reaction of formamide with arylcarboxylic acid (Eur.J.Org.Chem.,2013,5737-5742), aryl halide (Org.Lett.,2002,4,2849-2851) or aryl aldehyde (ACS Chem. Catal., 2015, 5, 884-891) and the like undergo coupling reactions; (4) transition metal-catalyzed cross-coupling reactions of isocyanates with aryl Grignard reagents (Angew. Chem. Int. Ed., 2018, 57, 12126-12130), arylboronic acids (Chem. Commun., 2007, 3577-3579), organotin reagents (Chem. Lett., 2004, 33, 1364-1365) to prepare arylamide compounds. However, the above synthesis methods have the disadvantages of cumbersome steps and harsh reaction conditions, and require the addition of additional coupling agents, bases or metal catalysts to promote the reaction, which will produce metal salts or halides that are harmful to the environment, have poor atom economy, and are not in line with the development concept of "green chemistry". Therefore, there is an urgent need in this field for a preparation method that is simple and efficient, does not require the participation of transition metal catalysts and coupling agents, has a wide range of substrate applicability, and uses simple compounds as raw materials to synthesize arylamide compounds in one step. Summary of the Invention

[0005] The purpose of this section is to summarize some aspects of the embodiments of the present invention and briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section and the abstract and title of this application to avoid obscuring the purpose of this section, the abstract and the title of the invention, and such simplifications or omissions should not be used to limit the scope of the present invention.

[0006] In view of the above problems and / or the problems existing in the prior art, the present invention is proposed.

[0007] One of the objects of the present invention is to provide a method for preparing an arylamide compound without a catalyst or a coupling agent.

[0008] To solve the above technical problems, the present invention provides the following technical solution: a method for preparing an arylamide compound under catalyst-free and coupling agent-free conditions, wherein a compound represented by formula I and a compound represented by formula II undergo a coupling reaction in an anhydrous chlorine-containing organic solvent to obtain a compound represented by formula III;

[0009]

[0010] Ar3B (Formula II);

[0011]

[0012] In Formula I and Formula III, R is selected from one of phenyl, 4-tolyl, 4-methoxyphenyl, 4-trifluorotolyl, 4-cyanophenyl, 4-chlorophenyl, 4-nitrophenyl, 4-trifluoromethoxyphenyl, 3-tolyl, 2-chlorophenyl, 3-bromophenyl, 4-methyl-3-chlorophenyl, 1-naphthyl, benzyl, ethyl, n-octyl, and cyclohexyl;

[0013] In formula II and formula III, Ar is selected from one of phenyl, 4-tolyl, 3,4-methylenedioxyphenyl, 4-fluorophenyl, 4-methoxyphenyl, 4-tert-butylphenyl, 2-tolyl, 3-methoxyphenyl, 3,5-dimethylphenyl, 1-naphthyl, 3-methyl-4-methoxyphenyl, and 2-thienyl.

[0014] The chemical equation of the reaction of the present invention is as follows:

[0015]

[0016] As a preferred embodiment of the method for preparing an arylamide compound in the absence of a catalyst and a coupling agent of the present invention, the specific method comprises: adding an isocyanate and a triarylborane to a Schlenk tube equipped with a stirrer, replacing the reaction tube with nitrogen three times, and adding an organic solvent using a syringe under a nitrogen atmosphere, and heating the mixture in an oil bath; after completion of the reaction, cooling to room temperature, concentrating the reaction solution using a rotary evaporator, and then separating and purifying the mixture by silica gel column chromatography to obtain the arylamide compound.

[0017] As a preferred embodiment of the method for preparing aromatic amide compounds in the absence of catalysts and coupling agents of the present invention, the molar volume ratio of the compound represented by formula I, the compound represented by formula II and the chlorine-containing organic solvent is 0.3 mmol: 0.3-0.45 mmol: 1-2.5 mL.

[0018] As a preferred embodiment of the method for preparing aromatic amide compounds in the absence of catalysts and coupling agents of the present invention, the molar volume ratio of the compound represented by formula I, the compound represented by formula II and the chlorine-containing organic solvent is 0.3 mmol:0.36 mmol:1.5 mL.

[0019] As a preferred embodiment of the method for preparing aromatic amide compounds in the absence of a catalyst and a coupling agent of the present invention, the chlorine-containing organic solvent is selected from one or more of dichloromethane, chloroform, chlorobenzene, o-dichlorobenzene, 1,2-dichloroethane, 1,1,2-trichloroethane, and 1,1,2,2-tetrachloroethane.

[0020] As a preferred embodiment of the method for preparing aromatic amide compounds in the absence of a catalyst and a coupling agent, the chlorine-containing organic solvent is 1,1,2-trichloroethane.

[0021] As a preferred embodiment of the method for preparing aromatic amide compounds in the absence of catalyst and coupling agent, the reaction is carried out at a temperature of 100 to 140°C.

[0022] As a preferred embodiment of the method for preparing aromatic amide compounds in the absence of a catalyst and a coupling agent, the reaction is carried out at a temperature of 120°C.

[0023] As a preferred embodiment of the method for preparing aromatic amide compounds in the absence of a catalyst and a coupling agent, the reaction time is 12 to 24 hours.

