A method for electrocatalytic synthesis of N-phenylbenzoxazine amine

Abstract

The present invention relates to the field of electrocatalytic synthesis technology, and in particular to a method for electrocatalytic synthesis of N-phenylbenzoxazinamine. The method comprises: mixing a compound having formula I, a compound having formula II, tetrabutylammonium iodide, acetonitrile and triethylamine to obtain a mixture; reacting the obtained mixture for 3 hours at a current of 5 mA and a temperature of 20 to 30 ° C with platinum sheets as cathode and anode to obtain N-phenylbenzoxazinamine. The present invention adopts an electrocatalytic method to synthesize N-phenylbenzoxazinamine. The method is a novel electrocatalytic synthesis method with simple operation, mild conditions, and no expensive metal catalysts, oxidants, etc. are required in the reaction system. The reaction can obtain various substituted N-phenylbenzoxazinamines in good yield.

Description

Technical Field

[0001] The present invention relates to the technical field of electrocatalytic synthesis, in particular to a method for electrocatalytic synthesis of N-phenylbenzoxazinamine. Background Art

[0002] Six-membered heterocyclic rings containing N, O, and S groups can form a variety of pharmaceutically active molecules, and these scaffolds are widely used as building blocks for bioactive molecules. Benzoxazine derivatives exhibit numerous unique biological and pharmaceutical properties, such as progesterone receptor modulators, anxiolytics, and anti-HIV agents. Related molecules, such as the 2-amino-4-H-1,3-benzothiazine scaffold, also possess unique biological properties and are gaining increasing attention in medicinal chemistry.

[0003] Given the broad pharmacological activity of this class of compounds, synthetic chemists have developed a series of methods for synthesizing benzoxazine derivatives in recent years, including metal-catalyzed tandem addition-cyclization reactions and oxidative synthesis, as well as non-metal-catalyzed / dehydrogenative sulfidation methods. However, the synthesis of such heterocyclic skeletons often requires expensive and complex reaction substrates, transition metal catalysts, acids, bases, and strong oxidants, and is accompanied by long reaction times and harsh conditions. For example, H. Ghosh reported a method for constructing benzoxazines using o-aminobenzyl alcohol and isothiocyanates under the catalysis of iodobenzene acetate. Furthermore, Han also reported a method for synthesizing benzoxazines using o-aminobenzyl alcohol and aldehydes under the catalysis of cuprous chloride and oxygen.

[0004] Based on the current research status, an environmentally friendly, simple and efficient method is needed to synthesize benzoxazine derivatives. Summary of the Invention

[0005] In order to solve the above problems, the present invention provides a method for electrocatalytic synthesis of N-phenylbenzoxazinamine. By electrocatalysis, a compound having formula I and a compound having formula II are used as substrates. Under electrocatalytic conditions, tetrabutylammonium iodide is used as an electrolyte, and triethylamine is used as a base to synthesize a series of benzoxazinamine compounds in a mild, green and efficient manner.

[0006] In order to achieve the above object, the present invention provides the following technical solutions:

[0007] The present invention provides a method for electrocatalytic synthesis of N-phenylbenzoxazinamine, comprising the following steps:

[0008] 1) mixing a compound having formula I, a compound having formula II, tetrabutylammonium iodide, acetonitrile and triethylamine to obtain a mixture;

[0009]

[0010]

[0011] where R 1 Any one selected from hydrogen, methyl, phenyl, 4-fluoro-phenyl and 4-chloro-phenyl, R 2 Any one selected from hydrogen and methyl;

[0012] R 3 -NCs

[0013] Formula II;

[0014] Among them, R 3 Any one selected from phenyl, 4-fluoro-phenyl, 4-methyl-phenyl, 4-trifluoromethyl-phenyl and 2-methyl-phenyl;

[0015] 2) reacting the mixture obtained in step 1) for 3 h at a current of 5 mA and a temperature of 20-30° C. using platinum sheets as cathodes and anodes to obtain N-phenylbenzoxazinamine;

[0016] The structural formula of the N-phenylbenzoxazinamine is shown in Formula III;

[0017]

[0018] Preferably, in step 1), the molar ratio of the compound of formula I, the compound of formula II, the molar ratio of tetrabutylammonium iodide, the volume of acetonitrile and triethylamine is 0.2 mmol:0.3 mmol:0.3 mmol:6 mL:0.3 mmol.

