Electrochemical synthesis of a sulfoximine n-h arylated derivative

Abstract

The application discloses an electrochemical synthesis method of N-arylation of a sulfoximine compound, and steps are as follows: in a three-necked flask, a sulfoximine compound, a carbon monoxide balloon, a phenylhydrazine hydrochloride compound and a solvent are added, a carbon rod is used as an anode, a zinc sheet is used as a cathode, stirring is conducted under a current of 4 mA, and after crude products of reaction are separated and purified, N-arylation products of the sulfoximine compound can be obtained. The application develops an electrochemical N-H aryl acylation reaction of a phenylhydrazine hydrochloride compound, carbon monoxide and a sulfoximine compound, can construct a series of sulfoximine N-H aryl acylation derivatives, has good functional group tolerance, and is easy to scale up. The reaction uses current as an oxidation method, avoids pollution of metal copper salt and halogen waste; the reaction is closed, carbon monoxide and oxygen are not mixed to participate in the reaction, and chemical explosion is avoided; meanwhile, the synthesis only needs normal temperature and pressure, energy loss is reduced, and physical explosion is eliminated.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to an electrochemical synthesis method for sulfoxide imine NH aromatic acylated derivatives. Background Technology

[0002] The core functional motif of sulfoxide imine NH aromatic acylated compounds is found in a variety of bioactive natural products and drugs. Traditionally, sulfoxide imine NH aromatic acylated compounds are prepared by reacting sulfoxide imine with acyl halides or halobenes with carbon monoxide. Under transition metal catalysis, sulfoxide imine, iodobenzene, and carbon monoxide are involved. An equivalent amount of chemical oxidant is used to promote the reaction. In recent years, electrochemical synthesis has gained increasing attention due to its avoidance of the use of catalysts and external oxidants, aligning with the requirements of green and sustainable chemistry. Summary of the Invention

[0003] The purpose of this invention is to address the shortcomings and deficiencies of existing technologies by providing a method for synthesizing electrochemical sulfoxide imine NH aromatic acylation derivatives.

[0004] The present invention utilizes phenylhydrazine hydrochloride, carbon monoxide, and sulfoxide-imine compounds as raw materials, tetrabutylammonium iodide as the electrolyte, 1,2-dichloroethane as the solvent, triethylamine and potassium phosphate as additives, bis(triphenylphosphine)palladium dichloride as the catalyst, graphite felt as the anode, and zinc sheet as the cathode. The reaction is carried out under stirring at a current of 4 mA to construct sulfoxide-imine NH-aromatic derivatives in one step. This method uses current instead of an oxidant, exhibiting a certain degree of atom economy. The reaction is highly selective, simple to operate, and has good functional group tolerance, demonstrating potential application value.

[0005] The objective of this invention is achieved through the following technical solution.

[0006] An electrochemical synthesis method for preparing sulfoxide imine NH aromatic acylated derivatives includes the following preparation process:

[0007] In an unseparated electrolytic cell, phenylhydrazine hydrochloride, carbon monoxide, sulfoxide imine, catalyst, additives, and solvent are added. Graphite rods are used as the anode and cathode, and the reaction is stirred under a current of 4 mA. The crude product is separated and purified to obtain sulfoxide imine NH aromatic acylated compounds.

[0008] Furthermore, the preparation equation for the NH aromatic acylation of sulfoxide imine is shown below:

[0009] In the formula, R 1 Selected from one of the substituents 4-cyano or 4-trifluoromethyl; R 2The electrolyte is one of the following: 4-methoxy, 4-chloro, thiophene, and thiophenylthiobenzyl substituents; the palladium catalyst is one of the following: tetrabutylammonium fluoride, tetrabutylammonium iodide, tetrabutylammonium tetrafluoroborate, and tetrabutylammonium hexafluorophosphate; the palladium catalyst is one of the following: palladium acetate, palladium trifluoroacetate, palladium dichloride, and palladium chloride; the solvent is selected from one or more of dichloromethane, dichloroethane, 1,2-dichloroethane, and ethyl acetate; the base is one or more of the following: triethylamine, potassium phosphate, cesium carbonate, sodium trifluoromethanesulfonate, sodium carbonate, potassium carbonate, and sodium acetate; the electrode is one or more of the following: carbon rod, graphite felt, platinum sheet, stainless steel sheet, platinum wire, zinc sheet, and glassy carbon rod.

