Method for electrooxidation synthesis of fluoroalkyl-substituted benzo-seven-membered nitrogen heterocyclic ring

Abstract

The invention relates to the technical field of chemical synthesis, and particularly discloses a method for electrooxidation synthesis of fluoroalkyl-substituted benzo-seven-membered nitrogen heterocycle, which specifically comprises the following steps: step 1, under the condition of energization, aryl diazonium salt and fluorine-containing sodium methanesulfinate compounds react in an electrolyte and a solvent to obtain a fluorine-substituted benzo-seven-membered nitrogen heterocycle, and the fluorine-substituted benzo-seven-membered nitrogen heterocycle is obtained; the benzo seven-membered nitrogen heterocyclic ring is obtained. Step 2, generating a benzo-seven-membered nitrogen heterocyclic compound from a fluorine-containing sodium methanesulfinate compound and a substituted aryl diazonium salt in an electrolyte under the promotion of electricity, in the method, a transition metal catalyst is not needed, and the method is carried out only under the action of current, so that the method is energy-saving and economical; the free radical source used in the reaction is cheap and easy to obtain, the cost is low, the seven-membered nitrogen heterocyclic compound can be directly synthesized, and compared with the prior art, the synthesis cost is reduced.

Description

Technical Field

[0001] The invention relates to the technical field of chemical synthesis, in particular to a method for electro-oxidation synthesis of fluoroalkyl-substituted benzo seven-membered nitrogen heterocycles. Background Art

[0002] Heterocyclic compounds are widely present in drug molecules and natural products. Finding greener and novel synthesis methods for heterocyclic compounds is the direction of efforts of many synthetic chemists.

[0003] Free radical chemistry has achieved a revival and has become a powerful tool for building new chemical bonds. The rapid development of free radical chemistry has opened up a new path for the synthesis of heterocyclic compounds with new substitution characteristics. Previously, Li Yi's research group at Fuzhou University designed a method to react diazonium salts with trifluoroalkyl groups to construct a benzo-7-membered nitrogen heterocycle under photocatalysis. The reaction mechanism is shown in the following formula: (Reference: Org. Lett. 2024, 26, 3622-2627.)

[0004]

[0005] However, the above reaction requires the use of one equivalent of the chemical oxidant tert-butyl hydroperoxide to initiate the generation of free radicals, which has a high reaction cost, low environmental friendliness, and does not achieve the direct synthesis of trifluoromethyl or difluoromethyl substituted products. Therefore, it is very necessary to obtain trifluoromethyl substituted benzo seven-membered nitrogen heterocyclic products through electrochemistry. Summary of the invention

[0006] In view of the technical problems that the prior art requires the use of one equivalent of chemical oxidant tert-butyl hydroperoxide to initiate the generation of free radicals, the reaction cost is high, the environmental friendliness is low, and the direct synthesis of trifluoromethyl or difluoromethyl substituted products cannot be achieved, the present invention provides a method for electro-oxidation synthesis of fluoroalkyl substituted benzo seven-membered nitrogen heterocycles.

[0007] The technical solution adopted by the present invention is: a method for electro-oxidation synthesis of fluoroalkyl-substituted benzo seven-membered nitrogen heterocycle, which specifically comprises the following steps:

[0008] Step 1: Under the condition of passing electric current, an aromatic diazonium salt reacts with a fluorinated sodium methanesulfinate compound in an electrolyte and a solvent to obtain the benzo seven-membered nitrogen heterocycle.

[0009] The structure of the aryl diazonium salt is shown in formula (I):

[0010]

[0011] The structure of the fluorinated sodium methanesulfinate is shown in formula (II):

[0012]

[0013] In formula (I) to formula (II), R 1 It is an electron-withdrawing group such as a nitro group, a halogen atom, a cyano group, an acyl group, a carboxyl group, or an electron-donating group such as an amino group, a methyl group, a methoxy group, etc.;

[0014] Among them, R 1 The substitution position can be at the 3, 4, 5, or 6 position of the benzene ring.

