Method for electrochemical synthesis of alpha-branched amine compound

Abstract

The invention belongs to the technical field of chemical synthesis, and particularly relates to a method for electrochemical synthesis of an alpha-branched amine compound. The specific synthesis method comprises the following steps: taking imine and a p-toluene nitrile compound as raw materials, and mixing the raw materials, electrolyte, an oxidizing agent and a solvent to obtain a reaction solution; and electrolyzing the reaction liquid, so that the imine and the p-toluene nitrile compound are subjected to a cross-coupling reaction, and the alpha-branched amine compound is obtained. The electrochemical method provided by the invention is not influenced by a highly active or special pre-functionalized nucleophilic reagent, and has the advantages of wide substrate universality, good product functional group compatibility, simple operation, short reaction time and high product yield, and the universality and expandability of the synthesized alpha-branched amine compound are improved.

Description

Technical Field

[0001] The present invention belongs to the technical field of chemical synthesis, and particularly relates to a method for electrochemically synthesizing α-branched amine compounds. Background Art

[0002] α-Branched amine derivatives are a series of compounds with heteroatoms, widely present in various natural products, drugs, and bioactive molecules. Due to the particularity of their structure and the presence of nitrogen atoms in the structure, α-branched amine derivatives are widely used in the pharmaceutical, food, and dye industries. In the pharmaceutical field, α-branched amine compounds are key intermediates for synthesizing various drugs, such as anti-tumor drugs, antiviral drugs, and antibiotics. For example, α-aminonitrile compounds, as pharmacophores, are widely present in diabetes drugs and anti-tumor active molecules; their branched-chain structure can enhance the stability and targeting of drug molecules. In the dye field, α-branched amine compounds, as branched-chain substituents of dye molecules, can regulate their electron cloud density and conjugated system, thereby changing the absorption wavelength and color performance of dyes. For example, introducing a branched amine group into azo dyes can achieve brighter colors and higher light fastness.

[0003] Currently, the use of metal catalysts to catalyze the alkenylation reaction of amines in the prior art is an effective method for synthesizing α-branched amine derivatives. Literature 1: L. Li, Y. C. Liu and H. Shi, J. Am. Chem. Soc., 2021, 143, 4154-4161. Literature 1 reported that under heating conditions at 120 °C, using amines and diphenylacetylene as raw materials, α-branched amine derivatives were obtained through metal nickel-catalyzed alkenylation reaction. Literature 2: L. Leng and J. M. Ready, ACS Catal., 2020, 10, 13196-13201. Literature 2 reported that at room temperature, using amines and alkyl bromides as raw materials, α-branched amine derivatives were obtained through metal iridium-catalyzed alkylation reaction.

[0004] Although α-branched amine derivatives can be obtained through the above synthesis methods, during the synthesis process, affected by highly active or special pre-functionalized nucleophiles, the complexity of reaction operations and reaction costs are increased, thus limiting the generality and scalability of the above synthesis methods. Summary of the Invention

[0005] In order to solve the technical problem that during the synthesis of α-branched amine derivatives, affected by highly active or special pre-functionalized nucleophiles, the complexity of reaction operations and reaction costs are increased, thus limiting the generality and scalability of the above synthesis methods, the present invention provides a method for electrochemically synthesizing α-branched amine compounds.

[0006] The object of the present invention is to provide a method for electrochemically synthesizing α-branched amine compounds, comprising the following steps:

[0007] Using the imine shown in Formula 1 and the p-tolunitrile compound shown in Formula 2 as raw materials, mixing the raw materials, electrolyte, oxidant and solvent to obtain a reaction solution; and electrolyzing the reaction solution to cause a cross-coupling reaction between the imine shown in Formula 1 and the p-tolunitrile compound shown in Formula 2 to obtain the α-branched amine compound shown in Formula 3;

[0008] The specific reaction formula is as follows:

[0009]

[0010] Wherein, R 1 is phenyl, thienyl, furyl, naphthyl or substituted phenyl; R 1 The substituents of the substituted phenyl in are at least one of methyl, isopropyl, tert-butyl, methoxy, methylthio, trifluoromethyl, trifluoromethoxy, difluoromethoxy, methyl formate, fluorine atom, chlorine atom, bromine atom, phenyl, pyridyl and benzyloxy; R 2 is phenyl or substituted phenyl, R 2 The substituents of the substituted phenyl in are at least one of methyl, ethyl, n-propyl, tert-butyl, fluorine atom and chlorine atom; R 3 is a hydrogen atom, a fluorine atom or a cyano group.

[0011] It should be noted that the present invention uses a quaternary ammonium salt as the electrolyte for the electrolysis reaction. The quaternary ammonium salt dissociates into cations and anions in the solvent, which can enhance the conductivity of the reaction solution, enable the current to pass through the reaction more efficiently, and ensure the smooth progress of the electrolysis reaction. During the exploration process of the present invention, it was found that when no electrolyte was added during the reaction process, the electrolysis reaction could not proceed. In addition, the quaternary ammonium salt can stabilize the reaction intermediate through electrostatic interaction, avoiding the rapid decomposition of the intermediate or the occurrence of side reactions. The ions in the quaternary ammonium salt, especially the cations, can promote the migration and transfer of free radicals, improving the efficiency of the electrolysis reaction.

[0012] Preferably, the electrolyte is one of ammonium tetrabutyl perchlorate, ammonium tetrabutyl hexafluorophosphate, ammonium tetrabutyl tetrafluoroborate, ammonium tetrabutyl acetate, ammonium tetrabutyl iodide, ammonium tetrabutyl hydrogen sulfate, ammonium tetrabutyl nitrate, phosphonium tetrabutyl bromide, ammonium tetraethyl perchlorate, ammonium tetraethyl hexafluorophosphate and ammonium tetraethyl bromide; More preferably, the electrolyte is ammonium tetrabutyl perchlorate.

[0013] Preferably, the concentration of the electrolyte in the reaction solution is 0.03 mol / L to 0.3 mol / L.

[0014] The oxidant can effectively oxidize the reaction substrate, enabling the formation of free radicals from imines and p-tolunitrile compounds, undergoing a cross-coupling reaction to form α-branched amine compounds; the oxidation reaction of the oxidant is also crucial for the electrolysis reaction. Therefore, in the present invention, by adding an oxidant, the oxidant can improve the selectivity of the electrolysis reaction, avoid generating too many by-products, and make the generated target product purer. At the same time, the oxidant can act as a catalyst, catalyzing multiple reaction cycles during the reaction process and improving the reaction efficiency.

[0015] Preferably, the oxidant is one of 2,2,6,6-tetramethylpiperidine oxide, nitroxyl radical piperidinol, 1,4-diazabicyclo[2.2.2]octane, diisopropylethylamine, and ferrocene; more preferably, the oxidant is 2,2,6,6-tetramethylpiperidine oxide.

[0016] Preferably, the molar ratio of the imine shown in Formula 1 to the p-tolunitrile compound shown in Formula 2 is 1:2 to 9.

[0017] Preferably, the molar ratio of the imine shown in Formula 1 to the oxidant is 1:0.25 to 5.

[0018] Preferably, the conditions for electrolysis are: the electrolysis current is 6 mA to 15 mA, and the electrolysis time is 3 h to 6 h.

[0019] Preferably, the anode is one of graphite, platinum, and graphite felt; more preferably, the anode is graphite.

[0020] Preferably, the cathode is one of graphite, nickel, platinum, copper, zinc, and aluminum; more preferably, the cathode is platinum.

[0021] Preferably, R 1 The number of substituents of the substituted phenyl group in is 1, 2, or 3.

[0022] Preferably, the solvent is one of N,N-dimethylformamide, N,N-dimethylacetamide, and dimethyl sulfoxide; more preferably, the solvent is N,N-dimethylformamide.

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] The present invention provides a new method for electro-synthesizing α-branched amine compounds with easily available raw materials, mild conditions and environmental friendliness. In the present invention, imines and p-tolunitrile compounds are used as raw materials, and quaternary ammonium salts are used as electrolytes. In the presence of an oxidation medium, α-branched amine compounds with potential pharmaceutical applications are synthesized at room temperature and in an air atmosphere. The present invention uses "electrons" in the electrochemical reaction process as redox reaction reagents to cause cross-coupling reactions between imines and p-tolunitrile compounds to obtain α-branched amine compounds. The electrochemical method of the present invention is not affected by highly active or special pre-functionalized nucleophilic reagents, and has a wide substrate generality, good compatibility of product functional groups, simple operation, short reaction time and high product yield, improving the generality and scalability of the synthesis of α-branched amine compounds. In addition, the reaction device used in the present invention is simple, the electrode material can be reused, and it is easy to scale up production, meeting the concept of green chemistry. Description of the Drawings

[0025] Figure 1 It is a reaction mechanism diagram for preparing α-branched amine compounds in Example 1; among them, 1a is N-benzylideneaniline, 2a is p-tolunitrile, 3a is the α-branched amine product, A is protonated N-benzylideneaniline, B is benzyl α-amino radical, C is benzyl radical, D is amine, and E is radical cation. Detailed Embodiments

[0026] In order to enable those skilled in the art to better understand and implement the technical solution of the present invention, the present invention will be further described below in conjunction with specific embodiments and drawings.

