A method for the preparation of primary amides from carboxylic acids mediated by bromodifluoroacetamides

Abstract

The application discloses a method for preparing primary amide by using bromine difluoroacetamide to mediate carboxylic acid, and relates to the technical field of organic synthesis. The method effectively solves the problem of poor direct condensation reactivity in the traditional route, and does not need to use expensive condensing agents or metal catalysts, thereby avoiding the harsh requirement of the acyl chloride method on anhydrous operation. The method exhibits excellent reaction efficiency and wide substrate universality under an air atmosphere, and has good compatibility with acid-sensitive groups. Notably, the reaction condition is mild, special equipment and anhydrous and anaerobic control are not needed, and post-treatment is simple, so that the production cost and waste discharge are significantly reduced. The above advantages jointly provide a practical and sustainable green synthesis route for the large-scale preparation of primary amide compounds.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, specifically to a method for preparing primary amides from carboxylic acids mediated by bromodifluoroacetamide. Background Technology

[0002] Amide bonds are among the most fundamental and stable structural units in organic chemistry, widely found in natural products, drug molecules, functional materials, and polymers. More than a quarter of known drug molecules, as well as the vast majority of peptides and proteins, contain amide structures. Therefore, developing efficient, green, and atom-economical amide synthesis methods is a research hotspot and core challenge in the fields of synthetic chemistry and medicinal chemistry.

[0003] The synthesis of primary amides is more challenging than that of secondary and tertiary amides, primarily due to the limited selectivity of nitrogen sources and inherent obstacles in the reaction pathway. Secondary and tertiary amides can be obtained by direct condensation of various alkylamines or aromatic amines with carboxylic acids, while the synthesis of primary amides almost entirely depends on ammonia or amino anions. Both have insurmountable drawbacks: ammonia has weak nucleophilicity, making it difficult to directly attack the carbonyl carbon of carboxylic acids, and it readily undergoes acid-base neutralization with carboxylic acids to form thermodynamically stable ammonium carboxylate salts, which are difficult to further dehydrate into the target primary amide; although amino anions have extremely strong nucleophilicity, their alkali metal salts have extremely poor solubility in conventional organic solvents, hindering their application in homogeneous reactions.

[0004] To enhance reactivity, traditional methods for preparing primary amides often require the use of liquid ammonia or are carried out in high-pressure, closed systems, which are cumbersome and pose safety hazards. Catalytic methods developed in recent years using urea as an alternative ammonia source exhibit extremely low reactivity towards aromatic carboxylic acids, typically requiring high temperatures and long reaction times, and have limited substrate versatility. Other catalytic methods, due to the use of metal catalysts, make it difficult to control reaction costs.

[0005] In addition, other existing methods for preparing primary amides from carboxylic acids also have many problems: direct condensation requires high-temperature heating, which easily leads to product decomposition and is not suitable for heat-sensitive substrates; the acyl chloride method has high activity but is sensitive to moisture, has harsh operation, and is not friendly to acid-sensitive groups; the condensing agent method has mild conditions but expensive reagents, and byproducts are difficult to separate, increasing production costs and waste emissions; the enzyme catalysis method has mild conditions but a limited substrate spectrum, and cannot be promoted as a general method; the nitrile hydrolysis method has lengthy steps, and improper control of hydrolysis conditions can easily lead to over-hydrolysis, affecting the yield.

[0006] In summary, developing a method that can efficiently and universally convert various carboxylic acids directly into primary amides under mild conditions is a technical challenge that urgently needs to be solved in the field of organic synthesis. Summary of the Invention

[0007] The purpose of this invention is to provide a method for preparing primary amides from carboxylic acids mediated by bromodifluoroacetamide, so as to solve the technical problems mentioned in the background art.

[0008] To achieve the above objectives, the present invention provides the following technical solution: a method for preparing primary amides from carboxylic acids mediated by bromodifluoroacetamide, using bromodifluoroacetamide as an activating agent for carboxylic acids and an ammonia source for amidation, acetone as a solvent, water as a co-solvent, and cesium carbonate as a base, converting carboxylic acids into primary amides in an air atmosphere at 90°C, specifically including the following steps: S1: Feeding: Add carboxylic acid, bromodifluoroacetamide, and cesium carbonate to a reaction tube equipped with a magnetic stirrer. The molar ratio of carboxylic acid, bromodifluoroacetamide, and cesium carbonate is 1:2:2. S2: Add solvent, add acetone and water to the reaction tube, wherein the ratio of carboxylic acid to acetone is 0.2 mmol: 2 mL, and the molar ratio of carboxylic acid to water is 1:20; S3: Reaction, seal the reaction tube, place the reaction tube in a 90℃ heating module and stir the reaction for 12 hours; S4: Post-treatment: After the reaction solution is cooled to room temperature, acetone is removed by rotary evaporation and recovered. The residual solid is purified by silica gel rapid column chromatography with petroleum ether and ethyl acetate as eluents to obtain the primary amide product.

[0009] Furthermore, the reaction tube is a 20mL glass reaction tube, and the sealed reaction tube used in S3 is a rubber stopper-sealed reaction tube, which does not require anhydrous and oxygen-free control.

[0010] Furthermore, the carboxylic acid includes at least aromatic carboxylic acids, heterocyclic carboxylic acids, unsaturated carboxylic acids, aliphatic carboxylic acids, and pharmaceutical carboxylic acids.

[0011] Furthermore, the aromatic carboxylic acid includes at least benzoic acid, substituted benzoic acid, 1-naphthoic acid, 2-naphthoic acid, and p-phenylbenzoic acid; The substituents of the substituted benzoic acid include at least nitro, trifluoromethyl, methoxy, tert-butyl, and iodine.

[0012] Furthermore, the heterocyclic carboxylic acid includes at least 2-pyridinecarboxylic acid, 2-quinolinecarboxylic acid, and furanylacrylic acid.

[0013] Furthermore, the unsaturated carboxylic acids include at least cinnamic acid, substituted cinnamic acid, enoic acid, and dienoic acid; The substituted cinnamic acid includes at least 4-methoxycinnamic acid, the enoic acid includes only (Z)-4-decenoic acid, and the dienoic acid includes at least 9 (Z),12 (E)-octadecadienoic acid.

[0014] Furthermore, the aliphatic carboxylic acids include at least chain fatty acids, cycloalkane carboxylic acids, and adamantane carboxylic acids; The chain fatty acids include at least caprylic acid, oleic acid, palmitic acid, and icosanoic acid.

[0015] Furthermore, the drug-type carboxylic acids include at least naproxen, ibuprofen, oxapzin, ciprofibrate, p-chlorophenoxyisobutyric acid, ketoibuprofen, flurbiprofen, loxoprofen, gemfibrozil, itococcal acid, indomethacin, bendazac, adapalene, sulindac, febuxostat, rosin acid, and dehydrocholic acid.

[0016] Furthermore, the volume ratio of petroleum ether to ethyl acetate is adjusted according to the type of carboxylic acid substrate.

[0017] Furthermore, the acetone solvent recovered in S4 can be recycled in the solvent addition process of S2.

[0018] Compared with the prior art, the beneficial effects of the present invention are: 1. This invention uses bromodifluoroacetamide as the core reagent and innovatively uses it simultaneously as a carboxylic acid activator and amidation ammonia source to construct a new method for the preparation of primary amides with a simple reaction system and convenient operation. This reagent effectively avoids the prominent problems of strong odor, strong corrosiveness and high environmental pressure in traditional processes. While ensuring excellent reaction efficiency, it exhibits good stability, safety and environmentally friendly characteristics, and has outstanding potential for industrial scale-up.

[0019] 2. The process reaction conditions of this invention are mild and do not require a strictly anhydrous and oxygen-free environment, which significantly reduces the requirements for production equipment and operation, and improves the safety and practicality of the process. Using acetone as a solvent not only enables efficient conversion, but also facilitates the recovery and recycling of the solvent after the reaction, thereby effectively reducing production costs and environmental impact, and fully embodying the core concept of green chemistry.