[0015] R 2 is a H or fluorine atom;

[0016] X is O, S or nitrogen atom;

[0017] Step 2, using a fluorinated sodium methanesulfinate compound to react with a substituted aryl diazonium salt in an electrolyte to generate a benzo seven-membered nitrogen heterocyclic compound under the promotion of electricity. The specific reaction formula is shown in the following formula:

[0018]

[0019] The present invention is further configured such that the reaction in step 1 is carried out under a constant current, and the current fluctuation range is 3-10 mA.

[0020] The present invention is further configured such that the electrolyte in step one is one of tetrabutylammonium tetrafluoroborate, lithium tert-butoxide, tetrabutylammonium iodate, tetraethylammonium perchlorate, tetraethylammonium hexafluorophosphate and tetrabutylammonium perchlorate, and the concentration is 0.05 to 1 mol / L.

[0021] The present invention is further configured such that the solvent in step 1 is one of acetonitrile, water, dichloroethane, methanol, isopropanol, ethyl acetate, N,N-dimethylformamide and tetrahydrofuran.

[0022] The present invention is further configured such that the reaction temperature in step 1 is 25-70°C.

[0023] The present invention is further configured such that the reaction atmosphere in step 1 is one of air and nitrogen; the anode material is a carbon electrode, and the cathode material is Ni or Pt.

[0024] The beneficial effects of the present invention are as follows: compared with the prior art, in the present invention, no transition metal catalyst is required, the reaction is carried out only under the action of electric current, and energy-saving and economical; the free radical source used in the reaction is cheap and easy to obtain, and the cost is low, and a seven-membered nitrogen heterocyclic compound can be directly synthesized, and the synthesis cost is reduced compared with the prior art. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 The product obtained in Example 1 of the present invention 1 HNMR spectrum;

[0026] Figure 2 The product obtained in Example 1 of the present invention 13 CNMR spectrum;

[0027] Figure 3 The product obtained in Example 1 of the present invention 19 F-NMR spectrum;

[0028] Figure 4 The product obtained in Example 2 of the present invention 1 HNMR spectrum;

[0029] Figure 5 The product obtained in Example 2 of the present invention 1 CNMR spectrum;

[0030] Figure 6 The product obtained in Example 2 of the present invention 19 F-NMR spectrum;

[0031] Figure 7 For the product obtained in Example 3 of the present invention 1 HNMR spectrum;

[0032] Figure 8 For the product obtained in Example 3 of the present invention 13 CNMR spectrum;

[0033] Fig. 9 For the product obtained in Example 3 of the present invention 19 F-NMR spectrum;

[0034] Fig.10 The product obtained in Example 4 of the present invention 1 HNMR spectrum;

[0035] Fig.11 The product obtained in Example 4 of the present invention 1 CNMR spectrum;

[0036] Fig.12 The product obtained in Example 4 of the present invention 19 F-NMR spectrum;

[0037] Fig.13 The product obtained in Example 5 of the present invention 1 HNMR spectrum;

[0038] Fig.14 The product obtained in Example 5 of the present invention 13 CNMR spectrum;

[0039] Fig.15The product obtained in Example 5 of the present invention 19 F-NMR spectrum;

[0040] Fig.16 The product obtained in Example 6 of the present invention 1 HNMR spectrum;

[0041] Fig.17 The product obtained in Example 6 of the present invention 13 CNMR spectrum;

[0042] Fig.18 The product obtained in Example 6 of the present invention 19 F-NMR spectrum;

[0043] Fig.19 It is a device diagram of the reaction process in the present invention. DETAILED DESCRIPTION

[0044] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0045] Referring to 1-19, in order to solve the problems existing in the background technology, the present application proposes the following technical solution: a method for electro-oxidation synthesis of fluoroalkyl-substituted benzo seven-membered nitrogen heterocycle, specifically comprising the following steps:

[0046] Step 1: Under the condition of passing electric current, an aromatic diazonium salt reacts with a fluorinated sodium methanesulfinate compound in an electrolyte and a solvent to obtain the benzo seven-membered nitrogen heterocycle.