[0019] Preferably, the specification of the anode in step 2) is 1 cm×1 cm×0.1 cm;

[0020] The specifications of the cathode are 1 cm×1 cm×0.1 cm.

[0021] Preferably, the compound having formula I in step 1) is any one of the following compounds:

[0022]

[0023] Preferably, the compound of formula II in step 1) is any one of the following compounds:

[0024]

[0025]

[0026] Preferably, after the reaction in step 2), a reactant is obtained, the acetonitrile is evaporated under reduced pressure, and then the reactant is separated and purified by silica gel column chromatography to obtain N-phenylbenzoxazinamine.

[0027] Preferably, the mobile phase used in the silica gel column chromatography separation and purification is petroleum ether and ethyl acetate.

[0028] Preferably, the volume ratio of petroleum ether to ethyl acetate is 5:1.

[0029] Beneficial effects of the present invention:

[0030] The present invention utilizes a novel electrochemically catalyzed, one-pot method for synthesizing N-phenylbenzoxazinamines, which is simple to operate. The reaction system does not require expensive metal catalysts or toxic oxidants, and the reaction can proceed at room temperature under mild conditions, making it environmentally friendly. The reaction can yield various substituted N-phenylbenzoxazinamines in good yields.

[0031] Currently, there are several strategies for synthesizing this class of compounds, including using o-aminobenzyl alcohol and isothiocyanate compounds as substrates, iodobenzene acetate as a catalyst, and trifluoroethanol as a solvent; or using o-aminobenzyl alcohol and benzaldehyde compounds as substrates, cuprous chloride as a catalyst, and oxygen as an oxidant. Compared to these methods, this method offers milder reaction conditions, employing tetrabutylammonium iodide as an electrolyte, eliminating the need for high temperatures and metal catalysts. This method eliminates the dangers of elemental iodine as a flammable chemical, making it simple to operate and environmentally friendly and efficient.

[0032] On this basis, C(+) / Pt(-) with a yield of 69%, C(+) / C(-) with a yield of 66%, and C(+) / Ni(-) with a yield of 44% were selected, and the yield was reduced.

[0033] On this basis, tetrabutylammonium tetrafluoroborate, tetrabutylammonium hexafluorophosphate, and tetrabutylammonium perchlorate were selected, and the yields of sodium perchlorate were all 0%, the yield of sodium iodide was 42%, and the yield of potassium iodide was 45%, and the yields were reduced.

[0034] On this basis, potassium carbonate with a yield of 57%, sodium carbonate with a yield of 43%, cesium carbonate with a yield of 65%, sodium hydroxide with a yield of 30%, and 4-dimethylaminopyridine with a yield of 60% were selected, and the yield was reduced. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments are briefly introduced below.

[0036] Figure 1 This is the hydrogen spectrum of the N-phenylbenzoxazinamine compound prepared in Example 1;

[0037] Figure 2 This is the carbon spectrum of the N-phenylbenzoxazinamine compound prepared in Example 1;

[0038] Figure 3 This is the hydrogen spectrum of the N-phenylbenzoxazinamine compound prepared in Example 2;

[0039] Figure 4 This is the carbon spectrum of the N-phenylbenzoxazinamine compound prepared in Example 2;

[0040] Figure 5 This is the hydrogen spectrum of the N-phenylbenzoxazinamine compound prepared in Example 3;

[0041] Figure 6 This is the carbon spectrum of the N-phenylbenzoxazinamine compound prepared in Example 3;

[0042] Figure 7 This is the hydrogen spectrum of the N-phenylbenzoxazinamine compound prepared in Example 4;

[0043] Figure 8 This is the carbon spectrum of the N-phenylbenzoxazinamine compound prepared in Example 4;

[0044] Figure 9 This is the hydrogen spectrum of the N-phenylbenzoxazinamine compound prepared in Example 5;

[0045] Figure 10 This is the carbon spectrum of the N-phenylbenzoxazinamine compound prepared in Example 5;

