An electrochemical method for preparing N-aroylsulfoximine compounds

Abstract

An electrochemical method for preparing N-aroyl sulfoximine compounds, steps as follows: in air atmosphere, sulfoximine compound, hydroxamic acid are added into a reactor (a diaphragmless electrolytic cell) in a molar ratio of 1:3, an electrolyte tetrabutylammonium tetrafluoroborate is added, and an acetone solution is added; the mixture is stirred by a magnetic stirring device, so that it is dissolved, two electrodes are inserted, a graphite rod electrode is used as the positive electrode, and a platinum sheet electrode is used as the negative electrode, a direct current stabilized power supply is used as the constant voltage 6 V, the power-on time is 2.5 h, after the reaction is completed, the solvent is removed by vacuum evaporation to obtain a crude product, and the N-aroyl sulfoximine compound is obtained by column chromatography purification. The present application has the advantages that the reaction condition is green and mild, and can be smoothly carried out at room temperature; the operation is simple, and all operations can be carried out in an open system; the electrochemical anodic oxidation is used as the oxidation method in the reaction, so that the pollution of the chemical oxidant is avoided; and the raw material is easy to obtain, the reaction yield is high, the functional group compatibility is good, and the substrate application range is wide.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of organic synthesis, and particularly relates to an electrochemical method for preparing N-aroyl sulfoximine compounds. BACKGROUND

[0002] Sulfoximines are an important class of molecules in organic and biochemistry, as this structural motif is widely used as drugs, agrochemicals, organocatalysts, homogeneous catalytic ligands and directing groups for C-H bond activation reactions. As the mononitrogen analogue of sulfones, sulfoximines are an important structural motif widely found in many biologically active natural products and drugs, including protease inhibitors, antiasthmatics, antispasmodics, anxiolytics, anticonvulsants and anticoagulants. Therefore, the exploration of sulfoximines, especially the development of novel and efficient synthetic methods for their derivatization, will help better understand and further improve their applications in organic, medicinal chemistry and other related fields.

[0003] Benzylic hydroxamic acids are widely used in the fields of biomedical, drug synthesis, natural product synthesis and material synthesis due to their interesting chemical, biological properties and good reactivity, and many hydroxamic acids and their derivatives are widely present in natural products with various biological activities, synthetic intermediates and chiral ligands, and they can also form bidentate ligand complexes with various metal ions, and their metal complexes are also used as anthelmintics. Therefore, in view of their potential applications in organic, medical and other fields, it is necessary to explore the reactivity and synthetic methods of benzylic hydroxamic acids. SUMMARY

[0004] In view of the above problems, the present application provides an electrochemical method for preparing N-aroyl sulfoximine compounds, which has the advantages of green and mild reaction conditions, can be smoothly carried out at room temperature, simple operation, all operations can be carried out in an open system, avoids pollution of chemical oxidants by using electrochemical anodic oxidation as an oxidation method, and the like.

[0005] To achieve the above object, the present application provides the following technical scheme: an electrochemical method for preparing N-aroyl sulfoximine compounds, the preparation method comprising the following steps:

[0006] In an air atmosphere, a sulfoximine compound and a hydroxamic acid are added to a reactor (a diaphragmless electrolytic cell) at a molar ratio of 1:3, a tetrabutylammonium tetrafluoroborate electrolyte is added, and a solvent acetone solution is added; the mixture is stirred by a magnetic stirring device to dissolve it, two electrodes are inserted, a graphite rod electrode is used as the anode, a platinum sheet electrode is used as the cathode, a direct current stabilized power supply is used at a constant voltage of 6 V, the power-on time is 2.5 h, after the reaction is completed, the solvent is removed by evaporation under reduced pressure to obtain a crude product, and column chromatography is used for purification to obtain the N-aroyl sulfoximine compound.

[0007] In the step, the reactor is a diaphragmless electrolytic cell, and the N-aroyl sulfoximine compound is prepared by an electrochemical reaction, and a preparation method reaction formula is as follows:

[0008]

[0009] In the formula, R1=phenyl, 4-methylphenyl, 4-chlorophenyl, thiophene or benzyl; R2=methyl, ethyl or benzyl; R3=4-cyanophenyl, 4-methoxyphenyl or 4-chlorophenyl.