[0027] In the description of the present invention, unless otherwise specified, the reagents used are commercially available, and the methods used are conventional techniques in the art.

[0028] It should be noted that in electro-synthesis, the main role of the electrolyte is to provide ionic conductivity, enabling the current to flow in the solution, thereby promoting the progress of the redox reaction. Different electrolytes have different ionic properties, solubility and conductivity, and these properties will affect the reaction rate, selectivity and product purity.

[0029] The present invention uses quaternary ammonium salts as electrolytes for electrolytic reactions. The electrolytes dissociate into cations and anions in the reaction to form an ionic conduction path; ensure the directional migration of ions in the solution when electrons are transferred through the external circuit, thereby maintaining electrical neutrality; at the same time, adjust the solution polarity through ion-ion interactions, affecting the solubility and reactivity of the reaction substrates.

[0030] In a specific embodiment of the present invention, the electrolyte is one of tetrabutylammonium perchlorate, tetrabutylammonium hexafluorophosphate, tetrabutylammonium tetrafluoroborate, tetrabutylammonium acetate, tetrabutylammonium iodide, tetrabutylammonium hydrogen sulfate, tetrabutylammonium nitrate, tetrabutylphosphonium bromide, tetraethylammonium perchlorate, tetraethylammonium hexafluorophosphate, and tetraethylammonium bromide.

[0031] When the anion in the electrolyte is hexafluorophosphate or tetrafluoroborate, PF6 - or BF4 - has good solubility and high conductivity; however, it may reduce the solubility of the imine in the solution, resulting in a decrease in the reaction rate. When the anion in the electrolyte is iodide or bromide: it is easily oxidized to I2 or Br2 at the anode, leading to electrode corrosion or side reactions and reducing the yield. When the anion in the electrolyte is hydrogen sulfate: it may release H + , resulting in an acidic environment and triggering substrate hydrolysis or side reactions. When the electrolyte is tetrabutylammonium perchlorate, tetrabutylammonium perchlorate combines the highly oxidatively stable ClO4- anion and the large-volume TBA + cation, enhancing solubility and conductivity and suppressing side reactions. And it is superior to the low solubility caused by the smaller cation in tetraethylammonium. In a more preferred specific embodiment, the electrolyte is tetrabutylammonium perchlorate.

[0032] In the electrochemical process, the redox mediator acts as a medium for electron transfer, helping the substrate lose electrons, promoting the oxidation reaction at the anode, and enabling the reaction to proceed under milder conditions. In a specific embodiment of the present invention, the oxidant is one of 2,2,6,6-tetramethylpiperidine-N-oxide, nitroxide piperidinol, 1,4-diazabicyclo[2.2.2]octane, diisopropylethylamine, and ferrocene.

[0033] Ferrocene has a relatively high oxidation potential, and may not be able to effectively oxidize a specific substrate or requires a higher current, resulting in a decrease in efficiency. 1,4-Diazabicyclo[2.2.2]octane may decompose to produce nitrogen or highly reactive intermediates, interfering with the main reaction. Diisopropylethylamine mainly acts as a base, and if used as an oxidant, it may be inefficient due to mismatched oxidation potential. While 2,2,6,6-tetramethylpiperidine-N-oxide has a moderate oxidation potential, which is suitable for mildly oxidizing imines to generate iminium cations and promoting C-N bond formation; at the same time, the nitroxide radical has high stability, is not easily decomposed, and has few by-products. More preferably, the oxidant is 2,2,6,6-tetramethylpiperidine-N-oxide.

[0034] Example 1

[0035] This example provides a method for electrochemically synthesizing α-branched amine compounds.

[0036] Into a 10 mL Schlenk reaction tube, 54.4 mg of N-benzylideneaniline represented by formula 1a, 175.7 mg of p-tolunitrile represented by formula 2a, 341.9 mg of tetrabutylammonium perchlorate, 23.4 mg of 2,2,6,6-tetramethylpiperidine N-oxide, and 5 mL of N,N-dimethylformamide were successively added to obtain a reaction solution. Using a graphite sheet with dimensions of 10 mm × 10 mm × 1.0 mm as the anode and a platinum sheet with dimensions of 10 mm × 10 mm × 0.3 mm as the cathode, the cathode and anode were placed in the reaction solution and were oppositely arranged with a distance of 3 mm, and the relative surface area of the anode and cathode was 100 mm 2 ; The electrolytic reaction was stirred for 4 h at room temperature under a constant current of 10 mA to obtain a reaction mixture; the reaction mixture was extracted with ethyl acetate and then washed with a saturated NaCl aqueous solution to obtain an organic layer; the organic layer was dried with Na2SO4, the solvent was removed under reduced pressure after filtration, and then separated by silica gel column chromatography; among them, the eluent was a mixed solution of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate was 20:1, to obtain 72.0 mg of the α-branched amine compound represented by formula 3a, with a yield of 80%; the preparation reaction route is as follows:

[0037]

[0038] The data of the 1H NMR spectrum of the α-branched amine compound represented by formula 3a are as follows: 1 H NMR(600MHz,CDCl3)δ7.51(d,J=8.4Hz,2H),7.29-7.22(m,5H),7.15(d,J=8.4Hz,2H),7.07(dd,J=7.8,7.2Hz,2H),6.65(t,J=7.2Hz,1H),6.49(d,J=7.8Hz,2H),4.61(t,J=7.2Hz,1H),4.07(s,1H),3.17-3.11(m,2H).

[0039] The data of the 13C NMR spectrum are as follows: 13 C NMR(151MHz,CDCl3)δ146.8,143.5,142.4,132.3,130.1,129.3,128.8,127.6,126.5,119.0,118.0,113.7,110.7,59.0,44.8.

[0040] The mass spectrometry data are as follows: C 21 H 18 The HRMS theoretical value of N2 [M+H] + : 299.15428; the measured value: 299.15427. It shows that the α-branched amine compound was successfully synthesized in this invention.

[0041] Example 2

[0042] This example provides a method for electrochemically synthesizing α-branched amine compounds.

[0043] The difference between this example and Example 1 is as follows:

[0044] In this example, the electrolysis time is 3 h, and 60.2 mg of α-branched amine compounds are obtained, with a yield of 67%.

[0045] Example 3

[0046] This example provides a method for electrochemically synthesizing α-branched amine compounds.

[0047] The difference between this example and Example 1 is as follows:

[0048] In this example, ferrocene is replaced with 2,2,6,6-tetramethylpiperidine 1-oxyl, and 32.5 mg of α-branched amine compounds are obtained, with a yield of 36%.

[0049] Example 4

[0050] This example provides a method for electrochemically synthesizing α-branched amine compounds.

[0051] The difference between this example and Example 1 is as follows:

[0052] In this example, the compound shown in Formula 1b is used to replace the compound shown in Formula 1a, and 63.7 mg of α-branched amine compounds shown in Formula 3b are obtained, with a yield of 68%; the preparation reaction route is as follows:

[0053]

[0054] The 1H NMR data of the α-branched amine compounds shown in Formula 3b are as follows: 1 H NMR(600MHz,CDCl3)δ7.54(d,J=7.8Hz,2H),7.18(d,J=8.4Hz,2H),7.15 - 7.08(m,6H),6.67(t,J=7.2Hz,1H),6.52 - 6.51(m,2H),4.60(t,J=6.6Hz,1H),4.05(s,1H),3.19 - 3.12(m,2H),2.33(s,3H).

[0055] The 13C NMR data are as follows: 1313C NMR (151 MHz, CDCl3) δ 146.9, 143.7, 139.3, 137.2, 132.3, 130.2, 129.5, 129.3, 126.5, 119.0, 117.9, 113.7, 110.6, 58.7, 44.8, 21.2.

[0056] The mass spectrometry data are as follows: C 22 H 20 The HRMS theoretical value of N2 [M+Na] + : 335.15187; measured value: 335.15167. It indicates that the α-branched amine compound was successfully synthesized in this invention.

[0057] Example 5

[0058] This example provides a method for electrochemically synthesizing α-branched amine compounds.