[0046] Figure 11 This is the hydrogen spectrum of the N-phenylbenzoxazinamine compound prepared in Example 6;

[0047] Figure 12 This is the carbon spectrum of the N-phenylbenzoxazinamine compound prepared in Example 6;

[0048] Figure 13 This is the hydrogen spectrum of the N-phenylbenzoxazinamine compound prepared in Example 7;

[0049] Figure 14 This is the carbon spectrum of the N-phenylbenzoxazinamine compound prepared in Example 7;

[0050] Figure 15 This is the hydrogen spectrum of the N-phenylbenzoxazinamine compound prepared in Example 8;

[0051] Figure 16 This is the carbon spectrum of the N-phenylbenzoxazinamine compound prepared in Example 8;

[0052] Figure 17 This is the hydrogen spectrum of the N-phenylbenzoxazinamine compound prepared in Example 9;

[0053] Figure 18 This is the carbon spectrum of the N-phenylbenzoxazinamine compound prepared in Example 9;

[0054] Figure 19 This is the hydrogen spectrum of the N-phenylbenzoxazinamine compound prepared in Example 10;

[0055] Figure 20 This is the carbon spectrum of the N-phenylbenzoxazinamine compound prepared in Example 10. DETAILED DESCRIPTION

[0056] The present invention provides a method for electrocatalytic synthesis of N-phenylbenzoxazinamine, comprising the following steps:

[0057] 1) mixing a compound having formula I, a compound having formula II, tetrabutylammonium iodide, acetonitrile and triethylamine to obtain a mixture;

[0058]

[0059] where R 1 Any one selected from hydrogen, methyl, phenyl, 4-fluoro-phenyl and 4-chloro-phenyl, R 2 Any one selected from hydrogen and methyl;

[0060] R 3 -NCs

[0061] Formula II;

[0062] Among them, R 3 Any one selected from phenyl, 4-fluoro-phenyl, 4-methyl-phenyl, 4-trifluoromethyl-phenyl and 2-methyl-phenyl;

[0063] 2) reacting the mixture obtained in step 1) for 3 h at a current of 5 mA and a temperature of 20-30° C. using platinum sheets as cathodes and anodes to obtain N-phenylbenzoxazinamine;

[0064] The structural formula of the N-phenylbenzoxazinamine is shown in Formula III;

[0065]

[0066] In the present invention, the molar ratio of the compound of formula I, the molar ratio of the compound of formula II, the molar ratio of tetrabutylammonium iodide, the volume of acetonitrile and triethylamine is preferably 0.2 mmol:0.3 mmol:0.3 mmol:6 mL:0.3 mmol.

[0067] In the present invention, the compound having formula I is preferably any one of the following compounds;

[0068]

[0069] In the present invention, the compound having formula II is preferably any one of the following compounds;

[0070]

[0071] In the present invention, the specifications of the anode are preferably 1 cm×1 cm×0.1 cm; the specifications of the cathode are preferably 1 cm×1 cm×0.1 cm.

[0072] In the present invention, after the reaction, a reactant is obtained, and the reactant is preferably distilled under reduced pressure to remove acetonitrile, and then separated and purified by silica gel column chromatography to obtain N-phenylbenzoxazinamine. The present invention does not specifically limit the method for distilling acetonitrile under reduced pressure, and conventional methods can be used. In the present invention, the mobile phase used for the silica gel column chromatography separation and purification is preferably petroleum ether and ethyl acetate. In the present invention, the volume ratio of petroleum ether and ethyl acetate is preferably 5:1. The present invention does not specifically limit the method for separation and purification by silica gel column chromatography, and conventional methods can be used.