[0010] 2. According to the synthesis method described above, the molar ratio of the sulfoxide imine compound to the phenylhydrazine hydrochloride compound is 1:2.

[0011] 3. According to the synthesis method described above, the solvent is 1,2-dichloroethane.

[0012] Beneficial effects of this invention:

[0013] 1. This invention uses inexpensive and readily available sulfoxide imine and phenylhydrazine hydrochloride as raw materials. The sulfoxide imine is prepared by the corresponding sulfide, and the phenylhydrazine hydrochloride can be purchased commercially directly.

[0014] 2. The reaction conditions of this invention are mild and the substrate range is broad.

[0015] 3. This invention uses electrochemical anodic oxidation, which avoids the pollution caused by metal oxidant waste in traditional carbonylation reactions.

[0016] 4. This invention can regulate the reaction rate by adjusting the current, which is beneficial for gram-scale preparation.

[0017] 5. This invention can obtain the target product in just one step, with a high yield, good functional group compatibility, simple post-processing, and good application potential. Attached Figure Description

[0018] Figure 1 The hydrogen spectrum of the product obtained in Example 1 of this invention;

[0019] Figure 2 The carbon spectrum of the product obtained in Example 1 of this invention;

[0020] Figure 3 The hydrogen spectrum of the product obtained in Example 2 of this invention;

[0021] Figure 4 The carbon spectrum of the product obtained in Example 2 of this invention;

[0022] Figure 5 The hydrogen spectrum of the product obtained in Example 3 of this invention;

[0023] Figure 6 The carbon spectrum of the product obtained in Example 3 of this invention;

[0024] Figure 7 The hydrogen spectrum of the product obtained in Example 4 of this invention;

[0025] Figure 8 The carbon spectrum of the product obtained in Example 4 of this invention;

[0026] Figure 9 The hydrogen spectrum of the product obtained in Example 5 of this invention;

[0027] Figure 10 The carbon spectrum of the product obtained in Example 5 of this invention;

[0028] Figure 11 The hydrogen spectrum of the product obtained in Example 6 of this invention;

[0029] Figure 12 The carbon spectrum of the product obtained in Example 6 of this invention; Detailed Implementation

[0030] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings, so that those skilled in the art can better understand the advantages and features of the present invention, thereby making a clearer definition of the scope of protection of the present invention. The embodiments described in this invention are only some embodiments of the present invention, not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0031] Example 1:

[0032] A graphite felt electrode (electrode size: 10 mm × 15 mm × 0.5 mm) was assembled as the anode in a 10 mL diaphragm-free electrolytic cell, and a zinc sheet (size: 10 mm × 15 mm × 0.1 mm) was used as the cathode. Then, methylphenyl sulfoxide imide (38.8 mg, 0.25 mmol), p-cyanohydrazine hydrochloride (80.5 mg, 0.5 mmol), bis(triphenylphosphine) palladium dichloride (12.3 mg, 7 mmol%), potassium phosphate (15.9 mg, 30 mmol%), triethylamine (130 mg, 1.3 mmol), and 6 mL of DCE were added. The reaction was carried out at a constant current of 4 mA with stirring at room temperature for 13 hours. After the reaction, the solvent was removed under reduced pressure to obtain the crude product, which was purified by column chromatography to obtain 48.3 mg of the target product, with a yield of 68%. The structural formula of the obtained product is as follows:

[0033]

[0034] The structural characterization data of the obtained product are shown below:

[0035] 1 H NMR (500 MHz, CDCl3) δ 8.26 (d, J = 8.2 Hz, 2H), 8.06 (d, J = 7.8Hz, 2H), 7.72 (dd, J = 8.0, 5.6 Hz, 3H), 7.66 (t, J = 7.7 Hz, 2H), 3.50 (s,3H). 13 C{ 1 H} NMR (125 MHz, CDCl3) δ 172.4, 139.5, 138.4, 134.2, 132.0, 129.9,129.9, 127.1, 118.5, 115.3, 44.4.