[0010] Preferably, the electrolyte is tetrabutylammonium tetrafluoroborate, and the molar concentration is 0.05 M.

[0011] The present application has the following beneficial effects:

[0012] 1. The present application uses electrochemical anodic oxidation as an oxidation method, which is green and environmentally friendly, does not need external oxidants, and avoids pollution caused by the use of equivalent chemical oxidants in traditional oxidation methods.

[0013] 2. The present application does not need a transition metal catalyst, and the reaction condition is relatively mild, and has good atom economy.

[0014] 3. The present application can realize gram-scale scale-up experiments, and can smoothly react to obtain the target product in a good yield, and has certain potential value in industrial production.

[0015] 4. The present application can obtain the target product in one step, has high yield, good functional group compatibility, wide substrate range, simple post-treatment, and has good application potential. BRIEF DESCRIPTION OF DRAWINGS

[0016] Figure 1 The hydrogen spectrum of the product obtained in Example 1 of the present application is shown in the figure;

[0017] Figure 2 The carbon spectrum of the product obtained in Example 1 of the present application is shown in the figure;

[0018] Figure 3 The hydrogen spectrum of the product obtained in Example 2 of the present application is shown in the figure;

[0019] Figure 4 The carbon spectrum of the product obtained in Example 2 of the present application is shown in the figure;

[0020] Figure 5 The hydrogen spectrum of the product obtained in Example 3 of the present application is shown in the figure;

[0021] Figure 6 The carbon spectrum of the product obtained in Example 3 of the present application is shown in the figure;

[0022] Figure 7The hydrogen spectrum of the product obtained in Example 4 of the present application;

[0023] Figure 8 The carbon spectrum of the product obtained in Example 4 of the present application;

[0024] Figure 9 The hydrogen spectrum of the product obtained in Example 5 of the present application;

[0025] Figure 10 The carbon spectrum of the product obtained in Example 5 of the present application;

[0026] Figure 11 The hydrogen spectrum of the product obtained in Example 6 of the present application;

[0027] Figure 12 The carbon spectrum of the product obtained in Example 6 of the present application;

[0028] Figure 13 The hydrogen spectrum of the product obtained in Example 7 of the present application;

[0029] Figure 14 The carbon spectrum of the product obtained in Example 7 of the present application;

[0030] Figure 15 The hydrogen spectrum of the product obtained in Example 8 of the present application;

[0031] Figure 16 The carbon spectrum of the product obtained in Example 8 of the present application; DETAILED DESCRIPTION

[0032] The technical solutions in the embodiments of the present application will be described clearly and completely below with reference to the drawings, so that the persons skilled in the art can better understand the advantages and features of the present application, and the protection scope of the present application can be defined more clearly. The embodiments described in the present application are only some of the embodiments of the present application, but not all the embodiments. Based on the embodiments in the present application, all the other embodiments obtained by the persons skilled in the art without creative labor fall within the protection scope of the present application.

[0033] Example 1:

[0034] In a 10 ml three necked flask, an anode electrode material was graphite rod electrode (electrode size: diameter Φ 4 mm), a cathode electrode material was platinum sheet electrode (electrode size: 10 mm X 10 mm X 0.1 mm), as a reactor diaphragmless electrolytic cell. Subsequently, S-methyl-S-phenylsulfoximine (15.5 mg, 0.1 mmol), 4- methoxyphenylhydrazine hydrochloride (48.6 mg, 0.3 mmol), acetone 3 ml were added in the reactor (diaphragmless electrolytic cell), and the reaction was stirred at room temperature for 2.5 hours under a constant voltage of 6 V. After the reaction was completed, the solvent was distilled off under reduced pressure to obtain a crude product, which was purified by column chromatography to obtain 25 mg of the target product at a yield of 88%. The structural formula of the obtained product is as follows:

[0035]

[0036] The structural characterization data of the obtained product are as follows:

[0037] 1 H NMR (500 MHz, Chloroform-d) δ 8.26 (d, J = 8.6 Hz, 2H), 8.05 (d, J= 8.4 Hz, 2H), 7.77-7.68 (m, 3H), 7.65 (t, J = 7.7 Hz, 2H), 3.50 (s, 3H). 13 C{ 1 H} NMR (125 MHz, Chloroform-d) δ 172.4, 139.5, 138.4, 134.2, 132.0, 129.9,129.9, 127.1, 118.5, 115.3, 44.4.