[0020] 3. The method of this invention uses widely available and inexpensive raw materials, has good universality for various carboxylic acid substrates, and achieves ideal product yields. Most importantly, it provides an economical, efficient, and practical route for the conversion of inexpensive and readily available carboxylic acids into high-value-added primary amides, and has significant promotional value in academic research and industrial applications in the fields of medicine and chemical engineering. Attached Figure Description

[0021] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0022] Figure 1 This is a schematic diagram of the conventional carboxylic acid primary amidation conversion reaction of the present invention; Figure 2 This is a schematic diagram of the reaction for the amidation modification of the drug-like carboxylic acid in this invention. Detailed Implementation

[0023] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments.

[0024] See Figure 1 and Figure 2 This invention uses bromodifluoroacetamide as both an activating agent for carboxylic acids and an ammonia source for amidation, acetone as a solvent, water as a co-solvent, and cesium carbonate as a base. The carboxylic acid is efficiently converted into a primary amide in an air atmosphere at 90°C. The reaction is carried out in a conventional reaction tube without the need for anhydrous and oxygen-free control or special equipment.

[0025] The specific preparation method includes the following steps: Feeding: In a reaction tube equipped with a magnetic stirrer, carboxylic acid, bromodifluoroacetamide, and cesium carbonate are added sequentially, wherein the amount of carboxylic acid is 0.2 mmol (1.0 equivalent), the amount of bromodifluoroacetamide is 0.4 mmol (2.0 equivalent), and the amount of cesium carbonate is 0.4 mmol (2.0 equivalent). Add solvent: Add 2 ml of acetone to the reaction tube using a syringe, and then add 4 mmol of water using a microsyringe; Reaction: Seal the reaction tube with a rubber stopper, place the reaction tube in a heating module preheated to 90°C, and stir the reaction for 12 hours; Post-processing: After the reaction was completed, the reaction solution was cooled to room temperature, and the acetone solvent was removed by rotary evaporation and recovered. The residual solid was purified by silica gel rapid column chromatography with petroleum ether and ethyl acetate as eluents to obtain the primary amide target product.

[0026] The carboxylic acid substrates of this invention have broad applicability, including aromatic carboxylic acids, heterocyclic carboxylic acids, unsaturated carboxylic acids, aliphatic carboxylic acids, and pharmaceutical carboxylic acids. Aromatic carboxylic acids include benzoic acid, substituted benzoic acid, and naphtholic acid. Heterocyclic carboxylic acids include pyridinecarboxylic acid, quinolinecarboxylic acid, and furanylacrylic acid. Unsaturated carboxylic acids include cinnamic acid and enoic acid. Aliphatic carboxylic acids include chain fatty acids, cycloalkane carboxylic acids, and adamantanecarboxylic acid. Pharmaceutical carboxylic acids include nonsteroidal anti-inflammatory drugs such as naproxen, ibuprofen, oxapzin, and ciprofibrate, as well as lipid-lowering carboxylic acids.

[0027] All reactions in the invention were carried out in 20 mL glass reaction tubes equipped with magnetic stirrers. All reagents used were commercially available analytical grade reagents, requiring no further purification. The product structures were determined by ¹H NMR, ¹³C NMR, and ¹³C NMR. 9Characterization was performed using F NMR (if necessary) and HRMS. Nuclear magnetic resonance spectroscopy was performed using a 600 MHz nuclear magnetic resonance spectrometer, and high-resolution mass spectrometry was performed using an ESI-TOF mass spectrometer.

[0028] Example 1: Benzamide is prepared from benzoic acid. The chemical structural formula of benzamide is as follows:

[0029] At room temperature, 0.2 mmol / L benzoic acid, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate 2 were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating element preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (16.2 mg, 67%). 1 H NMR (600MHz, DMSO) δ 7.96 (s, 1H), 7.87 (d, J = 7.4 Hz, 2H), 7.51 (t, J = 7.3 Hz, 1H), 7.44 (t, J = 7.6 Hz, 2H), 7.34 (s, 1H). 13 C NMR (151 MHz, DMSO) δ 167.9,134.2, 131.1, 128.1, 127.34. HRMS (ESI-TOF) m / z [M+H] + calcd for C7H8NO,122.0606; found, 122.0610. Example 2: p-Nitrobenzoic acid was used to prepare p-nitrobenzoamide. The chemical structural formula of p-nitrobenzoamide is as follows:

[0030] At room temperature, 0.2 mmol / L p-nitrobenzoic acid, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate 2 were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a yellow solid product (15.3 mg, 46%). 1 H NMR (600MHz, DMSO) δ 8.29 (d, J = 8.7 Hz, 2H), 8.27 (s, 1H), 8.09 (d, J = 8.7 Hz, 2H), 7.71 (s, 1H). 13 C NMR (151 MHz, DMSO) δ 166.2, 149.0, 140.0, 128.9, 123.4.HRMS (ESI-TOF) m / z [M+H] + calcd for C7H7N2O3, 167.0457; found, 167.0460. Example 3: p-Trifluoromethylbenzamide was prepared from p-trifluoromethylbenzoic acid. The chemical structural formula of p-trifluoromethylbenzamide is as follows:

[0031] At room temperature, 0.2 mmol / L p-trifluoromethylbenzoic acid, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate 2 were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (26.8 mg, 71%). 1H NMR (600 MHz, DMSO) δ 8.19 (s, 1H), 8.06 (d, J = 8.1 Hz, 2H), 7.82 (d, J = 8.2Hz, 2H), 7.61 (s, 1H). 13 C NMR (151 MHz, DMSO) δ 166.7, 138.1, 131.5, 131.3, 131.0, 130.8, 128.3, 126.6, 125.2, 124.8, 123.0, 121.2. 19 F NMR (565 MHz, DMSO)δ -61.40 (s). HRMS (ESI-TOF) m / z [M+H] + calcd for C8H7NOF3, 190.0480; found, 190.0484. Example 4: p-Methoxybenzamide was prepared from p-methoxybenzoic acid. The chemical structural formula of p-methoxybenzamide is as follows: .

[0032] At room temperature, 0.2 mmol / L p-methoxybenzoic acid, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate 2 were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating element preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (27.2 mg, 90%). 1 H NMR (600 MHz, DMSO) δ 7.85 (d, J = 8.8 Hz, 2H), 7.83 (s, 1H), 7.17 (s, 1H), 6.97 (d, J = 8.8 Hz, 2H), 3.80 (s, 3H). 13 C NMR (151 MHz, DMSO) δ 167.4, 161.6,129.3, 126.5, 113.3, 55.3. HRMS (ESI-TOF) m / z [M+H] + calcd for C8H10 NO2,152.0712; found, 152.0716. Example 5: p-tert-butylbenzoic acid was used to prepare p-tert-butylbenzamide. The chemical structural formula of p-tert-butylbenzamide is as follows:

[0033] At room temperature, 0.2 mmol / L p-tert-butylbenzoic acid, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate 2 were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating element preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (16.3 mg, 46%). 1 H NMR (600 MHz, DMSO) δ 7.88 (s, 1H), 7.80 (d, J = 8.3 Hz, 2H), 7.45 (d, J = 8.3Hz, 2H), 7.24 (s, 1H), 1.29 (s, 9H). 13 C NMR (151 MHz, DMSO) δ 167.8, 153.9,131.5, 127.3, 124.9, 34.5, 30.9. HRMS (ESI-TOF) m / z [M+H] + calcd for C 11 H 16 NO, 178.1232; found, 178.1236. Example 6: p-Phenylenic acid was used to prepare p-phenylbenzamide. The chemical structural formula of p-phenylbenzamide is as follows:

[0034] At room temperature, 0.2 mmol / L p-phenylbenzoic acid, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate 2 were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating element preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (18.5 mg, 47%). 1 H NMR(600 MHz, DMSO) δ 8.05 (s, 1H), 7.98 (d, J = 8.3 Hz, 2H), 7.75 (d, J = 8.3Hz, 2H), 7.72 (d, J = 7.4 Hz, 2H), 7.48 (t, J = 7.7 Hz, 2H), 7.41 (d, J = 3.4Hz, 1H), 7.39 (d, J = 7.4Hz, 1H). 13 C NMR (151 MHz, DMSO) δ 167.6, 142.8,139.2, 133.1, 129.0, 128.2, 128.0, 126.9, 126.5. HRMS (ESI-TOF) m / z [M+H] + calcd for C 13 H 12 NO, 198.0919; found, 198.0924. Example 7: o-iodobenzoic acid was used to prepare o-iodobenzoamide. The chemical structural formula of o-iodobenzoamide is as follows:

[0035] At room temperature, 0.2 mmol / L o-iodobenzoic acid, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate 2 were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (47.4 mg, 96%). 1 H NMR(600 MHz, DMSO) δ 7.87 (d, J = 7.9 Hz, 1H), 7.80 (s, 1H), 7.49 (s, 1H), 7.42(t, J = 7.5 Hz, 1H), 7.34 (dd, J = 7.5, 1.1 Hz, 1H), 7.14 (td, J = 7.7, 1.4Hz, 1H). 13 C NMR (151 MHz, DMSO) δ 170.6, 143.0, 139.1, 130.5, 127.8, 127.7,93.0. HRMS (ESI-TOF) m / z [M+H] + calcd for C7H7NOI, 247.9572; found, 247.9576. Example 8: 3,5-Dimethoxybenzoic acid was used to prepare 3,5-dimethoxybenzamide. The chemical structural formula of 3,5-dimethoxybenzamide is as follows:

[0036] At room temperature, 0.2 mmol / L 1.0 Equivalent of 3,5-dimethoxybenzoic acid, 0.4 mmol / L 2.0 Equivalent of bromodifluoroacetamide 2, and 0.4 mmol / L 2.0 Equivalent of cesium carbonate were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (28.2 mg, 78%).1 HNMR (600 MHz, DMSO) δ 7.95 (s, 1H), 7.37 (s, 1H), 7.04 (d, J = 2.2 Hz, 2H), 6.63 (s, 1H), 3.77 (s, 6H). 13 C NMR (151 MHz, DMSO) δ 167.4, 160.3, 136.4,105.4, 103.1, 55.3. HRMS (ESI-TOF) m / z [M+H] + calcd for C9H 12 NO3, 182.0817; found, 182.0821. Example 9: 3,4,5-Trimethoxybenzoic acid was used to prepare 3,4,5-trimethoxybenzamide. The chemical structural formula of 3,4,5-trimethoxybenzamide is as follows:

[0037] At room temperature, 0.2 mmol / L 1.0 Equivalent of 3,4,5-trimethoxybenzoic acid, 0.4 mmol / L 2.0 Equivalent of bromodifluoroacetamide 2, and 0.4 mmol / L 2.0 Equivalent of cesium carbonate were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (29.1 mg, 69%). 1 H NMR (600 MHz, DMSO) δ 7.96 (s, 1H), 7.33 (s, 1H), 7.22 (s, 2H), 3.81 (s, 6H), 3.70 (s, 3H). 13 C NMR (151 MHz, DMSO) δ 167.3, 152.5, 129.4, 105.1,60.0, 56.0. HRMS (ESI-TOF) m / z [M+H] + calcd for C 10 H 14 NO4, 212.0923; found, 212.0926. Example 10: 1-Naphthoic acid was used to prepare 1-naphthoic acid-based amide. The chemical structural formula of 1-naphthoic acid-based amide is as follows:

[0038] At room temperature, 0.2 mmol / L 1.0 Equivalent of 1-naphthoic acid, 0.4 mmol / L 2.0 Equivalent of bromodifluoroacetamide 2, and 0.4 mmol / L 2.0 Equivalent of cesium carbonate were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (26.0 mg, 76%). 1 H NMR (600MHz, DMSO) δ 8.32 (d, J = 8.0 Hz, 1H), 8.01 (s, 1H), 7.99 (s, 1H), 7.98 – 7.93(m, 1H), 7.65 (d, J = 7.0 Hz, 1H), 7.59 (d, J = 9.3 Hz, 1H), 7.58 – 7.50 (m, 3H). 13 C NMR (151 MHz, DMSO) δ 170.6, 134.6, 133.2, 129.7, 128.1, 126.6, 126.1,125.6, 125.1, 124.9, 39.91 (s), 39.82 – 39.48 (m), 39.39 (s), 39.36 (s), 39.15 (d, J = 21.0 Hz). HRMS (ESI-TOF) m / z [M+H] + calcd for C 11 H 10 NO, 172.0762; found, 172.0764. Example 11: 2-Naphthoic acid was used to prepare 2-naphthoamide. The chemical structural formula of 2-naphthoamide is as follows:

[0039] At room temperature, 0.2 mmol / L 1.0 Equivalent of 2-naphthoic acid, 0.4 mmol / L 2.0 Equivalent of bromodifluoroacetamide 2, and 0.4 mmol / L 2.0 Equivalent of cesium carbonate were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (18.1 mg, 53%).

[0040] 1 H NMR (600 MHz, DMSO) δ 8.49 (s, 1H), 8.14 (s, 1H), 8.00 (d, J = 7.7Hz, 1H), 7.97 (s, 2H), 7.96 (s, 1H), 7.65 – 7.54 (m, 2H), 7.48 (s, 1H). 13 C NMR (151 MHz, DMSO) δ 167.9, 134.1, 132.1, 131.6, 128.8, 127.7, 127.5, 126.6,124.4. HRMS (ESI-TOF) m / z [M+H] + calcd for C 11 H 10 NO, 172.0762; found, 172.0765. Example 12: 2-Pyridinecarboxylic acid was used to prepare 2-pyridinecarboxamide. The chemical structural formula of 2-pyridinecarboxamide is as follows:

[0041] At room temperature, 0.2 mmol / L 1.0 Equivalent of 2-pyridinecarboxylic acid, 0.4 mmol / L 2.0 Equivalent of bromodifluoroacetamide 2, and 0.4 mmol / L 2.0 Equivalent of cesium carbonate were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (10.0 mg, 41%). 1 H NMR (600 MHz, DMSO) δ 8.63 (dd, J = 4.7, 0.7 Hz, 1H), 8.11 (s, 1H), 8.04 (d, J =7.7 Hz, 1H), 8.01 – 7.96 (m, 1H), 7.64 (s, 1H), 7.60 – 7.55 (m, 1H). 13 C NMR (151 MHz, DMSO) δ 166.0, 150.3, 148.4, 137.6, 126.4, 121.8. HRMS (ESI-TOF) m / z [M+H] + calcd for C6H7N2O, 123.0558; found, 123.0557. Example 13: 2-Quinolinecarboxylic acid was used to prepare 2-quinolinecarboxamide. The chemical structural formula of 2-quinolinecarboxamide is as follows:

[0042] At room temperature, 0.2 mmol / L 1.0 Equivalent of 2-quinolinecarboxylic acid, 0.4 mmol / L 2.0 Equivalent of bromodifluoroacetamide 2, and 0.4 mmol / L 2.0 Equivalent of cesium carbonate were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (20.0 mg, 58%). 1H NMR(600 MHz, DMSO) δ 8.54 (d, J = 8.5 Hz, 1H), 8.28 (s, 1H), 8.16 (d, J = 8.5Hz, 1H), 8.12 (d, J = 8.4 Hz, 1H), 8.06 (d, J = 8.1 Hz, 1H), 7.86 (dd, J =8.2, 7.1 Hz, 1H), 7.77 (s, 1H), 7.71 (t, J = 7.5 Hz, 1H). 13 C NMR (151 MHz, DMSO) δ 166.12 (s), 150.36 (s), 145.99 (s), 137.60 (s), 130.29 (s), 129.20 (s), 128.68 (s), 127.93 (s), 118.50 (s), 39.91 (s), 39.71 (d, J = 20.8 Hz), 39.50 (s), 39.29 (d, J = 20.9 Hz), 39.08 (s). HRMS (ESI-TOF) m / z [M+H] + calcdfor C 10 H9N2O, 173.0715; found, 173.0719. Example 14: Preparation of (E)-4-methoxycinnamic acid from (E)-4-methoxycinnamic acid; the chemical structural formula of (E)-4-methoxycinnamic acid is as follows:

[0043] At room temperature, 0.2 mmol / L (E)-4-methoxycinnamic acid, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate 2 were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (27.3 mg, 77%). 1HNMR (600 MHz, DMSO) δ 7.50 (d, J = 8.7 Hz, 2H), 7.45 (s, 1H), 7.37 (d, J =15.8 Hz, 1H), 7.00 (s, 1H), 6.96 (d, J = 8.7 Hz, 2H), 6.47 (d, J = 15.8 Hz,1H), 3.78 (s, 3H). 13 C NMR (151 MHz, DMSO) δ 167.0, 160.3, 138.8, 129.0, 127.4,119.8, 114.3, 55.2. HRMS (ESI-TOF) m / z [M+H] + calcd for C 10 H 12 NO2, 178.0868;found, 178.0865. Example 15: Preparation of (E)-3-(furan-2-yl)acrylamide from (E)-3-(furan-2-yl)acrylic acid. The chemical structural formula of (E)-3-(furan-2-yl)acrylamide is as follows:

[0044] At room temperature, 0.2 mmol / L (E)-3-(furan-2-yl)acrylic acid, 0.4 mmol / L 2.0 Equivalents of bromodifluoroacetamide 2, and 0.4 mmol / L 2.0 Equivalents of cesium carbonate were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a yellow solid product (16.2 mg, 59%). 1 H NMR (600 MHz, DMSO) δ 7.75 (s, 1H), 7.55 (s, 1H), 7.22 (d, J = 15.6Hz, 1H), 7.06 (s, 1H), 6.75 (d, J = 3.3 Hz, 1H), 6.57 (dd, J = 3.2, 1.8 Hz,1H), 6.40 (d, J = 15.7 Hz, 1H). 13C NMR (151 MHz, DMSO) δ 166.4, 150.9, 144.6,126.5, 119.6, 113.5, 112.3. HRMS (ESI-TOF) m / z [M+H] + calcd for C7H8NO2,138.0555; found, 138.0560. Example 16: Ferrocene carboxylic acid was used to prepare ferrocene carboxamide. The chemical structural formula of ferrocene carboxamide is as follows:

[0045] At room temperature, 0.2 mmol / L ferroceneic acid, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate 2 were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a brown solid product (29.3 mg, 64%). 1 H NMR (600 MHz, DMSO) δ 7.31 (s, 1H), 6.93 (s, 1H), 4.76 (s, 2H), 4.32 (s, 2H), 4.16 (s, 5H). 13 C NMR (151 MHz, DMSO) δ 171.1, 76.4, 69.9, 69.3, 68.5. HRMS(ESI-TOF) m / z [M+H] + calcd for C 11 H 11 NOFe, 229.0190; found, 229.0191. Example 17: 2-Naphthylacetamide was prepared from 2-naphthylacetic acid. The chemical structural formula of 2-naphthylacetamide is as follows:

[0046] At room temperature, 0.2 mmol / L 1.0 Equivalent of 2-naphthaleneacetic acid, 0.4 mmol / L 2.0 Equivalent of bromodifluoroacetamide 2, and 0.4 mmol / L 2.0 Equivalent of cesium carbonate were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (33.7 mg, 91%). 1 H NMR (600MHz, DMSO) δ 7.90 – 7.81 (m, 3H), 7.76 (s, 1H), 7.53 (d, J = 18.5 Hz, 1H), 7.51 – 7.41 (m, 3H), 6.94 (s, 1H), 3.56 (s, 2H). 13 C NMR (151 MHz, DMSO) δ172.1, 134.2, 133.0, 131.7, 127.7, 127.4, 126.0, 125.4, 42.3. HRMS (ESI-TOF) m / z [M+H] + calcd for C 12 H 12 NO, 186.0919; found, 186.0922. Example 18: 3,4-Dimethoxyphenylacetamide was prepared from 3,4-dimethoxyphenylacetic acid. The chemical structural formula of 3,4-dimethoxyphenylacetamide is as follows:

[0047] At room temperature, 0.2 mmol / L 1.0 Equivalent of 3,4-dimethoxyphenylacetic acid, 0.4 mmol / L 2.0 Equivalent of bromodifluoroacetamide 2, and 0.4 mmol / L 2.0 Equivalent of cesium carbonate were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (19.9 mg, 51%). 1 HNMR (600 MHz, DMSO) δ 7.34 (s, 1H), 6.86 (d, J = 8.2 Hz, 2H), 6.80 (s, 1H), 6.76 (dd, J = 8.1, 1.3 Hz, 1H), 3.73 (s, 3H), 3.72 (s, 3H), 3.28 (s, 2H). 13 CNMR (151 MHz, DMSO) δ 172.4, 148.6, 147.4, 128.9, 121.0, 113.1, 111.9, 55.6,55.4, 41.8. HRMS (ESI-TOF) m / z [M+H] + calcd for C 10 H 14 NO3, 196.0974; found, 196.0979. Example 19: 4-Pyrenebutyric acid was used to prepare 4-pyrenebutyramide. The chemical structural formula of 4-pyrenebutyramide is as follows:

[0048] At room temperature, 0.2 mmol / L 1.0 Equivalent of 4-pyrenebutyric acid, 0.4 mmol / L 2.0 Equivalent of bromodifluoroacetamide 2, and 0.4 mmol / L 2.0 Equivalent of cesium carbonate were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a yellow solid product (42.5 mg, 74%). 1 H NMR (600 MHz, DMSO) δ 8.38 (d, J = 9.2 Hz, 1H), 8.25 (t, J = 7.7 Hz, 2H), 8.20 (dd, J = 8.5, 5.6 Hz, 2H), 8.15 – 8.07 (m, 2H), 8.04 (t, J = 7.6 Hz, 1H),7.93 (d, J = 7.8 Hz, 1H), 7.35 (s, 1H), 6.83 (s, 1H), 3.35 – 3.27 (m, 2H),2.24 (t, J = 7.3 Hz, 2H), 2.06 – 1.95 (m, 2H). 13 C NMR (151 MHz, DMSO) δ 174.1,136.6, 130.9, 130.4, 129.3, 128.1, 127.5, 127.2, 126.5, 126.1, 124.9, 124.8,124.2, 123.5, 34.7, 32.3, 27.4. HRMS (ESI-TOF) m / z [M+Na] + calcd for C 20 H 17 NONa,310.1208; found, 310.1212. Example 20: Phenoxyacetamide was prepared from phenoxyacetic acid. The chemical structural formula of phenoxyacetamide is as follows:

[0049] At room temperature, 0.2 mmol / L phenoxyacetic acid, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate 2 were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (24.2 mg, 80%). 1 H NMR (600MHz, DMSO) δ 7.49 (s, 1H), 7.36 (s, 1H), 7.30 (t, J = 7.7 Hz, 2H), 6.96 (t, J= 7.7 Hz, 3H), 4.42 (s, 2H). 13 C NMR (151 MHz, DMSO) δ 169.9, 157.7, 129.4,121.0, 114.6, 66.7. HRMS (ESI-TOF) m / z [M+H] + calcd for C8H 10 NO2, 152.0712; found, 1152.0711. Example 21: 2-Naphthoxyacetamide was prepared from 2-naphthoxyacetic acid. The chemical structural formula of 2-naphthoxyacetamide is as follows:

[0050] At room temperature, 0.2 mmol / L 1.0 Equivalent of 2-naphthoxyacetic acid, 0.4 mmol / L 2.0 Equivalent of bromodifluoroacetamide 2, and 0.4 mmol / L 2.0 Equivalent of cesium carbonate were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (31.8 mg, 79%). 1H NMR(600 MHz, DMSO) δ 8.39 (d, J = 8.0 Hz, 1H), 7.91 – 7.83 (m, 1H), 7.63 (s,1H), 7.57 – 7.50 (m, 3H), 7.50 (s, 1H), 7.41 (t, J = 7.9 Hz, 1H), 6.91 (d, J= 7.7 Hz, 1H), 4.64 (s, 2H). 13 C NMR (151 MHz, DMSO) δ 169.7, 153.3, 134.0,127.3, 126.5, 125.9, 125.2, 124.8, 122.1, 120.5, 105.5, 67.2. HRMS (ESI-TOF) m / z [M+H] + calcd for C 12 H 12 NO2, 202.0868; found, 202.0861. Example 22: 4-Benzoylbutyric acid was used to prepare 4-benzoylbutyramide. The chemical structural formula of 4-benzoylbutyramide is as follows:

[0051] At room temperature, 0.2 mmol / L 1.0 Equivalent of 4-benzoylbutyric acid, 0.4 mmol / L 2.0 Equivalent of bromodifluoroacetamide 2, and 0.4 mmol / L 2.0 Equivalent of cesium carbonate were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (32.1 mg, 84%). 1H NMR(600 MHz, DMSO) δ 7.95 (d, J = 7.3 Hz, 2H), 7.62 (t, J = 7.4 Hz, 1H), 7.52(t, J = 7.7 Hz, 2H), 7.30 (s, 1H), 6.77 (s, 1H), 3.02 (t, J = 7.2 Hz, 2H), 2.14 (t, J = 7.4 Hz, 2H), 1.83 (p, J = 7.3 Hz, 2H). 13 C NMR (151 MHz, DMSO) δ199.8, 174.0, 136.6, 133.1, 128.7, 127.9, 37.4, 34.2, 19.8. HRMS (ESI-TOF) m / z [M+Na] + calcd for C 11 H 13 NO2Na, 214.0844; found, 214.0848. Example 23: Adamantane carboxylic acid was used to prepare adamantane formamide. The chemical structural formula of adamantane formamide is as follows:

[0052] At room temperature, 0.2 mmol / L adamantane carboxylic acid, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate 2 were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (16.1 mg, 45%). 1 H NMR (600 MHz, DMSO) δ 6.90 (s, 1H), 6.64 (s, 1H), 1.94 (s, 3H), 1.75 (d, J = 2.1Hz, 6H), 1.65 (q, J = 12.0 Hz, 6H). 13C NMR (151 MHz, DMSO) δ 179.2, 39.6,38.7, 36.1, 27.7. HRMS (ESI-TOF) m / z [M+H] + calcd for C 11 H 18 NO, 180.1388; found, 180.1391. Example 24: (Z)-4-decenoic acid was used to prepare (Z)-4-decenoamide. The chemical structural formula of (Z)-4-decenoamide is as follows:

[0053] At room temperature, 0.2 mmol / L (Z)-4-decenoic acid, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate 2 were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a yellow solid product (32.4 mg, 96%). 1 H NMR(600 MHz, DMSO) δ 7.22 (s, 1H), 6.70 (s, 1H), 5.48 – 5.28 (m, 2H), 2.15 (dd,J = 13.6, 6.7 Hz, 2H), 2.07 (t, J = 7.6 Hz, 2H), 1.93 (dd, J = 13.3, 6.4 Hz, 2H), 1.33 – 1.21 (m, 6H), 0.85 (t, J = 7.0 Hz, 3H). 13 C NMR (151 MHz, DMSO) δ173.7, 130.2, 129.1, 35.1, 31.9, 30.7, 28.6, 28.0, 21.9. HRMS (ESI-TOF) m / z [M+H] + calcd for C 10 H 20 NO, 170.1545; found, 170.1548. Example 25: Preparation of 9(Z),12(E)-octadecadienoic acid to 9(Z),12(E)-octadecadienoamide: The chemical structural formula of 9(Z),12(E)-octadecadienoamide is as follows:

[0054] At room temperature, 0.2 mmol / L 1.0 Equivalent of 9(Z),12(E)-octadecadienoic acid, 0.4 mmol / L 2.0 Equivalent of bromodifluoroacetamide 2, and 0.4 mmol / L 2.0 Equivalent of cesium carbonate were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L of water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a yellow oily product (48.0 mg, 86%).

[0055] 1 H NMR (600 MHz, DMSO) δ 7.19 (s, 1H), 6.64 (s, 1H), 5.32 (tdd, J =17.9, 10.9, 7.2 Hz, 4H), 2.73 (t, J = 6.8 Hz, 2H), 2.05 – 1.98 (m, 6H), 1.50– 1.43 (m, 2H), 1.34 – 1.22 (m, 14H), 0.86 (t, J = 7.0 Hz, 3H). 13 C NMR (151MHz, DMSO) δ 174.2, 129.6, 127.7, 35.1, 30.9, 29.0, 28.7, 26.6, 25.1, 21.9,13.8. HRMS (ESI-TOF) m / z [M+H] + calcd for C 18 H 34 NO, 280.2640; found, 280.2644. Example 26: Oleamide was prepared from oleic acid. The chemical structural formula of oleamide is as follows:

[0056] At room temperature, 0.2 mmol / L oleic acid, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate 2 were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (48.9 mg, 87%). 1 H NMR (600MHz, DMSO) δ 7.19 (s, 1H), 6.64 (s, 1H), 5.31 (t, J = 5.0 Hz, 2H), 2.04 –1.94 (m, 6H), 1.50 – 1.41 (m, 2H), 1.32 – 1.20 (m, 20H), 0.85 (t, J = 6.9 Hz, 3H). 13 C NMR (151 MHz, DMSO) δ 174.2, 129.5, 35.1, 31.3, 29.1, 28.9, 28.5,26.6, 25.1, 22.1, 13.9. HRMS (ESI-TOF) m / z [M+H] + calcd for C 18 H 36 NO, 282.2797; found, 282.2800. Example 27: Octanoic acid is used to prepare octanoamide. The chemical structural formula of octanoamide is as follows:

[0057] At room temperature, 0.2 mmol / L octanoic acid, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate 2 were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (21.2 mg, 74%).1 H NMR (600MHz, DMSO) δ 7.22 (s, 1H), 6.67 (s, 1H), 2.01 (t, J = 7.5 Hz, 2H), 1.50 –1.41 (m, 2H), 1.31 – 1.17 (m, 8H), 0.85 (t, J = 7.0 Hz, 3H). 13 C NMR (151 MHz, DMSO) δ 174.3, 39.0, 38.9, 35.1, 31.2, 28.7, 28.5, 25.1, 22.1, 13.9. [M+H] + calcd for C8H 18 NO, 144.1388; found, 144.1380. Example 28: Palmitic acid is used to prepare palmitamide. The chemical structural formula of palmitamide is as follows:

[0058] At room temperature, 0.2 mmol / L palmitic acid, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (38.3 mg, 75%). 1 H NMR (600MHz, CDCl3) δ 5.53 (d, J = 120.5 Hz, 2H), 2.21 (t, J = 7.6 Hz, 2H), 1.63 (dt, J =14.9, 7.5 Hz, 2H), 1.35 – 1.21 (m, 24H), 0.87 (t, J = 7.0 Hz, 3H). 13C NMR (151MHz, CDCl3) δ 175.7, 36.0, 31.9, 29.7, 29.7, 29.6, 29.5, 29.3, 29.3, 29.2,25.5, 22.7, 14.1. HRMS (ESI-TOF) m / z [M+H] + calcd for C 16 H 34 NO, 256.2640; found, 256.2644. Example 29: 3-Dicosodecanedioic acid was used to prepare 3-dodecanoic acid amide. The chemical structural formula of 3-dodecanoic acid amide is as follows:

[0059] At room temperature, 0.2 mmol / L (1.0 equivalent) of 3-dodecanoic acid, 0.4 mmol / L (2.0 equivalent) of bromodifluoroacetamide 2, and 0.4 mmol / L (2.0 equivalent) of cesium carbonate were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L of water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (50.2 mg, 74%). 1 H NMR(600 MHz, CDCl3) δ 5.43 (s, 2H), 2.22 (t, J = 7.6 Hz, 2H), 1.66 – 1.60 (m,2H), 1.46 – 1.06 (m, 36H), 0.88 (t, J = 7.0 Hz, 3H). 13 C NMR (151 MHz, CDCl3) δ175.6, 35.9, 31.9, 29.7, 29.6, 29.5, 29.4, 29.3, 29.2, 25.5, 22.7, 14.1. HRMS(ESI-TOF) m / z [M+H] + calcd for C 22 H 46 NO, 340.3579; found, 340.3582. mp (uncorrected, capillary): 110-113 °C Example 30: Naproxen was used to prepare naproxenamide, and the chemical structural formula of naproxenamide is as follows:

[0060] At room temperature, 0.2 mmol / L naproxen (1.0 equivalent), 0.4 mmol / L bromodifluoroacetamide 2 (2.0 equivalent), and 0.4 mmol / L cesium carbonate (2.0 equivalent) were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating element preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (35.7 mg, 78%). 1 H NMR (600MHz, DMSO) δ 7.76 (dd, J = 17.2, 8.7 Hz, 2H), 7.71 (s, 1H), 7.45 (dd, J =8.4, 1.6 Hz, 2H), 7.27 (d, J = 2.4 Hz, 1H), 7.14 (dd, J = 8.9, 2.5 Hz, 1H), 6.85 (s, 1H), 3.85 (s, 3H), 3.71 (q, J = 7.0 Hz, 1H), 1.39 (d, J = 7.1 Hz, 3H). 13 HRMS (ESI-TOF) m / z [M+H] + calcdfor C 14 H 16 NO2, 230.1181; found, 230.1181. Example 31: Ibuprofen is used to prepare ibuprofenamide. The chemical structural formula of ibuprofenamide is as follows:

[0061] At room temperature, 0.2 mmol / L ibuprofen, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (35.3 mg, 86%). 1 H NMR (600MHz, DMSO) δ 7.33 (s, 1H), 7.22 (d, J = 8.0 Hz, 2H), 7.07 (d, J = 7.9 Hz,2H), 6.77 (s, 1H), 3.53 (q, J = 7.0 Hz, 1H), 2.40 (d, J = 7.1 Hz, 2H), 1.80 (dp, J = 13.5, 6.7 Hz, 1H), 1.29 (d, J = 7.1 Hz, 3H), 0.85 (d, J = 6.6 Hz, 6H). 13 C NMR (151 MHz, DMSO) δ 175.4, 139.6, 139.1, 128.6, 126.9, 44.5, 44.2,29.6, 22.1, 18.4. HRMS (ESI-TOF) m / z [M+H] + calcd for C 13 H 20 NO, 206.1545; found, 206.1550. Example 32: Oxaprazin was used to prepare oxaprazinamide, the chemical structural formula of which is as follows:

[0062] At room temperature, 0.2 mmol / L oxaprazine, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate 2 were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (50.2 mg, 86%). 1 H NMR (600MHz, DMSO) δ 7.54 (dd, J = 22.3, 7.2 Hz, 4H), 7.47 (s, 1H), 7.45 – 7.31 (m,6H), 6.92 (s, 1H), 3.04 (t, J = 7.4 Hz, 2H), 2.63 (t, J = 7.4 Hz, 2H). 13 C NMR(151 MHz, DMSO) δ 172.5, 162.8, 144.5, 134.3, 132.1, 128.9, 128.7, 128.6,128.5, 128.1, 127.3, 126.3, 31.4, 23.2. HRMS (ESI-TOF) m / z [M+H] + calcd forC 18 H 17 N2O2, 293.1290; found, 293.1291. Example 33: Cyclopropylfibrate was used to prepare cyclopropylfibrate amide. The chemical structural formula of cyclopropylfibrate amide is as follows:

[0063] At room temperature, 0.2 mmol / L cyclopropofol, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (49.9 mg, 87%). 1 H NMR (600MHz, DMSO) δ 7.52 (s, 1H), 7.25 (s, 1H), 7.21 (d, J = 8.4 Hz, 2H), 6.87 (d, J= 8.3 Hz, 2H), 3.04 – 2.97 (m, 1H), 2.10 – 1.99 (m, 2H), 1.41 (s, 6H). 13 C NMR (151 MHz, DMSO) δ 175.7, 154.3, 129.5, 127.8, 119.2, 79.9, 61.9, 33.9, 24.9,24.8, 24.7. HRMS (ESI-TOF) m / z [M+H] + calcd for C 13 H 16 NO2Cl2, 288.0558; found, 288.0564. Example 34: p-Chlorophenoxyisobutyric acid was used to prepare p-chlorophenoxyisobutyramide. The chemical structural formula of p-chlorophenoxyisobutyramide is as follows:

[0064] At room temperature, 0.2 mmol / L p-chlorophenoxyisobutyric acid, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (30.2 mg, 71%). 1 H NMR (600 MHz, DMSO) δ 7.55 (s, 1H), 7.32 (d, J = 8.9 Hz, 2H), 7.27 (s, 1H), 6.90 (d, J = 8.9 Hz, 2H), 1.41 (s, 6H). 13 C NMR (151 MHz, DMSO) δ 175.4, 153.9,128.9, 125.7, 121.3, 80.3, 24.8. HRMS (ESI-TOF) m / z [M+H] + calcd forC 10 H 13 NO2Cl, 214.0635; found, 214.0638. Example 35: Ketoibuprofen amide was prepared from ketoibuprofen. The chemical structural formula of ketoibuprofen amide is as follows:

[0065] At room temperature, 0.2 mmol / L 1.0 Equivalent of ketoibuprofen, 0.4 mmol / L 2.0 Equivalent of bromodifluoroacetamide 2, and 0.4 mmol / L 2.0 Equivalent of cesium carbonate were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (31.9 mg, 63%). 1H NMR(600 MHz, DMSO) δ 7.77 – 7.71 (m, 3H), 7.68 (t, J = 7.4 Hz, 1H), 7.63 (d, J =7.6 Hz, 1H), 7.57 (dd, J = 14.7, 7.1 Hz, 3H), 7.50 (d, J = 7.7 Hz, 1H), 7.48(s, 1H), 6.88 (s, 1H), 3.69 (q, J = 7.0 Hz, 1H), 1.35 (d, J = 7.1 Hz, 3H). 13 CNMR (151 MHz, DMSO) δ 195.7, 174.9, 142.8, 137.1, 136.9, 132.6, 131.6, 129.5,128.5, 128.4, 128.0, 44.7, 18.4. HRMS (ESI-TOF) m / z [M+H] + calcd forC 16 H 15 NO2Na, 276.1000; found, 276.1005. Example 36: Flurbiprofen amide was prepared from flurbiprofen. The chemical structural formula of flurbiprofen amide is as follows:

[0066] At room temperature, 0.2 mmol / L flurbiprofen, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating element preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (42.3 mg, 87%). 1H NMR (600MHz, DMSO) δ 7.53 (d, J = 7.9 Hz, 2H), 7.46 (dt, J = 13.7, 6.7 Hz, 4H), 7.38(t, J = 7.3 Hz, 1H), 7.25 (d, J = 3.3 Hz, 1H), 7.24 (s, 1H), 6.93 (s, 1H), 3.66 (q, J = 7.0 Hz, 1H), 1.36 (d, J = 7.1 Hz, 3H). 13 C NMR (151 MHz, DMSO) δ174.7, 159.6, 158.0, 144.3, 144.3, 135.0, 130.4, 130.3, 128.6, 128.6, 128.5,127.6, 126.3, 126.2, 123.8, 123.8, 114.9, 114.7, 44.4, 18.2. 19 F NMR (565 MHz, DMSO) δ -118.80. HRMS (ESI-TOF) m / z [M+H] + calcd for C 15 H 15 NOF, 244.1138; found, 244.1142. Example 37: Loxoprofen was used to prepare loxoprofen amide. The chemical structural formula of loxoprofen amide is as follows:

[0067] At room temperature, 0.2 mmol / L loxoprofen, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate 2 were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (44.1 mg, 90%). 1H NMR (600MHz, DMSO) δ 7.32 (s, 1H), 7.22 (d, J = 8.0 Hz, 2H), 7.10 (d, J = 7.9 Hz,2H), 6.76 (s, 1H), 3.53 (q, J = 7.0 Hz, 1H), 2.94 (dd, J = 13.6, 4.0 Hz, 1H), 2.43 (dd, J = 13.6, 9.7 Hz, 1H), 2.39 – 2.30 (m, 1H), 2.23 (dd, J = 18.6, 8.2Hz, 1H), 2.06 (dt, J = 18.7, 9.5 Hz, 1H), 1.97 – 1.89 (m, 1H), 1.88 – 1.79 (m, 1H), 1.74 – 1.61 (m, 1H), 1.47 (qd, J = 10.8, 6.7 Hz, 1H), 1.29 (d, J =7.1 Hz, 3H). 13 C NMR (151 MHz, DMSO) δ 219.22, 175.4, 1344.0, 138.1, 128.5,127.2, 50.0, 44.5, 37.5, 34.5, 28.7, 20.0, 18.4. HRMS (ESI-TOF) m / z [M+H] + calcd for C 15 H 19 NO2Na, 268.1313; found, 268.1307. Example 38: Gemfibrozil was used to prepare gemfibrozilamide, the chemical structural formula of which is as follows:

[0068] At room temperature, 0.2 mmol / L gemfibrozil, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating element preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (26.9 mg, 54%).1 H NMR (600MHz, DMSO) δ 7.03 (s, 1H), 6.97 (d, J = 7.4 Hz, 1H), 6.78 (s, 1H), 6.69 (s,1H), 6.61 (d, J = 7.4 Hz, 1H), 3.88 (t, J = 6.2 Hz, 2H), 2.24 (s, 3H), 2.09(s, 3H), 1.63 (dt, J = 9.2, 6.0 Hz, 2H), 1.59 – 1.51 (m, 2H), 1.08 (s, 6H). 13 CNMR (151 MHz, DMSO) δ 178.9, 156.5, 136.0, 130.0, 122.5, 120.4, 112.1, 67.8,41.0, 36., 25.3, 24.7, 21.0, 15.5. HRMS (ESI-TOF) m / z [M+H] + calcd forC 15 H 23 NO2, 272.1626; found, 272.1625. Example 39: The preparation of isocrine from isocrine, and the chemical structural formula of isocrine is as follows:

[0069] At room temperature, 0.2 mmol / L (1.0 Equivalent) of isochoric acid, 0.4 mmol / L (2.0 Equivalent) of bromodifluoroacetamide 2, and 0.4 mmol / L (2.0 Equivalent) of cesium carbonate were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L of water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (40.1 mg, 75%). 1H NMR (600MHz, DMSO) δ 7.99 (d, J = 1.9 Hz, 1H), 7.78 (d, J = 7.6 Hz, 1H), 7.64 (t, J =7.3 Hz, 1H), 7.58 – 7.50 (m, 3H), 7.48 (dd, J = 8.4, 2.1 Hz, 1H), 7.04 (d, J= 8.4 Hz, 1H), 6.92 (s, 1H), 5.27 (s, 2H), 3.42 (s, 2H). 13 C NMR (151 MHz, DMSO) δ 190.1, 172.1, 159.6, 139.9, 136.6, 135.9, 132.9, 131.3, 130.2, 129.1,128.7, 128.2, 124.5, 120.4, 72.7, 41.0. HRMS (ESI-TOF) m / z [M+H] + calcd forC 16 H 13 NO3Na, 290.0793; found, 290.0797. Example 40: Indomethacin was used to prepare indomethacinamide. The chemical structural formula of indomethacinamide is as follows:

[0070] At room temperature, 0.2 mmol / L indomethacin, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating element preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (50.6 mg, 71%). 1H NMR (600MHz, DMSO) δ 7.69 (d, J = 8.5 Hz, 2H), 7.64 (d, J = 8.5 Hz, 2H), 7.43 (s,1H), 7.11 (d, J = 2.2 Hz, 1H), 6.96 (s, 1H), 6.94 (d, J = 9.0 Hz, 1H), 6.71(dd, J = 9.0, 2.3 Hz, 1H), 3.76 (s, 3H), 3.47 (s, 2H), 2.23 (s, 3H). 13 C NMR(151 MHz, DMSO) δ 171.5, 167.8, 155.5, 137.5, 135.0, 134.2, 131.1, 130.9,130.3, 128.9, 114.5, 114.4, 111.1, 102.0, 55.4, 30.9, 13.2. HRMS (ESI-TOF) m / z [M+H] + calcd for C 19 H 18 N2O3Cl, 357.1006; found, 357.1010. Example 41: The preparation of benzydamide from benzydanoic acid, the chemical structural formula of benzydamide is as follows:

[0071] At room temperature, 0.2 mmol / L benzyl ether acid, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate 2 were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (50.0 mg, 89%). 1H NMR (600MHz, DMSO) δ 7.75 (d, J = 8.1 Hz, 1H), 7.61 (s, 1H), 7.54 (d, J = 8.6 Hz,1H), 7.37 (dd, J = 11.4, 3.8 Hz, 2H), 7.28 (t, J = 7.3 Hz, 2H), 7.23 (t, J =7.3 Hz, 1H), 7.20 (t, J = 6.5 Hz, 2H), 7.07 (t, J = 7.5 Hz, 1H), 5.45 (s,2H), 4.73 (s, 2H). 13 C NMR (151 MHz, DMSO) δ 169.5, 154.4, 141.4, 137.7, 128.4,127.5, 127.3, 127.1, 119.8, 119.3, 111.8, 109.5, 66.9, 51.3. HRMS (ESI-TOF) m / z [M+H] + calcd for C 16 H 16 N3O2, 282.1243; found, 282.1247. Example 42: Adapalene was prepared into adapaleneamide. The chemical structural formula of adapaleneamide is as follows:

[0072] At room temperature, 0.2 mmol / L adapalene, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating element preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (29.6 mg, 36%). 1H NMR (600MHz, DMSO) δ 8.49 (s, 1H), 8.18 (s, 1H), 8.12 (s, 1H), 8.04 (dd, J = 8.4, 3.6Hz, 2H), 7.97 (d, J = 8.4 Hz, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.62 (d, J = 8.1Hz, 1H), 7.57 (s, 1H), 7.44 (s, 1H), 7.10 (d, J = 8.4 Hz, 1H), 3.85 (s, 3H), 2.13 (s, 6H), 2.06 (s, 3H), 1.75 (s, 6H). 13 C NMR (151 MHz, DMSO) δ 167.9,158.4, 139.4, 138.0, 134.6, 131.6, 131.2, 130.9, 129.3, 127.9, 127.5, 125.7,125.6, 124.9, 124.7, 124.0, 112.7, 55.3, 40.1, 36.6, 36.5, 28.4. HRMS (ESI-TOF) m / z [M+H] + calcd for C 28 H 30 NO2, 412.2277; found, 412.2280. Example 43: Sulinac was used to prepare sulinamide. The chemical structural formula of sulinamide is as follows:

[0073] At room temperature, 0.2 mmol / L sulindac, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate 2 were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (28.4 mg, 40%). 1 H NMR (600 MHz, DMSO) δ 7.79 (d, J = 8.2 Hz, 2H), 7.72 (d, J = 8.2Hz, 2H), 7.55 (s, 1H), 7.34 (s, 1H), 7.16 (dd, J = 8.4, 5.2 Hz, 1H), 7.11(dd, J = 9.3, 2.4 Hz, 1H), 7.00 (s, 1H), 6.71 (td, J = 9.3, 2.4 Hz, 1H), 3.40(s, 2H), 2.82 (s, 3H), 2.18 (s, 3H). 13 C NMR (151 MHz, DMSO) δ 170.8, 163.3,161.7, 147.4, 147.3, 146.2, 140.5, 138.6, 137.6, 133.8, 129.9, 129.5, 129.1,123.9, 123.1, 123.0, 110.3, 110.2, 106.2, 106.1, 43.1, 32.5, 10. 19 F NMR (565MHz, DMSO) δ -113.67. HRMS (ESI-TOF) m / z [M+H] + calcd for C 20 H 19NO2SF, 356.1121; found, 356.1125. Example 44: Febuxostat was used to prepare febuxostat amide. The chemical structural formula of febuxostat amide is as follows:

[0074] At room temperature, 0.2 mmol / L febuxostat, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate 2 were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (35.3 mg, 56%). 1 H NMR (600MHz, DMSO) δ 8.20 (d, J = 2.3 Hz, 1H), 8.15 (dd, J = 8.9, 2.3 Hz, 1H), 7.63(s, 2H), 7.36 (d, J = 9.0 Hz, 1H), 4.02 (q, J = 7.1 Hz, 1H), 3.99 (d, J = 6.5Hz, 2H), 2.60 (s, 3H), 2.13 – 2.04 (m, 1H), 1.98 (s, 1H), 1.17 (t, J = 7.1Hz, 1H), 1.02 (d, J = 6.7 Hz, 6H). 13 C NMR (151 MHz, DMSO) δ 170.3, 163.7,162.6, 161.7, 155.0, 132.8, 131.1, 126.8, 125.5, 115.4, 113.9, 101.5, 75.1,59.7, 27.6, 20.7, 18.7, 17.0, 14.0. HRMS (ESI-TOF) m / z [M+H] + calcd forC 16 H 18 N3O2S, 316.1120; found, 316.1122. mp (uncorrected, capillary): 152-154 °C Example 45: Abrasive acid was used to prepare abrasive amides. The chemical structural formula of abrasive amides is as follows:

[0075] At room temperature, 0.2 mmol / L rosin acid, 0.4 mmol / L bromodifluoroacetamide 2, and 0.4 mmol / L cesium carbonate 2 were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (16.3 mg, 27%). 1 H NMR (600MHz, DMSO) δ 7.03 (s, 1H), 6.73 (s, 1H), 5.71 (s, 1H), 5.32 (s, 1H), 2.19 (dt, J = 13.5, 6.7 Hz, 1H), 2.10 – 1.97 (m, 2H), 1.91 (s, 2H), 1.84 – 1.63 (m, 5H), 1.57 – 1.46 (m, 2H), 1.41 (d, J = 12.7 Hz, 1H), 1.15 (d, J = 7.0 Hz,1H), 1.12 (s, 3H), 1.10 – 1.04 (m, 2H), 0.97 (dd, J = 6.7, 2.3 Hz (6H), 0.75 (s, 3H). 13 C NMR (151 MHz, DMSO) δ 179.8, 144.1, 134.8, 122.4, 120.7, 50.4,45.2, 44.5, 37.7, 37.0, 34.2, 34.1, 26.8, 24.8, 21.9, 21.3, 20.7, 17.9, 16.9,13.8. HRMS (ESI-TOF) m / z [M+H] + calcd for C 20 H 32NO, 302.2484; found, 302.2485. Example 46: Dehydrocholic acid was used to prepare dehydrocholate. The chemical structural formula of dehydrocholate is as follows:

[0076] At room temperature, 0.2 mmol / L (1.0 Equivalent) of dehydrocholic acid, 0.4 mmol / L (2.0 Equivalent) of bromodifluoroacetamide 2, and 0.4 mmol / L (2.0 Equivalent) of cesium carbonate were weighed into a 20 mL reaction tube equipped with a magnetic stirrer. 2 mL of acetone was injected into the reaction tube using a syringe, followed by the addition of 4 mmol / L of water using a microsyringe. After the materials were added, the reaction tube was sealed with a rubber stopper, and then stirred in a heating module preheated to 90°C for 12 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and the solvent was removed by rotary evaporation to recover the acetone solvent. The residual solid was purified by rapid silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding a white solid product (61.8 mg, 77%). 1 H NMR (600MHz, DMSO) δ 7.23 (s, 1H), 6.66 (s, 1H), 3.04 (t, J = 11.7 Hz, 1H), 2.98 (dd,J = 13.0, 5.4 Hz, 1H), 2.83 (t, J = 12.7 Hz, 1H), 2.49 – 2.41 (m, 1H), 2.30 (td, J = 14.7, 5.3 Hz, 1H), 2.22 (dt, J = 27.5, 13.7 Hz, 2H), 2.15 – 2.04 (m,2H), 2.00 – 1.93 (m, 4H), 1.89 – 1.81 (m, 3H), 1.81 – 1.76 (m, 1H), 1.69 (td,J = 11.1, 5.9 Hz, 2H), 1.49 (td,J = 14.5, 3.9 Hz, 1H), 1.33 (s, 3H), 1.28 –1.16 (m, 4H), 1.00 (s, 3H), 0.76 (d, J = 6.3 Hz, 3H). 13C NMR (151 MHz, DMSO) δ212.0, 209.7, 209.6, 174.6, 56.2, 51.2, 48.0, 46.0, 45.4, 44.5, 44.0, 42.5,38.4, 36.2, 35.6, 35.1, 34.6, 32.3, 31.0, 27.3, 24.6, 21.1, 18.8, 11.5. HRMS(ESI-TOF) m / z [M+H] + calcd for C 24 H 36 NO4, 402.2644; found, 402.2643. In summary: This invention provides a method for preparing primary amides using bromodifluoroacetamide as a carboxylic acid activating agent and amidation ammonia source. This method effectively solves the problem of poor direct condensation reactivity in traditional routes, while eliminating the need for expensive condensing agents or metal catalysts and avoiding the stringent requirement of anhydrous operation in the acyl chloride method. This method exhibits excellent reaction efficiency and broad substrate universality even under air atmosphere, especially good compatibility with acid-sensitive groups. Notably, the reaction conditions are mild, requiring no special equipment or anhydrous and oxygen-free control, and the post-processing is simple, significantly reducing production costs and waste emissions. These advantages collectively provide a practical and sustainable green synthetic route for the large-scale preparation of primary amide compounds.

[0077] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from its spirit or essential characteristics. Therefore, the embodiments should be considered in all respects as exemplary and non-limiting, and the scope of the invention is defined by the appended claims rather than the foregoing description. Thus, all variations falling within the meaning and scope of equivalents of the claims are intended to be included within the present invention. No reference numerals in the claims should be construed as limiting the scope of the claims.

Claims

1. A method for preparing primary amides from carboxylic acids mediated by bromodifluoroacetamide, characterized in that: Includes the following steps: S1: Feeding: Add carboxylic acid, bromodifluoroacetamide, and cesium carbonate to a reaction tube equipped with a magnetic stirrer; S2: Add solvent, add acetone and water to the reaction tube; S3: Reaction, seal the reaction tube, place the reaction tube in the heating module and stir the reaction; S4: Post-treatment: After the reaction solution is cooled to room temperature, acetone is removed by rotary evaporation and recovered. The residual solid is purified by silica gel rapid column chromatography with petroleum ether and ethyl acetate as eluents to obtain the primary amide product.

2. The method for preparing primary amides from carboxylic acids mediated by bromodifluoroacetamide according to claim 1, characterized in that: The molar ratio of carboxylic acid, bromodifluoroacetamide, and cesium carbonate in S1 is 1:2:2; The reaction tube in S2 is a 20mL glass reaction tube, the ratio of carboxylic acid to acetone is 0.2 mmol: 2 mL, and the molar ratio of carboxylic acid to water is 1:

20. The sealed reaction tube used in S3 is a rubber stopper sealed reaction tube, which does not require anhydrous and oxygen-free control; The temperature of the heating module is 90°C, and the stirring reaction time is 12 hours.

3. The method for preparing primary amides from carboxylic acids mediated by bromodifluoroacetamide according to claim 1, characterized in that: The carboxylic acids include at least aromatic carboxylic acids, heterocyclic carboxylic acids, unsaturated carboxylic acids, aliphatic carboxylic acids, and pharmaceutical carboxylic acids.

4. The method for preparing primary amides from carboxylic acids mediated by bromodifluoroacetamide according to claim 3, characterized in that: The aromatic carboxylic acids include at least benzoic acid, substituted benzoic acid, 1-naphthoic acid, 2-naphthoic acid, and p-phenylbenzoic acid; The substituents of the substituted benzoic acid include at least nitro, trifluoromethyl, methoxy, tert-butyl, and iodine.

5. The method for preparing primary amides from carboxylic acids mediated by bromodifluoroacetamide according to claim 3, characterized in that: The heterocyclic carboxylic acids include at least 2-pyridinecarboxylic acid, 2-quinolinecarboxylic acid, and furanylacrylic acid.

6. The method for preparing primary amides from carboxylic acids mediated by bromodifluoroacetamide according to claim 3, characterized in that: The unsaturated carboxylic acids include at least cinnamic acid, substituted cinnamic acid, enoic acid, and dienoic acid; The substituted cinnamic acid includes at least 4-methoxycinnamic acid, the enoic acid includes only (Z)-4-decenoic acid, and the dienoic acid includes at least 9 (Z),12 (E)-octadecadienoic acid.

7. The method for preparing primary amides from carboxylic acids mediated by bromodifluoroacetamide according to claim 3, characterized in that: The aliphatic carboxylic acids include at least chain fatty acids, cycloalkane carboxylic acids, and adamantane carboxylic acid; The chain fatty acids include at least caprylic acid, oleic acid, palmitic acid, and icosanoic acid.

8. The method for preparing primary amides from carboxylic acids mediated by bromodifluoroacetamide according to claim 3, characterized in that: The drug-type carboxylic acids include at least naproxen, ibuprofen, oxapzin, ciprofibrate, p-chlorophenoxyisobutyric acid, ketoibuprofen, flurbiprofen, loxoprofen, gemfibrozil, itococcal acid, indomethacin, bendazac, adapalene, sulindac, febuxostat, rosin acid, and dehydrocholic acid.

9. The method for preparing primary amides from carboxylic acids mediated by bromodifluoroacetamide according to claim 1, characterized in that: The volume ratio of petroleum ether to ethyl acetate is adjusted according to the type of carboxylic acid substrate.

10. The method for preparing primary amides from carboxylic acids mediated by bromodifluoroacetamide according to claim 1, characterized in that: The acetone solvent recovered in S4 can be recycled in the solvent addition process of S2.

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