[0073] In the present invention, the reaction formula of the N-phenylbenzoxazinamine is as follows:

[0074]

[0075] In order to further illustrate the present invention, the present invention is described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0076] Example 1

[0077] The preparation method of this embodiment comprises the following steps:

[0078] Compound 1a (0.2 mmol), tetrabutylammonium iodide (0.3 mmol), acetonitrile (6 mL), compound 2a (0.3 mmol), and triethylamine (0.3 mmol) were added sequentially to a 30 mL electrolytic cell, and a stirrer was placed. A platinum electrode (1.0 cm × 1.0 cm × 0.1 cm) was used as the anode and a platinum electrode (1.0 cm × 1.0 cm × 0.1 cm) was used as the cathode. A constant current of 5 mA was applied, and the reaction was incubated at room temperature (25°C) for 3 h. The reaction progress was monitored by thin-layer chromatography until the reaction was complete. The solvent was evaporated from the reaction solution under reduced pressure, and the residue was separated and purified by silica gel column chromatography using petroleum ether / ethyl acetate (volume ratio of 5:1) as the mobile phase to obtain compound 3aa in 89% yield. The reaction equation is as follows:

[0079]

[0080] 1H NMR (400MHz, CDCl3, ppm):7.49-7.47(m,2H),7.39(m,5H),7.31-7.26(m,3H), 7.18(d,J=7.6Hz,1H),7.05-6.96(m,2H),6.75(d,J=7.6Hz,1H),6.29(s,1H); 13 C NMR (100MHz, CDCl3, ppm): δ = 150.6, 141.3, 138.6, 138.6, 129.2, 129.1, 129.0, 128.8, 128.1, 125.1, 124.0, 123.4, 123.0, 122.5, 119.5, 80.0; HRMS calcd for C 20 H 17 N2O[M+H] + 301.1335; found:301.1333.

[0081] Example 2

[0082] The preparation method of this embodiment comprises the following steps:

[0083] Compound 1a (0.2 mmol), tetrabutylammonium iodide (0.3 mmol), acetonitrile (6 mL), compound 2b (0.3 mmol), and triethylamine (0.3 mmol) were sequentially added to a 30 mL electrolytic cell, and a stirrer was placed. A platinum electrode (1.0 cm × 1.0 cm × 0.1 cm) was used as the anode and a platinum electrode (1.0 cm × 1.0 cm × 0.1 cm) was used as the cathode. A constant current of 5 mA was applied at room temperature (25°C) for 3 h. The reaction progress was monitored by thin-layer chromatography until the reaction was complete. The solvent was evaporated from the reaction solution under reduced pressure, and the residue was separated and purified by silica gel column chromatography using petroleum ether / ethyl acetate (volume ratio of 5:1) as the mobile phase to obtain compound 3ab in 87% yield. The reaction equation is as follows:

[0084]

[0085] 1 H NMR (400MHz, CDCl3, ppm): 7.39-7.29 (m, 7H), 7.26-7.22 (m, 1H), 7.07 (d, J = 7.6Hz, 1H), 6.98-6.90 (m, 3H), 6.74 (d, J = 7.6Hz, 1H), 6.25 (s, 1H); 13CNMR (100MHz, CDCl3, ppm): δ = 160.1, 157.6, 151.0, 140.9, 138.5, 135.3, 129.2 (d, J = 16Hz, 1C), 128.8 ,128.0,125.2,123.7,123.2,122.0(d,J=7.9Hz,1C),121.6,115.5(d,J=22.3Hz,1C),80.1; HRMScalcd for C 20 H 16 FN2O[M+H] + 319.1241; found:319.1244.

[0086] Example 3

[0087] The preparation method of this embodiment comprises the following steps:

[0088] Compound 1a (0.2 mmol), tetrabutylammonium iodide (0.3 mmol), acetonitrile (6 mL), compound 2c (0.3 mmol), and triethylamine (0.3 mmol) were added sequentially to a 30 mL electrolytic cell, and a stirrer was placed. A platinum electrode (1.0 cm × 1.0 cm × 0.1 cm) was used as the anode and a platinum electrode (1.0 cm × 1.0 cm × 0.1 cm) was used as the cathode. A constant current of 5 mA was applied at room temperature (25°C) for 3 h. The reaction progress was monitored by thin-layer chromatography until the reaction was complete. The solvent was evaporated from the reaction solution under reduced pressure, and the residue was separated and purified by silica gel column chromatography using petroleum ether / ethyl acetate (volume ratio of 5:1) as the mobile phase to obtain compound 3ac in a 79% yield. The reaction equation is as follows:

[0089]