[0024] As a preferred embodiment of the method for preparing aromatic amide compounds in the absence of a catalyst and a coupling agent, the reaction time is 16 hours.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] This method uses inexpensive and readily available isocyanates and triarylboranes as raw materials, eliminating the need for toxic transition metals and chemically dosed additives such as coupling agents or bases. This reduces production costs and minimizes the emission of environmentally harmful metal salts or halides. The chemical conversion process offers high product yields, good functional group tolerance, and a wide range of substrate applications, meeting the requirements for sustainable synthetic chemistry development. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for describing the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. Those skilled in the art can also derive other drawings based on these drawings without inventive effort. Among them:

[0028] Figure 1 This is the hydrogen nuclear magnetic resonance spectrum of the product of Example 1 of the present invention;

[0029] Figure 2This is the carbon NMR spectrum of the product of Example 1 of the present invention. DETAILED DESCRIPTION

[0030] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific implementation methods of the present invention are described in detail below in conjunction with the embodiments of the specification.

[0031] In the following description, many specific details are set forth to facilitate a full understanding of the present invention. However, the present invention may also be implemented in other ways different from those described herein. Those skilled in the art may make similar generalizations without violating the connotation of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0032] Secondly, the term "one embodiment" or "embodiment" herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The phrase "in one embodiment" appearing in various places throughout this specification does not necessarily refer to the same embodiment, nor does it refer to a separate or selective embodiment that is mutually exclusive of other embodiments.

[0033] Unless otherwise specified, the raw materials used in the examples were purchased commercially.

[0034] Example 1

[0035] To a 10 mL Schlenk tube equipped with a stirrer, p-toluene isocyanate (0.3 mmol, 40.0 mg) and triphenylborane (0.36 mmol, 87.2 mg) were added. The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. The mixture was then purified by silica gel column chromatography (eluent: petroleum ether:ethyl acetate = 4:1) to yield 53.1 mg of a white solid in an 84% yield.

[0036] The product structural formula is:

[0037]

[0038] The above product was characterized and the results were as follows:

[0039] H NMR spectrum data: 1 H NMR (400MHz, CDCl3) δ8.01 (brs, 1H), 7.87-7.83 (m, 2H), 7.55-7.49 (m, 3H), 7.44 (m, 2H), 7.15 (d, J = 8.2Hz, 2H), 2.34 (s, 3H).

[0040] C NMR data:13 C NMR (101MHz, CDCl3) δ165.9, 135.5, 135.1, 134.3, 131.8×2, 129.6×2, 128.8×2, 127.1×2, 120.5, 21.0.

[0041] Example 2

[0042] To a 10 mL Schlenk tube equipped with a stirrer, p-toluene isocyanate (0.3 mmol, 40.0 mg) and tri(4-methylphenyl)borane (0.36 mmol, 102.3 mg) were added. The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. The mixture was then purified by silica gel column chromatography (eluent: petroleum ether:ethyl acetate = 4:1) to yield 41.9 mg of a white solid in a 62% yield.

[0043] The product structural formula is:

[0044]

[0045] The above product was characterized and the results were as follows:

[0046] H NMR spectrum data: 1 H NMR (400MHz, CDCl3) δ8.14(brs,1H),7.74(d,J=8.2Hz,2H),7.53(d,J=8.5Hz ,2H),7.20(d,J=7.9Hz,2H),7.13(d,J=8.3Hz,2H),2.39(s,3H),2.33(s,3H).

[0047] C NMR data: 13 C NMR (101MHz, CDCl3) δ165.9, 142.1, 135.6, 134.0, 132.2, 129.5×2, 129.3×2, 127.2×2, 120.6×2, 21.5, 21.0.

[0048] Example 3

[0049] To a 10 mL Schlenk tube equipped with a stirrer, p-toluene isocyanate (0.3 mmol, 40.0 mg) and tris(5-benzo[d][1,3]dioxa)borane (0.36 mmol, 134.7 mg) were added. The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. The mixture was then purified by column chromatography on silica gel (eluent: petroleum ether:ethyl acetate = 4:1) to yield 61.4 mg of a white solid in 80% yield.

[0050] The product structural formula is:

[0051]

[0052] The above product was characterized and the results were as follows:

[0053] H NMR spectrum data: 1 H NMR (400MHz, CDCl3) δ7.78(s,1H),7.49(d,J=8.0Hz,2H),7.39-7.34(m,2H),7.15(d,J=7.9Hz,2H),6.84(d,J=8.1Hz,1H),6.04(s,2H),2.33(s,3H).

[0054] C NMR data: 13 C NMR (101MHz, CDCl3) δ165.1,150.7,148.2,135.4,134.2,129.7×2,129.3,121.8,120.4×2,108.2,107.8,101.9,21.0.

[0055] Example 4

[0056] To a 10 mL Schlenk tube equipped with a stirrer, p-toluene isocyanate (0.3 mmol, 40.0 mg) and tris(4-fluorophenyl)borane (0.36 mmol, 106.6 mg) were added. The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. The mixture was then purified by column chromatography on silica gel (eluent: petroleum ether:ethyl acetate = 4:1) to yield 39.9 mg of a white solid in a 58% yield.