[0059] The difference between this example and Example 1 is:

[0060] In this example, the compound shown in Formula 1c was used to replace the compound shown in Formula 1a, and 72.6 mg of the α-branched amine compound shown in Formula 3c was obtained with a yield of 71%; the preparation reaction route is as follows:

[0061]

[0062] The 1H NMR data of the α-branched amine compound shown in Formula 3c are as follows: 1 1H NMR (600 MHz, CDCl3) δ 7.53 (d, J = 7.8 Hz, 2H), 7.20 - 7.16 (m, 6H), 7.12 - 7.09 (m, 2H), 6.68 (t, J = 7.2 Hz, 1H), 6.52 (d, J = 7.8 Hz, 2H), 4.61 (t, J = 6.6 Hz, 1H), 4.06 (s, 1H), 3.16 (d, J = 6.6 Hz, 1H), 2.93 - 2.86 (m, 1H), 1.25 (dd, J = 7.2, 2.4 Hz, 6H).

[0063] The 13C NMR data are as follows: 13 13C NMR (151 MHz, CDCl3) δ 148.2, 146.9, 143.8, 139.7, 132.2, 130.1, 129.2, 126.8, 126.4, 119.0, 117.8, 113.6, 110.5, 58.6, 44.8, 33.8, 24.0, 24.0.

[0064] The mass spectrometry data are as follows: C 24 H 24The theoretical HRMS value of N2 [M+K] + : 379.15711; Measured value: 379.15695. It indicates that the α-branched amine compound has been successfully synthesized in this invention.

[0065] Example 6

[0066] This example provides a method for electrochemically synthesizing α-branched amine compounds.

[0067] The difference between this example and Example 1 is as follows:

[0068] In this example, the compound shown in Formula 1d is used to replace the compound shown in Formula 1a, and 72.2 mg of the α-branched amine compound shown in Formula 3d is obtained, with a yield of 68%; the preparation reaction route is as shown in Reaction

[0069] shown in Formula 6:

[0070]

[0071] The 1H NMR data of the α-branched amine compound shown in Formula 3d are as follows: 1 H NMR(600MHz,CDCl3)δ7.54(d,J=7.8Hz,2H),7.33(d,J=7.8Hz,2H),7.20(d,J=7.8Hz,4H),7.10(dd,J=7.8,7.2Hz,2H),6.68(t,J=7.2Hz,1H),6.52(d,J=7.8Hz,2H),4.62(t,J=7.2Hz,1H),4.05(s,1H),3.19 - 3.12(m,2H),1.32(s,9H).

[0072] The 13C NMR data are as follows: 13 C NMR(151MHz,CDCl3)δ150.5,147.0,143.8,139.3,132.2,130.1,129.3,126.1,125.7,119.0,117.9,113.6,110.6,58.6,44.7,34.6,31.5.

[0073] The mass spectrometry data are as follows: C 25 H 26 The theoretical HRMS value of N2 [M+K] + : 393.17276; Measured value: 393.17215. It indicates that the α-branched amine compound has been successfully synthesized in this invention.

[0074] Example 7

[0075] This example provides a method for electrochemically synthesizing α-branched amine compounds.

[0076] The difference between this example and Example 1 is as follows:

[0077] In this example, the compound shown in Formula 1e is used to replace the compound shown in Formula 1a to obtain 60.0 mg of the α-branched amine compound shown in Formula 3e, and the yield is 61%; the preparation reaction route is as follows:

[0078]

[0079] The data of the 1H NMR spectrum of the α-branched amine compound shown in Formula 3e are as follows: 1 H NMR(600MHz,CDCl3)δ7.53(d,J=7.8Hz,2H),7.16(dd,J=8.4,2.4Hz,4H),7.11(dd,J=8.4,7.8Hz,2H),6.84(d,J=8.4Hz,2H),6.68(t,J=7.2Hz,1H),6.53(d,J=7.8Hz,2H),4.59(t,J=7.2Hz,1H),4.07(s,1H),3.79(s,3H),3.18(dd,J=13.8,6.6Hz,1H),3.11(dd,J=13.8,6.6Hz,1H).

[0080] The data of the 13C NMR spectrum are as follows: 13 C NMR(151MHz,CDCl3)δ158.9,146.9,143.6,134.2,132.2,130.2,129.2,127.6,119.0,117.9,114.1,113.7,110.5,58.4,55.3,44.8.

[0081] The mass spectrometry data are as follows: C 22 H 20 The HRMS theoretical value of N2O [M+H] + : 329.16484; the measured value: 329.16431. It indicates that the α-branched amine compound has been successfully synthesized in this invention.

[0082] Example 8

[0083] This example provides a method for electrochemically synthesizing α-branched amine compounds.

[0084] The difference between this example and Example 1 is as follows:

[0085] In this example, the compound shown in Formula 1f is used to replace the compound shown in Formula 1a to obtain 70.2 mg of the α-branched amine compound shown in Formula 3f, and the yield is 68%; the preparation reaction route is as follows:

[0086]

[0087] The data of the 1H NMR spectrum of the α-branched amine compound shown in Formula 3f are as follows: 1 H NMR(600MHz,CDCl3)δ7.54(d,J=7.8Hz,2H),7.19-7.16(m,6H),7.09(t,J=7.2Hz,2H),6.68(t,J=7.2Hz,1H),6.50(d,J=7.8Hz,2H),4.59(t,J=6.6Hz,1H),4.13(s,1H),3.18-3.10(m,2H),2.47(s,3H).

[0088] The data of the 13C NMR spectrum are as follows: 13 C NMR(151MHz,CDCl3)δ146.6,143.4,139.2,137.6,132.3,130.2,129.3,127.1,126.8,118.9,118.1,113.7,110.7,58.6,44.7,15.8.

[0089] The mass spectrometry data are as follows: C 22 H 20 The HRMS theoretical value of C + H

[0090] Example 9

[0091] This example provides a method for electrochemically synthesizing α-branched amine compounds.

[0092] The difference between this example and Example 1 is:

[0093] In this example, the compound shown in Formula 1g is used to replace the compound shown in Formula 1a, and 58.2 mg of the α-branched amine compound shown in Formula 3g is obtained, with a yield of 53%; the preparation reaction route is as follows:

[0094]

[0095] The data of the 1H NMR spectrum of the α-branched amine compound shown in Formula 3g are as follows: 11H NMR (600 MHz, CDCl3) δ 7.58 (t, J = 9.0 Hz, 4H), 7.42 (d, J = 8.4 Hz, 2H), 7.22 (d, J = 8.4 Hz, 2H), 7.11 (t, J = 7.8 Hz, 2H), 6.71 (t, J = 7.8 Hz, 1H), 6.49 (d, J = 7.8 Hz, 2H), 4.72 (t, J = 6.6 Hz, 1H), 4.16 (s, 1H), 3.18 (d, J = 7.2 Hz, 2H).

[0096] The data of 13C NMR are as follows: 13 13C NMR (151 MHz, CDCl3) δ 146.8, 146.4, 142.8, 132.4, 130.1, 129.8 (d, J = 31.7 Hz) 129.3, 126.9, 125.8 (q, J = 3.0 Hz), 124.2 (q, J = 271.8 Hz), 118.8, 118.4, 113.7, 111.0, 58.6, 44.7.

[0097] The data of mass spectrometry are as follows: C 22 H 17 The HRMS theoretical value of F3N2 [M + H] + : 367.14166; measured value: 367.14172. It indicates that the α-branched amine compound was successfully synthesized in this invention.

[0098] Example 10

[0099] This example provides a method for electrochemically synthesizing α-branched amine compounds.

[0100] The difference between this example and Example 1 is that

[0101] In this example, the compound shown in Formula 1h was used to replace the compound shown in Formula 1a, and 69.9 mg of the α-branched amine compound shown in Formula 3h was obtained, with a yield of 61%; the preparation reaction route is as shown in Reaction

[0102] shown in Formula 10:

[0103]

[0104] The data of 1H NMR of the α-branched amine compound shown in Formula 3h are as follows: 11H NMR (600 MHz, CDCl3) δ 7.56 (d, J = 8.4 Hz, 2H), 7.30 - 7.28 (m, 2H), 7.19 (d, J = 7.8 Hz, 2H), 7.16 (d, J = 8.4 Hz, 2H), 7.10 (dd, J = 8.4, 7.8 Hz, 2H), 6.70 (t, J = 7.2 Hz, 1H), 6.48 (d, J = 7.8 Hz, 2H), 4.64 (t, J = 7.2 Hz, 1H), 4.08 (s, 1H), 3.18 - 3.11 (m, 2H).

[0105] The data of 13C NMR are as follows: 13 13C NMR (151 MHz, CDCl3) δ 148.5, 146.5, 143.0, 141.2, 132.4, 130.1, 129.4, 127.9, 121.3, 118.8, 118.3, 113.7, 111.0, 58.4, 44.9.