[0038] Example 2:

[0039] In a 10 ml three necked flask, an anode electrode material was graphite rod electrode (electrode size: diameter Φ 4 mm), a cathode electrode material was platinum sheet electrode (electrode size: 10 mm X 10 mm X 0.1 mm), as a reactor diaphragmless electrolytic cell. Subsequently, S-methyl-S-(4-methylphenyl)sulfoximine (16.9 mg, 0.1 mmol), 4- methoxyphenylhydrazine hydrochloride (48.6 mg, 0.3 mmol), acetone 3 ml were added in the reactor (diaphragmless electrolytic cell), and the reaction was stirred at room temperature for 2.5 hours under a constant voltage of 6 V. After the reaction was completed, the solvent was distilled off under reduced pressure to obtain a crude product, which was purified by column chromatography to obtain 16.4 mg of the target product at a yield of 70%. The structural formula of the obtained product is as follows:

[0040]

[0041] The structural characterization data of the product obtained is as follows:

[0042] 1 H NMR (500 MHz, Chloroform-d) δ 8.26 (d, J = 8.7 Hz, 2H), 7.93 (d, J= 9.1 Hz, 2H), 7.72 (d, J = 8.7 Hz, 2H), 7.44 (d, J = 7.9 Hz, 2H), 3.49 (s,3H), 2.49 (s, 3H). 13 C{ 1 H} NMR (125 MHz, Chloroform-d) δ 172.4, 145.4, 139.6,135.3, 131.9, 130.5, 129.9, 127.1, 118.5, 115.3, 44.5, 21.7.

[0043] Example 3:

[0044] In a 10 ml three-necked flask, the anode electrode material was graphite rod electrode (electrode size: diameter Φ 4 mm), the cathode electrode material was platinum sheet electrode (electrode size: 10 mm X 10 mm X 0.1 mm), as the reactor diaphragmless electrolytic cell. Then S-methyl-S-(4-chlorophenyl) sulfoximine (18.9 mg, 0.1 mmol), 4- hydroxy-3-nitrobenzaldehyde (48.6 mg, 0.3 mmol), acetone 3 ml were added in the reactor (diaphragmless electrolytic cell), and the reaction was stirred at room temperature for 2.5 hours under constant voltage 6 V. After the reaction was completed, the solvent was removed by evaporation under reduced pressure to obtain the crude product, which was purified by column chromatography to obtain 30.2 mg of the target product, with a yield of 95%. The structural formula of the product obtained is as follows:

[0045]

[0046] The structural characterization data of the product obtained is as follows:

[0047] 1 H NMR (500 MHz, Chloroform-d) δ 8.29-8.16 (m, 2H), 8.03-7.92 (m,2H), 7.76-7.66 (m, 2H), 7.66-7.57 (m, 2H), 3.49 (s, 3H). 13 C{ 1H} NMR (125 MHz, Chloroform-d) δ 172.3, 141.1, 139.2, 136.8, 132.0, 130.2, 129.9, 128.6,118.4, 115.5, 44.4.

[0048] Example 4:

[0049] In a 10 ml three-necked flask, an anode electrode material was graphite rod electrode (electrode size: diameter Φ 4 mm), a cathode electrode material was platinum sheet electrode (electrode size: 10 mm X 10 mm X 0.1 mm), as a reactor no diaphragm electrolytic cell. Subsequently in the reactor (no diaphragm electrolytic cell) was added S-methyl-S-(3-thiophene) sulfoximine (16.1 mg, 0.1 mmol), p-cyanobenzo hydroxamic acid (48.6 mg, 0.3 mmol), acetone 3 ml, stirring at room temperature under constant voltage 6 V for 2.5 hours. After the reaction was completed, the solvent was removed by evaporation under reduced pressure to obtain the crude product, which was purified by column chromatography to obtain 24.4 mg of the target product, with a yield of 84%. The structural formula of the product obtained is as follows:

[0050]

[0051] The structural characterization data of the product obtained are as follows:

[0052] 1 H NMR (500 MHz, Chloroform-d) δ 8.30 (dd, J = 3.2, 1.4 Hz, 1H), 8.28-8.19 (m, 2H), 7.78-7.68 (m, 2H), 7.58 (dd, J = 5.2, 3.1 Hz, 1H), 7.51 (dd, J = 5.3, 1.4 Hz, 1H), 3.58 (s, 3H). 13 C{ 1 H} NMR (125 MHz, Chloroform-d) δ 172.2, 139.4, 137.9, 132.7, 132.0, 129.9, 129.2, 125.2, 118.5, 115.4, 44.6.

[0053] Example 5:

[0054] In 10 ml of three necked flask, the anode electrode material was graphite rod electrode (electrode size: diameter Φ 4 mm), the cathode electrode material was platinum sheet electrode (electrode size: 10 mm X 10 mm X 0.1 mm), as the reactor no diaphragm electrolytic cell. Subsequently in the reactor (no diaphragm electrolytic cell) was added S-ethyl-S-phenyl sulfoximine (16.9 mg, 0.1 mmol), 4- chlorobenzenesulfinic acid (48.6 mg, 0.3 mmol), acetone 3 ml, constant voltage 6 V stirring reaction at room temperature for 2.5 hours. After the reaction was completed, the solvent was removed by evaporation under reduced pressure to obtain the crude product, which was purified by column chromatography to obtain 24.1 mg of the target product, with a yield of 81%. The structure of the product obtained is as follows:

[0055]

[0056] The structural characterization data of the product obtained are as follows:

[0057] 1 H NMR (500 MHz, Chloroform-d) δ 8.27 (d, J = 8.0 Hz, 2H), 7.99 (d, J= 7.8 Hz, 2H), 7.72 (d, J = 7.9 Hz, 3H), 7.64 (t, J = 7.7 Hz, 2H), 3.63 (ddp,J = 21.6, 14.4, 7.3 Hz, 2H), 1.34 (t, J = 7.4 Hz, 3H). 13 C{ 1 H} NMR (125 MHz,Chloroform-d) δ 172.3, 139.6, 135.9, 134.1, 131.9, 129.9, 129.8, 127.9,118.5, 115.3, 50.7, 7.1.

[0058] Example 6:

[0059] In a 10 ml three necked flask, an anode electrode material was graphite rod electrode (electrode size: diameter Φ 4 mm), a cathode electrode material was platinum sheet electrode (electrode size: 10 mm X 10 mm X 0.1 mm), as a reactor diaphragmless electrolytic cell. Subsequently, in the reactor (diaphragmless electrolytic cell) was added S, S-dibenzylsulfoximine (24.5 mg, 0.1 mmol), 4- methoxybenzohydroxamic acid (50.1 mg, 0.3 mmol), acetone 3 ml, stirred at room temperature under constant voltage 6 V for 2.5 hours. After the reaction was completed, the solvent was removed by evaporation under reduced pressure to obtain a crude product, which was purified by column chromatography to obtain 20.0 mg of the target product, with a yield of 69%. The structural formula of the obtained product is as follows:

[0060]

[0061] The structural characterization data of the obtained product are as follows:

[0062] 1 H NMR (500 MHz, Chloroform-d) δ 8.17 (d, J = 8.1 Hz, 2H), 7.70 (d, J= 8.1 Hz, 2H), 7.50-7.34 (m, 10H), 4.82 (d, J = 13.6 Hz, 2H), 4.67 (d, J =13.6 Hz, 2H). 13 C{ 1 H} NMR (125 MHz, Chloroform-d) δ 172.1, 139.5, 131.9,131.3, 129.8, 129.7, 129.2, 125.8, 118.5, 115.3, 56.8.