[0057] The product structural formula is:

[0058]

[0059] The above product was characterized and the results were as follows:

[0060] H NMR spectrum data: 1 H NMR (400MHz, CDCl3) δ7.88-7.85(m,3H),7.49(d,J=8.4Hz,2H),7.17-7.11(m,4H),2.34(s,3H).

[0061] C NMR data: 13 C NMR (101MHz, CDCl3) δ 165.0 (d, J = 252.5Hz), 164.8, 135.3, 134.5, 131.3 (d, J = 3.3Hz), 129.7, 129.6 (d, J = 9.0Hz), 120.6, 115.9 (d, J = 21.9Hz), 21.0.

[0062] NMR fluorine spectrum data: 19 F NMR (376MHz,CDCl3)δ-107.56.

[0063] Example 5

[0064] To a 10 mL Schlenk tube equipped with a stirrer, p-toluene isocyanate (0.3 mmol, 40.0 mg) and tris(4-methoxyphenyl)borane (0.36 mmol, 119.6 mg) were added. The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. The mixture was then purified by column chromatography on silica gel (eluent: petroleum ether:ethyl acetate = 4:1) to yield 56.3 mg of a white solid in a 78% yield.

[0065] The product structural formula is:

[0066]

[0067] The above product was characterized and the results were as follows:

[0068] H NMR spectrum data: 1 H NMR (400MHz, CDCl3) δ8.03(s,1H),7.82(d,J=8.8Hz,2H),7.51(d,J=8Hz,2H),7.13(d,J=8.0Hz,2H),6.90(d,J=8.8Hz,2H),3.84(s,3H),2.33(s,3H).

[0069] C NMR data: 13 C NMR (101MHz, CDCl3) δ165.5, 162.4, 135.6, 134.0, 129.6×2, 129.0×2, 127.2, 120.5×2, 113.9×2, 55.5, 21.0.

[0070] Example 6

[0071] To a 10 mL Schlenk tube equipped with a stirrer, p-toluene isocyanate (0.3 mmol, 40.0 mg) and tris(3-methoxyphenyl)borane (0.36 mmol, 119.6 mg) were added. The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. The mixture was then purified by silica gel column chromatography (eluent: petroleum ether:ethyl acetate = 4:1) to yield 51.2 mg of a white solid in a 71% yield.

[0072] The product structural formula is:

[0073]

[0074] The above product was characterized and the results were as follows:

[0075] H NMR spectrum data: 1 H NMR (400MHz, CDCl3): δ7.86 (s, 1H), 7.52 (d, J = 8.2Hz, 2H), 7.44-7.41 (m, 1H), 7.39 -7.33(m,2H),7.17(d,J=8.1Hz,2H),7.08-7.05(m,1H),3.85(s,3H),2.34(s,3H).

[0076] C NMR data: 13 C NMR (101MHz, CDCl3) δ165.7,160.0,136.7,135.4,134.4,129.8×2,129.7×2,120.4,118.8,118.1×2,112.5,55.6,21.0.

[0077] Example 7

[0078] To a 10 mL Schlenk tube equipped with a stirrer, p-toluene isocyanate (0.3 mmol, 40.0 mg) and tri(1-naphthyl)borane (0.36 mmol, 141.2 mg) were added. The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. The mixture was then purified by column chromatography on silica gel (eluent: petroleum ether:ethyl acetate = 4:1) to yield 47.9 mg of a white solid in a 61% yield.

[0079] The product structural formula is:

[0080]

[0081] The above product was characterized and the results were as follows:

[0082] H NMR spectrum data: 1 H NMR (400MHz, CDCl3): δ7.86 (brs, 1H), 7.52 (d, J = 8.2Hz, 2H), 7.43 (m, 1H), 7.38- 7.36(m,2H),7.17(d,J=8.1Hz,2H),7.087.05(m,1H),3.85(s,3H),2.34(s,3H).

[0083] C NMR data: 13 C NMR (101MHz, CDCl3) δ165.7,160.0,136.7,135.4,134.4,129.8×2,129.7×2,120.4,118.8,118.1×2,112.5,55.6,21.0.

[0084] Example 8

[0085] To a 10 mL Schlenk tube equipped with a stirrer, add p-toluene isocyanate (0.3 mmol, 40.0 mg) and tris(3,5-dimethylphenyl)borane (0.36 mmol, 117.5 mg). The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. Purification followed by silica gel column chromatography (eluent: petroleum ether:ethyl acetate = 4:1) afforded 44.5 mg of a white solid in a 62% yield.

[0086] The product structural formula is:

[0087]

[0088] The above product was characterized and the results were as follows:

[0089] H NMR spectrum data: 1 H NMR (400MHz, CDCl3): δ7.77 (s, 1H), 7.53 (d, J = 8.4Hz, 2H), 7.46 (d, J = 1.5Hz, 2H), 7.18-7.16 (m, 3H), 2.38 (s 6H), 2.34 (s, 3H).

[0090] C NMR data: 13 C NMR (101MHz, CDCl3) δ166.2, 138.6×2, 135.6, 135.2, 134.2, 133.4, 129.7×2, 124.9×2, 120.3×2, 21.4×2, 21.0.