[0106] The data of mass spectrometry are as follows: C 22 H 17 The HRMS theoretical value of F3N2O [M + H] + : 383.13657; measured value: 383.13632. It indicates that the α - branched amine compound was successfully synthesized in this invention.

[0107] Example 11

[0108] This example provides a method for electrochemically synthesizing α - branched amine compounds.

[0109] The difference between this example and Example 1 is that:

[0110] In this example, the compound shown in Formula 1i was used to replace the compound shown in Formula 1a, and 86.4 mg of the α - branched amine compound shown in Formula 3i was obtained with a yield of 79%; the preparation reaction route is as follows:

[0111]

[0112] The data of 1H NMR of the α - branched amine compound shown in Formula 3i are as follows: 11H NMR(600 MHz, CDCl3) δ 7.52 (d, J = 7.8 Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H), 7.16 (d, J = 8.4 Hz, 2H), 7.07 (t, J = 8.4 Hz, 2H), 7.03 (d, J = 8.4 Hz, 2H), 6.66 (t, J = 7.2 Hz, 1H), 6.59 - 6.34 (m, 3H), 4.60 (t, J = 6.6 Hz, 1H), 4.11 (s, 1H), 3.15 - 3.08 (m, 2H).

[0113] The data of 13C NMR are as follows: 13 13C NMR(151 MHz, CDCl3) δ 150.5, 150.4, 150.4, 146.5, 143.2, 139.6, 132.3, 130.1, 129.3, 127.9, 119.8, 118.9, 118.2, 117.7, 116.0, 114.2, 113.7, 110.8, 58.4, 44.8.

[0114] The data of mass spectrometry are as follows: C 22 H 18 The HRMS theoretical value of F2N2O [M + H] + : 365.14600; the measured value: 365.14600. It indicates that the α - branched amine compound has been successfully synthesized in this invention.

[0115] Example 12

[0116] This example provides a method for electrochemically synthesizing α - branched amine compounds.

[0117] The difference between this example and Example 1 is that

[0118] In this example, the compound shown in Formula 1j is used to replace the compound shown in Formula 1a, and 68.4 mg of the α - branched amine compound shown in Formula 3j is obtained, with a yield of 64%; its preparation reaction route is as follows:[[]]

[0119]

[0120] The data of 1H NMR of the α - branched amine compound shown in Formula 3j are as follows: 11H NMR (600 MHz, CDCl3) δ 7.97 (d, J = 8.4 Hz, 2H), 7.54 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 7.17 (d, J = 8.4 Hz, 2H), 7.07 (t, J = 8.4 Hz, 2H), 6.68 (t, J = 7.2 Hz, 1H), 6.46 (d, J = 8.4 Hz, 2H), 4.68 (t, J = 7.2 Hz, 1H), 4.11 (s, 3H), 3.90 (s, 1H), 3.20 - 3.14 (m, 2H).

[0121] The data of 13C NMR are as follows: 13 13C NMR (151 MHz, CDCl3) δ 166.9, 147.8, 146.5, 142.9, 132.4, 130.2, 130.1, 129.6, 129.3, 126.6, 118.8, 118.4, 113.7, 111.0, 58.9, 52.2, 44.7.

[0122] The data of mass spectrometry are as follows: C 23 H 20 The theoretical value of HRMS for C19H18N2O2 [M + H] + : 357.15975; the measured value: 357.15924. It indicates that the α - branched amine compound has been successfully synthesized in this invention.

[0123] Example 13

[0124] This example provides a method for electrochemically synthesizing α - branched amine compounds.

[0125] The difference between this example and Example 1 is that

[0126] In this example, the compound shown in Formula 1k is used to replace the compound shown in Formula 1a, and 58.8 mg of the α - branched amine compound shown in Formula 3k is obtained, with a yield of 62%; the preparation reaction route is as follows:

[0127]

[0128] The data of 1H NMR of the α - branched amine compound shown in Formula 3k are as follows: 11H NMR(600 MHz, CDCl3) δ 7.50 (d, J = 8.4 Hz, 2H), 7.24 - 7.18 (m, 4H), 7.09 - 7.06 (m, 2H), 7.04 - 7.00 (m, 2H), 6.66 (t, J = 7.2 Hz, 1H), 6.52 - 6.50 (m, 2H), 4.96 (s, 1H), 4.10 (s, 1H), 3.20 (dd, J = 13.8, 6.0 Hz, 1H), 3.12 (dd, J = 13.8, 7.2 Hz, 1H).

[0129] The data of 13C NMR are as follows: 13 13C NMR(151 MHz, CDCl3) δ 160.6 (d, J = 244.6 Hz), 146.4, 143.4, 132.3, 130.1, 129.3, 129.1 (d, J = 13.6 Hz), 129.1 (d, J = 7.6 Hz), 127.9 (d, J = 4.5 Hz), 124.5 (d, J = 3.0 Hz), 118.9, 118.2, 115.7 (d, J = 22.7 Hz), 113.6, 110.7, 53.0, 43.1.

[0130] The mass spectrometry data are as follows: C 21 H 17 The HRMS theoretical value of C16H17FN2 [M + Na] + : 339.12680; Measured value: 339.12598. It indicates that the α-branched amine compound has been successfully synthesized in this invention.

[0131] Example 14

[0132] This example provides a method for electrochemically synthesizing α-branched amine compounds.

[0133] The difference between this example and Example 1 is as follows:

[0134] In this example, the compound shown in Formula 1l is used to replace the compound shown in Formula 2a, and 75.8 mg of the α-branched amine compound shown in Formula 3l is obtained with a yield of 76%; its preparation reaction route is as follows:

[0135]

[0136] The data of 1H NMR of the α-branched amine compound shown in Formula 3l are as follows: 11H NMR (600 MHz, CDCl3) δ 7.46 (d, J = 8.4 Hz, 2H), 7.30 (s, 1H), 7.24 - 7.23 (m, 2H), 7.19 (d, J = 7.8 Hz, 2H), 7.13 - 7.09 (m, 3H), 6.70 (d, J = 7.8 Hz, 1H), 6.48 (d, J = 7.8 Hz, 2H), 4.59 (t, J = 6.6 Hz, 1H), 4.06 (s, 1H), 3.14 (d, J = 6.6 Hz, 2H).

[0137] The data of 13C NMR are as follows: 13 13C NMR (151 MHz, CDCl3) δ 146.4, 144.8, 143.0, 134.5, 132.2, 129.9, 129.2, 127.6, 126.4, 124.7, 118.8, 118.0, 113.5, 110.5, 58.4, 44.5.

[0138] The data of mass spectrometry are as follows: C 21 H 17 The HRMS theoretical value of ClN2 [M + Na] + : 355.09725; Measured value: 355.09624. It indicates that the α-branched amine compound has been successfully synthesized in this invention.

[0139] Example 15

[0140] This example provides a method for electrochemically synthesizing α-branched amine compounds.

[0141] The difference between this example and Example 1 is that:

[0142] In this example, the compound shown in Formula 1m is used to replace the compound shown in Formula 1a, and 63.2 mg of the α-branched amine compound shown in Formula 3m is obtained, with a yield of 56%; the preparation reaction route is as follows:

[0143]

[0144] The data of 1H NMR of the α-branched amine compound shown in Formula 3m are as follows: 1 1H NMR (600 MHz, CDCl3) δ 7.56 - 7.55 (m, 2H), 7.44 - 7.41 (m, 2H), 7.18 (d, J = 8.4 Hz, 1H), 7.13 (dd, J = 10.8, 2.4 Hz, 2H), 7.11 - 7.08 (m, 2H), 6.69 (t, J = 7.2 Hz, 1H), 6.48 - 6.46 (m, 2H), 4.59 (t, J = 6.6 Hz, 1H), 4.06 (s, 1H), 3.17 - 3.09 (m, 2H).

[0145] The data of the carbon-13 NMR spectrum are as follows: 13 C NMR(151MHz,CDCl3)δ146.5,143.0,141.6,132.4,132.0,130.1,129.3,128.3,121..3,118.9,118.3,113.7,110.9,58.5,44.8。

[0146] The data of the mass spectrum are as follows: C 21 H 17 The theoretical value of HRMS of BrN2 [M+H] + : 377.06479; measured value: 377.06482. It indicates that the α-branched amine compound has been successfully synthesized in this invention.

[0147] Example 16

[0148] This example provides a method for electrochemically synthesizing α-branched amine compounds.

