Method for electrochemical synthesis of amide compounds

Abstract

According to the novel method for electrochemical synthesis of the amide compound, alpha-carbonyl sulfur ylide, alkylamine and azidotrimethylsilane serve as raw materials, an amide structure is efficiently constructed through electrochemical reaction, and a target amidation product can be obtained with nearly equivalent yield. The method provided by the invention is carried out under mild conditions, does not need a condensing agent and a catalyst, does not have additional byproducts, and shows environmental friendliness; the method has the advantages of good functional group tolerance, extremely high reaction yield and simple purification mode, can be applied to electrochemical continuous flow reaction, is suitable for industrial production, and has extremely high industrial application value.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and more specifically to a method for the electrochemical synthesis of amide compounds. Background Technology

[0002] As one of the most critical and ubiquitous functional groups in organic and biochemistry, the amide bond endows amide compounds with a wide range of important applications. These compounds play a crucial bridging role in multiple fields, including chemistry, life sciences, materials science, and industrial applications. Statistics show that over 25% of drug molecules contain amide structures, highlighting their special status in medicinal chemistry. From proteins that form the basis of life to nylon textiles used in everyday wear, to drugs for treating diseases, and even key components in industrial production and scientific research, amide compounds are virtually ubiquitous, possessing both fundamental and pivotal application value.

[0003] Currently, the synthesis of amides mainly employs the following methods: 1. Acid-amine condensation method: The condensation reaction of carboxylic acids with amines is one of the most common strategies for constructing amide bonds. This is usually achieved with the aid of condensing agents, such as carbodiimide condensing agents like 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI) or onium salt condensing agents. This method is widely used in both laboratory and industrial scales. However, carbodiimide condensing agents have low yields for carboxylic acid substrates with steric hindrance at the α-position of the acid or electron-withdrawing groups; while onium salt condensing agents have limitations such as high cost. 2. Acyl halide method: Acyl chlorides or acyl bromides can react rapidly with aliphatic or aromatic amines to generate amides in high yields. These types of reactions are usually exothermic processes; Third, the acid anhydride method: Acid anhydrides can also be used as acylation reagents for amines, but their reactivity is usually lower than that of the corresponding acyl halides, so the reaction rate with amines is relatively slow; Fourth, ammonolysis of esters: The reaction of esters with ammonia is one of the common methods for preparing amides in the laboratory, but it usually requires the promotion of strong bases or reagents such as trimethylaluminum (AlMe3) to proceed smoothly; Fifth, rearrangement and addition reactions: Various rearrangement and addition pathways, including the Ritter reaction, Beckmann rearrangement, Schmidt rearrangement and Overman rearrangement, also provide important means for the construction of amides, but these reactions often have specific requirements for the substrate and their application range is relatively limited. Summary of the Invention

[0004] Existing methods for synthesizing amides typically rely on condensing agents or catalysts and suffer from harsh reaction conditions and low efficiency. Some reaction byproducts are difficult to separate, leading to challenges in product purification. To address these issues, this invention proposes a novel electrochemical method for synthesizing amide compounds. This method uses α-carbonylthioylide, alkylamine, and azidotrimethylsilane as raw materials to efficiently construct amide structures through electrochemical reactions, generating the target amide product D.

[0005] To achieve the above objectives, the technical solution of the present invention is as follows: An electrochemical method for synthesizing amide compound D, using compounds A, B, and C as raw materials, is shown in the following reaction formula:

[0006] in, R1 is selected from C1-6 alkyl or cycloalkyl groups. , or Where X is O or S; R2 is selected from C1-6 alkyl or cycloalkyl groups. , or , where X is 0 or S; m is an integer from 1 to 3; R3 is H, or R2 and R3 together with N atoms form a five-membered ring or a six-membered ring; R4 is H, a C1-6 alkyl group, one or more halogen-substituted C1-6 alkyl groups, halogen, C1-6 alkoxy or cyano groups; R5 is H, a C1-6 alkyl group, one or more halogen-substituted C1-6 alkyl groups, halogen, C1-6 alkoxy or cyano groups.

[0007] R2 and R3 together with N atoms form a five-membered or six-membered ring, namely a tetrahydropyrrole ring, a piperidine ring, or a morpholine ring.

[0008] As used herein, the term "halogen" refers to fluorine, chlorine, bromine, or iodine, preferably fluorine, chlorine, or bromine.

[0009] The term "C" used in this article 16 "Alkyl" refers to a saturated straight-chain or branched hydrocarbon group having 16 carbon atoms, such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl, etc. The term "C" as used in this article... 16 The cycloalkyl group is cyclohexyl.

[0010] The term "C" as used in this invention 16 "Alkoxy" refers to a saturated straight-chain or branched alkoxy group with 16 carbon atoms, such as methoxy, ethoxy, tert-butoxy, etc.

[0011] The term "one or more halogen-substituted C1-6 alkyl groups" as used in this invention refers to straight-chain or branched C1-6 alkyl groups substituted with multiple halogens, such as trifluoromethyl, difluoromethyl, etc.

[0012] According to one embodiment of the present invention, R1 is any one of C1-6 alkyl, phenyl, halophenyl, methylphenyl, methoxyphenyl, tert-butylphenyl, trifluoromethylphenyl, cyanophenyl, naphthyl, thiophenyl, and furanyl. R2 is any one of alkyl, benzyl, halobenzyl, alkylbenzyl, methoxybenzyl, methylenethiophenyl, methylenefuranyl, and methylenenaphthyl.