[0091] Example 9

[0092] To a 10 mL Schlenk tube equipped with a stirrer, add p-toluene isocyanate (0.3 mmol, 40.0 mg) and tris(4-tert-butylphenyl)borane (0.36 mmol, 147.8 mg). The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. Purification followed by silica gel column chromatography (eluent: petroleum ether:ethyl acetate = 4:1) afforded 51.3 mg of a white solid in a 64% yield.

[0093] The product structural formula is:

[0094]

[0095] The above product was characterized and the results were as follows:

[0096] H NMR spectrum data: 1 H NMR (400MHz, CDCl3): δ7.83-7.79(m,3H),7.52(d,J=8.4Hz,2H),7.48(d,J=8.5Hz,2H),7.16(d,J=8.2Hz,2H),2.34(s,3H),1.35(s,9H).

[0097] C NMR data: 13C NMR (101MHz, CDCl3) δ165.7, 155.4, 135.6, 134.2, 132.3, 129.7×2, 127.0×2, 125.8×2, 120.3×2, 35.1, 31.3×3, 21.0.

[0098] Example 10

[0099] To a 10 mL Schlenk tube equipped with a stirrer, p-toluene isocyanate (0.3 mmol, 40.0 mg) and tri(2-methylphenyl)borane (0.36 mmol, 102.3 mg) were added. The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. The mixture was then purified by silica gel column chromatography (eluent: petroleum ether:ethyl acetate = 4:1) to yield 42.7 mg of a white solid in a 63% yield.

[0100] The product structural formula is:

[0101]

[0102] The above product was characterized and the results were as follows:

[0103] H NMR spectrum data: 1 H NMR (400MHz, CDCl3) δ7.54(brs,1H),7.50(d,J=8.1Hz,2H),7.45(d,J=7.6Hz,1H),7.3 5(t,J=7.4Hz,1H),7.25-7.21(m,2H),7.17(d,J=8.0Hz,2H),2.49(s,3H),2.35(s,3H).

[0104] C NMR data: 13 C NMR (101MHz, CDCl3) δ168.1,136.7,136.5,135.6,134.3,131.3,130.3,129.7×2,126.7,126.0×2,120.1,21.0,19.9.

[0105] Example 11

[0106] To a 10 mL Schlenk tube equipped with a stirrer, p-toluene isocyanate (0.3 mmol, 40.0 mg) and tris(3-methyl-4-methoxyphenyl)borane (0.36 mmol, 134.7 mg) were added. The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. The mixture was then purified by silica gel column chromatography (eluent: petroleum ether:ethyl acetate = 4:1) to yield 51.8 mg of a white solid in a 68% yield.

[0107] The product structural formula is:

[0108]

[0109] The above product was characterized and the results were as follows:

[0110] H NMR spectrum data: 1 H NMR (400MHz, CDCl3) δ7.76(brs,1H),7.71(dd,J=8.5,2.4Hz,1H),7.66(d,J=1.8Hz,1H),7.52(d,J =8.4Hz,2H),7.16(d,J=8.3Hz,2H),6.86(d,J=8.5Hz,1H),3.89(s,3H),2.34(s,3H),2.26(s,3H).

[0111] C NMR data: 13 C NMR (101MHz, CDCl3) δ165.5,160.7,135.7,134.0,129.7×2,129.6,127.1,126.8,126.5,120.3×2,109.6,55.6,21.0,16.5.

[0112] Example 12

[0113] To a 10 mL Schlenk tube equipped with a stirrer, add p-toluene isocyanate (0.3 mmol, 40.0 mg) and tri(2-thienyl)borane (0.36 mmol, 93.7 mg). The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. Purification followed by silica gel column chromatography (eluent: petroleum ether:ethyl acetate = 4:1) afforded 53.4 mg of a white solid in an 82% yield.

[0114] The product structural formula is:

[0115]

[0116] The above product was characterized and the results were as follows:

[0117] H NMR spectrum data: 1 H NMR (400MHz, CDCl3) δ7.92 (s, 1H), 7.63 (d, J = 3.8Hz, 1H), 7.49 (d, J = 7.9Hz, 3H), 7.14-7.07 (m, 3H), 2.33 (s, 3H).

[0118] C NMR data: 13 C NMR (101MHz, CDCl3) δ160.2,139.6,135.1,134.4,130.7,129.6×2,128.5,127.9×2,120.6,21.0.

[0119] Example 13

[0120] To a 10 mL Schlenk tube equipped with a stirrer, add 4-methoxyphenyl isocyanate (0.3 mmol, 44.7 mg) and triphenylborane (0.36 mmol, 87.2 mg). The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. Purification followed by silica gel column chromatography (eluent: petroleum ether:ethyl acetate = 4:1) afforded 41.5 mg of a white solid in a 61% yield.

[0121] The product structural formula is:

[0122]

[0123] The above product was characterized and the results were as follows:

[0124] H NMR spectrum data: 1 H NMR (400MHz, CDCl3) δ7.86 (d, J = 7.6Hz, 2H), 7.81 (brs, 1H), 7.55-7.52 (m, 3H), 7.49-7.45 (m, 2H), 6.92-6.89 (m, 2H), 3.82 (s, 3H).