[0090] 1 H NMR (400MHz, CDCl3, ppm): 7.38-7.36 (m, 5H), 7.29-7.22 (m, 3H), 7.12 (d, J = 8Hz, 1H), 7 .06-7.04(m,2H),6.96-6.92(m,1H),6.72(d,J=7.2Hz,1H),6.24(s,1H),2.28(s,3H); 13 C NMR (100MHz, CDCl3, ppm): δ = 151.3, 141.5, 138.7, 136.2, 132.6, 129.5, 129. 2,129.0,128.8,128.1,125.1,123.9,123.1,122.2,120.1,80.0,20.8; HRMS calcd forC 21 H19 N2O[M+H] + 315.1492; found:315.1491.

[0091] Example 4

[0092] The preparation method of this embodiment comprises the following steps:

[0093] Compound 1a (0.2 mmol), tetrabutylammonium iodide (0.3 mmol), acetonitrile (6 mL), compound 2d (0.3 mmol), and triethylamine (0.3 mmol) were added sequentially to a 30 mL electrolytic cell, and a stirrer was placed. A platinum electrode (1.0 cm × 1.0 cm × 0.1 cm) was used as the anode and a platinum electrode (1.0 cm × 1.0 cm × 0.1 cm) was used as the cathode. A constant current of 5 mA was applied at room temperature (25°C) for 3 h. The reaction progress was monitored by thin-layer chromatography until the reaction was complete. The solvent was evaporated from the reaction solution under reduced pressure, and the residue was separated and purified by silica gel column chromatography using petroleum ether / ethyl acetate (volume ratio of 5:1) as the mobile phase to obtain compound 3ad in 84% yield. The reaction equation is as follows:

[0094]

[0095] 1 H NMR (400MHz, CDCl3, ppm):7.48-7.45(m,4H),7.40-7.33(m,5H),7.28-7.23(m, 1H),7.09(d,J=6.8Hz,1H),7.01-6.97(m,1H),6.77(d,J=8Hz,1H),6.29(s,1H); 13 C NMR (100MHz, CDCl3, ppm): δ=150.6,142.9,140.2,138.2,129.4,129.3,128.9,128.0,126.1( HRMS calcd for C 21 H 16 F3N2O[M+H] + 369.1209; found:369.1205.

[0096] Example 5

[0097] The preparation method of this embodiment comprises the following steps:

[0098] Compound 1a (0.2 mmol), tetrabutylammonium iodide (0.3 mmol), acetonitrile (6 mL), compound 2e (0.3 mmol), and triethylamine (0.3 mmol) were sequentially added to a 30 mL electrolytic cell, and a stirrer was placed. A platinum electrode (1.0 cm × 1.0 cm × 0.1 cm) was used as the anode and a platinum electrode (1.0 cm × 1.0 cm × 0.1 cm) was used as the cathode. A constant current of 5 mA was applied at room temperature (25°C) for 3 h. The reaction progress was monitored by thin-layer chromatography until the reaction was complete. The solvent was evaporated from the reaction solution under reduced pressure, and the residue was separated and purified by silica gel column chromatography using petroleum ether / ethyl acetate (volume ratio of 5:1) as the mobile phase to obtain compound 3ae in a yield of 71%. The reaction equation is as follows:

[0099]

[0100] 1 H NMR (400MHz, CDCl3, ppm): 7.75 (d, J = 8.4Hz, 1H), 7.39-7.34 (m, 5H), 7.27-7.23 (m, 1H), 7.20-7.1 3(m,2H),7.09(d,J=8Hz,1H),7.02-6.94(m,2H),6.74(d,J=7.6Hz,1H),6.26(s,1H),2.20(s,3H); 13 C NMR (100MHz, CDCl3, ppm): δ=151.2,141.2,138.6,137.0,130.5,129.2,129.1,1 28.8,128.1,126.7,125.1,123.9,123.8,123.2,122.5,121.9,80.1,17.9; HRMS calcd for C 21 H 19 N2O[M+H] + 315.1492; found:315.1491.