[0036] Example 2:

[0037] A graphite felt electrode (electrode size: 10 mm × 15 mm × 0.5 mm) was assembled as the anode in a 10 mL diaphragm-free electrolytic cell, and a zinc sheet (size: 10 mm × 15 mm × 0.1 mm) was used as the cathode. Then, methylphenyl sulfoxide imine (38.8 mg, 0.25 mmol), p-trifluoromethyl phenylhydrazine hydrochloride (106.3 mg, 0.5 mmol), bis(triphenylphosphine) palladium dichloride (12.3 mg, 7 mmol%), potassium phosphate (15.9 mg, 30 mmol%), triethylamine (130 mg, 1.3 mmol), and 6 mL of DCE were added. The reaction was carried out at a constant current of 4 mA with stirring at room temperature for 13 hours. After the reaction, the solvent was removed under reduced pressure to obtain the crude product, which was purified by column chromatography to obtain 49.9 mg of the target product, with a yield of 61%. The structural formula of the obtained product is as follows:

[0038]

[0039] 1 H NMR (500 MHz, CDCl3) δ 8.29 (d, J = 8.0 Hz, 2H), 8.14-8.01 (m, 2H), 7.77-7.51 (m, 5H), 3.50 (s, 3H). 13 C{ 1H} NMR (125 MHz, CDCl3) δ 172.9, 138.8,138.6, 134.1, 133.5 (d, J = 32.5 Hz), 129.8, 129.8, 127.1, 125.1 (q. J = 3.8Hz), 122.8, 44.4.

[0040] Example 3:

[0041] A graphite felt electrode (electrode size: 10 mm × 15 mm × 0.5 mm) was assembled as the anode in a 10 mL three-necked flask, and a zinc sheet (electrode size: 10 mm × 15 mm × 0.1 mm) was used as the cathode. Then, p-methyl sulfoxide imide (42.3 mg, 0.25 mmol), phenylhydrazine hydrochloride (74.4 mg, 0.5 mmol), bis(triphenylphosphine) palladium dichloride (12.3 mg, 7 mmol%), potassium phosphate (15.9 mg, 30 mmol%), triethylamine (130 mg, 1.3 mmol), and 6 mL of DCE were added. The reaction was stirred at room temperature for 13 hours under a constant current of 4 mA. After the reaction, the solvent was removed under reduced pressure to obtain the crude product, which was purified by column chromatography to give 38.9 mg of the target product, with a yield of 57%. The structural formula of the obtained product is as follows:

[0042]

[0043] The structural characterization data of the obtained product are shown below:

[0044] 1 H NMR (500 MHz, CDCl3) δ 8.20 (d, J = 7.0 Hz, 2H), 7.96 (d, J = 8.0Hz, 2H), 7.56-7.49 (m, 1H), 7.44 (t, J = 7.8 Hz, 4H), 3.48 (s, 3H), 2.49 (s,3H). 13 C{ 1 H} NMR (125 MHz, CDCl3) δ 174.3, 144.9, 136.0, 135.7, 132.1, 130.3,129.4, 128.0, 127.2, 44.5, 21.6.

[0045] Example 4:

[0046] A graphite felt electrode (electrode size: 10 mm × 15 mm × 0.5 mm) was assembled as the anode in a 10 mL diaphragm-free electrolytic cell, and a zinc sheet (size: 10 mm × 15 mm × 0.1 mm) was used as the cathode. Then, 47.3 mg of thionyl chloride (0.25 mmol), phenylhydrazine hydrochloride (74.4 mg, 0.5 mmol), 12.3 mg of palladium dichloride (7 mmol%), potassium phosphate (15.9 mg, 30 mmol%), triethylamine (130 mg, 1.3 mmol), and 6 mL of DCE were added. The reaction was carried out at a constant current of 4 mA with stirring at room temperature for 13 hours. After the reaction, the solvent was removed under reduced pressure to obtain the crude product, which was purified by column chromatography to obtain 48.4 mg of the target product, with a yield of 60%. The structural formula of the obtained product is as follows:

[0047]

[0048] The structural characterization data of the obtained product are shown below:

[0049] 1 H NMR (500 MHz, CDCl3) δ 8.24-8.13 (m, 2H), 8.01 (d, J = 8.7 Hz, 2H), 7.61 (d, J = 8.7 Hz, 2H), 7.57-7.51 (m, 1H), 7.44 (t, J = 7.6 Hz, 2H), 3.48(s, 3H). 13 C{ 1 H} NMR (125 MHz, CDCl3) δ 174.2, 140.7, 137.5, 135.3, 132.4,130.1, 129.5, 128.7, 128.1, 44.4.