[0125] C NMR data: 13C NMR (101MHz, CDCl3) δ156.7, 135.1, 131.8, 131.1, 128.8×2, 127.1×2, 122.3×2, 114.3×2, 55.6.

[0126] Example 14

[0127] To a 10 mL Schlenk tube equipped with a stirrer, add 4-trifluoromethylphenylisocyanate (0.3 mmol, 56.1 mg) and triphenylborane (0.36 mmol, 87.2 mg). The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. Purification followed by silica gel column chromatography (eluent: petroleum ether:ethyl acetate = 4:1) afforded 59.2 mg of a white solid in a 74% yield.

[0128] The product structural formula is:

[0129]

[0130] The above product was characterized and the results were as follows:

[0131] H NMR spectrum data: 1 H NMR (400MHz, DMSO-d6) δ10.59(s,1H),8.03(d,J=8.5Hz,2H),7.98(d,J=7.1Hz,2H),7.72(d,J=8.4Hz,2H),7.64-7.60(m,1H),7.57-7.53(m,2H).

[0132] C NMR data: 13 C NMR (101MHz, DMSO-d6) δ 166.1, 142.9 (d, J = 1.5Hz), 134.5, 132.0, 128.5, 127.8, 126.0 (q, J = 4.0Hz), 123.8, 123.5, 123.1, 120.1.

[0133] NMR fluorine spectrum data: 19 F NMR(376MHz,DMSO-d6)δ-60.24.

[0134] Example 15

[0135] To a 10 mL Schlenk tube equipped with a stirrer, add 4-cyanophenyl isocyanate (0.3 mmol, 43.2 mg) and triphenylborane (0.36 mmol, 87.2 mg). The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. Purification followed by silica gel column chromatography (eluent: petroleum ether:ethyl acetate = 4:1) afforded 42.1 mg of a white solid in a 63% yield.

[0136] The product structural formula is:

[0137]

[0138] The above product was characterized and the results were as follows:

[0139] H NMR spectrum data: 1 H NMR (400MHz, CDCl3) δ8.23(brs,1H),7.87(d,J=7.6Hz,2H),7.81(d,J=8.8Hz,2H),7.64-7.57(m,3H),7.49(t,J=7.6Hz,2H).

[0140] C NMR data: 13 C NMR (101MHz, CDCl3) δ166.1, 142.2, 134.2, 133.4×2, 132.6, 129.1×2, 127.3×2, 120.1×2, 119.0, 107.4.

[0141] Example 16

[0142] To a 10 mL Schlenk tube equipped with a stirrer, add 4-chlorophenyl isocyanate (0.3 mmol, 46.1 mg) and triphenylborane (0.36 mmol, 87.2 mg). The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. Purification followed by silica gel column chromatography (eluent: petroleum ether:ethyl acetate = 4:1) afforded 50.3 mg of a white solid in a 72% yield.

[0143] The product structural formula is:

[0144]

[0145] The above product was characterized and the results were as follows:

[0146] H NMR spectrum data: 1 H NMR (400MHz, DMSO-d6) δ10.38(brs,1H),7.96-7.93(m,2H),7.82(d,J=8.9Hz,2H),7.62-7.58(m,1H),7.56-7.51(m,2H),7.41(d,J=8.9Hz,2H).

[0147] C NMR data: 13 C NMR (101MHz, DMSO-d6) δ165.7, 138.2, 134.7, 131.7, 128.5×2, 128.4×2, 127.7×2, 127.3, 121.8×2.

[0148] Example 17

[0149] To a 10 mL Schlenk tube equipped with a stirrer, add 3-toluene isocyanate (0.3 mmol, 39.9 mg) and triphenylborane (0.36 mmol, 87.2 mg). The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. Purification followed by silica gel column chromatography (eluent: petroleum ether:ethyl acetate = 4:1) afforded 44.6 mg of a white solid in a 70% yield.

[0150] The product structural formula is:

[0151]

[0152] The above product was characterized and the results were as follows:

[0153] H NMR spectrum data: 1 H NMR(400MHz, CDCl3)δ7.91(s,1H),7.86-7.83(m,2H),7.54-7.50(m,2H),7.47-7.40(m ,3H),7.44-7.37(m,1H),7.25-7.21(m,1H),6.95(dd,J=7.6,1.4Hz,1H),2.34(s,3H).

[0154] C NMR data: 13 C NMR (101MHz, CDCl3) δ165.9,139.1,138.0,135.2,131.9,129.0,128.9×2,127.1×2,125.5,121.0,117.4,21.6.

[0155] Example 18

[0156] To a 10 mL Schlenk tube equipped with a stirrer, add 2-chlorophenyl isocyanate (0.3 mmol, 46.1 mg) and triphenylborane (0.36 mmol, 87.2 mg). The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. Purification followed by silica gel column chromatography (eluent: petroleum ether:ethyl acetate = 4:1) afforded 62.6 mg of a white solid in a 90% yield.

[0157] The product structural formula is:

[0158]

[0159] The above product was characterized and the results were as follows:

[0160] H NMR spectrum data: 1 H NMR(400MHz, CDCl3)δ8.58(dd,J=8.3,1.5Hz,1H),8.46(s,1H),7.94-7.92(m,2H),7.61- 7.51(m.1H),7.55-7.51(m,2H),7.44-7.41(s,1H),7.37-7.32(m,1H),7.11-7.07(m,1H).