[0013] According to one embodiment of the present invention, compound D is selected from:

[0014] According to one embodiment of the present invention, the molar ratio of α-carbonylsulfonyl ylide compound (A), amine compound (B) and azidotrimethylsilane (C) is 1:1:1 to 3:1:3.

[0015] According to one embodiment of the present invention, the electrolytic cell used in the electrochemical synthesis method is an undivided electrolytic cell; the electrode is one or more of graphite sheets, graphite felt, carbon paper, glassy carbon mesh, platinum sheets, and nickel foam. Further, the anode is one or more of graphite sheets, graphite felt, carbon paper, and glassy carbon mesh, and the cathode is one or more of graphite sheets, graphite felt, carbon paper, glassy carbon mesh, platinum sheets, and nickel foam.

[0016] According to one embodiment of the present invention, the solvent is one of N,N-dimethylformamide, dimethyl sulfoxide, N-methylpyrrolidone, and acetonitrile.

[0017] According to one embodiment of the present invention, the reaction time is 2-6 h.

[0018] According to one embodiment of the present invention, the current is 5-10 mA.

[0019] According to one embodiment of the present invention, the graphite electrode is the anode and the platinum electrode is the cathode; the electrolyte is tetrabutylammonium hexafluorophosphate with a concentration of 0.1 M; the current is 5 mA; and the solvent is dimethyl sulfoxide.

[0020] According to one embodiment of the present invention, the reaction temperature is 25 °C.

[0021] According to one embodiment of the present invention, the molar ratio of the α-carbonyl thioylide compound, the amine compound, and the azidotrimethylsilane is 2:1:2, and the concentration of the amine compound is 0.05 M.

[0022] According to one embodiment of the present invention, the reaction is characterized in that, after the reaction is completed, water is added to quench the reaction, and the product is extracted three times with ethyl acetate. The organic phases are combined and then washed once with a saturated sodium chloride aqueous solution to obtain the organic phase. The solvent is concentrated under reduced pressure, and the product can be obtained without column chromatography purification.

[0023] Beneficial effects: This invention provides a method for the electrochemical synthesis of amide compounds. Through a highly efficient electrochemical strategy, α-carbonylthioylide, azidotrimethylsilane, and amine compounds are amidated, yielding the amidated products in near-equivalent yields. This method is carried out under mild conditions, requiring no high temperatures, metal catalysts, or chemical redox reagents, exhibiting environmental friendliness, high functional group tolerance, extremely high reaction yields, and simple purification methods. Furthermore, it can be applied to continuous electrochemical reactions, making it suitable for industrial production and possessing significant industrial application value. Detailed Implementation

[0024] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present application will be clearly and completely described below in conjunction with the embodiments of the present application. Obviously, the described embodiments are only some embodiments of the present application, and not all embodiments. Unless otherwise specified, any range described in the present invention includes the endpoint value, any value between the endpoint values, and any sub-range formed by the endpoint value or any value between the endpoint values. Unless otherwise specified, all percentages mentioned in the present invention are mass percentages.

[0025] The following examples further illustrate the content of this invention, but are not intended to limit the invention.

[0026] Example 1: Preparation of N-benzylbenzamide D1

[0027] The specific operating steps were as follows: 0.4 mmol of thioyl ylide and 0.4 mmol of tetrabutylammonium hexafluorophosphate were weighed into a 10 mL electrolytic cell. The electrolytic cell was equipped with a 1.5 cm × 1.0 cm × 0.1 cm graphite sheet as the anode and a 1.5 cm × 1.0 cm × 0.1 cm platinum sheet as the cathode. 4 mL of dimethyl sulfoxide was added as solvent, along with 0.2 mmol of benzylamine and 0.4 mmol of azide-trimethylsilane. The reaction was carried out at room temperature for 6 h with an electrolytic current of 5 mA, monitored by TLC until the substrate was completely depleted. After the reaction was completed, the mixture was quenched with water, extracted three times with ethyl acetate, and the organic phases were combined. The organic phase was then washed once with a saturated sodium chloride aqueous solution to obtain the organic phase. The solvent was concentrated under reduced pressure to obtain the product.

[0028] Table 1. Effect of different substrate ratios on the preparation of compound D1

[0029] As shown in Table 1, the product yield is highest when the substrate ratio is 3:1:3.

[0030] Table 2. Effect of different anode materials on the preparation of compound D1

[0031] As shown in Table 2, the product yield is highest when the anode material is graphite sheet.

[0032] Table 3. Effect of different cathode materials on the preparation of compound D1

[0033] As shown in Table 3, the product yield is highest when the cathode material is a platinum sheet.

[0034] Table 4. Effect of different solvents on the preparation of compound D1

[0035] As shown in Table 4, the product yield is highest when the solvent is dimethyl sulfoxide.

[0036] Table 5. Effect of different times on the preparation of compound D1

[0037] As shown in Table 5, the product yield is highest when the time is 6 hours.

[0038] Table 6. Effect of different currents (equal charge Q=I×t) on the preparation of compound D1

[0039] As shown in Table 6, the product yield is highest when the current is 5 mA and the reaction time is 6 h.