[0047] The structure of the aryl diazonium salt is shown in formula (I):

[0048]

[0049] The structure of the fluorinated sodium methanesulfinate is shown in formula (II):

[0050]

[0051] In formula (I) to formula (II), R 1 It is an electron-withdrawing group such as a nitro group, a halogen atom, a cyano group, an acyl group, a carboxyl group, or an electron-donating group such as an amino group, a methyl group, a methoxy group, etc.;

[0052] Among them, R 1 The substitution position can be at the 3, 4, 5, or 6 position of the benzene ring.

[0053] R 2 is a H or fluorine atom;

[0054] X is O, S or nitrogen atom;

[0055] Step 2, using a fluorinated sodium methanesulfinate compound to react with a substituted aryl diazonium salt in an electrolyte to generate a benzo seven-membered nitrogen heterocyclic compound under the promotion of electricity. The specific reaction formula is shown in the following formula:

[0056]

[0058] The above technical solution is explained as follows: During the reaction, the fluorinated methanesulfinic acid anion first loses electrons at the anode to become a fluorinated free radical A, and the free radical A attacks the terminal olefin carbon to generate a thermodynamically more stable free radical B. Then, the free radical B hits the nitrogen-nitrogen double bond and cyclizes into a more stable new free radical positive ion C. The free radical C then reacts with the fluorinated methanesulfinic acid anion to obtain a benzo seven-membered nitrogen heterocycle. The reaction mechanism is speculated to be as shown in the following formula:

[0059]

[0060] The reaction in step 1 is carried out under a constant current, and the current fluctuation range is 3-10 mA. The actual current size is 3-10 mA, and more preferably under 4 mA, at which the product yield is the highest.

[0061] The electrolyte in step 1 is one of tetrabutylammonium tetrafluoroborate, lithium tert-butoxide, tetrabutylammonium iodate, tetraethylammonium perchlorate, tetraethylammonium hexafluorophosphate and tetrabutylammonium perchlorate, and the concentration is 0.05 to 1 mol / L. The electrolyte actually selected is tetrabutylammonium tetrafluoroborate, and the solution concentration is 0.1M.

[0062] Wherein, the solvent in step 1 is one of acetonitrile, water, dichloroethane, methanol, isopropanol, ethyl acetate, N,N-dimethylformamide and tetrahydrofuran. The actual solvent used is an acetonitrile system.

[0063] The reaction temperature in step 1 is 25-70° C. The reaction temperature is 25-70° C. If the reaction temperature is too high or too low, the conversion rate of the reactants will be reduced. As a further preferred embodiment, the reaction temperature is 45° C.

[0064] Among them, the reaction atmosphere in step 1 is one of air and nitrogen; the reaction atmosphere is air, and the reactor is open to the air environment, that is, it is an open system during the reaction process to avoid the accumulation of hydrogen generated at the cathode causing excessive pressure or explosion hazard; in addition, the reaction time can be monitored by TLC, and the reaction can be completed by stirring at 45°C for 2 to 5 hours. As a further preferred embodiment, the reaction time is 2 hours.

[0065] The anode material is a carbon electrode, and the cathode material is Ni or Pt. In practice, the anode material is graphite felt (GF), and the cathode material is a platinum sheet or nickel foam. As a further preferred embodiment, the cathode uses a platinum sheet.