[0161] C NMR data: 13 C NMR (101MHz, CDCl3) δ165.4,134.9,134.8,132.3,129.2,129.1×2,127.2×2,124.9,123.2,121.6.

[0162] Example 19

[0163] To a 10 mL Schlenk tube equipped with a stirrer, add 3-bromophenyl isocyanate (0.3 mmol, 59.4 mg) and triphenylborane (0.36 mmol, 87.2 mg). The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. Purification followed by silica gel column chromatography (eluent: petroleum ether:ethyl acetate = 4:1) afforded 57.3 mg of a white solid in a 69% yield.

[0164] The product structural formula is:

[0165]

[0166] The above product was characterized and the results were as follows:

[0167] H NMR spectrum data: 1 H NMR (400MHz, CDCl3) δ8.15 (s, 1H), 7.88 (t, J = 2.0Hz, 1H), 7.83-7.80 (m, 2H), 7 .55-7.50(m,2H),7.44-7.40(m,2H),7.26-7.24(m,1H),7.17(t,J=8.0Hz,1H).

[0168] C NMR data: 13 C NMR (101MHz, CDCl3) δ166.1,139.3,134.5,132.2,130.4,128.9×2,127.6,127.2×2,123.4,122.7,119.0.

[0169] Example 20

[0170] To a 10 mL Schlenk tube equipped with a stirrer, add 4-nitrobenzene isocyanate (0.3 mmol, 49.2 mg) and triphenylborane (0.36 mmol, 87.2 mg). The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. Purification followed by silica gel column chromatography (eluent: petroleum ether:ethyl acetate = 4:1) afforded 61.4 mg of a yellow solid in an 84% yield.

[0171] The product structural formula is:

[0172]

[0173] The above product was characterized and the results were as follows:

[0174] H NMR spectrum data: 1 H NMR (400MHz, CDCl3) δ8.28(d,J=9.1Hz,2H),8.08(s,1H),7.91-7.89(m,2H),7.86(d,J=9.2Hz,2H),7.64-7.60(m,1H),7.56-7.52(m,2H).

[0175] C NMR data: 13C NMR (101MHz, CD3OD) δ169.0, 146.4, 144.8, 135.8, 133.4, 129.7×2, 128.8×2, 125.7×2, 121.3×2.

[0176] Example 21

[0177] To a 10 mL Schlenk tube equipped with a stirrer, add 4-trifluoromethoxyphenyl isocyanate (0.3 mmol, 60.9 mg) and triphenylborane (0.36 mmol, 87.2 mg). The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. Purification followed by silica gel column chromatography (eluent: petroleum ether:ethyl acetate = 4:1) afforded 64.8 mg of a white solid in a 77% yield.

[0178] The product structural formula is:

[0179]

[0180] The above product was characterized and the results were as follows:

[0181] H NMR spectrum data: 1 H NMR (400MHz, CD3OD) δ7.94-7.92(m,2H),7.81(d,J=9.1Hz,2H),7.61-7.56(m,1H),7.53-7.49(m,2H),7.27(d,J=8.6Hz,2H).

[0182] C NMR data: 13 C NMR (101MHz, CD3OD) δ 168.9, 146.7 (q, J = 2.1Hz), 139.1, 136.0, 133.0, 129.7, 128.7, 123.4, 122.6, 120.7.

[0183] Example 22

[0184] To a 10 mL Schlenk tube equipped with a stirrer, add 1-naphthyl isocyanate (0.3 mmol, 50.8 mg) and triphenylborane (0.36 mmol, 87.2 mg). The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. Purification followed by silica gel column chromatography (eluent: petroleum ether:ethyl acetate = 4:1) afforded 39.9 mg of a white solid in a 54% yield.

[0185] The product structural formula is:

[0186]

[0187] The above product was characterized and the results were as follows:

[0188] H NMR spectrum data: 1 H NMR (400MHz, CDCl3) δ8.21(brs,1H),8.07(d,J=7.4Hz,1H),8.01(d,J=7.5Hz,2H),7.92(t,J=5.7Hz,2H),7.76(d,J=8.3Hz,1H),7.61-7.52(m,6H).

[0189] C NMR data: 13 C NMR (101MHz, CDCl3) δ166.4,135.0,134.3,132.5,132.1,129.0×2,129.0,127.6,127.3×2,126.6,126.3,126.2,125.9,121.4,120.8.

[0190] Example 23

[0191] To a 10 mL Schlenk tube equipped with a stirrer, add 4-methyl-3-chlorophenyl isocyanate (0.3 mmol, 50.3 mg) and triphenylborane (0.36 mmol, 87.2 mg). The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. Purification followed by silica gel column chromatography (eluent: petroleum ether:ethyl acetate = 4:1) afforded 53.4 mg of a white solid in a 72% yield.

[0192] The product structural formula is:

[0193]

[0194] The above product was characterized and the results were as follows:

[0195] H NMR spectrum data: 1 H NMR (400MHz, CDCl3) δ7.99 (s, 1H), 7.85-7.82 (m, 2H), 7.72 (d, J = 2.3Hz, 1H) ,7.55-7.51(m,1H),7.47-7.39(m,3H),7.17(d,J=8.2Hz,1H),2.34(s,3H).