[0149] The difference between this example and Example 1 is:

[0150] In this example, the compound shown in Formula 1n is used to replace the compound shown in Formula 1a, and 50.6 mg of the α-branched amine compound shown in Formula 3n is obtained, with a yield of 45%; the preparation reaction route is as follows:

[0151]

[0152] The data of the proton NMR spectrum of the α-branched amine compound shown in Formula 3n are as follows: 1 H NMR(600MHz,CDCl3)δ7.59-7.58(m,2H),7.55(dd,J=8.4,6.0Hz,4H),7.44(t,J=7.2Hz,2H),7.36(d,J=7.2Hz,1H),7.33(d,J=8.4Hz,2H),7.22(d,J=8.4Hz,2H),7.11(dd,J=9.0,7.8Hz,2H),6.69(t,J=7.2Hz,1H),6.54(d,J=7.8Hz,2H),4.68(t,J=7.2Hz,1H),4.09(s,1H),3.20(d,J=6.6Hz,2H)。

[0153] The data of the carbon-13 NMR spectrum are as follows: 1313C NMR (151 MHz, CDCl3) δ 146.8, 143.5, 141.5, 140.7, 140.5, 132.4, 130.2, 129.3, 128.9, 127.5, 127.5, 127.1, 127.0, 119.0, 118.1, 113.8, 110.8, 58.8, 44.9.

[0154] The mass spectrometry data are as follows: C 27 H 22 The HRMS theoretical value of N2 [M + H] + : 375.18558; measured value: 375.18539. It indicates that the α-branched amine compound has been successfully synthesized in this invention.

[0155] Example 17

[0156] This example provides a method for electrochemically synthesizing α-branched amine compounds.

[0157] The difference between this example and Example 1 is:

[0158] In this example, the compound shown in Formula 1o is used to replace the compound shown in Formula 1a, and 51.8 mg of the α-branched amine compound shown in Formula 3o is obtained with a yield of 46%; the preparation reaction route is as follows:

[0159]

[0160] The data of 1H NMR of the α-branched amine compound shown in Formula 3o are as follows: 1 1H NMR (600 MHz, CDCl3) δ 8.68 (d, J = 4.8 Hz, 1H), 7.94 (d, J = 8.4 Hz, 2H), 7.74 (td, J = 7.8, 1.8 Hz, 1H), 7.70 (d, J = 7.8 Hz, 1H), 7.53 (d, J = 7.8 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 7.24 - 7.21 (m, 1H), 7.19 (d, J = 8.4 Hz, 2H), 7.09 (t, J = 7.8 Hz, 2H), 6.67 (t, J = 7.2 Hz, 1H), 6.52 (d, J = 8.4 Hz, 2H), 4.69 (t, J = 6.6 Hz, 1H), 4.15 (s, 1H), 3.23 - 3.16 (m, 2H).

[0161] The data of 13C NMR are as follows: 1313C NMR (151 MHz, CDCl3) δ 157.0, 149.8, 146.7, 143.3, 138.7, 136.9, 132.3, 130.2, 129.3, 127.4, 127.0, 122.3, 120.6, 118.9, 118.1, 113.8, 110.7, 58.8, 44.7.

[0162] The mass spectrometry data are as follows: C 26 H 21 The HRMS theoretical value of N3 [M + H] + : 376.18082; measured value: 376.18085. It indicates that the α-branched amine compound was successfully synthesized in this invention.

[0163] Example 18

[0164] This example provides a method for electrochemically synthesizing α-branched amine compounds.

[0165] The difference between this example and Example 1 is:

[0166] In this example, the compound shown in Formula 1p was used to replace the compound shown in Formula 1a, and 59.4 mg of the α-branched amine compound shown in Formula 3p was obtained with a yield of 49%; the preparation reaction route is as follows:

[0167]

[0168] The 1H NMR data of the α-branched amine compound shown in Formula 3p are as follows: 1 1H NMR (600 MHz, CDCl3) δ 7.41 (d, J = 8.4 Hz, 2H), 7.36 - 7.31 (m, 4H), 7.28 - 7.25 (m, 1H), 7.15 (t, J = 7.8 Hz, 1H), 7.06 - 7.03 (m, 4H), 6.88 (d, J = 1.8 Hz, 1H), 6.81 - 6.79 (m, 2H), 6.63 (t, J = 7.2 Hz, 1H), 6.48 (d, J = 7.8 Hz, 2H), 4.94 (dd, J = 13.2, 11.4 Hz, 2H), 4.52 (t, J = 7.2 Hz, 1H), 4.08 (s, 1H), 3.07 - 3.00 (m, 2H).

[0169] The 13C NMR data are as follows: 1313C NMR (151 MHz, CDCl3) δ 159.0, 146.7, 144.2, 143.4, 136.8, 132.0, 129.9, 129.6, 129.1, 128.5, 127.9, 127.5, 119.1, 118.9, 117.7, 113.5, 113.4, 113.1, 110.2, 69.8, 58.7, 44.4。

[0170] The mass spectrometry data are as follows: C 28 H 24 The HRMS theoretical value of N2O [M+Na] + : 427.17808; measured value: 427.17776. It indicates that the α-branched amine compound has been successfully synthesized in this invention.

[0171] Example 19

[0172] This example provides a method for electrochemically synthesizing α-branched amine compounds.

[0173] The difference between this example and Example 1 is that:

[0174] In this example, the compound shown in Formula 1q is used to replace the compound shown in Formula 1a, and 63.6 mg of the α-branched amine compound shown in Formula 3q is obtained, with a yield of 65%; the preparation reaction route is as follows:

[0175]

[0176] The data of the nuclear magnetic resonance hydrogen spectrum of the α-branched amine compound shown in Formula 3q are as follows: 1 1H NMR (600 MHz, CDCl3) δ 7.55 (d, J = 8.4 Hz, 2H), 7.21 (d, J = 7.8 Hz, 2H), 7.13 - 7.06 (m, 4H), 7.00 (dd, J = 7.8, 1.8 Hz, 1H), 6.68 (t, J = 7.2 Hz, 1H), 6.54 - 6.53 (m, 2H), 4.58 (t, J = 7.2 Hz, 1H), 4.05 (s, 1H), 3.18 - 3.12 (m, 2H), 2.25 (s, 3H), 2.25 (s, 3H).

[0177] The data of the nuclear magnetic resonance carbon spectrum are as follows: 13 13C NMR (151 MHz, CDCl3) δ 147.0, 143.8, 139.8, 136.9, 135.8, 132.2, 130.1, 130.0, 129.2, 127.7, 123.8, 119.0, 117.8, 113.6, 110.5, 58.7, 44.8, 20.0, 19.5.

[0178] The mass spectrometry data are as follows: C 23 H 22 The HRMS theoretical value of N2 [M+H] + : 327.18558; measured value: 327.18527. It indicates that the α-branched amine compound has been successfully synthesized in the present invention.

[0179] Example 20

[0180] This example provides a method for electrochemically synthesizing α-branched amine compounds.

[0181] The difference between this example and Example 1 is:

[0182] In this example, the compound shown in Formula 1r is used to replace the compound shown in Formula 1a, and 52.5 mg of the α-branched amine compound shown in Formula 3r is obtained, with a yield of 53%; the preparation reaction route is as follows:

[0183]

[0184] The data of the 1H NMR spectrum of the α-branched amine compound shown in Formula 3r are as follows: 1 H NMR(600MHz,CDCl3)δ7.54(d,J=8.4Hz,2H),7.23(d,J=7.8Hz,2H),7.12 - 7.08(m,3H),6.86(d,J=2.4Hz,1H),6.85(s,1H),6.68(t,J=7.2Hz,1H),6.53(d,J=7.8Hz,2H),4.93(t,J=7.2Hz,1H),4.08(s,1H),3.21(dd,J=13.8,6.6Hz,1H),3.14(dd,J=13.8,7.2Hz,1H),2.31(s,3H).

[0185] The data of the 13C NMR spectrum are as follows: 13 C NMR(151MHz,CDCl3)δ160.5(d,J=244.6Hz),146.5,143.5,139.6(d,J=7.6Hz),132.3,130.1,129.3,127.7(d,J=6.0Hz),125.8(d,J=13.6Hz),125.3(d,J=3.0Hz),119.0,118.2,116.3(d,J=21.1Hz),113.6,110.7,53.0,43.2,21.1.

[0186] The mass spectrometry data are as follows: C 22 H 19 The HRMS theoretical value of FN2 [M+H]+ : 331.16050; Measured value: 331.16025. It indicates that the α-branched amine compound has been successfully synthesized in the present invention.

[0187] Example 21

[0188] This example provides a method for electrochemically synthesizing α-branched amine compounds.