[0101] Example 6

[0102] The preparation method of this embodiment comprises the following steps:

[0103] Compound 1b (0.2 mmol), tetrabutylammonium iodide (0.3 mmol), acetonitrile (6 mL), compound 2a (0.3 mmol), and triethylamine (0.3 mmol) were sequentially added to a 30 mL electrolytic cell, and a stirrer was placed. A platinum electrode (1.0 cm × 1.0 cm × 0.1 cm) was used as the anode and a platinum electrode (1.0 cm × 1.0 cm × 0.1 cm) was used as the cathode. A constant current of 5 mA was applied at room temperature (25°C) for 3 h. The reaction progress was monitored by thin-layer chromatography until the reaction was complete. The solvent was evaporated from the reaction solution under reduced pressure, and the residue was separated and purified by silica gel column chromatography using petroleum ether / ethyl acetate (volume ratio of 5:1) as the mobile phase to obtain compound 3ba with a yield of 82%. The reaction equation is as follows:

[0104]

[0105] 1 H NMR (400MHz, CDCl3, ppm): 7.44 (d, J = 8Hz, 2H), 7.36-7.32 (m, 2H), 7.30-7.25 (m, 3H),7.16(d,J=8Hz,1H),7.09-6.97(m,4H),6.73(d,J=7.6Hz,1H),6.26(s,1H); 13 CNMR (100MHz, CDCl3, ppm): δ = 163.1 (d, J = 246.9Hz, 1C), 150.6, 141.3, 138.6, 134.6, 130.0 (d, J = 8.3 HRMS calcd for C 20 H 16 FN2O[M+H] + 319.1241; found:319.1244.

[0106] Example 7

[0107] The preparation method of this embodiment comprises the following steps:

[0108] Compound 1c (0.2 mmol), tetrabutylammonium iodide (0.3 mmol), acetonitrile (6 mL), compound 2a (0.3 mmol), and triethylamine (0.3 mmol) were sequentially added to a 30 mL electrolytic cell, and a stirrer was placed. A platinum electrode (1.0 cm × 1.0 cm × 0.1 cm) was used as the anode and a platinum electrode (1.0 cm × 1.0 cm × 0.1 cm) was used as the cathode. A constant current of 5 mA was applied at room temperature (25°C) for 3 h. The reaction progress was monitored by thin-layer chromatography until completion. The solvent was evaporated from the reaction solution under reduced pressure, and the residue was separated and purified by silica gel column chromatography using petroleum ether / ethyl acetate (volume ratio 5:1) as the mobile phase to obtain compound 3ca in 75% yield. The reaction equation is as follows:

[0109]

[0110] 1 H NMR (400MHz, CDCl3, ppm): 7.42 (d, J = 8Hz, 2H), 7.37-7.33 (m, 2H), 7.30-7.24 (m, 5H),7.14(d,J=8Hz,1H),7.04-6.96(m,2H),6.73(d,J=7.2Hz,1H),6.24(s,1H); 13 CNMR (100MHz, CDCl3, ppm): δ = 150.6, 141.2, 138.7, 137.2, 135.0, 129.5, 129.4, 129.0, 129.0, 125.0, 123.4, 123.4, 123.1, 122.5, 119.8, 79.2; HRMS calcd for C 20 H 16 ClN2O[M+H] + 335.0946; found:335.0945.

[0111] Example 8

[0112] The preparation method of this embodiment comprises the following steps:

[0113] Compound 1d (0.2 mmol), tetrabutylammonium iodide (0.3 mmol), acetonitrile (6 mL), compound 2a (0.3 mmol), and triethylamine (0.3 mmol) were added sequentially to a 30 mL electrolytic cell, and a stirrer was placed. A platinum electrode (1.0 cm × 1.0 cm × 0.1 cm) was used as the anode and a platinum electrode (1.0 cm × 1.0 cm × 0.1 cm) was used as the cathode. A constant current of 5 mA was applied at room temperature (25°C) for 3 h. The reaction progress was monitored by thin-layer chromatography until the reaction was complete. The solvent was evaporated from the reaction solution under reduced pressure, and the residue was separated and purified by silica gel column chromatography using petroleum ether / ethyl acetate (volume ratio of 5:1) as the mobile phase to obtain compound 3da in a 93% yield. The reaction equation is as follows:

[0114]