[0196] C NMR data: 13 C NMR (101MHz, CDCl3) δ165.9,136.8,134.7,134.6,132.3,132.1,131.1,128.9×2,127.2×2,121.1,118.8,19.6.

[0197] Example 24

[0198] To a 10 mL Schlenk tube equipped with a stirrer, benzyl isocyanate (0.3 mmol, 39.9 mg) and triphenylborane (0.36 mmol, 87.2 mg) were added. The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. The mixture was then purified by column chromatography on silica gel (eluent: petroleum ether:ethyl acetate = 4:1) to yield 38.6 mg of a white solid in a 61% yield.

[0199] The product structural formula is:

[0200]

[0201] The above product was characterized and the results were as follows:

[0202] H NMR spectrum data: 1 H NMR (400MHz, CDCl3) δ7.72 (dd, J=8.4, 1.4Hz, 2H), 7.42-7.40 (m, 1H), 7.33 (td, J=7.4, 1. 4Hz,2H),7.27-7.25(m,4H),7.23-7.19(m,1H),6.60(s,1H),4.55(dd,J=5.7,1.8Hz,2H).

[0203] C NMR data: 13C NMR (101MHz, CDCl3) δ167.5, 138.3, 134.4, 131.6, 128.8×2, 128.6×2, 127.9×2, 127.6, 127.1×2, 44.1.

[0204] Example 25

[0205] To a 10 mL Schlenk tube equipped with a stirrer, add ethyl isocyanate (0.3 mmol, 21.3 mg) and triphenylborane (0.36 mmol, 87.2 mg). The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. Purification followed by silica gel column chromatography (eluent: petroleum ether:ethyl acetate = 4:1) afforded 24.5 mg of a white solid in a 55% yield.

[0206] The product structural formula is:

[0207]

[0208] The above product was characterized and the results were as follows:

[0209] H NMR spectrum data: 1 H NMR(400MHz, CDCl3)δ7.77(t,J=1.4Hz,1H),7.75(d,J=1.5Hz,1H),7.51-7.47(m,1H), 7.44-7.38(m,2H),6.22(brs,1H),3.50(qd,J=7.3,5.6Hz,2H),1.25(t,J=7.3Hz,3H).

[0210] C NMR data: 13 C NMR (101MHz, CDCl3) δ167.7, 134.9, 131.5, 128.7×2, 126.9×2, 35.1, 15.0.

[0211] Example 26

[0212] To a 10 mL Schlenk tube equipped with a stirrer, add octyl isocyanate (0.3 mmol, 46.6 mg) and triphenylborane (0.36 mmol, 87.2 mg). The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. Purification followed by silica gel column chromatography (eluent: petroleum ether:ethyl acetate = 4:1) afforded 41.2 mg of a white solid in a 59% yield.

[0213] The product structural formula is:

[0214]

[0215] The above product was characterized and the results were as follows:

[0216] H NMR spectrum data: 1 H NMR (400MHz, CDCl3) δ7.78-7.75(m,2H),7.51-7.46(m,1H),7.44-7.39(m,2H),6.23(brs,1 H),3.44(td,J=7.3,5.7Hz,2H),1.64-1.59(m,2H),1.33-1.26(m,10H),0.90-0.86(m,3H).

[0217] C NMR data: 13 C NMR (101MHz, CDCl3) δ167.7,134.9,131.4,128.6×2,127.0×2,40.2,31.9,29.8,29.4,29.3,27.1,22.7,14.2.

[0218] Example 27

[0219] To a 10 mL Schlenk tube equipped with a stirrer, add cyclohexyl isocyanate (0.3 mmol, 37.6 mg) and triphenylborane (0.36 mmol, 87.2 mg). The reaction tube was purged with nitrogen three times, and 1,1,2-trichloroethane (1.5 mL) was added via syringe under a nitrogen atmosphere. The mixture was heated to 120°C in an oil bath and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and concentrated using a rotary evaporator. Purification followed by silica gel column chromatography (eluent: petroleum ether:ethyl acetate = 4:1) afforded 28.4 mg of a white solid in a 47% yield.

[0220] The product structural formula is:

[0221]

[0222] The above product was characterized and the results were as follows:

[0223] H NMR spectrum data: 1 H NMR (400MHz, CDCl3) δ7.76-7.74(m,2H),7.51-7.47(m,1H),7.45-7.40(m,2H),5.96(s,1H),4.03-3.94 (m,1H),2.06-2.02(m,2H),1.79-1.72(m,2H),1.69-1.64(m,1H),1.49-1.38(m,2H),1.29-1.19(m,3H).

[0224] Example 28

[0225] Example 28 is basically the same as Example 1, except that the solvent and the amount of solvent added are different, as shown in Table 1 below.

[0226] Table 1

[0227]

[0228]

[0229] As can be seen from the data in Table 1, under the same reaction conditions, the product yield is very low when non-chlorine-containing organic solvents such as dimethyl sulfoxide and 1,4-dioxane are used; while the product yield is significantly improved when chlorine-containing organic solvents are used. Among them, the product yield obtained by using 1,1,2-trichloroethane as the solvent is the highest, reaching 84%.