[0040] Examination of substrate universality Compounds D1-D41 in the table below were prepared under the optimal reaction conditions described in the above examples.

[0041]

[0042] Examples of electrochemical continuous flow reactions: Preparation of N-benzylbenzamide D1

[0043] Specific operating steps: A mixed solution of sulfur ylide substrate (0.02 mol / L), tetrabutylammonium hexafluorophosphate (0.02 mol / L), benzylamine (0.01 mol / L), and azidotrimethylsilane (0.02 mol / L) dissolved in dimethyl sulfoxide was pumped into a flowing electrolytic cell (graphite sheet as anode, platinum sheet as cathode) using a micro-injection pump under air atmosphere. The flow rate was controlled at 0.3 mL / min, and an appropriate current was applied to ensure complete conversion of the material in a single pass through the electrolytic cell. The eluent (10 mL) after 33.3 minutes was collected and concentrated under reduced pressure using a rotary evaporator. 10 mL of water was added to the concentrated residue, followed by extraction three times with ethyl acetate (10 mL each time). The organic phase was then washed once with a saturated sodium chloride aqueous solution to obtain the organic phase. The solvent was concentrated under reduced pressure to obtain the product.

[0044] In summary, this invention provides an electrochemical method for synthesizing amide compounds. Through an efficient electrochemical strategy, α-carbonylthioylide, azide-trimethylsilane, and amine compounds are amidated, resulting in the efficient synthesis of a series of amide compounds. The method is carried out under mild conditions, requires no condensing agents or catalysts, produces no significant byproducts, exhibits environmental friendliness, and demonstrates good functional group tolerance. It boasts high reaction yields, simple purification, and eliminates the need for column chromatography, demonstrating excellent synthetic practicality and suitability for industrial production. Furthermore, it can be applied to continuous electrochemical reactions, possessing significant industrial application value.

[0045] The specific structures and structural analysis data of compounds D1-D41 are as follows.

