CN115896824A - Electrochemical method for preparing alpha-keto amide compound - Google Patents
Electrochemical method for preparing alpha-keto amide compound Download PDFInfo
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Abstract
An electrochemical process for preparing an α -ketoamide compound comprising the steps of: in an air atmosphere, adding a sulfoximine compound and an alpha-keto acid into a reactor in a molar ratio of 1; stirring the mixture by a magnetic stirring device to dissolve the mixture, inserting two electrodes, electrifying the mixture for 6 hours by using a graphite electrode as a positive electrode and a stainless steel electrode as a negative electrode at 4mA, evaporating the solvent under reduced pressure after the reaction is finished to obtain a crude product, and purifying the crude product by column chromatography to obtain the alpha-ketoamide compound. Compared with the traditional synthesis method, the method has the advantages that the reaction condition is mild, and the reaction can be smoothly carried out at room temperature; the operation is simple, and all the operations can be carried out in an open system; the reaction uses current as an oxidation method, so that the pollution of transition metal or chemical oxidant is avoided; easy raw material obtaining, good functional group compatibility and wide substrate application range.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to an electrochemical method for preparing an alpha-keto amide compound.
Background
The core functional motif of alpha-ketoamides is present in a variety of natural products and drugs with biological activity. Conventional α -ketoamides are prepared from amines with α -keto acids or acyl halides. Under the catalysis of transition metal, amine or amide reacts with phenylglyoxal, alkyne, aryl acetaldehyde, methyl ketone, alpha-oxycarboxylic acid, 1-aryl ethanol and phenylacetic acid to obtain alpha-ketoamide. Which uses an equivalent amount of chemical oxidant to facilitate the reaction. In recent years, electrochemical synthesis has received increasing attention because it avoids the use of catalysts and external oxidants to meet the requirements of green and sustainable chemistry.
Disclosure of Invention
Aiming at the problems, the invention provides an electrochemical method for preparing alpha-ketoamide, which has mild reaction conditions and can be smoothly carried out at room temperature; the operation is simple, and all the operations can be carried out in an open system; the reaction uses current as an oxidation method, so that the use of a chemical oxidant is avoided; the raw materials are easy to obtain, the reaction yield is high, the compatibility of functional groups is good, and the application range of a substrate is wide;
in order to achieve the purpose, the invention provides the following technical scheme: an electrochemical process for the preparation of an α -ketoamide, the process comprising the steps of:
in an air atmosphere, adding a sulfoximine compound and an alpha-keto acid into a reactor in a molar ratio of 1; stirring the mixture by a magnetic stirring device to dissolve the mixture, inserting two electrodes, electrifying for 4mA by adopting a graphite electrode as a positive electrode and 6h by adopting a stainless steel (iron sheet) electrode as a negative electrode, evaporating the solvent under reduced pressure after the reaction is finished to obtain a crude product, and purifying by column chromatography to obtain the alpha-keto amide compound.
In the step, the reactor is a diaphragm-free electrolytic cell, and the alpha-ketoamide compound is prepared by electrochemical reaction, wherein the preparation method has the following reaction formula:
in the formula R 1 = phenyl, substituted phenyl and alkyl; r 2 = phenyl group, substituted aromatic heterocyclic compound; the solvent is acetonitrile.
Preferably, the anode electrode plate is a carbon rod electrode, and the cathode electrode plate is a stainless steel (iron plate) electrode.
Preferably, in the step, the reaction is carried out under open conditions and room temperature conditions, the power supply used for the reaction is a 30V/3A direct current stabilized power supply, and the electrifying current is 4 milliamperes.
Preferably, the solvent is an acetonitrile solvent.
Preferably, in the step, the eluent used for column chromatography purification is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 2.
The invention has the beneficial effects that:
1. the invention adopts cheap and easily obtained sulfoxide imine and alpha-keto acid as raw materials, the sulfoxide imine is prepared from corresponding thioether, and the alpha-keto acid can be prepared from corresponding acetophenone.
2. The method can be operated under the air condition, is not sensitive to water and oxygen, has relatively mild reaction condition and is simple to operate.
3. The invention adopts current as oxidant, has low cost and avoids the pollution of traditional transition metal catalyst or equivalent chemical oxidant.
4. The method can obtain the target product by only one step, and has the advantages of high yield, good functional group compatibility, simple post-treatment and good application potential.