[0066] Embodiment 1:

[0067] In a reaction tube, diazonium salt 1a (157.2 mg, 0.6 mmol, 2.0 equiv.), NaSO2CF32a (46.8 mg, 0.3 mmol, 1.0 equiv.), nBu4NBF4 (131 mg, 0.4 mmol, 1.3 equiv.) were accurately added and dissolved in solvent MeCN (4 mL). The anode was graphite felt GF, the electrode specifications were (10 mm × 15 mm × 6 mm), and the cathode was a platinum sheet electrode with specifications (10 mm × 15 mm × 0.25 mm). The electro-oxidation reaction was carried out at 45 ° C, the current was maintained at 4 mA, and it lasted for 2 hours. All solvents were transferred to a round-bottom flask. Silica was added to the flask and the solvent was evaporated in vacuo. PE / EA (v / v, 5:1) was used as the eluent and purified by silica gel column chromatography to obtain the corresponding product 3aa with a yield of 78%. The reaction formula is as follows:

[0068]

[0069] The product 3aa prepared in this example 1 H NMR spectrum is shown in Figure 1 , 13 C NMR spectrum is shown in Figure 2 , 19 F NMR spectrum is shown in Figure 3 ; NMR data of product 3a: 1 H NMR (400MHz, CDCl3) δ7.52 (s, 1H), 6.92 (d, J = 8.1Hz, 1H), 6.73 (d, J = 8.1Hz, 1H), 6.59 (s, 1H), 4.69 (s, 2H), 3.06 (q, J = 10.8Hz, 2H), 2.29 (s, 3H); 13CNMR(151MHz, CDCl3)δ147.5,137.1,137.0,134.1,125.9(q,J=277.8Hz),122.7,121.3,118.1,72.3,41.7(q,J=30.2Hz),20.7; 19 F NMR (565MHz,CDCl3)δ-64.39.

[0070] Embodiment 2:

[0071] In the reaction tube, diazonium salt 1b (148.2 mg, 0.6 mmol, 2.0 equiv.), NaSO2CF32a (46.8 mg, 0.3 mmol, 1.0 equiv.), nBu4NBF4 (131 mg, 0.4 mmol, 1.3 equiv.) were accurately added and dissolved in solvent MeCN (4 mL). The anode was graphite felt GF, the electrode specifications were (10 mm × 15 mm × 6 mm), and the cathode was a platinum sheet electrode with specifications (10 mm × 15 mm × 0.25 mm). The electro-oxidation reaction was carried out at 45 ° C, the current was maintained at 4 mA, and it lasted for 2 hours. All solvents were transferred to a round-bottom flask. Silica was added to the flask and the solvent was evaporated in vacuo. PE / EA (v / v, 5:1) was used as the eluent and purified by silica gel column chromatography to obtain the corresponding product 3ba with a yield of 58%. The reaction formula is as follows:

[0072]

[0073] The product 3ba prepared in this example 1 H NMR spectrum is shown in Figure 4 , 13 C NMR spectrum is shown in Figure 5 , 19 F NMR spectrum is shown in Figure 6 ; NMR data of product 3ba: 1 HNMR (600MHz, CDCl3) δ7.47(s,1H),7.03–7.00(m,2H),6.92(td,J=7.7,1.3Hz,1H),6.80–6.78(m,1H),4.72(s,2H),3.06(q,J=10.8Hz,2H); 13 CNMR (151MHz, CDCl3) δ149.6,137.5,137.3,125.5(q,J=277.8Hz),124.4,123.0,121.6,117.8,72.15,41.8(q,J=30.2Hz); 19 F NMR (565MHz,CDCl3)δ-64.41.

[0074] Embodiment 3:

[0075] In a reaction tube, diazonium salt 1c (195.0 mg, 0.6 mmol, 2.0 equiv.), NaSO2CF32a (46.8 mg, 0.3 mmol, 1.0 equiv.), nBu4NBF4 (131 mg, 0.4 mmol, 1.3 equiv.) were accurately added and dissolved in solvent MeCN (4 mL). The anode was graphite felt GF with an electrode specification of (10 mm × 15 mm × 6 mm), and the cathode was a platinum sheet electrode with a specification of (10 mm × 15 mm × 0.25 mm). The electro-oxidation reaction was carried out at 45 °C, and the current was maintained at 4 mA for 2 hours. All solvents were transferred to a round-bottom flask. Silica was added to the flask and the solvent was evaporated in vacuo. Purification was carried out by silica gel column chromatography using PE / EA (v / v, 5:1) as the eluent to obtain the corresponding product 3ca with a yield of 59%. The reaction formula is as follows:

[0076]

[0077] The product 3ca prepared in this example 1 H NMR spectrum is shown in Figure 7 , 13 C NMR spectrum is shown in Figure 8 , 19 F NMR spectrum is shown in Fig. 9 ; NMR data of product 3ca: 1 H NMR (600MHz, CDCl3) δ7.43 (s, 1H), 6.99 (dd, J = 8.5, 2.2Hz, 1H), 6.92 (d, J = 2.2Hz, 1H), 6.87 (d, J = 8.5Hz, 1H), 4.68 (s, 2H), 3.06 (q, J = 10.2Hz, 2H); 13 C NMR (151MHz, CDCl3) δ148.5, 138.6, 138.2, 125.4 (q, J = 277.8Hz), 125.5, 123.0, 120.3, 116.5, 71.9, 41.8 (q, J = 30.2Hz). 19 F NMR (565MHz,CDCl3)δ-64.35.

[0078] Embodiment 4:

[0079] In the reaction tube, diazonium salt 1d (169.2 mg, 0.6 mmol, 2.0 equiv.), NaSO2CF32a (46.8 mg, 0.3 mmol, 1.0 equiv.), nBu4NBF4 (131 mg, 0.4 mmol, 1.3 equiv.) were accurately added and dissolved in solvent MeCN (4 mL). The anode was graphite felt GF, the electrode specifications were (10 mm × 15 mm × 6 mm), and the cathode was a platinum sheet electrode with specifications (10 mm × 15 mm × 0.25 mm). The electro-oxidation reaction was carried out at 45 ° C, the current was maintained at 4 mA, and it lasted for 2 hours. All solvents were transferred to a round-bottom flask. Silica was added to the flask and the solvent was evaporated in vacuo. PE / EA (v / v, 5:1) was used as the eluent and purified by silica gel column chromatography to obtain the corresponding product 3da with a yield of 64%. The reaction formula is as follows:

[0080]

[0081] The product 3da prepared in this example 1 H NMR spectrum is shown in Fig.10 , 13 C NMR spectrum is shown in Fig.11 , 19 F NMR spectrum is shown in Fig.12 ; NMR data of product 3da: 1 H NMR (400MHz, CDCl3) δ7.42 (s, 1H), 6.93 (d, J = 8.5Hz, 1H), 6.85 (dd, J = 8.6, 2.1Hz, 1H), 6.78 (s, 1H), 4.68 (s, 2H), 3.06 (q, J = 10.7Hz, 2H); 13 CNMR (151MHz, CDCl3) δ148.0, 138.5, 137.9, 129.2, 126.4 (q, J = 277.8Hz), 122.7, 122.6, 117.4, 72.0, 41.8 (q, J = 30.2Hz). 19 F NMR (565MHz,CDCl3)δ-64.36.

[0082] Embodiment 5:

[0083] In a reaction tube, diazonium salt 1e (182.4 mg, 0.6 mmol, 2.0 equiv.), NaSO2CF32a (46.8 mg, 0.3 mmol, 1.0 equiv.), and nBu4NBF4 (131 mg, 0.4 mmol, 1.3 equiv.) were accurately added and dissolved in solvent MeCN (4 mL). The anode was graphite felt GF with an electrode specification of (10 mm × 15 mm × 6 mm), and the cathode was a platinum sheet electrode with a specification of (10 mm × 15 mm × 0.25 mm). The electro-oxidation reaction was carried out at 45 °C, and the current was maintained at 4 mA for 2 hours. All solvents were transferred to a round-bottom flask. Silica was added to the flask and the solvent was evaporated in vacuo. PE / EA (v / v, 5:1) was used as the eluent and purified by silica gel column chromatography to obtain the corresponding product 3ea with a yield of 85%. The reaction formula is as follows:

[0084]

[0085] The product 3ea prepared in this example 1 H NMR spectrum is shown in Fig.13 , 13 C NMR spectrum is shown in Fig.14 , 19 F NMR spectrum is shown in Fig.15 ; NMR data of product 3ea: 1 HNMR (400MHz, CDCl3) δ7.44(s,1H),6.94(s,2H),6.77(s,1H),4.70(s,2H),3.05(q,J=10.8Hz,2H),1.30(s,9H). 13 C NMR (151MHz, CDCl3) δ147.6, 147.3, 137.1, 136.6, 125.5 (q, J = 277.8Hz), 121.0, 120.2, 114.7, 72.2, 41.9 (q, J = 28.7Hz), 34.4, 31.5. 19 F NMR (565MHz,CDCl3)δ-64.41.

[0086] Embodiment 6:

[0087] In the reaction tube, diazonium salt 1f (232.2 mg, 0.6 mmol, 2.0 equiv.), NaSO2CF32a (46.8 mg, 0.3 mmol, 1.0 equiv.), nBu4NBF4 (131 mg, 0.4 mmol, 1.3 equiv.) were accurately added and dissolved in solvent MeCN (4 mL). The anode was graphite felt GF, the electrode specifications were (10 mm × 15 mm × 6 mm), and the cathode was a platinum sheet electrode with specifications (10 mm × 15 mm × 0.25 mm). The electro-oxidation reaction was carried out at 45 ° C, the current was maintained at 4 mA, and it lasted for 2 hours. All solvents were transferred to a round-bottom flask. Silica was added to the flask and the solvent was evaporated in vacuo. PE / EA (v / v, 5:1) was used as the eluent and purified by silica gel column chromatography to obtain the corresponding product 3fa with a yield of 74%. The reaction formula is as follows:

[0088]

[0089] The product 3fa prepared in this example 1 H NMR spectrum is shown in Fig.16 , 13 C NMR spectrum is shown in Fig.17 , 19 F NMR spectrum is shown in Fig.18 ; NMR data of product 3fa: 1 HNMR(400MHz, CDCl3)δ7.37–7.32(m,3H),7.15–7.08(m,3H),6.96–6.90(m,2 H), 6.55 (d, J = 8.0Hz, 1H), 4.38 (s, 2H), 2.87 (q, J = 10.8Hz, 2H), 2.31 (s, 3H). 13 C NMR (101MHz, CDCl3) δ 144.0, 142.3, 136.1, 130.5 (q, J = 175.7Hz) 133.2, 129. 4,128.6,127.7,126.8,124.0,123.1,117.9,52.1,42.7(q,J=29.2Hz),21.7. 19 F NMR (565MHz,CDCl3)δ-64.21.

[0090] Embodiment 7:

[0091] The same as Example 1, the only difference is that the reaction conditions (Table 1) are changed. The yield of preparing benzo seven-membered nitrogen heterocycle by electrochemical free radical reaction under different reaction conditions is statistically analyzed.

[0092]

[0093] Table 1 Optimization of reaction conditions

[0094] Grouping Solvents Electrolytes temperature Yield / % 1 MeCN <![CDATA[Et4NClO4]]> 45℃ 41 2 <![CDATA[MeCN:H2O=4:1]]> <![CDATA[Et4NClO4]]> 45℃ 0 3 1,4-dioxane <![CDATA[Et4NClO4]]> 45℃ 27 4 DCE <![CDATA[Et4NClO4]]> 45℃ 34 5 DCE:MeCN=1:1 <![CDATA[Et4NClO4]]> 45℃ 40 6 MeCN <![CDATA[nBu4NF4]]> 45℃ 78 7 MeCN <![CDATA[nBu4NPF6]]> 45℃ 40 8 MeCN <![CDATA[nBu4NF4]]> 20℃ 29 9 MeCN <![CDATA[nBu4NF4]]> 60℃ 40 <![CDATA[10 [b] ]]> MeCN <![CDATA[nBu4NF4]]> 45℃ 24 <![CDATA[11 [c] ]]> MeCN <![CDATA[nBu4NF4]]> 45℃ 50