[0046] Compound D1: N-benzylbenzamide, white solid, 0.2 mmol. Scale: 99% isolated (41.8 mg). 1 H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 7.2 Hz, 2H), 7.49(t, J = 7.2 Hz, 1H), 7.41 (t, J = 7.2 Hz, 2H), 7.32 (m, 5H), 6.63 (br s, 1H), 4.62 (d, J = 6.0 Hz, 2H). 13 C NMR (101 MHz, CDCl3) δ 167.5, 138.3, 134.5,131.6, 128.9, 128.7, 128.0, 127.7, 127.1, 44.2. Compound D2: N-(2-fluorobenzyl)benzamide, yellow solid, 0.2 mmol. Scale: 88% isolated (40.3 mg). 1 H NMR (400 MHz, CDCl3) δ 7.81-7.72 (m, 2H), 7.53-7.43 (m, 1H), 7.41-7.33 (m, 3H), 7.29-7.19 (m, 1H), 7.12-6.98 (m, 2H), 6.75(br s, 1H), 4.65 (d, J = 6.0 Hz, 2H). 13 C NMR (101 MHz, CDCl3) δ 167.6, 161.1(d, J = 246.9 Hz), 134.3, 131.7, 130.4 (d, J = 4.3 Hz), 129.4 (d, J = 8.2Hz), 128.6, 127.1, 125.3 (d, J = 14.8 Hz), 124.4 (d, J = 3.4 Hz), 115.5 (d, J = 21.3 Hz), 38.1 (d, J = 3.9 Hz). 19 F NMR (376 MHz, CDCl3) δ -118.8. Compound D3: N-(3-fluorobenzyl)benzamide, yellow solid, 0.2 mmol scale: 92% (45.8 mg) isolated. 1 H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 7.2 Hz, 2H), 7.47 (t, J = 7.6 Hz, 1H), 7.38 (t, J = 7.6 Hz, 2H), 7.30-7.20 (m, 1H),7.06 (d, J = 7.6 Hz, 1H), 6.99 (d, J = 10 Hz, 1H), 6.96-6.89 (m, 2H), 4.56(d, J = 6.0 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 167.7, 163.1 (d, J = 247.3Hz), 141.0 (d, J = 7.3 Hz), 134.2, 131.8, 130.3 (d, J = 8.2 Hz), 128.7,127.1, 123.3 (d, J = 2.9 Hz), 114.5 (d, J = 40.7 Hz), 114.5 (d, J = 2.4 Hz), 43.5. 19 F NMR (376 MHz, CDCl3) δ -112.6. Compound D4: N-(3-chlorobenzyl)benzamide, yellow solid, 0.2 mmol scale: 90% isolated (44.1 mg), 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 7.2 Hz, 2H), 7.49 (t, J = 7.2 Hz, 1H), 7.39 (t, J = 8.0 Hz, 2H), 7.29 (s, 1H), 7.25-7.14 (m, 3H), 6.92 (br s, 1H), 4.55 (d, J = 6.0 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 167.7, 140.5, 134.6, 134.1, 131.8, 130.1, 128.7, 127.8, 127.7,127.1, 125.9, 43.5. Compound D5: N-(3-bromobenzyl)benzamide, yellow solid, 0.2 mmol scale: 92% (53.2 mg) isolated. 1 H NMR (400 MHz, CDCl3) δ 7.82-7.73 (m, 2H), 7.54-7.43 (m, 2H), 7.42-7.36 (m, 3H), 7.23 (s, 1H), 7.17 (t, J = 7.6 Hz, 1H), 6.86(br s, 1H), 4.56 (d, J = 6.0Hz, 2H).13 C NMR (101 MHz, CDCl3) δ 167.7, 140.8,134.1, 131.8, 130.8, 130.7, 130.4, 128.7, 127.2, 126.5, 122.8, 43.5. Compound D6: N-(4-fluorobenzyl)benzamide, yellow solid, 0.2 mmol scale: 97% (44.4 mg) isolated. 1 H NMR (400 MHz, CDCl3) δ 7.88-7.69 (m, 2H), 7.53-7.44 (m, 1H), 7.39 (t, J = 7.6 Hz, 2H), 7.32-7.22 (m, 2H), 6.98 (t, J = 8.4Hz, 2H), 6.83 (br s, 1H), 4.55 (d, J = 5.6 Hz, 2H). 13 C NMR (101 MHz, CDCl3) δ167.6, 162.3 (d, J = 246.8 Hz), 134.3, 134.2 (d, J = 3.3 Hz), 131.7, 129.6 (d, J = 8.2 Hz), 128.7, 127.1, 115.6 (d, J = 21.7 Hz), 43.4. 19 F NMR (376 MHz, CDCl3) δ -114.9. Compound D7: N-(4-chlorobenzyl)benzamide, yellow solid, 0.2 mmol scale: 94% (46.1 mg) isolated. 1 H NMR (400 MHz, CDCl3) δ 7.82-7.73 (m, 2H), 7.53-7.44 (m, 1H), 7.38 (m, 2H), 7.31-7.17 (m, 4H), 6.82 (br s, 1H), 4.53 (d, J =5.6 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 167.6, 136.9, 134.2, 133.4, 131.8,129.3, 128.9, 128.7, 127.1, 43.4. Compound D8: N-(4-bromobenzyl)benzamide, yellow solid, 0.2 mmol scale: 86% (49.7 mg) isolated. 1 H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 7.2 Hz,2H), 7.54-7.44 (m, 1H), 7.46-7.34 (m, 4H), 7.17 (d, J = 8.4 Hz,2H), 6.88 (brs, 1H), 4.52 (d, J = 6.0 Hz, 2H). 13 C NMR (101 MHz, CDCl3) δ 167.7, 137.5, 134.2, 131.9, 131.8, 129.6, 128.7, 127.1, 121.5, 43.4. Compound D9: N-(4-iodobenzyl)benzamide, yellow solid, 0.2 mmol scale: 77% (51.9 mg) isolated. 1 H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 6.8 Hz, 2H), 7.61 (d, J = 8.4 Hz, 2H), 7.48 (t, J = 7.6 Hz, 1H), 7.38 (t, J = 7.6 Hz, 2H), 7.03 (d, J = 8.4 Hz, 2H), 6.92 (br s, 1H), 4.50 (d, J = 6.0 Hz, 2H). 13 CNMR (101 MHz, CDCl3) δ 167.6, 138.2, 137.8, 134.2, 131.8, 129.8, 128.7,127.1, 93.0, 43.5. Compound D10: N-(2-methylbenzyl)benzamide, yellow solid, 0.2 mmol scale: 90% (40.5 mg) isolated. 