[0115] 1 H NMR (400MHz, CDCl3, ppm): 7.39 (d, J = 7.2Hz, 2H), 7.30-7.26 (m, 2H), 7.23-7.19 (m, 1H), 7.06-7.02 (m, 1H), 7.02-6.98 (m, 3H), 5.22 (s, 2H); 13 C NMR (100MHz, CDCl3, ppm): δ = 152.0, 141.1, 139.6, 129.1, 128.9, 123.7, 123.1, 123.0, 121.1, 120.8, 120.5, 67.7; HRMScalcd for C 14 H 13 N2O[M+H] + 225.1022; found:225.1020.

[0116] Example 9

[0117] The preparation method of this embodiment comprises the following steps:

[0118] Compound 1e (0.2 mmol), tetrabutylammonium iodide (0.3 mmol), acetonitrile (6 mL), compound 2a (0.3 mmol), and triethylamine (0.3 mmol) were sequentially added to a 30 mL electrolytic cell, and a stirrer was placed. A platinum electrode (1.0 cm × 1.0 cm × 0.1 cm) was used as the anode and a platinum electrode (1.0 cm × 1.0 cm × 0.1 cm) was used as the cathode. A constant current of 5 mA was applied at room temperature (25°C) for 3 h. The reaction progress was monitored by thin-layer chromatography until the reaction was complete. The solvent was evaporated from the reaction solution under reduced pressure, and the residue was separated and purified by silica gel column chromatography using petroleum ether / ethyl acetate (volume ratio of 5:1) as the mobile phase to obtain compound 3ea in a 69% yield. The reaction equation is as follows:

[0119]

[0120] 1 H NMR (400MHz, CDCl3, ppm): 7.36 (d, J = 7.6Hz, 2H), 7.28-7.24 (m, 2H), 7.03-6.99 (m, 2H), 6.89 (d, J = 8Hz, 1H), 6.78 (s, 1H), 5.17 (s, 2H), 2.28 (s, 3H); 13 C NMR (100MHz, CDCl3, ppm): δ = 151.7, 139.8, 138.6, 132.5, 129.6, 128.9, 124.3, 122.9, 120.9, 120.7, 120.4, 67.8, 20.9; HRMS calcd for C 15 H 15 N2O[M+H] + 239.1179; found:239.1179.

[0121] Example 10

[0122] The preparation method of this embodiment includes the following steps

[0123] Compound 1f (0.2 mmol), tetrabutylammonium iodide (0.3 mmol), acetonitrile (6 mL), compound 2a (0.3 mmol), and triethylamine (0.3 mmol) were sequentially added to a 30 mL electrolytic cell, and a stirrer was placed. A platinum electrode (1.0 cm × 1.0 cm × 0.1 cm) was used as the anode and a platinum electrode (1.0 cm × 1.0 cm × 0.1 cm) was used as the cathode. A constant current of 5 mA was applied at room temperature (25°C) for 3 h. The reaction progress was monitored by thin-layer chromatography until the reaction was complete. The solvent was evaporated from the reaction solution under reduced pressure, and the residue was separated and purified by silica gel column chromatography using petroleum ether / ethyl acetate (volume ratio of 5:1) as the mobile phase to obtain compound 3fa in 84% yield. The reaction equation is as follows:

[0124]

[0125] 1 H NMR (400MHz, CDCl3, ppm): 7.43 (d, J = 8Hz, 2H), 7.31-7.27 (m, 2H), 7.23-7.19 (m, 1H), 7.04-7.00 (m, 4H), 6.55 (br s,1H),5.45-5.40(m,1H),1.66(d,J=7.2Hz,2H); 13CNMR (100MHz, CDCl3, ppm): δ = 151.5, 140.8, 139.4, 129.0, 128.9, 125.8, 123.2, 123.1, 122.9, 121.7, 120.1, 74.5, 20.4; HRMS calcd for C 15 H 15 N2O[M+H] + 239.1179; found:239.1176.

[0126] Comparative Example 1

[0127] On the basis of Example 1, the anode and cathode were changed to a carbon rod as the anode and a platinum sheet as the cathode. Other conditions remained unchanged. The yield of compound 3aa was 69%.