[0050] Example 5:

[0051] A graphite felt electrode (electrode size: 10 mm × 15 mm × 0.5 mm) was assembled as the anode in a 10 mL diaphragm-free electrolytic cell, and a zinc sheet (size: 10 mm × 15 mm × 0.1 mm) was used as the cathode. Then, 3-thiophene sulfoxide imine (40.3 mg, 0.25 mmol), phenylhydrazine hydrochloride (74.4 mg, 0.5 mmol), bis(triphenylphosphine) palladium dichloride (12.3 mg, 7 mmol%), potassium phosphate (15.9 mg, 30 mmol%), triethylamine (130 mg, 1.3 mmol), and 6 mL of DCE were added. The reaction was carried out at a constant current of 4 mA with stirring at room temperature for 13 hours. After the reaction, the solvent was removed under reduced pressure to obtain the crude product, which was purified by column chromatography to obtain 47.7 mg of the target product, with a yield of 72%. The structural formula of the obtained product is as follows:

[0052]

[0053] The structural characterization data of the obtained product are shown below:

[0054] 1 H NMR (500 MHz, CDCl3) δ 8.26 (dd, J = 3.0, 1.5 Hz, 1H), 8.17 (dd, J= 7.9, 1.6 Hz, 2H), 7.51 (tdd, J = 6.8, 6.1, 5.3, 2.7 Hz, 3H), 7.42 (t, J =7.7 Hz, 2H), 3.54 (s, 3H). 13 C{ 1 H} NMR (125 MHz, CDCl3) δ 174.2, 138.5, 135.5,132.4, 132.3, 129.4, 129.0, 128.1, 125.3, 44.6.

[0055] Example 6:

[0056] A graphite felt electrode (electrode size: 10 mm × 15 mm × 0.5 mm) was assembled as the anode in a 10 mL diaphragm-free electrolytic cell, and a zinc sheet (size: 10 mm × 15 mm × 0.1 mm) was used as the cathode. Then, phenylbenzyl sulfoxide imide (57.8 mg, 0.25 mmol), phenylhydrazine hydrochloride (74.4 mg, 0.5 mmol), bis(triphenylphosphine) palladium dichloride (12.3 mg, 7 mmol%), potassium phosphate (15.9 mg, 30 mmol%), triethylamine (130 mg, 1.3 mmol), and 6 mL of DCE were added. The reaction was carried out at a constant current of 4 mA with stirring at room temperature for 13 hours. After the reaction, the solvent was removed under reduced pressure to obtain the crude product, which was purified by column chromatography to obtain 75.4 mg of the target product, with a yield of 90%. The structural formula of the obtained product is as follows:

[0057]

[0058] The structural characterization data of the obtained product are shown below:

[0059] 1 H NMR (500 MHz, CDCl3) δ 8.21 (d, J = 7.6 Hz, 2H), 7.73 (d, J = 7.8Hz, 2H), 7.65 (t, J = 7.4 Hz, 1H), 7.55 (t, J = 7.4 Hz, 1H), 7.47 (dt, J =19.8, 7.6 Hz, 4H), 7.32 (t, J = 7.5 Hz, 1H), 7.23 (t, J = 7.5 Hz, 2H), 7.03(d, J = 7.5 Hz, 2H), 5.17-4.63 (m, 2H). 13 C{ 1 H} NMR (125 MHz, CDCl3) δ 174.6,135.8, 135.5, 133.9, 132.2, 131.3, 129.5, 129.2, 129.1, 128.6, 128.6, 128.1,127.4, 62.2.

Claims

1. An electrochemical synthesis method for preparing sulfoxide imine NH aromatic acylated derivatives, comprising the following preparation process: In a three-necked flask, phenylhydrazine hydrochloride, carbon monoxide balloon, sulfoxide imine, catalyst, additive, and solvent are added. A graphite rod is used as the anode and a zinc sheet is used as the cathode. The reaction is stirred under a current of 4 mA. The crude product is separated and purified by a chromatography column to obtain sulfoxide imine NH aromatic acylated compounds. The above reaction is shown in the following equation: ； In the formula, R1 is selected from 4-cyano or 4-trifluoromethyl substituents; R2 is one of 4-methyl, thiophene, or thiophenylthiobenzyl substituents; the electrolyte is tetrabutylammonium iodide; the palladium catalyst is bis(triphenylphosphine)palladium dichloride; the solvent is 1,2-dichloroethane; and the base is potassium phosphate and triethylamine.

2. The method for synthesizing a sulfoxide imine NH aromatic acylated derivative according to claim 1, characterized in that, The molar ratio of the sulfoxide imine compound to the phenylhydrazine hydrochloride compound is 1:2.

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