1 H NMR (400 MHz, CDCl3) δ 7.82-7.73 (m, 2H), 7.54-7.45 (m, 1H), 7.40 (t, J = 8.0 Hz, 2H), 7.29 (d, J = 6.8 Hz, 1H), 7.23-7.15(m, 3H), 6.46 (br s, 1H), 4.61 (d, J = 5.6 Hz, 2H), 2.36 (s, 3H). 13 C NMR (101MHz, CDCl3) δ 167.4, 136.6, 135.9, 134.4, 131.6, 130.7, 128.7, 128.6, 127.9,127.1, 126.3, 42.4, 19.1. Compound D11: N-(4-methylbenzyl)benzamide, yellow solid, 0.2 mmol scale: 87% (39.2 mg) isolated. 1 H NMR (400 MHz, CDCl3) δ 7.82-7.75 (m, 2H), 7.53-7.44 (m, 1H), 7.40 (t, J = 8.4 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 7.15 (d, J = 8.0 Hz, 2H), 6.65 (br s, 1H), 4.57 (d, J = 5.6 Hz, 2H), 2.34 (s, 3H). 13 CNMR (101 MHz, CDCl3) δ 167.5, 137.3, 135.3, 134.5, 131.5, 129.5, 128.6,127.9, 127.1, 43.9, 21.2. Compound D12: N-(4-methoxybenzyl)benzamide, yellow solid, 0.2 mmol. Scale: 80% isolated (38.6 mg). 1H NMR (400 MHz, CDCl3) δ 7.81-7.73 (m, 2H), 7.52-7.43 (m, 1H), 7.42-7.36 (m, 2H), 7.26 (d, J = 8.8 Hz, 2H), 6.86 (d, J =8.4 Hz, 2H), 6.57 (br s, 1H), 4.55 (d, J = 5.6 Hz (2H), 3.78 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 167.4, 159.2, 134.5, 131.6, 130.4, 129.4, 128.7, 127.1,114.2, 55.4, 43.7. Compound D13: N-(3,4-dimethylbenzyl)benzamide, yellow solid, 0.2 mmol. Scale: 84% (40.2 mg) isolated. 1 H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 6.8Hz, 2H), 7.49 (t, J = 7.2 Hz, 1H), 7.45-7.36 (m, 2H), 7.15-6.99 (m, 3H), 6.57(br s, 1H), 4.56 (d, J = 5.6 Hz, 2H), 2.25 (s, 6H). 13 C NMR (101 MHz, CDCl3) δ167.4, 137.1, 136.0, 135.7, 134.6, 131.5, 130.0, 129.4, 128.6, 127.1, 125.5,44.0, 19.8, 19.5. Compound D14: N-cyclohexylbenzamide, yellow solid, 0.2 mmol. Scale: 97% isolated (39.4 mg). 1H NMR (400 MHz, CDCl3) δ 7.77-7.71 (m, 2H), 7.50-7.43 (m,1H), 7.42-7.36 (m, 2H), 6.11 (br s, 1H), 3.95 (m, 1H), 2.01 (m, 2H), 1.78-1.69 (m, 2H), 1.68-1.57 (m, 1H), 1.48-1.30 (m, 2H), 1.30-1.10 (m, 3H). 13 C NMR (101 MHz, CDCl3) δ 166.8, 135.2, 131.3, 128.6, 127.0, 48.8, 33.3, 25.6, 25.0. Compound D15: 1-benzoylpiperidine, yellow oil, 0.2 mmol. Scale: 92% isolated (34.8 mg). 1 H NMR (400 MHz, CDCl3) δ 7.37 (s, 5H), 3.69 (s, 2H), 3.32 (s,2H), 1.66 (s, 4H), 1.50 (s, 2H). 13 C NMR (101 MHz, CDCl3) δ 170.4, 136.6,129.4, 128.5, 126.9, 48.8, 43.2, 26.6, 25.7, 24.7. Compound D16: Morpholino(phenyl) methyl ketone, yellow oil, 0.2 mmol. Scale: 85% isolated (32.5 mg). 1 H NMR (400 MHz, CDCl3) δ 7.46-7.34 (m, 5H), 3.94-3.27 (m, 8H). 13 C NMR (101 MHz, CDCl3) δ 170.5, 135.4, 130.0, 128.7, 127.2, 67.0, 48.3,42.6. Compound D17: Phenyl(pyrrolidone-1-yl) methyl ketone, yellow oil, 0.2 mmol. Scale: 85% (29.8 mg) isolated. 1 H NMR (400 MHz, CDCl3) δ 7.52-7.46 (m, 2H), 7.37 (d, J= 5.6 Hz, 3H), 3.63 (t, J = 6.8 Hz, 2H), 3.40 (t, J = 6.8 Hz, 2H), 1.98-1.89(m, 2H), 1.89-1.80 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 169.8, 137.3, 129.8,128.3, 127.1, 49.7, 46.2, 26.5, 24.5. Compound D18: N-tert-butylbenzamide, white solid, 0.2 mmol. Scale: 84% isolated (29.8 mg). 1 H NMR (400 MHz, CDCl3) δ 7.76-7.67 (m, 2H), 7.53-7.42 (m,1H), 7.43-7.37 (m, 2H), 5.95 (br s, 1H), 1.47 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 167.0, 136.0, 131.2, 128.6, 126.8, 51.7, 29.0. Compound D19: N-isopropylbenzamide, yellow solid, 0.2 mmol. Scale: 96% isolated (31.3 mg). 1 H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 6.8 Hz, 2H), 7.49-7.43(m, 1H), 7.42-7.36 (m, 2H), 6.06 (br s, 1H), 4.36-4.19 (m, 1H), 1.25 (d, J =6.4 Hz, 6H). 13 C NMR (101 MHz, CDCl3) δ 166.8, 135.1, 131.3, 128.6, 126.9, 42.0, 22.9. Compound D20: N-isobutylbenzamide, yellow solid, 0.2 mmol. Scale: 98% isolated (34.7 mg). 1H NMR (400 MHz, CDCl3) δ 7.80-7.71 (m, 2H), 7.53-7.43 (m,1H), 7.42-7.36 (m, 2H), 6.44 (br s, 1H), 3.33-3.15 (m, 2H), 1.88 (m, 1H),0.95 (d, J = 6.4 Hz, 6H). 13 C NMR (101 MHz, CDCl3) δ 167.8, 135.0, 131.4,128.6, 127.0, 47.4, 28.7, 20.3. Compound D21: N-butylbenzamide, yellow oil, 0.2 mmol. Scale: 95% isolated (33.7 mg). 