[0230] When 1,1,2-trichloroethane is used as the solvent, the product yield gradually increases with the increase in the amount of 1,1,2-trichloroethane added. However, the amount of 1,1,2-trichloroethane added should not be too much. Excessive 1,1,2-trichloroethane will instead lead to a decrease in the product yield.

[0231] Example 29

[0232] Example 29 is basically the same as Example 1, except that the reaction temperature and reaction time are different, as shown in Table 2 below.

[0233] Table 2

[0234] Reaction temperature (℃) Reaction time (h) Yield (%) Room temperature 24 0 60 24 17 100 24 50 110 16 72 120 16 84 140 16 77 120 24 76 120 20 82 120 12 78 120 8 69

[0235] The data in Table 2 show that the reaction cannot proceed at room temperature, but increasing the reaction temperature facilitates the reaction. When the reaction temperature reaches 120°C, the product yield reaches 84% ​​after 16 hours of reaction. However, the reaction temperature should not be too high. When the reaction temperature is 140°C for 16 hours, the product yield decreases to 77%.

[0236] At a reaction temperature of 120°C, appropriately extending the reaction time is beneficial to the reaction, and the product yield is the highest after 16 hours of reaction. However, further extending the reaction time will lead to a decrease in product yield.

[0237] The invention utilizes isocyanate and triarylborane to generate a coupling reaction in the absence of a catalyst and a coupling agent. The reaction operation is simple and the amide bond can be constructed quickly and efficiently.

[0238] The reaction process of the present invention avoids the use of toxic transition metals and chemically dosed additives such as coupling agents or bases, which not only reduces production costs but also reduces the emission of environmentally harmful metal salts or halides, thereby reducing environmental pollution.

[0239] The present invention uses isocyanate and triarylborane as raw materials, both of which are inexpensive and readily available. This chemical transformation offers high product yields, good functional group tolerance, and a wide range of substrate applications, meeting the requirements for sustainable synthetic chemistry development. It has significant research value and industrial application prospects in the fields of organic synthesis and pharmaceutical synthesis.

[0240] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present invention, which should all be included in the scope of the claims of the present invention.

Claims

1. A method for preparing an arylamide compound without a catalyst or a coupling agent, characterized in that: In an anhydrous chlorine-containing organic solvent, the compound represented by formula I undergoes a coupling reaction with the compound represented by formula II to obtain the compound represented by formula III; (Formula I); (Formula II); (Formula III); In Formula I and Formula III, R is selected from one of phenyl, 4-tolyl, 4-methoxyphenyl, 4-trifluorotolyl, 4-cyanophenyl, 4-chlorophenyl, 4-nitrophenyl, 4-trifluoromethoxyphenyl, 3-tolyl, 2-chlorophenyl, 3-bromophenyl, 4-methyl-3-chlorophenyl, 1-naphthyl, benzyl, ethyl, n-octyl, and cyclohexyl; In formula II and formula III, Ar is selected from one of phenyl, 4-tolyl, 3,4-methylenedioxyphenyl, 4-fluorophenyl, 4-methoxyphenyl, 4-tert-butylphenyl, 2-tolyl, 3-methoxyphenyl, 3,5-dimethylphenyl, 1-naphthyl, 3-methyl-4-methoxyphenyl, and 2-thienyl; The chlorine-containing organic solvent is selected from one or more of dichloromethane, chloroform, chlorobenzene, o-dichlorobenzene, 1,2-dichloroethane, 1,1,2-trichloroethane, and 1,1,2,2-tetrachloroethane.

2. The method for preparing an arylamide compound without a catalyst or a coupling agent according to claim 1, wherein: The molar volume ratio of the compound represented by formula I, the compound represented by formula II and the chlorine-containing organic solvent is 0.3 mmol: 0.3-0.45 mmol: 1-2.5 mL.

3. The method for preparing an arylamide compound without a catalyst or a coupling agent as claimed in claim 2, wherein: The molar volume ratio of the compound represented by formula I, the compound represented by formula II and the chlorine-containing organic solvent is 0.3 mmol:0.36 mmol:1.5 mL.

4. The method for preparing an arylamide compound without a catalyst or a coupling agent according to claim 1, wherein: The chlorine-containing organic solvent is 1,1,2-trichloroethane.

5. The method for preparing an arylamide compound without a catalyst or a coupling agent according to any one of claims 1 to 3, wherein: The reaction is carried out at a temperature of 100-140°C.

6. The method for preparing an arylamide compound without a catalyst or a coupling agent according to claim 5, wherein: The reaction was carried out at a temperature of 120°C.

7. The method for preparing an arylamide compound without a catalyst or a coupling agent according to any one of claims 1 to 3 and 6, characterized in that: The reaction time is 12 to 24 hours.

8. The method for preparing an arylamide compound in the absence of a catalyst and a coupling agent as claimed in claim 7, wherein: The reaction time was 16 hours.

9. The method for preparing an arylamide compound in the absence of a catalyst or a coupling agent according to any one of claims 1 to 3, 6, and 8, wherein: The method also includes the step of purifying the obtained compound.

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