Drawings
FIG. 1 is a hydrogen spectrum of the product obtained in example 1 of the present invention;
FIG. 2 is a chart showing the carbon spectrum of the product obtained in example 1 of the present invention;
FIG. 3 is a hydrogen spectrum of the product obtained in example 2 of the present invention;
FIG. 4 is a chart showing a carbon spectrum of a product obtained in example 2 of the present invention;
FIG. 5 is a hydrogen spectrum of the product obtained in example 3 of the present invention;
FIG. 6 is a carbon spectrum of the product obtained in example 3 of the present invention;
FIG. 7 is a hydrogen spectrum of the product obtained in example 4 of the present invention;
FIG. 8 is a carbon spectrum of the product obtained in example 4 of the present invention;
FIG. 9 is a hydrogen spectrum of the product obtained in example 5 of the present invention;
FIG. 10 is a chart showing a carbon spectrum of a product obtained in example 5 of the present invention;
Detailed Description
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, and thus the scope of the present invention is more clearly defined. The embodiments described herein are only a few embodiments of the present invention, rather than all embodiments, and all other embodiments that can be derived by one of ordinary skill in the art without inventive faculty based on the embodiments described herein are intended to fall within the scope of the present invention.
Example 1:
a carbon rod electrode (electrode size: diameter. Phi.6 mm) was installed as an anode and a stainless steel sheet (size: 10 mm. Times.10 mm. Times.0.1 mm) was installed as a cathode in a 10mL diaphragm-free electrolytic cell, followed by addition of p-methylsulfoxylimine (33.8mg, 0.20mmol), benzoylformic acid (90.0mg, 0.6mmol), and acetonitrile 5mL, and the reaction was stirred at room temperature under a constant current of 4mA for 6 hours. After the reaction is finished, the solvent is evaporated under reduced pressure to obtain a crude product, and the crude product is purified by column chromatography to obtain 57.8mg of a target product, wherein the yield is 96%. The resulting product has the following structural formula:
the structural characterization data of the resulting product are shown below:
1 H NMR(500MHz,Chloroform-d)δ8.10-8.01(m,2H),7.95(dd,J＝8.4,2.1Hz,2H),7.60(td,J＝6.6,5.7,3.6Hz,1H),7.47(t,J＝7.8Hz,2H),7.45-7.39(m,2H),3.47(s,3H),2.47(s,3H)； 13 C NMR(125MHz,Chloroform-d)δ190.3,173.3,145.8,134.5,134.2,132.8,130.6,130.2,128.7,127.2,45.0,21.7.
example 2:
a carbon rod electrode (electrode size: diameter. Phi.6 mm) was installed as an anode and a stainless steel sheet (size: 10 mm. Times.10 mm. Times.0.1 mm) was installed as a cathode in a 10mL diaphragm-free electrolytic cell, followed by addition of p-thionyl chloride imine (37.8mg, 0.20mmol), benzoylformic acid (90.0mg, 0.6mmol), and acetonitrile 5mL, and the reaction was stirred at room temperature under a constant current of 4mA for 6 hours. After the reaction is finished, the solvent is evaporated under reduced pressure to obtain a crude product, and the crude product is purified by column chromatography to obtain 38.5mg of a target product, wherein the yield is 60%. The resulting product has the following structural formula:
the structural characterization data of the resulting product are shown below:
1 H NMR(500MHz,Chloroform-d)δ8.09-7.98(m,4H),7.68-7.57(m,3H),7.49(t,J＝7.7Hz,2H),3.50(s,3H)； 13 C NMR(125MHz,Chloroform-d)δ190.0,173.2,141.4,136.1,134.4,133.8,132.6,130.3,130.2,128.7,44.9.
example 3:
a carbon rod electrode (electrode size: diameter. Phi.6 mm) was installed as an anode and a stainless steel sheet (size: 10 mm. Times.10 mm. Times.0.1 mm) was installed as a cathode in a 10mL diaphragm-free electrolytic cell, followed by addition of 2-thiophenesulfsulfoximine (32.2mg, 0.20mmol), benzoylformic acid (90.0mg, 0.6mmol), and acetonitrile (5 mL), and the reaction was stirred at room temperature under a constant current of 4mA for 6 hours. After the reaction is finished, the solvent is evaporated under reduced pressure to obtain a crude product, and the crude product is purified by column chromatography to obtain 46.3mg of a target product, wherein the yield is 79%. The resulting product has the following structural formula:
the structural characterization data of the resulting product are shown below:
1 H NMR(500MHz,Chloroform-d)δ8.31(dt,J＝3.6,1.8Hz,1H),8.10-7.96(m,2H),7.61(td,J＝7.3,3.7Hz,1H),7.57(dt,J＝5.5,2.8Hz,1H),7.54-7.50(m,1H),7.48(td,J＝7.8,2.0Hz,2H),3.55(d,J＝2.3Hz,3H). 13 C NMR(125MHz,Chloroform-d)δ190.2,173.2,136.8,134.3,133.3,132.7,130.2,129.6,128.7,125.1,45.1.