1 H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 7.2 Hz, 2H), 7.48-7.43 (m, 1H), 7.42-7.35 (m, 2H), 6.42 (br s, 1H), 3.47-3.34 (m, 2H), 1.62-1.52 (m, 2H), 1.44-1.32 (m, 2H), 0.93 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 167.7, 134.9, 131.3, 128.6, 127.0, 39.9, 31.8, 20.2, 13.9. Compound D22: N-phenylethylbenzamide, yellow solid, 0.2 mmol. Scale: 90% isolated (40.5 mg). 1 H NMR (400 MHz, CDCl3) δ 7.71-7.67 (m, 2H), 7.51-7.43(m, 1H), 7.41-7.34 (m, 2H), 7.34-7.27 (m, 2H), 7.26-7.19 (m, 3H), 6.38 (br s,1H), 3.74-3.63 (m, 2H), 2.92 (t, J = 7.2 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ167.7, 139.1, 134.8, 131.5, 128.9, 128.8, 128.7, 127.0, 126.7, 41.3, 35.8. Compound D23: N-(naphthyl-2-ylmethyl)benzamide, brown solid, 0.2 mmol. Scale: 53% (27.7 mg) isolated. 1 H NMR (400 MHz, CDCl3) δ 7.85-7.74 (m, 6H),7.54-7.35 (m, 6H), 6.67 (br s, 1H), 4.78 (d, J = 5.6 Hz, 2H). 13 C NMR (101MHz, CDCl3) δ 167.6, 135.8, 134.5, 133.5, 132.9, 131.7, 128.8, 127.9, 127.8,127.1, 126.6, 126.4, 126.1, 44.4. Compound D24: N-(thiophene-2-ylmethyl)benzamide, brown solid, 0.2 mmol. Scale: 72% isolated (31.3 mg). 1 H NMR (400 MHz, CDCl3) δ 7.81-7.75 (m, 2H),7.53-7.45 (m, 1H), 7.45-7.36 (m, 2H), 7.28-7.20 (m, 1H), 7.06-6.99 (m, 1H),6.98-6.93 (m, 1H), 6.64 (br s, 1H), 4.79 (d, J = 6.0 Hz, 2H). 13 C NMR (101MHz, CDCl3) δ 167.3, 140.9, 134.3, 131.7, 128.7, 127.1, 127.1, 126.3, 125.4,38.9. Compound D25: N-(furan-2-ylmethyl)benzamide, brown solid, 0.2 mmol. Scale: 60% isolated (24.1 mg). 1 H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 6.8Hz, 2H), 7.50 (t,J = 7.6 Hz, 1H), 7.42 (t, J = 7.6 Hz, 2H), 7.38 (s, 1H), 6.47 (br s, 1H), 6.32 (d, J = 14.4 Hz, 2H), 4.64 (d, J = 5.6 Hz, 2H). 13 C NMR (101 MHz, CDCl3) δ 167.4, 151.3, 142.5, 134.3, 131.8, 128.7, 127.1, 110.7,107.9, 37.2. Compound D26: N-benzyl-3-fluorobenzamide, yellow solid, 0.2 mmol scale: 93% (42.6 mg) isolated. 1 H NMR (400 MHz, CDCl3) δ 7.56-7.47 (m, 2H), 7.42-7.26 (m, 6H), 7.23-7.13 (m, 1H), 6.63 (br s, 1H), 4.60 (d, J = 6.0 Hz, 2H). 13 C NMR (101 MHz, CDCl3) δ 166.3 (d, J = 2.7 Hz), 162.8 (d, J = 248.8 Hz), 138.0, 136.7 (d, J = 6.8 Hz), 130.3 (d, J = 14.0 Hz), 128.8, 128.0, 127.9,122.6 (d, J = 3.1 Hz), 118.5 (d, J = 18.3 Hz), 114.6 (d, J = 16.5 Hz), 44.2. 19 F NMR (376 MHz, CDCl3) δ -111.7. Compound D27: N-benzyl-3-chlorobenzamide, yellow solid, 0.2 mmol scale: 96% (47.1 mg) isolated. 1 H NMR (400 MHz, CDCl3) δ 7.77 (t, J= 2 Hz, 1H), 7.64 (d, J = 7.6 Hz, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.40-7.24 (m, 6H), 6.73(br s, 1H), 4.59 (d, J = 5.6 Hz, 2H). 13 C NMR (101 MHz, CDCl3) δ 166.3, 138.0,136.2, 134.8, 131.6, 130.0, 128.9, 128.0, 127.8, 127.5, 125.2, 44.3. Compound D28: N-benzyl-3-bromobenzamide, white solid, 0.2 mmol scale: 92% isolated (53.2 mg). 1 H NMR (400 MHz, CDCl3) δ 7.91 (t, J = 2.0 Hz, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.40-7.18 (m, 6H), 6.68 (br s, 1H), 4.58 (d, J = 5.6 Hz, 2H). 13 C NMR (101 MHz, CDCl3) δ 166.2,138.0, 136.4, 134.6, 130.4, 130.2, 128.9, 128.0, 127.8, 125.7, 122.8, 44.3. Compound D29: N-benzyl-4-fluorobenzamide, yellow solid, 0.2 mmol scale: 88% (40.3 mg) isolated. 1 H NMR (400 MHz, CDCl3) δ 7.84-7.74 (m, 2H), 7.36-7.27 (m, 5H), 7.07 (t, J = 8.8 Hz, 2H), 6.63 (br s, 1H), 4.60 (d, J = 6.0 Hz, 2H). 13 C NMR (101 MHz, CDCl3) δ 166.6, 164.8 (d,J = 252.9 Hz), 138.2, 130.6 (d, J = 2.9 Hz), 129.5 (d, J = 8.9 Hz), 128.9, 127.9, 127.7, 115.6 (d, J =21.7 Hz), 44.2. 19 F NMR (376 MHz, CDCl3) δ -108.0. Compound D30: N-benzyl-4-cyanobenzamide, yellow solid, 0.2 mmol. Scale: 92% isolated (43.4 mg). 1 H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 8.0Hz, 2H), 7.64 (d, J = 6.8 Hz, 2H), 7.38-7.24 (m, 5H), 7.04 (br s, 1H), 4.58(d, J = 6.0 Hz, 2H). 13 C NMR (101 MHz, CDCl3) δ 165.8, 138.3, 137.7, 132.5, 128.9, 127.9, 127.9, 127.1, 118.1, 115.1, 44.4. Compound D31: N-(4-iodobenzyl)benzamide, yellow solid, 0.2 mmol. Scale: 94% (52.5 mg) isolated. 1 H NMR (400 MHz, DMSO-d6) δ 9.34 (t, J = 6.0Hz, 1H), 8.11 (d, J = 8.0 Hz, 2H), 7.85 (d, J = 8.4 Hz, 2H), 7.37-7.30 (m,4H), 7.28-7.21 (m, 1H), 4.51 (d, J = 6.0 Hz, 2H). 