[0128] Comparative Example 2

[0129] On the basis of Example 1, the anode and cathode electrodes were changed to carbon rods as the anode and cathode as the cathode, and other conditions remained unchanged. The yield of compound 3aa was 66%.

[0130] Comparative Example 3

[0131] On the basis of Example 1, the anode and cathode electrodes were changed to carbon rod as the anode and nickel sheet as the cathode. Other conditions remained unchanged. The yield of compound 3aa was 44%.

[0132] Comparative Example 4

[0133] On the basis of Example 1, the electrolyte was changed to sodium iodide, and other conditions remained unchanged. The yield of compound 3aa was 42%.

[0134] Comparative Example 5

[0135] On the basis of Example 1, the electrolyte was changed to potassium iodide as the electrolyte, and other conditions remained unchanged. The yield of compound 3aa was 45%.

[0136] Comparative Example 6

[0137] On the basis of Example 1, the base was changed to sodium carbonate as the base, and other conditions remained unchanged. The yield of compound 3aa was 43%.

[0138] Comparative Example 7

[0139] On the basis of Example 1, the base was changed to potassium carbonate as the base, and other conditions remained unchanged. The yield of compound 3aa was 57%.

[0140] Comparative Example 8

[0141] On the basis of Example 1, the base was changed to cesium carbonate as the base, and other conditions remained unchanged. The yield of compound 3aa was 65%.

[0142] Comparative Example 9

[0143] On the basis of Example 1, the base was changed to sodium hydroxide as the base, and other conditions remained unchanged. The yield of compound 3aa was 30%.

[0144] Comparative Example 10

[0145] On the basis of Example 1, the base was changed to 4-dimethylaminopyridine, and other conditions remained unchanged. The yield of compound 3aa was 60%.

[0146] Although the above embodiment provides a detailed description of the present invention, it is only a part of the embodiments of the present invention, not all of the embodiments. People can also obtain other embodiments based on this embodiment without creativity, and these embodiments all fall within the scope of protection of the present invention.

Claims

1. A method for electrocatalytic synthesis of N-phenylbenzoxazinamine, characterized in that: The following steps are involved: 1) mixing a compound having formula I, a compound having formula II, tetrabutylammonium iodide, acetonitrile and triethylamine to obtain a mixture; where R 1 Any one selected from hydrogen, methyl, phenyl, 4-fluoro-phenyl and 4-chloro-phenyl, R 2 Any one selected from hydrogen and methyl; R 3 -NCS Formula II; Among them, R 3 Any one selected from phenyl, 4-fluoro-phenyl, 4-methyl-phenyl, 4-trifluoromethyl-phenyl and 2-methyl-phenyl; 2) reacting the mixture obtained in step 1) for 3 h at a current of 5 mA and a temperature of 20-30° C. with platinum sheets as cathode and anode to obtain N-phenylbenzoxazinamine; The structural formula of the N-phenylbenzoxazinamine is shown in Formula III; 2. The method according to claim 1, characterized in that In step 1), the molar ratio of the compound of formula I, the compound of formula II, the molar ratio of tetrabutylammonium iodide, the volume of acetonitrile and triethylamine is 0.2 mmol:0.3 mmol:0.3 mmol:6 mL:0.3 mmol.

3. The method according to claim 1, characterized in that The specifications of the anode in step 2) are 1 cm×1 cm×0.1 cm; The specifications of the cathode are 1 cm×1 cm×0.1 cm.

4. The method according to claim 1, wherein The compound of formula I in step 1) is any one of the following compounds:

5. The method according to claim 1, wherein The compound of formula II in step 1) is any one of the following compounds:

6. The method according to claim 1, characterized in that After the reaction in step 2), a reactant is obtained, acetonitrile is distilled off from the reactant under reduced pressure, and then the reactant is separated and purified by silica gel column chromatography to obtain N-phenylbenzoxazinamine.

7. The method according to claim 6, characterized in that The mobile phases used in the silica gel column chromatography separation and purification are petroleum ether and ethyl acetate.

8. The method according to claim 7, characterized in that The volume ratio of the petroleum ether to ethyl acetate is 5:1.

Images