example 4:
a carbon rod electrode (electrode size: diameter. Phi.6 mm) was installed as an anode and a stainless steel sheet (size: 10 mm. Times.10 mm. Times.0.1 mm) as a cathode in a 10mL diaphragm-free electrolytic cell, followed by addition of sulfoximine (31.0 mg, 0.20mmol), p-toluic acid (98.4 mg,0.6 mmol), and acetonitrile 5mL, and the reaction was stirred at room temperature under a constant current of 4mA for 6 hours. After the reaction is finished, the solvent is evaporated under reduced pressure to obtain a crude product, and the crude product is purified by column chromatography to obtain 43.9mg of a target product, wherein the yield is 73%. The resulting product has the following structural formula:
the structural characterization data of the resulting product are shown below:
1 H NMR(500MHz,Chloroform-d)δ8.09(dd,J＝7.3,2.2Hz,2H),7.99-7.93(m,2H),7.77-7.69(m,1H),7.68-7.61(m,2H),7.28(dd,J＝8.3,2.8Hz,2H),3.49(s,3H),2.43(s,3H)； 13 C NMR(125MHz,Chloroform-d)δ189.9,173.5,145.4,137.7,134.5,130.4,130.2,129.9,129.4,127.2,44.8,21.9.
example 5:
a carbon rod electrode (electrode size: diameter. Phi.6 mm) was installed as an anode and a stainless steel sheet (size: 10 mm. Times.10 mm. Times.0.1 mm) was installed as a cathode in a 10mL diaphragm-free electrolytic cell, followed by addition of sulfoximine (31.0 mg, 0.20mmol), m-methoxybenzoylformic acid (108mg, 0.6 mmol), and 5mL acetonitrile, and the reaction was stirred at room temperature under a constant current of 4mA for 6 hours. After the reaction is finished, the solvent is evaporated under reduced pressure to obtain a crude product, and the crude product is purified by column chromatography to obtain 39.3mg of a target product, wherein the yield is 62%. The resulting product has the following structural formula:
the structural characterization data of the resulting product are shown below:
1 H NMR(500MHz,Chloroform-d)δ8.12-8.02(m,2H),7.78-7.71(m,1H),7.69-7.60(m,3H),7.59-7.54(m,1H),7.39(td,J＝8.0,2.3Hz,1H),7.22-7.13(m,1H),3.85(s,3H),3.50(s,3H)； 13 C NMR(125MHz,Chloroform-d)δ190.0,173.3,159.8,137.6,134.5,134.0,130.0,129.7,127.2,123.4,121.4,113.2,55.5,44.8.
Claims (5)
1. an electrochemical process for the preparation of an α -ketoamide compound, characterized in that: the preparation method comprises the following steps: in an air atmosphere, adding a sulfoximine compound and alpha-keto acid into a reactor in a molar ratio of 1; stirring the mixture by using a magnetic stirring device to dissolve the mixture, inserting two electrodes, electrifying for 6 hours by using a graphite electrode as a positive electrode and a stainless steel electrode as a negative electrode and 4mA, evaporating the solvent under reduced pressure after the reaction is finished to obtain a crude product, and purifying by using column chromatography to obtain an alpha-keto amide compound;
in the step, the reactor is a diaphragm-free electrolytic cell, and the alpha-keto amide compound is prepared by electrochemical reaction, and the reaction equation is as follows:
in the formula R 1 = phenyl, substituted phenyl and alkyl; r 2 = phenyl group, substituted aromatic heterocyclic compound; the solvent is acetonitrile.
2. The electrochemical process for producing an α -ketoamide compound according to claim 1, wherein: the anode electrode plate is a carbon rod electrode, and the cathode electrode plate is a stainless steel (iron sheet) electrode.
3. The electrochemical process for producing an α -ketoamide compound according to claim 1, wherein: in the step, the reaction is carried out under the open condition and the room temperature condition, the power supply used for the reaction is a 30V/3A direct current stabilized power supply, and the electrifying current is 4 milliamperes.
4. The electrochemical process for producing an α -ketoamide compound according to claim 1, characterized in that: the solvent is acetonitrile.
5. The electrochemical process for producing an α -ketoamide compound according to claim 1, characterized in that: in the step, an eluent used for column chromatography purification is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is 2.
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