13 C NMR (101 MHz, DMSO-d6) δ165.1, 139.4, 138.1, 131.2 (q, J= 32.1 Hz), 128.3, 128.2, 127.3, 126.9,125.4, 124.0 (q, J = 272.0 Hz), 42.8. 19 F NMR (376 MHz, DMSO-d6) δ -61.3. Compound D32: N-benzyl-2-methoxybenzamide, yellow oil, 0.2 mmol scale: 97% (46.8 mg) isolated. 1 H NMR (400 MHz, CDCl3) δ 8.27-8.22 (m, 1H), 8.19(br s, 1H), 7.48-7.39 (m, 1H), 7.38-7.30 (m, 4H), 7.29-7.22 (m, 1H), 7.08 (t, J = 7.6 Hz, 1H), 6.95 (d, J = 8.4 Hz, 1H), 4.68 (d, J = 5.6 Hz, 2H), 3.89 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 165.4, 157.6, 138.9, 132.9, 132.4, 128.7,127.6, 127.3, 121.5, 121.4, 111.4, 56.0, 43.8. Compound D33: N-benzyl-3-methylbenzamide, yellow solid, 0.2 mmol scale: 84% (37.8 mg) isolated. 1 H NMR (400 MHz, CDCl3) δ 7.62 (s, 1H), 7.59-7.54(m, 1H), 7.34 (d, J = 4.8 Hz, 4H), 7.32-7.28 (m, 3H), 6.59 (br s, 1H), 4.62(d, J = 6.0 Hz, 2H), 2.37 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 167.7, 138.5,138.4, 134.4, 132.3, 128.8, 128.5, 128.0, 127.9, 127.6, 124.0, 44.1, 21.4. Compound D34: N-benzyl-4-methoxybenzamide, yellow solid, 0.2 mmol. Scale: 85% isolated (41.0 mg). 1 H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.8Hz, 2H), 7.36-7.23 (m, 5H), 6.88 (d, J = 8.8 Hz, 2H), 6.58 (br s, 1H), 4.59(d, J = 5.6 Hz, 2H), 3.82 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 167.1, 162.3,138.6, 128.9, 128.8, 128.0, 127.6, 126.7, 113.8, 55.5, 44.1. Compound D35: N-benzyl-4-tert-butylbenzamide, yellow solid, 0.2 mmol. Scale: 90% isolated (48.1 mg). 1 H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 8.8Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H), 7.35-7.27 (m, 5H), 6.65 (br s, 1H), 4.62(d, J = 5.6 Hz, 2H), 1.33 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 167.5, 155.1, 138.5, 131.6, 128.8, 127.9, 127.6, 127.0, 125.6, 44.1, 35.0, 31.3. Compound D36: N-benzyl-3,5-dimethylbenzamide, yellow solid, 0.2 mmol. Scale: 86% isolated (41.1 mg). 1 H NMR (400 MHz, CDCl3) δ 7.40 (s, 2H), 7.35(d, J= 4.8 Hz, 4H), 7.32-7.27 (m, 1H), 7.15-7.09 (m, 1H), 6.52 (br s, 1H), 4.62 (d, J = 5.6 Hz, 2H), 2.33 (s, 6H). 13 C NMR (101 MHz, CDCl3) δ 167.9,138.5, 138.3, 134.5, 133.2, 128.8, 128.0, 127.6, 124.9, 44.1, 21.3. Compound D37: N-benzylcyclohexaneformamide, yellow solid, 0.2 mmol. Scale: 59% (25.6 mg) isolated. 1 H NMR (400 MHz, CDCl3) δ 7.35-7.30 (m, 2H), 7.29-7.23(m, 3H), 5.82 (br s, 1H), 4.42 (d, J = 6.0 Hz, 2H), 2.17-2.05 (m, 1H), 1.88(d, J = 13.6 Hz, 2H), 1.83-1.73 (m, 2H), 1.71-1.62 (m, 1H), 1.54-1.38 (m,2H), 1.34-1.13 (m, 3H). 13 C NMR (101 MHz, CDCl3) δ 176.1, 138.6, 128.8, 127.8,127.6, 45.7, 43.5, 29.8, 25.8. Compound D38: N-benzylneopentamide, black oil, 0.2 mmol. Scale: 51% (19.5 mg) isolated. 1 H NMR (400 MHz, CDCl3) δ 7.36-7.31 (m, 2H), 7.30-7.22 (m,3H), 5.93 (br s, 1H), 4.43 (d, J = 5.6 Hz, 2H), 1.23 (s, 9H). 13 C NMR (101MHz, CDCl3) δ 178.5, 138.8, 128.9, 127.8, 127.6, 43.7, 38.9, 27.7. Compound D39: N-benzyl-2-naphthylcarboxamide, yellow solid, 0.2 mmol. Scale: 91% isolated (47.5 mg). 1 H NMR (400 MHz, CDCl3) δ 8.30 (s, 1H), 8.01-7.74(m, 4H), 7.59-7.43 (m, 2H), 7.40-7.25 (m, 5H), 6.84 (br s, 1H), 4.68 (d, J =5.6 Hz, 2H). 13 C NMR (101 MHz, CDCl3) δ 167.6, 138.3, 134.9, 132.7, 131.7,129.0, 128.9, 128.6, 128.0, 127.9, 127.8, 127.6, 127.6, 126.9, 123.7, 44.4. Compound D40: N-benzylthiophene-2-carboxamide, yellow solid, 0.2 mmol. Scale: 88% isolated (38.2 mg). 1 H NMR (400 MHz, CDCl3) δ 7.53 (dd, J = 3.6, 1.2 Hz, 1H), 7.45 (dd, J = 4.8, 1.2 Hz, 1H), 7.35-7.22 (m, 5H), 7.12-6.97 (m, 1H), 6.63 (br s, 1H), 4.57 (d, J = 5.6 Hz, 2H). 13 C NMR (101 MHz, CDCl3) δ 162.0,138.9, 138.2, 130.2, 128.9, 128.3, 128.0, 127.8, 127.7, 44.1. Compound D41: N-benzylfuran-2-carboxamide, black oil, 0.2 mmol. Scale: 26% (10.5 mg) isolated. 1 H NMR (400 MHz, CDCl3) δ 7.42 (dd, J = 2.0, 1.2 Hz, 1H), 7.35 (d, J = 4.4 Hz, 4H), 7.34-7.25 (m, 1H), 7.15 (dd, J= 3.2, 0.8 Hz,1H), 6.64 (br s, 1H), 6.50 (q, J = 1.6 Hz, 1H), 4.62 (d, J = 6.0 Hz, 2H). 13 CNMR (101 MHz, CDCl3) δ 158.4, 148.0, 144.0, 138.1, 128.9, 128.1, 127.8,114.6, 112.3, 43.3.。