[0189] The difference between this example and Example 1 is:

[0190] In this example, the compound shown in Formula 1s is used to replace the compound shown in Formula 1a, and 37.8 mg of the α-branched amine compound shown in Formula 3s is obtained, with a yield of 37%; the preparation reaction route is as follows:

[0191]

[0192] The data of the 1H NMR spectrum of the α-branched amine compound shown in Formula 3s are as follows: 1 H NMR(600MHz,CDCl3)δ7.55(d,J = 7.8Hz,2H),7.24(d,J = 7.8Hz,2H),7.08(dd,J = 8.4,7.2Hz,,2H),6.80(s,2H),6.65(t,J = 7.8Hz,1H),6.42(d,J = 7.8Hz,2H),4.98(t,J = 7.2Hz,1H),3.94(s,1H),3.27 - 3.20(m,2H),2.40(s,6H),2.25(s,3H).

[0193] The data of the 13C NMR spectrum are as follows: 13 C NMR(151MHz,CDCl3)δ147.1,144.2,136.7,135.7,134.3,132.3,130.0,129.3,119.0,117.6,112.7,110.6,55.5,41.2,21.2,20.8.

[0194] The mass spectrometry data are as follows: C 24 H 24 The HRMS theoretical value of N2 [M + H] + : 341.20123; Measured value: 341.20093. It indicates that the α-branched amine compound has been successfully synthesized in the present invention.

[0195] Example 22

[0196] This example provides a method for electrochemically synthesizing α-branched amine compounds.

[0197] The difference between this example and Example 1 is:

[0198] In this example, the compound shown in Formula 1t was used to replace the compound shown in Formula 1a, and 68.4 mg of the α-branched amine compound shown in Formula 3t was obtained with a yield of 75%; the preparation reaction route is as follows:

[0199]

[0200] The data of the 1H NMR spectrum of the α-branched amine compound shown in Formula 3t are as follows: 1 H NMR(600MHz,CDCl3)δ7.54(d,J=7.8Hz,2H),7.29(dd,J=5.4,3.0Hz,1H),7.16(d,J=7.8Hz,2H),7.13(dd,J=8.4,7.8Hz,2H),7.00(d,J=2.4Hz,1H),6.98(dd,J=5.4,1.2Hz,1H),6.71(t,J=7.2Hz,1H),6.56(d,J=7.8Hz,2H),4.79(t,J=6.6Hz,1H),3.98(s,1H),3.20(qd,J=13.8,6.6Hz,2H).

[0201] The data of the 13C NMR spectrum are as follows: 13 C NMR(151MHz,CDCl3)δ146.8,143.6,143.5,132.2,130.2,129.4,126.6,126.0,121.4,119.0,118.2,113.7,110.7,55.0,43.7.

[0202] The mass spectrometry data are as follows: C 19 H 16 The theoretical value of HRMS for C + H

[0203] Example 23

[0204] This example provides a method for electrochemically synthesizing α-branched amine compounds.

[0205] The difference between this example and Example 1 is as follows:

[0206] In this example, the compound shown in Formula 1u was used to replace the compound shown in Formula 1a, and 52.8 mg of the α-branched amine compound shown in Formula 3u was obtained with a yield of 61%; the preparation reaction route is as follows:

[0207]

[0208] The 1H NMR data of the α-branched amine compound shown in Formula 3u are as follows: 1 H NMR(600MHz,CDCl3)δ7.55(d,J=8.4Hz,2H),7.38(t,J=1.8Hz,1H),7.24(d,J=8.4Hz,2H),7.21(d,J=0.6Hz,1H),7.18-7.15(m,2H),6.74(t,J=7.2Hz,1H),6.62-6.60(m,2H),6.31(d,J=0.6Hz,1H),4.69(t,J=6.6Hz,1H),3.88(s,1H),3.21(dd,J=13.8,6.6Hz,1H),3.13(dd,J=13.8,7.2Hz,1H).

[0209] The 13C NMR data are as follows: 13 C NMR(151MHz,CDCl3)δ146.7,143.6,143.5,139.7,132.2,130.3,129.4,126.8,118.9,118.2,113.7,110.6,108.9,51.0,42.7.

[0210] The mass spectrometry data are as follows: C 19 H 16 The HRMS theoretical value of N2O [M+H] + : 289.13354; measured value: 289.13342. It indicates that the α-branched amine compound of the present invention is successfully synthesized.

[0211] Example 24

[0212] This example provides a method for electrochemically synthesizing an α-branched amine compound.

[0213] The difference between this example and Example 1 is that

[0214] in this example, the compound shown in Formula 1v is used to replace the compound shown in Formula 1a, and 60.6 mg of the α-branched amine compound shown in Formula 3v is obtained, with a yield of 58%; the preparation reaction route is as follows:

[0215]

[0216] The 1H NMR data of the α-branched amine compound shown in Formula 3v are as follows: 11H NMR (600 MHz, CDCl3) δ 8.14 (d, J = 8.4 Hz, 1H), 7.91 (d, J = 7.8 Hz, 1H), 7.76 (d, J = 7.8 Hz, 1H), 7.56 - 7.49 (m, 5H), 7.36 (t, J = 7.8 Hz, 1H), 7.22 - 7.20 (m, 2H), 7.02 (dd, J = 8.4, 7.2 Hz, 2H), 6.62 (t, J = 7.2 Hz, 1H), 6.45 - 6.44 (m, 2H), 5.48 (dd, J = 8.4, 5.4 Hz, 1H), 4.16 (s, 1H), 3.40 (dd, J = 15.0, 4.8 Hz, 1H), 3.12 (dd, J = 14.4, 2.4 Hz, 1H).

[0217] The data of 13C NMR are as follows: 13 13C NMR (151 MHz, CDCl3) δ 146.7, 143.7, 137.4, 134.2, 132.3, 130.7, 129.9, 129.5, 129.3, 128.1, 126.5, 125.8, 125.7, 123.5, 122.0, 118.9, 118.0, 113.5, 110.7, 54.3, 43.4.

[0218] The data of mass spectrum are as follows: C 25 H 20 The HRMS theoretical value of N2 [M + Na] + : 371.15187; the measured value: 371.15179. It indicates that the α-branched amine compound has been successfully synthesized in this invention.

[0219] Example 25

[0220] This example provides a method for electrochemically synthesizing α-branched amine compounds.

[0221] The difference between this example and Example 1 is:

[0222] In this example, the compound shown in Formula 1w is used to replace the compound shown in Formula 1a, and 52.4 mg of the α-branched amine compound shown in Formula 3w is obtained, with a yield of 56%; the preparation reaction route is as follows:

[0223]

[0224] The data of 1H NMR of the α-branched amine compound shown in Formula 3w are as follows: 11H NMR (600 MHz, CDCl3) δ 7.50 (d, J = 8.4 Hz, 2H), 7.29 - 7.27 (m, 2H), 7.24 - 7.21 (m, 3H), 7.14 (d, J = 8.4 Hz, 2H), 6.95 (t, J = 7.8 Hz, 1H), 6.48 (d, J = 7.8 Hz, 1H), 6.34 (s, 1H), 6.29 (dd, J = 8.4, 2.4 Hz, 1H), 4.60 (t, J = 7.2 Hz, 1H), 4.01 (s, 1H), 3.16 - 3.09 (m, 2H), 2.18 (s, 3H).

[0225] The data of 13C NMR are as follows: 13 13C NMR (151 MHz, CDCl3) δ 146.8, 143.6, 142.5, 139.0, 132.2, 130.1, 129.1, 128.8, 127.5, 126.5, 119.0, 118.9, 114.6, 110.6, 110.6, 58.9, 44.8, 21.6.

[0226] The data of mass spectrum are as follows: C 22 H 20 The HRMS theoretical value of N2 [M + H] + : 313.16993; measured value: 313.16983. It indicates that the α-branched amine compound has been successfully synthesized in this invention.

[0227] Example 26

[0228] This example provides a method for electrochemically synthesizing α-branched amine compounds.

[0229] The difference between this example and Example 1 is as follows:

[0230] In this example, the compound shown in Formula 1x is used to replace the compound shown in Formula 1a, and 60.8 mg of the α-branched amine compound shown in Formula 3x is obtained, with a yield of 61%; the preparation reaction route is as follows:

[0231]

[0232] The data of 1H NMR of the α-branched amine compound shown in Formula 3x are as follows: 11H NMR (600 MHz, CDCl3) δ 7.52 (dd, J = 6.6, 1.8 Hz, 2H), 7.30 - 7.28 (m, 2H), 7.25 - 7.22 (m, 3H), 7.16 (d, J = 7.8 Hz, 2H), 6.91 (d, J = 9.0 Hz, 2H), 6.43 (dt, J = 9.0, 2.4 Hz, 2H), 4.58 (t, J = 7.2 Hz, 1H), 3.94 (s, 1H), 3.16 - 3.10 (m, 2H), 2.47 (q, J = 7.8 Hz, 2H), 1.13 (t, J = 7.8 Hz, 3H).