[0063] Example 7:

[0064] In a 10 ml three necked flask, an anode electrode material was graphite rod electrode (electrode size: diameter Φ 4 mm), a cathode electrode material was platinum sheet electrode (electrode size: 10 mm X 10 mm X 0.1 mm), as a reactor diaphragmless electrolytic cell. Subsequently, in the reactor (diaphragmless electrolytic cell) was added S- methyl-S-phenylsulfoximine (15.5 mg, 0.1 mmol), 4-methoxybenzohydroxamic acid (50.1 mg, 0.3 mmol), acetone 3 ml, stirred at room temperature under constant voltage 6 V for 2.5 hours. After the reaction was completed, the solvent was removed by evaporation under reduced pressure to obtain a crude product, which was purified by column chromatography to obtain 20.0 mg of the target product, with a yield of 69%. The structural formula of the obtained product is as follows:

[0065]

[0066] The structural characterization data of the product obtained are as follows:

[0067] 1 H NMR (500 MHz, DMSO-d6) δ 8.04 (d, J = 7.7 Hz, 2H), 7.92 (d, J =8.5 Hz, 2H), 7.77 (t, J = 7.4 Hz, 1H), 7.74-7.65 (m, 2H), 7.27 (d, J = 7.8Hz, 2H), 3.60 (s, 3H), 2.37 (s, 3H). 13 C{ 1 H} NMR (125 MHz, DMSO-d6) δ 173.1,142.6, 139.3, 134.1, 133.4, 130.0, 129.4, 129.2, 127.5, 43.8, 21.6.

[0068] Example 8:

[0069] In a 10 ml three-necked flask, the anode electrode material was graphite rod electrode (electrode size: diameter Φ 4 mm), and the cathode electrode material was platinum sheet electrode (electrode size: 10 mm X 10 mm X 0.1 mm), as a reactor without diaphragm electrolytic cell. Then S-methyl-S-phenyl sulfoximine (15.5 mg, 0.1 mmol), p-chlorophenyl hydroxamic acid (51.3 mg, 0.3 mmol), acetone 3 ml were added in the reactor (without diaphragm electrolytic cell), and the reaction was stirred at room temperature for 2.5 hours under constant voltage 6 V. After the reaction was completed, the solvent was removed by evaporation under reduced pressure to obtain the crude product, which was purified by column chromatography to obtain 18.8 mg of the target product, with a yield of 64%. The structural formula of the product obtained is as follows:

[0070]

[0071] The structural characterization data of the product obtained are as follows:

[0072] 1H NMR (500 MHz, Chloroform-d) δ 8.11 (td, J = 5.8, 5.1, 2.4 Hz, 2H), 8.06 (t, J = 4.2 Hz, 2H), 7.72 (t, J = 7.3 Hz, 1H), 7.65 (t, J = 7.5 Hz, 2H), 7.39 (td, J = 5.6, 5.0, 2.4 Hz, 2H), 3.49 (s, 3H). 13 C{ 1 H} NMR (125 MHz,Chloroform-d) δ 173.2, 138.8, 138.5, 134.1, 134.0, 130.9, 129.8, 128.3, 127.1, 44.4.

Claims

1. An electrochemical method for preparing N-aryl sulfoxide imine compounds, characterized in that: The preparation method includes the following steps: In an air atmosphere, sulfoxide imine compounds and hydroxamic acid are added to a membraneless electrolytic cell at a molar ratio of 1:3, and the electrolyte tetrabutylammonium tetrafluoroborate is added. Then, acetone solution is added as a solvent. The mixture is stirred with a magnetic stirrer to dissolve it. Two electrodes are inserted, with a graphite rod electrode as the positive electrode and a platinum sheet electrode as the negative electrode. A DC regulated power supply is used to maintain a constant voltage of 6V for 2.5 h. After the reaction is completed, the solvent is removed by vacuum distillation to obtain the crude product, which is then purified by column chromatography to obtain the N-aramid sulfoxide imine compound. In the aforementioned steps, the reactor is a diaphragm-free electrolytic cell, and the N-aramid sulfoxide imine compound is prepared by an electrochemical anodic oxidation reaction, the reaction equation of which is as follows: ， In the formula, R1 = phenyl, 4-methylphenyl, 4-chlorophenyl, thiophene or benzyl; R2 = methyl, ethyl or benzyl; R3 = 4-cyanophenyl, 4-methoxyphenyl or 4-chlorophenyl.

2. The electrochemical method for preparing N-aramid sulfoxide imine compounds according to claim 1, characterized in that: The electrolyte is tetrabutylammonium tetrafluoroborate with a molar concentration of 0.05 M.

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