Claims

1. A method for the electrochemical synthesis of amide compound D, using compounds A, B, and C as raw materials, with the following reaction formula: ； in, R1 is selected from C1-6 alkyl or cycloalkyl groups. , or X is either O or S; R2 is selected from C1-6 alkyl or cycloalkyl groups. , or X is either 0 or S; m is an integer from 1 to 3; R3 is H, or R2 and R3 together with N atoms form a five-membered ring or a six-membered ring; R4 is H, a C1-6 alkyl group, one or more halogen-substituted C1-6 alkyl groups, halogen, C1-6 alkoxy or cyano groups; R5 is H, a C1-6 alkyl group, one or more halogen-substituted C1-6 alkyl groups, halogen, C1-6 alkoxy or cyano groups.

2. The method as described in claim 1, characterized in that: The term "halogen" refers to fluorine, chlorine, bromine, or iodine; the term "C" refers to... 16 The alkyl group is selected from methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, or isohexyl; the "C" 16 The alkoxy group is selected from methoxy, ethoxy, or tert-butoxy.

3. The method as described in claim 1, characterized in that, The compound D is selected from: 。 4. The method according to any one of claims 1-3, characterized in that: The molar ratio of α-carbonyl thioylide compound (A), amine compound (B), and azidotrimethylsilane (C) is 1:1:1 to 3:1:3, by mass percentage.

5. The method according to any one of claims 1-3, characterized in that: The electrochemical synthesis method uses an undivided electrolytic cell; the electrodes are one or more of graphite sheets, graphite felt, carbon paper, reticulated glassy carbon, platinum sheets, and nickel foam.

6. The method as described in claim 5, characterized in that: The anode is one or more of graphite sheets, graphite felt, carbon paper, and glassy carbon mesh, and the cathode is one or more of graphite sheets, graphite felt, carbon paper, glassy carbon mesh, platinum sheets, and nickel foam.

7. The method according to any one of claims 1-6, characterized in that: The solvent is one of N,N-dimethylformamide, dimethyl sulfoxide, N-methylpyrrolidone, and acetonitrile.

8. The method according to any one of claims 1-7, characterized in that: The reaction time is 2-6 hours.

9. The method according to any one of claims 1-8, characterized in that: The current is 5-10 mA.

10. The method as described in claim 1, characterized in that: The electrode is a graphite sheet as the anode and a platinum sheet as the cathode; the electrolyte is tetrabutylammonium hexafluorophosphate with a concentration of 0.1 M; the current is 5 mA; and the solvent is dimethyl sulfoxide.

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