[0095] Reaction parameters:

[0096] Reaction parameter conditions of groups 1 to 9 [a]: 1a (0.60 mmol, 2.0 equiv), 2a (0.30 mmol, 1.0 equiv), solvent (4 mL), air, the amount of electrolyte is 1.3 times that of 2a, current (4.0 mA), 2 h.

[0097] [b] is the reaction time of 1.5h.

[0098] [c] is the reaction time of 2.5h.

[0099] In summary, the reaction in the present invention does not require a transition metal catalyst and is carried out only under the action of electric current, which is energy-saving and economical; the free radical source used in the reaction is cheap and easy to obtain, and the cost is low, and a seven-membered nitrogen heterocyclic compound can be directly synthesized, which reduces the synthesis cost compared with the prior art.

[0100] While the embodiments of the present invention have been shown and described, it will be apparent to those skilled in the art that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for electro-oxidative synthesis of fluoroalkyl-substituted benzo seven-membered nitrogen heterocycles, characterized in that: The specific steps include: Step 1: Under the condition of passing electric current, an aromatic diazonium salt reacts with a fluorinated sodium methanesulfinate compound in an electrolyte and a solvent to obtain the benzo seven-membered nitrogen heterocycle. The structure of the aryl diazonium salt is shown in formula (I): The structure of the fluorinated sodium methanesulfinate is shown in formula (II): In formula (I) to formula (II), R 1 It is an electron-withdrawing group such as a nitro group, a halogen atom, a cyano group, an acyl group, a carboxyl group, or an electron-donating group such as an amino group, a methyl group, a methoxy group, etc.; Among them, R 1 The substitution position can be at the 3, 4, 5, or 6 position of the benzene ring. R 2 is a H or fluorine atom; X is O, S or nitrogen atom; Step 2, using a fluorinated sodium methanesulfinate compound to react with a substituted aryl diazonium salt in an electrolyte to generate a benzo seven-membered nitrogen heterocyclic compound under the promotion of electricity. The specific reaction formula is shown in the following formula:

2. The method for electro-oxidation synthesis of fluoroalkyl-substituted benzo seven-membered nitrogen heterocycle according to claim 1, characterized in that: The reaction in step 1 is carried out under a constant current, and the current fluctuation range is 3 to 10 mA.

3. The method for electro-oxidative synthesis of fluoroalkyl-substituted benzo seven-membered nitrogen heterocycle according to claim 1, characterized in that: The electrolyte in step 1 is one of tetrabutylammonium tetrafluoroborate, lithium tert-butoxide, tetrabutylammonium iodate, tetraethylammonium perchlorate, tetraethylammonium hexafluorophosphate and tetrabutylammonium perchlorate, and the concentration is 0.05 to 1 mol / L.

4. The method for electro-oxidation synthesis of fluoroalkyl-substituted benzo seven-membered nitrogen heterocycle according to claim 1, characterized in that: The solvent in step 1 is one of acetonitrile, water, dichloroethane, methanol, isopropanol, ethyl acetate, N,N-dimethylformamide and tetrahydrofuran.

5. The method for electro-oxidation synthesis of fluoroalkyl-substituted benzo seven-membered nitrogen heterocycle according to claim 1, characterized in that: The reaction temperature in step 1 is 25-70°C.

6. The method for electro-oxidative synthesis of fluoroalkyl-substituted benzo seven-membered nitrogen heterocycle according to claim 5, characterized in that: The reaction atmosphere in step 1 is one of air and nitrogen; the anode material is a carbon electrode, and the cathode material is Ni or Pt.

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