[0233] The data of 13C NMR are as follows: 13 13C NMR (151 MHz, CDCl3) δ 144.8, 143.7, 142.7, 133.9, 132.3, 130.2, 128.8, 128.6, 127.6, 126.6, 119.0, 113.8, 110.7, 59.3, 45.0, 28.0, 15.9.

[0234] The data of mass spectrometry are as follows: C 23 H 22 The HRMS theoretical value of N2 [M + K] + : 365.14146; measured value: 365.14087. It indicates that the α - branched amine compound of the present invention is successfully synthesized.

[0235] Example 27

[0236] This example provides a method for electrochemically synthesizing α - branched amine compounds.

[0237] The difference between this example and Example 1 is:

[0238] In this example, the compound shown by formula 1y is used to replace the compound shown by formula 1a, and 66.2 mg of the α - branched amine compound shown by formula 3y is obtained, with a yield of 65%; the preparation reaction route is as follows:

[0239]

[0240] The data of 1H NMR of the α - branched amine compound shown by formula 3y are as follows: 11H NMR (600 MHz, CDCl3) δ 7.51 (d, J = 8.4 Hz, 2H), 7.30 - 7.22 (m, 5H), 7.15 (d, J = 8.4 Hz, 2H), 6.89 (d, J = 8.4 Hz, 2H), 6.43 (d, J = 8.4 Hz, 2H), 4.57 (t, J = 6.6 Hz, 1H), 3.95 (s, 1H), 3.16 - 3.10 (m, 2H), 2.40 (t, J = 7.8 Hz, 2H), 1.55 - 1.49 (m, 1H), 0.88 (t, J = 7.2 Hz, 3H).

[0241] The data of 13C NMR are as follows: 13 13C NMR (151 MHz, CDCl3) δ 144.8, 143.6, 142.7, 132.3, 132.3, 130.2, 129.2, 128.8, 127.5, 126.6, 119.0, 113.7, 110.6, 59.3, 45.0, 37.2, 24.9, 14.0.

[0242] The data of mass spectrum are as follows: C 24 H 24 The HRMS theoretical value of C + H2N2 [M + H]: 341.20123; measured value: 341.20117. It indicates that the α - branched amine compound has been successfully synthesized in this invention.

[0243] Example 28

[0244] This example provides a method for electrochemically synthesizing α - branched amine compounds.

[0245] The difference between this example and Example 1 is that:

[0246] In this example, the compound shown in Formula 1z is used to replace the compound shown in Formula 1a, and 68.0 mg of the α - branched amine compound shown in Formula 3z is obtained, with a yield of 64%; the preparation reaction route is as follows:

[0247]

[0248] The data of 1H NMR of the α - branched amine compound shown in Formula 56 are as follows: 11H NMR (600 MHz, CDCl3) δ 7.52 (d, J = 8.4 Hz, 2H), 7.31 - 7.23 (m, 5H), 7.27 - 7.22 (m, 3H), 7.17 (d, J = 8.4 Hz, 2H), 7.12 - 7.09 (m, 2H), 6.46 - 6.43 (m, 2H), 4.57 (t, J = 7.2 Hz, 1H), 3.99 (s, 1H), 3.16 - 3.10 (m, 2H), 1.22 (s, 9H).

[0249] The data of 13C NMR are as follows: 13 13C NMR (151 MHz, CDCl3) δ 144.5, 143.7, 142.8, 140.8, 132.3, 130.2, 128.9, 127.6, 126.6, 126.1, 119.0, 113.4, 110.7, 59.4, 45.1, 34.0, 31.6.

[0250] The data of mass spectrometry are as follows: C 25 H 26 The HRMS theoretical value of N2 [M + H] + : 355.21688; measured value: 355.21667. It indicates that the α-branched amine compound has been successfully synthesized in this invention.

[0251] Example 29

[0252] This example provides a method for electrochemically synthesizing α-branched amine compounds.

[0253] The difference between this example and Example 1 is:

[0254] In this example, the compound shown in Formula 1X is used to replace the compound shown in Formula 1a, and 40.8 mg of the α-branched amine compound shown in Formula 3X is obtained, with a yield of 43%; the preparation reaction route is as follows:

[0255]

[0256] The data of 1H NMR of the α-branched amine compound shown in Formula 3X are as follows: 11H NMR(600MHz,CDCl3)δ7.53(d,J=7.8Hz,2H),7.30(t,J=7.2Hz,2H),7.26 - 7.22(m,3H),7.17(d,J=8.4Hz,2H),6.93(ddd,J=12.0,8.4,1.2Hz,1H),6.81(t,J=7.8Hz,1H),6.59 - 6.55(m,1H),6.44 - 6.41(m,1H),4.60(t,J=7.2Hz,1H),4.35(s,1H),3.22 - 3.15(m,2H).

[0257] The data of 13C NMR are as follows: 13 13C NMR(151MHz,CDCl3)δ151.7(d,J=238.6Hz),143.3,142.0,135.3(d,J=12.1Hz),132.4,130.2,128.9,127.8,126.5,124.6(d,J=3.0Hz),119.0,117.4(d,J=7.6Hz),114.5(d,J=18.1Hz),113.5(d,J=3.0Hz),110.9,59.0,45.0.

[0258] The data of mass spectrometry are as follows: C 21 H 17 The HRMS theoretical value of C + H

[0259] Example 30

[0260] This example provides a method for electrochemically synthesizing α - branched amine compounds.

[0261] The difference between this example and Example 1 is that:

[0262] In this example, the compound shown in Formula 1Y is used to replace the compound shown in Formula 1a, and 74.6 mg of the α - branched amine compound shown in Formula 3Y is obtained, with a yield of 75%; the preparation reaction route is as follows:

[0263]

[0264] The data of 1H NMR of the α - branched amine compound shown in Formula 60 are as follows: 11H NMR (600 MHz, CDCl3) δ 7.51 (d, J = 7.8 Hz, 2H), 7.28 (t, J = 7.2 Hz, 2H), 7.25 - 7.23 (m, 1H), 7.21 - 7.19 (m, 2H), 7.14 (d, J = 8.4 Hz, 2H), 7.01 - 6.98 (m, 2H), 6.41 - 6.39 (m, 2H), 4.56 (t, J = 7.2 Hz, 1H), 4.11 (s, 1H), 3.16 - 3.10 (m, 2H).

[0265] The data of 13C NMR are as follows: 13 13C NMR (151 MHz, CDCl3) δ 145.3, 143.2, 141.8, 132.3, 130.1, 129.1, 128.9, 127.7, 126.5, 122.6, 118.9, 114.8, 110.7, 59.1, 44.8.

[0266] The data of mass spectrometry are as follows: C 21 H 17 The HRMS theoretical value of ClN2 [M + K] + : 371.07118; Measured value: 371.07019. It indicates that the α - branched amine compound has been successfully synthesized in this invention.

[0267] Example 31

[0268] This example provides a method for electrochemically synthesizing α - branched amine compounds.

[0269] The difference between this example and Example 1 is:

[0270] In this example, the compound shown in Formula 2A is used to replace the compound shown in Formula 2a, and 44.6 mg of the α - branched amine compound shown in Formula 3A is obtained, with a yield of 47%; its preparation reaction route is as follows:

[0271]

[0272] The data of 1H NMR of the α - branched amine compound shown in Formula 3A are as follows: 1 1H NMR (600 MHz, CDCl3) δ 7.30 - 7.26 (m, 6H), 7.24 - 7.21 (m, 1H), 7.10 - 7.06 (m, 3H), 6.65 (t, J = 7.2 Hz, 1H), 6.52 - 6.50 (m, 2H), 4.63 (t, J = 6.6 Hz, 1H), 4.22 (s, 1H), 3.23 (dd, J = 13.8, 7.8 Hz, 1H), 3.09 (dd, J = 13.8, 6.6 Hz, 1H).

[0273] The data of the carbon-13 nuclear magnetic resonance spectrum are as follows: 13 C NMR(151MHz,CDCl3)δ161.8(d,J=249.2Hz),146.7,142.2,132.6(d,J=6.0Hz),131.6(d,J=15.1Hz),129.3,128.9,128.1(d,J=4.5Hz),127.7,126.4,119.1(d,J=25.7Hz),118.0,117.7(d,J=3.0Hz),113.6,112.1(d,J=10.6Hz),58.4,38.2。

[0274] The data of the mass spectrum are as follows: C 21 H 17 The theoretical value of HRMS of FN2 [M + H] + : 317.14485; Measured value: 317.14484.

[0275] Example 32

[0276] This example provides a method for electrochemically synthesizing α-branched amine compounds.

[0277] The difference between this example and Example 1 is:

[0278] In this example, the compound shown in Formula 2B is used to replace the compound shown in Formula 2a, and 56.2 mg of the α-branched amine compound shown in Formula 3B is obtained, with a yield of 58%; the preparation reaction route is as follows:

[0279]

[0280] The data of the proton nuclear magnetic resonance spectrum of the α-branched amine compound shown in Formula 3B are as follows: 1 H NMR(600MHz,CDCl3)δ7.70(d,J=8.4Hz,1H),7.58(dd,J=7.8,1.2Hz,1H),7.52(d,J=1.2Hz,1H),7.31-7.25(m,5H),7.10-7.06(m,2H),6.67(t,J=7.8Hz,1H),6.55(d,J=8.4Hz,2H),4.72(dd,J=8.4,6.0Hz,1H),4.28(brs.,1H),3.39-3.31(m,2H)。

[0281] The data of the carbon-13 nuclear magnetic resonance spectrum are as follows: 1313C NMR (151 MHz, CDCl3) δ 146.3, 143.9, 141.4, 134.1, 133.5, 130.7, 129.4, 129.1, 128.1, 126.4, 118.6, 117.5, 117.2, 116.8, 116.5, 114.0, 59.2, 43.1。

[0282] The mass spectrometry data are as follows: C 22 H 17 The HRMS theoretical value of N3 [M+H] + : 324.14952; Measured value: 324.14926. It indicates that the α-branched amine compound has been successfully synthesized in this invention.

[0283] Comparative Example 1

[0284] This comparative example provides a method for electrochemically synthesizing α-branched amine compounds.

[0285] The difference between this comparative example and Example 1 is:

[0286] No electricity was applied in this comparative example.

[0287] Comparative Example 2

[0288] This comparative example provides a method for electrochemically synthesizing α-branched amine compounds.

[0289] The difference between this comparative example and Example 1 is:

[0290] Tetrabutylammonium perchlorate was not added in this comparative example.

[0291] Comparative Example 3

[0292] This comparative example provides a method for electrochemically synthesizing α-branched amine compounds.

[0293] The difference between this comparative example and Example 1 is:

[0294] 2,2,6,6-Tetramethylpiperidine N-oxide was not added in this comparative example.

[0295] Comparative Example 4

[0296] This comparative example provides a method for electrochemically synthesizing α-branched amine compounds.

[0297] The difference between this comparative example and Example 1 is:

[0298] Cesium carbonate was additionally added in this comparative example.

[0299] Comparative Example 5

[0300] This comparative example provides a method for electrochemically synthesizing α-branched amine compounds.

[0301] The difference between this comparative example and Example 1 is as follows:

[0302] Propionic acid was additionally added in this comparative example.

[0303] As Figure 1 shown, N-benzylideneaniline undergoes protonation to obtain protonated N-benzylideneaniline; and a benzyl α-amino radical is generated through single-electron transfer during the cathode electrolysis process; subsequently, a hydrogen atom transfer between p-tolunitrile and the benzyl α-amino radical generates a benzyl radical and an amine; in addition, the 2,2,6,6-tetramethylpiperidine 1-oxyl cation generated by the anodic oxidation of 2,2,6,6-tetramethylpiperidine 1-oxyl can oxidize the amine through SET to form a radical cation, and then this radical cation undergoes deprotonation to regenerate the benzyl α-amino radical. The benzyl α-amino radical reacts with p-tolunitrile to produce a transient benzyl radical; the benzyl radical then undergoes a radical-radical cross-coupling with another molecule of the benzyl α-amino radical to form an α-branched amine product.

[0304] Table 1 shows the actual yields of the synthesis of α-branched amine compounds under different reaction conditions.

[0305] As can be seen from Table 1, compared with Example 1, the reaction in Comparative Example 1 was carried out without power supply. After the reaction ended, the target product was not obtained after post-treatment; this indicates that the reaction cannot proceed without power supply. Compared with Example 1, in Comparative Example 2, tetrabutylammonium perchlorate electrolyte was not added to the reaction. After the reaction ended, the target product was not obtained after post-treatment; this indicates that the reaction cannot proceed without adding an electrolyte. Compared with Example 1, in Comparative Example 3, 2,2,6,6-tetramethylpiperidine 1-oxyl was not added to the reaction. After the reaction ended, 8.3 mg of Compound 6 was obtained after post-treatment, and the yield was 9%; this indicates that not adding a redox mediator is not conducive to the reaction. Compared with Example 1, in Comparative Example 4, cesium carbonate was additionally added to the reaction. After the reaction ended, 40.8 mg of Compound 6 was obtained after post-treatment, and the yield was 46%; this indicates that additionally adding an inorganic base is not conducive to the reaction. Compared with Example 1, in Comparative Example 5, propionic acid was additionally added to the reaction. After the reaction ended, the target product was not obtained after post-treatment; this indicates that additionally adding an acid makes the reaction unable to proceed.

[0306] Table 1 Yield of the synthesis of α-branched amine compounds under different reaction conditions

[0307]

[0308] It should be noted that when numerical ranges are involved in the present invention, it should be understood that both endpoints of each numerical range and any value between the two endpoints can be selected. Since the step methods used are the same as those in the embodiments, in order to prevent repetition, the present invention describes preferred embodiments. Although the preferred embodiments of the present invention have been described, once those skilled in the art learn the basic creative concept, additional changes and modifications can be made to these embodiments, and these changes and modifications all fall within the scope of the present invention.

[0309] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. If these modifications and variations of the present invention fall within the scope of equivalent technologies of the present invention, the present invention also intends to include these changes and variations.

Claims

1. A method for electrochemically synthesizing α-branched amine compounds, characterized in that, It includes the following steps: Using the imine shown in Formula 1 and the p-tolunitrile compound shown in Formula 2 as raw materials, mixing the raw materials, electrolyte, oxidant and solvent to obtain a reaction solution; electrolyzing the reaction solution to cause a cross-coupling reaction between the imine shown in Formula 1 and the p-tolunitrile compound shown in Formula 2 to obtain the α-branched amine compound shown in Formula 3; The electrolyte is a quaternary ammonium salt; the oxidant is one of 2,2,6,6-tetramethylpiperidine oxide, nitroxide piperidinol, 1,4-diazabicyclo[2.2.2]octane, diisopropylethylamine and ferrocene; The specific reaction formula is as follows: Among them, R 1 is phenyl, thienyl, furyl, naphthyl or substituted phenyl; R 1 The substituents of the substituted phenyl in are at least one of methyl, isopropyl, tert-butyl, methoxy, methylthio, trifluoromethyl, trifluoromethoxy, difluoromethoxy, methyl formate group, fluorine atom, chlorine atom, bromine atom, phenyl, pyridyl and benzyloxy; R 2 is phenyl or substituted phenyl; R 2 The substituent of the substituted phenyl in is at least one of methyl, ethyl, n-propyl, tert-butyl, fluorine atom and chlorine atom; R 3 is a hydrogen atom, a fluorine atom or a cyano group.

2. The method for electrochemically synthesizing α-branched amine compounds according to claim 1, wherein The electrolyte is one of tetrabutylammonium perchlorate, tetrabutylammonium hexafluorophosphate, tetrabutylammonium tetrafluoroborate, tetrabutylammonium acetate, tetrabutylammonium iodide, tetrabutylammonium hydrogen sulfate, tetrabutylammonium nitrate, tetrabutylphosphonium bromide, tetraethylammonium perchlorate, tetraethylammonium hexafluorophosphate and tetraethylammonium bromide.

3. The method for electrochemically synthesizing α-branched amine compounds according to claim 1, characterized in that, The concentration of the electrolyte in the reaction solution is 0.03 mol / L to 0.3 mol / L.

4. The method for electrochemically synthesizing α-branched amine compounds according to claim 1, characterized in that, The molar ratio of the imine shown in Formula 1 to the p-tolunitrile compound shown in Formula 2 is 1:2 to 9.

5. The method for electrochemically synthesizing α-branched amine compounds according to claim 1, characterized in that, The molar ratio of the imine shown in Formula 1 to the oxidant is 1:0.25 to 5.

6. The method for electrochemically synthesizing α-branched amine compounds according to claim 1, wherein, The conditions for electrolysis are: the electrolysis current is 6 mA to 15 mA, and the electrolysis time is 3 h to 6 h.

7. The method for electrochemically synthesizing α-branched amine compounds according to claim 1, wherein The solvent is one of N,N-dimethylformamide, N,N-dimethylacetamide and dimethyl sulfoxide.

8. The method for electrochemically synthesizing α-branched amine compounds according to claim 1, characterized in that, R 1 The number of substituents of the substituted phenyl group is 1, 2 or 3.

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